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Sample records for cartilage repair tissue

  1. Quantitative ultrasound biomicroscopy for the analysis of healthy and repair cartilage tissue

    OpenAIRE

    Gelse, K; A Olk; Eichhorn, S.; B Swoboda; M Schoene; K Raum

    2010-01-01

    The increasing spectrum of different cartilage repair strategies requires the introduction of adequate non-destructive methods to analyse their outcome in-vivo, i.e. arthroscopically. The validity of non-destructive quantitative ultrasound biomicroscopy (UBM) was investigated in knee joints of five miniature pigs. After 12 weeks, six 5-mm defects, treated with different cartilage repair approaches, provided tissues with different structural qualities. Healthy articular cartilage from each con...

  2. Quantitative ultrasound biomicroscopy for the analysis of healthy and repair cartilage tissue

    Directory of Open Access Journals (Sweden)

    K Gelse

    2010-02-01

    Full Text Available The increasing spectrum of different cartilage repair strategies requires the introduction of adequate non-destructive methods to analyse their outcome in-vivo, i.e. arthroscopically. The validity of non-destructive quantitative ultrasound biomicroscopy (UBM was investigated in knee joints of five miniature pigs. After 12 weeks, six 5-mm defects, treated with different cartilage repair approaches, provided tissues with different structural qualities. Healthy articular cartilage from each contralateral unoperated knee joint served as a control. The reflected and backscattered ultrasound signals were processed to estimate the integrated reflection coefficient (IRC and apparent integrated backscatter (AIB parameters. The cartilage repair tissues were additionally assessed biomechanically by cyclic indentation, histomorphologically and immunohistochemically. UBM allowed high-resolution visualisation of the structure of the joint surface and subchondral bone plate, as well as determination of the cartilage thickness and demonstrated distinct differences between healthy cartilage and the different repair cartilage tissues with significant higher IRC values and a steeper negative slope of the depth-dependent backscatter amplitude AIBslope for healthy cartilage. Multimodal analyses revealed associations between IRC and the indentation stiffness. Furthermore, AIBslope and AIB at the cartilage-bone boundary (AIBdC were associated with the quality of the repair matrices and the subchondral bone plate, respectively. This ex-vivo pilot study confirms that UBM can provide detailed imaging of articular cartilage and the subchondral bone interface also in repaired cartilage defects, and furthermore, contributes in certain aspects to a basal functional characterization of various forms of cartilage repair tissues. UBM could be further established to be applied arthroscopically in-vivo.

  3. Tissue engineering for articular cartilage repair – the state of the art

    OpenAIRE

    Johnstone, B.; Alini, M.; M Cucchiarini; GR Dodge; Eglin, D.; F Guilak; Madry, H.; Mata, A.; RL Mauck; CE Semino; MJ Stoddart

    2013-01-01

    Articular cartilage exhibits little capacity for intrinsic repair, and thus even minor injuries or lesions may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. While there have been numerous attempts to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, there remain significant challenges in the clinical application of cell-based therapies for cartilage repair. This paper reviews the cu...

  4. A tissue regeneration approach to bone and cartilage repair

    CERN Document Server

    Dunstan, Colin; Rosen, Vicki

    2015-01-01

    Reviewing exhaustively the current state of the art of tissue engineering strategies for regenerating bones and joints through the use of biomaterials, growth factors and stem cells, along with an investigation of the interactions between biomaterials, bone cells, growth factors and added stem cells and how together skeletal tissues can be optimised, this book serves to highlight the importance of biomaterials composition, surface topography, architectural and mechanical properties in providing support for tissue regeneration. Maximizing reader insights into the importance of the interplay of these attributes with bone cells (osteoblasts, osteocytes and osteoclasts) and cartilage cells (chondrocytes), this book also provides a detailed reference as to how key signalling pathways are activated. The contribution of growth factors to drive tissue regeneration and stem cell recruitment is discussed along with a review the potential and challenges of adult or embryonic mesenchymal stem cells to further enhance the...

  5. Tissue engineering for articular cartilage repair – the state of the art

    Directory of Open Access Journals (Sweden)

    B Johnstone

    2013-05-01

    Full Text Available Articular cartilage exhibits little capacity for intrinsic repair, and thus even minor injuries or lesions may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. While there have been numerous attempts to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, there remain significant challenges in the clinical application of cell-based therapies for cartilage repair. This paper reviews the current state of cartilage tissue engineering with respect to different cell sources and their potential genetic modification, biomaterial scaffolds and growth factors, as well as preclinical testing in various animal models. This is not intended as a systematic review, rather an opinion of where the field is moving in light of current literature. While significant advances have been made in recent years, the complexity of this problem suggests that a multidisciplinary approach – combining a clinical perspective with expertise in cell biology, biomechanics, biomaterials science and high-throughput analysis will likely be necessary to address the challenge of developing functional cartilage replacements. With this approach we are more likely to realise the clinical goal of treating both focal defects and even large-scale osteoarthritic degenerative changes in the joint.

  6. The vascularized periosteum flap as novel tissue engineering model for repair of cartilage defects.

    Science.gov (United States)

    Harhaus, Leila; Huang, Jung-Ju; Kao, Shu-Wei; Wu, Yen-Lin; Mackert, Gina Alicia; Höner, Bernd; Cheng, Ming-Huei; Kneser, Ulrich; Cheng, Chao-Min

    2015-06-01

    Periosteum is a promising tissue engineering scaffold in research of cartilage repair; so far however, periosteum transfers have not been realized successfully because of insufficient nourishment of the graft. In a translational approach we, for the first time, designed a vascularized periosteum flap as 'independent' biomaterial with its own blood supply to address this problem and to reconstruct circumscript cartilage defects. In six 3-month-old New Zealand rabbits, a critical size cartilage defect of the medial femur condyle was created and covered by a vascularized periosteum flap pedicled on the saphenous vessels. After 28 days, formation of newly built cartilage was assessed macroscopically, histologically and qualitatively via biomechanical compression testing, as well as on molecular biological level via immunohistochemistry. All wounds healed completely, all joints were stable and had full range of motion. All flaps survived and were perfused through their pulsating pedicles. They showed a stable attachment to the bone, although partially incomplete adherence. Hyaline cartilage with typical columnar cell distribution and positive Collagen II staining was formed in the transferred flaps. Biomechanical testing revealed a significantly higher maximum load than the positive control, but a low elasticity. This study proved that vascularization of the periosteum flap is the essential step for flap survival and enables the flap to transform into cartilage. Reconstruction of circumscript cartilage defects seems to be possible. Although these are the first results out of a pilot project, this technique, we believe, can have a wide range of potential applications and high relevance in the clinical field. PMID:25754287

  7. How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Juan Antonio Marchal

    2013-03-01

    Full Text Available Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i skin; (ii cartilage; (iii bone; (iv nerve; and (v cardiac.

  8. The Application of Polysaccharide Biocomposites to Repair Cartilage Defects

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    Feng Zhao

    2014-01-01

    Full Text Available Owing to own nature of articular cartilage, it almost has no self-healing ability once damaged. Despite lots of restore technologies having been raised in the past decades, no repair technology has smoothly substituted for damaged cartilage using regenerated cartilage tissue. The approach of tissue engineering opens a door to successfully repairing articular cartilage defects. For instance, grafting of isolated chondrocytes has huge clinical potential for restoration of cartilage tissue and cure of chondral injury. In this paper, SD rats are used as subjects in the experiments, and they are classified into three groups: natural repair (group A, hyaluronic acid repair (group B, and polysaccharide biocomposites repair (hyaluronic acid hydrogel containing chondrocytes, group C. Through the observation of effects of repairing articular cartilage defects, we concluded that cartilage repair effect of polysaccharide biocomposites was the best at every time point, and then the second best was hyaluronic acid repair; both of them were better than natural repair. Polysaccharide biocomposites have good biodegradability and high histocompatibility and promote chondrocytes survival, reproduction, and spliting. Moreover, polysaccharide biocomposites could not only provide the porous network structure but also carry chondrocytes. Consequently hyaluronic acid-based polysaccharide biocomposites are considered to be an ideal biological material for repairing articular cartilage.

  9. A bioactive hybrid three-dimensional tissue-engineering construct for cartilage repair.

    Science.gov (United States)

    Ainola, Mari; Tomaszewski, Waclaw; Ostrowska, Barbara; Wesolowska, Ewa; Wagner, H Daniel; Swieszkowski, Wojciech; Sillat, Tarvo; Peltola, Emilia; Konttinen, Yrjö T

    2016-01-01

    The aim was to develop a hybrid three-dimensional-tissue engineering construct for chondrogenesis. The hypothesis was that they support chondrogenesis. A biodegradable, highly porous polycaprolactone-grate was produced by solid freeform fabrication. The polycaprolactone support was coated with a chitosan/polyethylene oxide nanofibre sheet produced by electrospinning. Transforming growth factor-β3-induced chondrogenesis was followed using the following markers: sex determining region Y/-box 9, runt-related transcription factor 2 and collagen II and X in quantitative real-time polymerase chain reaction, histology and immunostaining. A polycaprolactone-grate and an optimized chitosan/polyethylene oxide nanofibre sheet supported cellular aggregation, chondrogenesis and matrix formation. In tissue engineering constructs, the sheets were seeded first with mesenchymal stem cells and then piled up according to the lasagne principle. The advantages of such a construct are (1) the cells do not need to migrate to the tissue engineering construct and therefore pore size and interconnectivity problems are omitted and (2) the cell-tight nanofibre sheet and collagen-fibre network mimic a cell culture platform for mesenchymal stem cells/chondrocytes (preventing escape) and hinders in-growth of fibroblasts and fibrous scarring (preventing capture). This allows time for the slowly progressing, multiphase true cartilage regeneration. PMID:26341661

  10. In-situ crosslinkable and self-assembling elastin-like polypeptide block copolymers for cartilage tissue repair

    Science.gov (United States)

    Lim, Dong Woo

    This work describes the development of genetically engineered elastin-like polypeptide (ELP) block copolymers as in-situ gelling scaffolds for cartilage tissue repair. The central hypothesis underlying this work is that ELP based biopolymers can be exploited as injectable biomaterials by rapid chemical crosslinking. To prove this, gene libraries encoding ELP having different molecular weights and amino acid sequences, and ELP block copolymers composed of various ELP blocks having diverse amino acid composition, length, and phase transition behavior were synthesized by recursive directional ligation, expressed in E. Coli and purified by inverse transition cycling. Mannich-type condensation of hydroxymethylphosphines (HMPs) with primary- and secondary-amines of amino acids was developed as a new crosslinking method of polypeptides. Chemically crosslinked ELP hydrogels were formed rapidly in an aqueous solution by reaction of ELPs containing periodic lysine residues with HMPs. The crosslinking density and mechanical property of the ELP hydrogels were controlled at the sequence level by varying the Lys density in ELPs composed of mono-block as well as by segregation of the Lys residues within specific blocks of tri-block architectures. Fibroblasts embedded in ELP hydrogels survived the crosslinking process and were viable after in vitro culture for at least 3 days. The DNA content of fibroblasts within the tri-block gels was significantly higher than that in the mono-block gels at day 3. These results suggest that the HMP crosslinked ELP block copolymer hydrogels show finely tuned mechanical properties and different microenvironments for cell viability as well as potential as in-situ crosslinkable biopolymers for tissue repair applications with load-bearing environments. As an alternative, rheological behavior of the ELP block copolymers and ELP-grafted hyaluronic acids (HAs) as artificial extracellular matrices (ECMs) showed that they were thermally aggregated into

  11. MR imaging of cartilage repair procedures

    International Nuclear Information System (INIS)

    It is becoming increasingly important for the radiologist to evaluate the appearance and outcome of cartilage repair procedures. MR imaging is currently the best method for such evaluation but it is necessary to use cartilage-specific sequences and to modify those sequences when necessary to minimize artifacts from retained metal within the joint. This article reviews the surgical technique of the more commonly performed cartilage repair procedures, currently recommended techniques for the MR imaging evaluation of articular cartilage and cartilage repair procedures, and the MR imaging appearance of cartilage repair procedures and of the most frequently encountered complications following such procedures. (orig.)

  12. Advanced Strategies for Articular Cartilage Defect Repair

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    Fergal J. O'Brien

    2013-02-01

    Full Text Available Articular cartilage is a unique tissue owing to its ability to withstand repetitive compressive stress throughout an individual’s lifetime. However, its major limitation is the inability to heal even the most minor injuries. There still remains an inherent lack of strategies that stimulate hyaline-like articular cartilage growth with appropriate functional properties. Recent scientific advances in tissue engineering have made significant steps towards development of constructs for articular cartilage repair. In particular, research has shown the potential of biomaterial physico-chemical properties significantly influencing the proliferation, differentiation and matrix deposition by progenitor cells. Accordingly, this highlights the potential of using such properties to direct the lineage towards which such cells follow. Moreover, the use of soluble growth factors to enhance the bioactivity and regenerative capacity of biomaterials has recently been adopted by researchers in the field of tissue engineering. In addition, gene therapy is a growing area that has found noteworthy use in tissue engineering partly due to the potential to overcome some drawbacks associated with current growth factor delivery systems. In this context, such advanced strategies in biomaterial science, cell-based and growth factor-based therapies that have been employed in the restoration and repair of damaged articular cartilage will be the focus of this review article.

  13. Preclinical Studies for Cartilage Repair

    OpenAIRE

    Hurtig, Mark B.; Buschmann, Michael D; Fortier, Lisa A; Hoemann, Caroline D; Hunziker, Ernst B.; Jurvelin, Jukka S.; Mainil-Varlet, Pierre; McIlwraith, C. Wayne; Sah, Robert L.; Whiteside, Robert A.

    2011-01-01

    Investigational devices for articular cartilage repair or replacement are considered to be significant risk devices by regulatory bodies. Therefore animal models are needed to provide proof of efficacy and safety prior to clinical testing. The financial commitment and regulatory steps needed to bring a new technology to clinical use can be major obstacles, so the implementation of highly predictive animal models is a pressing issue. Until recently, a reductionist approach using acute chondral...

  14. Effects of In Vitro Low Oxygen Tension Preconditioning of Adipose Stromal Cells on Their In Vivo Chondrogenic Potential: Application in Cartilage Tissue Repair

    Science.gov (United States)

    Gauthier, Olivier; Lesoeur, Julie; Sourice, Sophie; Masson, Martial; Fellah, Borhane Hakim; Geffroy, Olivier; Lallemand, Elodie; Weiss, Pierre

    2013-01-01

    Purpose Multipotent stromal cell (MSC)-based regenerative strategy has shown promise for the repair of cartilage, an avascular tissue in which cells experience hypoxia. Hypoxia is known to promote the early chondrogenic differentiation of MSC. The aim of our study was therefore to determine whether low oxygen tension could be used to enhance the regenerative potential of MSC for cartilage repair. Methods MSC from rabbit or human adipose stromal cells (ASC) were preconditioned in vitro in control or chondrogenic (ITS and TGF-β) medium and in 21 or 5% O2. Chondrogenic commitment was monitored by measuring COL2A1 and ACAN expression (real-time PCR). Preconditioned rabbit and human ASC were then incorporated into an Si-HPMC hydrogel and injected (i) into rabbit articular cartilage defects for 18 weeks or (ii) subcutaneously into nude mice for five weeks. The newly formed tissue was qualitatively and quantitatively evaluated by cartilage-specific immunohistological staining and scoring. The phenotype of ASC cultured in a monolayer or within Si-HPMC in control or chondrogenic medium and in 21 or 5% O2 was finally evaluated using real-time PCR. Results/Conclusions 5% O2 increased the in vitro expression of chondrogenic markers in ASC cultured in induction medium. Cells implanted within Si-HPMC hydrogel and preconditioned in chondrogenic medium formed a cartilaginous tissue, regardless of the level of oxygen. In addition, the 3D in vitro culture of ASC within Si-HPMC hydrogel was found to reinforce the pro-chondrogenic effects of the induction medium and 5% O2. These data together indicate that although 5% O2 enhances the in vitro chondrogenic differentiation of ASC, it does not enhance their in vivo chondrogenesis. These results also highlight the in vivo chondrogenic potential of ASC and their potential value in cartilage repair. PMID:23638053

  15. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    Science.gov (United States)

    Im, Gun-Il

    2016-04-01

    Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair. PMID:26559963

  16. Regulatory Challenges for Cartilage Repair Technologies.

    Science.gov (United States)

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible. PMID:26069647

  17. Articular cartilage repair and the evolving role of regenerative medicine

    Directory of Open Access Journals (Sweden)

    Pieter K Bos

    2010-10-01

    Full Text Available Pieter K Bos1, Marloes L van Melle1, Gerjo JVM van Osch1,21Department of Orthopaedic Surgery, Erasmus MC, Rotterdam, the Netherlands; 2Department of Otorhinolaryngology, Erasmus MC, Rotterdam, the NetherlandsAbstract: Among the growing applications of regenerative medicine, clinical articular cartilage repair has now been used for 2 decades and forms a successful example of translational medicine. Cartilage is characterized by a limited intrinsic repair capacity following injury. Articular cartilage defects cause symptoms, are not spontaneously repaired, and are generally believed to result in early osteoarthritis. Marrow stimulation techniques, osteochondral transplantation, and cell-based therapies, such as autologous chondrocyte implantation (ACI and use of mesenchymal stem cells (MSCs, are used for tissue regeneration, symptom relief, and prevention of further joint degeneration. The exact incidence of cartilage defects and the natural outcome of joints with these lesions are unclear. Currently available cartilage repair techniques are designed for defect treatment in otherwise healthy joints and limbs, mostly in young adults. The natural history studies presented in this review estimated that the prevalence of cartilage lesions in this patient group ranges from 5% to 11%. The background and results from currently available randomized clinical trials of the three mostly used cartilage repair techniques are outlined in this review. Osteochondral transplantation, marrow stimulation, and ACI show improvement of symptoms with an advantage for cell-based techniques, but only a suggestion that risk for joint degeneration can be reduced. MSCs, characterized by their good proliferative capacity and the potential to differentiate into different mesenchymal lineages, form an attractive alternative cell source for cartilage regeneration. Moreover, MSCs provide a regenerative microenvironment by the secretion of bioactive factors. This trophic activity

  18. Chitosan/Poly(ɛ-caprolactone) blend scaffolds for cartilage repair

    NARCIS (Netherlands)

    Neves, Sara C.; Moreira Teixeira, Liliana S.; Moroni, Lorenzo; Reis, Rui L.; Blitterswijk, van Clemens A.; Alves, Natália M.; Karperien, Marcel; Mano, João F.

    2011-01-01

    Chitosan (CHT)/poly(ɛ-caprolactone) (PCL) blend 3D fiber-mesh scaffolds were studied as possible support structures for articular cartilage tissue (ACT) repair. Micro-fibers were obtained by wet-spinning of three different polymeric solutions: 100:0 (100CHT), 75:25 (75CHT) and 50:50 (50CHT) wt.% CHT

  19. Cartilage Tissue Engineering: the effect of different biomaterials, cell types and culture methods

    NARCIS (Netherlands)

    W.J.C.M. Marijnissen (Willem)

    2006-01-01

    textabstractChapter 1 outlines the normal structure and composition of articular cartilage and the inefficient spontaneous healing response after focal damage. Current surgical treatment options are briefly discussed and tissue engineering techniques for the repair of articular cartilage defects

  20. PHOTOCROSSLINKABLE HYDROGELS FOR CARTILAGE TISSUE ENGINEERING

    NARCIS (Netherlands)

    Levett, Peter Andrew

    2015-01-01

    For millions of people, damaged cartilage is a major source of pain and disability. As those people often discover upon seeking medical treatment, once damaged, cartilage is very difficult to repair. Finding better clinical therapies for damaged cartilage has generated a huge amount of research inte

  1. Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques

    Directory of Open Access Journals (Sweden)

    Ashvin K. Dewan

    2014-01-01

    Full Text Available Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells and associated scaffolds (natural or synthetic, hydrogels or membranes. ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient’s knee as evaluated by multiple clinical indices and the quality of regenerated tissue. Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients.

  2. Multimodal evaluation of tissue-engineered cartilage

    OpenAIRE

    Mansour, Joseph M.; Welter, Jean F.

    2013-01-01

    Tissue engineering (TE) has promise as a biological solution and a disease modifying treatment for arthritis. Although cartilage can be generated by TE, substantial inter- and intra-donor variability makes it impossible to guarantee optimal, reproducible results. TE cartilage must be able to perform the functions of native tissue, thus mechanical and biological properties approaching those of native cartilage are likely a pre-requisite for successful implantation. A quality-control assessment...

  3. Electrospun Cartilage-Derived Matrix Scaffolds for Cartilage Tissue Engineering

    OpenAIRE

    Garrigues, N. William; Little, Dianne; Sanchez-Adams, Johannah; David S Ruch; Guilak, Farshid

    2014-01-01

    Macroscale scaffolds created from cartilage-derived matrix (CDM) demonstrate chondroinductive properties, but many fabrication methods do not allow for control of nanoscale architecture. In this regard, electrospun scaffolds have shown significant promise for cartilage tissue engineering. However, nanofibrous materials generally exhibit a relatively small pore size and require techniques such as multi-layering or the inclusion of sacrificial fibers to enhance cellular infiltration. The object...

  4. Multimodal evaluation of tissue-engineered cartilage.

    Science.gov (United States)

    Mansour, Joseph M; Welter, Jean F

    2013-02-01

    Tissue engineering (TE) has promise as a biological solution and a disease modifying treatment for arthritis. Although cartilage can be generated by TE, substantial inter- and intra-donor variability makes it impossible to guarantee optimal, reproducible results. TE cartilage must be able to perform the functions of native tissue, thus mechanical and biological properties approaching those of native cartilage are likely a pre-requisite for successful implantation. A quality-control assessment of these properties should be part of the implantation release criteria for TE cartilage. Release criteria should certify that selected tissue properties have reached certain target ranges, and should be predictive of the likelihood of success of an implant in vivo. Unfortunately, it is not currently known which properties are needed to establish release criteria, nor how close one has to be to the properties of native cartilage to achieve success. Achieving properties approaching those of native cartilage requires a clear understanding of the target properties and reproducible assessment methodology. Here, we review several main aspects of quality control as it applies to TE cartilage. This includes a look at known mechanical and biological properties of native cartilage, which should be the target in engineered tissues. We also present an overview of the state of the art of tissue assessment, focusing on native articular and TE cartilage. Finally, we review the arguments for developing and validating non-destructive testing methods for assessing TE products. PMID:23606823

  5. Repair of articular cartilage defects in minipigs by microfracture surgery and BMSCs transplantation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the feasibility of minimal invasive repair of cartilage defect by arthroscope-aided microfracture surgery and autologous transplantation of mesenchymal stem cells. Methods: Bone marrow of minipigs was taken out and the bone marrow derived mesenchymal stem cells (BMSCs) were isolated and cultured to passage 3. Then 6 minipigs were randomly divided into 2 groups with 6 knees in each group. After the articular cartilage defect was induced in each knee. the left defect received microfracture surgery and was injected with 2. 5 ml BMSCs cells at a concentration of 3×107 cells/ml into the articular cavity; while right knee got single microfracture or served as blank control group. The animals were killed at 8 or 16 weeks, and the repair tissue was histologically and immunohistochemically examined for the presence of type Ⅱ collagen and glycosaminoglycans (GAGs) at 8 and 16 weeks. Results:Eight weeks after the surgery, the overlying articular surface of the cartilage defect showed normal color and integrated to adjacent cartilage. And 16 weeks after surgery, hyaline cartilage was observed at the repairing tissues and immunostaining indicated the diffuse presence of this type Ⅱ collagen and GAGs throughout the repair cartilage in the treated defects. Single microfracture group had the repairing of fibro-cartilage, while during the treatment, the defects of blank group were covered with fewer fiber tissues, and no blood capillary growth or any immunological rejection was observed. Conclusion:Microfracture technique and BMSCs transplantation to repair cartilage defect is characterized with minimal invasion and easy operation, and it will greatly promote the regeneration repair of articular cartilage defect.

  6. A Novel Approach to Stimulate Cartilage Repair: Targeting Collagen Turnover

    NARCIS (Netherlands)

    Y.M. Bastiaansen-Jenniskens (Yvonne Maria)

    2009-01-01

    textabstractOA is a complex disease of which the ethiopathology is not completely known and therapies to repair cartilage are still under investigation. The increase of collagen type II expression in osteoarthritic cartilage suggests an activated repair mechanism that is however ineffective in repai

  7. Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues.

    Science.gov (United States)

    Pallante-Kichura, Andrea L; Cory, Esther; Bugbee, William D; Sah, Robert L

    2013-11-01

    The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These

  8. A Novel Approach to Stimulate Cartilage Repair: Targeting Collagen Turnover

    OpenAIRE

    Bastiaansen-Jenniskens, Yvonne Maria

    2009-01-01

    textabstractOA is a complex disease of which the ethiopathology is not completely known and therapies to repair cartilage are still under investigation. The increase of collagen type II expression in osteoarthritic cartilage suggests an activated repair mechanism that is however ineffective in repairing or maintaining the ECM homeostasis. We therefore investigated the ability to modulate the formation of a functional collagen type II network that can ultimately contribute to innovation of car...

  9. Characterization of the collagen component of cartilage repair tissue of the talus with quantitative MRI: comparison of T2 relaxation time measurements with a diffusion-weighted double-echo steady-state sequence (dwDESS)

    Energy Technology Data Exchange (ETDEWEB)

    Kretzschmar, M.; Hainc, N.; Studler, U. [University Hospital Basel, Department of Radiology, Basel (Switzerland); Bieri, O. [University Hospital Basel, Division of Radiological Physics, Basel (Switzerland); Miska, M. [University Hospital, Department of Orthopedics, Heidelberg (Germany); Wiewiorski, M.; Valderrabano, V. [University Hospital Basel, Department of Orthopedic Surgery, Basel (Switzerland)

    2015-04-01

    The purpose of this study was to characterize the collagen component of repair tissue (RT) of the talus after autologous matrix-induced chondrogenesis (AMIC) using quantitative T2 and diffusion-weighted imaging. Mean T2 values and diffusion coefficients of AMIC-RT and normal cartilage of the talus of 25 patients with posttraumatic osteochondral lesions and AMIC repair were compared in a cross-sectional design using partially spoiled steady-state free precession (pSSFP) for T2 quantification, and diffusion-weighted double-echo steady-state (dwDESS) for diffusion measurement. RT and cartilage were graded with modified Noyes and MOCART scores on morphological sequences. An association between follow-up interval and quantitative MRI measures was assessed using multivariate regression, after stratifying the cohort according to time interval between surgery and MRI. Mean T2 of the AMIC-RT and cartilage were 43.1 ms and 39.1 ms, respectively (p = 0.26). Mean diffusivity of the RT (1.76 μm{sup 2}/ms) was significantly higher compared to normal cartilage (1.46 μm{sup 2}/ms) (p = 0.0092). No correlation was found between morphological and quantitative parameters. RT diffusivity was lowest in the subgroup with follow-up >28 months (p = 0.027). Compared to T2-mapping, dwDESS demonstrated greater sensitivity in detecting differences in the collagen matrix between AMIC-RT and cartilage. Decreased diffusivity in patients with longer follow-up times may indicate an increased matrix organization of RT. (orig.)

  10. Biodegradable CSMA/PECA/Graphene Porous Hybrid Scaffold for Cartilage Tissue Engineering

    OpenAIRE

    Liao, Jinfeng; Qu, Ying; Chu, BingYang; Zhang, Xiaoning; Qian, ZhiYong

    2015-01-01

    Owing to the limited repair capacity of articular cartilage, it is essential to develop tissue-engineered cartilage for patients suffering from joint disease and trauma. Herein, we prepared a novel hybrid scaffold composed of methacrylated chondroitin sulfate (CSMA), poly(ethylene glycol) methyl ether-ε-caprolactone-acryloyl chloride (MPEG-PCL-AC, PECA was used as abbreviation for MPEG-PCL-AC) and graphene oxide (GO) and evaluated its potential application in cartilage tissue engineering. To ...

  11. Improved cartilage repair via in vitro pre-maturation of MSC-seeded hyaluronic acid hydrogels

    International Nuclear Information System (INIS)

    Functional repair of focal cartilage defects requires filling the space with neotissue that has compressive properties comparable to native tissue and integration with adjacent host cartilage. While poor integration is a common complication with current clinical treatments, reports of tissue engineering advances in the development of functional compressive properties rarely include analyses of their potential for integration. Our objective was thus to assess both the maturation and integration of mesenchymal stem cell (MSC)-laden hyaluronic acid (HA) hydrogels in an in vitro cartilage defect model. Furthermore, we considered the effects of an initial period of pre-maturation as well as various material formulations to maximize both construct compressive properties and integration strength. MSCs were encapsulated in 1%, 3% and 5% methacrylated HA (MeHA) or 2% agarose (Ag) and gelled directly (in situ) within an in vitro cartilage defect or were formed and then pre-cultured for 4 weeks before implantation. Results showed that the integration strength of pre-cultured repair constructs was equal to (1% MeHA) or greater than (2% Ag) the integration of in situ repaired cartilage. Moreover, MSC chondrogenesis and maturation was restricted by the in situ repair environment with constructs maturing to a much lesser extent than pre-matured constructs. These results indicate that construct pre-maturation may be an essential element of functional cartilage repair. (paper)

  12. Fibrin for tissue engineering of cartilage

    OpenAIRE

    Eyrich, Daniela

    2006-01-01

    Since the beginning of the 1990s a plethora of research approaches towards cartilage engineering for plastic and reconstructive surgery have been undertaken. However, a general standard method for generation of cartilage tissue equivalent is still lacking. The goal of this thesis is based on the project �Bavarian Research Cooperation for Tissue Engineering and Rapid Prototyping� (ForTEPro) for development of individually customized implants for facial and reconstructive surgery. The main o...

  13. Articular cartilage: from formation to tissue engineering.

    Science.gov (United States)

    Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

    2016-05-26

    Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue. PMID:26923076

  14. Evaluation of nasal cartilage using three-dimensional soft tissue images in patients with unilateral cleft lip

    International Nuclear Information System (INIS)

    In the treatment of nasal deformities associated with cleft lip and palate, deformities of the alar cartilage and upper lateral cartilage are usually repaired. It is very useful if deformities of the nasal cartilage are evaluated preoperatively. We created three-dimensional CT images of soft tissues by the volume rendering method, the nasal cartilage. In 26 patients with unilateral cleft lip and palate, the alar cartilage, upper lateral cartilage, and septal cartilage were evaluated morphologically. As a result, in each case, these cartilages were deviated and deformed. However, the size of both the alar cartilage and the upper lateral cartilage on the cleft side were approximately similar to those on the healthy side. It is suggested that using this method formulated for the imaging of cartilaginous morphology, preoperative planning and follow-up can be performed easily. (author)

  15. Experimental articular cartilage repair in the Göttingen minipig

    DEFF Research Database (Denmark)

    Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke;

    2015-01-01

    BACKGROUND: A gold standard treatment for articular cartilage injuries is yet to be found, and a cost-effective and predictable large animal model is needed to bridge the gap between in vitro studies and clinical studies. Ideally, the animal model should allow for testing of clinically relevant...... treatments and the biological response should be reproducible and comparable to humans. This allows for a reliable translation of results to clinical studies.This study aimed at verifying the Göttingen minipig as a pre-clinical model for articular cartilage repair by testing existing clinical cartilage...

  16. Effects of low-intensity pulsed ultrasound in repairing injured articular cartilage

    Institute of Scientific and Technical Information of China (English)

    JIA Xiao-lin; CHEN Wen-zhi; ZHOU Kun; WANG Zhi-biao

    2005-01-01

    Objective: To investigate the effects of low-intensity pulsed ultrasound in repairing injured articular cartilage. Methods: Ten adult New Zealand rabbits with bilateral full-thickness osteochondral defects on the cartilage surface of intercondylar fossas were used in this study. The wounds in the left knees were treated with low-intensity pulsed ultrasound as the experimental group. The right knees received no treatment as the control group. All the animals were killed at 8 weeks after injury and the tissues in the wounds were collected for gross appearance grading, histological grading and proteoglycan quantity. Results: The scores of the gross appearance grades, histological grades and the optical density of toluidine blue of the tissues in the experimental group were significantly higher than those of the controls at 8 weeks after injury (P<0.05). Conclusions: Low-intensity pulsed ultrasound can accelerate the repair of injured articular cartilage.

  17. Tissue engineering of cartilage in space

    OpenAIRE

    Freed, Lisa E.; Langer, Robert; Martin, Ivan; Pellis, Neal R.; Vunjak-Novakovic, Gordana

    1997-01-01

    Tissue engineering of cartilage, i.e., the in vitro cultivation of cartilage cells on synthetic polymer scaffolds, was studied on the Mir Space Station and on Earth. Specifically, three-dimensional cell-polymer constructs consisting of bovine articular chondrocytes and polyglycolic acid scaffolds were grown in rotating bioreactors, first for 3 months on Earth and then for an additional 4 months on either Mir (10−4–10−6 g) or Earth (1 g). This mission provided a unique opportunity to study the...

  18. Tissue engineering of cartilages using biomatrices

    DEFF Research Database (Denmark)

    Melrose, J.; Chuang, C.; Whitelock, J.

    2008-01-01

    cartilage engineering approaches and many of these are discussed and their in vitro and in vivo applications covered in this review. Tissue engineering is entering an exciting era; significant advances have been made; however, many technical challenges remain to be solved before this technology becomes......Tissue engineering is an exciting new cross-disciplinary methodology which applies the principles of engineering and structure-function relationships between normal and pathological tissues to develop biological substitute to restore, maintain or improve tissue function. Tissue engineering...

  19. Polymers in Cartilage Defect Repair of the Knee: Current Status and Future Prospects

    Directory of Open Access Journals (Sweden)

    Ralph M. Jeuken

    2016-06-01

    Full Text Available Cartilage defects in the knee are often seen in young and active patients. There is a need for effective joint preserving treatments in patients suffering from cartilage defects, as untreated defects often lead to osteoarthritis. Within the last two decades, tissue engineering based techniques using a wide variety of polymers, cell sources, and signaling molecules have been evaluated. We start this review with basic background information on cartilage structure, its intrinsic repair, and an overview of the cartilage repair treatments from a historical perspective. Next, we thoroughly discuss polymer construct components and their current use in commercially available constructs. Finally, we provide an in-depth discussion about construct considerations such as degradation rates, cell sources, mechanical properties, joint homeostasis, and non-degradable/hybrid resurfacing techniques. As future prospects in cartilage repair, we foresee developments in three areas: first, further optimization of degradable scaffolds towards more biomimetic grafts and improved joint environment. Second, we predict that patient-specific non-degradable resurfacing implants will become increasingly applied and will provide a feasible treatment for older patients or failed regenerative treatments. Third, we foresee an increase of interest in hybrid construct, which combines degradable with non-degradable materials.

  20. Use of Adult Stem Cells for Cartilage Tissue Engineering: Current Status and Future Developments

    Directory of Open Access Journals (Sweden)

    Catherine Baugé

    2015-01-01

    Full Text Available Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. So, in recent years, researchers and surgeons have been working hard to elaborate cartilage repair interventions for patients who suffer from cartilage damage. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or hypertrophic cartilage. In the next years, the development of new strategies using adult stem cells, in scaffolds, with supplementation of culture medium and/or culture in low oxygen tension should improve the quality of neoformed cartilage. Through these solutions, some of the latest technologies start to bring very promising results in repairing cartilage from traumatic injury or chondropathies. This review discusses the current knowledge about the use of adult stem cells in the context of cartilage tissue engineering and presents clinical trials in progress, as well as in the future, especially in the field of bioprinting stem cells.

  1. Optimization and translation of MSC-based hyaluronic acid hydrogels for cartilage repair

    Science.gov (United States)

    Erickson, Isaac E.

    2011-12-01

    Traumatic injury and disease disrupt the ability of cartilage to carry joint stresses and, without an innate regenerative response, often lead to degenerative changes towards the premature development of osteoarthritis. Surgical interventions have yet to restore long-term mechanical function. Towards this end, tissue engineering has been explored for the de novo formation of engineered cartilage as a biologic approach to cartilage repair. Research utilizing autologous chondrocytes has been promising, but clinical limitations in their yield have motivated research into the potential of mesenchymal stem cells (MSCs) as an alternative cell source. MSCs are multipotent cells that can differentiate towards a chondrocyte phenotype in a number of biomaterials, but no combination has successfully recapitulated the native mechanical function of healthy articular cartilage. The broad objective of this thesis was to establish an MSC-based tissue engineering approach worthy of clinical translation. Hydrogels are a common class of biomaterial used for cartilage tissue engineering and our initial work demonstrated the potential of a photo-polymerizable hyaluronic acid (HA) hydrogel to promote MSC chondrogenesis and improved construct maturation by optimizing macromer and MSC seeding density. The beneficial effects of dynamic compressive loading, high MSC density, and continuous mixing (orbital shaker) resulted in equilibrium modulus values over 1 MPa, well in range of native tissue. While compressive properties are crucial, clinical translation also demands that constructs stably integrate within a defect. We utilized a push-out testing modality to assess the in vitro integration of HA constructs within artificial cartilage defects. We established the necessity for in vitro pre-maturation of constructs before repair to achieve greater integration strength and compressive properties in situ. Combining high MSC density and gentle mixing resulted in integration strength over 500 k

  2. A Novel Biodegradable Polyurethane Matrix for Auricular Cartilage Repair: An In Vitro and In Vivo Study.

    Science.gov (United States)

    Iyer, Kartik; Dearman, Bronwyn L; Wagstaff, Marcus J D; Greenwood, John E

    2016-01-01

    Auricular reconstruction poses a challenge for reconstructive and burns surgeons. Techniques involving cartilage tissue engineering have shown potential in recent years. A biodegradable polyurethane matrix developed for dermal reconstruction offers an alternative to autologous, allogeneic, or xenogeneic biologicals for cartilage reconstruction. This study assesses such a polyurethane matrix for this indication in vivo and in vitro. To evaluate intrinsic cartilage repair, three pigs underwent auricular surgery to create excisional cartilage ± perichondrial defects, measuring 2 × 3 cm in each ear, into which acellular polyurethane matrices were implanted. Biopsies were taken at day 28 for histological assessment. Porcine chondrocytes ± perichondrocytes were cultured and seeded in vitro onto 1 × 1 cm polyurethane scaffolds. The total culture period was 42 days; confocal, histological, and immunohistochemical analyses of scaffold cultures were performed on days 14, 28, and 42. In vivo, the polyurethane matrices integrated with granulation tissue filling all biopsy samples. Minimal neocartilage invasion was observed marginally on some samples. Tissue composition was identical between ears whether perichondrium was left intact, or not. In vitro, the polyurethane matrix was biocompatible with chondrocytes ± perichondrocytes and supported production of extracellular matrix and Type II collagen. No difference was observed between chondrocyte culture alone and chondrocyte/perichondrocyte scaffold coculture. The polyurethane matrix successfully integrated into the auricular defect and was a suitable scaffold in vitro for cartilage tissue engineering, demonstrating its potential application in auricular reconstruction. PMID:26284639

  3. Bioprinted Scaffolds for Cartilage Tissue Engineering.

    Science.gov (United States)

    Kang, Hyun-Wook; Yoo, James J; Atala, Anthony

    2015-01-01

    Researchers are focusing on bioprinting technology as a viable option to overcome current difficulties in cartilage tissue engineering. Bioprinting enables a three-dimensional (3-D), free-form, computer-designed structure using biomaterials, biomolecules, and/or cells. The inner and outer shape of a scaffold can be controlled by this technology with great precision. Here, we introduce a hybrid bioprinting technology that is a co-printing process of multiple materials including high-strength synthetic polymer and cell-laden hydrogel. The synthetic polymer provides mechanical support for shape maintenance and load bearing, while the hydrogel provides the biological environment for artificial cartilage regeneration. This chapter introduces the procedures for printing of a 3-D scaffold using our hybrid bioprinting technology and includes the source materials for preparation of 3-D printing. PMID:26445837

  4. Extracorporeal shockwave therapy promotes chondrogenesis in cartilage tissue engineering: A hypothesis based on previous evidence.

    Science.gov (United States)

    Ji, Qiaodan; He, Chengqi

    2016-06-01

    The dearth of intrinsic regenerative capacity of articular cartilage makes it a challenge to deal with the cartilage defects. Among all the recommended clinical options, cartilage tissue engineering (CTE) which is highlighted of dominant features and less drawbacks for functional cartilage restoration, has been emphasized recently. Shock waves, a mode of therapeutic mechanical forces, utilized in extracorporeal shockwave therapy (ESWT), is hypothesized to enhance proliferation, chondrogenic differentiation, and cartilage extracellular matrix production of target cells seeded on bioactive scaffolds. The hypothesis is firstly based on cellular mechanotransduction by which cells convent the shockwave mechanical signals into biochemical responses via integrins, iron channels, cytoskeletal filaments, growth factor receptors and nuclei. Secondly, by modulating gene expression and up-regulating the release of various growth factors which are of vital importance in three-dimensional cartilage culture environment, ESWT holds a promising potential to favor the cell sources (e.g. chondrocytes and stem cells) to mimic the optimal functional cartilage. In all, on the basis of cellular mechanotransduction and previous evidence, the hypothesis is developed to support the beneficial effects of ESWT on chondrogenesis in CTE. If this hypothesis is confirmed, shockwaves may allow a better success in combination with other stimulating factors for cartilage repair. There is a paucity of studies investigating the assistant role of shockwave stimulation in CTE. Further research is required to elucidate the mechanisms, and explore effectiveness and appropriate protocols of this novel stimulative factor in cartilage tissue engineering. PMID:27142133

  5. Bone Cysts After Osteochondral Allograft Repair of Cartilage Defects in Goats Suggest Abnormal Interaction Between Subchondral Bone and Overlying Synovial Joint Tissues

    OpenAIRE

    Pallante-Kichura, Andrea L.; Cory, Esther; Bugbee, William D.; Sah, Robert L.

    2013-01-01

    The efficacy of osteochondral allografts (OCA) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12 months in vivo. The ob...

  6. Composite Scaffolds for Cartilage Tissue Engineering

    OpenAIRE

    Moutos, Franklin T.; Guilak, Farshid

    2008-01-01

    Tissue engineering remains a promising therapeutic strategy for the repair or regeneration of diseased or damaged tissues. Previous approaches have typically focused on combining cells and bioactive molecules (e.g., growth factors, cytokines, and DNA fragments) with a biomaterial scaffold that function as a template to control the geometry of the newly formed tissue, while facilitating the attachment, proliferation, and differentiation of embedded cells. Biomaterial scaffolds also play a cruc...

  7. PLGA-based microcarriers induce mesenchymal stem cell chondrogenesis and stimulate cartilage repair in osteoarthritis.

    Science.gov (United States)

    Morille, Marie; Toupet, Karine; Montero-Menei, Claudia N; Jorgensen, Christian; Noël, Danièle

    2016-05-01

    In the present study, we aimed at evaluating the ability of novel PLGA-P188-PLGA-based microspheres to induce the differentiation of mesenchymal stem/stromal cells (MSC) into chondrocytes. To this aim, we tested microspheres releasing TGFβ3 (PAM-T) in vitro and in situ, in a pathological osteoarthritic (OA) environment. We first evaluated the chondrogenic differentiation of human MSCs seeded onto PAM-T in vitro and confirmed the up-regulation of chondrogenic markers while the secretome of the cells was not changed by the 3D environment. We then injected human MSC seeded onto PAM-T in the knee joints of mice with collagenase-induced OA. After 6 weeks, histological analysis revealed that formation of a cartilage-like tissue occurred at the vicinity of PAM-T that was not observed when MSCs were seeded onto PAM. We also noticed that the endogenous articular cartilage was less degraded. The extent of cartilage protection was further analysed by confocal laser microscopy. When MSCs seeded onto PAM-T were injected early after OA induction, protection of cartilage against degradation was evidenced and this effect was associated to a higher survival of MSCs in presence of TGFβ3. This study points to the interest of using MSCs seeded onto PAM for cartilage repair and stimulation of endogenous cartilage regeneration. PMID:26945456

  8. Cartilage Tissue Engineering: What Have We Learned in Practice?

    Science.gov (United States)

    Doran, Pauline M

    2015-01-01

    Many technologies that underpin tissue engineering as a research field were developed with the aim of producing functional human cartilage in vitro. Much of our practical experience with three-dimensional cultures, tissue bioreactors, scaffold materials, stem cells, and differentiation protocols was gained using cartilage as a model system. Despite these advances, however, generation of engineered cartilage matrix with the composition, structure, and mechanical properties of mature articular cartilage has not yet been achieved. Currently, the major obstacles to synthesis of clinically useful cartilage constructs are our inability to control differentiation to the extent needed, and the failure of engineered and host tissues to integrate after construct implantation. The aim of this chapter is to distil from the large available body of literature the seminal approaches and experimental techniques developed for cartilage tissue engineering and to identify those specific areas requiring further research effort. PMID:26445827

  9. Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair

    OpenAIRE

    Mithoefer, Kai; Saris, Daniel B.F.; Farr, Jack; Kon, Elizaveta; Zaslav, Kenneth; Cole, Brian J.; Ranstam, Jonas; Yao, Jian; Shive, Matthew; Levine, David; Dalemans, Wilfried; Brittberg, Mats

    2011-01-01

    Objective: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. Design: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for t...

  10. A biomimetic three-dimensional woven composite scaffold for functional tissue engineering of cartilage

    Science.gov (United States)

    Moutos, Franklin T.; Freed, Lisa E.; Guilak, Farshid

    2007-02-01

    Tissue engineering seeks to repair or regenerate tissues through combinations of implanted cells, biomaterial scaffolds and biologically active molecules. The rapid restoration of tissue biomechanical function remains an important challenge, emphasizing the need to replicate structural and mechanical properties using novel scaffold designs. Here we present a microscale 3D weaving technique to generate anisotropic 3D woven structures as the basis for novel composite scaffolds that are consolidated with a chondrocyte-hydrogel mixture into cartilage tissue constructs. Composite scaffolds show mechanical properties of the same order of magnitude as values for native articular cartilage, as measured by compressive, tensile and shear testing. Moreover, our findings showed that porous composite scaffolds could be engineered with initial properties that reproduce the anisotropy, viscoelasticity and tension-compression nonlinearity of native articular cartilage. Such scaffolds uniquely combine the potential for load-bearing immediately after implantation in vivo with biological support for cell-based tissue regeneration without requiring cultivation in vitro.

  11. A stem cell-based approach to cartilage repair.

    Science.gov (United States)

    Johnson, Kristen; Zhu, Shoutian; Tremblay, Matthew S; Payette, Joshua N; Wang, Jianing; Bouchez, Laure C; Meeusen, Shelly; Althage, Alana; Cho, Charles Y; Wu, Xu; Schultz, Peter G

    2012-05-11

    Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (median effective concentration = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor β subunit (CBFβ), and induces chondrogenesis by regulating the CBFβ-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis. PMID:22491093

  12. Hyaluronic Acid-Binding Scaffold for Articular Cartilage Repair

    OpenAIRE

    Unterman, Shimon A.; Gibson, Matthew; Lee, Janice H.; Crist, Joshua; Chansakul, Thanissara; Yang, Elaine C.; Jennifer H. Elisseeff

    2012-01-01

    Hyaluronic acid (HA) is an extracellular matrix molecule with multiple physical and biological functions found in many tissues, including cartilage. HA has been incorporated in a number of biomaterial and scaffold systems. Howegver, HA in the material may be difficult to control if it is not chemically modified and chemical modification of HA may negatively impact biological function. In this study, we developed a poly(ethylene glycol) hydrogel with noncovalent HA-binding capabilities and eva...

  13. Effect of nitric oxide synthase inhibitor on proteoglycan metabolism in repaired articular cartilage in rabbits

    Institute of Scientific and Technical Information of China (English)

    孙炜; 金大地; 王吉兴; 秦立赟; 刘晓霞

    2003-01-01

    Objective: To study the effect of nitric oxide synthase inhibitor, S-methyl thiocarbamate (SMT), on proteoglycan metabolism in repaired articular cartilage in rabbits. Methods: Twenty-four male New Zealand white rabbits, aged 8 months and weighing 2.5 kg±0.2 kg, were used in this study. Cartilage defects in full thickness were created on the intercondylar articular surface of bilateral femurs of all the rabbits. Then the rabbits were randomly divided into 3 groups (n=8 in each group). The defects in one group were filled with fibrin glue impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2, BMP group), in one group with fibrin glue impregnated with rhBMP-2 and hypodermic injection with SMT (SMT group) and in the other group with nothing (control group). All the animals were killed at one year postoperatively. The tissue sections were stained with safranine O-fast green and analyzed by Quantiment 500 system to determine the content of glycosaminoglycan through measuring the percentage of safranine O-stained area, the thickness of cartilages and the mean gray scale (average stain intensity). Radiolabelled sodium sulphate (Na235SO4) was used to assess the proteoglycan synthesis. Results: At one year postoperatively, the percentage of safranine O-stained area, the mean gray scale and the cartilage thickness of the repaired tissues in SMT group were significantly higher than those of BMP group (P<0.01) and the control group (P<0.05). Result of incorporation of Na235SO4 showed that the proteoglycan synthesis in SMT group was higher than those of BMP group and the control group (P<0.01). Conclusions: SMT, a nitric oxide synthase inhibitor, can significantly increase the content of glycosaminoglycan and proteoglycan synthesis, and computer-based image analysis is a reliable method for evaluating proteoglycan metabolism.

  14. Cartilage tissue engineering: towards a biomaterial-assisted mesenchymal stem cell therapy

    Science.gov (United States)

    Vinatier, Claire; Bouffi, Carine; Merceron, Christophe; Gordeladze, Jan; Brondello, Jean-Marc; Jorgensen, Christian; Weiss, Pierre; Guicheux, Jérôme; Noël, Danièle

    2009-01-01

    Injuries to articular cartilage are one of the most challenging issues of musculoskeletal medicine due to the poor intrinsic ability of this tissue for repair. Despite progress in orthopaedic surgery, the lack of efficient modalities of treatment for large chondral defects has prompted research on tissue engineering combining chondrogenic cells, scaffold materials and environmental factors. The aim of this review is to focus on the recent advances made in exploiting the potentials of cell therapy for cartilage engineering. These include: 1) defining the best cell candidates between chondrocytes or multipotent progenitor cells, such as multipotent mesenchymal stromal cells (MSC), in terms of readily available sources for isolation, expansion and repair potential; 2) engineering biocompatible and biodegradable natural or artificial matrix scaffolds as cell carriers, chondrogenic factors releasing factories and supports for defect filling, 3) identifying more specific growth factors and the appropriate scheme of application that will promote both chondrogenic differentiation and then maintain the differentiated phenotype overtime and 4) evaluating the optimal combinations that will answer to the functional demand placed upon cartilage tissue replacement in animal models and in clinics. Finally, some of the major obstacles generally encountered in cartilage engineering are discussed as well as future trends to overcome these limiting issues for clinical applications. PMID:19804369

  15. Articular chondrocytes and mesenchymal stem cells seeded on biodegradable scaffolds for the repair of cartilage in a rat osteochondral defect model.

    Science.gov (United States)

    Dahlin, Rebecca L; Kinard, Lucas A; Lam, Johnny; Needham, Clark J; Lu, Steven; Kasper, F Kurtis; Mikos, Antonios G

    2014-08-01

    This work investigated the ability of co-cultures of articular chondrocytes and mesenchymal stem cells (MSCs) to repair articular cartilage in osteochondral defects. Bovine articular chondrocytes and rat MSCs were seeded in isolation or in co-culture onto electrospun poly(ɛ-caprolactone) (PCL) scaffolds and implanted into an osteochondral defect in the trochlear groove of 12-week old Lewis rats. Additionally, a blank PCL scaffold and untreated defect were investigated. After 12 weeks, the extent of cartilage repair was analyzed through histological analysis, and the extent of bone healing was assessed by quantifying the total volume of mineralized bone in the defect through microcomputed tomography. Histological analysis revealed that the articular chondrocytes and co-cultures led to repair tissue that consisted of more hyaline-like cartilage tissue that was thicker and possessed more intense Safranin O staining. The MSC, blank PCL scaffold, and empty treatment groups generally led to the formation of fibrocartilage repair tissue. Microcomputed tomography revealed that while there was an equivalent amount of mineralized bone formation in the MSC, blank PCL, and empty treatment groups, the defects treated with chondrocytes or co-cultures had negligible mineralized bone formation. Overall, even with a reduced number of chondrocytes, co-cultures led to an equal level of cartilage repair compared to the chondrocyte samples, thus demonstrating the potential for the use of co-cultures of articular chondrocytes and MSCs for the in vivo repair of cartilage defects. PMID:24927682

  16. The use of dynamic culture devices in articular cartilage tissue engineering.

    OpenAIRE

    Akmal, M.

    2006-01-01

    Tissue engineered repair of articular cartilage has now become a clinical reality with techniques for cell culture having advanced from laboratory experimentation to clinical application. Despite the advances in the use of this technology in clinical applications, the basic cell culture techniques for autologous chondrocytes are still based on primitive in-vitro monolayer culture methods. Articular chondrocytes are known to undergo fibroblastic change in monolayer culture as this is not their...

  17. Articular cartilage repair with recombinant human type II collagen/polylactide scaffold in a preliminary porcine study.

    Science.gov (United States)

    Muhonen, Virpi; Salonius, Eve; Haaparanta, Anne-Marie; Järvinen, Elina; Paatela, Teemu; Meller, Anna; Hannula, Markus; Björkman, Mimmi; Pyhältö, Tuomo; Ellä, Ville; Vasara, Anna; Töyräs, Juha; Kellomäki, Minna; Kiviranta, Ilkka

    2016-05-01

    The purpose of this study was to investigate the potential of a novel recombinant human type II collagen/polylactide scaffold (rhCo-PLA) in the repair of full-thickness cartilage lesions with autologous chondrocyte implantation technique (ACI). The forming repair tissue was compared to spontaneous healing (spontaneous) and repair with a commercial porcine type I/III collagen membrane (pCo). Domestic pigs (4-month-old, n = 20) were randomized into three study groups and a circular full-thickness chondral lesion with a diameter of 8 mm was created in the right medial femoral condyle. After 3 weeks, the chondral lesions were repaired with either rhCo-PLA or pCo together with autologous chondrocytes, or the lesion was only debrided and left untreated for spontaneous repair. The repair tissue was evaluated 4 months after the second operation. Hyaline cartilage formed most frequently in the rhCo-PLA treatment group. Biomechanically, there was a trend that both treatment groups resulted in better repair tissue than spontaneous healing. Adverse subchondral bone reactions developed less frequently in the spontaneous group (40%) and the rhCo-PLA treated group (50%) than in the pCo control group (100%). However, no statistically significant differences were found between the groups. The novel rhCo-PLA biomaterial showed promising results in this proof-of-concept study, but further studies will be needed in order to determine its effectiveness in articular cartilage repair. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:745-753, 2016. PMID:26573959

  18. Image-Guided Techniques Improve the Short-Term Outcome of Autologous Osteochondral Cartilage Repair Surgeries

    OpenAIRE

    Kunz, Manuela; Devlin, Steven M.; Hurtig, Mark B.; Waldman, Stephen D.; Rudan, John F.; Bardana, Davide D.; Stewart, A. James

    2013-01-01

    Objective: Autologous osteochondral cartilage repair is a valuable reconstruction option for cartilage defects, but the accuracy to harvest and deliver osteochondral grafts remains problematic. We investigated whether image-guided methods (optically guided and template guided) can improve the outcome of these procedures. Design: Fifteen sheep were operated to create traumatic chondral injuries in each knee. After 4 months, the chondral defect in one knee was repaired using (a) conventional ap...

  19. Expandable Scaffold Improves Integration of Tissue-Engineered Cartilage: An In Vivo Study in a Rabbit Model.

    Science.gov (United States)

    Wang, Chen-Chie; Yang, Kai-Chiang; Lin, Keng-Hui; Liu, Yen-Liang; Yang, Ya-Ting; Kuo, Tzong-Fu; Chen, Ing-Ho

    2016-06-01

    One of the major limitations of tissue-engineered cartilage is poor integration of chondrocytes and scaffold structures with recipient tissue. To overcome this limitation, an expandable scaffold with a honeycomb-like structure has been developed using microfluidic technology. In this study, we evaluated the performance of this expandable gelatin scaffold seeded with rabbit chondrocytes in vivo. The chondrocyte/scaffold constructs were implanted into regions of surgically introduced cylindrical osteochondral defects in rabbit femoral condyles. At 2, 4, and 6 months postsurgery, the implanted constructs were evaluated by gross and histological examinations. As expected, the osteochondral defects, which were untreated or transplanted with blank scaffolds, showed no signs of repair, whereas the defects transplanted with chondrocyte/scaffold constructs showed significant cartilage regeneration. Furthermore, the expandable scaffolds seeded with chondrocytes had more regenerated cartilage tissue and better integration with the recipient tissue than autologous chondrocyte implantation. Biomechanical tests revealed that the chondrocyte/scaffold group had the highest compressive strength among all groups at all three time points and endured a similar compressive force to normal cartilage after 6 months of implantation. Histological examinations revealed that the chondrocytes were distributed uniformly within the scaffolds, maintained a normal phenotype, and secreted functional components of the extracellular matrix. Histomorphometric assessment showed a remarkable total interface of up to 87% integration of the expandable scaffolds with the host tissue at 6 months postoperation. In conclusion, the expandable scaffolds improved chondrocyte/scaffold construct integration with the host tissue and were beneficial for cartilage repair. PMID:27193498

  20. Computational model for the analysis of cartilage and cartilage tissue constructs.

    Science.gov (United States)

    Smith, David W; Gardiner, Bruce S; Davidson, John B; Grodzinsky, Alan J

    2016-04-01

    We propose a new non-linear poroelastic model that is suited to the analysis of soft tissues. In this paper the model is tailored to the analysis of cartilage and the engineering design of cartilage constructs. The proposed continuum formulation of the governing equations enables the strain of the individual material components within the extracellular matrix (ECM) to be followed over time, as the individual material components are synthesized, assembled and incorporated within the ECM or lost through passive transport or degradation. The material component analysis developed here naturally captures the effect of time-dependent changes of ECM composition on the deformation and internal stress states of the ECM. For example, it is shown that increased synthesis of aggrecan by chondrocytes embedded within a decellularized cartilage matrix initially devoid of aggrecan results in osmotic expansion of the newly synthesized proteoglycan matrix and tension within the structural collagen network. Specifically, we predict that the collagen network experiences a tensile strain, with a maximum of ~2% at the fixed base of the cartilage. The analysis of an example problem demonstrates the temporal and spatial evolution of the stresses and strains in each component of a self-equilibrating composite tissue construct, and the role played by the flux of water through the tissue. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23784936

  1. Computational model for the analysis of cartilage and cartilage tissue constructs

    Science.gov (United States)

    Smith, David W.; Gardiner, Bruce S.; Davidson, John B.; Grodzinsky, Alan J.

    2013-01-01

    We propose a new non-linear poroelastic model that is suited to the analysis of soft tissues. In this paper the model is tailored to the analysis of cartilage and the engineering design of cartilage constructs. The proposed continuum formulation of the governing equations enables the strain of the individual material components within the extracellular matrix (ECM) to be followed over time, as the individual material components are synthesized, assembled and incorporated within the ECM or lost through passive transport or degradation. The material component analysis developed here naturally captures the effect of time-dependent changes of ECM composition on the deformation and internal stress states of the ECM. For example, it is shown that increased synthesis of aggrecan by chondrocytes embedded within a decellularized cartilage matrix initially devoid of aggrecan results in osmotic expansion of the newly synthesized proteoglycan matrix and tension within the structural collagen network. Specifically, we predict that the collagen network experiences a tensile strain, with a maximum of ~2% at the fixed base of the cartilage. The analysis of an example problem demonstrates the temporal and spatial evolution of the stresses and strains in each component of a self-equilibrating composite tissue construct, and the role played by the flux of water through the tissue. PMID:23784936

  2. Cartilage Repair and Subchondral Bone Migration Using 3D Printing Osteochondral Composites: A One-Year-Period Study in Rabbit Trochlea

    Directory of Open Access Journals (Sweden)

    Weijie Zhang

    2014-01-01

    Full Text Available Increasing evidences show that subchondral bone may play a significant role in the repair or progression of cartilage damage in situ. However, the exact change of subchondral bone during osteochondral repair is still poorly understood. In this paper, biphasic osteochondral composite scaffolds were fabricated by 3D printing technology using PEG hydrogel and β-TCP ceramic and then implanted in rabbit trochlea within a critical size defect model. Animals were euthanized at 1, 2, 4, 8, 16, 24, and 52 weeks after implantation. Histological results showed that hyaline-like cartilage formed along with white smooth surface and invisible margin at 24 weeks postoperatively, typical tidemark formation at 52 weeks. The repaired subchondral bone formed from 16 to 52 weeks in a “flow like” manner from surrounding bone to the defect center gradually. Statistical analysis illustrated that both subchondral bone volume and migration area percentage were highly correlated with the gross appearance Wayne score of repaired cartilage. Therefore, subchondral bone migration is related to cartilage repair for critical size osteochondral defects. Furthermore, the subchondral bone remodeling proceeds in a “flow like” manner and repaired cartilage with tidemark implies that the biphasic PEG/β-TCP composites fabricated by 3D printing provides a feasible strategy for osteochondral tissue engineering application.

  3. Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair: International Cartilage Repair Society Recommendations Based on Current Scientific Evidence and Standards of Clinical Care

    OpenAIRE

    Mithoefer, Kai; Saris, Daniel B.F.; Farr, Jack; Kon, Elizaveta; Zaslav, Kenneth; Cole, Brian J.; Ranstam, Jonas; Yao, Jian; Shive, Matthew; Levine, David; Dalemans, Wilfried; Brittberg, Mats

    2011-01-01

    Objective: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. Design: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for t...

  4. Comparison of ultrasound and optical coherence tomography techniques for evaluation of integrity of spontaneously repaired horse cartilage.

    Science.gov (United States)

    Virén, T; Huang, Y P; Saarakkala, S; Pulkkinen, H; Tiitu, V; Linjama, A; Kiviranta, I; Lammi, M J; Brünott, A; Brommer, H; Van Weeren, R; Brama, P A J; Zheng, Y P; Jurvelin, J S; Töyräs, J

    2012-04-01

    The aim of this study was to compare sensitivity of ultrasound and optical coherence tomography (OCT) techniques for the evaluation of the integrity of spontaneously repaired horse cartilage. Articular surfaces of horse intercarpal joints, featuring both intact tissue and spontaneously healed chondral or osteochondral defects, were imaged ex vivo with arthroscopic ultrasound and laboratory OCT devices. Quantitative ultrasound (integrated reflection coefficient (IRC), apparent integrated backscattering coefficient (AIB) and ultrasound roughness index (URI)) and optical parameters (optical reflection coefficient (ORC), optical roughness index (ORI) and optical backscattering (OBS)) were determined and compared with histological integrity and mechanical properties of the tissue. Spontaneously healed tissue could be quantitatively discerned from the intact tissue with ultrasound and OCT techniques. Furthermore, several significant correlations (p < 0.05) were detected between ultrasound and OCT parameters. Superior resolution of OCT provided a more accurate measurement of cartilage surface roughness, while the ultrasound backscattering from the inner structures of the cartilage matched better with the histological findings. Since the techniques were found to be complementary to each other, dual modality imaging techniques could provide a useful tool for the arthroscopic evaluation of the integrity of articular cartilage. PMID:22439802

  5. Dedifferentiated Human Articular Chondrocytes Redifferentiate to a Cartilage-Like Tissue Phenotype in a Poly(ε-Caprolactone)/Self-Assembling Peptide Composite Scaffold

    OpenAIRE

    Lourdes Recha-Sancho; Moutos, Franklin T.; Jordi Abellà; Farshid Guilak; Semino, Carlos E.

    2016-01-01

    Adult articular cartilage has a limited capacity for growth and regeneration and, with injury, new cellular or biomaterial-based therapeutic platforms are required to promote repair. Tissue engineering aims to produce cartilage-like tissues that recreate the complex mechanical and biological properties found in vivo. In this study, a unique composite scaffold was developed by infiltrating a three-dimensional (3D) woven microfiber poly (ε-caprolactone) (PCL) scaffold with the RAD16-I self-asse...

  6. Kartogenin induces cartilage-like tissue formation in tendon–bone junction

    Science.gov (United States)

    Zhang, Jianying; Wang, James H-C

    2014-01-01

    Tendon–bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs. PMID:25419468

  7. Kartogenin induces cartilage-like tissue formation in tendon-bone junction

    Institute of Scientific and Technical Information of China (English)

    Jianying Zhang; James H-C Wang

    2014-01-01

    Tendon-bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs.

  8. Kartogenin induces cartilage-like tissue formation in tendon-bone junction.

    Science.gov (United States)

    Zhang, Jianying; Wang, James H-C

    2014-01-01

    Tendon-bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs. PMID:25419468

  9. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Mirahmadi, Fereshteh [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad, E-mail: Tafazoli@aut.ac.ir [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali, E-mail: mashokrgozar@pasteur.ac.ir [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Bonakdar, Shahin [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of)

    2013-12-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds.

  10. Image-Guided Techniques Improve the Short-Term Outcome of Autologous Osteochondral Cartilage Repair Surgeries

    Science.gov (United States)

    Devlin, Steven M.; Hurtig, Mark B.; Waldman, Stephen D.; Rudan, John F.; Bardana, Davide D.; Stewart, A. James

    2013-01-01

    Objective: Autologous osteochondral cartilage repair is a valuable reconstruction option for cartilage defects, but the accuracy to harvest and deliver osteochondral grafts remains problematic. We investigated whether image-guided methods (optically guided and template guided) can improve the outcome of these procedures. Design: Fifteen sheep were operated to create traumatic chondral injuries in each knee. After 4 months, the chondral defect in one knee was repaired using (a) conventional approach, (b) optically guided method, or (c) template-guided method. For both image-guided groups, harvest and delivery sites were preoperatively planned using custom-made software. During optically guided surgery, instrument position and orientation were tracked and superimposed onto the surgical plan. For the template-guided group, plastic templates were manufactured to allow an exact fit between template and the joint anatomy. Cylindrical holes within the template guided surgical tools according to the plan. Three months postsurgery, both knees were harvested and computed tomography scans were used to compare the reconstructed versus the native pre-injury joint surfaces. For each repaired defect, macroscopic (International Cartilage Repair Society [ICRS]) and histological repair (ICRS II) scores were assessed. Results: Three months after repair surgery, both image-guided surgical approaches resulted in significantly better histology scores compared with the conventional approach (improvement by 55%, P < 0.02). Interestingly, there were no significant differences found in cartilage surface reconstruction and macroscopic scores between the image-guided and the conventional surgeries. PMID:26069658

  11. Development and potential of a biomimetic chitosan/type Ⅱ collagen scaffold for cartilage tissue engineering

    Institute of Scientific and Technical Information of China (English)

    SHI De-hai; CAI Dao-zhang; ZHOU Chang-ren; RONG Li-min; WANG Kun; XU Yi-chun

    2005-01-01

    Background Damaged articular cartilage has very limited capacity for spontaneous healing. Tissue engineering provides a new hope for functional cartilage repair. Creation of an appropriate cell carrier is one of the critical steps for successful tissue engineering. With the supposition that a biomimetic construct might promise to generate better effects, we developed a novel composite scaffold and investigated its potential for cartilage tissue engineering. Methods Chitosan of 88% deacetylation was prepared via a modified base reaction procedure. A freeze-drying process was employed to fabricate a three-dimensional composite scaffold consisting of chitosan and type Ⅱcollagen. The scaffold was treated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. Ultrastructure and tensile strength of the matrix were carried out to assess its physico-chemical properties. After subcutaneous implantation in rabbits, its in vivo biocompatibility and degradability of the scaffold were determined. Its capacity to sustain chondrocyte growth and biosynthesis was evaluated through cell-scaffold co-culture in vitro. Results The fabricated composite matrix was porous and sponge-like with interconnected pores measuring from 100-250 μm in diameter. After cross-linking, the scaffold displayed enhanced tensile strength. Subcutaneous implantation results indicated the composite matrix was biocompatible and biodegradable. In intro cell-scaffold culture showed the scaffold sustained chondrocyte proliferation and differentiation, and maintained the spheric chondrocytic phenotype. As indicated by immunohistochemical staining, the chondrocytes synthesized type Ⅱ collagen. Conclusions Chitosan and type Ⅱ collagen can be well blended and developed into a porous 3-D biomimetic matrix. Results of physico-chemical and biological tests suggest the composite matrix satisfies the constraints specified for a tissue-engineered construct and may be used as a chondrocyte

  12. The development of the collagen fibre network in tissue-engineered cartilage constructs in vivo. Engineered cartilage reorganises fibre network

    Directory of Open Access Journals (Sweden)

    H Paetzold

    2012-04-01

    Full Text Available For long term durability of tissue-engineered cartilage implanted in vivo, the development of the collagen fibre network orientation is essential as well as the distribution of collagen, since expanded chondrocytes are known to synthesise collagen type I. Typically, these properties differ strongly between native and tissue-engineered cartilage. Nonetheless, the clinical results of a pilot study with implanted tissue-engineered cartilage in pigs were surprisingly good. The purpose of this study was therefore to analyse if the structure and composition of the artificial cartilage tissue changes in the first 52 weeks after implantation. Thus, collagen network orientation and collagen type distribution in tissue-engineered cartilage-carrier-constructs implanted in the knee joints of Göttinger minipigs for 2, 26 or 52 weeks have been further investigated by processing digitised microscopy images of histological sections. The comparison to native cartilage demonstrated that fibre orientation over the cartilage depth has a clear tendency towards native cartilage with increasing time of implantation. After 2 weeks, the collagen fibres of the superficial zone were oriented parallel to the articular surface with little anisotropy present in the middle and deep zones. Overall, fibre orientation and collagen distribution within the implants were less homogenous than in native cartilage tissue. Despite a relatively low number of specimens, the consistent observation of a continuous approximation to native tissue is very promising and suggests that it may not be necessary to engineer the perfect tissue for implantation but rather to provide an intermediate solution to help the body to heal itself.

  13. Tissue Engineering of Muscles and Cartilages Using Polyelectrolyte Hydrogels

    OpenAIRE

    Hyuck Joon Kwon

    2014-01-01

    The prevalent nature of osteoarthritis that causes the erosion of joint surfaces and loss of mobility and muscle dystrophy that weakens the musculoskeletal system and hampers locomotion underlies the importance of developing functional replacement or regeneration of muscle and cartilage tissues. Polyelectrolyte gels have high potential as cellular scaffolds due to characteristic properties similar to biological matrixes. A number of in vitro and in vivo studies demonstrated that polyelectroly...

  14. Streamlined bioreactor-based production of human cartilage tissues.

    Science.gov (United States)

    Tonnarelli, B; Santoro, R; Adelaide Asnaghi, M; Wendt, D

    2016-01-01

    Engineered tissue grafts have been manufactured using methods based predominantly on traditional labour-intensive manual benchtop techniques. These methods impart significant regulatory and economic challenges, hindering the successful translation of engineered tissue products to the clinic. Alternatively, bioreactor-based production systems have the potential to overcome such limitations. In this work, we present an innovative manufacturing approach to engineer cartilage tissue within a single bioreactor system, starting from freshly isolated human primary chondrocytes, through the generation of cartilaginous tissue grafts. The limited number of primary chondrocytes that can be isolated from a small clinically-sized cartilage biopsy could be seeded and extensively expanded directly within a 3D scaffold in our perfusion bioreactor (5.4 ± 0.9 doublings in 2 weeks), bypassing conventional 2D expansion in flasks. Chondrocytes expanded in 3D scaffolds better maintained a chondrogenic phenotype than chondrocytes expanded on plastic flasks (collagen type II mRNA, 18-fold; Sox-9, 11-fold). After this "3D expansion" phase, bioreactor culture conditions were changed to subsequently support chondrogenic differentiation for two weeks. Engineered tissues based on 3D-expanded chondrocytes were more cartilaginous than tissues generated from chondrocytes previously expanded in flasks. We then demonstrated that this streamlined bioreactor-based process could be adapted to effectively generate up-scaled cartilage grafts in a size with clinical relevance (50 mm diameter). Streamlined and robust tissue engineering processes, as the one described here, may be key for the future manufacturing of grafts for clinical applications, as they facilitate the establishment of compact and closed bioreactor-based production systems, with minimal automation requirements, lower operating costs, and increased compliance to regulatory guidelines. PMID:27232665

  15. Single-step scaffold-based cartilage repair in the knee: A systematic review.

    Science.gov (United States)

    Fischer, Stefan; Kisser, Agnes

    2016-12-01

    Chondral lesions are difficult-to-treat entities that often affect young and active people. Moreover, cartilage has limited intrinsic healing potential. The purpose of this systematic literature review was to analyse whether the single-step scaffold-based cartilage repair in combination with microfracturing (MFx) is more effective and safe in comparison to MFx alone. From the three identified studies, it seems that the single-step scaffold-assisted cartilage repair in combination with MFx leads to similar short- to medium-term (up to five years follow-up) results, compared to MFx alone. All of the studies have shown improvements regarding joint functionality, pain and partly quality of life. PMID:27408497

  16. A review of decellularized stem cell matrix: a novel cell expansion system for cartilage tissue engineering

    OpenAIRE

    M Pei; Li JT; Shoukry, M; Y Zhang

    2011-01-01

    Cell-based therapy is a promising biological approach for the treatment of cartilage defects. Due to the small size of autologous cartilage samples available for cell transplantation in patients, cells need to be expanded to yield a sufficient cell number for cartilage repair. However, chondrocytes and adult stem cells tend to become replicatively senescent once they are expanded on conventional plastic flasks. Many studies demonstrate that the loss of cell properties is concomitant with the ...

  17. Effect of low-energy shock waves in microfracture holes in the repair of articular cartilage defects in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    WANG Qi; LI Zhong-li; FU Yang-mu; WANG Zhi-gang; WEI Min; ZHAO Bin; ZHANG Li; ZHU Juan-li

    2011-01-01

    Background Microfracture is a type of bone marrow stimulation in arthroscopic cartilage repair. However, the overall concentration of the mesenchymal stem cells is quite low and declines with age, and in the end the lesion is filled by fibrocartilage. The aim of this research was to investigate a novel method of enhancing microfracture by determining whether low-energy shock waves in microfracture holes would facilitate cartilage repair in a rabbit model.Methods Full-thickness cartilage defects were created at the medial femoral condyle of 36 mature New Zealand white rabbits without penetrating subchondral bone. The rabbits were randomly divided into three groups. In experimental group A, low-energy shock-wave therapy was performed in microfracture holes (diameter, 1 mm) at an energy flux density (EFD) of 0.095 m J/mm2 and 200 impulses by DolorClast Master (Electro Medical Systems SA, Switzerland)microprobe (diameter, 0.8 mm). In experimental group B, microfracture was performed alone. The untreated rabbits served as a control group. At 4, 8, and 12 weeks after the operations, repair tissues at the defects were analyzed stereologically, histologically, and immunohistochemically.Results The defects were filled gradually with repair tissues in experimental groups A and B, and no repair tissues had formed in the control group at 12 weeks. Repair tissues in experimental group A contained more chondrocytes,proteoglycans, and collagen type Ⅱ than those in experimental group B. In experimental group B, fibrous tissues had formed at the defects at 8 and 12 weeks. Histological analysis of experimental group A showed a better Wakitani score (P <0.05) than in experimental group B at 8 and 12 weeks after the operation.Conclusions In the repair of full-thickness articular cartilage defects in rabbits, low-energy shock waves in microfracture holes facilitated the production of hyaline-like cartilage repair tissues more than microfracture alone. This model demonstrates a new

  18. Xenotransplantation of pig chondrocytes: therapeutic potential and barriers for cartilage repair.

    Science.gov (United States)

    Sommaggio, R; Uribe-Herranz, M; Marquina, M; Costa, C

    2016-01-01

    Transplantation may be the best option for the repair of many cartilage lesions including early osteoarthritis. Currently, autologous and allogeneic chondrocytes are grafted into cartilage defects to treat selected patients with moderate clinical success. However, their limited use justifies exploring novel therapies for cartilage repair. Xenotransplantation could become a solution by offering high cell availability, quality and genetic engineering capabilities. The rejection process of xenogeneic cartilage is thus being elucidated in order to develop counteractive strategies. Initial studies determined that pig cartilage xenografts are rejected by a slow process comprising humoral and cellular responses in which the galactose α1,3-galactose antigen participates. Since then, our group has identified key mechanisms of the human response to pig chondrocytes (PCs). In particular, human antibody and complement contribute to PC rejection by inducing a pro-inflammatory milieu. Furthermore, PCs express and up-regulate molecules which are functionally relevant for a variety of cellular immune responses (SLA-I, the potent co-stimulatory molecule CD86, and adhesion molecules VCAM-1 and ICAM-1). These participate by triggering a T cell response, as well as supporting a prominent role of the innate immune responses led by natural killer (NK) cells and monocytes/macrophages. Human NK cells lyse PCs by using selected NK activating receptors, whereas human monocytes are activated by PCs to secrete cytokines and chemokines. All this knowledge sets the bases for the development of genetic engineering approaches designed to avert rejection of xenogeneic chondrocytes and leads the way to developing new clinical applications for cartilage repair. PMID:27377665

  19. Directing chondrogenic differentiation of mesenchymal stem cells with a solid-supported chitosan thermogel for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Hydrogels are attractive for cartilage tissue engineering because of their high plasticity and similarity with the native cartilage matrix. However, one critical drawback of hydrogels for osteochondral repair is their inadequate mechanical strength. To address this limitation, we constructed a solid-supported thermogel comprising a chitosan hydrogel system and demineralized bone matrix. Scanning electron microscopy, the equilibrium scanning ratio, the biodegradation rate, biomechanical tests, biochemical assays, metabolic activity tests, immunostaining and cartilage-specific gene expression analysis were used to evaluate the solid-supported thermogel. Compared with pure hydrogel or demineralized matrix, the hybrid biomaterial showed superior porosity, equilibrium swelling and degradation rate. The hybrid scaffolds exhibited an increased mechanical strength: 75% and 30% higher compared with pure hydrogels and demineralized matrix, respectively. After three days culture, bone-derived mesenchymal stem cells (BMSCs) maintained viability above 90% in all three materials; however, the cell retention of the hybrid scaffolds was more efficient and uniform than the other materials. Matrix production and chondrogenic differentiation of BMSCs in the hybrid scaffolds were superior to its precursors, based on glycosaminoglycan quantification and hyaline cartilage marker expression after three weeks in culture. Its easy preparation, favourable biophysical properties and chondrogenic capacity indicated that this solid-supported thermogel could be an attractive biomaterial framework for cartilage tissue engineering. (paper)

  20. The benefits and limitations of animal models for translational research in cartilage repair.

    Science.gov (United States)

    Moran, Conor J; Ramesh, Ashwanth; Brama, Pieter A J; O'Byrne, John M; O'Brien, Fergal J; Levingstone, Tanya J

    2016-12-01

    Much research is currently ongoing into new therapies for cartilage defect repair with new biomaterials frequently appearing which purport to have significant regenerative capacity. These biomaterials may be classified as medical devices, and as such must undergo rigorous testing before they are implanted in humans. A large part of this testing involves in vitro trials and biomechanical testing. However, in order to bridge the gap between the lab and the clinic, in vivo preclinical trials are required, and usually demanded by regulatory approval bodies. This review examines the in vivo models in current use for cartilage defect repair testing and the relevance of each in the context of generated results and applicability to bringing the device to clinical practice. Some of the preclinical models currently used include murine, leporine, ovine, caprine, porcine, canine, and equine models. Each of these has advantages and disadvantages in terms of animal husbandry, cartilage thickness, joint biomechanics and ethical and licencing issues. This review will examine the strengths and weaknesses of the various animal models currently in use in preclinical studies of cartilage repair. PMID:26915001

  1. Characterization of pediatric microtia cartilage: a reservoir of chondrocytes for auricular reconstruction using tissue engineering strategies.

    Science.gov (United States)

    Melgarejo-Ramírez, Y; Sánchez-Sánchez, R; García-López, J; Brena-Molina, A M; Gutiérrez-Gómez, C; Ibarra, C; Velasquillo, C

    2016-09-01

    The external ear is composed of elastic cartilage. Microtia is a congenital malformation of the external ear that involves a small reduction in size or a complete absence. The aim of tissue engineering is to regenerate tissues and organs clinically implantable based on the utilization of cells and biomaterials. Remnants from microtia represent a source of cells for auricular reconstruction using tissue engineering. To examine the macromolecular architecture of microtia cartilage and behavior of chondrocytes, in order to enrich the knowledge of this type of cartilage as a cell reservoir. Auricular cartilage remnants were obtained from pediatric patients with microtia undergoing reconstructive procedures. Extracellular matrix composition was characterized using immunofluorescence and histological staining methods. Chondrocytes were isolated and expanded in vitro using a mechanical-enzymatic protocol. Chondrocyte phenotype was analyzed using qualitative PCR. Microtia cartilage preserves structural organization similar to healthy elastic cartilage. Extracellular matrix is composed of typical cartilage proteins such as type II collagen, elastin and proteoglycans. Chondrocytes displayed morphological features similar to chondrocytes derived from healthy cartilage, expressing SOX9, COL2 and ELN, thus preserving chondral phenotype. Cell viability was 94.6 % during in vitro expansion. Elastic cartilage from microtia has similar characteristics, both architectural and biochemical to healthy cartilage. We confirmed the suitability of microtia remnant as a reservoir of chondrocytes with potential to be expanded in vitro, maintaining phenotypical features and viability. Microtia remnants are an accessible source of autologous cells for auricular reconstruction using tissue engineering strategies. PMID:27566509

  2. Perichondrium/cartilage composite graft for repairing large tympanic membrane perforations and hearing improvement

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-wei; YANG Hua; GAO Ru-zhen; YU Rong; GAO Zhi-qiang

    2010-01-01

    Background The main risk factors for postoperative failure in tympanoplasties are large perforations that are difficult to repair, annular perforations, and a tympanic membrane (TM) with extensive granular myringitis that require middle ear exploration and mastoidectomy. The aim of this study was to investigate a novel technique of perichondrium/cartilage composite graft for repairing the large TM perforation in the patient of otitis media.Methods Retrospective chart reviews were conducted for 102 patients with large tympanic membrane perforations, who had undergone tympanoplasty from August 2005 to August 2008. Tympanoplasty or tympanomastoidectomy using a perichondrium/cartilage composite graft was analyzed. The tragal or conchal perichondrium/cartilage was used to replace the tympanic membrane in patients.Results Patients aged from 13 to 67 years were followed up in average for 24 months (10-36 months). Seventy-four ears (72.61%) were used the tragal perichondrium/cartilage as graft material and 27 ears (27.39%) were used the conchal perichondrium/cartilage. Graft take was successful in all patients. Postoperative complications such as wound infection, hematoma, or sensorineural hearing loss were not identified. Nine patients (8.82%) had the partial ossicular replacement prosthesis, 14 patients (13.72%) using the autologous curved incus and 79 patients (77.45%) without prosthesis. Successful closure occurred in 92% of the ears. A total of 85.8% patients achieved a postoperative hearing improvement.Conclusions The graft underlay tympanoplasty using perichonddum/cartilage composite is effective for the majority of patients with large perforation. The hearing was improved even if the mastoidectomy was required in the patients with otitis media with extensive granulation.

  3. Method of tissue repair using a composite material

    Science.gov (United States)

    Hutchens, Stacy A.; Woodward, Jonathan; Evans, Barbara R.; O'Neill, Hugh M.

    2016-03-01

    A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

  4. Method of tissue repair using a composite material

    Energy Technology Data Exchange (ETDEWEB)

    Hutchens, Stacy A.; Woodward, Jonathan; Evans, Barbara R.; O' Neill, Hugh M.

    2016-03-01

    A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

  5. Method of tissue repair using a composite material

    Energy Technology Data Exchange (ETDEWEB)

    Hutchens, Stacy A; Woodward, Jonathan; Evans, Barbara R; O' Neill, Hugh M

    2014-03-18

    A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

  6. Adult stem cells and tissue repair.

    Science.gov (United States)

    Körbling, M; Estrov, Z; Champlin, R

    2003-08-01

    Recently, adult stem cells originating from bone marrow or peripheral blood have been suggested to contribute to repair and genesis of cells specific for liver, cardiac and skeletal muscle, gut, and brain tissue. The mechanism involved has been termed transdifferentiation, although other explanations including cell fusion have been postulated. Using adult stem cells to generate or repair solid organ tissue obviates the immunologic, ethical, and teratogenic issues that accompany embryonic stem cells. PMID:12931235

  7. Peripheral blood mononuclear cells enhance cartilage repair in in vivo osteochondral defect model

    OpenAIRE

    Hopper, Niina; Wardale, John; Brooks, Roger; Power, Roger; Power, Jonathan, 1941-; Rushtown, Neil; Henson, Frances

    2015-01-01

    This study characterized peripheral blood mononuclear cells (PBMC) in terms of their potential in cartilage repair and investigated their ability to improve the healing in a pre-clinical large animal model. Human PBMCs were isolated with gradient centrifugation and adherent PBMC’s were evaluated for their ability to differentiate into adipogenic, chondrogenic and osteogenic lineages and also for their expression of musculoskeletal genes. The phenotype of the PBMCs was evaluated using Stro-1, ...

  8. The benefits and limitations of animal models for translational research in cartilage repair

    OpenAIRE

    Moran, Conor J.; Ramesh, Ashwanth; Brama, Pieter A. J.; O’Byrne, John M.; O’Brien, Fergal J; Levingstone, Tanya J

    2016-01-01

    Much research is currently ongoing into new therapies for cartilage defect repair with new biomaterials frequently appearing which purport to have significant regenerative capacity. These biomaterials may be classified as medical devices, and as such must undergo rigorous testing before they are implanted in humans. A large part of this testing involves in vitro trials and biomechanical testing. However, in order to bridge the gap between the lab and the clinic, in vivo preclinical trials are...

  9. 3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Derek H. Rosenzweig

    2015-07-01

    Full Text Available Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS and polylactic acid (PLA scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo.

  10. Flavonoid Compound Icariin Activates Hypoxia Inducible Factor-1α in Chondrocytes and Promotes Articular Cartilage Repair.

    Science.gov (United States)

    Wang, Pengzhen; Zhang, Fengjie; He, Qiling; Wang, Jianqi; Shiu, Hoi Ting; Shu, Yinglan; Tsang, Wing Pui; Liang, Shuang; Zhao, Kai; Wan, Chao

    2016-01-01

    Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1α) has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1α may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1α expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1α in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1α mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10-6 M) increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2α1) and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM) synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic marker genes

  11. Flavonoid Compound Icariin Activates Hypoxia Inducible Factor-1α in Chondrocytes and Promotes Articular Cartilage Repair.

    Directory of Open Access Journals (Sweden)

    Pengzhen Wang

    Full Text Available Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1α has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1α may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1α expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1α in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1α mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10-6 M increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2α1 and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic

  12. Osteochondral allograft transplantation in cartilage repair: Graft storage paradigm, translational models, and clinical applications.

    Science.gov (United States)

    Bugbee, William D; Pallante-Kichura, Andrea L; Görtz, Simon; Amiel, David; Sah, Robert

    2016-01-01

    The treatment of articular cartilage injury and disease has become an increasingly relevant part of orthopaedic care. Articular cartilage transplantation, in the form of osteochondral allografting, is one of the most established techniques for restoration of articular cartilage. Our research efforts over the last two decades have supported the transformation of this procedure from experimental "niche" status to a cornerstone of orthopaedic practice. In this Kappa Delta paper, we describe our translational and clinical science contributions to this transformation: (1) to enhance the ability of tissue banks to process and deliver viable tissue to surgeons and patients, (2) to improve the biological understanding of in vivo cartilage and bone remodeling following osteochondral allograft (OCA) transplantation in an animal model system, (3) to define effective surgical techniques and pitfalls, and (4) to identify and clarify clinical indications and outcomes. The combination of coordinated basic and clinical studies is part of our continuing comprehensive academic OCA transplant program. Taken together, the results have led to the current standards for OCA processing and storage prior to implantation and also novel observations and mechanisms of the biological and clinical behavior of OCA transplants in vivo. Thus, OCA transplantation is now a successful and increasingly available treatment for patients with disabling osteoarticular cartilage pathology. PMID:26234194

  13. Quantitative magnetic resonance imaging (MRI) evaluation of cartilage repair after microfracture treatment for full-thickness cartilage defect models in rabbit knee joints: correlations with histological findings

    International Nuclear Information System (INIS)

    To evaluate repair tissue (RT) after microfracture treatment for full-thickness cartilage defect models using quantitative MRI and investigate the correlations between MRI and histological findings. The animal experiment was approved by the Animal Care and Use Committee of our college. Thirty-six full-thickness cartilage defect models in rabbit knee joints were assigned to the microfracture or joint debridement group (as control). Each group consisted of 3-week, 5-week, and 7-week subgroups. MR imaging, including a three-dimensional double-echo steady-state sequence (3D-DESS), and T2 mapping were performed at 3, 5, and 7 weeks postoperatively. The thickness and T2 indices of RT were calculated. After MRI scans at each time point, operation sites were removed to make hematoxylin-eosin (H and E)-stained sections. Histological results were evaluated using the modified O'Driscoll score system. Comparisons were made between the two groups with respect to the MRI and histological findings, and correlation analysis was performed within each group. The thickness index and histological O'Driscoll score of RT in the two groups increased over time, while the T2 index decreased. The thickness index and histological O'Driscoll score of the microfracture group were higher than in the joint debridement group at each time point. The T2 index of the microfracture group was lower than in the joint debridement group at 3 weeks (P = 0.006), while it was higher than in the joint debridement group at 5 and 7 weeks (P = 0.025 and 0.025). The thickness index was positively correlated with the histological O'Driscoll score in both groups (microfracture: rs = 0.745, P s = 0.680, P = 0.002). The T2 index was negatively correlated with the histological O'Driscoll score in both groups (microfracture: rs = -0.715, P = 0.002; joint debridement: rs = -0.826, P < 0.001). Significant improvement over time after microfracture can be expected on the basis of the quantitative MRI finding and

  14. Quantitative magnetic resonance imaging (MRI) evaluation of cartilage repair after microfracture treatment for full-thickness cartilage defect models in rabbit knee joints: correlations with histological findings

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Hongyue; Feng, Xiaoyuan; Chen, Shuang [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Li, Hong; Hua, Yinghui [Fudan University, Department of Sports Medicine, Huashan Hospital, Shanghai (China); Chen, Zhongqing [Fudan University, Department of Pathology, Huashan Hospital, Shanghai (China)

    2014-11-26

    To evaluate repair tissue (RT) after microfracture treatment for full-thickness cartilage defect models using quantitative MRI and investigate the correlations between MRI and histological findings. The animal experiment was approved by the Animal Care and Use Committee of our college. Thirty-six full-thickness cartilage defect models in rabbit knee joints were assigned to the microfracture or joint debridement group (as control). Each group consisted of 3-week, 5-week, and 7-week subgroups. MR imaging, including a three-dimensional double-echo steady-state sequence (3D-DESS), and T2 mapping were performed at 3, 5, and 7 weeks postoperatively. The thickness and T2 indices of RT were calculated. After MRI scans at each time point, operation sites were removed to make hematoxylin-eosin (H and E)-stained sections. Histological results were evaluated using the modified O'Driscoll score system. Comparisons were made between the two groups with respect to the MRI and histological findings, and correlation analysis was performed within each group. The thickness index and histological O'Driscoll score of RT in the two groups increased over time, while the T2 index decreased. The thickness index and histological O'Driscoll score of the microfracture group were higher than in the joint debridement group at each time point. The T2 index of the microfracture group was lower than in the joint debridement group at 3 weeks (P = 0.006), while it was higher than in the joint debridement group at 5 and 7 weeks (P = 0.025 and 0.025). The thickness index was positively correlated with the histological O'Driscoll score in both groups (microfracture: r{sub s} = 0.745, P < 0.001; joint debridement: r{sub s} = 0.680, P = 0.002). The T2 index was negatively correlated with the histological O'Driscoll score in both groups (microfracture: r{sub s} = -0.715, P = 0.002; joint debridement: r{sub s} = -0.826, P < 0.001). Significant improvement over time after

  15. The Effects of Extracellular Matrix on Tissue Engineering Construction of Cartilage in Vitro

    Institute of Scientific and Technical Information of China (English)

    YU Li; LI Fa-tao; TANG Ming-qiao; YAN Wei-qun

    2006-01-01

    The effects of various cartilage extracellular matrix on the construction of rabbit growth plate cartilage tissue in vitro were studied. The results show that collagen, proteoglycan and hyaluronic acid can promote the growth of cultured chondrocytes but the effects of various cartilage extracellular matrix(ECM)on chondrocyte differentiation are different. Collagen can promote the hypertrophy of chondrocytes while proteoglycan and hyaluronic acid inhibit the transition of mature chondrocytes into hypertrophied chondrocytes.

  16. Water-based polyurethane 3D printed scaffolds with controlled release function for customized cartilage tissue engineering.

    Science.gov (United States)

    Hung, Kun-Che; Tseng, Ching-Shiow; Dai, Lien-Guo; Hsu, Shan-hui

    2016-03-01

    Conventional 3D printing may not readily incorporate bioactive ingredients for controlled release because the process often involves the use of heat, organic solvent, or crosslinkers that reduce the bioactivity of the ingredients. Water-based 3D printing materials with controlled bioactivity for customized cartilage tissue engineering is developed in this study. The printing ink contains the water dispersion of synthetic biodegradable polyurethane (PU) elastic nanoparticles, hyaluronan, and bioactive ingredients TGFβ3 or a small molecule drug Y27632 to replace TGFβ3. Compliant scaffolds are printed from the ink at low temperature. These scaffolds promote the self-aggregation of mesenchymal stem cells (MSCs) and, with timely release of the bioactive ingredients, induce the chondrogenic differentiation of MSCs and produce matrix for cartilage repair. Moreover, the growth factor-free controlled release design may prevent cartilage hypertrophy. Rabbit knee implantation supports the potential of the novel 3D printing scaffolds in cartilage regeneration. We consider that the 3D printing composite scaffolds with controlled release bioactivity may have potential in customized tissue engineering. PMID:26774563

  17. In end stage osteoarthritis, cartilage tissue pentosidine levels are inversely related to parameters of cartilage damage

    NARCIS (Netherlands)

    Vos, P.A.J.M.; Mastbergen, S.C.; Huisman, A.M.; Boer, T.N.de; Groot, J.de; Polak, A.A.; Lafeber, F.P.J.G.

    2012-01-01

    Objectives: Age is the most prominent predisposition for development of osteoarthritis (OA). Age-related changes of articular cartilage are likely to play a role. Advanced glycation endproducts (AGEs) accumulate in cartilage matrix with increasing age and adversely affect the biomechanical propertie

  18. Recurrence rate of repaired hard palate oronasal fistula with conchal cartilage graft

    Directory of Open Access Journals (Sweden)

    Hosein Abdali

    2014-01-01

    Full Text Available Background: After cleft palate repair, oronasal fistula (ONF formation is one of the considerable and troublesome complications. Conchal cartilage graft is one option that can be used in recurrent fistula correction. The aim of the current study is investigating the recurrence rate of the hard palate ONF or ONF at the junction of hard and soft palate after utilizing conchal cartilage graft and comparing this rate with other methods. Materials and Methods: In this observational prospective study, 29 patients suffering from ONF with small, medium and large sizes who were referring to Alzahra university hospital, Isfahan, Iran and Fateme Zahra university hospital, Tehran, Iran between November 2011 and November 2012 were enrolled. All patients had midline cleft palate, 29.6% of them had cleft lip too that was repaired previously. All patients were followed-up for 2 years (every 2 months after repair. Results: The mean (range age of studied samples was 10.7 (2-23 years. 16 patients (55.7% were female, and reminders were male. During 2 years followup, we detected recurrence of ONF in 6 patients (20.68% and the success rate was 79.32%. The recurrence rate, after applying the current approach, among who experienced the several times of recurrence was significantly higher than among those who experienced first time of recurrence (33.3% vs. 7.1%; P 0.1. Conclusion: Using of conchal cartilage graft for recurrent ONF with ≤1 cm was safe and efficacious, in ONF >1 cm conchal cartilage graft can be used as a primary method and if recurrence occurred chooses other complex procedure.

  19. Novel nano-rough polymers for cartilage tissue engineering

    Directory of Open Access Journals (Sweden)

    Balasundaram G

    2014-04-01

    , the present in vitro results of increased chondrocyte functions on NPU and NPCL suggest these materials may be suitable for numerous polymer-based cartilage tissue-engineering applications and, thus, deserve further investigation.Keywords: chondrocytes, polyurethane, polycaprolactone, nano-roughened polymers, cartilage applications

  20. Cartilage Engineering and Microgravity

    Science.gov (United States)

    Toffanin, R.; Bader, A.; Cogoli, A.; Carda, C.; Fantazzini, P.; Garrido, L.; Gomez, S.; Hall, L.; Martin, I.; Murano, E.; Poncelet, D.; Pörtner, R.; Hoffmann, F.; Roekaerts, D.; Ronney, P.; Triebel, W.; Tummers, M.

    2005-06-01

    The complex effects of mechanical forces and growth factors on articular cartilage development still need to be investigated in order to identify optimal conditions for articular cartilage repair. Strictly controlled in vitro studies under modelled or space microgravity conditions can improve our understanding of the fundamental role of gravity in articular cartilage development. The main objective of this Topical Team is to use modelled microgravity as a tool to elucidate the fundamental science of cartilage regeneration. Particular attention is, therefore, given to the effects of physical forces under altered gravitational conditions, applied using controlled bioreactor systems, on cell metabolism, cell differentiation and tissue development. Specific attention is also directed toward the potential advantages of using magnetic resonance methods for the non-destructive characterisation of scaffolds, chondrocytes-polymer constructs and tissue engineered cartilage.

  1. Mesenchymal stem cells promote articular cartilage repair and regeneration%间充质干细胞促进关节软骨的修复与再生

    Institute of Scientific and Technical Information of China (English)

    朱瑜琪; 王金荣; 王智耀

    2015-01-01

    marrow, adipose and umbilical cord have strong chondrogenic and cloning capacities. Bone marrow mesenchymal stem cels have a stronger differentiation potential, and can be used for repair of cartilage injury. Umbilical cord-derived mesenchymal stem cels have a low tumorigenicity. Adipose-derived stem cels can proliferate and grow faster. Stem cels combined with natural carrier materials, such as colagen, gelatin, fibrin and alginate, can promote cel adhesion, differentiation and proliferation, in order to build an effective tissue engineered cartilage for repair of articular cartilage defects.

  2. Advances in treatment of articular cartilage injuries

    Directory of Open Access Journals (Sweden)

    Yuan-cheng LI

    2013-05-01

    Full Text Available Cartilage is a kind of terminally differentiated tissue devoid of vessel or nerve, and it is difficult to repair by itself after damage. Many studies for the treatment of cartilage injuries were performed in recent years aiming at repair of the structure and restoration of its function for injured joint. This article reviews the traditional methods of treatment for cartilage injuries, such as joint lavage with the aid of arthroscope, abrasion chondroplasty, laser abrasion and chondroplasty, and drilling of the subchondral bone-marrow space. The research advances in treatment of articular cartilage injuries with tissue engineering were summarized.

  3. Design and characterization of a tissue-engineered bilayer scaffold for osteochondral tissue repair.

    Science.gov (United States)

    Giannoni, Paolo; Lazzarini, Erica; Ceseracciu, Luca; Barone, Alberto C; Quarto, Rodolfo; Scaglione, Silvia

    2015-10-01

    Treatment of full-thickness cartilage defects relies on osteochondral bilayer grafts, which mimic the microenvironment and structure of the two affected tissues: articular cartilage and subchondral bone. However, the integrity and stability of the grafts are hampered by the presence of a weak interphase, generated by the layering processes of scaffold manufacturing. We describe here the design and development of a bilayer monolithic osteochondral graft, avoiding delamination of the two distinct layers but preserving the cues for selective generation of cartilage and bone. A highly porous polycaprolactone-based graft was obtained by combining solvent casting/particulate leaching techniques. Pore structure and interconnections were designed to favour in vivo vascularization only at the bony layer. Hydroxyapatite granules were added as bioactive signals at the site of bone regeneration. Unconfined compressive tests displayed optimal elastic properties and low residual deformation of the graft after unloading (< 3%). The structural integrity of the graft was successfully validated by tension fracture tests, revealing high resistance to delamination, since fractures were never displayed at the interface of the layers (n = 8). Ectopic implantation of grafts in nude mice, after seeding with bovine trabecular bone-derived mesenchymal stem cells and bovine articular chondrocytes, resulted in thick areas of mature bone surrounding ceramic granules within the bony layer, and a cartilaginous alcianophilic matrix in the chondral layer. Vascularization was mostly observed in the bony layer, with a statistically significant higher blood vessel density and mean area. Thus, the easily generated osteochondral scaffolds, since they are mechanically and biologically functional, are suitable for tissue-engineering applications for cartilage repair. PMID:23172816

  4. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage

    DEFF Research Database (Denmark)

    Day, J; Ding, Ming; van der Linden, JC; Hvid, I; Sumner, DR; Weinans, H

    2001-01-01

    the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an......In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage....... Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were...

  5. Nanocomposite Scaffold for Chondrocyte Growth and Cartilage Tissue Engineering: Effects of Carbon Nanotube Surface Functionalization

    OpenAIRE

    Chahine, Nadeen O.; Collette, Nicole M.; Thomas, Cynthia B.; Genetos, Damian C.; Loots, Gabriela G

    2014-01-01

    The goal of this study was to assess the long-term biocompatibility of single-wall carbon nanotubes (SWNTs) for tissue engineering of articular cartilage. We hypothesized that SWNT nanocomposite scaffolds in cartilage tissue engineering can provide an improved molecular-sized substrate for stimulation of chondrocyte growth, as well as structural reinforcement of the scaffold's mechanical properties. The effect of SWNT surface functionalization (-COOH or -PEG) on chondrocyte viability and bioc...

  6. Nanocomposite scaffold for chondrocyte growth and cartilage tissue engineering: effects of carbon nanotube surface functionalization.

    Science.gov (United States)

    Chahine, Nadeen O; Collette, Nicole M; Thomas, Cynthia B; Genetos, Damian C; Loots, Gabriela G

    2014-09-01

    functionalization may promote ECM expression in this culture system. The results of this study indicate that SWNTs exhibit a unique potential for cartilage tissue engineering, where functionalization with bioactive molecules may provide an improved substrate for stimulation of cellular growth and repair. PMID:24593020

  7. Surface modification of polycaprolactone scaffolds fabricated via selective laser sintering for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chih-Hao [Department of Chemical and Materials Engineering, Chang Gung University, Kweishan, Taoyuan 333, Taiwan, ROC (China); Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Craniofacial Research Center, Chang Gung University, Kweishann, Taoyuan 333, Taiwan, ROC (China); Lee, Ming-Yih [Graduate Institute of Medical Mechatronics, Chang Gung University, Kweishan, Taoyuan 333, Taiwan, ROC (China); Shyu, Victor Bong-Hang; Chen, Yi-Chieh; Chen, Chien-Tzung [Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Craniofacial Research Center, Chang Gung University, Kweishann, Taoyuan 333, Taiwan, ROC (China); Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Kweishan, Taoyuan 333, Taiwan, ROC (China); Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan 333, Taiwan, ROC (China)

    2014-07-01

    Surface modified porous polycaprolactone scaffolds fabricated via rapid prototyping techniques were evaluated for cartilage tissue engineering purposes. Polycaprolactone scaffolds manufactured by selective laser sintering (SLS) were surface modified through immersion coating with either gelatin or collagen. Three groups of scaffolds were created and compared for both mechanical and biological properties. Surface modification with collagen or gelatin improved the hydrophilicity, water uptake and mechanical strength of the pristine scaffold. From microscopic observations and biochemical analysis, collagen-modified scaffold was the best for cartilage tissue engineering in terms of cell proliferation and extracellular matrix production. Chondrocytes/collagen-modified scaffold constructs were implanted subdermally in the dorsal spaces of female nude mice. Histological and immunohistochemical staining of the retrieved implants after 8 weeks revealed enhanced cartilage tissue formation. We conclude that collagen surface modification through immersion coating on SLS-manufactured scaffolds is a feasible scaffold for cartilage tissue engineering in craniofacial reconstruction. - Highlights: • Selective laser sintered polycaprolactone scaffolds are prepared. • Scaffolds are surface modified through immersion coating with gelatin or collagen. • Collagen-scaffold is the best for cartilage tissue engineering in vitro. • Chondrocytes/collagen-scaffold reveals enhanced cartilage tissue formation in vivo.

  8. Surface modification of polycaprolactone scaffolds fabricated via selective laser sintering for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Surface modified porous polycaprolactone scaffolds fabricated via rapid prototyping techniques were evaluated for cartilage tissue engineering purposes. Polycaprolactone scaffolds manufactured by selective laser sintering (SLS) were surface modified through immersion coating with either gelatin or collagen. Three groups of scaffolds were created and compared for both mechanical and biological properties. Surface modification with collagen or gelatin improved the hydrophilicity, water uptake and mechanical strength of the pristine scaffold. From microscopic observations and biochemical analysis, collagen-modified scaffold was the best for cartilage tissue engineering in terms of cell proliferation and extracellular matrix production. Chondrocytes/collagen-modified scaffold constructs were implanted subdermally in the dorsal spaces of female nude mice. Histological and immunohistochemical staining of the retrieved implants after 8 weeks revealed enhanced cartilage tissue formation. We conclude that collagen surface modification through immersion coating on SLS-manufactured scaffolds is a feasible scaffold for cartilage tissue engineering in craniofacial reconstruction. - Highlights: • Selective laser sintered polycaprolactone scaffolds are prepared. • Scaffolds are surface modified through immersion coating with gelatin or collagen. • Collagen-scaffold is the best for cartilage tissue engineering in vitro. • Chondrocytes/collagen-scaffold reveals enhanced cartilage tissue formation in vivo

  9. [Tissue engineered skin and regenerative wound repair].

    Science.gov (United States)

    Han, Chun-mao; Wang, Xin-gang

    2013-04-01

    Various skin defects resulting from mechanical injury, burns, chronic ulcers, and resection of tumor etc. are very common in clinic. The traditional treatment measure, such as grafting of autologous split-thickness skin remains the gold standard. However, its limitations are obvious, such as shortage of donor sites, creation of new injury, and scar formation. To realize regenerative or scarless repair of tissue defects has always been the dream of human being. The advent of tissue engineered skin (TES) provides an ideal access to tissue regeneration. After decades of development, several kinds of TES products have been developed and used in clinic, with promising effects. However, a large number of basic scientific problems regarding TES, as well as difficulties in translation of basic research to bedside should be taken into serious consideration. This article presents a comprehensive overview of strategies of construction of TES, the role of TES in regenerative wound repair, and its opportunities and challenges. PMID:23985197

  10. Assessment of cartilage repair after chondrocyte transplantation with a fibrin-hyaluronan matrix – Correlation of morphological MRI, biochemical T2 mapping and clinical outcome

    International Nuclear Information System (INIS)

    Objective: To evaluate change over time of clinical scores, morphological MRI of cartilage appearance and quantitative T2 values after implantation with BioCart™II, a second generation matrix-assisted implantation system. Methods: Thirty-one patients were recruited 6–49 months post surgery for cartilage defect in the femoral condyle. Subjects underwent MRI (morphological and T2-mapping sequences) and completed the International Knee Documentation Committee (IKDC) questionnaire. MRI scans were scored using the MR Observation of Cartilage Repair Tissue (MOCART) system and cartilage T2-mapping values were registered. Analysis included correlation of IKDC scores, MOCART and T2 evaluation with each other, with implant age and with previous surgical intervention history. Results: IKDC score significantly correlated with MOCART score (r = −0.39, p = 0.031), inversely correlated with previous interventions (r = −0.39, p = 0.034) and was significantly higher in patients with longer follow-up time (p = 0.0028). MOCART score was slight, but not significantly higher in patients with longer term implants (p = 0.199). T2 values were significantly lower in patients with longer duration implants (p < 0.001). This trend was repeated in patients with previous interventions, although to a lesser extent. Conclusions: Significant improvement with time from BioCart™II implantation can be expected by IKDC scoring and MRI T2-mapping values. Patients with previous knee operations can also benefit from this procedure.

  11. A method to screen and evaluate tissue adhesives for joint repair applications

    Directory of Open Access Journals (Sweden)

    Dehne Tilo

    2012-09-01

    Full Text Available Abstract Background Tissue adhesives are useful means for various medical procedures. Since varying requirements cause that a single adhesive cannot meet all needs, bond strength testing remains one of the key applications used to screen for new products and study the influence of experimental variables. This study was conducted to develop an easy to use method to screen and evaluate tissue adhesives for tissue engineering applications. Method Tissue grips were designed to facilitate the reproducible production of substrate tissue and adhesive strength measurements in universal testing machines. Porcine femoral condyles were used to generate osteochondral test tissue cylinders (substrates of different shapes. Viability of substrates was tested using PI/FDA staining. Self-bonding properties were determined to examine reusability of substrates (n = 3. Serial measurements (n = 5 in different operation modes (OM were performed to analyze the bonding strength of tissue adhesives in bone (OM-1 and cartilage tissue either in isolation (OM-2 or under specific requirements in joint repair such as filling cartilage defects with clinical applied fibrin/PLGA-cell-transplants (OM-3 or tissues (OM-4. The efficiency of the method was determined on the basis of adhesive properties of fibrin glue for different assembly times (30 s, 60 s. Seven randomly generated collagen formulations were analyzed to examine the potential of method to identify new tissue adhesives. Results Viability analysis of test tissue cylinders revealed vital cells (>80% in cartilage components even 48 h post preparation. Reuse (n = 10 of test substrate did not significantly change adhesive characteristics. Adhesive strength of fibrin varied in different test settings (OM-1: 7.1 kPa, OM-2: 2.6 kPa, OM-3: 32.7 kPa, OM-4: 30.1 kPa and was increasing with assembly time on average (2.4-fold. The screening of the different collagen formulations revealed a substance with significant

  12. Chitosan-Based Hyaluronic Acid Hybrid Polymer Fibers as a Scaffold Biomaterial for Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Shintarou Yamane

    2010-12-01

    Full Text Available An ideal scaffold material is one that closely mimics the natural environment in the tissue-specific extracellular matrix (ECM. Therefore, we have applied hyaluronic acid (HA, which is a main component of the cartilage ECM, to chitosan as a fundamental material for cartilage regeneration. To mimic the structural environment of cartilage ECM, the fundamental structure of a scaffold should be a three-dimensional (3D system with adequate mechanical strength. We structurally developed novel polymer chitosan-based HA hybrid fibers as a biomaterial to easily fabricate 3D scaffolds. This review presents the potential of a 3D fabricated scaffold based on these novel hybrid polymer fibers for cartilage tissue engineering.

  13. Engineering Cartilage

    Science.gov (United States)

    ... Research Matters NIH Research Matters March 3, 2014 Engineering Cartilage Artistic rendering of human stem cells on ... situations has been a major goal in tissue engineering. Cartilage contains water, collagen, proteoglycans, and chondrocytes. Collagens ...

  14. Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Nehrer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail: stefan.nehrer@meduniwien.ac.at; Domayer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Dorotka, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Schatz, K. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bindreiter, U. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Kotz, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-01-15

    Repair of articular cartilage represents a significant clinical problem and although various new techniques - including the use of autologous chondrocytes - have been developed within the last century the clinical efficacy of these procedures is still discussed controversially. Although autologous chondrocyte transplantation (ACT) has been widely used with success, it has several inherent limitations, including its invasive nature and problems related to the use of the periosteal flap. To overcome these problems autologous chondrocytes transplantation combined with the use of biodegradable scaffolds has received wide attention. Among these, a hyaluronan-based scaffold has been found useful for inducing hyaline cartilage regeneration. In the present study, we have investigated the mid-term efficacy and safety of Hyalograft[reg] C grafts in a group of 36 patients undergoing surgery for chronic cartilage lesions of the knee. Clinical Outcome was assessed prospectively before and at 12, 24, and 36 months after surgery. No major adverse events have been reported during the 3-year follow-up. Significant improvements of the evaluated scores were observed (P < 0.02) at 1 year and a continued increase of clinical performance was evident at 2 and 3 years follow-up. Patients under 30 years of age with single lesions showed statistically significant improvements at all follow-up visits compared to those over 30 with multiple defects (P < 0.01). Hyalograft[reg] C compares favorably with classic ACT and is particularly indicated in younger patients with single lesions. The graft can be implanted through a miniarthrotomy and needs no additional fixation with sutures except optional fibrin gluing at the defect borders. These results suggest that Hyalograft[reg] C is a valid alternative to ACT.

  15. Evaluation of the implant type tissue-engineered cartilage by scanning acoustic microscopy.

    Science.gov (United States)

    Tanaka, Yoko; Saijo, Yoshifumi; Fujihara, Yuko; Yamaoka, Hisayo; Nishizawa, Satoru; Nagata, Satoru; Ogasawara, Toru; Asawa, Yukiyo; Takato, Tsuyoshi; Hoshi, Kazuto

    2012-02-01

    The tissue-engineered cartilages after implantation were nonuniform tissues which were mingling with biodegradable polymers, regeneration cartilage and others. It is a hard task to evaluate the biodegradation of polymers or the maturation of regenerated tissues in the transplants by the conventional examination. Otherwise, scanning acoustic microscopy (SAM) system specially developed to measure the tissue acoustic properties at a microscopic level. In this study, we examined acoustic properties of the tissue-engineered cartilage using SAM, and discuss the usefulness of this devise in the field of tissue engineering. We administered chondrocytes/atelocollagen mixture into the scaffolds of various polymers, and transplanted the constructs in the subcutaneous areas of nude mice for 2 months. We harvested them and examined the sound speed and the attenuation in the section of each construct by the SAM. As the results, images mapping the sound speed exhibited homogenous patterns mainly colored in blue, in all the tissue-engineered cartilage constructs. Contrarily, the images of the attenuation by SAM showed the variation of color ranged between blue and red. The low attenuation area colored in red, which meant hard materials, were corresponding to the polymer remnant in the toluidine blue images. The localizations of blue were almost similar with the metachromatic areas in the histology. In conclusion, the SAM is regarded as a useful tool to provide the information on acoustic properties and their localizations in the transplants that consist of heterogeneous tissues with various components. PMID:22138383

  16. Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

    OpenAIRE

    Jessop, Zita M.; Javed, Muhammad; Otto, Iris A.; Combellack, Emman J.; Morgan, Siân; Breugem, Corstiaan C; Archer, Charles W.; Khan, Ilyas M.; Lineaweaver, William C.; Kon, Moshe; Malda, Jos; Whitaker, Iain S

    2016-01-01

    Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity...

  17. Non-viral gene activated matrices for mesenchymal stem cells based tissue engineering of bone and cartilage.

    Science.gov (United States)

    Raisin, Sophie; Belamie, Emmanuel; Morille, Marie

    2016-10-01

    Recent regenerative medicine and tissue engineering strategies for bone and cartilage repair have led to fascinating progress of translation from basic research to clinical applications. In this context, the use of gene therapy is increasingly being considered as an important therapeutic modality and regenerative technique. Indeed, in the last 20 years, nucleic acids (plasmid DNA, interferent RNA) have emerged as credible alternative or complement to proteins, which exhibited major issues including short half-life, loss of bioactivity in pathologic environment leading to high dose requirement and therefore high production costs. The relevance of gene therapy strategies in combination with a scaffold, following a so-called "Gene-Activated Matrix (GAM)" approach, is to achieve a direct, local and sustained delivery of nucleic acids from a scaffold to ensure efficient and durable cell transfection. Among interesting cells sources, Mesenchymal Stem Cells (MSC) are promising for a rational use in gene/cell therapy with more than 1700 clinical trials approved during the last decade. The aim of the present review article is to provide a comprehensive overview of recent and ongoing work in non-viral genetic engineering of MSC combined with scaffolds. More specifically, we will show how this inductive strategy can be applied to orient stem cells fate for bone and cartilage repair. PMID:27467418

  18. Cartilage repair materials used for repair of sports-induced knee cartilage injuries%软骨修复材料在运动性膝关节软骨损伤修复中的作用

    Institute of Scientific and Technical Information of China (English)

    孙皓; 左健

    2011-01-01

    BACKGROUND: To evaluate the effect of cartilage repair materials on the repair of knee cartilage injuries so as to support a certain experience for medical and scientific research workers.METHODS: An electronic search of Wanfang database was performed using the keywords of “biomaterials; articular cartilage;injuries; repair” to retrieve articles about repair materials for knee cartilage injuries published between 2000-01 and 2011-03.Repetitive articles, review and Meta analysis were excluded, and finally 26 articles were eligible.RESULTS: Knee cartilage injuries are commonly seen in sports-induced injuries. The main treatment is to repair cartilage defects in the knee with autogenous bone graft. The new cartilage substitute material is still in the phase of animal tests. The long-term efficacy and biomechanical changes in model animals need further studies, and then the related clinical trials can be done.CONCLUSION: There are many important and difficult problems to be explored in the basic and clinical research concerning the repair of knee cartilage injuries. However, a new progress from biomaterial grafts to reconstructed active bone is realized in the repair of knee cartilage injuries. With the development and research of various new-type materials, the repair of knee cartilage injuries can be increasingly perfect.%背景:评价软骨修复材料在膝关节软骨损伤修复中的效果,为医务、科研工作者的研究提供一定的借鉴.方法:采用电子检索的方式,在万方数据库(http://www.wanfangdata.com.cn/)中检索2000-01/2011-03关于修复材料在膝关节软骨损伤研究的文章,关键词为"生物材料;关节软骨;缺损;修复".排除重复研究、普通综述或Meta分析类文章,筛选纳入26篇文献进行评价.结果:膝关节软骨损伤在运动性损伤中较为常见,现在主要的治疗方法是自体骨软骨移植修复膝关节软骨缺损.新型的软骨替代材料研究仍处于动物试验阶段,且

  19. Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage

    Directory of Open Access Journals (Sweden)

    CH Evans

    2009-12-01

    Full Text Available We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2 was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified (“gene activated” tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible.

  20. Chondroitin Sulfate- and Decorin-Based Self-Assembling Scaffolds for Cartilage Tissue Engineering

    Science.gov (United States)

    Recha-Sancho, Lourdes; Semino, Carlos E.

    2016-01-01

    Cartilage injury and degenerative tissue progression remain poorly understood by the medical community. Therefore, various tissue engineering strategies aim to recover areas of damaged cartilage by using non-traditional approaches. To this end, the use of biomimetic scaffolds for recreating the complex in vivo cartilage microenvironment has become of increasing interest in the field. In the present study, we report the development of two novel biomaterials for cartilage tissue engineering (CTE) with bioactive motifs, aiming to emulate the native cartilage extracellular matrix (ECM). We employed a simple mixture of the self-assembling peptide RAD16-I with either Chondroitin Sulfate (CS) or Decorin molecules, taking advantage of the versatility of RAD16-I. After evaluating the structural stability of the bi-component scaffolds at a physiological pH, we characterized these materials using two different in vitro assessments: re-differentiation of human articular chondrocytes (AC) and induction of human adipose derived stem cells (ADSC) to a chondrogenic commitment. Interestingly, differences in cellular morphology and viability were observed between cell types and culture conditions (control and chondrogenic). In addition, both cell types underwent a chondrogenic commitment under inductive media conditions, and this did not occur under control conditions. Remarkably, the synthesis of important ECM constituents of mature cartilage, such as type II collagen and proteoglycans, was confirmed by gene and protein expression analyses and toluidine blue staining. Furthermore, the viscoelastic behavior of ADSC constructs after 4 weeks of culture was more similar to that of native articular cartilage than to that of AC constructs. Altogether, this comparative study between two cell types demonstrates the versatility of our novel biomaterials and suggests a potential 3D culture system suitable for promoting chondrogenic differentiation. PMID:27315119

  1. [Great Scandinavian Jahre Prize 1993. Studies of cartilage and bone yields new knowledge of tissue homeostasis].

    Science.gov (United States)

    Heinegård, D

    1994-01-01

    Increased knowledge of connective tissue, such as cartilage and bone, has improved our understanding of tissue replenishment under normal and pathological conditions. Although developments in this field are still at an early stage, it is already possible to discern avenues for future development leading to new diagnostic and therapeutic methods in connective tissue diseases. In this article, Dick Heinegård, the second recipient of the Jahre Prize for 1993, gives an account of his research. PMID:8121785

  2. Cold Atmospheric Plasma Modified Electrospun Scaffolds with Embedded Microspheres for Improved Cartilage Regeneration

    OpenAIRE

    Wei Zhu; Castro, Nathan J.; Xiaoqian Cheng; Michael Keidar; Lijie Grace Zhang

    2015-01-01

    Articular cartilage is prone to degeneration and possesses extremely poor self-healing capacity due to inherent low cell density and the absence of a vasculature network. Tissue engineered cartilage scaffolds show promise for cartilage repair. However, there still remains a lack of ideal biomimetic tissue scaffolds which effectively stimulate cartilage regeneration with appropriate functional properties. Therefore, the objective of this study is to develop a novel biomimetic and bioactive ele...

  3. Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: Comparisons with the normal articular cartilage

    Directory of Open Access Journals (Sweden)

    Kurokawa Takayuki

    2011-09-01

    Full Text Available Abstract Background We have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid and poly-(N, N'-Dimetyl acrylamide, at the bottom of the defect. The purpose of this study was to clarify gene expression profile of the regenerated tissue in comparison with that of the normal articular cartilage. Methods We created a cylindrical osteochondral defect in the rabbit femoral grooves. Then, we implanted the DN gel plug at the bottom of the defect. At 2 and 4 weeks after surgery, the regenerated tissue was analyzed using DNA microarray and immunohistochemical examinations. Results The gene expression profiles of the regenerated tissues were macroscopically similar to the normal cartilage, but showed some minor differences. The expression degree of COL2A1, COL1A2, COL10A1, DCN, FMOD, SPARC, FLOD2, CHAD, CTGF, and COMP genes was greater in the regenerated tissue than in the normal cartilage. The top 30 genes that expressed 5 times or more in the regenerated tissue as compared with the normal cartilage included type-2 collagen, type-10 collagen, FN, vimentin, COMP, EF1alpha, TFCP2, and GAPDH genes. Conclusions The tissue regenerated by using the DN gel was genetically similar but not completely identical to articular cartilage. The genetic data shown in this study are useful for future studies to identify specific genes involved in spontaneous cartilage regeneration.

  4. Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

    Science.gov (United States)

    Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

    2016-02-01

    This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process. PMID:26855751

  5. In vitro and in vivo evaluation of chitosan–gelatin scaffolds for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Chitosan–gelatin polyelectrolyte complexes were fabricated and evaluated as tissue engineering scaffolds for cartilage regeneration in vitro and in vivo. The crosslinker for the gelatin component was selected among glutaraldehyde, bisepoxy, and a water-soluble carbodiimide (WSC) based upon the proliferation of chondrocytes on the crosslinked gelatin. WSC was found to be the most suitable crosslinker. Complex scaffolds made from chitosan and gelatin with a component ratio equal to one possessed the proper degradation rate and mechanical stability in vitro. Chondrocytes were able to proliferate well and secrete abundant extracellular matrix in the chitosan–gelatin (1:1) complex scaffolds crosslinked by WSC (C1G1WSC) compared to the non-crosslinked scaffolds. Implantation of chondrocytes-seeded scaffolds in the defects of rabbit articular cartilage confirmed that C1G1WSC promoted the cartilage regeneration. The neotissue formed the histological feature of tide line and lacunae in 6.5 months. The amount of glycosaminoglycans in C1G1WSC constructs (0.187 ± 0.095 μg/mg tissue) harvested from the animals after 6.5 months was 14 wt.% of that in normal cartilage (1.329 ± 0.660 μg/mg tissue). The average compressive modulus of regenerated tissue at 6.5 months was about 0.539 MPa, which approached to that of normal cartilage (0.735 MPa), while that in the blank control (3.881 MPa) was much higher and typical for fibrous tissue. Type II collagen expression in C1G1WSC constructs was similarly intense as that in the normal hyaline cartilage. According to the above results, the use of C1G1WSC scaffolds may enhance the cartilage regeneration in vitro and in vivo. - Highlights: • We developed a chitosan–gelatin scaffold crosslinked with carbodiimide. • Neocartilage formation was more evident in crosslinked vs. non-crosslinked scaffolds. • Histological features of tide line and lacunae were observed in vivo at 6.5 months. • Compressive modulus of regenerated

  6. Apparatus for enhancing tissue repair in mammals

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

    2007-01-01

    An apparatus is disclosed for enhancing tissue repair in mammals, with the apparatus comprising: a sleeve for encircling a portion of a mammalian body part, said sleeve comprising an electrically conductive coil capable of generating an electromagnetic field when an electrical current is applied thereto, means for supporting the sleeve on the mammalian body part; and means for supplying the electrically conductive coil with a square wave time varying electrical current sufficient to create a time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss within the interior of the coil in order that when the sleeve is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss is generated on the mammalian body part for an extended period of time, tissue regeneration within the mammalian body part is increased to a rate in excess of the normal tissue regeneration rate that would occur without application of the time varying electromagnetic force.

  7. Peripheral Blood Mononuclear Cells Enhance Cartilage Repair in in vivo Osteochondral Defect Model.

    Science.gov (United States)

    Hopper, Niina; Wardale, John; Brooks, Roger; Power, Jonathan; Rushton, Neil; Henson, Frances

    2015-01-01

    This study characterized peripheral blood mononuclear cells (PBMC) in terms of their potential in cartilage repair and investigated their ability to improve the healing in a pre-clinical large animal model. Human PBMCs were isolated with gradient centrifugation and adherent PBMC's were evaluated for their ability to differentiate into adipogenic, chondrogenic and osteogenic lineages and also for their expression of musculoskeletal genes. The phenotype of the PBMCs was evaluated using Stro-1, CD34, CD44, CD45, CD90, CD106, CD105, CD146 and CD166 cell surface markers. Osteochondral defects were created in the medial femoral condyle (MFC) of 24 Welsh mountain sheep and evaluated at a six month time point. Four cell treatment groups were evaluated in combination with collagen-GAG-scaffold: (1) MSC alone; (2) MSCs and PBMCs at a ratio of 20:1; (3) MSCs and PBMC at a ratio of 2:1 and (4) PBMCs alone. Samples from the surgical site were evaluated for mechanical properties, ICRS score and histological repair. Fresh PBMC samples were 90% positive for hematopoietic cell surface markers and negative for the MSC antibody panel (stem cell markers in hypoxic culture and lacked CD34/45 positive cells (cells had acquired an MSC-like phenotype and transformed in hypoxia from their original hematopoietic lineage. Four key genes in muskuloskeletal biology were significantly upregulated in adherent PBMCs by hypoxia: BMP2 4.2-fold (p = 0.0007), BMP6 10.7-fold (p = 0.0004), GDF5 2.0-fold (p = 0.002) and COL1 5.0-fold (p = 0.046). The monolayer multilineage analysis confirmed the trilineage mesenchymal potential of the adherent PBMCs. PBMC cell therapy was equally good as bone marrow MSC therapy for defects in the ovine large animal model. Our results show that PBMCs support cartilage healing and oxygen tension of the environment was found to have a key effect on the derivation of a novel adherent cell population with an MSC-like phenotype. This study presents a novel and easily

  8. Cartilage-derived extracellular matrix extract promotes chondrocytic phenotype in three-dimensional tissue culture.

    Science.gov (United States)

    Youngstrom, Daniel W; Cakstina, Inese; Jakobsons, Eriks

    2016-05-01

    Cell transplantation is a promising regenerative therapy for cartilage degeneration. However, obtaining sufficient numbers of cells for this purpose is a challenge, due a lack of autologous donor tissue and the difficulty of culturing chondrocytes in vitro. Tissue engineering strategies that induce or maintain chondrocytic phenotype may solve these problems by (1) broadening the range of available donor tissue, and (2) facilitating the expansion of these cells while controlling phenotypic drift. In this study, bone marrow-derived mesenchymal stem cells (MSCs) and cartilage-derived cells (CDCs) were cultured on composite hydrogels containing agarose and homogenized cartilage extracellular matrix (ECM). MSCs cultured on agarose-ECM scaffolds did not show significant signs of chondrogenic differentiation in the absence of additional cues. However, CDCs cultured on agarose-ECM scaffolds proliferated more rapidly than their ECM-free counterparts and MSCs, while retaining chondrocytic morphology. These results were corroborated via expression of cartilage marker genes: in autologous constructs, SOX 9 expression was upregulated by 12.6 ± 5.3-fold, and COL II was upregulated by 2.0 ± 0.3-fold. Agarose-ECM composite hydrogels are therefore useful for expanding partially differentiated CDCs for applications in regenerative medicine. PMID:25707441

  9. Evaluation of the repair of full-thickness articular cartilage defects filled with autologous exogenous fibrin clot: An experimental study in the shoulder joint of dogs

    Directory of Open Access Journals (Sweden)

    Avki S.

    2003-01-01

    Full Text Available To determine whether the optimizing effect of an exogenous fibrin clot in the repair of full–thickness articular cartilage defects is valid when joint motions are restricted, standard osteochondral defects were constituted in the articular surface of the humeral head in 16 adult dogs. The defects in 8 dogs were packed with fibrin clots that had been prepared exogenously from each animal and the defects of the other animals were left empty. The operated limbs were inactivated for 2 weeks postoperatively and the healing response was then examined using routine histology at 2, 4, 8 and 12-week intervals. Although the clot-filled and control (empty defects initially healed through proliferation of fibrous connective tissue; the clot-filled defects finally modulated into fibrocartilage with completed subchondral bone formation. The clot-filled defects demonstrated a more advanced reparative tissue which was congruent with the intact articular surface from 4 weeks after the intervention.

  10. Thermogel-Coated Poly(ε-Caprolactone) Composite Scaffold for Enhanced Cartilage Tissue Engineering

    OpenAIRE

    Shao-Jie Wang; Zheng-Zheng Zhang; Dong Jiang; Yan-Song Qi; Hai-Jun Wang; Ji-Ying Zhang; Jian-Xun Ding; Jia-Kuo Yu

    2016-01-01

    A three-dimensional (3D) composite scaffold was prepared for enhanced cartilage tissue engineering, which was composed of a poly(ε-caprolactone) (PCL) backbone network and a poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA–PEG–PLGA) thermogel surface. The composite scaffold not only possessed adequate mechanical strength similar to native osteochondral tissue as a benefit of the PCL backbone, but also maintained cell-friendly microenvironment of th...

  11. High intensity focused ultrasound as a tool for tissue engineering: Application to cartilage.

    Science.gov (United States)

    Nover, Adam B; Hou, Gary Y; Han, Yang; Wang, Shutao; O'Connell, Grace D; Ateshian, Gerard A; Konofagou, Elisa E; Hung, Clark T

    2016-02-01

    This article promotes the use of High Intensity Focused Ultrasound (HIFU) as a tool for affecting the local properties of tissue engineered constructs in vitro. HIFU is a low cost, non-invasive technique used for eliciting focal thermal elevations at variable depths within tissues. HIFU can be used to denature proteins within constructs, leading to decreased permeability and potentially increased local stiffness. Adverse cell viability effects remain restricted to the affected area. The methods described in this article are explored through the scope of articular cartilage tissue engineering and the fabrication of osteochondral constructs, but may be applied to the engineering of a variety of different tissues. PMID:26724968

  12. Selective laser sintered poly-ε-caprolactone scaffold hybridized with collagen hydrogel for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Selective laser sintering (SLS), an additive manufacturing (AM) technology, can be used to produce tissue engineering scaffolds with pre-designed macro and micro features based on computer-aided design models. An in-house SLS machine was built and 3D poly-ε-caprolactone (PCL) scaffolds were manufactured using a layer-by-layer design of scaffold struts with varying orientations (0°/45°/0°/45°, 0°/90°/0°/90°, 0°/45°/90°/135°), producing scaffolds with pores of different shapes and distribution. To better enhance the scaffold properties, chondrocytes were seeded in collagen gel and loaded in scaffolds for cartilage tissue engineering. Gel uptake and dynamic mechanical analysis demonstrated the better suitability of the 0°/90°/0°/90° scaffolds for reconstructive cartilage tissue engineering purposes. Chondrocytes were then seeded onto the 0°/90°/0°/90° scaffolds in collagen I hydrogel (PCL/COL1) and compared to medium-suspended cells in terms of their cartilage-like tissue engineering parameters. PCL/COL1 allowed better cell proliferation when compared to PCL or two-dimensional tissue culture polystyrene. Scanning electron microscopy and confocal microscopy observations demonstrated a similar trend for extracellular matrix production and cell survival. Glycosaminoglycan and collagen II quantification also demonstrated the superior matrix secretion properties of PCL/COL1 hybrid scaffolds. Collagen-gel-suspended chondrocytes loaded in SLS-manufactured PCL scaffolds may provide a means of producing tissue-engineered cartilage with customized shapes and designs via AM technology. (paper)

  13. Chitosan Scaffolds Containing Hyaluronic Acid for Cartilage Tissue Engineering

    NARCIS (Netherlands)

    Correia, Clara R.; Moreira Teixeira, Liliana S.; Moroni, Lorenzo; Reis, Rui L.; Blitterswijk, van Clemens A.; Karperien, Marcel; Mano, João F.

    2011-01-01

    Scaffolds derived from natural polysaccharides are very promising in tissue engineering applications and regenerative medicine, as they resemble glycosaminoglycans in the extracellular matrix (ECM). In this study, we have prepared freeze-dried composite scaffolds of chitosan (CHT) and hyaluronic aci

  14. Tissue Engineering of Cartilage on Ground-Based Facilities

    DEFF Research Database (Denmark)

    Aleshcheva, Ganna; Bauer, Johann; Hemmersbach, Ruth;

    2016-01-01

    Investigations under simulated microgravity offer the opportunity for a better understanding of the influence of altered gravity on cells and the scaffold-free threedimensional (3D) tissue formation. To investigate the shortterm influence, human chondrocytes were cultivated for 2h, 4 h, 16 h, and...

  15. A tetracycline expression system in combination with Sox9 for cartilage tissue engineering.

    Science.gov (United States)

    Yao, Yi; He, Yu; Guan, Qian; Wu, Qiong

    2014-02-01

    Cartilage tissue engineering using controllable transcriptional therapy together with synthetic biopolymer scaffolds shows higher potential for overcoming chondrocyte degradation and constructing artificial cartilages both in vivo and in vitro. Here, the potential regulating tetracycline expression (Tet-on) system was used to express Sox9 both in vivo and in vitro. Chondrocyte degradation was measured in vitro and overcome by Soxf9 expression. Experiments confirmed the feasibility of the combined use of Sox9 and Tet-on system in cartilage tissue engineering. Engineered poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) scaffolds were seeded with recombinant chondrocytes which were transfected with Tet-induced Sox9 expression; the scaffolds were implanted under the skin of 8-week-old rats. The experimental group was injected with Dox in the abdomen, while the control group was injected with normal saline. After 4 or 8 days of implantation in vivo, the newly formed pieces of articular chondrocytes were taken out and measured. Dox injection in vivo showed positive effect on recombinant chondrocytes, in which Sox9 expression was up-regulated by an inducible system with specific matrix proteins. The results demonstrate this controllable transcriptional therapy is a potential approach for tissue engineering. PMID:24321708

  16. Chitosan Scaffolds Containing Hyaluronic Acid for Cartilage Tissue Engineering

    OpenAIRE

    Correia, Clara R.; Moreira Teixeira, Liliana S.; Moroni, Lorenzo; Reis, Rui L.; Blitterswijk, van, C.A.; Karperien, Marcel; Mano, João F.

    2011-01-01

    Scaffolds derived from natural polysaccharides are very promising in tissue engineering applications and regenerative medicine, as they resemble glycosaminoglycans in the extracellular matrix (ECM). In this study, we have prepared freeze-dried composite scaffolds of chitosan (CHT) and hyaluronic acid (HA) in different weight ratios containing either no HA (control) or 1%, 5%, or 10% of HA. We hypothesized that HA could enhance structural and biological properties of CHT scaffolds. To test thi...

  17. Thermogel-Coated Poly(ε-Caprolactone Composite Scaffold for Enhanced Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Shao-Jie Wang

    2016-05-01

    Full Text Available A three-dimensional (3D composite scaffold was prepared for enhanced cartilage tissue engineering, which was composed of a poly(ε-caprolactone (PCL backbone network and a poly(lactide-co-glycolide-block-poly(ethylene glycol-block-poly(lactide-co-glycolide (PLGA–PEG–PLGA thermogel surface. The composite scaffold not only possessed adequate mechanical strength similar to native osteochondral tissue as a benefit of the PCL backbone, but also maintained cell-friendly microenvironment of the hydrogel. The PCL network with homogeneously-controlled pore size and total pore interconnectivity was fabricated by fused deposition modeling (FDM, and was impregnated into the PLGA–PEG–PLGA solution at low temperature (e.g., 4 °C. The PCL/Gel composite scaffold was obtained after gelation induced by incubation at body temperature (i.e., 37 °C. The composite scaffold showed a greater number of cell retention and proliferation in comparison to the PCL platform. In addition, the composite scaffold promoted the encapsulated mesenchymal stromal cells (MSCs to differentiate chondrogenically with a greater amount of cartilage-specific matrix production compared to the PCL scaffold or thermogel. Therefore, the 3D PCL/Gel composite scaffold may exhibit great potential for in vivo cartilage regeneration.

  18. Full-thickness cartilage defects are repaired via a microfracture technique and intraarticular injection of the small-molecule compound kartogenin

    OpenAIRE

    Xu, Xingquan; Shi, Dongquan; Shen, Yeshuai; Xu, Zhihong; Dai, Jin; Chen, Dongyang; Teng, Huajian; Jiang, Qing

    2015-01-01

    Introduction Microfracture does not properly repair full-thickness cartilage defects. The purpose of this study was to evaluate the effect of intraarticular injection of the small-molecule compound kartogenin (KGN) on the restoration of a full-thickness cartilage defect treated with microfracture in a rabbit model. Methods Full-thickness cartilage defects (3.5 mm in diameter and 3 mm in depth) were created in the patellar groove of the right femurs of 24 female New Zealand White rabbits. The ...

  19. Repair of sciatic nerve defects using tissue engineered nerves

    OpenAIRE

    Zhang, Caishun; Lv, Gang

    2013-01-01

    In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engine...

  20. Transforming growth factor beta 1 effects on cartilage tissue metabolism%转化生长因子β1对软骨组织代谢影响的研究进展*★

    Institute of Scientific and Technical Information of China (English)

    郭铁峰; 周明旺; 李盛华; 孙凤岐; 穆欢喜

    2013-01-01

      背景:转化生长因子β1可以介导软骨合成、抑制胶原和蛋白多糖分解,在诱导软骨分化和维持软骨表型上起着重要作用,实现软骨缺损的功能性修复。  目的:从生物学特性、在生物工程中的应用、基因多态性、信号通路及微小 RNA等方面综述转化生长因子β1对软骨组织代谢影响的研究进展。  方法:以“transforming growth factor-β1,Cartilage Differentiation,cartilage matrix”为英文检索词,以“转化生长因子β1,软骨分化,软骨基质”为中文检索词。经第一作者检索2007/2012CNKI数据库及SPRINGERLINK数据库有关转化生长因子β1对软骨组织代谢影响的研究进展方面的文献130篇,根据纳入排除标准保留54篇进行总结。  结果与结论:转化生长因子β1可诱导间充质细胞向软骨细胞分化,促进软骨特异性基质的合成,保护软骨基质不被各种蛋白酶水解破坏,能够增强软骨组织自身再生能力,实现使软骨的损伤逆转,在软骨修复领域展现了巨大的潜在应用价值。%BACKGROUND:Transforming growth factor beta 1 can mediate cartilage synthesis and inhibit decomposition of col agen and protein polysaccharide, which has a most important effect on induction of cartilage differentiation in vitro and maintenance of cartilage phenotype, realizing the functional repair of cartilage defects. OBJECTIVE:Based on the biological characteristics, applications in biotechnology, gene polymorphism, signaling pathways and microRNA, to introduce research progress of transforming growth factor beta 1 influence on cartilage tissue metabolism. METHODS:The first author searched CNKI and SPRINGERLINK databases (2007/2012) to retrieve articles related to transforming growth factor beta 1 influence on cartilage tissue metabolism using the key words of“transforming growth factor beta 1, cartilage differentiation, cartilage matrix

  1. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications.

    Science.gov (United States)

    Xu, Tao; Binder, Kyle W; Albanna, Mohammad Z; Dice, Dennis; Zhao, Weixin; Yoo, James J; Atala, Anthony

    2013-03-01

    Bioprinting is an emerging technique used to fabricate viable, 3D tissue constructs through the precise deposition of cells and hydrogels in a layer-by-layer fashion. Despite the ability to mimic the native properties of tissue, printed 3D constructs that are composed of naturally-derived biomaterials still lack structural integrity and adequate mechanical properties for use in vivo, thus limiting their development for use in load-bearing tissue engineering applications, such as cartilage. Fabrication of viable constructs using a novel multi-head deposition system provides the ability to combine synthetic polymers, which have higher mechanical strength than natural materials, with the favorable environment for cell growth provided by traditional naturally-derived hydrogels. However, the complexity and high cost associated with constructing the required robotic system hamper the widespread application of this approach. Moreover, the scaffolds fabricated by these robotic systems often lack flexibility, which further restrict their applications. To address these limitations, advanced fabrication techniques are necessary to generate complex constructs with controlled architectures and adequate mechanical properties. In this study, we describe the construction of a hybrid inkjet printing/electrospinning system that can be used to fabricate viable tissues for cartilage tissue engineering applications. Electrospinning of polycaprolactone fibers was alternated with inkjet printing of rabbit elastic chondrocytes suspended in a fibrin-collagen hydrogel in order to fabricate a five-layer tissue construct of 1 mm thickness. The chondrocytes survived within the printed hybrid construct with more than 80% viability one week after printing. In addition, the cells proliferated and maintained their basic biological properties within the printed layered constructs. Furthermore, the fabricated constructs formed cartilage-like tissues both in vitro and in vivo as evidenced by the

  2. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications

    International Nuclear Information System (INIS)

    Bioprinting is an emerging technique used to fabricate viable, 3D tissue constructs through the precise deposition of cells and hydrogels in a layer-by-layer fashion. Despite the ability to mimic the native properties of tissue, printed 3D constructs that are composed of naturally-derived biomaterials still lack structural integrity and adequate mechanical properties for use in vivo, thus limiting their development for use in load-bearing tissue engineering applications, such as cartilage. Fabrication of viable constructs using a novel multi-head deposition system provides the ability to combine synthetic polymers, which have higher mechanical strength than natural materials, with the favorable environment for cell growth provided by traditional naturally-derived hydrogels. However, the complexity and high cost associated with constructing the required robotic system hamper the widespread application of this approach. Moreover, the scaffolds fabricated by these robotic systems often lack flexibility, which further restrict their applications. To address these limitations, advanced fabrication techniques are necessary to generate complex constructs with controlled architectures and adequate mechanical properties. In this study, we describe the construction of a hybrid inkjet printing/electrospinning system that can be used to fabricate viable tissues for cartilage tissue engineering applications. Electrospinning of polycaprolactone fibers was alternated with inkjet printing of rabbit elastic chondrocytes suspended in a fibrin–collagen hydrogel in order to fabricate a five-layer tissue construct of 1 mm thickness. The chondrocytes survived within the printed hybrid construct with more than 80% viability one week after printing. In addition, the cells proliferated and maintained their basic biological properties within the printed layered constructs. Furthermore, the fabricated constructs formed cartilage-like tissues both in vitro and in vivo as evidenced by the

  3. In Vitro Engineering of High Modulus Cartilage-Like Constructs

    OpenAIRE

    Finlay, Scott; Seedhom, Bahaa B.; Carey, Duane O.; Bulpitt, Andy J.; Treanor, Darren E.; Kirkham, Jennifer

    2016-01-01

    To date, the outcomes of cartilage repair have been inconsistent and have frequently yielded mechanically inferior fibrocartilage, thereby increasing the chances of damage recurrence. Implantation of constructs with biochemical composition and mechanical properties comparable to natural cartilage could be advantageous for long-term repair. This study attempted to create such constructs, in vitro, using tissue engineering principles. Bovine synoviocytes were seeded on nonwoven polyethylene ter...

  4. A fibrin/hyaluronic acid hydrogel for the delivery of mesenchymal stem cells and potential for articular cartilage repair

    OpenAIRE

    Snyder, Timothy N; Madhavan, Krishna; Intrator, Miranda; Dregalla, Ryan C.; Park, Daewon

    2014-01-01

    Background Osteoarthritis (OA) is a degenerative joint disease affecting approximately 27 million Americans, and even more worldwide. OA is characterized by degeneration of subchondral bone and articular cartilage. In this study, a chondrogenic fibrin/hyaluronic acid (HA)-based hydrogel seeded with bone marrow-derived mesenchymal stem cells (BMSCs) was investigated as a method of regenerating these tissues for OA therapy. This chondrogenic hydrogel system can be delivered in a minimally invas...

  5. The tissue injury and repair in cancer radiotherapy

    International Nuclear Information System (INIS)

    One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed. (author)

  6. Protocols for the in vitro design of animal articular cartilage based on tissue engineering methods

    Directory of Open Access Journals (Sweden)

    Diego Correa

    2012-10-01

    Full Text Available The articular cartilage is the structure that covers the joint ends. It has some specific tasks crucial to the correct joint physiology. It may experience a large amount of injuries that could generate considerable disabilities. Unfortunately its selfrepair capacity is too limited; therefore, many treatments have been developed with partial success, given the suboptimal biomechanical behavior of the resultant tissue. Given that, Tissue Engineering offers an alternative, based on the design of a new tissue with biological and biomechanical features which resembles the native tissue. In this work, the authors describe the methodologies followed to accomplish that goal, studying the chondrocytes harvesting, the cellular cultures, the scaffold seeding processes, the mechanical stimulation and the structural and biomechanical evaluation. Finally, exposed some of the preliminary results, as a experimental validation of the methods proposed are.

  7. Derivation of chondrogenically-committed cells from human embryonic cells for cartilage tissue regeneration.

    Directory of Open Access Journals (Sweden)

    Nathaniel S Hwang

    Full Text Available BACKGROUND: Heterogeneous and uncontrolled differentiation of human embryonic stem cells (hESCs in embryoid bodies (EBs limits the potential use of hESCs for cell-based therapies. More efficient strategies are needed for the commitment and differentiation of hESCs to produce a homogeneous population of specific cell types for tissue regeneration applications. METHODOLOGY/PRINCIPAL FINDINGS: We report here that significant chondrocytic commitment of feeder-free cultured human embryonic stem cells (FF-hESCs, as determined by gene expression and immunostaining analysis, was induced by co-culture with primary chondrocytes. Furthermore, a dynamic expression profile of chondrocyte-specific genes was observed during monolayer expansion of the chondrogenically-committed cells. Chondrogenically-committed cells synergistically responded to transforming growth factor-beta1 (TGF-beta1 and beta1-integrin activating antibody by increasing tissue mass in pellet culture. In addition, when encapsulated in hydrogels, these cells formed cartilage tissue both in vitro and in vivo. In contrast, the absence of chondrocyte co-culture did not result in an expandable cell population from FF-hESCs. CONCLUSIONS/SIGNIFICANCE: The direct chondrocytic commitment of FF-hESCs can be induced by morphogenetic factors from chondrocytes without EB formation and homogenous cartilage tissue can be formed in vitro and in vivo.

  8. Cartilage Tissue Engineering with Silk Fibroin Scaffolds Fabricated by Indirect Additive Manufacturing Technology

    Directory of Open Access Journals (Sweden)

    Chih-Hao Chen

    2014-03-01

    Full Text Available Advanced tissue engineering (TE technology based on additive manufacturing (AM can fabricate scaffolds with a three-dimensional (3D environment suitable for cartilage regeneration. Specifically, AM technology may allow the incorporation of complex architectural features. The present study involves the fabrication of 3D TE scaffolds by an indirect AM approach using silk fibroin (SF. From scanning electron microscopic observations, the presence of micro-pores and interconnected channels within the scaffold could be verified, resulting in a TE scaffold with both micro- and macro-structural features. The intrinsic properties, such as the chemical structure and thermal characteristics of SF, were preserved after the indirect AM manufacturing process. In vitro cell culture within the SF scaffold using porcine articular chondrocytes showed a steady increase in cell numbers up to Day 14. The specific production (per cell basis of the cartilage-specific extracellular matrix component (collagen Type II was enhanced with culture time up to 12 weeks, indicating the re-differentiation of chondrocytes within the scaffold. Subcutaneous implantation of the scaffold-chondrocyte constructs in nude mice also confirmed the formation of ectopic cartilage by histological examination and immunostaining.

  9. Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications

    Directory of Open Access Journals (Sweden)

    Jaewoo Pak

    2016-01-01

    Full Text Available Osteoarthritis (OA is one of the most common debilitating disorders among the elderly population. At present, there is no definite cure for the underlying causes of OA. However, adipose tissue-derived stem cells (ADSCs in the form of stromal vascular fraction (SVF may offer an alternative at this time. ADSCs are one type of mesenchymal stem cells that have been utilized and have demonstrated an ability to regenerate cartilage. ADSCs have been shown to regenerate cartilage in a variety of animal models also. Non-culture-expanded ADSCs, in the form of SVF along with platelet rich plasma (PRP, have recently been used in humans to treat OA and other cartilage abnormalities. These ADSCs have demonstrated effectiveness without any serious side effects. However, due to regulatory issues, only ADSCs in the form of SVF are currently allowed for clinical uses in humans. Culture-expanded ADSCs, although more convenient, require clinical trials for a regulatory approval prior to uses in clinical settings. Here we present a systematic review of currently available clinical studies involving ADSCs in the form of SVF and in the culture-expanded form, with or without PRP, highlighting the clinical effectiveness and safety in treating OA.

  10. A controlled double-duration inducible gene expression system for cartilage tissue engineering

    Science.gov (United States)

    Ma, Ying; Li, Junxiang; Yao, Yi; Wei, Daixu; Wang, Rui; Wu, Qiong

    2016-01-01

    Cartilage engineering that combines competent seeding cells and a compatible scaffold is increasingly gaining popularity and is potentially useful for the treatment of various bone and cartilage diseases. Intensive efforts have been made by researchers to improve the viability and functionality of seeding cells of engineered constructs that are implanted into damaged cartilage. Here, we designed an integrative system combining gene engineering and the controlled-release concept to solve the problems of both seeding cell viability and functionality through precisely regulating the anti-apoptotic gene bcl-2 in the short-term and the chondrogenic master regulator Sox9 in the long-term. Both in vitro and in vivo experiments demonstrated that our system enhances the cell viability and chondrogenic effects of the engineered scaffold after introduction of the system while restricting anti-apoptotic gene expression to only the early stage, thereby preventing potential oncogenic and overdose effects. Our system was designed to be modular and can also be readily adapted to other tissue engineering applications with minor modification. PMID:27222430

  11. A controlled double-duration inducible gene expression system for cartilage tissue engineering.

    Science.gov (United States)

    Ma, Ying; Li, Junxiang; Yao, Yi; Wei, Daixu; Wang, Rui; Wu, Qiong

    2016-01-01

    Cartilage engineering that combines competent seeding cells and a compatible scaffold is increasingly gaining popularity and is potentially useful for the treatment of various bone and cartilage diseases. Intensive efforts have been made by researchers to improve the viability and functionality of seeding cells of engineered constructs that are implanted into damaged cartilage. Here, we designed an integrative system combining gene engineering and the controlled-release concept to solve the problems of both seeding cell viability and functionality through precisely regulating the anti-apoptotic gene bcl-2 in the short-term and the chondrogenic master regulator Sox9 in the long-term. Both in vitro and in vivo experiments demonstrated that our system enhances the cell viability and chondrogenic effects of the engineered scaffold after introduction of the system while restricting anti-apoptotic gene expression to only the early stage, thereby preventing potential oncogenic and overdose effects. Our system was designed to be modular and can also be readily adapted to other tissue engineering applications with minor modification. PMID:27222430

  12. Prefabrication of 3D cartilage contructs: towards a tissue engineered auricle--a model tested in rabbits.

    Directory of Open Access Journals (Sweden)

    Achim von Bomhard

    Full Text Available The reconstruction of an auricle for congenital deformity or following trauma remains one of the greatest challenges in reconstructive surgery. Tissue-engineered (TE three-dimensional (3D cartilage constructs have proven to be a promising option, but problems remain with regard to cell vitality in large cell constructs. The supply of nutrients and oxygen is limited because cultured cartilage is not vascular integrated due to missing perichondrium. The consequence is necrosis and thus a loss of form stability. The micro-surgical implantation of an arteriovenous loop represents a reliable technology for neovascularization, and thus vascular integration, of three-dimensional (3D cultivated cell constructs. Auricular cartilage biopsies were obtained from 15 rabbits and seeded in 3D scaffolds made from polycaprolactone-based polyurethane in the shape and size of a human auricle. These cartilage cell constructs were implanted subcutaneously into a skin flap (15 × 8 cm and neovascularized by means of vascular loops implanted micro-surgically. They were then totally enhanced as 3D tissue and freely re-implanted in-situ through microsurgery. Neovascularization in the prefabricated flap and cultured cartilage construct was analyzed by microangiography. After explantation, the specimens were examined by histological and immunohistochemical methods. Cultivated 3D cartilage cell constructs with implanted vascular pedicle promoted the formation of engineered cartilaginous tissue within the scaffold in vivo. The auricles contained cartilage-specific extracellular matrix (ECM components, such as GAGs and collagen even in the center oft the constructs. In contrast, in cultivated 3D cartilage cell constructs without vascular pedicle, ECM distribution was only detectable on the surface compared to constructs with vascular pedicle. We demonstrated, that the 3D flaps could be freely transplanted. On a microangiographic level it was evident that all the skin flaps

  13. In vitro precultivation alleviates post-implantation inflammation and enhances development of tissue-engineered tubular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Luo Xusong; Zhou Guangdong; Liu Wei; Zhang Wenjie; Cui Lei; Cao Yilin [Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Cen Lian, E-mail: guangdongzhou@126.co, E-mail: yilincao@yahoo.co [National Tissue Engineering Center of China, Shanghai 200011 (China)

    2009-04-15

    Tissue-engineered tubular cartilage is a promising graft for tracheal reconstruction. But polylactic acid/polyglycolic acid (PLA/PGA) fibers, the frequently used scaffolds for cartilage engineering, often elicit an obvious inflammation response following implantation into immunocompetent animals. We propose that the inflammation could be alleviated by in vitro precultivation. In this study, after in vitro culture for either 2 days (direct implantation group (DI)) or for 2 weeks (precultivation implantation group (PI)), autologous tubular chondrocyte-PLA/PGA constructs were subcutaneously implanted into rabbits. In the PI group, after 2 weeks of precultivation, most of the fibers were found to be completely embedded in an extracellular matrix (ECM) produced by the chondrocytes. Importantly, no obvious inflammatory reaction was observed after in vivo implantation and homogeneous cartilage-like tissue was formed with biomechanical properties close to native tracheal cartilage at 4 weeks post-implantation. In the DI group, however, an obvious inflammatory reaction was observed within and around the cell-scaffold constructs at 1 week implantation and only sporadic cartilage islands separated by fibrous tissue were observed at 4 weeks. These results demonstrated that the post-implantation inflammatory reaction could be alleviated by in vitro precultivation, which contributes to the formation of satisfactory tubular cartilage for tracheal reconstruction.

  14. In vitro precultivation alleviates post-implantation inflammation and enhances development of tissue-engineered tubular cartilage

    International Nuclear Information System (INIS)

    Tissue-engineered tubular cartilage is a promising graft for tracheal reconstruction. But polylactic acid/polyglycolic acid (PLA/PGA) fibers, the frequently used scaffolds for cartilage engineering, often elicit an obvious inflammation response following implantation into immunocompetent animals. We propose that the inflammation could be alleviated by in vitro precultivation. In this study, after in vitro culture for either 2 days (direct implantation group (DI)) or for 2 weeks (precultivation implantation group (PI)), autologous tubular chondrocyte-PLA/PGA constructs were subcutaneously implanted into rabbits. In the PI group, after 2 weeks of precultivation, most of the fibers were found to be completely embedded in an extracellular matrix (ECM) produced by the chondrocytes. Importantly, no obvious inflammatory reaction was observed after in vivo implantation and homogeneous cartilage-like tissue was formed with biomechanical properties close to native tracheal cartilage at 4 weeks post-implantation. In the DI group, however, an obvious inflammatory reaction was observed within and around the cell-scaffold constructs at 1 week implantation and only sporadic cartilage islands separated by fibrous tissue were observed at 4 weeks. These results demonstrated that the post-implantation inflammatory reaction could be alleviated by in vitro precultivation, which contributes to the formation of satisfactory tubular cartilage for tracheal reconstruction.

  15. Quantifying the lubricity of mechanically tough polyvinyl alcohol hydrogels for cartilage repair.

    Science.gov (United States)

    Ling, Doris; Bodugoz-Senturk, Hatice; Nanda, Salil; Braithwaite, Gavin; Muratoglu, Orhun K

    2015-12-01

    Polyvinyl alcohol hydrogels are biocompatible and can be used as synthetic articular cartilage. Their mechanical characteristics can be tailored by various techniques such as annealing or blending with other hydrophilic polymers. In this study, we quantified the coefficient of friction of various candidate polyvinyl alcohol hydrogels against cobalt-chrome alloy or swine cartilage using a new rheometer-based method. We investigated the coefficient of friction of polyvinyl alcohol-only hydrogels and blends with polyethylene glycol, polyacrylic acid, and polyacrylamide against swine cartilage and polished cobalt-chrome surfaces. The addition of the functional groups to polyvinyl alcohol, such as acrylamide (semi-interpenetrating network) and acrylic acid (blend), significantly reduced the coefficient of friction. The coefficient of friction of the polyvinyl alcohol-only hydrogel was measured as 0.4 ± 0.03 against cobalt-chrome alloy, and 0.09 ± 0.004 against cartilage, while those measurements for the polyvinyl alcohol-polyacrylic acid blends and polyvinyl alcohol-polyacrylamide semi-interpenetrating network were 0.07 ± 0.01 and 0.1 ± 0.003 against cobalt-chrome alloy, and 0.03 ± 0.001 and 0.02 ± 0.001 against cartilage, respectively. There was no significant or minimal difference in the coefficient of friction between samples from different regions of the knee, or animals, or when the cartilage samples were frozen for 1 day or 2 days before testing. However, changing lubricant from deionized water to ionic media, for example, saline or simulated body fluid, increased the coefficient of friction significantly. PMID:26614798

  16. An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering

    Science.gov (United States)

    Chen, Feng; Yu, Songrui; Liu, Bing; Ni, Yunzhou; Yu, Chunyang; Su, Yue; Zhu, Xinyuan; Yu, Xiaowei; Zhou, Yongfeng; Yan, Deyue

    2016-01-01

    In this study, an enzymatically cross-linked injectable and biodegradable hydrogel system comprising carboxymethyl pullulan-tyramine (CMP-TA) and chondroitin sulfate-tyramine (CS-TA) conjugates was successfully developed under physiological conditions in the presence of both horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) for cartilage tissue engineering (CTTE). The HRP crosslinking method makes this injectable system feasible, minimally invasive and easily translatable for regenerative medicine applications. The physicochemical properties of the mechanically stable hydrogel system can be modulated by varying the weight ratio and concentration of polymer as well as the concentrations of crosslinking reagents. Additionally, the cellular behaviour of porcine auricular chondrocytes encapsulated into CMP-TA/CS-TA hydrogels demonstrates that the hydrogel system has a good cyto-compatibility. Specifically, compared to the CMP-TA hydrogel, these CMP-TA/CS-TA composite hydrogels have enhanced cell proliferation and increased cartilaginous ECM deposition, which significantly facilitate chondrogenesis. Furthermore, histological analysis indicates that the hydrogel system exhibits acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable pullulan/chondroitin sulfate composite hydrogels presented here are expected to be useful biomaterial scaffold for regenerating cartilage tissue.

  17. Nanopolymers Delivery of the Bone Morphogenetic Protein-4 Plasmid to Mesenchymal Stem Cells Promotes Articular Cartilage Repair In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Junjun Shi

    2012-01-01

    Full Text Available The clinical application of viral vectors for gene therapy is limited for biosafety consideration. In this study, to promote articular cartilage repair, poly (lactic-co glycolic acid (PLGA nanopolymers were used as non-viral vectors to transfect rabbit mesenchymal stem cells (MSCs with the pDC316-BMP4-EGFP plasmid. The cytotoxicity and transfection efficiency in vitro were acceptable measuring by CCK-8 and flow cytometry. After transfection, Chondrogenic markers (mRNA of Col2a1, Sox9, Bmp4, and Agg of experimental cells (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers were increased more than those of control cells (MSCs being transfected with naked BMP-4 plasmid alone. In vivo study, twelve rabbits (24 knees with large full thickness articular cartilage defects were randomly divided into the experimental group (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers and the control group (MSCs being transfected with naked BMP-4 plasmid. The experimental group showed better regeneration than the control group 6 and 12 weeks postoperatively. Hyaline-like cartilage formed at week 12 in the experimental group, indicating the local delivery of BMP-4 plasmid to MSCs by PLGA nanopolymers improved articular cartilage repair significantly. PLGA nanopolymers could be a promising and effective non-viral vector for gene therapy in cartilage repair.

  18. The role of connexins in tissue injury repair

    OpenAIRE

    Glass, B. J. L.

    2014-01-01

    Skin integrity is essential for sustaining life and it is important to understand the processes involved in its maintenance and repair. There are several key stages involved in wound healing that rely on the complex communication through gap junctions and their connexins to ensure the resolution of the wound. Gap junctions are expressed in all cells linked with tissue repair and provide a regulated pathway linking the cytoplasm of neighbouring cells and allowing signals to pass freely between...

  19. Water-stable three-dimensional ultrafine fibrous scaffolds from keratin for cartilage tissue engineering.

    Science.gov (United States)

    Xu, Helan; Cai, Shaobo; Xu, Lan; Yang, Yiqi

    2014-07-22

    Intrinsically water-stable scaffolds composed of ultrafine keratin fibers oriented randomly and evenly in three dimensions were electrospun for cartilage tissue engineering. Keratin has been recognized as a biomaterial that could substantially support the growth and development of multiple cell lines. Besides, three-dimensional (3D) ultrafine fibrous structures were preferred in tissue engineering due to their structural similarity to native extracellular matrices in soft tissues. Recently, we have developed a nontraditional approach to developing 3D fibrous scaffolds from alcohol-soluble corn protein, zein, and verified their structural advantages in tissue engineering. However, keratin with highly cross-linked molecular structures could not be readily dissolved in common solvents for fiber spinning, which required the remarkable drawability of solution. So far, 3D fibrous scaffolds from pure keratin for biomedical applications have not been reported. In this research, the highly cross-linked keratin from chicken feathers was de-cross-linked and disentangled into linear and aligned molecules with preserved molecular weights, forming highly stretchable spinning dope. The solution was readily electrospun into scaffolds with ultrafine keratin fibers oriented randomly in three dimensions. Due to the highly cross-linked molecular structures, keratin scaffolds showed intrinsic water stability. Adipose-derived mesenchymal stem cells could penetrate much deeper, proliferate, and chondrogenically differentiate remarkably better on the 3D keratin scaffolds than on 2D PLA fibrous scaffolds, 3D soy protein fibrous scaffolds, or 3D commercial nonfibrous scaffolds. In summary, the electrospun 3D ultrafine fibrous scaffolds from keratin could be promising candidates for cartilage tissue engineering. PMID:25010870

  20. pH-responsive, redox-sensitive hollow particles for the repair of load-bearing soft tissue

    OpenAIRE

    Bird, Robert

    2012-01-01

    This thesis presents an investigation of pH-responsive, redox-sensitive poly(MMA-co- MAA) and poly(EA-co-MAA) hollow particles for the repair of load-bearing soft tissues, such as articular cartilage and the intervertebral disc. Hollow particles continue to attract major interest due to their numerous potential applications. The new method for hollow particle preparation presented in this thesis does not require the use of a colloidal template and is well suited for scaling up. Hollow particl...

  1. Fibrocytes and the tissue niche in lung repair.

    Science.gov (United States)

    Andersson-Sjöland, Annika; Nihlberg, Kristian; Eriksson, Leif; Bjermer, Leif; Westergren-Thorsson, Gunilla

    2011-01-01

    Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases. PMID:21658209

  2. Fibrocytes and the tissue niche in lung repair

    Directory of Open Access Journals (Sweden)

    Bjermer Leif

    2011-06-01

    Full Text Available Abstract Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases.

  3. Matrix metalloproteinase-8 overexpression prevents proper tissue repair

    DEFF Research Database (Denmark)

    Danielsen, Patricia L; Holst, Anders V; Maltesen, Henrik R; Bassi, Maria R; Holst, Peter J; Heinemeier, Katja M; Olsen, Jørgen; Danielsen, Carl Christian; Poulsen, Steen S; Jorgensen, Lars N; Agren, Magnus S

    2011-01-01

    The collagenolytic matrix metalloproteinase-8 (MMP-8) is essential for normal tissue repair but is often overexpressed in wounds with disrupted healing. Our aim was to study the impact of a local excess of this neutrophil-derived proteinase on wound healing using recombinant adenovirus-driven tra......The collagenolytic matrix metalloproteinase-8 (MMP-8) is essential for normal tissue repair but is often overexpressed in wounds with disrupted healing. Our aim was to study the impact of a local excess of this neutrophil-derived proteinase on wound healing using recombinant adenovirus...

  4. Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.

    Science.gov (United States)

    Klotz, Barbara J; Gawlitta, Debby; Rosenberg, Antoine J W P; Malda, Jos; Melchels, Ferry P W

    2016-05-01

    Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications. PMID:26867787

  5. T2 star relaxation times for assessment of articular cartilage at 3 T: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Mamisch, Tallal Charles [University Bern, Department of Orthopedic Surgery, Inselspital, Bern (Switzerland); University Bern, Magnetic Resonance Spectroscopy and Methodology, Department of Clinical Research, Bern (Switzerland); Hughes, Timothy [Siemens Medical Solutions, Erlangen (Germany); Mosher, Timothy J. [Penn State University College of Medicine, Musculoskeletal Imaging and MRI, Department of Radiology, Hershey, PA (United States); Mueller, Christoph [University of Erlangen, Department of Trauma Surgery, Erlangen (Germany); Trattnig, Siegfried [Medical University of Vienna, MR Center - High Field MR, Department of Radiology, Vienna (Austria); Boesch, Chris [University Bern, Magnetic Resonance Spectroscopy and Methodology, Department of Clinical Research, Bern (Switzerland); Welsch, Goetz Hannes [University of Erlangen, Department of Trauma Surgery, Erlangen (Germany); Medical University of Vienna, MR Center - High Field MR, Department of Radiology, Vienna (Austria)

    2012-03-15

    T2 mapping techniques use the relaxation constant as an indirect marker of cartilage structure, and the relaxation constant has also been shown to be a sensitive parameter for cartilage evaluation. As a possible additional robust biomarker, T2* relaxation time is a potential, clinically feasible parameter for the biochemical evaluation of articular cartilage. The knees of 15 healthy volunteers and 15 patients after microfracture therapy (MFX) were evaluated with a multi-echo spin-echo T2 mapping technique and a multi-echo gradient-echo T2* mapping sequence at 3.0 Tesla MRI. Inline maps, using a log-linear least squares fitting method, were assessed with respect to the zonal dependency of T2 and T2* relaxation for the deep and superficial regions of healthy articular cartilage and cartilage repair tissue. There was a statistically significant correlation between T2 and T2* values. Both parameters demonstrated similar spatial dependency, with longer values measured toward the articular surface for healthy articular cartilage. No spatial variation was observed for cartilage repair tissue after MFX. Within this feasibility study, both T2 and T2* relaxation parameters demonstrated a similar response in the assessment of articular cartilage and cartilage repair tissue. The potential advantages of T2*-mapping of cartilage include faster imaging times and the opportunity for 3D acquisitions, thereby providing greater spatial resolution and complete coverage of the articular surface. (orig.)

  6. T2 star relaxation times for assessment of articular cartilage at 3 T: a feasibility study

    International Nuclear Information System (INIS)

    T2 mapping techniques use the relaxation constant as an indirect marker of cartilage structure, and the relaxation constant has also been shown to be a sensitive parameter for cartilage evaluation. As a possible additional robust biomarker, T2* relaxation time is a potential, clinically feasible parameter for the biochemical evaluation of articular cartilage. The knees of 15 healthy volunteers and 15 patients after microfracture therapy (MFX) were evaluated with a multi-echo spin-echo T2 mapping technique and a multi-echo gradient-echo T2* mapping sequence at 3.0 Tesla MRI. Inline maps, using a log-linear least squares fitting method, were assessed with respect to the zonal dependency of T2 and T2* relaxation for the deep and superficial regions of healthy articular cartilage and cartilage repair tissue. There was a statistically significant correlation between T2 and T2* values. Both parameters demonstrated similar spatial dependency, with longer values measured toward the articular surface for healthy articular cartilage. No spatial variation was observed for cartilage repair tissue after MFX. Within this feasibility study, both T2 and T2* relaxation parameters demonstrated a similar response in the assessment of articular cartilage and cartilage repair tissue. The potential advantages of T2*-mapping of cartilage include faster imaging times and the opportunity for 3D acquisitions, thereby providing greater spatial resolution and complete coverage of the articular surface. (orig.)

  7. Minced articular cartilage--basic science, surgical technique, and clinical application.

    Science.gov (United States)

    McCormick, Frank; Yanke, Adam; Provencher, Matthew T; Cole, Brian J

    2008-12-01

    Minced articular cartilage procedures are attractive surgical approaches for repairing articular cartilage, as they are 1-staged, autologous, and inserted on a carrier that can potentially be placed arthroscopically. The principle of mincing the autologous donor cartilage is to create a larger surface area for cartilage expansion. Placement on a scaffold carrier allows for a chondro-inductive and chondro-conductive milieu. Early animal and preclinical models have demonstrated hyaline-like tissue repair. Further work needs to be conducted in this promising approach. PMID:19011553

  8. 3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation.

    Science.gov (United States)

    Smeriglio, Piera; Lai, Janice H; Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Human articular cartilage is highly susceptible to damage and has limited self-repair and regeneration potential. Cell-based strategies to engineer cartilage tissue offer a promising solution to repair articular cartilage. To select the optimal cell source for tissue repair, it is important to develop an appropriate culture platform to systematically examine the biological and biomechanical differences in the tissue-engineered cartilage by different cell sources. Here we applied a three-dimensional (3D) biomimetic hydrogel culture platform to systematically examine cartilage regeneration potential of juvenile, adult, and osteoarthritic (OA) chondrocytes. The 3D biomimetic hydrogel consisted of synthetic component poly(ethylene glycol) and bioactive component chondroitin sulfate, which provides a physiologically relevant microenvironment for in vitro culture of chondrocytes. In addition, the scaffold may be potentially used for cell delivery for cartilage repair in vivo. Cartilage tissue engineered in the scaffold can be evaluated using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. Utilizing these outcomes, we were able to characterize the differential regenerative potential of chondrocytes of varying age, both at the gene expression level and in the biochemical and biomechanical properties of the engineered cartilage tissue. The 3D culture model could be applied to investigate the molecular and functional differences among chondrocytes and progenitor cells from different stages of normal or aberrant development. PMID:26484414

  9. The 23rd Annual Meeting of the European Tissue Repair Society (ETRS) in Reims, France

    DEFF Research Database (Denmark)

    Von den Hoff, Johannes W; Ågren, Sven Per Magnus; Coulomb, Bernard;

    2014-01-01

    The 23rd Annual Meeting of the European Tissue Repair Society, Reims, France, October 23 to 25, 2013 focused on tissue repair and regenerative medicine covering topics such as stem cells, biomaterials, tissue engineering, and burns.......The 23rd Annual Meeting of the European Tissue Repair Society, Reims, France, October 23 to 25, 2013 focused on tissue repair and regenerative medicine covering topics such as stem cells, biomaterials, tissue engineering, and burns....

  10. Imaging of articular cartilage

    Directory of Open Access Journals (Sweden)

    Bhawan K Paunipagar

    2014-01-01

    Full Text Available We tried to review the role of magnetic resonance imaging (MRI in understanding microscopic and morphologic structure of the articular cartilage. The optimal protocols and available spin-echo sequences in present day practice are reviewed in context of common pathologies of articular cartilage. The future trends of articular cartilage imaging have been discussed with their appropriateness. In diarthrodial joints of the body, articular cartilage is functionally very important. It is frequently exposed to trauma, degeneration, and repetitive wear and tear. MRI has played a vital role in evaluation of articular cartilage. With the availability of advanced repair surgeries for cartilage lesions, there has been an increased demand for improved cartilage imaging techniques. Recent advances in imaging strategies for native and postoperative articular cartilage open up an entirely new approach in management of cartilage-related pathologies.

  11. Dedifferentiated Human Articular Chondrocytes Redifferentiate to a Cartilage-Like Tissue Phenotype in a Poly(ε-Caprolactone/Self-Assembling Peptide Composite Scaffold

    Directory of Open Access Journals (Sweden)

    Lourdes Recha-Sancho

    2016-06-01

    Full Text Available Adult articular cartilage has a limited capacity for growth and regeneration and, with injury, new cellular or biomaterial-based therapeutic platforms are required to promote repair. Tissue engineering aims to produce cartilage-like tissues that recreate the complex mechanical and biological properties found in vivo. In this study, a unique composite scaffold was developed by infiltrating a three-dimensional (3D woven microfiber poly (ε-caprolactone (PCL scaffold with the RAD16-I self-assembling nanofibers to obtain multi-scale functional and biomimetic tissue-engineered constructs. The scaffold was seeded with expanded dedifferentiated human articular chondrocytes and cultured for four weeks in control and chondrogenic growth conditions. The composite constructs were compared to control constructs obtained by culturing cells with 3D woven PCL scaffolds or RAD16-I independently. High viability and homogeneous cell distribution were observed in all three scaffolds used during the term of the culture. Moreover, gene and protein expression profiles revealed that chondrogenic markers were favored in the presence of RAD16-I peptide (PCL/RAD composite or alone under chondrogenic induction conditions. Further, constructs displayed positive staining for toluidine blue, indicating the presence of synthesized proteoglycans. Finally, mechanical testing showed that constructs containing the PCL scaffold maintained the initial shape and viscoelastic behavior throughout the culture period, while constructs with RAD16-I scaffold alone contracted during culture time into a stiffer and compacted structure. Altogether, these results suggest that this new composite scaffold provides important mechanical requirements for a cartilage replacement, while providing a biomimetic microenvironment to re-establish the chondrogenic phenotype of human expanded articular chondrocytes.

  12. Quantitative magnetic resonance imaging (MRI) evaluation of cartilage repair after microfracture (MF) treatment for adult unstable osteochondritis dissecans (OCD) in the ankle: correlations with clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Hongyue; Lu, Rong; Feng, Xiaoyuan; Chen, Shuang [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Shang, Xiliang; Li, Hong; Hua, Yinghui [Fudan University, Department of Sports Medicine, Huashan Hospital, Shanghai (China)

    2014-08-15

    To quantitatively evaluate cartilage repair after microfracture (MF) for ankle osteochondritis dissecans (OCD) using MRI and analyse correlations between MRI and clinical outcome. Forty-eight patients were recruited and underwent MR imaging, including 3D-DESS, T2-mapping and T2-STIR sequences, and completed American Orthopaedic Foot and Ankle Society (AOFAS) scoring. Thickness index, T2 index of repair tissue (RT) and volume of subchondral bone marrow oedema (BME) were calculated. Subjects were divided into two groups: group A (3-12 months post-op), and group B (12-24 months post-op). Student's t test was used to compare the MRI and AOFAS score between two groups and Pearson's correlation coefficient to analyse correlations between them. Thickness index and AOFAS score of group B were higher than group A (P < 0.001, P < 0.001). T2 index and BME of group B were lower than group A (P < 0.001, P = 0.012). Thickness index, T2 index and BME were all correlated with AOFAS score (r = 0.416, r = -0.475, r = -0.353), but BME was correlated with neither thickness index nor T2 index. Significant improvement from MF can be expected on the basis of the outcomes of quantitative MRI and AOFAS score. MRI was correlated with AOFAS score. BME is insufficient as an independent predictor to evaluate repair quality, but reduction of BME can improve the patient's clinical outcome. (orig.)

  13. A comparison study of different physical treatments on cartilage matrix derived porous scaffolds for tissue engineering applications

    International Nuclear Information System (INIS)

    Native cartilage matrix derived (CMD) scaffolds from various animal and human sources have drawn attention in cartilage tissue engineering due to the demonstrable presence of bioactive components. Different chemical and physical treatments have been employed to enhance the micro-architecture of CMD scaffolds. In this study we have assessed the typical effects of physical cross-linking methods, namely ultraviolet (UV) light, dehydrothermal (DHT) treatment, and combinations of them on bovine articular CMD porous scaffolds with three different matrix concentrations (5%, 15% and 30%) to assess the relative strengths of each treatment. Our findings suggest that UV and UV–DHT treatments on 15% CMD scaffolds can yield architecturally optimal scaffolds for cartilage tissue engineering. (paper)

  14. Zebrafish Heart Regeneration as a Model for Cardiac Tissue Repair

    OpenAIRE

    Major, Robert J.; Poss, Kenneth D.

    2007-01-01

    Heart disease remains the leading cause of mortality throughout the world. Mammals have an extremely limited capacity to repair lost or damaged heart tissue, thus encouraging biologists to seek out models for heart regeneration. Zebrafish exhibit a robust regenerative capacity in a variety of tissues including the fin, spinal cord, retina, and heart, making it the sole regenerative vertebrate organism currently amenable to genetic manipulation. Future studies will utilize functional approache...

  15. Comparison of three types of chondrocytes in collagen scaffolds for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Lu [Department of Plastic and Reconstructive Surgery, Shanghai Tissue Engineering Center, Shanghai 9th People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Spector, Myron, E-mail: luzhangmd@gmail.co [Tissue Engineering, VA Boston Healthcare System, Boston, MA (United States)

    2009-08-15

    The objective of this study was to compare the chondrogenesis in type I and II collagen scaffolds seeded with chondrocytes from three types of cartilage, after four weeks of culture: auricular (AU), articular (AR) and meniscal (ME). Related aims were to investigate the expression of a contractile muscle actin isoform, alpha-smooth muscle actin (SMA), in the cells in the scaffold and to determine the presence of a lubricating glycoprotein, lubricin, in the constructs. Adult goat AU, AR and ME chondrocytes were seeded into two types of collagen scaffolds: type II collagen and type I/III collagen. After four weeks of culture, the constructs were prepared for histochemical and immunohistochemical analysis of the distribution of glycosaminoglycan (GAG), types I and II collagen, elastin, SM and lubricin. AU constructs contained substantially more tissue than the AR and ME samples. The AU constructs exhibited neocartilage, but no elastin. There were no notable differences between the type I and II collagen scaffolds. Novel findings were the expression of SMA by the AU cells in the scaffolds and the presence of lubricin in the AR and AU constructs. AU cells have the capability to produce cartilage in collagen scaffolds under conditions in which there is little histogenesis by AR and ME cells.

  16. Analyzing Biological Performance of 3D-Printed, Cell-Impregnated Hybrid Constructs for Cartilage Tissue Engineering.

    Science.gov (United States)

    Izadifar, Zohreh; Chang, Tuanjie; Kulyk, William; Chen, Xiongbiao; Eames, B Frank

    2016-03-01

    Three-dimensional (3D) bioprinting of hybrid constructs is a promising biofabrication method for cartilage tissue engineering because a synthetic polymer framework and cell-impregnated hydrogel provide structural and biological features of cartilage, respectively. During bioprinting, impregnated cells may be subjected to high temperatures (caused by the adjacent melted polymer) and process-induced mechanical forces, potentially compromising cell function. This study addresses these biofabrication issues, evaluating the heat distribution of printed polycaprolactone (PCL) strands and the rheological property and structural stability of alginate hydrogels at various temperatures and concentrations. The biocompatibility of parameters from these studies was tested by culturing 3D hybrid constructs bioprinted with primary cells from embryonic chick cartilage. During initial two-dimensional culture expansion of these primary cells, two morphologically and molecularly distinct cell populations ("rounded" and "fibroblastic") were isolated. The biological performance of each population was evaluated in 3D hybrid constructs separately. The cell viability, proliferation, and cartilage differentiation were observed at high levels in hybrid constructs of both cell populations, confirming the validity of these 3D bioprinting parameters for effective cartilage tissue engineering. Statistically significant performance variations were observed, however, between the rounded and fibroblastic cell populations. Molecular and morphological data support the notion that such performance differences may be attributed to the relative differentiation state of rounded versus fibroblastic cells (i.e., differentiated chondrocytes vs. chondroprogenitors, respectively), which is a relevant issue for cell-based tissue engineering strategies. Taken together, our study demonstrates that bioprinting 3D hybrid constructs of PCL and cell-impregnated alginate hydrogel is a promising approach for

  17. Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model

    OpenAIRE

    Chung, Jun Young; Song, Minjung; Ha, Chul-Won; Kim, Jin-A; Lee, Choong-Hee; Park, Yong-Beom

    2014-01-01

    Introduction The present work was designed to explore the feasibility and efficacy of articular cartilage repair using composites of human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) and four different hydrogels in a rat model. Methods Full-thickness articular cartilage defects were created at the trochlear groove of femur in both knees of rats. Composites of hUCB-MSCs and four different hydrogels (group A, 4% hyaluronic acid; group B, 3% alginate:30% pluronic (1:1, v/v); ...

  18. Host Responses in Tissue Repair and Fibrosis

    Science.gov (United States)

    Duffield, Jeremy S.; Lupher, Mark; Thannickal, Victor J.

    2013-01-01

    Myofibroblasts accumulate in the spaces between organ structures and produce extracellular matrix (ECM) proteins, including collagen I. They are the primary “effector” cells in tissue remodeling and fibrosis. Previously, leukocyte progenitors termed fibrocytes and myofibroblasts generated from epithelial cells through epithelial-to-mesenchymal transition (EMT) were considered the primary sources of ECM-producing myofibroblasts in injured tissues. However, genetic fate mapping experiments suggest that mesenchyme-derived cells, known as resident fibroblasts, and pericytes are the primary precursors of scar-forming myofibroblasts, whereas epithelial cells, endothelial cells, and myeloid leukocytes contribute to fibrogenesis predominantly by producing key fibrogenic cytokines and by promoting cell-to-cell communication. Numerous cytokines derived from T cells, macrophages, and other myeloid cell populations are important drivers of myofibroblast differentiation. Monocyte-derived cell populations are key regulators of the fibrotic process: They act as a brake on the processes driving fibrogenesis, and they dismantle and degrade established fibrosis. We discuss the origins, modes of activation, and fate of myofibroblasts in various important fibrotic diseases and describe how manipulation of macrophage activation could help ameliorate fibrosis. PMID:23092186

  19. Transplantation of sheep embrionic stem cells in cartilage lesions: preliminary observations

    OpenAIRE

    Rocca, Stefano; Antuofermo, Elisabetta; Dattena, Maria; Manunta, Maria Lucia Gabriella M.; Pilichi, Susanna; Meloni, Floriana; Leoni, Antonio

    2007-01-01

    Once damaged, joint cartilage never completely regenerates. This is due to absence of vascularisation, slow cellular turnover and impossibility for inflammation mediators to reach the cartilage lesion. Even small lesions involve alteration in joint functionality and can cause invalidating pathologies. Treatment is complex and the surgical techniques used to repair the joint surfaces do not give satisfactory and durable results because the new tissue produced is fibrous cartilage. The...

  20. Preparing PCL/PLGA Hybrid Nanofiber Scaffold Capable of Controlled Releasing of Insulin for Cartilage Tissue Engineering Application

    Directory of Open Access Journals (Sweden)

    A Basiri

    2014-08-01

    Conclusion: Biological activity of insulin has been maintained during 22 days of controlled release from hybrid nanofiber PCL/PLGA scaffold. Chondrocytes were distributed evenly throughout the scaffold and revealed a rounded morphology. Therefore, this scaffold provides a suitable carrier for chondrocyte growth as well as formation of tissue engineered cartilage.

  1. Flexible and Elastic Scaffolds for Cartilage Tissue Engineering Prepared by Stereolithography Using Poly(trimethylene carbonate)-Based Resins

    NARCIS (Netherlands)

    Schuller-Ravoo, Sigrid; Teixeira, Sandra M.; Feijen, Jan; Grijpma, Dirk W.; Poot, Andre A.

    2013-01-01

    The aim of this study is to investigate the applicability of flexible and elastic poly(trimethylene carbonate) (PTMC) structures prepared by stereolithography as scaffolds for cartilage tissue engineering. A three-armed methacrylated PTMC macromer with a molecular weight of 3100gmol(-1) is used to b

  2. Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue

    Science.gov (United States)

    Armstrong, James P. K.; Shakur, Rameen; Horne, Joseph P.; Dickinson, Sally C.; Armstrong, Craig T.; Lau, Katherine; Kadiwala, Juned; Lowe, Robert; Seddon, Annela; Mann, Stephen; Anderson, J. L. Ross; Perriman, Adam W.; Hollander, Anthony P.

    2015-06-01

    Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show that pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer-surfactant complexes can provide a reservoir of oxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achieved through the development of a new cell functionalization methodology based on polymer-surfactant conjugation, which allows the delivery of functional proteins to the hMSC membrane. This new approach circumvents the need for cell surface engineering using protein chimerization or genetic transfection, and we demonstrate that the surface-modified hMSCs retain their ability to proliferate and to undergo multilineage differentiation. The functionalization technology is facile, versatile and non-disruptive, and in addition to tissue oxygenation, it should have far-reaching application in a host of tissue engineering and cell-based therapies.

  3. Microstructure and properties of nano-fibrous PCL-b-PLLA scaffolds for cartilage tissue engineering

    Directory of Open Access Journals (Sweden)

    L He

    2009-10-01

    Full Text Available Nano-fibrous scaffolds which could potentially mimic the architecture of extracellular matrix (ECM have been considered a good candidate matrix for cell delivery in tissue engineering applications. In the present study, a semicrystalline diblock copolymer, poly(e-caprolactone-block-poly(L-lactide (PCL-b-PLLA, was synthesized and utilized to fabricate nano-fibrous scaffolds via a thermally induced phase separation process. Uniform nano-fibrous networks were created by quenching a PCL-b-PLLA/THF homogenous solution to -20ºC or below, followed by further gelation for 2 hours due to the presence of PLLA and PCL microcrystals. However, knot-like structures as well as continuously smooth pellicles appeared among the nano-fibrous network with increasing gelation temperature. DSC analysis indicated that the crystallization of PCL segments was interrupted by rigid PLLA segments, resulting in an amorphous phase at high gelation temperatures. Combining TIPS (thermally induced phase separation with salt-leaching methods, nano-fibrous architecture and interconnected pore structures (144±36 mm in diameter with a high porosity were created for in vitro culture of chondrocytes. Specific surface area and protein adsorption on the surface of the nano-fibrous scaffold were three times higher than on the surface of the solid-walled scaffold. Chondrocytes cultured on the nano-fibrous scaffold exhibited a spherical condrocyte-like phenotype and secreted more cartilage-like extracellular matrix (ECM than those cultured on the solid-walled scaffold. Moreover, the protein and DNA contents of cells cultured on the nano-fibrous scaffold were 1.2-1.4 times higher than those on the solid-walled scaffold. Higher expression levels of collagen II and aggrecan mRNA were induced on the nano-fibrous scaffold compared to on the solid-walled scaffold. These findings demonstrated that scaffolds with a nano-fibrous architecture could serve as superior scaffolds for cartilage tissue

  4. Kartogenin induces cartilage-like tissue formation in tendon–bone junction

    OpenAIRE

    Zhang, Jianying; Wang, James H-C.

    2014-01-01

    Tendon–bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells...

  5. Ultrasonography and Radiography Evaluation of the Cartilage Graft in Repair of Experimentally Induced Radial Bone Defect in Rabbit

    Directory of Open Access Journals (Sweden)

    Foad Sadi

    2010-01-01

    Full Text Available We would like to thank to the Faculty of Specialized Veterinary Sciences research council. Science and Research Branch of Islamic Azad University, Punak Tehran for approval and financial support to finish this project. Problems statement: The purpose of this research was to determine the biological effect of cartilage graft as a bone defect filler and osteogenetic stimulation to speed up bone healing too. Approach: Sixteen adult male New Zealand white rabbits having body weight ranged from 3.0-3.5 Kg. Under general anesthesia, a segmental full thickness bone defect of 10 mm in length was created in the middle of the right radial shaft in all rabbits. They were divided into two groups of 6 rabbits each. Group I was considered as control and the fractured site was fixed using finger bone plate with 4 screws, whereas the ear cartilage of 1×1 cm graft was used to fill the gap after fracture fixation in Group II. Rabbits in two groups were subdivided into 2 subgroups of 1 and 2 months duration with 4 rabbits in each. Radiography and two dimensional and color Doppler sonography were done before and after creating defects and on 15, 30 and 60 days to evaluate local reaction as far as new blood vessels network and callus formation are concerned. Results: On the radiographs during the whole process, bone repair in Group I was not as perfect as those in Group II samples and trace of internal callus filled the gap incompletely in 60 days in Group I, whereas in Group II internal callus almost was formed on 30 days and in addition intercortical callus was seen supporting to cover and filled the gap completely in this group. Sonographic findings confirmed the protrusion of newly formed blood vascular network in 30 days in Group I and from 15 days in Group II and remarkably increased till end of observation period. Conclusion: Cartilage graft is suitable alternative bone filler and radiography and sonography are reliable techniques to trace local reaction at

  6. Comparison of Engineered Peptide-Glycosaminoglycan Microfibrous Hybrid Scaffolds for Potential Applications in Cartilage Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Steven M. Romanelli

    2015-07-01

    Full Text Available Advances in tissue engineering have enabled the ability to design and fabricate biomaterials at the nanoscale that can actively mimic the natural cellular environment of host tissue. Of all tissues, cartilage remains difficult to regenerate due to its avascular nature. Herein we have developed two new hybrid polypeptide-glycosaminoglycan microfibrous scaffold constructs and compared their abilities to stimulate cell adhesion, proliferation, sulfated proteoglycan synthesis and soluble collagen synthesis when seeded with chondrocytes. Both constructs were designed utilizing self-assembled Fmoc-protected valyl cetylamide nanofibrous templates. The peptide components of the constructs were varied. For Construct I a short segment of dentin sialophosphoprotein followed by Type I collagen were attached to the templates using the layer-by-layer approach. For Construct II, a short peptide segment derived from the integrin subunit of Type II collagen binding protein expressed by chondrocytes was attached to the templates followed by Type II collagen. To both constructs, we then attached the natural polymer N-acetyl glucosamine, chitosan. Subsequently, the glycosaminoglycan chondroitin sulfate was then attached as the final layer. The scaffolds were characterized by Fourier transform infrared spectroscopy (FT-IR, differential scanning calorimetry (DSC, atomic force microscopy and scanning electron microscopy. In vitro culture studies were carried out in the presence of chondrocyte cells for both scaffolds and growth morphology was determined through optical microscopy and scanning electron microscopy taken at different magnifications at various days of culture. Cell proliferation studies indicated that while both constructs were biocompatible and supported the growth and adhesion of chondrocytes, Construct II stimulated cell adhesion at higher rates and resulted in the formation of three dimensional cell-scaffold matrices within 24 h. Proteoglycan

  7. Effect of microcavitary alginate hydrogel with different pore sizes on chondrocyte culture for cartilage tissue engineering

    International Nuclear Information System (INIS)

    In our previous work, a novel microcavitary hydrogel was proven to be effective for proliferation of chondrocytes and maintenance of chondrocytic phenotype. In present work, we further investigated whether the size of microcavity would affect the growth and the function of chondrocytes. By changing the stirring rate, gelatin microspheres in different sizes including small size (80–120 μm), middle size (150–200 μm) and large size (250–300 μm) were prepared. And then porcine chondrocytes were encapsulated into alginate hydrogel with various sizes of gelatin microspheres. Cell Counting Kit-8 (CCK-8), Live/dead staining and real-time PCR were used to analyze the effect of the pore size on cell proliferation and expression of specific chondrocytic genes. According to all the data, cells cultivated in microcavitary hydrogel, especially in small size, had preferable abilities of proliferation and higher expression of cartilaginous markers including type II collagen, aggrecan and cartilage oligomeric matrix protein (COMP). Furthermore, it was shown by western blot assay that the culture of chondrocytes in microcavitary hydrogel could improve the proliferation of cells potentially by inducing the Erk1/2-MAPK pathway. Taken together, this study demonstrated that chondrocytes favored microcavitary alginate hydrogel with pore size within the range of 80–120 μm for better growth and ECM synthesis, in which Erk1/2 pathway was involved. This culture system would be promising for cartilage tissue engineering. - Highlights: • A novel model with microcavitary structure was set up to study the interaction between cells and materials. • Microcavitary alginate hydrogel could enhance the proliferation of chondrocytes and promote the expression of cartilaginous genes as compared with plain alginate hydrogel. • Cells in microcavitary alginate hydrogel with pore size within the range of 80–120 μm were capable of better growth and ECM synthesis

  8. Effect of microcavitary alginate hydrogel with different pore sizes on chondrocyte culture for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Lei; Yao, Yongchang [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Wang, Dong-an, E-mail: DAWang@ntu.edu.sg [National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457 (Singapore); Chen, Xiaofeng, E-mail: chenxf@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China)

    2014-01-01

    In our previous work, a novel microcavitary hydrogel was proven to be effective for proliferation of chondrocytes and maintenance of chondrocytic phenotype. In present work, we further investigated whether the size of microcavity would affect the growth and the function of chondrocytes. By changing the stirring rate, gelatin microspheres in different sizes including small size (80–120 μm), middle size (150–200 μm) and large size (250–300 μm) were prepared. And then porcine chondrocytes were encapsulated into alginate hydrogel with various sizes of gelatin microspheres. Cell Counting Kit-8 (CCK-8), Live/dead staining and real-time PCR were used to analyze the effect of the pore size on cell proliferation and expression of specific chondrocytic genes. According to all the data, cells cultivated in microcavitary hydrogel, especially in small size, had preferable abilities of proliferation and higher expression of cartilaginous markers including type II collagen, aggrecan and cartilage oligomeric matrix protein (COMP). Furthermore, it was shown by western blot assay that the culture of chondrocytes in microcavitary hydrogel could improve the proliferation of cells potentially by inducing the Erk1/2-MAPK pathway. Taken together, this study demonstrated that chondrocytes favored microcavitary alginate hydrogel with pore size within the range of 80–120 μm for better growth and ECM synthesis, in which Erk1/2 pathway was involved. This culture system would be promising for cartilage tissue engineering. - Highlights: • A novel model with microcavitary structure was set up to study the interaction between cells and materials. • Microcavitary alginate hydrogel could enhance the proliferation of chondrocytes and promote the expression of cartilaginous genes as compared with plain alginate hydrogel. • Cells in microcavitary alginate hydrogel with pore size within the range of 80–120 μm were capable of better growth and ECM synthesis.

  9. Use of Environmental and Physical Stimuli in Cartilage Tissue Engineering Engineering

    OpenAIRE

    Das, Ruud

    2014-01-01

    markdownabstract__Abstract__ Articular cartilage enables friction-free, and thus painless, joint movement, while also functioning as a shock absorber. Although articular cartilage is made up of only few main components, natural healing fails to re-establish the native organization of the extracellular matrix and surgical intervention has only limited success in long term follow up. The relatively simple composition of articular cartilage, combined with a high prevalence of damage, make it an ...

  10. Role of Chondrocytes in Cartilage Formation, Progression of Osteoarthritis and Cartilage Regeneration

    Science.gov (United States)

    Akkiraju, Hemanth; Nohe, Anja

    2016-01-01

    Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their function leads to degenerative diseases like Osteoarthritis (OA). OA is characterized by cartilage degradation, osteophyte formation and stiffening of joints. Cartilage degeneration is a consequence of chondrocyte hypertrophy along with the expression of proteolytic enzymes. Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) are an example of these enzymes that degrade the ECM. Signaling cascades involved in limb patterning and cartilage repair play a role in OA progression. However, the regulation of these remains to be elucidated. Further the role of stem cells and mature chondrocytes in OA progression is unclear. The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term. However, many questions are unanswered such as the efficacy of MSCs usage in therapy. This review focuses on the role of chondrocytes in cartilage formation and the progression of OA. Moreover, it summarizes possible alternative therapeutic approaches using MSC infusion for cartilage restoration. PMID:27347486

  11. Construction of tissue-engineered cartilage using human placenta-derived stem cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Human placenta-derived stem cells (hPDSCs) were isolated by trypsinization and further induced into cartilage cells in vitro.The engineered cartilage was constructed by combining hPDSCs with collagen sponge and the cartilage formation was observed by implantation into nude mice.Results showed that hPDSCs featured mesenchymal stem cells and maintained proliferation in vitro for over 30 passages while remaining undifferentiated.All results indicated that hPDSCs have the potential to differentiate into functional cartilage cells in vitro when combined with collagen sponge,which provided experimental evidence for prospective clinical application.

  12. BST-CarGel® Treatment Maintains Cartilage Repair Superiority over Microfracture at 5 Years in a Multicenter Randomized Controlled Trial

    OpenAIRE

    Shive, Matthew S.; Stanish, William D; McCormack,Robert; Forriol, Francisco; Mohtadi, Nicholas; Pelet, Stéphane; Desnoyers, Jacques; Méthot, Stéphane; Vehik, Kendra; Restrepo, Alberto

    2015-01-01

    Objective The efficacy and safety of BST-CarGel®, a chitosan scaffold for cartilage repair was compared with microfracture alone at 1 year during a multicenter randomized controlled trial in the knee. This report was undertaken to investigate 5-year structural and clinical outcomes. Design The international randomized controlled trial enrolled 80 patients, aged 18 to 55 years, with grade III or IV focal lesions on the femoral condyles. Patients were randomized to receive BST-CarGel® treatment...

  13. Evaluation of Three-Dimensional Chitosan-Agarose-Gelatin Cryogel Scaffold for the Repair of Subchondral Cartilage Defects: An In Vivo Study in a Rabbit Model

    OpenAIRE

    Gupta, Ankur; Bhat, Sumrita; Jagdale, Pankaj R.; Bhushan P Chaudhari; Lidgren, Lars; Gupta, Kailash C.; Kumar, Ashok

    2014-01-01

    In this study, the potential of a chitosan-agarose-gelatin (CAG) cryogel scaffold for the repair of subchondral cartilage defects was explored in female New Zealand white rabbits. Custom-made CAG cryogel scaffold was implanted in a surgically created subchondral defect (diameter of 4 mm, depth of 4 mm) in knee joint of rabbit. The repair of the subchondral defect was evaluated at regular time interval by both macroscopic as well as microscopic examinations. The gross evaluation of the scaffol...

  14. Research trends in biomimetic medical materials for tissue engineering: 3D bioprinting, surface modification, nano/micro-technology and clinical aspects in tissue engineering of cartilage and bone.

    Science.gov (United States)

    Chen, Cen; Bang, Sumi; Cho, Younghak; Lee, Sahnghoon; Lee, Inseop; Zhang, ShengMin; Noh, Insup

    2016-01-01

    This review discusses about biomimetic medical materials for tissue engineering of bone and cartilage, after previous scientific commentary of the invitation-based, Korea-China joint symposium on biomimetic medical materials, which was held in Seoul, Korea, from October 22 to 26, 2015. The contents of this review were evolved from the presentations of that symposium. Four topics of biomimetic medical materials were discussed from different research groups here: 1) 3D bioprinting medical materials, 2) nano/micro-technology, 3) surface modification of biomaterials for their interactions with cells and 4) clinical aspects of biomaterials for cartilage focusing on cells, scaffolds and cytokines. PMID:27148455

  15. Experimental study of tissue-engineered cartilage allograft with RNAi chondrocytes in vivo

    Directory of Open Access Journals (Sweden)

    Wang ZH

    2014-05-01

    Full Text Available Zhenghui Wang,1 Xiaoli Li,2 Xi-Jing He,3 Xianghong Zhang,1 Zhuangqun Yang,4 Min Xu,1 Baojun Wu,1 Junbo Tu,5 Huanan Luo,1 Jing Yan11Department of Otolaryngology – Head and Neck Surgery, 2Department of Dermatology, 3Department of Orthopedics, The Second Hospital, Xi’an Jiaotong University, 4Department of Plastic and Burns Surgery, The First Hospital, Xi’an Jiaotong University, 5Department of Oral and Maxillofacial Plastic Surgery, The Stomatological Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaPurpose: To determine the effects of RNA interference (RNAi on chondrocyte proliferation, function, and immunological rejection after allogenic tissue-engineered cartilage transplantation within bone matrix gelatin scaffolds.Methods: Seven million rat normal and RNAi chondrocytes were harvested and separately composited with fibrin glue to make the cell suspension, and then transplanted subcutaneously into the back of Sprague Dawley rats after being cultured for 10 days in vitro. Untransplanted animals served as the control group. The allograft and immunological response were examined at 1, 2, 4, 8, and 12 months postoperatively with hematoxylin and eosin histochemical staining, immunohistochemical staining (aggrecan, type II collagen, class I and II major histocompatibility complex, and flow cytometry for peripheral blood cluster of differentiation 4+ (CD4+ and CD8+ T-cells.Results: There was no infection or death in the rats except one, which died in the first week. Compared to the control group, the RNAi group had fewer eukomonocytes infiltrated, which were only distributed around the graft. The ratio of CD4+/CD8+ T-cells in the RNAi group was significantly lower than the normal one (P<0.05. There were many more positively stained chondrocytes and positively stained areas around the cells in the RNAi group, which were not found in the control group.Conclusion: The aggrecanase-1 and aggrecanase-2 RNAi for chondrocytes

  16. Steric Interference of Adhesion Supports In-Vitro Chondrogenesis of Mesenchymal Stem Cells on Hydrogels for Cartilage Repair

    Science.gov (United States)

    Goldshmid, Revital; Cohen, Shlomit; Shachaf, Yonatan; Kupershmit, Ilana; Sarig-Nadir, Offra; Seliktar, Dror; Wechsler, Roni

    2015-01-01

    Recent studies suggest the presence of cell adhesion motifs found in structural proteins can inhibit chondrogenesis. In this context, the current study aims to determine if a polyethylene glycol (PEG)-modified fibrinogen matrix could support better chondrogenesis of human bone marrow mesenchymal stem cells (BM-MSC) based on steric interference of adhesion, when compared to a natural fibrin matrix. Hydrogels used as substrates for two-dimensional (2D) BM-MSC cultures under chondrogenic conditions were made from cross-linked PEG-fibrinogen (PF) and compared to thrombin-activated fibrin. Cell morphology, protein expression, DNA and sulfated proteoglycan (GAG) content were correlated to substrate properties such as stiffness and adhesiveness. Cell aggregation and chondrogenic markers, including collagen II and aggrecan, were observed on all PF substrates but not on fibrin. Shielding fibrinogen’s adhesion domains and increasing stiffness of the material are likely contributing factors that cause the BM-MSCs to display a more chondrogenic phenotype. One composition of PF corresponding to GelrinC™—a product cleared in the EU for cartilage repair—was found to be optimal for supporting chondrogenic differentiation of BM-MSC while minimizing hypertrophy (collagen X). These findings suggest that semi-synthetic biomaterials based on ECM proteins can be designed to favourably affect BM-MSC towards repair processes involving chondrogenesis. PMID:26411496

  17. Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis

    International Nuclear Information System (INIS)

    The goal of this study was to use bioengineered injectable microgels to enhance the action of bone morphogenetic protein 2 (BMP2) and stimulate cartilage matrix repair in a reversible animal model of osteoarthritis (OA). A module of perlecan (PlnD1) bearing heparan sulfate (HS) chains was covalently immobilized to hyaluronic acid (HA) microgels for the controlled release of BMP2 in vivo. Articular cartilage damage was induced in mice using a reversible model of experimental OA and was treated by intra-articular injection of PlnD1-HA particles with BMP2 bound to HS. Control injections consisted of BMP2-free PlnD1-HA particles, HA particles, free BMP2 or saline. Knees dissected following these injections were analyzed using histological, immunostaining and gene expression approaches. Our results show that knees treated with PlnD1-HA/BMP2 had lesser OA-like damage compared to control knees. In addition, the PlnD1-HA/BMP2-treated knees had higher mRNA levels encoding for type II collagen, proteoglycans and xylosyltransferase 1, a rate-limiting anabolic enzyme involved in the biosynthesis of glycosaminoglycan chains, relative to control knees (PlnD1-HA). This finding was paralleled by enhanced levels of aggrecan in the articular cartilage of PlnD1-HA/BMP2-treated knees. Additionally, decreases in the mRNA levels encoding for cartilage-degrading enzymes and type X collagen were seen relative to controls. In conclusion, PlnD1-HA microgels constitute a formulation improvement compared to HA for efficient in vivo delivery and stimulation of proteoglycan and cartilage matrix synthesis in mouse articular cartilage. Ultimately, PlnD1-HA/BMP2 may serve as an injectable therapeutic agent for slowing or inhibiting the onset of OA after knee injury.

  18. Apparatus and method for enhancing tissue repair in mammals

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

    2009-01-01

    An apparatus is introduced for the use of enhancing tissue repair in mammals. The apparatus includes a sleeve; an electrically conductive coil; a sleeve support; an electrical circuit configured to supply the coil with a square wave time varying electrical current sufficient to create approximately 0.05 gauss to 0.5 gauss. When in use, the sleeve of the apparatus is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.5 gauss is generated on the mammalian body for an extended period of time so that the tissue is encouraged to be regenerated in the mammalian body part at a rate in excess of the normal tissue regeneration rate relative to regeneration without application of the time varying electromagnetic force.

  19. The application of POSS nanostructures in cartilage tissue engineering: the chondrocyte response to nanoscale geometry.

    Science.gov (United States)

    Oseni, Adelola O; Butler, Peter E; Seifalian, Alexander M

    2015-11-01

    Despite extensive research into cartilage tissue engineering (CTE), there is still no scaffold ideal for clinical applications. Various synthetic and natural polymers have been investigated in vitro and in vivo, but none have reached widespread clinical use. The authors investigate the potential of POSS-PCU, a synthetic nanocomposite polymer, for use in CTE. POSS-PCU is modified with silsesquioxane nanostructures that improve its biological and physical properties. The ability of POSS-PCU to support the growth of ovine nasoseptal chondrocytes was evaluated against a polymer widely used in CTE, polycaprolactone (PCL). Scaffolds with varied concentrations of the POSS molecule were also synthesized to investigate their effect on chondrocyte growth. Chondrocytes were seeded onto scaffold disks (PCU negative control; POSS-PCU 2%, 4%, 6%, 8%; PCL). Cytocompatibilty was evaluated using cell viability, total DNA, collagen and GAG assays. Chondrocytes cultured on POSS-PCU (2% POSS) scaffolds had significantly higher viability than PCL scaffolds (p PCU scaffolds compared with PCL (p > 0.05). POSS-PCU (6% and 8% POSS) had improved viability and proliferation over an 18 day culture period compared with 2% and 4% POSS-PCU (p PCU has excellent potential for use in CTE. It supports the growth of chondrocytes in vitro and the POSS modification significantly enhances the growth and proliferation of nasoseptal chondrocytes compared with traditional scaffolds such as PCL. PMID:23576328

  20. Use of bone morphogenetic proteins in mesenchymal stem cell stimulation of cartilage and bone repair

    OpenAIRE

    Scarfì, Sonia

    2016-01-01

    The extracellular matrix-associated bone morphogenetic proteins (BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed i...

  1. Lubricin is expressed in chondrocytes derived from osteoarthritic cartilage encapsulated in poly(ethylene glycol diacrylate scaffold

    Directory of Open Access Journals (Sweden)

    G. Musumeci

    2011-09-01

    Full Text Available Osteoarthritis (OA is characterized by degenerative changes within joints that involved quantitative and/or qualitative alterations of cartilage and synovial fluid lubricin, a mucinous glycoprotein secreted by synovial fibroblasts and chondrocytes. Modern therapeutic methods, including tissue-engineering techniques, have been used to treat mechanical damage of the articular cartilage but to date there is no specific and effective treatment. This study aimed at investigating lubricin immunohistochemical expression in cartilage explant from normal and OA patients and in cartilage constructions formed by Poly (ethylene glycol (PEG based hydrogels (PEG-DA encapsulated OA chondrocytes. The expression levels of lubricin were studied by immunohistochemistry: i in tissue explanted from OA and normal human cartilage; ii in chondrocytes encapsulated in hydrogel PEGDA from OA and normal human cartilage. Moreover, immunocytochemical and western blot analysis were performed in monolayer cells from OA and normal cartilage. The results showed an increased expression of lubricin in explanted tissue and in monolayer cells from normal cartilage, and a decreased expression of lubricin in OA cartilage. The chondrocytes from OA cartilage after 5 weeks of culture in hydrogels (PEGDA showed an increased expression of lubricin compared with the control cartilage. The present study demonstrated that OA chondrocytes encapsulated in PEGDA, grown in the scaffold and were able to restore lubricin biosynthesis. Thus our results suggest the possibility of applying autologous cell transplantation in conjunction with scaffold materials for repairing cartilage lesions in patients with OA to reduce at least the progression of the disease.

  2. Cellular responses of embryonic hyaline cartilage to experimental wounding in vitro.

    Science.gov (United States)

    Walker, E A; Verner, A; Flannery, C R; Archer, C W

    2000-01-01

    It is well established that the reparative potential of many tissues is greatest during embryonic development. Despite the extensive literature documenting repair in nonembryonic cartilage models, there is no comparable wealth of experience relating to embryonic cartilage repair. With the embryonic chick sternum as a model of hyaline cartilage, this paper accounts cellular responses and alterations in extracellular matrix composition in response to experimental wounding in vitro. Creation of an experimental lesion induced a rapid (apoptosis and the expression of alpha5 and alpha6 integrin subunits. PMID:10716275

  3. Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage.

    Science.gov (United States)

    Brunger, Jonathan M; Huynh, Nguyen P T; Guenther, Caitlin M; Perez-Pinera, Pablo; Moutos, Franklin T; Sanchez-Adams, Johannah; Gersbach, Charles A; Guilak, Farshid

    2014-03-01

    The ability to develop tissue constructs with matrix composition and biomechanical properties that promote rapid tissue repair or regeneration remains an enduring challenge in musculoskeletal engineering. Current approaches require extensive cell manipulation ex vivo, using exogenous growth factors to drive tissue-specific differentiation, matrix accumulation, and mechanical properties, thus limiting their potential clinical utility. The ability to induce and maintain differentiation of stem cells in situ could bypass these steps and enhance the success of engineering approaches for tissue regeneration. The goal of this study was to generate a self-contained bioactive scaffold capable of mediating stem cell differentiation and formation of a cartilaginous extracellular matrix (ECM) using a lentivirus-based method. We first showed that poly-L-lysine could immobilize lentivirus to poly(ε-caprolactone) films and facilitate human mesenchymal stem cell (hMSC) transduction. We then demonstrated that scaffold-mediated gene delivery of transforming growth factor β3 (TGF-β3), using a 3D woven poly(ε-caprolactone) scaffold, induced robust cartilaginous ECM formation by hMSCs. Chondrogenesis induced by scaffold-mediated gene delivery was as effective as traditional differentiation protocols involving medium supplementation with TGF-β3, as assessed by gene expression, biochemical, and biomechanical analyses. Using lentiviral vectors immobilized on a biomechanically functional scaffold, we have developed a system to achieve sustained transgene expression and ECM formation by hMSCs. This method opens new avenues in the development of bioactive implants that circumvent the need for ex vivo tissue generation by enabling the long-term goal of in situ tissue engineering. PMID:24550481

  4. Studies of mineralization in tissue culture: optimal conditions for cartilage calcification

    Science.gov (United States)

    Boskey, A. L.; Stiner, D.; Doty, S. B.; Binderman, I.; Leboy, P.

    1992-01-01

    The optimal conditions for obtaining a calcified cartilage matrix approximating that which exists in situ were established in a differentiating chick limb bud mesenchymal cell culture system. Using cells from stage 21-24 embryos in a micro-mass culture, at an optimal density of 0.5 million cells/20 microliters spot, the deposition of small crystals of hydroxyapatite on a collagenous matrix and matrix vesicles was detected by day 21 using X-ray diffraction, FT-IR microscopy, and electron microscopy. Optimal media, containing 1.1 mM Ca, 4 mM P, 25 micrograms/ml vitamin C, 0.3 mg/ml glutamine, no Hepes buffer, and 10% fetal bovine serum, produced matrix resembling the calcifying cartilage matrix of fetal chick long bones. Interestingly, higher concentrations of fetal bovine serum had an inhibitory effect on calcification. The cartilage phenotype was confirmed based on the cellular expression of cartilage collagen and proteoglycan mRNAs, the presence of type II and type X collagen, and cartilage type proteoglycan at the light microscopic level, and the presence of chondrocytes and matrix vesicles at the EM level. The system is proposed as a model for evaluating the events in cell mediated cartilage calcification.

  5. Cellular forces and matrix assembly coordinate fibrous tissue repair.

    Science.gov (United States)

    Sakar, Mahmut Selman; Eyckmans, Jeroen; Pieters, Roel; Eberli, Daniel; Nelson, Bradley J; Chen, Christopher S

    2016-01-01

    Planar in vitro models have been invaluable tools to identify the mechanical basis of wound closure. Although these models may recapitulate closure dynamics of epithelial cell sheets, they fail to capture how a wounded fibrous tissue rebuilds its 3D architecture. Here we develop a 3D biomimetic model for soft tissue repair and demonstrate that fibroblasts ensconced in a collagen matrix rapidly close microsurgically induced defects within 24 h. Traction force microscopy and time-lapse imaging reveal that closure of gaps begins with contractility-mediated whole-tissue deformations. Subsequently, tangentially migrating fibroblasts along the wound edge tow and assemble a progressively thickening fibronectin template inside the gap that provide the substrate for cells to complete closure. Unlike previously reported mechanisms based on lamellipodial protrusions and purse-string contraction, our data reveal a mode of stromal closure in which coordination of tissue-scale deformations, matrix assembly and cell migration act together to restore 3D tissue architecture. PMID:26980715

  6. Cell-based and biomaterial approaches to connective tissue repair

    Science.gov (United States)

    Stalling, Simone Suzette

    Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in

  7. Mesenchymal Stem Cells: Application for Immunomodulation and Tissue Repair

    DEFF Research Database (Denmark)

    Horwood, Nicole J.; Dazzi, Francesco; Zaher, Walid; Kassem, Moustapha

    Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth and...... differentiation of hematopoietic stem cells (HSC) and hematopoiesis. These cells have been described as important immunoregulators due to their ability to suppress T cells proliferation. MSC can also directly contribute to tissue repair by migrating to sites of injury and providing a source of cells for...... differentiation and/or providing bystander support for resident stromal cells. This chapter discusses the cellular and molecular properties of MSC, the mechanisms by which they can modulate immune responses and the clinical applications of MSC in disorders such as graft-versus-host disease and aplastic anaemia...

  8. Leukocyte and Platelet Rich Plasma (L-PRP) Versus Leukocyte and Platelet Rich Fibrin (L-PRF) For Articular Cartilage Repair of the Knee: A Comparative Evaluation in an Animal Model

    OpenAIRE

    Kazemi, Davoud; Fakhrjou, Ashraf

    2015-01-01

    Background: Articular cartilage injuries of the knee are among the most debilitating injuries leading to osteoarthritis due to limited regenerative capability of cartilaginous tissue. The use of platelet concentrates containing necessary growth factors for cartilage healing has recently emerged as a new treatment method. Objectives: The efficacy of two types of different platelet concentrates were compared in the treatment of acute articular cartilage injuries of the knee in an animal model. ...

  9. Fibroblast growth factors as tissue repair and regeneration therapeutics.

    Science.gov (United States)

    Nunes, Quentin M; Li, Yong; Sun, Changye; Kinnunen, Tarja K; Fernig, David G

    2016-01-01

    Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine) or systemically (endocrine). The fibroblast growth factor (FGF) family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West, oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR) tyrosine kinases. We then summarise a selection of clinical reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair/regeneration. Alongside, the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation that has been largely overlooked in the West. PMID:26793421

  10. Development of Scaffold-Free Elastic Cartilaginous Constructs with Structural Similarities to Auricular Cartilage

    OpenAIRE

    Giardini-Rosa, Renata; Joazeiro, Paulo P.; Thomas, Kathryn; Collavino, Kristina; Weber, Joanna; Waldman, Stephen D.

    2014-01-01

    External ear reconstruction with autologous cartilage still remains one of the most difficult problems in the fields of plastic and reconstructive surgery. As the absence of tissue vascularization limits the ability to stimulate new tissue growth, relatively few surgical approaches are currently available (alloplastic implants or sculpted autologous cartilage grafts) to repair or reconstruct the auricle (or pinna) as a result of traumatic loss or congenital absence (e.g., microtia). Alternati...

  11. A HYBRID SCAFFOLD OF POLY(LACTIDE-CO-GLYCOLIDE) SPONGE FILLED WITH FIBRIN GEL FOR CARTILAGE TISSUE ENGINEERING

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Dan Li; Mei-cong Wang; Yang-lin Li; Chang-you Gao

    2011-01-01

    The poly(lactide-co-glycolide) (PLGA) sponge fabricated by a gelatin porogen leaching method was filled with fibrin gel to obtain a hybrid scaffold for chondrocytes culture in vitro. The fibrin gel evenly distributed in the hybrid scaffold with visible fibrinogen fibers after drying. In vitro culture it was found that in the hybrid scaffold the chondrocytes distributed more evenly and kept a round morphology as that in the normal cartilage. Although the chondrocytes seeded in the control PLGA sponges showed similar proliferation behavior with that in the hybrid scaffolds, they were remarkably elongated, forming a fibroblast-like morphology. Moreover, a larger amount of glycosaminoglycans was secreted in the hybrid scaffolds than that in the PLGA sponges after in vitro culture of chondrocytes for 4 weeks. The results suggest that the fibrin/PLGA hybrid scaffold may be favorably applied for cartilage tissue engineering.

  12. Pulp and periodontal tissue repair - regeneration or tissue metaplasia after dental trauma. A review

    DEFF Research Database (Denmark)

    Andreasen, Jens O

    2012-01-01

    Healing subsequent to dental trauma is known to be very complex, a result explained by the variability of the types of dental trauma (six luxations, nine fracture types, and their combinations). On top of that, at least 16 different cellular systems get involved in more severe trauma types each o...... tissue replaces the injured). In this study, a review is given of the impact of trauma to various dental tissues such as alveolar bone, periodontal ligament, cementum, Hertvigs epithelial root sheath, and the pulp....... them with a different potential for healing with repair, i.e. (re-establishment of tissue continuity without functional restitution) and regeneration (where the injured or lost tissue is replaced with new tissue with identical tissue anatomy and function) and finally metaplasia (where a new type of...

  13. Neural crest stem cell population in craniomaxillofacial development and tissue repair

    Directory of Open Access Journals (Sweden)

    M La Noce

    2014-10-01

    Full Text Available Neural crest cells, delaminating from the neural tube during migration, undergo an epithelial-mesenchymal transition and differentiate into several cell types strongly reinforcing the mesoderm of the craniofacial body area – giving rise to bone, cartilage and other tissues and cells of this human body area. Recent studies on craniomaxillofacial neural crest-derived cells have provided evidence for the tremendous plasticity of these cells. Actually, neural crest cells can respond and adapt to the environment in which they migrate and the cranial mesoderm plays an important role toward patterning the identity of the migrating neural crest cells. In our experience, neural crest-derived stem cells, such as dental pulp stem cells, can actively proliferate, repair bone and give rise to other tissues and cytotypes, including blood vessels, smooth muscle, adipocytes and melanocytes, highlighting that their use in tissue engineering is successful. In this review, we provide an overview of the main pathways involved in neural crest formation, delamination, migration and differentiation; and, in particular, we concentrate our attention on the translatability of the latest scientific progress. Here we try to suggest new ideas and strategies that are needed to fully develop the clinical use of these cells. This effort should involve both researchers/clinicians and improvements in good manufacturing practice procedures. It is important to address studies towards clinical application or take into consideration that studies must have an effective therapeutic prospect for humans. New approaches and ideas must be concentrated also toward stem cell recruitment and activation within the human body, overcoming the classical grafting.

  14. Stem cells in cartilage tissue engineering and influential factors%干细胞在软骨组织工程中的应用及其影响因素

    Institute of Scientific and Technical Information of China (English)

    王艳

    2013-01-01

    BACKGROUND:A variety of stem cells as seed cells for cartilage tissue engineering have been extensively studied. OBJECTIVE:To analyze the biological characteristics of different kinds of stem cells and their application in cartilage tissue engineering. METHODS:By retrieving recent studies on sources of stem cells and influential factors in cartilage tissue engineering, the authors focused on optimization of harvesting stem cells from different sources in bone tissue engineering, problems, and factors that affect cellgrowth, differentiation, reproduction and metabolism, which provide a theoretical basis for tissue-engineered cartilage repair. RESULTS AND CONCLUSION:A large number of experimental studies have confirmed that exogenous stem cells can be used as seed cells for cartilage tissue engineering. Influential factors relative to cartilage tissue engineering construction using seed cells include growth factors, cellscaffold, cellseeding density, oxygen concentration, stress and micro-gravity. However, tissue-engineered cartilage is stil in the stage of laboratory research, and stem cells for cartilage tissue engineering involves many issues, such as stem celltransformation, in vitro culture of stem cells, how to prolong the survival of cells, reduce cellantigenicity and enhance the host’s immune tolerance, which are yet to be resolved.%背景:至今各种干细胞作为软骨组织工程种子细胞已被广泛研究。  目的:分析不同干细胞的生物学特性及其在软骨组织工程中的研究与应用。  方法:通过检索近年来关于软骨组织工程研究中的干细胞来源及其影响因素的相关文献,针对软骨组织工程不同来源干细胞的优化获取、存在的问题、影响细胞分化生长、繁殖及代谢的因素进行了着重论述,为组织工程化软骨修复软骨缺损提供理论基础。  结果与结论:通过大量的实验研究证实外源性的干细胞可用于软骨组织

  15. Photodynamic damage to cartilage and synovial tissue grafted on a chick's chorioallantoic membrane

    Science.gov (United States)

    Fisher, M.; Nahir, A. M.; Kimel, Sol

    1997-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints causing pain deformities and disability. The highly vascular inflamed synovium has aggressive and destructive characteristics, it invades, erodes and gradually destroys cartilage and underlying bone. Photodynamic therapy (PDT) was performed using the chick chorioallantoic membrane (CAM) model to investigate the vitality of synovium and cartilage implanted on the CAM. Synovium, obtained from human patients, was grafted onto the CAM; gross microscopy and histology proved its vitality 7 days post grafting. Cartilage obtained from rabbit knee joint was also maintained on the CAM for 7 days. Its vitality was demonstrated by histology and by measuring metabolic and enzymatic activity of cartilage cells (chondrocytes) as well as the collagen and proteoglycans content. Selective PDT was performed using aluminum phthalocyanine tetrasulfonate (AlPcS4), a hydrophilic compound, soluble in biological solutions, as a photosensitizer. After irradiation with a diode laser (lambda equals 670 nm, 10 mW) damage was observed in vascularized synovium grafts, whereas avascular cartilage remained intact.

  16. Repairing allogenic thyroid cartilage defects using poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) seeded with chondrocytes%聚羟基烷酸酯聚合物负载软骨细胞修复同种异体喉软骨缺损

    Institute of Scientific and Technical Information of China (English)

    孙安科; 李万同; 刘松波; 张贺; 孙伟; 陈伟; 史春海; 唐维维

    2013-01-01

    ,直接应用初级组织工程软骨组织可节省时间、成本、工作量及操作环节,避免二次皮下手术的痛苦,是比较实用的方法之一。%BACKGROUND:A great development has been achieved in essential research on tissue engineered cartilage. However, its real application in otolaryngology has been rarely reported. It is faced with the topic to explore the simple and convenient method of repairing laryngeal cartilage by tissue engineering technique. OBJECTIVE:To compare the effect of porous spongy poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) seeded with chondrocytes or using senior tissue engineered cartilage in repairing al ogenic thyroid cartilage defects.METHODS:Chondrocytes at passage 3 were harvested from infant rabbits within 3 days. Porous spongy poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) seeded with chondrocytes composites were made by tissue engineering technique. The chondrocyte-poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) composites were co-cultured in vitro to form junior tissue engineered cartilage. And then respectively used for repairing the thyroid cartilage defects and directly transplanted with junior tissue engineered cartilage (experimental group A, n=5), or firstly the junior tissue engineered cartilage to be implanted subcutaneously for a period of time to further maturity for relative senior tissue engineered cartilage and secondly to be transplanted (experimental group B, n=5) into adult New Zealand white rabbits. Simple poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) sponge scaffold (control group A, n=4) and chondrocyte suspensions(control group B, n=4) were used as reparative materials in defect areas as control groups. Final y, the reparative effect was respectively studied grossly and histological y at 4 weeks (experimental group B) and 8 weeks (experimental group A, control group A and control group B) after transplantation. RESULTS AND CONCLUSION:The cartilage defects were wel repaired in the

  17. Kartogenin-Incorporated Thermogel Supports Stem Cells for Significant Cartilage Regeneration.

    Science.gov (United States)

    Li, Xuezhou; Ding, Jianxun; Zhang, Zhengzheng; Yang, Modi; Yu, Jiakuo; Wang, Jincheng; Chang, Fei; Chen, Xuesi

    2016-03-01

    Recently, cartilage tissue engineering (CTE) attracts increasing attention in cartilage defect repair. In this work, kartogenin (KGN), an emerging chondroinductive nonprotein small molecule, was incorporated into a thermogel of poly(L-lactide-co-glycolide)-poly(ethylene glycol)-poly(L-lactide-co-glycolide) (PLGA-PEG-PLGA) to fabricate an appropriate microenvironment of bone marrow mesenchymal stem cells (BMSCs) for effective cartilage regeneration. More integrative and smoother repaired articular surface, more abundant characteristic glycosaminoglycans (GAGs) and collagen II (COL II), and less degeneration of normal cartilage were obtained in the KGN and BMSCs coloaded thermogel group in vivo. In conclusion, the KGN-loaded PLGA-PEG-PLGA thermogel can be utilized as an alternative support for BMSCs to regenerate damaged cartilage in vivo. PMID:26844837

  18. Projection Stereolithographic Fabrication of Human Adipose Stem Cell-incorporated Biodegradable Scaffolds for Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Aaron X Sun

    2015-08-01

    Full Text Available Poor self-healing ability of cartilage necessitates the development of methods for cartilage regeneration. Scaffold construction with live stem cell incorporation and subsequent differentiation presents a promising route. Projection stereolithography (PSL offers high resolution and processing speed as well as the ability to fabricate scaffolds that precisely fit the anatomy of cartilage defects using medical imaging as the design template. We report here the use of a visible-light based PSL (VL-PSL system to encapsulate human adipose-derived stem cells (hASCs into a biodegradable polymer (poly-D,L-lactic acid/polyethylene glycol/ poly-D,L-lactic acid (PDLLA-PEG/hyaluronic acid (HA matrix to produce live cell constructs with customized architectures. After fabrication, hASCs showed high viability (84% and were uniformly distributed throughout the constructs, which possessed high mechanical property with a compressive modulus of 780 kPa. The hASC-seeded constructs were then cultured in Control or TGF-β3-containing chondrogenic medium for up to 28 days. In chondrogenic medium treated group (TGF-β3 group hASCs maintained 77% viability and expressed chondrogenic genes Sox9, collagen type II, and aggrecan at 11, 232, and 2.29 x 10(5 fold increases, respectively, compared to levels at day 0 in non-chondrogenic medium. The TGF-β3 group also produced a collagen type II and glycosaminoglycan (GAG-rich extracellular matrix, detected by immunohistochemistry, and Alcian blue and Safranin O staining suggesting robust chondrogenesis within the scaffold. Without chondroinductive addition (Control group, cell viability decreased with time (65% at 28 days and showed poor cartilage matrix deposition. After 28 days, mechanical strength of the TGF-β3 group remained high at 240 kPa. Thus, the PSL- and PLLA-PEG/HA based fabrication method using adult stem cells is a promising approach in producing mechanically competent engineered cartilage for joint cartilage

  19. In Vitro Engineering of High Modulus Cartilage-Like Constructs.

    Science.gov (United States)

    Finlay, Scott; Seedhom, Bahaa B; Carey, Duane O; Bulpitt, Andy J; Treanor, Darren E; Kirkham, Jennifer

    2016-04-01

    To date, the outcomes of cartilage repair have been inconsistent and have frequently yielded mechanically inferior fibrocartilage, thereby increasing the chances of damage recurrence. Implantation of constructs with biochemical composition and mechanical properties comparable to natural cartilage could be advantageous for long-term repair. This study attempted to create such constructs, in vitro, using tissue engineering principles. Bovine synoviocytes were seeded on nonwoven polyethylene terephthalate fiber scaffolds and cultured in chondrogenic medium for 4 weeks, after which uniaxial compressive loading was applied using an in-house bioreactor for 1 h per day, at a frequency of 1 Hz, for a further 84 days. The initial loading conditions, determined from the mechanical properties of the immature constructs after 4 weeks in chondrogenic culture, were strains ranging between 13% and 23%. After 56 days (sustained at 84 days) of loading, the constructs were stained homogenously with Alcian blue and for type-II collagen. Dynamic compressive moduli were comparable to the high end values for native cartilage and proportional to Alcian blue staining intensity. We suggest that these high moduli values were attributable to the bioreactor setup, which caused the loading regime to change as the constructs developed, that is, the applied stress and strain increased with construct thickness and stiffness, providing continued sufficient cell stimulation as further matrix was deposited. Constructs containing cartilage-like matrix with response to load similar to that of native cartilage could produce long-term effective cartilage repair when implanted. PMID:26850081

  20. In Vitro Engineering of High Modulus Cartilage-Like Constructs

    Science.gov (United States)

    Seedhom, Bahaa B.; Carey, Duane O.; Bulpitt, Andy J.; Treanor, Darren E.; Kirkham, Jennifer

    2016-01-01

    To date, the outcomes of cartilage repair have been inconsistent and have frequently yielded mechanically inferior fibrocartilage, thereby increasing the chances of damage recurrence. Implantation of constructs with biochemical composition and mechanical properties comparable to natural cartilage could be advantageous for long-term repair. This study attempted to create such constructs, in vitro, using tissue engineering principles. Bovine synoviocytes were seeded on nonwoven polyethylene terephthalate fiber scaffolds and cultured in chondrogenic medium for 4 weeks, after which uniaxial compressive loading was applied using an in-house bioreactor for 1 h per day, at a frequency of 1 Hz, for a further 84 days. The initial loading conditions, determined from the mechanical properties of the immature constructs after 4 weeks in chondrogenic culture, were strains ranging between 13% and 23%. After 56 days (sustained at 84 days) of loading, the constructs were stained homogenously with Alcian blue and for type-II collagen. Dynamic compressive moduli were comparable to the high end values for native cartilage and proportional to Alcian blue staining intensity. We suggest that these high moduli values were attributable to the bioreactor setup, which caused the loading regime to change as the constructs developed, that is, the applied stress and strain increased with construct thickness and stiffness, providing continued sufficient cell stimulation as further matrix was deposited. Constructs containing cartilage-like matrix with response to load similar to that of native cartilage could produce long-term effective cartilage repair when implanted. PMID:26850081

  1. A Comparison of the influence of material on in vitro cartilage tissue engineering with PCL, PGS, and POC 3D scaffold architecture seeded with chondrocytes

    OpenAIRE

    Jeong, Claire G.; Hollister, Scott J.

    2010-01-01

    The goal of this study was to determine material effects on cartilage regeneration for scaffolds with the same controlled architecture. The 3D polycaprolactone (PCL), poly (glycerol sebacate) (PGS), and poly (1,8 octanediol-co-citrate) (POC) scaffolds of the same design were physically characterized and tissue regeneration in terms of cell phenotype, cellular proliferation and differentiation, and matrix production were compared to find which material would be most optimal for cartilage regen...

  2. Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair.

    Science.gov (United States)

    Gnecchi, Massimiliano; Danieli, Patrizia; Malpasso, Giuseppe; Ciuffreda, Maria Chiara

    2016-01-01

    Tissue regeneration from transplanted mesenchymal stromal cells (MSC) either through transdifferentiation or cell fusion was originally proposed as the principal mechanism underlying their therapeutic action. However, several studies have now shown that both these mechanisms are very inefficient. The low MSC engraftment rate documented in injured areas also refutes the hypothesis that MSC repair tissue damage by replacing cell loss with newly differentiated cells. Indeed, despite evidence of preferential homing of MSC to the site of myocardial ischemia, exogenously administered MSC show poor survival and do not persist in the infarcted area. Therefore, it has been proposed that the functional benefits observed after MSC transplantation in experimental models of tissue injury might be related to the secretion of soluble factors acting in a paracrine fashion. This hypothesis is supported by pre-clinical studies demonstrating equal or even improved organ function upon infusion of MSC-derived conditioned medium (MSC-CM) compared with MSC transplantation. Identifying key MSC-secreted factors and their functional role seems a reasonable approach for a rational design of nextgeneration MSC-based therapeutics. Here, we summarize the major findings regarding both different MSC-mediated paracrine actions and the identification of paracrine mediators. PMID:27236669

  3. Implantation of a polycaprolactone scaffold with subchondral bone anchoring ameliorates nodules formation and other tissue alterations

    OpenAIRE

    Vikingsson, Line; Sancho-Tello, Mar??a; Ruiz-Saur??, Amparo; Martinez-Diaz, Santos; G??mez-Tejedor, Jos?? Antonio; Gallego Ferrer, Gloria; Carda, Carmen; Monllau Garc??a, Juan Carlos; G??mez Ribelles, Jos?? Luis

    2016-01-01

    PURPOSE: Articular cartilage has limited repair capacity. Two different implant devices for articular cartilage regeneration were tested in vivo in a sheep model to evaluate the effect of subchondral bone anchoring for tissue repair. METHODS: The implants were placed with press-fit technique in a cartilage defect after microfracture surgery in the femoral condyle of the knee joint of the sheep and histologic and mechanical evaluation was done 4.5 months later. The first group consisted of a b...

  4. Preparing PCL/PLGA Hybrid Nanofiber Scaffold Capable of Controlled Releasing of Insulin for Cartilage Tissue Engineering Application

    Directory of Open Access Journals (Sweden)

    A Basiri

    2014-08-01

    Full Text Available Introduction: Poly lactic co- glycolic acid (PLGA and poly caprolacton (PCL are highly applicable polymers in the field of drug delivery and tissue engineering scaffolds. Therefore, this study aimed to design an insulin-loaded PCL/PLGA hybrid nanofiber scaffold in order to be applied in attachment and growth of chondrocytes. Moreover, it can provide a vehicle for the controlled release of active insulin in a certain time period. Methods: Chondrocyte cells were isolated from septum cartilage tissue utilizing collagenase and were also cultured in monolayer, then the third-passage cells were seeded on the scaffolds. Insulin release from the PCL/PLGA hybrid nanofiber scaffold was examined by Radio Immuno Metric Assay (RIMA during 22 days. Adherence, distribution and morphology of cells were observed by H&E and alcian blue staining. Results: PCL/PLGA hybrid nanofiber scaffold revealed a slow and sustain release of insulin within three weeks. Chondrocytes were distributed evenly throughout the scaffolds. In addition, they sank into the pores of scaffold and maintained their rounded morphology. Conclusion: Biological activity of insulin has been maintained during 22 days of controlled release from hybrid nanofiber PCL/PLGA scaffold. Chondrocytes were distributed evenly throughout the scaffold and revealed a rounded morphology. Therefore, this scaffold provides a suitable carrier for chondrocyte growth as well as formation of tissue engineered cartilage.

  5. Increased synovial tissue NF-kappa B1 expression at sites adjacent to the cartilage-pannus junction in rheumatoid arthritis.

    NARCIS (Netherlands)

    Benito, M.J.; Murphy, E.P.; Berg, W.B. van den; Fitzgerald, O.; Bresnihan, B.

    2004-01-01

    OBJECTIVE: To compare the expression of the Rel/NF-kappa B subunits, NF-kappa B1 (p50) and RelA (p65), in paired synovial tissue samples selected from sites adjacent to and remote from the cartilage-pannus junction (CPJ) in patients with inflammatory arthritis. METHODS: Synovial tissue was selected

  6. Tissue-specific accelerated aging in nucleotide excision repair deficiency

    OpenAIRE

    Laura J. Niedernhofer

    2008-01-01

    Nucleotide excision repair (NER) is a multi-step DNA repair mechanism that removes helix-distorting modified nucleotides from the genome. NER is divided into two subpathways depending on the location of DNA damage in the genome and how it is first detected. Global genome NER identifies and repairs DNA lesions throughout the genome. This subpathway of NER primarily protects against the accumulation of mutations in the genome. Transcription-coupled (TC) NER rapidly repairs lesions in the transc...

  7. Lubricin reduces cartilage--cartilage integration.

    Science.gov (United States)

    Schaefer, Dirk B; Wendt, David; Moretti, Matteo; Jakob, Marcel; Jay, Gregory D; Heberer, Michael; Martin, Ivan

    2004-01-01

    Cartilage integration in vivo does not occur, such that even cartilage fissures do not heal. This could be due not only to the limited access of chondrocytes to the wound, but also to exogenous factors. In this paper, we tested the hypothesis that lubricin, a lubricating protein physiologically present in the synovial fluid, reduces the integrative cartilage repair capacity. Disk/ring composites of bovine articular cartilage were prepared using concentric circular blades and cultured for 6 weeks with or without treatment with 250 microg/ml lubricin applied three times per week. Following culture, the percentage of contact area between the disks and the rings, as assessed by light microscopy, were equal in both groups. The adhesive strength of the integration interface, as assessed by push-out mechanical tests, was markedly and significantly lower in lubricin-treated specimens (2.5 kPa) than in the controls (28.7 kPa). Histological observation of Safranin-O stained cross-sections confirmed the reduced integration in the lubricin treated composites. Our findings suggest that the synovial milieu, by providing lubrication of cartilage surfaces, impairs cartilage--cartilage integration. PMID:15299281

  8. 不同材料构建组织工程软骨及支架的应用%Applications of tissue-engineered cartilage and scaffold constructed using different materials

    Institute of Scientific and Technical Information of China (English)

    张新

    2012-01-01

    背景 组织工程技术的发展为软骨的再生和修复提供了新的途径,根据软骨自身的结构和特点,作为人工软骨的替代材料和支架材料应具有良好的生物力学性能.目的 总结运动性关节软骨损伤修复材料及其支架材料的应用进展及其生物替代材料的生物力学特征,评价目前组织工程软骨材料应用的性能及发展前景.方法 以"组织工程;软骨组织;支架材料;生物相容性"为关键词,应用计算机检索维普数据库和PubMed 数据库中1990-01/2011-04 关于组织工程软骨应用研究的文章,纳入与有关生物材料与组织工程软骨相关的文章;排除重复研究或Meta 分析类文章.以24 篇文献为主重点进行了讨论组织工程软骨材料的种类、性能及其应用效果和前景.结果 与结论 目前关节软骨修复领域以自体软骨移植效果为最佳,骨髓基质干细胞在离体试验及动物实验中研究较多,在临床应用中较少,尚在探索阶段.支架材料的应用比较繁复,天然材料、人工合成材料以及复合材料都存在一定的不足,虽然复合材料成为研究的热点,但是某些性能并不能很好地符合支架要求,并且在机体内这些材料所带来的长期影响还不能预见,这就迫切需要新材料的出现,来更好地满足组织软骨织支架的要求,达到修复和重建的目的.%BACKGROUND: The development of tissue engineering technology provides a new way for cartilage regeneration and repair;according to the structure and characteristics of cartilage, the substitute materials and scaffold materials, as artificial cartilage,should have good biomechanical properties.OBJECTIVE: To summarize the application progress of repair materials and scaffold materials for exercise-induced articularcartilage injury; to summarize the biomechanical properties of biological substitute materials; to evaluate the performance andprospects of the current application of tissue

  9. Tailored PVA/ECM Scaffolds for Cartilage Regeneration

    Directory of Open Access Journals (Sweden)

    Elena Stocco

    2014-01-01

    Full Text Available Articular cartilage lesions are a particular challenge for regenerative medicine due to cartilage low self-ability repair in case of damage. Hence, a significant goal of musculoskeletal tissue engineering is the development of suitable structures in virtue of their matrix composition and biomechanical properties. The objective of our study was to design in vitro a supporting structure for autologous chondrocyte growth. We realized a biohybrid composite scaffold combining a novel and nonspecific extracellular matrix (ECM, which is decellularized Wharton’s jelly ECM, with the biomechanical properties of the synthetic hydrogel polyvinyl alcohol (PVA. Wharton’s jelly ECM was tested for its ability in promoting scaffold colonization by chondrocytes and compared with polyvinyl alcohol itself and the more specific decellularized cartilage matrix. Our preliminary evidences highlighted the chance of using Wharton’s jelly ECM in combination with PVA hydrogels as an innovative and easily available scaffold for cartilage restoration.

  10. A radiation damage repair model for normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Partridge, Mike [Institute of Cancer Research, Downs Road, Sutton, SM2 5PT (United Kingdom)

    2008-07-07

    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions ({approx}2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 {mu}m h{sup -1} for large lesions (>15 000 cells)

  11. A radiation damage repair model for normal tissues

    Science.gov (United States)

    Partridge, Mike

    2008-07-01

    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions (~2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 µm h-1 for large lesions (>15 000 cells).

  12. The discrimination of type I and type II collagen and the label-free imaging of engineered cartilage tissue.

    Science.gov (United States)

    Su, Ping-Jung; Chen, Wei-Liang; Li, Tsung-Hsien; Chou, Chen-Kuan; Chen, Te-Hsuen; Ho, Yi-Yun; Huang, Chi-Hsiu; Chang, Shwu-Jen; Huang, Yi-You; Lee, Hsuan-Shu; Dong, Chen-Yuan

    2010-12-01

    Using excitation polarization-resolved second harmonic generation (SHG) microscopy, we measured SHG intensity as a function of the excitation polarization angle for type I and type II collagens. We determined the second order susceptibility (χ((2))) tensor ratios of type I and II collagens at each pixel, and displayed the results as images. We found that the χ((2)) tensor ratios can be used to distinguish the two types of collagen. In particular, we obtained χ(zzz)/χ(zxx) = 1.40 ± 0.04 and χ(xzx)/χ(zxx) = 0.53 ± 0.10 for type I collagen from rat tail tendon, and χ(zzz)/χ(zxx) = 1.14 ± 0.09 and χ(xzx)/χ(zxx) = 0.29 ± 0.11 for type II collagen from rat trachea cartilage. We also applied this methodology on the label-free imaging of engineered cartilage tissue which produces type I and II collagen simultaneously. By displaying the χ((2)) tensor ratios in the image format, the variation in the χ((2)) tensor ratios can be used as a contrast mechanism for distinguishing type I and II collagens. PMID:20875682

  13. 制备软骨组织工程支架的方法%Fabrication technologies of tissue-engineered cartilage scaffolds

    Institute of Scientific and Technical Information of China (English)

    倪硕; 李澎; 张卫国; 李鹏声; 贵浩然

    2014-01-01

    背景:软骨组织工程支架作为软骨细胞外基质的替代物,其外形和孔结构对实现其作用和功能具有非常重要的意义。  目的:回顾目前若干种常用软骨组织工程中三维多孔支架的制备方法。  方法:由第一作者检索2000至2013年PubMed数据库,ELSEVIER SCIENCEDIRECT、万方数据库、中国知网数据库。英文检索词为“Cartilage tissue engineering;scaffolds;fabrication”,中文检索词为“软骨组织工程;制备方法;支架材料;多孔支架”。  结果与结论:制备软骨组织工程支架的方法有相分离/冷冻干燥法、水凝胶技术、快速成型技术、静电纺丝法、溶剂浇铸/粒子沥滤法及气体发泡法等。目前研究发现,支架中孔径的大小对组织的重建有着直接的影响,孔径为100-250μm的孔有益于骨及软骨组织的再生。通过溶液浇铸/粒子沥滤法、气体发泡法所制备的支架孔径大小在这一范围内,因此比较适合用于骨、软骨组织工程支架的构建。研究人员通常将多种方法结合起来,以期能制备出生物和力学性能方面更加仿生的组织工程多孔支架。%BACKGROUND:Cartilage tissue engineering scaffold is a substitution for extracellular matrix, and there is a great significance on the shape and pore structure of the scaffold. OBJECTIVE:To retrospectively focus on the fabrication technology of three-dimensional porous cartilage tissue engineering scaffolds. METHODS:The first author searched PubMed, ELSEVIER SCIENCEDIRECT, Wanfang and CNKI databases (2000/2013) to retrieve relevant articles about the fabrication technology tissue-engineered cartilage scaffolds. The key words were“cartilage tissue engineering;scaffolds;fabrication”in English and Chinese, respectively. RESULTS AND CONCLUSION:The fabrication technologies of three-dimensional porous cartilage tissue engineering scaffolds are as fol ows:Phase separation

  14. Soft tissue reinforcement interposition flaps in hypospadias repair

    Directory of Open Access Journals (Sweden)

    Singh R

    2007-01-01

    Full Text Available Purpose: To discuss the role and mechanism of action of soft tissue reinforcement interposition flaps (STRIFs in hypospadias repairs (reinforced hypospadiac urethroplasties. Materials and Methods: Between 2000-2005, 120 consecutive hypospadiacs (distal 85, mid 20, proximal 15, who underwent primary reinforced urethroplasties employing different types of STRIFs, were retrospectively analyzed. The STRIFs were highly vascular soft tissue pedicled flaps (devoid of epithelium interposed between neo-urethras and the covering skin to reinforce the neo-urethras against fistula formation. The STRIFs were harvested, without much donor site deformity, from: preputial skin, penile skin and scrotal skin by de-epithelialization. Those from Buck′s fascia, corpus spongiosum and tunica vaginalis are STRIFs without epithelium anyway, therefore do not need de-epithelialization. Redo urethroplasties and micropenises were not included. Seven patients were excluded because they had incomplete follow-up. The remaining 113 (distal 84, mid 17, proximal 12 were followed up for nine to 40 months for number, size, location, spontaneous closure and persistence of urethro-cutaneous fistula (UCF, and other complications with regard to the severity of hypospadias, method of neourethral re-construction, types of STRIFs employed and skin cover used. A total of 158 STRIFs and 124 skin covers were used in 113 hypospadiac urethroplasties. Results: The first surgery was curative in 74 (65% of 113 patients. In the remaining 39 (35%, various complications included 12 urethro-cutaneous fistulas (UCFs, 10 urethral strictures, six cases each of penile torsion and meatal stenosis and five cases each of superficial necrosis and poor cosmesis. Of these 39 patients, 25 (64% recovered with conservative treatment and 14 (36% required re-operation, i.e. UCFs and strictures in four cases each and penile torsion, meatal stenosis and dog-ears in two cases each. All the 12 UCFs were single

  15. Experimental articular cartilage repair in the Göttingen minipig: the influence of multiple defects per knee

    OpenAIRE

    Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke; Vingtoft, Louise; Rölfing, Jan Hendrik Duedal; Ringgaard, Steffen; Lind, Martin

    2015-01-01

    Background A gold standard treatment for articular cartilage injuries is yet to be found, and a cost-effective and predictable large animal model is needed to bridge the gap between in vitro studies and clinical studies. Ideally, the animal model should allow for testing of clinically relevant treatments and the biological response should be reproducible and comparable to humans. This allows for a reliable translation of results to clinical studies.This study aimed at verifying the Göttingen ...

  16. Spontaneous Minced Cartilage Procedure for Unexpectedly Large Femoral Condyle Surface Defect.

    Science.gov (United States)

    Salzmann, G M; Baumann, G A; Preiss, S

    2016-01-01

    Articular cartilage defects at the knee joint are being identified and treated with increasing frequency. Chondrocytes may have strongest potential to generate high-quality repair tissue within the defective region, in particular when large diameter defects are present. Autologous chondrocyte implantation is not available in every country. We present a case where we spontaneously covered an acute cartilage defect, which was significantly larger than expected and loose during initial arthroscopic inspection after reading preoperative MRI, by mincing the separated fragment and directly implanting the autologous cartilage chips into the defective region. PMID:27504207

  17. Flexible and elastic scaffolds for cartilage tissue engineering prepared by stereolithography using poly(trimethylene carbonate)-based resins.

    Science.gov (United States)

    Schüller-Ravoo, Sigrid; Teixeira, Sandra M; Feijen, Jan; Grijpma, Dirk W; Poot, André A

    2013-12-01

    The aim of this study is to investigate the applicability of flexible and elastic poly(trimethylene carbonate) (PTMC) structures prepared by stereolithography as scaffolds for cartilage tissue engineering. A three-armed methacrylated PTMC macromer with a molecular weight of 3100 g mol(-1) is used to build designed scaffolds with a pore diameter of 350 ± 12 μm and a porosity of 54.0 ± 2.2%. Upon seeding of bovine chondrocytes in the scaffolds, the cells adhere and spread on the PTMC surface. After culturing for 6 weeks, also cells with a round morphology are present, indicative of the differentiated chondrocyte phenotype. Sulphated glycosaminoglycans and fibrillar collagens are deposited by the cells. During culturing for 6 weeks, the compression moduli of the constructs increases 50% to approximately 100 kPa. PMID:24214105

  18. Editorial Commentary: The Search for the Cartilage "Holy Grail": Are We There Yet?

    Science.gov (United States)

    Weber, Alexander E; Cole, Brian J

    2016-07-01

    A study by Zhang et al. provided a Level IV systematic review of 23 studies (13 clinical and 10 basic science) that examined the current state of single-stage procedures for cartilage repair. The results of this review suggested that in the short-term (minimum 2-year follow-up), single-stage cell-based cartilage procedures significantly improve pain and function from the preoperative state and provide comparable defect fill and tissue quality as compared with their predecessor 2-stage procedures. The authors should be commended for summarizing the current state of single-stage cartilage repair techniques; however, further work must be done to find the cartilage restoration "holy grail." PMID:27373184

  19. Development of large engineered cartilage constructs from a small population of cells.

    Science.gov (United States)

    Brenner, Jillian M; Kunz, Manuela; Tse, Man Yat; Winterborn, Andrew; Bardana, Davide D; Pang, Stephen C; Waldman, Stephen D

    2013-01-01

    Confronted with articular cartilage's limited capacity for self-repair, joint resurfacing techniques offer an attractive treatment for damaged or diseased tissue. Although tissue engineered cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for the repair of large defects. As routine cell expansion methods tend to elicit negative effects on chondrocyte function, we have developed an approach to generate phenotypically stable, large-sized engineered constructs (≥3 cm(2) ) directly from a small amount of donor tissue or cells (as little as 20,000 cells to generate a 3 cm(2) tissue construct). Using rabbit donor tissue, the bioreactor-cultivated constructs were hyaline-like in appearance and possessed a biochemical composition similar to native articular cartilage. Longer bioreactor cultivation times resulted in increased matrix deposition and improved mechanical properties determined over a 4 week period. Additionally, as the anatomy of the joint will need to be taken in account to effectively resurface large affected areas, we have also explored the possibility of generating constructs matched to the shape and surface geometry of a defect site through the use of rapid-prototyped defect tissue culture molds. Similar hyaline-like tissue constructs were developed that also possessed a high degree of shape correlation to the original defect mold. Future studies will be aimed at determining the effectiveness of this approach to the repair of cartilage defects in an animal model and the creation of large-sized osteochondral constructs. PMID:23197468

  20. Further proof of the plasticity of adult stem cells and their role in tissue repair

    OpenAIRE

    Prockop, Darwin J.

    2003-01-01

    In this issue, De Bari et al. (2003) present elegant data to counter the recent claims that adult stem cells have a limited plasticity. Further, they provide evidence that adult stem cells can seek out damaged tissues and repair them.

  1. Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis

    Directory of Open Access Journals (Sweden)

    Burchfield Jana S

    2008-10-01

    Full Text Available Abstract A new era has begun in the treatment of ischemic disease and heart failure. With the discovery that stem cells from diverse organs and tissues, including bone marrow, adipose tissue, umbilical cord blood, and vessel wall, have the potential to improve cardiac function beyond that of conventional pharmacological therapy comes a new field of research aiming at understanding the precise mechanisms of stem cell-mediated cardiac repair. Not only will it be important to determine the most efficacious cell population for cardiac repair, but also whether overlapping, common mechanisms exist. Increasing evidence suggests that one mechanism of action by which cells provide tissue protection and repair may involve paracrine factors, including cytokines and growth factors, released from transplanted stem cells into the surrounding tissue. These paracrine factors have the potential to directly modify the healing process in the heart, including neovascularization, cardiac myocyte apoptosis, inflammation, fibrosis, contractility, bioenergetics, and endogenous repair.

  2. Hematopoietic tissue repair under chronic low daily dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.

    1994-12-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3{minus}26.3 cGy d{sup {minus}1}). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 & 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity.

  3. Hematopoietic tissue repair under chronic low daily dose irradiation

    International Nuclear Information System (INIS)

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d-1). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 ampersand 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity

  4. FGF, TGFβ and Wnt crosstalk: embryonic to in vitro cartilage development from mesenchymal stem cells.

    Science.gov (United States)

    Cleary, Mairéad A; van Osch, Gerjo J V M; Brama, Pieter A; Hellingman, Catharine A; Narcisi, Roberto

    2015-04-01

    Articular cartilage is easily damaged, yet difficult to repair. Cartilage tissue engineering seems a promising therapeutic solution to restore articular cartilage structure and function, with mesenchymal stem cells (MSCs) receiving increasing attention for their promise to promote cartilage repair. It is known from embryology that members of the fibroblast growth factor (FGF), transforming growth factor-β (TGFβ) and wingless-type (Wnt) protein families are involved in controlling different differentiation stages during chondrogenesis. Individually, these pathways have been extensively studied but so far attempts to recapitulate embryonic development in in vitro MSC chondrogenesis have failed to produce stable and functioning articular cartilage; instead, transient hypertrophic cartilage is obtained. We believe a better understanding of the simultaneous integration of these factors will improve how we relate embryonic chondrogenesis to in vitro MSC chondrogenesis. This narrative review attempts to define current knowledge on the crosstalk between the FGF, TGFβ and Wnt signalling pathways during different stages of mesenchymal chondrogenesis. Connecting embryogenesis and in vitro differentiation of human MSCs might provide insights into how to improve and progress cartilage tissue engineering for the future. PMID:23576364

  5. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration

    Science.gov (United States)

    Meng, Qingyang; Man, Zhentao; Dai, Linghui; Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Ao, Yingfang

    2015-12-01

    Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.

  6. Preparation and characterization of polyvinyl alcohol hydrogels crosslinked by biodegradable polyurethane for tissue engineering of cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Bonakdar, Shahin [Biomedical Engineering Department, Amirkabir University of Technology, Tehran, 15875-4413 (Iran, Islamic Republic of); Emami, Shahriar Hojjati, E-mail: shahriar16@yahoo.com [Biomedical Engineering Department, Amirkabir University of Technology, Tehran, 15875-4413 (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, 13164 (Iran, Islamic Republic of); Farhadi, Afshin [Tehran Azad University of Medical Science, Amiralmomenin Hospital (Iran, Islamic Republic of); Ahmadi, Seyed Amir Hoshiar [Biomedical Engineering Department, Amirkabir University of Technology, Tehran, 15875-4413 (Iran, Islamic Republic of); Amanzadeh, Amir [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, 13164 (Iran, Islamic Republic of)

    2010-05-10

    Polyurethane was prepared from hexamethylene diisocyanate (HMDI) and polycaprolactone diol (PCL) with stoichiometry ratio of two in a reactor to form prepolymer. Polyvinyl alcohol (PVA) at PVA/prepolymer ratios of 8, 4, 2 and 1 was crosslinked with the former degradable polyester polyurethane. Fourier transform infrared (FTIR) was employed to confirm polyurethane formation during the course of reactions. FTIR spectrum revealed bands at 1729-1733 cm{sup -1} and 3347-3340 cm{sup -1} which indicates carbonyl and NH of amine groups, respectively. Polyurethane formation was also confirmed by the absence of the isocyanate peaks (NCO) at 2270 cm{sup -1}. Dynamic mechanical thermal analysis (DMTA) showed that by increasing prepolymer concentration glass transition temperature decreases from 26 deg. C for PVA to 19 deg. C for sample with PVA/prepolymer ratio of 4 and then it rises up to 31 deg. C. Water uptake measurements illustrated about four fold reduction in swelling ratio of PVA after crosslinking and the sample with equal amounts of PVA and PPU had water uptake of 100%, close to that of a natural cartilage and much less than PVA (425%). All samples had compressive modulus in the range of the articular cartilage (1.9-14.4 MPa). The morphology of the isolated cells on the samples was evaluated by scanning electron microscopy (SEM) and revealed cell attachment and proliferation. The cell viability (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT) and GAG expression (dimethylmethylene blue, DMMB) assays with human chondrocytes on the sample with PVA/prepolymer ratio of one showed about 14 and 33% increase in cell viability and GAG expression after 14 days of culture compare to the PVA, respectively.

  7. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone.

    Science.gov (United States)

    Muzzarelli, Riccardo A A; El Mehtedi, Mohamad; Bottegoni, Carlo; Aquili, Alberto; Gigante, Antonio

    2015-12-01

    The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010-2015 have met the expectations of an interdisciplinary audience. PMID:26690453

  8. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone

    Directory of Open Access Journals (Sweden)

    Riccardo A. A. Muzzarelli

    2015-12-01

    Full Text Available The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010–2015 have met the expectations of an interdisciplinary audience.

  9. Stereomicroscopic evaluation of the joint cartilage and bone tissue in osteoporosis

    Science.gov (United States)

    Vasile, Liliana; Torok, Rodica; Deleanu, Bogdan; Marchese, Cristian; Valeanu, Adina; Bodea, Rodica

    2012-06-01

    Aim of the study. Assessment by stereomicroscopy of the severity of lesions in osteoporotic bone at both sexes and to correlate micro-and macro-bone fracture due to low bone density values with the disease evolution. Material and method: The study material consists of fragments of bone from the femoral head, vertebral bone, costal and iliac crest biopsy obtained from patients aged over 70 years, female and male, treated in the County Hospital of Timisoara, Department of Orthopedics. For the purpose of studying the samples in stereomicroscopy and trough polarized light it has been used the Olympus Microscope SZ ×7 and an Olympus camera with 2,5 × digital zoom and a 3× optical zoom in the Vest Politechnic Univesity. Results and discussions: Subchondral bone presents osteolysis associated with a osteoporotic bone transformation. Pseudocystic chondrolisis was noted in the osteoarticular cartilage, in addition with areas of hemorrhagic postfractural necrosis. The osteoporotic bone exhibits ischemic necrosis and focal hemorrhagic necrosis adjacent fracture. Microporosity pattern of the bone observed by stereomicroscopy correspond to the spongy bone osteoporosis images. Morphometry of the bone spiculi reveals length of 154.88 and 498.32 μ. In men we found a greater thickness of bone trabeculi compared with bone texture porosity in women. The subchondral bone supports and fulfills an important role in transmitting forces from the overlying articular cartilage inducing the bone resorbtion. The femoral head fracture may be the final event of many accumulated bone microcracks. Conclusions: Bone fragility depends not only of the spongy bone but also of the cortical bone properties. Osteolysis produced by loss of balance in the process of remodeling in favor of bone resorption leads to the thinning of the subchondral bone at both sexes.

  10. Preparation and characterization of polyvinyl alcohol hydrogels crosslinked by biodegradable polyurethane for tissue engineering of cartilage

    International Nuclear Information System (INIS)

    Polyurethane was prepared from hexamethylene diisocyanate (HMDI) and polycaprolactone diol (PCL) with stoichiometry ratio of two in a reactor to form prepolymer. Polyvinyl alcohol (PVA) at PVA/prepolymer ratios of 8, 4, 2 and 1 was crosslinked with the former degradable polyester polyurethane. Fourier transform infrared (FTIR) was employed to confirm polyurethane formation during the course of reactions. FTIR spectrum revealed bands at 1729-1733 cm-1 and 3347-3340 cm-1 which indicates carbonyl and NH of amine groups, respectively. Polyurethane formation was also confirmed by the absence of the isocyanate peaks (NCO) at 2270 cm-1. Dynamic mechanical thermal analysis (DMTA) showed that by increasing prepolymer concentration glass transition temperature decreases from 26 deg. C for PVA to 19 deg. C for sample with PVA/prepolymer ratio of 4 and then it rises up to 31 deg. C. Water uptake measurements illustrated about four fold reduction in swelling ratio of PVA after crosslinking and the sample with equal amounts of PVA and PPU had water uptake of 100%, close to that of a natural cartilage and much less than PVA (425%). All samples had compressive modulus in the range of the articular cartilage (1.9-14.4 MPa). The morphology of the isolated cells on the samples was evaluated by scanning electron microscopy (SEM) and revealed cell attachment and proliferation. The cell viability (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT) and GAG expression (dimethylmethylene blue, DMMB) assays with human chondrocytes on the sample with PVA/prepolymer ratio of one showed about 14 and 33% increase in cell viability and GAG expression after 14 days of culture compare to the PVA, respectively.

  11. Rotator Cuff Repair

    Medline Plus

    Full Text Available ... You can see there's good cartilage. The white tissue is the cartilage. So he doesn't have ... can see where there's a break in the tissue. There's a hole and this tissue belongs attached ...

  12. Study on nano-structured hydroxyapatite/zirconia stabilized yttria on healing of articular cartilage defect in rabbit

    Directory of Open Access Journals (Sweden)

    Amir Sotoudeh

    2013-05-01

    Full Text Available PURPOSE: Articular Cartilage has limited potential for self-repair and tissue engineering approaches attempt to repair articular cartilage by scaffolds. We hypothesized that the combined hydroxyapatite and zirconia stabilized yttria would enhance the quality of cartilage healing. METHODS: In ten New Zealand white rabbits bilateral full-thickness osteochondral defect, 4 mm in diameter and 3 mm depth, was created on the articular cartilage of the patellar groove of the distal femur. In group I the scaffold was implanted into the right stifle and the same defect was created in the left stifle without any transplant (group II. Specimens were harvested at 12 weeks after implantation, examined histologically for morphologic features, and stained immunohistochemically for type-II collagen. RESULTS: In group I the defect was filled with a white translucent cartilage tissue In contrast, the defects in the group II remained almost empty. In the group I, the defects were mostly filled with hyaline-like cartilage evidenced but defects in group II were filled with fibrous tissue with surface irregularities. Positive immunohistochemical staining of type-II collagen was observed in group I and it was absent in the control group. CONCLUSION: The hydroxyapatite/yttria stabilized zirconia scaffold would be an effective scaffold for cartilage tissue engineering.

  13. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies.

    LENUS (Irish Health Repository)

    Moran, Ellen M

    2009-01-01

    INTRODUCTION: The aim of this study was to examine IL-17A in patients, following anti-TNF-alpha therapy and the effect of IL-17A on matrix turnover and cartilage degradation. METHODS: IL-17A expression was examined by ELISA and immunohistology in the rheumatoid arthritis (RA) joints. RA whole synovial tissue explant (RA ST), primary synovial fibroblasts (RASFC), human cartilage and chondrocyte cultures were stimulated with IL-17A +\\/- TNF-alpha and Oncostatin M (OSM). Matrix metalloproteinase (MMP) and tissue inhibitor (TIMP-1) were assessed by ELISA and zymography. Cartilage proteoglycan release was assessed histologically by Safranin-O staining. Clinical parameters, IL-17A, MMP\\/TIMP were assessed in patients pre\\/post biologic therapy. RESULTS: IL-17A levels were higher in RA vs osteoarthritis (OA)\\/normal joints (P < 0.05). IL-17A up-regulated MMP-1, -2, -9, and -13 in RA ST, RASFC, cartilage and chondrocyte cultures (P < 0.05). In combination with TNF-alpha and OSM, IL-17A shifted the MMP:TIMP-1 ratio in favor of matrix degradation (all P < 0.05). Cartilage proteoglycan depletion in response to IL-17A was mild; however, in combination with TNF-alpha or OSM showed almost complete proteoglycan depletion. Serum IL-17A was detected in 28% of patients commencing biologic therapy. IL-17A negative patients demonstrated reductions post therapy in serum MMP1\\/TIMP4, MMP3\\/TIMP1 and MMP3\\/TIMP4 ratios and an increase in CS846 (all P < 0.05). No significant changes were observed in IL-17A positive patients. CONCLUSIONS: IL-17A is produced locally in the inflamed RA joint. IL-17A promotes matrix turnover and cartilage destruction, especially in the presence of other cytokines, mimicking the joint environment. IL-17A levels are modulated in vivo, following anti-TNF therapy, and may reflect changes in matrix turnover.

  14. Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis.

    Science.gov (United States)

    Goldring, Steven R

    2012-08-01

    The articular cartilage and the subchondral bone form a biocomposite that is uniquely adapted to the transfer of loads across the diarthrodial joint. During the evolution of the osteoarthritic process biomechanical and biological processes result in alterations in the composition, structure and functional properties of these tissues. Given the intimate contact between the cartilage and bone, alterations of either tissue will modulate the properties and function of the other joint component. The changes in periarticular bone tend to occur very early in the development of OA. Although chondrocytes also have the capacity to modulate their functional state in response to loading, the capacity of these cells to repair and modify their surrounding extracellular matrix is relatively limited in comparison to the adjacent subchondral bone. This differential adaptive capacity likely underlies the more rapid appearance of detectable skeletal changes in OA in comparison to the articular cartilage. The OA changes in periarticular bone include increases in subchondral cortical bone thickness, gradual decreases in subchondral trabeular bone mass, formation of marginal joint osteophytes, development of bone cysts and advancement of the zone of calcified cartilage between the articular cartilage and subchondral bone. The expansion of the zone of calcified cartilage contributes to overall thinning of the articular cartilage. The mechanisms involved in this process include the release of soluble mediators from chondrocytes in the deep zones of the articular cartilage and/or the influences of microcracks that have initiated focal remodeling in the calcified cartilage and subchondral bone in an attempt to repair the microdamage. There is the need for further studies to define the pathophysiological mechanisms involved in the interaction between subchondral bone and articular cartilage and for applying this information to the development of therapeutic interventions to improve the

  15. 间充质干细胞源性微囊泡和诱导性多潜能干细胞促进关节软骨修复的进展%Articular cartilage repair using mesenchymal stem cells-derived microvesicles and induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    侯威宇; 程艳伟; 向川

    2015-01-01

    BACKGROUND:Induced pluripotent stem cels and mesenchymal stem cels-derived microvesicles have been confirmed in various tissue repairs, which are expected to become more effective and safe therapy for articular cartilage repair. OBJECTIVE:To overal understand the research progress in the use of induced pluripotent stem cels and mesenchymal stem cels-derived microvesicles in articular cartilage repair. METHODS: A computer-based search of PubMed and CNKI was performed by the first author for articles related to stem cel treatment of osteoarthritis published from 2003 to 2015. The keywords were “articular cartilage injury, bone marrow mesenchymal stem cels” in English and Chinese, respectively. In the same field, articles published recently or in authorized journals were preferred. RESULTS AND CONCLUSION:Articular cartilage injury is stil a difficulty in the orthopedics. Many repair methods have been reported, but they al have limitations. Induced pluripotent stem cels and mesenchymal stem cels-derived microvesicles bring a new hope for patients with articular cartilage injury. However, there are stil many problems to be solved, such as extracting and purifying a large amount of cels, proliferation and differentiation potentials, and mechanism underlying cartilage repair.%背景:间充质干细胞源性微囊泡和诱导性多潜能干细胞在多个领域的组织修复作用已被证实,两者有望成为修复关节软骨损伤更有效、更安全的治疗方法。目的:综述间充质干细胞源性微囊泡和诱导性多潜能干细胞促进软骨修复的研究进展。方法:由第一作者应用计算机检索PubMed、中国期刊全文数据库(CNKI)2003年至2015年8月相关文献,英文检索词为“Articular cartilage injury,Bone marrow mesenchymal stem cels”,中文检索词为“软骨损伤,骨髓间充质干细胞”。选择文章内容与干细胞治疗骨关节炎有关者,同一领域文献则选择近期发表在权威

  16. Implantation of scaffold-free engineered cartilage constructs in a rabbit model for chondral resurfacing.

    Science.gov (United States)

    Brenner, Jillian M; Ventura, Nicole M; Tse, M Yat; Winterborn, Andrew; Bardana, Davide D; Pang, Stephen C; Hurtig, Mark B; Waldman, Stephen D

    2014-02-01

    Joint resurfacing techniques offer an attractive treatment for damaged or diseased cartilage, as this tissue characteristically displays a limited capacity for self-repair. While tissue-engineered cartilage constructs have shown efficacy in repairing focal cartilage defects in animal models, a substantial number of cells are required to generate sufficient quantities of tissue for the repair of larger defects. In a previous study, we developed a novel approach to generate large, scaffold-free cartilaginous constructs from a small number of donor cells (20 000 cells to generate a 3-cm(2) tissue construct). As comparable thicknesses to native cartilage could be achieved, the purpose of the present study was to assess the ability of these constructs to survive implantation as well as their potential for the repair of critical-sized chondral defects in a rabbit model. Evaluated up to 6 months post-implantation, allogenic constructs survived weight bearing without a loss of implant fixation. Implanted constructs appeared to integrate near-seamlessly with the surrounding native cartilage and also to extensively remodel with increasing time in vivo. By 6 months post-implantation, constructs appeared to adopt both a stratified (zonal) appearance and a biochemical composition similar to native articular cartilage. In addition, constructs that expressed superficial zone markers displayed higher histological scores, suggesting that transcriptional prescreening of constructs prior to implantation may serve as an approach to achieve superior and/or more consistent reparative outcomes. As the results of this initial animal study were encouraging, future studies will be directed toward the repair of chondral defects in more mechanically demanding anatomical locations. PMID:24571514

  17. Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography

    OpenAIRE

    Palmer, Ashley W.; Guldberg, Robert E.; Levenston, Marc E.

    2006-01-01

    Small animal models of osteoarthritis are often used for evaluating the efficacy of pharmacologic treatments and cartilage repair strategies, but noninvasive techniques capable of monitoring matrix-level changes are limited by the joint size and the low radiopacity of soft tissues. Here we present a technique for the noninvasive imaging of cartilage at micrometer-level resolution based on detecting the equilibrium partitioning of an ionic contrast agent via microcomputed tomography. The appro...

  18. Nanocomposite hydrogels for cartilage tissue engineering: mesoporous silica nanofibers interlinked with siloxane derived polysaccharide.

    Science.gov (United States)

    Buchtová, Nela; Réthoré, Gildas; Boyer, Cécile; Guicheux, Jérôme; Rambaud, Frédéric; Vallé, Karine; Belleville, Philippe; Sanchez, Clément; Chauvet, Olivier; Weiss, Pierre; Le Bideau, Jean

    2013-08-01

    Injectable materials for mini-invasive surgery of cartilage are synthesized and thoroughly studied. The concept of these hybrid materials is based on providing high enough mechanical performances along with a good medium for chondrocytes proliferation. The unusual nanocomposite hydrogels presented herein are based on siloxane derived hydroxypropylmethylcellulose (Si-HPMC) interlinked with mesoporous silica nanofibers. The mandatory homogeneity of the nanocomposites is checked by fluorescent methods, which show that the silica nanofibres dispersion is realized down to nanometric scale, suggesting an efficient immobilization of the silica nanofibres onto the Si-HPMC scaffold. Such dispersion and immobilization are reached thanks to the chemical affinity between the hydrophilic silica nanofibers and the pendant silanolate groups of the Si-HPMC chains. Tuning the amount of nanocharges allows tuning the resulting mechanical features of these injectable biocompatible hybrid hydrogels. hASC stem cells and SW1353 chondrocytic cells viability is checked within the nanocomposite hydrogels up to 3 wt% of silica nanofibers. PMID:23666665

  19. The Effect of Negative Poisson’s Ratio Polyurethane Scaffolds for Articular Cartilage Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Yeong Jun Park

    2013-01-01

    Full Text Available An auxetic polyurethane (PU scaffold was prepared to investigate chondrocyte proliferation under compressive stimulation for cartilage regeneration. To give a negative Poisson’s ratio to the PU scaffold, volumetric compression with a 3 : 1 ratio was applied during heat treatment. For the control PU scaffold, the Poisson’s ratio was 0.9 ± 0.25 with elongation at 20% of the strain range. Poisson’s ratio for experimental specimens was approximately −0.4 ± 0.12 under the same conditions. In cell proliferation tests, cells were cultivated within the prepared scaffold under compression with a 20% strain range. With a 20% strain range elongation, the compressive load was approximately 0.3 N. The experimental group showed a 1.3 times higher cellular proliferation rate than that of the control group after 3 days in culture. At day 5 of culture, however, the rate of proliferation of the control group increased so that there was no significant difference between groups. However, collagen content (produced by the cells in the cell-proliferated medium was 1.5 times higher in the experimental group after 5 days in culture. This may have been due to the effectiveness of the auxetic structure of the scaffold. An isotropic compressive load was transmitted to the cells due to the negative Poisson ratio of the scaffold.

  20. Initial results of in vivo high-resolution morphological and biochemical cartilage imaging of patients after matrix-associated autologous chondrocyte transplantation (MACT) of the ankle

    International Nuclear Information System (INIS)

    The aim of this study was to use morphological as well as biochemical (T2 and T2* relaxation times and diffusion-weighted imaging (DWI)) magnetic resonance imaging (MRI) for the evaluation of healthy cartilage and cartilage repair tissue after matrix-associated autologous chondrocyte transplantation (MACT) of the ankle joint. Ten healthy volunteers (mean age, 32.4 years) and 12 patients who underwent MACT of the ankle joint (mean age, 32.8 years) were included. In order to evaluate possible maturation effects, patients were separated into short-term (6-13 months) and long-term (20-54 months) follow-up cohorts. MRI was performed on a 3.0-T magnetic resonance (MR) scanner using a new dedicated eight-channel foot-and-ankle coil. Using high-resolution morphological MRI, the magnetic resonance observation of cartilage repair tissue (MOCART) score was assessed. For biochemical MRI, T2 mapping, T2* mapping, and DWI were obtained. Region-of-interest analysis was performed within native cartilage of the volunteers and control cartilage as well as cartilage repair tissue in the patients subsequent to MACT. The overall MOCART score in patients after MACT was 73.8. T2 relaxation times (∝50 ms), T2* relaxation times (∝16 ms), and the diffusion constant for DWI (∝1.3) were comparable for the healthy volunteers and the control cartilage in the patients after MACT. The cartilage repair tissue showed no significant difference in T2 and T2* relaxation times (p≥0.05) compared to the control cartilage; however, a significantly higher diffusivity (∝1.5; p<0.05) was noted in the cartilage repair tissue. The obtained results suggest that besides morphological MRI and biochemical MR techniques, such as T2 and T2* mapping, DWI may also deliver additional information about the ultrastructure of cartilage and cartilage repair tissue in the ankle joint using high-field MRI, a dedicated multichannel coil, and sophisticated sequences. (orig.)

  1. A large lung gene expression study identifying fibulin-5 as a novel player in tissue repair in COPD

    NARCIS (Netherlands)

    Brandsma, Corry-Anke; van den Berge, Maarten; Postma, Dirkje S.; Jonker, Marnix R.; Brouwer, Sharon; Pare, Peter D.; Sin, Don D.; Bosse, Yohan; Laviolette, Michel; Karjalainen, Juha; Fehrmann, Rudolf S. N.; Nickle, David C.; Hao, Ke; Spanjer, Anita I. R.; Timens, Wim; Franke, Lude

    2015-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a progressive, incurable lung disease characterised by abnormal tissue repair causing emphysema and small airways fibrosis. Since current therapy cannot modify this abnormal repair, it is crucial to unravel its underlying molecular mechanism

  2. Optimization and evaluation of silk fibroin-chitosan freeze-dried porous scaffolds for cartilage tissue engineering application.

    Science.gov (United States)

    Vishwanath, Varshini; Pramanik, Krishna; Biswas, Amit

    2016-05-01

    Silk fibroin/chitosan blend has been reported to be an attractive biomaterial that provides a 3D porous structure with controllable pore size and mechanical property suitable for tissue engineering applications. However, there is no systematic study for optimizing the ratio of silk fibroin (SF) and chitosan (CS) which seems to influence the scaffold property to a great extent. The present research, therefore, investigates the effect of blend ratio of SF and CS on scaffold property and establishes the optimum value of blend ratio. Among the various blends, the scaffolds with blend ratio of SF/CS (80:20) were found to be superior. The scaffold possesses pore size in the range 71-210 μm and porosity of 82.2 ± 1.3%. The compressive strength of the scaffold was measured as 190 ± 0.2 kPa. The cell supportive property of the scaffold in terms of cell attachment, cell viability, and proliferation was confirmed by cell culture study using mesenchymal stem cells derived from umbilical cord blood. Furthermore, the assessment of glycosaminoglycan secretion on the scaffolds indicates its potentiality toward cartilage tissue regeneration. PMID:26830046

  3. Using synchrotron radiation inline phase-contrast imaging computed tomography to visualize three-dimensional printed hybrid constructs for cartilage tissue engineering.

    Science.gov (United States)

    Olubamiji, Adeola D; Izadifar, Zohreh; Zhu, Ning; Chang, Tuanjie; Chen, Xiongbiao; Eames, B Frank

    2016-05-01

    Synchrotron radiation inline phase-contrast imaging combined with computed tomography (SR-inline-PCI-CT) offers great potential for non-invasive characterization and three-dimensional visualization of fine features in weakly absorbing materials and tissues. For cartilage tissue engineering, the biomaterials and any associated cartilage extracellular matrix (ECM) that is secreted over time are difficult to image using conventional absorption-based imaging techniques. For example, three-dimensional printed polycaprolactone (PCL)/alginate/cell hybrid constructs have low, but different, refractive indices and thicknesses. This paper presents a study on the optimization and utilization of inline-PCI-CT for visualizing the components of three-dimensional printed PCL/alginate/cell hybrid constructs for cartilage tissue engineering. First, histological analysis using Alcian blue staining and immunofluorescent staining assessed the secretion of sulfated glycosaminoglycan (GAGs) and collagen type II (Col2) in the cell-laden hybrid constructs over time. Second, optimization of inline PCI-CT was performed by investigating three sample-to-detector distances (SDD): 0.25, 1 and 3 m. Then, the optimal SDD was utilized to visualize structural changes in the constructs over a 42-day culture period. The results showed that there was progressive secretion of cartilage-specific ECM by ATDC5 cells in the hybrid constructs over time. An SDD of 3 m provided edge-enhancement fringes that enabled simultaneous visualization of all components of hybrid constructs in aqueous solution. Structural changes that might reflect formation of ECM also were evident in SR-inline-PCI-CT images. Summarily, SR-inline-PCI-CT images captured at the optimized SDD enables visualization of the different components in hybrid cartilage constructs over a 42-day culture period. PMID:27140161

  4. The myofibroblast, multiple origins for major roles in normal and pathological tissue repair

    Directory of Open Access Journals (Sweden)

    Micallef Ludovic

    2012-06-01

    Full Text Available Abstract Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myofibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases.

  5. Novel Textile Scaffolds Generated by Flock Technology for Tissue Engineering of Bone and Cartilage

    OpenAIRE

    Thomas Hanke; Chokri Cherif; Wolfgang Pompe; Michael Gelinsky; Armin Springer; Birgit Mrozik; Anja Walther; Birgit Hoyer

    2012-01-01

    Textile scaffolds can be found in a variety of application areas in regenerative medicine and tissue engineering. In the present study we used electrostatic flocking—a well-known textile technology—to produce scaffolds for tissue engineering of bone. Flock scaffolds stand out due to their unique structure: parallel arranged fibers that are aligned perpendicularly to a substrate, resulting in mechanically stable structures with a high porosity. In compression tests we demonstrated good mechani...

  6. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    International Nuclear Information System (INIS)

    During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells

  7. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    Directory of Open Access Journals (Sweden)

    Nardulli Ann M

    2010-01-01

    Full Text Available Abstract Background During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH, ductal carcinoma in situ (DCIS and invasive breast cancer (IBC. Methods Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. Results We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Conclusions Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.

  8. Role of p53 gene in apoptotic repair of genotoxic tissue damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Fumio; Kakihara, Hiroyo; Kunugita, Naoki; Ootsuyama, Akira; Norimura, Toshiyuki [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

    2002-12-01

    When DNA is damaged by exposure to a small amount of radiation, it is repaired efficiently by innate mechanisms. However, if cellular damage is more extensive, DNA repair cannot be adequately completed. To clarify the role of the p53 gene in apoptotic tissue repair, the incidence of in-vivo radiation-induced somatic mutation was evaluated by measuring the T cell receptor (TCR) gene expression in p53(+/+) and p53(-/-) mice. After {gamma}-irradiation with 3 Gy,the TCR mutation frequency (MF) was higher in p53(+/+) mice than in the controls. However, when the mice were exposed to 3 Gy at a low dose rate, the TCR MF did not increase in the p53(+/+) mice, whereas it increased and remained elevated in p53(-/-) mice, which are unable to induce apoptosis. In p53(+/+) mice, the TCR MF peaked 9 days after {gamma}-irradiation with 3 Gy at a high dose rate, and then gradually decreased with a half-life of about 13 days. However, in p53(-/-) mice, the peak level of the TCR MF did not decline significantly with time. Hence, complete repair of mutagenic damage in irradiated tissues requires the integration of DNA repair and p53-dependent apoptotic tissue repair. (author)

  9. Tissue Engineering for Rotator Cuff Repair: An Evidence-Based Systematic Review

    Directory of Open Access Journals (Sweden)

    Nicola Maffulli

    2012-01-01

    Full Text Available The purpose of this systematic review was to address the treatment of rotator cuff tears by applying tissue engineering approaches to improve tendon healing, specifically platelet rich plasma (PRP augmentation, stem cells, and scaffolds. Our systematic search was performed using the combination of the following terms: “rotator cuff”, “shoulder”, “PRP”, “platelet rich plasma”, “stemcells”, “scaffold”, “growth factors”, and “tissue engineering”. No level I or II studies were found on the use of scaffolds and stem cells for rotator cuff repair. Three studies compared rotator cuff repair with or without PRP augmentation. All authors performed arthroscopic rotator cuff repair with different techniques of suture anchor fixation and different PRP augmentation. The three studies found no difference in clinical rating scales and functional outcomes between PRP and control groups. Only one study showed clinical statistically significant difference between the two groups at the 3-month followup. Any statistically significant difference in the rates of tendon rerupture between the control group and the PRP group was found using the magnetic resonance imaging. The current literature on tissue engineering application for rotator cuff repair is scanty. Comparative studies included in this review suggest that PRP augmented repair of a rotator cuff does not yield improved functional and clinical outcome compared with non-augmented repair at a medium and long-term followup.

  10. Role of p53 gene in apoptotic repair of genotoxic tissue damage in mice

    International Nuclear Information System (INIS)

    When DNA is damaged by exposure to a small amount of radiation, it is repaired efficiently by innate mechanisms. However, if cellular damage is more extensive, DNA repair cannot be adequately completed. To clarify the role of the p53 gene in apoptotic tissue repair, the incidence of in-vivo radiation-induced somatic mutation was evaluated by measuring the T cell receptor (TCR) gene expression in p53(+/+) and p53(-/-) mice. After γ-irradiation with 3 Gy,the TCR mutation frequency (MF) was higher in p53(+/+) mice than in the controls. However, when the mice were exposed to 3 Gy at a low dose rate, the TCR MF did not increase in the p53(+/+) mice, whereas it increased and remained elevated in p53(-/-) mice, which are unable to induce apoptosis. In p53(+/+) mice, the TCR MF peaked 9 days after γ-irradiation with 3 Gy at a high dose rate, and then gradually decreased with a half-life of about 13 days. However, in p53(-/-) mice, the peak level of the TCR MF did not decline significantly with time. Hence, complete repair of mutagenic damage in irradiated tissues requires the integration of DNA repair and p53-dependent apoptotic tissue repair. (author)

  11. Novel Textile Scaffolds Generated by Flock Technology for Tissue Engineering of Bone and Cartilage

    Directory of Open Access Journals (Sweden)

    Thomas Hanke

    2012-03-01

    Full Text Available Textile scaffolds can be found in a variety of application areas in regenerative medicine and tissue engineering. In the present study we used electrostatic flocking—a well-known textile technology—to produce scaffolds for tissue engineering of bone. Flock scaffolds stand out due to their unique structure: parallel arranged fibers that are aligned perpendicularly to a substrate, resulting in mechanically stable structures with a high porosity. In compression tests we demonstrated good mechanical properties of such scaffolds and in cell culture experiments we showed that flock scaffolds allow attachment and proliferation of human mesenchymal stem cells and support their osteogenic differentiation. These matrices represent promising scaffolds for tissue engineering.

  12. Modulation of tissue repair by regeneration enhancer elements.

    Science.gov (United States)

    Kang, Junsu; Hu, Jianxin; Karra, Ravi; Dickson, Amy L; Tornini, Valerie A; Nachtrab, Gregory; Gemberling, Matthew; Goldman, Joseph A; Black, Brian L; Poss, Kenneth D

    2016-04-14

    How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs. PMID:27049946

  13. Fabrication and characterization of a novel microparticle with gyrus-patterned surface and growth factor delivery for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Microparticles can serve as substrates for cell amplification and deliver the expanded cells to the site of the defect. It was hypothesized that a novel microparticle combined of sustained and localized delivery of proliferative growth factors and gyrus-patterned surface would influence the cell behaviours of adherence and expansion on the microparticle in the present study. To test the hypothesis, gelatin particles with diameter ranging from 280 to 350 μm were fabricated and were modified by cryogenic freeze-drying treatment and basic fibroblast growth factor (bFGF) incorporation. The results of in vitro chondrocyte culture illustrated that cells could proliferate more obviously on the microparticles with bFGF addition, but no correlation between attachment rate and bFGF was observed. On the other hand, microparticles with gyrus-patterned surface demonstrated the highest cell attachment rate and higher rate of cell growth, in particular on bFGF combined ones. It seems to be a promising candidate as a chondrocyte microparticle and could be the potential application in cartilage tissue engineering.

  14. Synthesis and 3D printing of biodegradable polyurethane elastomer by a water-based process for cartilage tissue engineering applications.

    Science.gov (United States)

    Hung, Kun-Che; Tseng, Ching-Shiow; Hsu, Shan-Hui

    2014-10-01

    Biodegradable materials that can undergo degradation in vivo are commonly employed to manufacture tissue engineering scaffolds, by techniques including the customized 3D printing. Traditional 3D printing methods involve the use of heat, toxic organic solvents, or toxic photoinitiators for fabrication of synthetic scaffolds. So far, there is no investigation on water-based 3D printing for synthetic materials. In this study, the water dispersion of elastic and biodegradable polyurethane (PU) nanoparticles is synthesized, which is further employed to fabricate scaffolds by 3D printing using polyethylene oxide (PEO) as a viscosity enhancer. The surface morphology, degradation rate, and mechanical properties of the water-based 3D-printed PU scaffolds are evaluated and compared with those of polylactic-co-glycolic acid (PLGA) scaffolds made from the solution in organic solvent. These scaffolds are seeded with chondrocytes for evaluation of their potential as cartilage scaffolds. Chondrocytes in 3D-printed PU scaffolds have excellent seeding efficiency, proliferation, and matrix production. Since PU is a category of versatile materials, the aqueous 3D printing process developed in this study is a platform technology that can be used to fabricate devices for biomedical applications. PMID:24729580

  15. Fabrication and characterization of a novel microparticle with gyrus-patterned surface and growth factor delivery for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Huang Sha [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Wang Yijuan [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Liang Tang [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Jin Fang [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Liu Shouxin [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Jin Yan, E-mail: yanjin@fmmu.edu.cn [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China)

    2009-05-05

    Microparticles can serve as substrates for cell amplification and deliver the expanded cells to the site of the defect. It was hypothesized that a novel microparticle combined of sustained and localized delivery of proliferative growth factors and gyrus-patterned surface would influence the cell behaviours of adherence and expansion on the microparticle in the present study. To test the hypothesis, gelatin particles with diameter ranging from 280 to 350 {mu}m were fabricated and were modified by cryogenic freeze-drying treatment and basic fibroblast growth factor (bFGF) incorporation. The results of in vitro chondrocyte culture illustrated that cells could proliferate more obviously on the microparticles with bFGF addition, but no correlation between attachment rate and bFGF was observed. On the other hand, microparticles with gyrus-patterned surface demonstrated the highest cell attachment rate and higher rate of cell growth, in particular on bFGF combined ones. It seems to be a promising candidate as a chondrocyte microparticle and could be the potential application in cartilage tissue engineering.

  16. Surgical problems in the excision and repair of radiated tissue

    International Nuclear Information System (INIS)

    Surgical procedures for tissues damaged by radiation are fraught with the possibility of multiple and serious complications. A knowledge of the altered pathophysiology of such tissues (chiefly diminished blood supply, fibrosis, and direct cellular reparative potential) is necessary for the surgeon to make a proper judgment. Recognition of the pathognomic signs in the skin is important. The possibility of malignant change must be kept in mind. Surgical treatment must include the excision of radiated tissues back to good blood supply, and then proper and adequate coverage by the simplest and best means. If the surrounding local tissues are so altered that they are unsuitable for coverage, structures from a distance must be used. Prior planning of the coverage before the excision pays dividends by preventing disastrous complications. (U.S.)

  17. Biodegradable chitosan scaffolds containing microspheres as carriers for controlled transforming growth factor-β1 delivery for cartilage tissue engineering

    Institute of Scientific and Technical Information of China (English)

    CAI Dao-zhang; ZENG Chun; QUAN Da-ping; BU Li-si; WANG Kun; LU Hua-ding; LI Xiao-feng

    2007-01-01

    TGF-β1 release group (92.4%±4.8%, P<0.05). Both the proliferation rate and production of collagen type Ⅱ in the transforming growth factor-β1 microsphere incorporated scaffolds were significantly higher than those in the scaffolds without microspheres, indicating that the activity of TGF-β1 was retained during microsphere fabrication and after growth factor release.Conclusion Chitosan microspheres can serve as delivery vehicles for controlled release of TGF-β1, and the released growth factor can augment chondrocytes proliferation and synthesis of extracellular matrix. Chitosan scaffolds incorporated with chitosan microspheres loaded with TGF-β1 possess a promising potential to be applied for controlled cytokine delivery and cartilage tissue engineering.

  18. 制备软骨组织工程支架的材料和方法★%Materials and methods for preparation of tissue-engineered cartilage scaffolds

    Institute of Scientific and Technical Information of China (English)

    贵浩然; 李澎; 张卫国

    2013-01-01

    BACKGROUND: Cartilage tissue engineering provides new ideas and approaches for repair of cartilage defects, and how to obtain the ideal scaffolds for tissue engineering is the core and difficulty. OBJECTIVE: To retrospectively analyze the material choice and preparation methods of tissue-engineered cartilage scaffolds. METHODS: The first author searched PubMed, ELSEVIER SCIENCEDIRECT, Wanfang and CNKI databases (2000/2012) to retrieve relevant articles about materials and methods to prepare tissue-engineered cartilage scaffolds. RESULTS AND CONCLUSION: Cartilage scaffold materials consist of natural biological material, synthetic polymer material and composite material. The fol owing methods can be used to prepare scaffolds materials such as phase separation, solvent casting/particulate leaching, gas foaming technology, rapid prototyping technology and electrospinning. The col agen, agarose, alginate as hydrogel natural materials can provide adequate biocompatibility, proliferation, adhesion and hydrophilicity. Meanwhile, synthetic polymer composite scaffolds prepared by electrospinning can guarantee the mechanical strength, shaping requirements, porosity, and biodegradation of the scaffolds. Therefore, it wil be more conducive to display the performance of the scaffolds if the natural materials are combined with synthetic polymer composite scaffolds using the embedded technology and surface modification technology.%  背景:软骨组织工程的研究为修复软骨缺损提供了新的思路和方法,其中如何获得理想的组织工程支架是这一研究的核心和难点。目的:回顾性分析软骨组织工程支架的材料选择和制备方法。方法:由第一作者检索2000至2012年 PubMed 数据库、ELSEVIER SCIENCEDIRECT、万方数据库、中国知网库有关制备软骨组织工程支架的材料选择和方法等方面的文献。结果与结论:软骨支架材料分为天然生物材料、人工合成高分子材料和复

  19. Chondrogenic Differentiation of Human Adipose-Derived Stem Cells: A New Path in Articular Cartilage Defect Management?

    Directory of Open Access Journals (Sweden)

    Jan-Philipp Stromps

    2014-01-01

    Full Text Available According to data published by the Centers for Disease Control and Prevention, over 6 million people undergo a variety of medical procedures for the repair of articular cartilage defects in the U.S. each year. Trauma, tumor, and age-related degeneration can cause major defects in articular cartilage, which has a poor intrinsic capacity for healing. Therefore, there is substantial interest in the development of novel cartilage tissue engineering strategies to restore articular cartilage defects to a normal or prediseased state. Special attention has been paid to the expansion of chondrocytes, which produce and maintain the cartilaginous matrix in healthy cartilage. This review summarizes the current efforts to generate chondrocytes from adipose-derived stem cells (ASCs and provides an outlook on promising future strategies.

  20. Microstructure and properties of nano-fibrous PCL-b-PLLA scaffolds for cartilage tissue engineering

    OpenAIRE

    L. He; B. Liu; G Xipeng; Xie, G; S. Liao; D Quan; Cai, D.; Lu, J.; S. Ramakrishna

    2009-01-01

    Nano-fibrous scaffolds which could potentially mimic the architecture of extracellular matrix (ECM) have been considered a good candidate matrix for cell delivery in tissue engineering applications. In the present study, a semicrystalline diblock copolymer, poly(e-caprolactone)-block-poly(L-lactide) (PCL-b-PLLA), was synthesized and utilized to fabricate nano-fibrous scaffolds via a thermally induced phase separation process. Uniform nano-fibrous networks were created by quenching a PCL-b-PLL...

  1. Development of new chitosan based biodegradable blends for bone and cartilage tissue engineering

    OpenAIRE

    Silva, Vitor Manuel Correlo da

    2009-01-01

    Tese de Doutoramento em Ciência e Tecnologia de Materiais - Engenharia de Tecidos - Materiais Híbridos A number of natural origin polymers are being employed in tissue engineering strategies. Natural origin polymers offer the advantage of being similar to macromolecular substances, which the biological environment is prepared to recognize and to deal with metabolically. Another attractive characteristic of natural polymers is their ability to be degraded by naturally occurring enz...

  2. Transcriptomic profiling of cartilage ageing

    OpenAIRE

    Mandy Jayne Peffers; Xuan Liu; Peter David Clegg

    2014-01-01

    The musculoskeletal system is severely affected by the ageing process, with many tissues undergoing changes that lead to loss of function and frailty. Articular cartilage is susceptible to age related diseases, such as osteoarthritis. Applying RNA-Seq to young and old equine cartilage, we identified an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage from older dono...

  3. Cartilage-specific over-expression of CCN family member 2/connective tissue growth factor (CCN2/CTGF stimulates insulin-like growth factor expression and bone growth.

    Directory of Open Access Journals (Sweden)

    Nao Tomita

    Full Text Available Previously we showed that CCN family member 2/connective tissue growth factor (CCN2 promotes the proliferation, differentiation, and maturation of growth cartilage cells in vitro. To elucidate the specific role and molecular mechanism of CCN2 in cartilage development in vivo, in the present study we generated transgenic mice overexpressing CCN2 and analyzed them with respect to cartilage and bone development. Transgenic mice were generated expressing a ccn2/lacZ fusion gene in cartilage under the control of the 6 kb-Col2a1-enhancer/promoter. Changes in cartilage and bone development were analyzed histologically and immunohistologically and also by micro CT. Primary chondrocytes as well as limb bud mesenchymal cells were cultured and analyzed for changes in expression of cartilage-related genes, and non-transgenic chondrocytes were treated in culture with recombinant CCN2. Newborn transgenic mice showed extended length of their long bones, increased content of proteoglycans and collagen II accumulation. Micro-CT analysis of transgenic bones indicated increases in bone thickness and mineral density. Chondrocyte proliferation was enhanced in the transgenic cartilage. In in vitro short-term cultures of transgenic chondrocytes, the expression of col2a1, aggrecan and ccn2 genes was substantially enhanced; and in long-term cultures the expression levels of these genes were further enhanced. Also, in vitro chondrogenesis was strongly enhanced. IGF-I and IGF-II mRNA levels were elevated in transgenic chondrocytes, and treatment of non-transgenic chondrocytes with recombinant CCN2 stimulated the expression of these mRNA. The addition of CCN2 to non-transgenic chondrocytes induced the phosphorylation of IGFR, and ccn2-overexpressing chondrocytes showed enhanced phosphorylation of IGFR. Our data indicates that the observed effects of CCN2 may be mediated in part by CCN2-induced overexpression of IGF-I and IGF-II. These findings indicate that CCN2

  4. Vascularization of engineered cartilage constructs in a mouse model.

    Science.gov (United States)

    Burghartz, Marc; Gehrke, Thomas; Storck, Katharina; Staudenmaier, Rainer; Mandlik, Veronika; Schurr, Christian; Hoang, Nguyen; Hagen, Rudolf; Kleinsasser, Norbert

    2015-02-01

    Tissue engineering of cartilage tissue offers a promising method for reconstructing ear, nose, larynx and trachea defects. However, a lack of sufficient nutrient supply to cartilage constructs limits this procedure. Only a few animal models exist to vascularize the seeded scaffolds. In this study, polycaprolactone (PCL)-based polyurethane scaffolds are seeded with 1 × 10(6) human cartilage cells and implanted in the right hind leg of a nude mouse using an arteriovenous flow-through vessel loop for angiogenesis for the first 3 weeks. Equally seeded scaffolds but without access to a vessel loop served as controls. After 3 weeks, a transposition of the vascularized scaffolds into the groin of the nude mouse was performed. Constructs (verum and controls) were explanted 1 and 6 weeks after transposition. Constructs with implanted vessels were well vascularized. The amount of cells increased in vascularized constructs compared to the controls but at the same time noticeably less extracellular matrix was produced. This mouse model provides critical answers to important questions concerning the vascularization of engineered tissue, which offers a viable option for repairing defects, especially when the desired amount of autologous cartilage or other tissues is not available and the nutritive situation at the implantation site is poor. PMID:25381568

  5. Full incorporation of Strattice™ Reconstructive Tissue Matrix in a reinforced hiatal hernia repair: a case report

    Directory of Open Access Journals (Sweden)

    Freedman Bruce E

    2012-08-01

    Full Text Available Abstract Introduction A non-cross-linked porcine acellular dermal matrix was used to reinforce an esophageal hiatal hernia repair. A second surgery was required 11 months later to repair a slipped Nissen; this allowed for examination of the hiatal hernia repair and showed the graft to be well vascularized and fully incorporated. Case presentation A 71-year-old Caucasian woman presented with substernal burning and significant dysphagia. An upper gastrointestinal series revealed a type III complex paraesophageal hiatal hernia. She underwent laparoscopic surgery to repair a hiatal hernia that was reinforced with a xenograft (Strattice™ Reconstructive Tissue Matrix, LifeCell, Branchburg, NJ, USA along with a Nissen fundoplication. A second surgery was required to repair a slipped Nissen; this allowed for examination of the hiatal repair and graft incorporation 11 months after the initial surgery. Conclusion In this case, a porcine acellular dermal matrix was an effective tool to reinforce the crural hiatal hernia repair. The placement of the mesh and method of fixation are believed to be crucial to the success of the graft. It was found to be well vascularized 11 months after the original placement with no signs of erosion, stricture, or infection. Further studies and long-term follow-up are required to support the findings of this case report.

  6. The Antagonistic Effect of Selenium on Lead-Induced Inflammatory Factors and Heat Shock Protein mRNA Level in Chicken Cartilage Tissue.

    Science.gov (United States)

    Zheng, Shufang; Song, Huanyu; Gao, Han; Liu, Chunpeng; Zhang, Ziwei; Fu, Jing

    2016-09-01

    Selenium (Se) is recognized as a necessary trace mineral in animal diets, including those of birds. Lead (Pb) is a toxic heavy metal and can damage organs in humans and animals. Complex antagonistic interactions between Se and heavy metals have been reported in previous studies. However, little is known regarding the effects of Se on Pb-induced toxicity and the expression of inflammatory factors and heat shock proteins (HSPs) in the cartilage of chickens. In this present study, we fed chickens either with Se or Pb or both Se and Pb supplement and later analyzed the mRNA expressions of inflammatory factors (inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2)) and HSPs (Hsp27, Hsp40, Hsp60, Hsp70, and Hsp90). The results showed that Se and Pb influenced the expression of inflammatory factors and HSP genes in the chicken cartilage tissues. Additionally, we also found that antagonistic interaction existed between Se and Pb supplementation. Our findings suggested that Se could exert a antagonistic effect on Pb in chicken cartilage tissues. PMID:26831653

  7. Human Cardiac Tissue Engineering: From Pluripotent Stem Cells to Heart Repair

    Science.gov (United States)

    Jackman, Christopher P.; Shadrin, Ilya Y.; Carlson, Aaron L.; Bursac, Nenad

    2014-01-01

    Engineered cardiac tissues hold great promise for use in drug and toxicology screening, in vitro studies of human physiology and disease, and as transplantable tissue grafts for myocardial repair. In this review, we discuss recent progress in cell-based therapy and functional tissue engineering using pluripotent stem cell-derived cardiomyocytes and we describe methods for delivery of cells into the injured heart. While significant hurdles remain, notable advances have been made in the methods to derive large numbers of pure human cardiomyocytes, mature their phenotype, and produce and implant functional cardiac tissues, bringing the field a step closer to widespread in vitro and in vivo applications. PMID:25599018

  8. Electrospun polycaprolactone scaffolds under strain and their application in cartilage tissue engineering

    Science.gov (United States)

    Nam, Jin

    Electrospinning is a promising fabrication method for three dimensional tissue engineering scaffolds due to its ability to produce a nano-/micro-sized non-woven fibrous structure which resembles the natural extracellular matrix. We investigated the mechanical behavior of two different electrospun microstructures. Polycaprolactone (PCL) fibers with or without "point-bonding" exhibited different deformation behaviors having significant biomedical consequences. While fibers with point-bonded structure failed due to the generation of voids by the fracture of fiber interconnections under strain, fibers without point-bonds produced a 'bamboo' structure with fiber joining visible at higher levels of strain. In addition, gelatin and PCL were electrospun and the residual solvent contents were systematically investigated. A simple and effective means of reducing residual solvent content was developed. The interaction between these electrospun matrices and chondrocytic cells were compared to other topographies having the same chemistry. Electrospun polycaprolactone fibers supported better proliferation and extracellular matrix production than the corresponding semi-porous and dense surfaces and even, at some time points, glass surfaces. The intrinsic capability of electrospinning to produce high porosity appears to offset the relative hydrophobicity of polycaprolactone resulting in a more uniform cell seeding. Electrospun fibers induced a higher level of glycosaminoglycans (GAG) production by providing a 'dynamic scaffold' in which chondrocytes are able to maintain a morphology associated with the appropriate phenotype. Finally, based on this study, a method producing macro-pores within an electrospun scaffold was developed. With this method, not only can cellular infiltration into a thick electrospun scaffold be facilitated, but scaffolds having designed, anisotropic structures can be produced that better approximate the final tissue.

  9. Chitosan microspheres with an extracellular matrix-mimicking nanofibrous structure as cell-carrier building blocks for bottom-up cartilage tissue engineering

    Science.gov (United States)

    Zhou, Yong; Gao, Huai-Ling; Shen, Li-Li; Pan, Zhao; Mao, Li-Bo; Wu, Tao; He, Jia-Cai; Zou, Duo-Hong; Zhang, Zhi-Yuan; Yu, Shu-Hong

    2015-12-01

    Scaffolds for tissue engineering (TE) which closely mimic the physicochemical properties of the natural extracellular matrix (ECM) have been proven to advantageously favor cell attachment, proliferation, migration and new tissue formation. Recently, as a valuable alternative, a bottom-up TE approach utilizing cell-loaded micrometer-scale modular components as building blocks to reconstruct a new tissue in vitro or in vivo has been proved to demonstrate a number of desirable advantages compared with the traditional bulk scaffold based top-down TE approach. Nevertheless, micro-components with an ECM-mimicking nanofibrous structure are still very scarce and highly desirable. Chitosan (CS), an accessible natural polymer, has demonstrated appealing intrinsic properties and promising application potential for TE, especially the cartilage tissue regeneration. According to this background, we report here the fabrication of chitosan microspheres with an ECM-mimicking nanofibrous structure for the first time based on a physical gelation process. By combining this physical fabrication procedure with microfluidic technology, uniform CS microspheres (CMS) with controlled nanofibrous microstructure and tunable sizes can be facilely obtained. Especially, no potentially toxic or denaturizing chemical crosslinking agent was introduced into the products. Notably, in vitro chondrocyte culture tests revealed that enhanced cell attachment and proliferation were realized, and a macroscopic 3D geometrically shaped cartilage-like composite can be easily constructed with the nanofibrous CMS (NCMS) and chondrocytes, which demonstrate significant application potential of NCMS as the bottom-up cell-carrier components for cartilage tissue engineering.Scaffolds for tissue engineering (TE) which closely mimic the physicochemical properties of the natural extracellular matrix (ECM) have been proven to advantageously favor cell attachment, proliferation, migration and new tissue formation

  10. Mesenchymal stem cells as a potent cell source for articular cartilage regeneration

    Institute of Scientific and Technical Information of China (English)

    Mohamadreza; Baghaban; Eslaminejad; Elham; Malakooty; Poor

    2014-01-01

    Since articular cartilage possesses only a weak capac-ity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is as-sociated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechani-cal properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical pro-cedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morpho-logical features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells(MSCs) to be an appropriate cellular mate-rial for articular cartilage repair. These cells were origi-nally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic dif-ferentiation is an inherent property of MSCs noticedat the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative proper-ties. Moreover, these cells possess a considerable im-munomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review.

  11. Tissue repair response as a function of dose in thioacetamide hepatotoxicity.

    OpenAIRE

    Mangipudy, R S; Chanda, S.; Mehendale, H M

    1995-01-01

    The purpose of the present study was to establish a dose-response relationship for thioacetamide (TA), where tissue regeneration as well as liver injury were two simultaneous but opposing responses. Male Sprague-Dawley rats were injected intraperitioneally with a 12-fold dose range of TA, and both liver injury and tissue repair were measured. Liver injury was assessed by serum enzyme elevations. Serum alanine aminotransferase (ALT) elevation did not show any dose response over a 12-fold dose ...

  12. Strategies for osteochondral repair: Focus on scaffolds

    OpenAIRE

    Seo, S J; Mahapatra, C.; Singh, R. K.; Knowles, J. C.; Kim, H. W.

    2014-01-01

    Interest in osteochondral repair has been increasing with the growing number of sports-related injuries, accident traumas, and congenital diseases and disorders. Although therapeutic interventions are entering an advanced stage, current surgical procedures are still in their infancy. Unlike other tissues, the osteochondral zone shows a high level of gradient and interfacial tissue organization between bone and cartilage, and thus has unique characteristics related to the ability to resist mec...

  13. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    Science.gov (United States)

    Duann, Pu; Lianos, Elias A.; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  14. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Pu Duann

    2016-05-01

    Full Text Available Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed.

  15. Telocytes as a Source of Progenitor Cells in Regeneration and Repair Through Granulation Tissue.

    Science.gov (United States)

    Díaz-Flores, Lucio; Gutiérrez, Ricardo; Pino García, Maria; González, Miriam; Díaz-Flores, Lucio; Francisco Madrid, Juan

    2016-01-01

    This review outlines the role of CD34+ stromal cells/telocytes (CD34+ SC/TCs) in repair and considers the following issues. Firstly, the conceptual aspects of repair, including regeneration and repair through granulation tissue (RTGT) as two types of repair, RTGT stages (inflammatory, proliferative, and remodeling), and tissue in repair as a substrate to assess the in vivo behavior of activated CD34+ SC/TCs. Subsequently, current knowledge of CD34+ SC/TCs, such as identification, characteristics, and functions, as well as possible stages (quiescent and activated) are taken into account. We then consider the role in regeneration of quiescent CD34+ SC/TCs (in unperturbed physiological conditions) as a nurse of stem cells (e.g., in the heart, skin, respiratory tree, gastrointestinal tract, liver, eye, and choroid plexus). Special attention is paid to the characteristics of activated CD34+ SC/TCs and the overlapping steps of activation with and without loss of CD34 expression and with and without gain of αSMA expression. With this contribution, we establish the role of CD34+ SC/TCs as progenitor cells and as a source of fibroblasts and myofibroblasts in repair through granulation tissue, fibrosis, and tumor stroma. Activated CD34+ SC/TCs in encapsulation and other processes (e.g., Reinke's edema, cutaneous myxoid cyst, mixomatous mitral valve degeneration, and fibrous papula of the face) are also outlined. Finally, similarities between modifications of CD34+ SC/TCs during in vivo activation and of multipotent mesenchymal stromal/stem cells in culture are examined in order to correlate the growing literature on CD34+ SC/TCs and the exponential research in cultured mesenchymal stromal/stem cells. PMID:26423297

  16. Green fluorescent protein as marker in chondrocytes overexpressing human insulin-like growth factor-1 for repair of articular cartilage defects in rabbits

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shao-kun; LIU Yi; SONG Zhi-ming; FU Chang-feng; XU Xin-xiang

    2007-01-01

    Objective:To label the primary articular chondrocytes overexpressing human insulin-like growth factor ( hIGF-1 ) with green fluorescent protein (GFP) for repair of articular cartilage defects in rabbits. Methods:GFP cDNA was inserted into pcDNA3.1-hIGF-1 to label the expression vector.The recombinant vector,pcGI,a mammalian expression vector with multiple cloning sites under two respective cytomegalovirus promoters/enhancers,was transfected into the primary articular chondrocytes with the help of lipofectamine.After the positive cell clones were selected by G418,G418-resistant chondrocytes were cultured in medium for 4 weeks.The stable expression of hIGF-1 in the articular chondrocytes was determined by in situ hybridization and immunocytochemical analysis and the GFP was confirmed under a fluorescence microscope. Methyl thiazolyl tetrazolium (MTT) and flow cytometer methods were employed to determine the effect of transfection on proliferation of chondrocytes. Gray value was used to analyze quantitatively the expression of type Ⅱ collagen. Results:The expression of hIGF-1 and GFP was confirmed in transfected chondrocytes by in situ hybridization, immunocytochemical analysis and fluorescence microscope observation. Green articular chondrocytes overexpressing hIGF-1 could expand and maintain their chondrogenic phenotypes for more than 4 weeks.After the transfection of IGF-1,the proliferation of chondrocytes was enhanced and the chondrocytes could effectively maintain the expression of type Ⅱ collagen. Conclusions:The hIGF-1 eukaryotic expression vector containing GFP marker gene has been successfully constructed.GFP,which can be visualized in real time and in situ, is stably expressed in articular chondrocytes overexpressing hIGF-1.The labeled articular chondrocytes overexpressing hIGF-1 can be applied in cell-mediated gene therapy as well as for other biomedical purposes of transgenic chondrocytes.

  17. Present status and applications of bacterial cellulose-based materials for skin tissue repair.

    Science.gov (United States)

    Fu, Lina; Zhang, Jin; Yang, Guang

    2013-02-15

    Bacterial cellulose (BC, also known as microbial cellulose, MC) is a promising natural polymer which is biosynthesized by certain bacteria. This review focused on BC-based materials which can be utilized for skin tissue repair. Firstly, it is illustrated that BC has unique structural and mechanical properties as compared with higher plant cellulose, and is thus expected to become a commodity material. Secondly, we summarized the basic properties and different types of BC, including self-assembled, oriented BC, and multiform BC. Thirdly, composites prepared by using BC in conjunction with other polymers are explored, and the research on BC for application in skin tissue engineering is addressed. Finally, experimental results and clinical treatments assessing the performance of wound healing materials based on BC were examined. With its superior mechanical properties, as well as its excellent biocompatibility, BC was shown to have great potential for biomedical application and very high clinical value for skin tissue repair. PMID:23399174

  18. Research Progress of Pulse Electromagnetic Field in Cartilage Defects Repair%脉冲电磁场用于软骨缺损修复的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘印

    2013-01-01

    软骨缺损是临床上常见的一种关节退行性病变,是由于关节处的组织失衡而导致的机械性或生物性损伤.脉冲电磁场作为非侵入性的疗法,已获广泛应用,可以促使软骨干细胞组织增生及分化,使骨髓中的干细胞移植到软骨缺损处,从而修复软骨组织.实验和研究表明,脉冲电磁场刺激对软骨缺损来说是一种有前途的治疗手段.总结分析有关脉冲电磁场治疗软骨缺损的体外、体内、临床研究概况,为今后的深入研究提供参考.%Cartilage defect is a clinically common kind of degenerative joint disease,due to the imbalance of joint organization in mechanical or biological damage.As a noninvasive treatment,pulse electromagnetic field has been widely used,it can stimulate the proliferation and differentiation of stem cells,the transplantation of the bone marrow stem cell into the cartilage defects place to repair cartilage fiber.Experiment and studies indicate that pulse electromagnetic field is a promising treatment for cartilage defect.Here is to provide a reference basis for I further studies from the perspectives of pulse electromagnetic field treatment of cartilage defects in vitro,in vivo,and in clinical.

  19. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series

    Directory of Open Access Journals (Sweden)

    Pak Jaewoo

    2011-07-01

    Full Text Available Abstract Introduction This is a series of clinical case reports demonstrating that a combination of percutaneously injected autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis. Case reports Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. Conclusions The MRI data for all the patients in this series showed significant positive changes. Probable bone formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.

  20. Application of chitosan and its derivatives in cartilage tissue engineering%壳聚糖及其衍生物在软骨组织工程中的应用

    Institute of Scientific and Technical Information of China (English)

    徐敬; 赵建宁; 徐海栋; 张雷

    2015-01-01

    . RESULTS AND CONCLUSION:Chitosan is a natural polymer from renewable resources, modification of chitosan has been found to be necessary for its advanced tissue engineering applications. The modification of chitosan can be divided into two categories including chemical modification and physical blending, which improve its biological properties such as biocompatibility and biodegradability. Recent studies have suggested that chondrocytes maintained round morphology and preserved synthesis of cel-specific extracel ular matrix molecules on chitosan substrates in vitro and chitosan scaffolds seeded with chondrocytes showed partial repair of cartilage defects in vitro. Chitosan and its derivatives are promising candidates as a supporting material for tissue engineering applications.

  1. Surgical anatomy and utility of pedicled vascularized tissue flaps for multilayered repair of skull base defects.

    Science.gov (United States)

    Safavi-Abbasi, Sam; Komune, Noritaka; Archer, Jacob B; Sun, Hai; Theodore, Nicholas; James, Jeffrey; Little, Andrew S; Nakaji, Peter; Sughrue, Michael E; Rhoton, Albert L; Spetzler, Robert F

    2016-08-01

    OBJECT The objective of this study was to describe the surgical anatomy and technical nuances of various vascularized tissue flaps. METHODS The surgical anatomy of various tissue flaps and their vascular pedicles was studied in 5 colored silicone-injected anatomical specimens. Medical records were reviewed of 11 consecutive patients who underwent repair of extensive skull base defects with a combination of various vascularized flaps. RESULTS The supraorbital, supratrochlear, superficial temporal, greater auricular, and occipital arteries contribute to the vascular supply of the pericranium. The pericranial flap can be designed based on an axial blood supply. Laterally, various flaps are supplied by the deep or superficial temporal arteries. The nasoseptal flap is a vascular pedicled flap based on the nasoseptal artery. Patients with extensive skull base defects can undergo effective repair with dual flaps or triple flaps using these pedicled vascularized flaps. CONCLUSIONS Multiple pedicled flaps are available for reconstitution of the skull base. Knowledge of the surgical anatomy of these flaps is crucial for the skull base surgeon. These vascularized tissue flaps can be used effectively as single or combination flaps. Multilayered closure of cranial base defects with vascularized tissue can be used safely and may lead to excellent repair outcomes. PMID:26613175

  2. A New Absorbable Synthetic Substitute With Biomimetic Design for Dural Tissue Repair.

    Science.gov (United States)

    Shi, Zhidong; Xu, Tao; Yuan, Yuyu; Deng, Kunxue; Liu, Man; Ke, Yiquan; Luo, Chengyi; Yuan, Tun; Ayyad, Ali

    2016-04-01

    Dural repair products are evolving from animal tissue-derived materials to synthetic materials as well as from inert to absorbable features; most of them lack functional and structural characteristics compared with the natural dura mater. In the present study, we evaluated the properties and tissue repair performance of a new dural repair product with biomimetic design. The biomimetic patch exhibits unique three-dimensional nonwoven microfiber structure with good mechanical strength and biocompatibility. The animal study showed that the biomimetic patch and commercially synthetic material group presented new subdural regeneration at 90 days, with low level inflammatory response and minimal to no adhesion formation detected at each stage. In the biological material group, no new subdural regeneration was observed and severe adhesion between the implant and the cortex occurred at each stage. In clinical case study, there was no cerebrospinal fluid leakage, and all the postoperation observations were normal. The biomimetic structure and proper rate of degradation of the new absorbable dura substitute can guide the meaningful reconstruction of the dura mater, which may provide a novel approach for dural defect repair. PMID:26526152

  3. Engineered cartilage covered ear implants for auricular cartilage reconstruction.

    Science.gov (United States)

    Lee, Sang Jin; Broda, Christopher; Atala, Anthony; Yoo, James J

    2011-02-14

    Cartilage tissues are often required for auricular tissue reconstruction. Currently, alloplastic ear-shaped medical implants composed of silicon and polyethylene are being used clinically. However, the use of these implants is often associated with complications, including inflammation, infection, erosion, and dislodgement. To overcome these limitations, we propose a system in which tissue-engineered cartilage serves as a shell that entirely covers the alloplastic implants. This study investigated whether cartilage tissue, engineered with chondrocytes and a fibrin hydrogel, would provide adequate coverage of a commercially used medical implant. To demonstrate the in vivo stability of cell-fibrin constructs, we tested variations of fibrinogen and thrombin concentration as well as cell density. After implantation, the retrieved engineered cartilage tissue was evaluated by histo- and immunohistochemical, biochemical, and mechanical analyses. Histomorphological evaluations consistently showed cartilage formation over the medical implants with the maintenance of dimensional stability. An initial cell density was determined that is critical for the production of matrix components such as glycosaminoglycans (GAG), elastin, type II collagen, and for mechanical strength. This study shows that engineered cartilage tissues are able to serve as a shell that entirely covers the medical implant, which may minimize the morbidity associated with implant dislodgement. PMID:21182236

  4. Cold Atmospheric Plasma Modified Electrospun Scaffolds with Embedded Microspheres for Improved Cartilage Regeneration.

    Directory of Open Access Journals (Sweden)

    Wei Zhu

    Full Text Available Articular cartilage is prone to degeneration and possesses extremely poor self-healing capacity due to inherent low cell density and the absence of a vasculature network. Tissue engineered cartilage scaffolds show promise for cartilage repair. However, there still remains a lack of ideal biomimetic tissue scaffolds which effectively stimulate cartilage regeneration with appropriate functional properties. Therefore, the objective of this study is to develop a novel biomimetic and bioactive electrospun cartilage substitute by integrating cold atmospheric plasma (CAP treatment with sustained growth factor delivery microspheres. Specifically, CAP was applied to a poly(ε-caprolactone electrospun scaffold with homogeneously distributed bioactive factors (transforming growth factor-β1 and bovine serum albumin loaded poly(lactic-co-glycolic acid microspheres. We have shown that CAP treatment renders electrospun scaffolds more hydrophilic thus facilitating vitronectin adsorption. More importantly, our results demonstrate, for the first time, CAP and microspheres can synergistically enhance stem cell growth as well as improve chondrogenic differentiation of human marrow-derived mesenchymal stem cells (such as increased glycosaminoglycan, type II collagen, and total collagen production. Furthermore, CAP can substantially enhance 3D cell infiltration (over two-fold increase in infiltration depth after 1 day of culture in the scaffolds. By integrating CAP, sustained bioactive factor loaded microspheres, and electrospinning, we have fabricated a promising bioactive scaffold for cartilage regeneration.

  5. Potential benefits and limitations of utilizing chondroprogenitors in cell-based cartilage therapy.

    Science.gov (United States)

    Jayasuriya, Chathuraka T; Chen, Qian

    2015-01-01

    Chondroprogenitor cells are a subpopulation of multipotent progenitors that are primed for chondrogenesis. They are believed to have the biological repertoire to be ideal for cell-based cartilage therapy. In addition to summarizing recent advances in chondroprogenitor cell characterization, this review discusses the projected pros and cons of utilizing chondroprogenitors in regenerative medicine and compares them with that of pre-existing methods, including autologous chondrocyte implantation (ACI) and the utilization of bone marrow derived mesenchymal stem cells (MSCs) for the purpose of cartilage tissue repair. PMID:26075411

  6. Biologic function and clinical potential of telomerase and associated proteins in cardiovascular tissue repair and regeneration

    OpenAIRE

    Madonna, Rosalinda; De Caterina, Raffaele; Willerson, James T.; Geng, Yong-Jian

    2010-01-01

    Telomeres comprise long tracts of double-stranded TTAGGG repeats that extend for 9–15 kb in humans. Telomere length is maintained by telomerase, a specialized ribonucleoprotein that prevents the natural ends of linear chromosomes from undergoing inappropriate repair, which could otherwise lead to deleterious chromosomal fusions. During the development of cardiovascular tissues, telomerase activity is strong but diminishes with age in adult hearts. Dysfunction of telomerase is associated with ...

  7. Innate Lymphoid Cells: Balancing Immunity, Inflammation, and Tissue Repair in the Intestine

    OpenAIRE

    Wojno, Elia D. Tait; Artis, David

    2012-01-01

    Innate lymphoid cells (ILCs) are a recently described group of innate immune cells that can regulate immunity, inflammation, and tissue repair in multiple anatomical compartments, particularly the barrier surfaces of the skin, airways, and intestine. Broad categories of ILCs have been defined based on transcription factor expression and the ability to produce distinct patterns of effector molecules. Recent studies have revealed that ILC populations can regulate commensal bacterial communities...

  8. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Matteini, P; Ratto, F; Rossi, F; Pini, R [Institute of Applied Physics ' Nello Carrara' , National Research Council, via Madonna del Piano 10 50019 Sesto Fiorentino (Italy)

    2014-07-31

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  9. Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis.

    Science.gov (United States)

    Pallio, Giovanni; Bitto, Alessandra; Pizzino, Gabriele; Galfo, Federica; Irrera, Natasha; Squadrito, Francesco; Squadrito, Giovanni; Pallio, Socrate; Anastasi, Giuseppe P; Cutroneo, Giuseppina; Macrì, Antonio; Altavilla, Domenica

    2016-01-01

    Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodeling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodeling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN), to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitrobenzenesulfonic acid (DNBS), 25 mg diluted in 0.8 ml 50% ethanol. After 6 h, animals were randomized to receive either PDRN (8 mg/kg/i.p.), or PDRN + the A2A antagonist [3,7-dimethyl-1-propargylxanthine (DMPX); 10 mg/kg/i.p.], or vehicle (0.8 ml saline solution) daily. In the second model, dextran sulfate sodium (DSS) was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 h animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxidase activity, and malondialdehyde. All these effects were abolished by the concomitant administration of the A2A antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases. PMID:27601997

  10. Dielectric study of interaction of water with normal and osteoarthritis femoral condyle cartilage.

    Science.gov (United States)

    Marzec, E; Olszewski, J; Kaczmarczyk, J; Richter, M; Trzeciak, T; Nowocień, K; Malak, R; Samborski, W

    2016-08-01

    The main goal of this paper is the in vitro study of healthy and osteoarthritis (OA) human cartilage using the dielectric spectroscopy in the alpha-dispersion region of the electric field and in the temperatures from 25 to 140°C. The activation energy of conductivity needed to break the bonds formed by water in the extracellular matrix takes the average values of 61kJ/mol and 44kJ/mol for the control and OA cartilages, respectively. At 28°C, the small difference appears in the permittivity decrement between the control and OA cartilages, while the conductivity increment is about 2 times higher for the control tissue than that for the OA tissue. At 75°C, the conductivity increment for both of these samples is 8 times higher than their respective permittivity decrement. In addition, at 140°C the values of these both parameters for the OA tissue decrease by 8 times as compared to those recorded for the control sample. The relaxation frequency of about 10kHz is similar for both of these samples. The knowledge on dielectric properties of healthy and OA cartilage may prove relevant to tissue engineering focused on the repair of cartilage lesions via the layered structure designing. PMID:27015448

  11. In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee

    Science.gov (United States)

    Chan, Deva D.; Cai, Luyao; Butz, Kent D.; Trippel, Stephen B.; Nauman, Eric A.; Neu, Corey P.

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment.

  12. Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Y T [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Tian, W M [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Yu, X [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Cui, F Z [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing, 100084 (China); Hou, S P [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing, 100054 (China); Xu, Q Y [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing, 100054 (China); Lee, In-Seop [Institute of Physics and Applied Physics, and Atomic-scale Surface Science Research Center, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2007-09-15

    A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue.

  13. Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

    Science.gov (United States)

    Wei, Y. T.; Tian, W. M.; Yu, X.; Cui, F. Z.; Hou, S. P.; Xu, Q. Y.; Lee, In-Seop

    2007-09-01

    A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue.

  14. Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

    International Nuclear Information System (INIS)

    A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue

  15. Drug delivery technologies and stem cells for tissue repair and regeneration.

    Science.gov (United States)

    Orive, Gorka; Cobos, Raquel; Gorriti, Janire; Pedraz, Jose L; Meregalli, Mirella; Torrente, Yvan

    2015-01-01

    In the last few years several technologies are being developed for eventually repairing or replacing damaged or injured tissues and even organs. Some of these emerging technologies include the design and development of new biomaterials, the optimization of nano- and micro-technologies for drug and cell delivery, the use of autologous proteins or the application of stem cells as therapeutics. Thus, several types of stem cells, e.g. ESCs, iPSCs, MSCs, CD133+ stem cells are being evaluated for tissue regeneration purposes. The present review describes some of these emerging technologies and discusses their potential benefits and challenges. PMID:25934974

  16. Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

    Directory of Open Access Journals (Sweden)

    Agathi-Vasiliki Goula

    2013-07-01

    Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

  17. Anatomical study of nasal cartilage in buffalo (Bubalus bubulus

    Directory of Open Access Journals (Sweden)

    Mahdi Yeganehzad

    2011-07-01

    Full Text Available This study used ten heads of adult buffalo taken from slaughterhouse. After transferring the samples to the anatomy hall, a split was carefully created on skin of muzzle and the skin was slowly separated from muscles and hypodermal connective tissue. Place of connection of cartilages to bone, cartilages to each other and shape of the cartilages were specified. In buffalo, nose apex has two nostrils fixed by bone and cartilage. After identifying and separating the cartilages, it was found that nasal cartilages in buffalo consisted of: 1 septum nasal located between two nostrils and reinforces it from inside. 2 dorso-lateral nasal cartilage constituting dorsal and lateral parts of the nostril. 3 ventro-lateral nasal cartilage constituting ventral and lateral parts of the nostril. 4 lateral accessory cartilage constituting lateral and ventral parts of the nostril. 5 medial accessory nasal cartilage located at Alar fold and connected to ventro-lateral nasal cartilage.

  18. Magnetic resonance imaging of articular cartilage at 3 tesla

    International Nuclear Information System (INIS)

    Smooth motor function can be maintained by articular cartilage. When the cartilage is injured, edema occurs, and as degeneration progresses, the cartilage thins and the cartilage matrix decreases. Magnetic resonance (MR) imaging allows noninvasive evaluation of these changes. Fat suppression proton density- and T2-weighted imaging are useful in the morphologic evaluation of articular cartilage. High resolution, 3-tesla MR imaging provides more detailed evaluation. Biochemical information from T2 mapping, T1ρ mapping, and delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) is useful for early diagnosis of cartilage injury and evaluation of cartilage repair. The role of MR imaging in evaluating articular cartilage will increase in the future aging society. (author)

  19. Composite Tissue Allotransplantation and Dysregulation in Tissue Repair and Regeneration: A Role for Mesenchymal Stem Cells

    OpenAIRE

    Antony, Anuja K.; Rodby, Katherine; Tobin, Matthew K; O’Connor, Megan I.; Pearl, Russell K.; DiPietro, Luisa A.; Breidenbach, Warren C.; Bartholomew, Amelia M.

    2013-01-01

    Vascularized composite tissue allotransplantation is a rapidly evolving area that has brought technological advances to the forefront of plastic surgery, hand surgery, and transplant biology. Composite tissue allografts (CTAs) may have profound functional, esthetic, and psychological benefits, but carry with them the risks of life-long immunosuppression and the inadequate abilities to monitor and prevent rejection. Allografts may suffer from additional insults further weakening their overall ...

  20. A new osteonecrosis animal model of the femoral head induced by microwave heating and repaired with tissue engineered bone

    OpenAIRE

    Li, Yanlin; Han, Rui; Geng, Chengkui; Wang, Yongnian; Wei, Lei

    2008-01-01

    The objective of this research was to induce a new animal model of osteonecrosis of the femoral head (ONFH) by microwave heating and then repair with tissue engineered bone. The bilateral femoral heads of 84 rabbits were heated by microwave at various temperatures. Tissue engineered bone was used to repair the osteonecrosis of femoral heads induced by microwave heating. The roentgenographic and histological examinations were used to evaluate the results. The femoral heads heated at 55°C for t...

  1. Gene Delivery of TGF-β3 and BMP2 in an MSC-Laden Alginate Hydrogel for Articular Cartilage and Endochondral Bone Tissue Engineering.

    Science.gov (United States)

    Gonzalez-Fernandez, Tomas; Tierney, Erica G; Cunniffe, Grainne M; O'Brien, Fergal J; Kelly, Daniel J

    2016-05-01

    Incorporating therapeutic genes into three-dimensional biomaterials is a promising strategy for enhancing tissue regeneration. Alginate hydrogels have been extensively investigated for cartilage and bone tissue engineering, including as carriers of transfected cells to sites of injury, making them an ideal gene delivery platform for cartilage and osteochondral tissue engineering. The objective of this study was to develop gene-activated alginate hydrogels capable of supporting nanohydroxyapatite (nHA)-mediated nonviral gene transfer to control the phenotype of mesenchymal stem cells (MSCs) for either cartilage or endochondral bone tissue engineering. To produce these gene-activated constructs, MSCs and nHA complexed with plasmid DNA (pDNA) encoding for transforming growth factor-beta 3 (pTGF-β3), bone morphogenetic protein 2 (pBMP2), or a combination of both (pTGF-β3-pBMP2) were encapsulated into alginate hydrogels. Initial analysis using reporter genes showed effective gene delivery and sustained overexpression of the transgenes were achieved. Confocal microscopy demonstrated that complexing the plasmid with nHA before hydrogel encapsulation led to transport of the plasmid into the nucleus of MSCs, which did not happen with naked pDNA. Gene delivery of TGF-β3 and BMP2 and subsequent cell-mediated expression of these therapeutic genes resulted in a significant increase in sulfated glycosaminoglycan and collagen production, particularly in the pTGF-β3-pBMP2 codelivery group in comparison to the delivery of either pTGF-β3 or pBMP2 in isolation. In addition, stronger staining for collagen type II deposition was observed in the pTGF-β3-pBMP2 codelivery group. In contrast, greater levels of calcium deposition were observed in the pTGF-β3- and pBMP2-only groups compared to codelivery, with a strong staining for collagen type X deposition, suggesting these constructs were supporting MSC hypertrophy and progression along an endochondral pathway. Together, these

  2. Porous poly (lactic-co-glycolide) microsphere sintered scaffolds for tissue repair applications

    International Nuclear Information System (INIS)

    In this paper, a new route to preparing porous poly (lactic-co-glycolide) (PLGA) scaffolds for bone tissue repair applications was developed. Novel porous PLGA scaffolds were fabricated via microsphere sintered technique and gas forming technique. Ammonium bicarbonate was used to regulate porosity of these porous scaffolds. Porosity of the scaffolds, and cell attachment, viability and proliferation on the scaffolds were evaluated. The results indicated that PLGA porous scaffolds were with the porosity from around 30% to 95% by regulating ammonium bicarbonate content from 0 to 10%. We also found that PLGA porous microsphere scaffolds benefited cell attachment and viability. Taken together, the achieved porous scaffolds have controlled porosity and also support mesenchymal stem cell proliferation, which could serve as potential scaffolds for bone repair applications.

  3. Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Yusuke Nakagawa

    Full Text Available Lubricin expression in the superficial cartilage will be a crucial factor in the success of cartilage regeneration. Mesenchymal stem cells (MSCs are an attractive cell source and the use of aggregates of MSCs has some advantages in terms of chondrogenic potential and efficiency of cell adhesion. Lubricin expression in transplanted MSCs has not been fully elucidated so far. Our goals were to determine (1 whether cartilage pellets of human MSCs expressed lubricin in vitro chondrogenesis, (2 whether aggregates of human MSCs promoted lubricin expression, and (3 whether aggregates of MSCs expressed lubricin in the superficial cartilage after transplantation into osteochondral defects in rats.For in vitro analysis, human bone marrow (BM MSCs were differentiated into cartilage by pellet culture, and also aggregated using the hanging drop technique. For an animal study, aggregates of BM MSCs derived from GFP transgenic rats were transplanted to the osteochondral defect in the trochlear groove of wild type rat knee joints. Lubricin expression was mainly evaluated in differentiated and regenerated cartilages.In in vitro analysis, lubricin was detected in the superficial zone of the pellets and conditioned medium. mRNA expression of Proteoglycan4 (Prg4, which encodes lubricin, in pellets was significantly higher than that of undifferentiated MSCs. Aggregates showed different morphological features between the superficial and deep zone, and the Prg4 mRNA expression increased after aggregate formation. Lubricin was also found in the aggregate. In a rat study, articular cartilage regeneration was significantly better in the MSC group than in the control group as shown by macroscopical and histological analysis. The transmission electron microscope showed that morphology of the superficial cartilage in the MSC group was closer to that of the intact cartilage than in the control group. GFP positive cells remained in the repaired tissue and expressed lubricin in

  4. Failed hypospadias repair: An algorithm for secondary reconstruction using remaining local tissue.

    Science.gov (United States)

    Nozohoor Ekmark, Ann; Svensson, Henry; Arnbjörnsson, Einar; Hansson, Emma

    2015-11-01

    Salvage hypospadias surgery is performed after failed primary reconstruction. Several treatment strategies have been suggested, all with pros and cons. The aim of this study was to evaluate our treatment algorithm for primary hypospadias repair applied to secondary cases in which a salvage procedure is indicated and, most importantly, local tissue is present. The algorithm was applied to 36 consecutive patients who had undergone a total of 109 surgical procedures before referral. In accordance with the algorithm, 12 patients without ventral curvature achieved a satisfactory result with one procedure by the use of local skin flaps. Six patients with moderate ventral curvature underwent orthoplasty, fistula closure, and/or urethral reconstruction using local skin flaps in one session. Eighteen patients with a severe ventral curvature or a proximal meatus were reconstructed in two stages using Byars' technique. After a median of two salvage procedures (range: 1-4), all patients but one, who awaits splitting of a skin bridge in the meatus, were successfully reconstructed. Two patients in active follow-up have potential problems requiring further surgery. Our findings indicate that failed hypospadias repairs are often due to an underestimation of the ventral curvature at the initial repair. Therefore, reevaluation of the degree of curvature is important. One-stage salvage repairs can be used, provided that none or minimal curvature remains. In cases of marked curvature, however, a meticulous resection of the chordee and ventral scarring is crucial. The subsequent repair of the large ventral defect and the long urethral reconstruction can, in most cases, be safely managed in a two-stage procedure. PMID:26195272

  5. Cartilage-selective genes identified in genome-scale analysis of non-cartilage and cartilage gene expression

    Directory of Open Access Journals (Sweden)

    Cohn Zachary A

    2007-06-01

    Full Text Available Abstract Background Cartilage plays a fundamental role in the development of the human skeleton. Early in embryogenesis, mesenchymal cells condense and differentiate into chondrocytes to shape the early skeleton. Subsequently, the cartilage anlagen differentiate to form the growth plates, which are responsible for linear bone growth, and the articular chondrocytes, which facilitate joint function. However, despite the multiplicity of roles of cartilage during human fetal life, surprisingly little is known about its transcriptome. To address this, a whole genome microarray expression profile was generated using RNA isolated from 18–22 week human distal femur fetal cartilage and compared with a database of control normal human tissues aggregated at UCLA, termed Celsius. Results 161 cartilage-selective genes were identified, defined as genes significantly expressed in cartilage with low expression and little variation across a panel of 34 non-cartilage tissues. Among these 161 genes were cartilage-specific genes such as cartilage collagen genes and 25 genes which have been associated with skeletal phenotypes in humans and/or mice. Many of the other cartilage-selective genes do not have established roles in cartilage or are novel, unannotated genes. Quantitative RT-PCR confirmed the unique pattern of gene expression observed by microarray analysis. Conclusion Defining the gene expression pattern for cartilage has identified new genes that may contribute to human skeletogenesis as well as provided further candidate genes for skeletal dysplasias. The data suggest that fetal cartilage is a complex and transcriptionally active tissue and demonstrate that the set of genes selectively expressed in the tissue has been greatly underestimated.

  6. Type I collagen degradation during tissue repair: comparison of mechanisms following fracture and acute coronary syndromes.

    Science.gov (United States)

    Stansfield, Rachel; Gossiel, Fatma; Morton, Allison; Newman, Christopher; Eastell, Richard

    2014-12-01

    There is turnover of type I collagen during tissue repair. The degradation of type I collagen by matrix metalloproteinases (MMPs) is reflected by serum ICTP and that by cathepsins by CTX-I. There is evidence for increases in ICTP after acute coronary syndromes (ACS) and in CTX-I during fracture repair. The involvement of the MMP pathway in fracture repair and cathepsins after myocardial infarction is unclear. We studied 74 men; 22 were admitted to the hospital on the day of their ACS (ST or non-ST elevation myocardial infarction) (mean age 56 years, range 39 to 82) and 9 attended hospital on the day of their tibial shaft fracture (mean age 33 years, range 21 to 79); we had 43 age-matched controls (mean age 54 years, range 20 to 82). Subjects with ACS and tibial shaft fracture were followed up for up to one year; control subjects were used to establish a reference interval. We measured serum ICTP by ELISA (reference interval 1.1 to 17.6 ng/mL) and CTX-I by chemiluminescence (reference interval 0.094 to 0.991 ng/mL). After ACS, the mean ICTP increased from 5.41 to 6.60 ng/mL within one day of admission (p<0.05); the mean CTX-I increased from 0.263 to 0.414 ng/mL (p<0.05). In two cases, the CTX increased to above the reference interval. After tibial shaft fracture, the mean ICTP increased from 5.51 to maximum of 8.71 ng/mL within 28 days of admission (p<0.01); the mean CTX increased from 0.200 to 0.374 ng/mL (p<0.001). In four cases, the CTX increased to above the reference interval. We conclude that the MMP and cathepsin pathways are both implicated in tissue repair in the bone and heart. This may have clinical implications; drugs that block either pathway (TIMPs, cathepsin K inhibitors) may affect the repair of both tissues. PMID:25193029

  7. Micro fracture surgery combined with sodium hyaluronate injection on repairing knee joint cartilage injury%微骨折术联合玻璃酸钠注射修复膝关节软骨损伤

    Institute of Scientific and Technical Information of China (English)

    付昌马; 钱春生; 章有才; 刘群; 周思启; 杨祖华

    2013-01-01

    Objective To research microfracture surgery combined with sodium hyahuronate injection repair knee cartilage injury patient outcomes,and analyse arthroscopic cartilage damage outerbridge grading cartilage damage in patients with or without a merger meniscus injury,whether the merger withinthe sideslip film folds of the treatment effect.Methods To select forty patients with knee cartilage damage who accepted arthroscopic surgery treatment in the third people' s hospital of hefei from april 2011 to January 2012,the trauma caused by cartilage damage in 9 cases,cartilage damage caused by arthritis in 31 cases.Divided them into three groups based on outerbridge different grade.Using two sample t-test to test knee function Lysholm score between each group before and after surgery,the knee function lysholm score before and after whether combined with the merger meniscus injury surgery,knee function Lysholm score before and after whether the merger medial synovial plica surgery and knee function Lysholm score before and after surgery in 40 cases of knee cartilage dmage used two sample t-test to compare.Results Knee cartilage injury patients included in the study,40 patients were involved in the result analysis,statistical results in the first three months of follow-up:①There had significant differences with knee function Lysholm score before and after surgery between each group (P <0.05).②The knee function Lysholm scores were significant different before and after whether combined with the merger meniscus injury surgery (P < 0.05).③There had significant differences with the knee function Lysholm score before and after whether the merger medial synovial plica surgery (P < 0.05).④The differences of knee function Lysholm score before and after surgery in 40 cases of knee cartilage damage patients was statistically significant(P < 0.05).Conclusions It would be receive a satisfactory therapeutic effect of micro fracture surgery combined with sodium hyaluronate

  8. Nerve autografts and tissue-engineered materials for the repair of peripheral nerve injuries: a 5-year bibliometric analysis

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2015-01-01

    Full Text Available With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and large-gap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords "pe-ripheral nerve injury", "autotransplant", "nerve graft", and "biomaterial", we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this field include Hannover Medical School (Germany, Washington University (USA, and Nantong University (China. The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad-ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientific contributions to this field of research.

  9. Nerve autografts and tissue-engineered materials for the repair of peripheral nerve injuries:a 5-year bibliometric analysis

    Institute of Scientific and Technical Information of China (English)

    Yuan Gao; Yu-ling Wang; Dan Kong; Bo Qu; Xiao-jing Su; Huan Li; Hong-ying Pi

    2015-01-01

    With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and large-gap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords“pe-ripheral nerve injury”,“autotransplant”,“nerve graft”, and“biomaterial”, we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this ifeld include Hannover Medical School (Germany), Washington University (USA), and Nantong University (China). The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad-ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientiifc contributions to this ifeld of research.

  10. Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation.

    Science.gov (United States)

    Cott, Catherine; Thuenauer, Roland; Landi, Alessia; Kühn, Katja; Juillot, Samuel; Imberty, Anne; Madl, Josef; Eierhoff, Thorsten; Römer, Winfried

    2016-06-01

    Pseudomonas aeruginosa is an opportunistic pathogen that induces severe lung infections such as ventilator-associated pneumonia and acute lung injury. Under these conditions, the bacterium diminishes epithelial integrity and inhibits tissue repair mechanisms, leading to persistent infections. Understanding the involved bacterial virulence factors and their mode of action is essential for the development of new therapeutic approaches. In our study we discovered a so far unknown effect of the P. aeruginosa lectin LecB on host cell physiology. LecB alone was sufficient to attenuate migration and proliferation of human lung epithelial cells and to induce transcriptional activity of NF-κB. These effects are characteristic of impaired tissue repair. Moreover, we found a strong degradation of β-catenin, which was partially recovered by the proteasome inhibitor lactacystin. In addition, LecB induced loss of cell-cell contacts and reduced expression of the β-catenin targets c-myc and cyclin D1. Blocking of LecB binding to host cell plasma membrane receptors by soluble l-fucose prevented these changes in host cell behavior and signaling, and thereby provides a powerful strategy to suppress LecB function. Our findings suggest that P. aeruginosa employs LecB as a virulence factor to induce β-catenin degradation, which then represses processes that are directly linked to tissue recovery. PMID:26862060

  11. Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation

    Science.gov (United States)

    Cott, Catherine; Thuenauer, Roland; Landi, Alessia; Kühn, Katja; Juillot, Samuel; Imberty, Anne; Madl, Josef; Eierhoff, Thorsten; Römer, Winfried

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that induces severe lung infections such as ventilator-associated pneumonia and acute lung injury. Under these conditions, the bacterium diminishes epithelial integrity and inhibits tissue repair mechanisms, leading to persistent infections. Understanding the involved bacterial virulence factors and their mode of action is essential for the development of new therapeutic approaches. In our study we discovered a so far unknown effect of the P. aeruginosa lectin LecB on host cell physiology. LecB alone was sufficient to attenuate migration and proliferation of human lung epithelial cells and to induce transcriptional activity of NF-κB. These effects are characteristic of impaired tissue repair. Moreover, we found a strong degradation of β-catenin, which was partially recovered by the proteasome inhibitor lactacystin. In addition, LecB induced loss of cell–cell contacts and reduced expression of the β-catenin targets c-myc and cyclin D1. Blocking of LecB binding to host cell plasma membrane receptors by soluble l-fucose prevented these changes in host cell behavior and signaling, and thereby provides a powerful strategy to suppress LecB function. Our findings suggest that P. aeruginosa employs LecB as a virulence factor to induce β-catenin degradation, which then represses processes that are directly linked to tissue recovery. PMID:26862060

  12. Role of endogenous Schwann cells in tissue repair after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Shu-xin Zhang; Fengfa Huang; Mary Gates; Eric G. Holmberg

    2013-01-01

    Schwann cells are glial cells of peripheral nervous system, responsible for axonal myelination and ensheathing, as well as tissue repair following a peripheral nervous system injury. They are one of several cell types that are widely studied and most commonly used for cell transplantation to treat spinal cord injury, due to their intrinsic characteristics including the ability to secrete a variety of neurotrophic factors. This mini review summarizes the recent findings of endogenous Schwann cells after spinal cord injury and discusses their role in tissue repair and axonal regeneration. After spinal cord injury, numerous endogenous Schwann cells migrate into the lesion site from the nerve roots, involving in the construction of newly formed repaired tissue and axonal myelination. These invading Schwann cells also can move a long distance away from the injury site both rostrally and caudally. In addition, Schwann cells can be induced to migrate by minimal insults (such as scar ablation) within the spinal cord and integrate with astrocytes under certain circumstances. More importantly, the host Schwann cells can be induced to migrate into spinal cord by transplantation of different cell types, such as exogenous Schwann cells, olfactory ensheathing cells, and bone marrow-derived stromal stem cells. Migration of endogenous Schwann cells following spinal cord injury is a common natural phenomenon found both in animal and human, and the myelination by Schwann cells has been examined effective in signal conduction electrophysiologically. Therefore, if the inherent properties of endogenous Schwann cells could be developed and utilized, it would offer a new avenue for the restoration of injured spinal cord.

  13. Use of synovium-derived stromal cells and chitosan/collagen type I scaffolds for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Gong Zhongcheng; Lin Zhaoquan [Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054 (China); Xiong Hui; Long Xing; Wei Lili; Li Jian; Wu Yang, E-mail: xinglong1957@yahoo.com.c [State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079 (China)

    2010-10-01

    The objective was to investigate synovium-derived stromal cells (SDSCs) coupled with chitosan/collagen type I (CS/COL-I) scaffolds for cartilage engineering. CS/COL-I scaffolds were fabricated through freeze-drying and cross-linked by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. SDSCs were isolated from synovium and cultured onto CS/COL-I scaffolds, constructs of which were incubated in serum-free chondrogenic medium with sequential application of TGF-{beta}1 and bFGF for up to 21 days and then implanted into nude mice. The physical characteristics of the scaffolds were examined. The quality of the in vitro constructs was assessed in terms of DNA content by PicoGreen assay and cartilaginous matrix by histological examination. The implants of the constructs were evaluated by histological and immunohistochemical examinations and reverse transcription PCR. Results indicated that the CS/COL-I scaffold showed porous structures, and the DNA content of SDSCs in CS/COL-I scaffolds increased at 1 week culture time. Both of the constructs in vitro and the implants were examined with positive stained GAGs histologically and the implants with positive collagen type II immunohistochemically. RT-PCR of the implants indicated that aggrecan and collagen type II expressed. It suggested that SDSCs coupled with CS/COL-I scaffolds treated sequentially with TGF-{beta}1 and bFGF in vitro were highly competent for engineered cartilage formation in vitro and in vivo.

  14. Repair of Sheep Metatarsus Defects by Using Tissue-engineering Technique

    Institute of Scientific and Technical Information of China (English)

    LI Zhanghua; YANG Yi; WANG Changyong; XIA Renyun; ZHANG Yufu; ZHAO Qiang; LIAO Wen; WANG Yonghong; LU Jianxi

    2005-01-01

    Tissue-engineering bone with porous β-tricalcium phosphate (β-TCP) ceramic and autologous bone marrow mesenchymal stem cells (MSC) was constructed and the effect of this composite on healing of segmental bone defects was investigated. 10-15 ml bone marrow aspirates were harvested from the iliac crestof sheep, and enriched for MSC by density gradient centrifugation over a Percoll cushion (1. 073 g/ml). After cultured and proliferated, tissue-engineering bones were constructed with these cells seeded onto porous β-TCP, and then the constructs were implanted in 8 sheep left metatarsus defect (25 mm in length) as experimental group. Porous β-TCP only were implanted to bridge same size and position defects in 8 sheep as control group, and 25 mm segmental bone defects of left metatarsus were left empty in 4 sheep as blank group. Sheep were sacrificed on the 6th, 12th, and 24th week postoperatively and the implants samples were examined by radiograph, histology, and biomechanical test. The 4 sheep in blank group were sacrificed on the 24th week postoperatively. The results showed that new bone tissues were observed either radiographic or histologically at the defects of experimental group as early as 6th week postoperatively, but not in control group, and osteoid tissue, woven bone and lamellar bone occurred earlier than in control group in which the bone defects were repaired in "creep substitution" way, because of the new bone formed in direct manner without progression through a cartilaginous intermediate. At the 24th week, radiographs and biomechanical test revealed an almost complete repair of the defect of experimental group, only partly in control group. The bone defects in blank group were non-healing at the 24th week. It was concluded that engineering bones constructed with porous β-TCP and autologous MSC were capable of repairing segmental bone defects in sheep metatarsus beyond "creep substitution" way and making it healed earlier. Porous β-TCP being

  15. Study of the collagen structure in the superficial zone and physiological state of articular cartilage using a 3D confocal imaging technique

    Directory of Open Access Journals (Sweden)

    Zheng Ming H

    2008-07-01

    Full Text Available Abstract Introduction The collagen structure in the superficial zone of articular cartilage is critical to the tissue's durability. Early osteoarthritis is often characterized with fissures on the articular surface. This is closely related to the disruption of the collagen network. However, the traditional histology can not offer visualization of the collagen structure in articular cartilage because it uses conventional optical microscopy that does not have insufficient imaging resolution to resolve collagen from proteoglycans in hyaline articular cartilage. This study examines the 3D collagen network of articular cartilage scored from 0 to 2 in the scoring system of International Cartilage Repair Society, and aims to develop a 3D histology for assessing early osteoarthritis. Methods Articular cartilage was visually classified into five physiological groups: normal cartilage, aged cartilage, cartilage with artificial and natural surface disruption, and fibrillated. The 3D collagen matrix of the cartilage was acquired using a 3D imaging technique developed previously. Traditional histology was followed to grade the physiological status of the cartilage in the scoring system of International Cartilage Repair Society. Results Normal articular cartilage contains interwoven collagen bundles near the articular surface, approximately within the lamina splendens. However, its collagen fibres in the superficial zone orient predominantly in a direction spatially oblique to the articular surface. With age and disruption of the articular surface, the interwoven collagen bundles are gradually disappeared, and obliquely oriented collagen fibres change to align predominantly in a direction spatially perpendicular to the articular surface. Disruption of the articular surface is well related to the disappearance of the interwoven collagen bundles. Conclusion A 3D histology has been developed to supplement the traditional histology and study the subtle changes in

  16. Composite three-dimensional woven scaffolds with interpenetrating network hydrogels to create functional synthetic articular cartilage.

    Science.gov (United States)

    Liao, I-Chien; Moutos, Franklin T; Estes, Bradley T; Zhao, Xuanhe; Guilak, Farshid

    2013-12-17

    The development of synthetic biomaterials that possess mechanical properties that mimic those of native tissues remains an important challenge to the field of materials. In particular, articular cartilage is a complex nonlinear, viscoelastic, and anisotropic material that exhibits a very low coefficient of friction, allowing it to withstand millions of cycles of joint loading over decades of wear. Here we show that a three-dimensionally woven fiber scaffold that is infiltrated with an interpenetrating network hydrogel can provide a functional biomaterial that provides the load-bearing and tribological properties of native cartilage. An interpenetrating dual-network "tough-gel" consisting of alginate and polyacrylamide was infused into a porous three-dimensionally woven poly(ε-caprolactone) fiber scaffold, providing a versatile fiber-reinforced composite structure as a potential acellular or cell-based replacement for cartilage repair. PMID:24578679

  17. Data describing the swelling behavior and cytocompatibility of biodegradable polyelectrolyte hydrogels incorporating poly(L-lysine) for applications in cartilage tissue engineering.

    Science.gov (United States)

    Lam, Johnny; Clark, Elisa C; Fong, Eliza L S; Lee, Esther J; Lu, Steven; Tabata, Yasuhiko; Mikos, Antonios G

    2016-06-01

    This data article presents data associated with the research article entitled "Evaluation of cell-laden polyelectrolyte hydrogels incorporating poly(L-lysine) for applications in cartilage tissue engineering" (Lam et al., 2016) [1]. Synthetic hydrogel composites fabricated using oligo(poly(ethylene glycol) fumarate) (OPF) macromers were utilized as vehicles for the incorporation of poly(L-lysine) (PLL) as well as the encapsulation of mesenchymal stem cells (MSCs). PLL-laden and PLL-free hydrogels were fabricated to characterize the main and interaction effects of OPF molecular weight, PLL molecular weight, and PLL loading density on the swelling and degradation of synthetic OPF hydrogels. Cells were then encapsulated within such hydrogels for in vitro culture and examined for viability, biochemical activity, and chondrogenic gene expression. These data, which are supplementary to the associated research article (Lam et al., 2016) [1], are presented here. PMID:27054167

  18. Reconstruction of focal cartilage defects in the talus with miniarthrotomy and collagen matrix

    OpenAIRE

    Walther, M.; Altenberger, S; Kriegelstein, S; Volkering, C; Röser, A.

    2014-01-01

    Surgical principal and objective Treatment of focal cartilage defects (traumatic or osteochondrosis dissecans) of the talus using a collagen matrix. The goal is to stabilize the superclot formed after microfracturing to accommodate cartilage repair. The procedure can be carried out via miniarthrotomy, without medial malleolus osteotomy. Indications International Cartilage Repair Society (ICRS) grade III and IV focal cartilage defects of the talus > 1.5 cm2. Contraindications Generalized osteo...

  19. Cartilage regeneration using a porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite

    Energy Technology Data Exchange (ETDEWEB)

    Ohyabu, Yohimi, E-mail: ooyabu.yoshimi@aist.go.jp [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, S7-5 Ookayama, Meguro, Tokyo 152-8550 (Japan); Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), Central-4, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566 (Japan); Adegawa, Takuro; Yoshioka, Tomohiko [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, S7-5 Ookayama, Meguro, Tokyo 152-8550 (Japan); Ikoma, Toshiyuki [Biomaterials Center, National Institute for Materials Science, 1-1 Sengen, Tsukuba, Ibaraki, 305-0047 (Japan); Uemura, Toshimasa [Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), Central-4, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566 (Japan); Tanaka, Junzo [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, S7-5 Ookayama, Meguro, Tokyo 152-8550 (Japan)

    2010-10-15

    Because cartilage has limited potential for self-repair, tissue engineering is expected to replace the present therapies for damaged cartilage, such as total knee arthroplasty. However, scaffolds suitable for cartilage tissue engineering have not been established. We synthesized a novel porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite (pCol-HAp/ChS), containing materials which resemble extracellular matrices in bone and cartilage tissues, which needs high compressive strength for clinical use. HAp/ChS had smaller crystals and a larger total surface area than HAp. SEM images showed pCol-HAp/ChS to have the roughest surface compared with pCol and pCol-HAp. The mechanical properties suggest that pCol-HAp/ChS and pCol/HAp are similar, and superior to pCol. Seeding experiments showed a uniform distribution of mesenchymal stem cells (MSCs) in pCol-HAp/ChS and pCol/HAp. Safranin O, Toluidine blue and Alcian blue staining after 2 weeks of culture revealed pCol-HAp/ChS to be the most chondrogenic in each case. In addition, MSCs in pCol-HAp/ChS produced more glycosaminoglycans, a cartilage matrix, than those in pCol-HAp. Further, pCol-HAp/ChS regenerated 15 times more cartilaginous tissue than pCol. From these results, pCol-HAp/ChS is expected to be a candidate for a scaffold for cartilage tissue engineering in place of collagen sponge.

  20. Cartilage regeneration using a porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite

    International Nuclear Information System (INIS)

    Because cartilage has limited potential for self-repair, tissue engineering is expected to replace the present therapies for damaged cartilage, such as total knee arthroplasty. However, scaffolds suitable for cartilage tissue engineering have not been established. We synthesized a novel porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite (pCol-HAp/ChS), containing materials which resemble extracellular matrices in bone and cartilage tissues, which needs high compressive strength for clinical use. HAp/ChS had smaller crystals and a larger total surface area than HAp. SEM images showed pCol-HAp/ChS to have the roughest surface compared with pCol and pCol-HAp. The mechanical properties suggest that pCol-HAp/ChS and pCol/HAp are similar, and superior to pCol. Seeding experiments showed a uniform distribution of mesenchymal stem cells (MSCs) in pCol-HAp/ChS and pCol/HAp. Safranin O, Toluidine blue and Alcian blue staining after 2 weeks of culture revealed pCol-HAp/ChS to be the most chondrogenic in each case. In addition, MSCs in pCol-HAp/ChS produced more glycosaminoglycans, a cartilage matrix, than those in pCol-HAp. Further, pCol-HAp/ChS regenerated 15 times more cartilaginous tissue than pCol. From these results, pCol-HAp/ChS is expected to be a candidate for a scaffold for cartilage tissue engineering in place of collagen sponge.

  1. Repair of acutely injured spinal cord through constructing tissue-engineered neural complex in adult rats

    Institute of Scientific and Technical Information of China (English)

    PU Yu; GUO Qing-shan; WANG Ai-min; WU Si-yu; XING Shu-xing; ZHANG Zhong-rong

    2007-01-01

    Objective: To construct tissue-engineered neural complex in vitro and study its effect in repairing acutely injured spinal cord in adult rats. Methods: Neural stem cells were harvested from the spinal cord of embryo rats and propagated in vitro. Then the neural stem cells were seeded into polyglycolic acid scaffolds and co-cultured with extract of embryonic spinal cord in vitro. Immunofluorescence histochemistry and scanning electron microscope were used to observe the microstructure of this complex. Animal model of spine semi-transection was made and tissue-engineered neural complex was implanted by surgical intervention. Six weeks after transplantation, functional evaluation and histochemistry were applied to evaluate the functional recovery and anatomic reconstruction. Results: The tissue-engineered neural complex had a distinct structure, which contained neonatal neurons, oligodendrocytes and astrocytes. After tissue-engineered neural complex was implanted into the injured spinal cord, the cell components such as neurons, astrocytes and oligodendrocytes, could survive and keep on developing. The adult rats suffering from spinal cord injury got an obvious neurological recovery in motor skills. Conclusions: The tissue-engineered neural complex appears to have therapeutic effects on the functional recovery and anatomic reconstruction of the adult rats with spinal cord injury.

  2. A light-reflecting balloon catheter for atraumatic tissue defect repair.

    Science.gov (United States)

    Roche, Ellen T; Fabozzo, Assunta; Lee, Yuhan; Polygerinos, Panagiotis; Friehs, Ingeborg; Schuster, Lucia; Whyte, William; Casar Berazaluce, Alejandra Maria; Bueno, Alejandra; Lang, Nora; Pereira, Maria J N; Feins, Eric; Wasserman, Steven; O'Cearbhaill, Eoin D; Vasilyev, Nikolay V; Mooney, David J; Karp, Jeffrey M; Del Nido, Pedro J; Walsh, Conor J

    2015-09-23

    A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinical translation. We developed a multifunctional, catheter-based technology with no implantable rigid components that functions by unfolding an adhesive-loaded elastic patch and deploying a double-balloon design to stabilize and apply pressure to the patch against the tissue defect site. The device uses a fiber-optic system and reflective metallic coating to uniformly disperse ultraviolet light for adhesive activation. Using this device, we demonstrate closure on the distal side of a defect in porcine abdominal wall, stomach, and heart tissue ex vivo. The catheter was further evaluated as a potential tool for tissue closure in vivo in rat heart and abdomen and as a perventricular tool for closure of a challenging cardiac septal defect in a large animal (porcine) model. Patches attached to the heart and abdominal wall with the device showed similar inflammatory response as sutures, with 100% small animal survival, indicating safety. In the large animal model, a ventricular septal defect in a beating heart was reduced to <1.6 mm. This new therapeutic platform has utility in a range of clinical scenarios that warrant minimally invasive and atraumatic repair of hard-to-reach defects. PMID:26400910

  3. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury: mechanisms of brain tissue repair.

    Science.gov (United States)

    Zhang, Zhen-Qiang; Song, Jun-Ying; Jia, Ya-Quan; Zhang, Yun-Ke

    2016-03-01

    Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically given Buyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. In rats administered Buyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrin αvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days). These data suggest that Buyanghuanwu decoction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury. PMID:27127482

  4. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury:mechanisms of brain tissue repair

    Institute of Scientific and Technical Information of China (English)

    Zhen-qiang Zhang; Jun-ying Song; Ya-quan Jia; Yun-ke Zhang

    2016-01-01

    Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically givenBuyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reper-fusion injury was established by middle cerebral artery occlusion. In rats administeredBuyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrinαvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects ofBuyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days). These data suggest thatBuyanghuanwu de-coction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury.

  5. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury: mechanisms of brain tissue repair

    Directory of Open Access Journals (Sweden)

    Zhen-qiang Zhang

    2016-01-01

    Full Text Available Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically given Buyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. In rats administered Buyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrin αvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days. These data suggest that Buyanghuanwu decoction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury.

  6. Experimental Study on Low Intensity Ultrasound and Tissue Engineering to Repair Segmental Bone Defects

    Institute of Scientific and Technical Information of China (English)

    YE Fagang; XIA Changsuo; XIA Renyun

    2006-01-01

    In order to evaluate the efficacy of low intensity ultrasound and tissue engineering technique to repair segmental bone defects, the rabbit models of 1.5-cm long rabbit radial segmental osteoperiosteum defects were established and randomly divided into 2 groups. All defects were implanted with the composite of calcium phosphate cement and bone mesenchymal stem cells, and additionally those in experimental group were subjected to low intensity ultrasound exposure, while those in control group to sham exposure. The animals were killed on the postoperative week 4, 8 and 12 respectively, and specimens were harvested. By using radiography and the methods of biomechanics, histomorphology and bone density detection, new bone formation and material degradation were observed. The results showed that with the prolongation of time after operation, serum alkaline phosphatase (AKP) levels in both groups were gradually increased, especially in experimental group,reached the peak at 6th week (experimental group: 1.26 mmol/L; control group: 0.58 mmol/L), suggesting the new bone formation in both two group, but the amount of new bone formation was greater and bone repairing capacity stronger in experimental group than in control group. On the 4th week in experimental group, chondrocytes differentiated into woven bone, and on the 12th week, remodeling of new lamellar bone and absorption of the composite material were observed. The mechanical strength of composite material and new born density in experimental group were significantly higher than in control group, indicating that low intensity ultrasound could not only effectively increase the formation of new bone, but also accelerate the calcification of new bone. It was concluded that low intensity ultrasound could evidently accelerate the healing of bone defects repaired by bone tissue engineering.

  7. A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xi; Li Yan; Gu Ning, E-mail: guning@seu.edu.c [Jiangsu Laboratory for Biomaterials and Devices, State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096 (China)

    2010-08-01

    A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced by the methods of solution blending and freeze drying. The results showed that basalt fibers can be uniformly dispersed in the PLLA matrix and significantly improve the mechanical properties and hydrophilicity of the PLLA matrix. The presence of basalt fibers may retard the polymer degradation rate and neutralize the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate the cytocompatibility of the composite. An MTT assay revealed that osteoblasts proliferated well for 7 days and there was little difference found in their viability on both PLLA and BF/PLLA films, which was consistent with the alkaline phosphatase (ALP) activity results. A fluorescent staining observation showed that osteoblasts grew well on the composites. SEM images displayed that osteoblasts tended to grow along the fiber axis. The formation of mineralized nodules was observed on the films by Alizarin red S staining. These results suggest that the presence of basalt fibers does not noticeably affect osteoblastic behavior and the designed composites are osteoblast compatible. It is concluded that basalt fibers, as reinforcing fibers, may have promising applications in hard tissue repair.

  8. A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair

    International Nuclear Information System (INIS)

    A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced by the methods of solution blending and freeze drying. The results showed that basalt fibers can be uniformly dispersed in the PLLA matrix and significantly improve the mechanical properties and hydrophilicity of the PLLA matrix. The presence of basalt fibers may retard the polymer degradation rate and neutralize the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate the cytocompatibility of the composite. An MTT assay revealed that osteoblasts proliferated well for 7 days and there was little difference found in their viability on both PLLA and BF/PLLA films, which was consistent with the alkaline phosphatase (ALP) activity results. A fluorescent staining observation showed that osteoblasts grew well on the composites. SEM images displayed that osteoblasts tended to grow along the fiber axis. The formation of mineralized nodules was observed on the films by Alizarin red S staining. These results suggest that the presence of basalt fibers does not noticeably affect osteoblastic behavior and the designed composites are osteoblast compatible. It is concluded that basalt fibers, as reinforcing fibers, may have promising applications in hard tissue repair.

  9. A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair.

    Science.gov (United States)

    Chen, Xi; Li, Yan; Gu, Ning

    2010-08-01

    A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced by the methods of solution blending and freeze drying. The results showed that basalt fibers can be uniformly dispersed in the PLLA matrix and significantly improve the mechanical properties and hydrophilicity of the PLLA matrix. The presence of basalt fibers may retard the polymer degradation rate and neutralize the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate the cytocompatibility of the composite. An MTT assay revealed that osteoblasts proliferated well for 7 days and there was little difference found in their viability on both PLLA and BF/PLLA films, which was consistent with the alkaline phosphatase (ALP) activity results. A fluorescent staining observation showed that osteoblasts grew well on the composites. SEM images displayed that osteoblasts tended to grow along the fiber axis. The formation of mineralized nodules was observed on the films by Alizarin red S staining. These results suggest that the presence of basalt fibers does not noticeably affect osteoblastic behavior and the designed composites are osteoblast compatible. It is concluded that basalt fibers, as reinforcing fibers, may have promising applications in hard tissue repair. PMID:20683132

  10. Traumatic dislocation of the incudostapedial joint repaired with fibrin tissue adhesive.

    Science.gov (United States)

    Nikolaidis, Vasilios

    2011-03-01

    We present a case of traumatic dislocation of the incudostapedial joint (ISJ) and a simple method for controlled application of the glue using commercial fibrin tissue adhesive. A 26-year-old female presented to our ENT clinic for hearing impairment to her left ear 2 months after a head trauma due to a motorcycle accident. The audiogram revealed a 40- to 50-dB HL conductive hearing loss with a notch configuration in bone conduction curve on the left ear. Computed tomography of the left temporal bone revealed a longitudinal fracture line. An exploratory tympanotomy was performed under general anesthesia. The ISJ was found dislocated while the incus was trapped by the edges of the bony lateral attic wall fracture. A small bony edge that impeded incus movement was removed and a small amount of the glue was precisely applied to the lenticular process of the incus with an angled incision knife. The long process of the incus was firmly pressed over the stapes for 30 seconds with a 90° hook and 60 seconds after the application of the glue the ISJ was repaired. One year after our patient achieved full airbone gap (ABG) closure (ABG, ≤10 dB HL), while she demonstrated overclosure in frequencies 2 and 4 kHz. Fibrin tissue glue allowed safe, rapid, and accurate repair of the ISJ and resulted in an anatomically normal articulation as the mass and shape of the ossicles was preserved. Moreover, our patient achieved full ABG closure. PMID:21344438

  11. Early efficacy study of matrix-induced autologous chondrocyte implantation repairing knee joint cartilage injury%基质诱导自体软骨细胞移植修复膝关节软骨损伤的早期疗效

    Institute of Scientific and Technical Information of China (English)

    王庆; 黄华扬; 张涛; 郑小飞; 李凭跃; 沈洪园; 陈加荣

    2016-01-01

    cartilage injury in 13 cases (11 males and 2 females) with knee joint cartilage injury from April 2012 to March 2013. The av⁃erage age was 27.5 years old. All cases were suffering from unilateral focal cartilage defect of knee joint with International Carti⁃lage Repair Society (ICRS) chondral defect classification system grade III or IV, visual analogue scale (VAS)>3, and all of which had corresponding pain symptoms. The average defect area was 4.2 cm2. Standardized rehabilitation exercise was carried out after matrix⁃induced autologous chondrocyte implantation. Patients were followed up for 1 years, and knee injury and use osteoarthritis outcome score(KOOS), International Knee Documentation Committee (IKDC), subjective knee form and Lysholm score were col⁃lected to assess the function. Meanwhile, magnetic resonance observation of cartilage repair tissue (MOCART) score was used to assess the magnetic resonance imaging. Results All patients had been followed⁃up for 1 year. One patient had meniscus repair under arthroscopy for the meniscus injury caused by downstairs sprain in 6.5 months postoperative, so the score of 12 months post⁃operative was excluded. The knee range of motion was decreased in 3 months postoperative (123.1°±8.0°) compared to preopera⁃tive one (135.4°±5.7°), and has no difference in 6 months (136.1°±6.1°) and 12 months postoperative (135.1°±3.6°) compared to preoperative one. The 5 subsets of KOOS score were decreased in 3 months compared to preoperative one, and were significantly increased in 6 months and 12 months. The IKDC has no difference in 3 months (26.1±3.9) compared to preoperative one (43.5± 6.5), and were significantly increased in 6 months (53.3±5.8) and 12 months (62.8±7.2) compared to preoperative one. The magnet⁃ic resonance observation of cartilage repair tissue (MOCART) score was increased in 12 month(73.3±17.9)compared to preopera⁃tive one(51.5 ± 12.6). Conclusion MACI is a good technology for knee

  12. Objective assessment of endogenous collagen in vivo during tissue repair by laser induced fluorescence.

    Science.gov (United States)

    Prabhu, Vijendra; Rao, Satish B S; Fernandes, Edward Mark; Rao, Anuradha C K; Prasad, Keerthana; Mahato, Krishna K

    2014-01-01

    Collagen, a triple helical protein with the primary role of mechanical function, provides tensile strength to the skin, and plays a pivotal task in tissue repair. During tissue regeneration, collagen level increases gradually and therefore, monitoring of such changes in vivo by laser induced fluorescence was the main objective behind the present study. In order to accomplish this, 15 mm diameter excisional wounds were created on six to eight week old Swiss albino mice. The collagen deposition accelerated upon irradiation of single exposure of 2 J/cm2 He-Ne laser dose immediately after wounding was recorded by laser induced autofluorescence in vivo along with un-illuminated and un-wounded controls. Autofluorescence spectra were recorded for each animal of the experimental groups on 0, 5, 10, 30, 45 and 60 days post-wounding, by exciting the granulation tissue/skin with 325 nm He-Cd laser. The variations in the average collagen intensities from the granulation tissue/skin of mice were inspected as a function of age and gender. Further, the spectral findings of the collagen synthesis in wound granulation tissue/un-wounded skin tissues were validated by Picro-Sirius red- polarized light microscopy in a blinded manner through image analysis of the respective collagen birefringence. The in vivo autofluorescence studies have shown a significant increase in collagen synthesis in laser treated animals as compared to the un-illuminated controls. Image analysis of the collagen birefringence further authenticated the ability of autofluorescence in the objective monitoring of collagen in vivo. Our results clearly demonstrate the potential of laser induced autofluorescence in the monitoring of collegen synthesis during tissue regeneration, which may have clinical implications. PMID:24874229

  13. Objective assessment of endogenous collagen in vivo during tissue repair by laser induced fluorescence.

    Directory of Open Access Journals (Sweden)

    Vijendra Prabhu

    Full Text Available Collagen, a triple helical protein with the primary role of mechanical function, provides tensile strength to the skin, and plays a pivotal task in tissue repair. During tissue regeneration, collagen level increases gradually and therefore, monitoring of such changes in vivo by laser induced fluorescence was the main objective behind the present study. In order to accomplish this, 15 mm diameter excisional wounds were created on six to eight week old Swiss albino mice. The collagen deposition accelerated upon irradiation of single exposure of 2 J/cm2 He-Ne laser dose immediately after wounding was recorded by laser induced autofluorescence in vivo along with un-illuminated and un-wounded controls. Autofluorescence spectra were recorded for each animal of the experimental groups on 0, 5, 10, 30, 45 and 60 days post-wounding, by exciting the granulation tissue/skin with 325 nm He-Cd laser. The variations in the average collagen intensities from the granulation tissue/skin of mice were inspected as a function of age and gender. Further, the spectral findings of the collagen synthesis in wound granulation tissue/un-wounded skin tissues were validated by Picro-Sirius red- polarized light microscopy in a blinded manner through image analysis of the respective collagen birefringence. The in vivo autofluorescence studies have shown a significant increase in collagen synthesis in laser treated animals as compared to the un-illuminated controls. Image analysis of the collagen birefringence further authenticated the ability of autofluorescence in the objective monitoring of collagen in vivo. Our results clearly demonstrate the potential of laser induced autofluorescence in the monitoring of collegen synthesis during tissue regeneration, which may have clinical implications.

  14. The use of PLDLA/PCL-T scaffold to repair osteochondral defects in vivo

    OpenAIRE

    Andrea Rodrigues Esposito; Angelo Carneiro Bonadio; Nathaly Oliveira Pereira; Túlio Pereira Cardoso; Maria Lourdes Peris Barbo; Eliana Aparecida de Rezende Duek

    2013-01-01

    The physiological repair of osteochondral lesions requires the development of a scaffold that is compatible with the structure of the damaged tissue, cartilage and bone. The aim of this study was to evaluate the biological performance of a PLDLA/PCL-T (90/10) scaffold for repairing osteochondral defects in rabbits. Polymeric scaffolds containing saccharose (75% w/v) were obtained by solvent casting and then implanted in the medial knee condyles of 12 New Zealand rabbits after osteochondral da...

  15. Inflammatory cytokines regulate endothelial cell survival and tissue repair functions via NF-κB signaling

    Directory of Open Access Journals (Sweden)

    Kanaji N

    2011-09-01

    Full Text Available Nobuhiro Kanaji1, Tadashi Sato2, Amy Nelson3, Xingqi Wang3, YingJi Li4, Miok Kim5, Masanori Nakanishi6, Hesham Basma3, Joel Michalski3, Maha Farid3, Michael Chandler3, William Pease3, Amol Patil3, Stephen I Rennard3, Xiangde Liu31Division of Hematology, Rheumatology and Respiratory Medicine, Kagawa University, Kagawa, Japan; 2Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan; 3Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska; 4Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan; 5Third Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan; 6Department of Internal Medicine, Jeju Medical College, Jeju, Republic of KoreaAbstract: Inflammation contributes to the development of fibrotic and malignant diseases. We assessed the ability of inflammatory cytokines to modulate endothelial cell survival and functions related to tissue repair/remodeling. Treatment with interleukin (IL-1ß or tumor necrosis factor (TNF-α (2 ng/mL led to human pulmonary artery endothelial cells becoming spindle-shaped fibroblast-like cells. However, immunoblot and DNA microarray showed no change in most endothelial and mesenchymal markers. In the presence of IL-1ß or TNF-α, cells were resistant to apoptosis induced by deprivation of serum and growth factor, and were more migratory. In addition, cells treated with IL-1ß or TNF-α contracted collagen gels more robustly. In contrast, transforming growth factor-ß1 did not induce these responses. RNA interference targeting nuclear factor (NF- κB p65 blocked the effects of IL-1ß or TNF-α on cell morphologic change, survival, migration, and collagen gel contraction. These results suggest that endothelial cells may contribute to tissue repair/remodeling via the NF-κB signaling in a milieu of airway inflammation.Keywords: NF-κB, IL-1ß, TNF-α, apoptosis, tissue repair

  16. Integration of Stem Cell to Chondrocyte-Derived Cartilage Matrix in Healthy and Osteoarthritic States in the Presence of Hydroxyapatite Nanoparticles.

    Science.gov (United States)

    Dua, Rupak; Comella, Kristin; Butler, Ryan; Castellanos, Glenda; Brazille, Bryn; Claude, Andrew; Agarwal, Arvind; Liao, Jun; Ramaswamy, Sharan

    2016-01-01

    We investigated the effectiveness of integrating tissue engineered cartilage derived from human bone marrow derived stem cells (HBMSCs) to healthy as well as osteoarthritic cartilage mimics using hydroxyapatite (HA) nanoparticles immersed within a hydrogel substrate. Healthy and diseased engineered cartilage from human chondrocytes (cultured in agar gels) were integrated with human bone marrow stem cell (HBMSC)-derived cartilaginous engineered matrix with and without HA, and evaluated after 28 days of growth. HBMSCs were seeded within photopolymerizable poly (ethylene glycol) diacrylate (PEGDA) hydrogels. In addition, we also conducted a preliminary in vivo evaluation of cartilage repair in rabbit knee chondral defects treated with subchondral bone microfracture and cell-free PEGDA with and without HA. Under in vitro conditions, the interfacial shear strength between tissue engineered cartilage derived from HBMSCs and osteoarthritic chondrocytes was significantly higher (p < 0.05) when HA nanoparticles were incorporated within the HBMSC culture system. Histological evidence confirmed a distinct spatial transition zone, rich in calcium phosphate deposits. Assessment of explanted rabbit knees by histology demonstrated that cellularity within the repair tissues that had filled the defects were of significantly higher number (p < 0.05) when HA was used. HA nanoparticles play an important role in treating chondral defects when osteoarthritis is a co-morbidity. We speculate that the calcified layer formation at the interface in the osteoarthritic environment in the presence of HA is likely to have attributed to higher interfacial strength found in vitro. From an in vivo standpoint, the presence of HA promoted cellularity in the tissues that subsequently filled the chondral defects. This higher presence of cells can be considered important in the context of accelerating long-term cartilage remodeling. We conclude that HA nanoparticles play an important role in engineered

  17. Integration of Stem Cell to Chondrocyte-Derived Cartilage Matrix in Healthy and Osteoarthritic States in the Presence of Hydroxyapatite Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Rupak Dua

    Full Text Available We investigated the effectiveness of integrating tissue engineered cartilage derived from human bone marrow derived stem cells (HBMSCs to healthy as well as osteoarthritic cartilage mimics using hydroxyapatite (HA nanoparticles immersed within a hydrogel substrate. Healthy and diseased engineered cartilage from human chondrocytes (cultured in agar gels were integrated with human bone marrow stem cell (HBMSC-derived cartilaginous engineered matrix with and without HA, and evaluated after 28 days of growth. HBMSCs were seeded within photopolymerizable poly (ethylene glycol diacrylate (PEGDA hydrogels. In addition, we also conducted a preliminary in vivo evaluation of cartilage repair in rabbit knee chondral defects treated with subchondral bone microfracture and cell-free PEGDA with and without HA. Under in vitro conditions, the interfacial shear strength between tissue engineered cartilage derived from HBMSCs and osteoarthritic chondrocytes was significantly higher (p < 0.05 when HA nanoparticles were incorporated within the HBMSC culture system. Histological evidence confirmed a distinct spatial transition zone, rich in calcium phosphate deposits. Assessment of explanted rabbit knees by histology demonstrated that cellularity within the repair tissues that had filled the defects were of significantly higher number (p < 0.05 when HA was used. HA nanoparticles play an important role in treating chondral defects when osteoarthritis is a co-morbidity. We speculate that the calcified layer formation at the interface in the osteoarthritic environment in the presence of HA is likely to have attributed to higher interfacial strength found in vitro. From an in vivo standpoint, the presence of HA promoted cellularity in the tissues that subsequently filled the chondral defects. This higher presence of cells can be considered important in the context of accelerating long-term cartilage remodeling. We conclude that HA nanoparticles play an important role in

  18. Clinical Evaluations of Soft and Hard Tissue Repair Using Osteo Gen in Periodontal Intraosseous Defects

    Directory of Open Access Journals (Sweden)

    Haghighati F

    2000-05-01

    Full Text Available The aim of this study was to evaluate the repair of hard and soft tissue using Osteo Gen and"ncomparing with flap curettage in periodontal defects. 36 periodontal intraosseous defects in sixteen"npatients involved moderate to advanced periodontitis were randomly selected and allocated to two"ngroups: test (22 and control groups (14. Slow resorption, excellent tissue compatibility, no exfoliation"nand root resorption were considered during healing. The average of pocket depth in test and control"ngroups was 3.16 and 2.73 mm, respectively. After 6 months, the average of bone repair was 2.18 mm"n(68.97% and 0.46 mm (16.84% in test and control groups. Bone apposition was obtained in test group"n(0.09 mm (2.84% while bone loss observed in control group (0.32 mm(l 1.72%. Initial pocket depths"nin test and control groups were 7.68mm and 6.61mm. After six months, re-entry surgery was performed"nand the measurement of new attachment was 3.45 mm (61.19% and 2.81 mm (51.28%. Recession of"nthe gingival margin was 1.22 mm (15.80% and 0,58 mm (8.77% for test and control groups,"nrespectively. By considering these findings, using of Osteo Gen can be recommended compare with flap"ncurettage in periodontal intraosseous defects.

  19. A biocompatible hybrid material with simultaneous calcium and strontium release capability for bone tissue repair.

    Science.gov (United States)

    Almeida, J Carlos; Wacha, András; Gomes, Pedro S; Alves, Luís C; Fernandes, M Helena Vaz; Salvado, Isabel M Miranda; Fernandes, M Helena R

    2016-05-01

    The increasing interest in the effect of strontium in bone tissue repair has promoted the development of bioactive materials with strontium release capability. According to literature, hybrid materials based on the system PDMS-SiO2 have been considered a plausible alternative as they present a mechanical behavior similar to the one of the human bone. The main purpose of this study was to obtain a biocompatible hybrid material with simultaneous calcium and strontium release capability. A hybrid material, in the system PDMS-SiO2-CaO-SrO, was prepared with the incorporation of 0.05mol of titanium per mol of SiO2. Calcium and strontium were added using the respective acetates as sources, following a sol-gel technique previously developed by the present authors. The obtained samples were characterized by FT-IR, solid-state NMR, and SAXS, and surface roughness was analyzed by 3D optical profilometry. In vitro studies were performed by immersion of the samples in Kokubo's SBF for different periods of time, in order to determine the bioactive potential of these hybrids. Surfaces of the immersed samples were observed by SEM, EDS and PIXE, showing the formation of calcium phosphate precipitates. Supernatants were analyzed by ICP, revealing the capability of the material to simultaneously fix phosphorus ions and to release calcium and strontium, in a concentration range within the values reported as suitable for the induction of the bone tissue repair. The material demonstrated to be cytocompatible when tested with MG63 osteoblastic cells, exhibiting an inductive effect on cell proliferation and alkaline phosphatase activity. PMID:26952443

  20. Tissue repair genes: the TiRe database and its implication for skin wound healing.

    Science.gov (United States)

    Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E

    2016-04-19

    Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that were shown to directly affect skin wound healing. To date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of skin wound healing-associated genes showed that skin wound healing genes are (i) over-conserved among vertebrates, but are under-conserved in invertebrates; (ii) enriched in extracellular and immuno-inflammatory genes; and display (iii) high interconnectivity and connectivity to other proteins. The latter may provide potential therapeutic targets. In addition, a slower or faster skin wound healing is indicative of an aging or longevity phenotype only when assessed in advanced ages, but not in the young. In the long run, we aim for TiRe to be a one-station resource that provides researchers and clinicians with the essential data needed for a better understanding of the mechanisms of wound healing, designing new experiments, and the development of new therapeutic strategies. TiRe is freely available online at http://www.tiredb.org. PMID:27049721

  1. Evaluation of a new range of light-activated surgical adhesives for tissue repair in a porcine model

    Science.gov (United States)

    Riley, Jill N.; Hodges, Diane E.; March, Keith L.; McNally-Heintzelman, Karen M.

    2001-05-01

    An in vitro study was conducted to determine the feasibility of using a new range of light-activated surgical adhesives for incision repair in a wide range of tissue types. Biodegradable polymer membranes of controlled porosity were fabricated with poly(L-lactic-co-glycolic acid) (PLGA) and salt particles using a solvent-casting and particulate- leaching technique. The porous membranes were doped with protein solder composed of 50%(w/v) bovine serum albumin solder and 0.5 mg/ml indocyanine green (ICG) dye mixed in deionized water. Tissue incisions were repaired using the surgical adhesive in conjunction with an 805-nm diode laser. Nine organs were tested ranging from skin to liver to the small intestine, as well as the coronary, pulmonary, carotid, femoral and splenetic arteries. Acute breaking strengths were measured and the data were analyzed by Student's T-test. Repairs formed on the small intestine were most successful followed by spleen, atrium, kidney, muscle and skin. The strongest vascular repairs were achieved in the carotid artery and femoral artery. The new surgical adhesive could possibly be used as a simple and effective method to stop bleeding and repair tissue quickly in an emergency situation, or as a substitute to mechanical staples or sutures in many clinical applications.

  2. Double-strand break repair by interchromosomal recombination: an in vivo repair mechanism utilized by multiple somatic tissues in mammals.

    Directory of Open Access Journals (Sweden)

    Ryan R White

    Full Text Available Homologous recombination (HR is essential for accurate genome duplication and maintenance of genome stability. In eukaryotes, chromosomal double strand breaks (DSBs are central to HR during specialized developmental programs of meiosis and antigen receptor gene rearrangements, and form at unusual DNA structures and stalled replication forks. DSBs also result from exposure to ionizing radiation, reactive oxygen species, some anti-cancer agents, or inhibitors of topoisomerase II. Literature predicts that repair of such breaks normally will occur by non-homologous end-joining (in G1, intrachromosomal HR (all phases, or sister chromatid HR (in S/G(2. However, no in vivo model is in place to directly determine the potential for DSB repair in somatic cells of mammals to occur by HR between repeated sequences on heterologs (i.e., interchromosomal HR. To test this, we developed a mouse model with three transgenes-two nonfunctional green fluorescent protein (GFP transgenes each containing a recognition site for the I-SceI endonuclease, and a tetracycline-inducible I-SceI endonuclease transgene. If interchromosomal HR can be utilized for DSB repair in somatic cells, then I-SceI expression and induction of DSBs within the GFP reporters may result in a functional GFP+ gene. Strikingly, GFP+ recombinant cells were observed in multiple organs with highest numbers in thymus, kidney, and lung. Additionally, bone marrow cultures demonstrated interchromosomal HR within multiple hematopoietic subpopulations including multi-lineage colony forming unit-granulocyte-erythrocyte-monocyte-megakaryocte (CFU-GEMM colonies. This is a direct demonstration that somatic cells in vivo search genome-wide for homologous sequences suitable for DSB repair, and this type of repair can occur within early developmental populations capable of multi-lineage differentiation.

  3. Engineering articular cartilage using newly developed carrageenan basedhydrogels

    OpenAIRE

    Popa, Elena Geta

    2014-01-01

    Articular cartilage holds specific functionality in the human body creating smooth gliding areas and allowing the joints to move easily without pain. However, due to its avascular nature and to the low metabolic activity of the constituent cells-the chondrocytes, cartilage has a low regenerative potential. The current surgical options to treat damaged cartilage are not long lasting and involve frequent revisions. Tissue engineering may provide an alternative approach for cartilage...

  4. S100B protein in tissue development,repair and regeneration

    Institute of Scientific and Technical Information of China (English)

    Guglielmo; Sorci; Francesca; Riuzzi; Cataldo; Arcuri; Claudia; Tubaro; Roberta; Bianchi; Ileana; Giambanco; Rosario; Donato

    2013-01-01

    The Ca 2+-binding protein of the EF-hand type,S100B,exerts both intracellular and extracellular regulatory activities.As an intracellular regulator,S100B is involved in the regulation of energy metabolism,transcription,protein phosphorylation,cell proliferation,survival,differentiation and motility,and Ca 2+ homeostasis,by interacting with a wide array of proteins(i.e.,enzymes,enzyme substrates,cytoskeletal subunits,scaffold/adaptor proteins,transcription factors,ubiquitin E3 ligases,ion channels) in a restricted number of cell types.As an extracellular signal,S100B engages the pattern recognition receptor,receptor for advanced glycation end-products(RAGE),on immune cells as well as on neuronal,astrocytic and microglial cells,vascular smooth muscle cells,skeletal myoblasts and cardiomyocytes.However,RAGE may not be the sole receptor activated by S100B,the protein being able to enhance bFGF-FGFR1 signaling by interacting with FGFR1-bound bFGF in particular cell types.Moreover,extracellular effects of S100B vary depending on its local concentration.Increasing evidence suggests that at the concentration found in extracellular fluids in normal physiological conditions and locally upon acute tissue injury,which is up to a few nM levels,S100B exerts trophic effects in the central and peripheral nervous system and in skeletal muscle tissue thus participating in tissue homeostasis.The present commentary summarizes results implicating intracellular and extracellular S100B in tissue development,repair and regeneration.

  5. In vitro cartilage production using an extracellular matrix-derived scaffold and bone marrow-derived mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yan-hong; YANG Qiang; XIA Qun; PENG Jiang; LU Shi-bi; GUO Quan-yi; MA Xin-long

    2013-01-01

    Background Cartilage repair is a challenging research area because of the limited healing capacity of adult articular cartilage.We had previously developed a natural,human cartilage extracellular matrix (ECM)-derived scaffold for in vivo cartilage tissue engineering in nude mice.However,before these scaffolds can be used in clinical applications in vivo,the in vitro effects should be further explored.Methods We produced cartilage in vitro using a natural cartilage ECM-derived scaffold.The scaffolds were fabricated by combining a decellularization procedure with a freeze-drying technique and were characterized by scanning electron microscopy (SEM),micro-computed tomography (micro-CT),histological staining,cytotoxicity assay,biochemical and biomechanical analysis.After being chondrogenically induced,the induction results of BMSCs were analyzed by histology and Immunohisto-chemistry.The attachment and viability assessment of the cells on scaffolds were analyzed using SEM and LIVE/DEAD staining.Cell-scaffold constructs cultured in vitro for 1 week and 3 weeks were analyzed using histological and immunohistochemical methods.Results SEM and micro-CT revealed a 3-D interconnected porous structure.The majority of the cartilage ECM was found in the scaffold following the removal of cellular debris,and stained positive for safranin O and collagen Ⅱ.Viability staining indicated no cytotoxic effects of the scaffold.Biochemical analysis showed that collagen content was (708.2±44.7)μg/mg,with GAG (254.7±25.9) μg/mg.Mechanical testing showed the compression moduli (E) were (1.226±0.288) and (0.052±0.007) MPa in dry and wet conditions,respectively.Isolated canine bone marrow-derived stem cells (BMSCs) were induced down a chondrogenic pathway,labeled with PKH26,and seeded onto the scaffold.Immunofluorescent staining of the cell-scaffold constructs indicated that chondrocyte-like cells were derived from seeded BMSCs and excreted ECM.The cell-scaffold constructs contained

  6. Molecular constituents of the extracellular matrix in rat liver mounting a hepatic progenitor cell response for tissue repair

    DEFF Research Database (Denmark)

    Vestentoft, Peter Siig; Jelnes, Peter; Andersen, Jesper Bøje; Tran, Thi Anh Thu; Jørgensen, Tenna; Rasmussen, Morten; Lange, Jette Bornholdt; Grøvdal, Lene Melsæther; Jensen, Charlotte Harken; Vogel, Lotte; Thorgeirsson, Snorri S; Bisgaard, Hanne Cathrine

    2013-01-01

    Tissue repair in the adult mammalian liver occurs in two distinct processes, referred to as the first and second tiers of defense. We undertook to characterize the changes in molecular constituents of the extracellular matrix when hepatic progenitor cells (HPCs) respond in a second tier of defense...... to liver injury....

  7. Design of a Novel Composite H2 S-Releasing Hydrogel for Cardiac Tissue Repair.

    Science.gov (United States)

    Mauretti, Arianna; Neri, Annalisa; Kossover, Olga; Seliktar, Dror; Nardo, Paolo Di; Melino, Sonia

    2016-06-01

    The design of 3D scaffolds is a crucial step in the field of regenerative medicine. Scaffolds should be degradable and bioresorbable as well as display good porosity, interconnecting pores, and topographic features; these properties favour tissue integration and vascularization. These requirements could be fulfilled by hybrid hydrogels using a combination of natural and synthetic components. Here, the mechanical and biological properties of a polyethylene glycol-fibrinogen hydrogel (PFHy) are improved in order to favour the proliferation and differentiation of human Sca-1(pos) cardiac progenitor cells (hCPCs). PFHys are modified by embedding air- or perfluorohexane-filled bovine serum albumin microbubbles (MBs) and characterized. Changes in cell morphology are observed in MBs-PFHys, suggesting that MBs could enhance the formation of bundles of cells and influence the direction of the spindle growth. The properties of MBs as carriers of active macromolecules are also exploited. For the first time, enzyme-coated MBs have been used as systems for the production of hydrogen sulfide (H2 S)-releasing scaffolds. Novel H2 S-releasing PFHys are produced, which are able to improve the growth of hCPCs. This novel 3D cell-scaffold system will allow the assessment of the effects of H2 S on the cardiac muscle regeneration with its potential applications in tissue repair. PMID:26857526

  8. Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

    Directory of Open Access Journals (Sweden)

    Marcelo G. Pereira

    2014-09-01

    Full Text Available This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA. Young male Wistar rats were supplemented with leucine (1.35 g/kg per day; then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA of regenerating myofibers (p > 0.05 from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I and Smad2/3 in regenerating muscles (p < 0.05. Leucine also reduced neonatal myosin heavy chain (MyHC-n (p < 0.05, increased adult MyHC-II expression (p < 0.05 and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05. Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.

  9. The effects of sodium hyaluronate on mRNA expressions of matrix metalloproteinase-1,-3 and tissue inhibitor of metalloproteinase-1 in cartilage and synovium of traumatic osteoarthritis model

    Institute of Scientific and Technical Information of China (English)

    邱波; 刘世清; 彭昊; 王海斌

    2005-01-01

    Objective: To observe the influence of intra-articular injection of sodium hyaluronate (HA) on the mRNA expressions of matrix metalloproteinase-1,-3 (MMP-1,-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in cartilage and synovium of traumatic osteoarthritis (OA).Methods: Sixteen white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) were divided into 2 groups randomly 5 weeks after transection. The experimental group rabbits received 0.3 ml of 1% HA by intra-articular injection once a week. Animals in the control group were treated under the same conditions using physiological saline. Ten weeks following surgery, cartilage and synovium were harvested. The mRNA expressions of MMP-1, MMP-3 and TIMP-1 were analyzed using reverse transcription-polymerase chain reaction (RT-PCR).Results: In synovium, the mRNA expression of MMP-3 was suppressed in the HA injection group. HA treatment had no effect on the MMP-3 expression in cartilage. No significant difference of MMP-1 and TIMP-1 expressions in cartilage and synovium was found between the HA injection group and the control group.Conclusions: One of the mechanisms of the therapeutic effect of HA may be the inhibition of expression of MMP-3 in synovium during early stage of traumatic OA.

  10. Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows

    Directory of Open Access Journals (Sweden)

    Foley Cathriona

    2012-09-01

    Full Text Available Abstract Background All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows. Previous histological analysis of the endometrium revealed elevated inflammation 15 days postpartum (DPP which was significantly decreased by 30 DPP. The current study generated a genome-wide transcriptomic profile of endometrial biopsies from these cows at both time points using mRNA-Seq. The pathway analysis tool GoSeq identified KEGG pathways enriched by significantly differentially expressed genes at both time points. Novel candidate genes associated with inflammatory resolution were subsequently validated in additional postpartum animals using quantitative real-time PCR (qRT-PCR. Results mRNA-Seq revealed 1,107 significantly differentially expressed genes, 73 of which were increased 15 DPP and 1,034 were increased 30 DPP. Early postpartum, enriched immune pathways (adjusted P P SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes were significantly elevated 30 DPP and are functionally associated with tissue repair and the restoration of uterine homeostasis postpartum. Conclusions The results of this study reveal an early activation of the immune response which undergoes a temporal functional change toward tissue proliferation and regeneration during endometrial involution in healthy postpartum cows. These molecular changes mirror the activation and resolution of endometrial inflammation during involution previously classified by the degree of neutrophil infiltration. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes may become potential markers for resolution of endometrial inflammation in

  11. Repair and regeneration of osteochondral defects in the articular joints.

    Science.gov (United States)

    Swieszkowski, Wojciech; Tuan, Barnabas Ho Saey; Kurzydlowski, Krzysztof J; Hutmacher, Dietmar W

    2007-11-01

    People suffering from pain due to osteoarthritic or rheumatoidal changes in the joints are still waiting for a better treatment. Although some studies have achieved success in repairing small cartilage defects, there is no widely accepted method for complete repair of osteochondral defects. Also joint replacements have not yet succeeded in replacing of natural cartilage without complications. Therefore, there is room for a new medical approach, which outperforms currently used methods. The aim of this study is to show potential of using a tissue engineering approach for regeneration of osteochondral defects. The critical review of currently used methods for treatment of osteochondral defects is also provided. In this study, two kinds of hybrid scaffolds developed in Hutmacher's group have been analysed. The first biphasic scaffold consists of fibrin and PCL. The fibrin serves as a cartilage phase while the porous PCL scaffold acts as the subchondral phase. The second system comprises of PCL and PCL-TCP. The scaffolds were fabricated via fused deposition modeling which is a rapid prototyping system. Bone marrow-derived mesenchymal cells were isolated from New Zealand White rabbits, cultured in vitro and seeded into the scaffolds. Bone regenerations of the subchondral phases were quantified via micro CT analysis and the results demonstrated the potential of the porous PCL and PCL-TCP scaffolds in promoting bone healing. Fibrin was found to be lacking in this aspect as it degrades rapidly. On the other hand, the porous PCL scaffold degrades slowly hence it provides an effective mechanical support. This study shows that in the field of cartilage repair or replacement, tissue engineering may have big impact in the future. In vivo bone and cartilage engineering via combining a novel composite, biphasic scaffold technology with a MSC has been shown a high potential in the knee defect regeneration in the animal models. However, the clinical application of tissue

  12. Repairing peripheral nerve defects with tissue engineered artificial nerves in rats

    Institute of Scientific and Technical Information of China (English)

    WEI Ai-lin; LIU Shi-qing; TAO Hai-ying; PENG Hao

    2008-01-01

    Objective: To observe the effect of tissue engineered nerves in repairing peripheral nerve defects ( about 1. 5 cm in length) in rats to provide data for clinical application.Methods: Glycerinated sciatic nerves (2 cm in length) from 10 Sprague Dawley ( SD) rats ( aged 4 months) were used to prepare homologous dermal acellular matrix. Other 10 neonate SD rats (aged 5-7 days) were killed by neck dislocation. After removing the epineurium, the separated sciatic nerve tracts were cut into small pieces, then digested by 2.5 g/L trypsin and 625 U/ml collagenase and cultured in Dulbecco's modified Eagle's medium (DMEM) for 3 weeks. After proliferation, the Schwann cells ( SCs) were identified and prepared for use. And other 40 female adult SD rats (weighing 200 g and aged 3 months) with sciatic nerve defects of 1.5 cm in length were randomly divided into four groups: the defects of 10 rats bridged with proliferated SCs and homologous dermal acellular matrix (the tissue engineered nerve group, Group A), 10 rats with no SCs but homologous dermal acellular matrix with internal scaffolds ( Group B ), 10 with autologous nerves ( Group C) , and the other 10 with nothing (the blank control group, Group D). The general status of the rats was observed, the wet weight of triceps muscle of calf was monitored, and the histological observation of the regenerated nerves were made at 12 weeks after operation.Results: The wounds of all 40 rats healed after operation and no death was found. No foot ulceration was found in Groups A, B and C, but 7 rats suffered from foot ulceration in Group D. The triceps muscles of calf were depauperated in the experimental sides in all the groups compared with the uninjured sides,which was much more obvious in Group D. The wet weight of triceps muscle of calf and nerve electrophysiologic monitoring showed no statistical difference between Group A and Group C,but statistical difference was found between Groups A and B and Groups B and D. And significant

  13. Postnatal development of articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.

    2010-01-01

    Articular cartilage (AC) is the thin layer of tissue that covers the ends of the bones in the synovial joints in mammals. Functional adult AC has depth-dependent mechanical properties that are not yet present at birth. These depth-dependent mechanical properties in adult life are the result of a dep

  14. Preparing PCL/PLGA Hybrid Nanofiber Scaffold Capable of Controlled Releasing of Insulin for Cartilage Tissue Engineering Application

    OpenAIRE

    Basiri, A.; GH Amooabediny; Vasei, M.; M Solimani

    2014-01-01

    Introduction: Poly lactic co- glycolic acid (PLGA) and poly caprolacton (PCL) are highly applicable polymers in the field of drug delivery and tissue engineering scaffolds. Therefore, this study aimed to design an insulin-loaded PCL/PLGA hybrid nanofiber scaffold in order to be applied in attachment and growth of chondrocytes. Moreover, it can provide a vehicle for the controlled release of active insulin in a certain time period. Methods: Chondrocyte cells were isolated from septum cart...

  15. MRI EVALUATION OF KNEE CARTILAGE

    Science.gov (United States)

    Rodrigues, Marcelo Bordalo; Camanho, Gilberto Luís

    2015-01-01

    Through the ability of magnetic resonance imaging (MRI) to characterize soft tissue noninvasively, it has become an excellent method for evaluating cartilage. The development of new and faster methods allowed increased resolution and contrast in evaluating chondral structure, with greater diagnostic accuracy. In addition, physiological techniques for cartilage assessment that can detect early changes before the appearance of cracks and erosion have been developed. In this updating article, the various techniques for chondral assessment using knee MRI will be discussed and demonstrated. PMID:27022562

  16. Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

    Directory of Open Access Journals (Sweden)

    GM Roomans

    2010-06-01

    Full Text Available Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a a ductal cell type in the submucosal glands of the proximal trachea, (b basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c variant Clara cells (Clarav-cells in the bronchioles and (d at the junctions between the bronchioles and the alveolar ducts, and (e alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a embryonic stem (ES cells, induced pluripotent stem (iPS cells, or amniotic fluid stem cells, (b side-population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema.

  17. Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair.

    Science.gov (United States)

    Min, Jouha; Choi, Ki Young; Dreaden, Erik C; Padera, Robert F; Braatz, Richard D; Spector, Myron; Hammond, Paula T

    2016-04-26

    Infections associated with orthopedic implants cause increased morbidity and significant healthcare cost. A prolonged and expensive two-stage procedure requiring two surgical steps and a 6-8 week period of joint immobilization exists as today's gold standard for the revision arthroplasty of an infected prosthesis. Because infection is much more common in implant replacement surgeries, these issues greatly impact long-term patient care for a continually growing part of the population. Here, we demonstrate that a single-stage revision using prostheses coated with self-assembled, hydrolytically degradable multilayers that sequentially deliver the antibiotic (gentamicin) and the osteoinductive growth factor (BMP-2) in a time-staggered manner enables both eradication of established biofilms and complete and rapid bone tissue repair around the implant in rats with induced osteomyelitis. The nanolayered construct allows precise independent control of release kinetics and loading for each therapeutic agent in an infected implant environment. Antibiotics contained in top layers can be tuned to provide a rapid release at early times sufficient to eliminate infection, followed by sustained release for several weeks, and the underlying BMP-2 component enables a long-term sustained release of BMP-2, which induced more significant and mechanically competent bone formation than a short-term burst release. The successful growth factor-mediated osteointegration of the multilayered implants with the host tissue improved bone-implant interfacial strength 15-fold when compared with the uncoated one. These findings demonstrate the potential of this layered release strategy to introduce a durable next-generation implant solution, ultimately an important step forward to future large animal models toward the clinic. PMID:26923427

  18. Stem cells for liver tissue repair:Current knowledge and perspectives

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Stem cells from extra- or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated.Therefore,they are being increasingly considered for future applications in liver cell therapy.In that field,liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation,while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures.However,the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype,both in vitro and in vivo.Furthermore,the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures.The present review focuses on the current knowledge of the stern cell potential for liver therapy.We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo.We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.

  19. Transcriptomic profiling of cartilage ageing.

    Science.gov (United States)

    Peffers, Mandy Jayne; Liu, Xuan; Clegg, Peter David

    2014-12-01

    The musculoskeletal system is severely affected by the ageing process, with many tissues undergoing changes that lead to loss of function and frailty. Articular cartilage is susceptible to age related diseases, such as osteoarthritis. Applying RNA-Seq to young and old equine cartilage, we identified an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage from older donors. Here we describe the contents and quality controls in detail for the gene expression and related results published by Peffers and colleagues in Arthritis Research and Therapy 2013 associated with the data uploaded to ArrayExpress (E-MTAB-1386). PMID:26484061

  20. Transcriptomic profiling of cartilage ageing

    Directory of Open Access Journals (Sweden)

    Mandy Jayne Peffers

    2014-12-01

    Full Text Available The musculoskeletal system is severely affected by the ageing process, with many tissues undergoing changes that lead to loss of function and frailty. Articular cartilage is susceptible to age related diseases, such as osteoarthritis. Applying RNA-Seq to young and old equine cartilage, we identified an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage from older donors. Here we describe the contents and quality controls in detail for the gene expression and related results published by Peffers and colleagues in Arthritis Research and Therapy 2013 associated with the data uploaded to ArrayExpress (E-MTAB-1386.

  1. Controlled-Potential Electromechanical Reshaping of Cartilage.

    Science.gov (United States)

    Hunter, Bryan M; Kallick, Jeremy; Kissel, Jessica; Herzig, Maya; Manuel, Cyrus; Protsenko, Dmitri; Wong, Brian J F; Hill, Michael G

    2016-04-25

    An alternative to conventional "cut-and-sew" cartilage surgery, electromechanical reshaping (EMR) is a molecular-based modality in which an array of needle electrodes is inserted into cartilage held under mechanical deformation by a jig. Brief (ca. 2 min) application of an electrochemical potential at the water-oxidation limit results in permanent reshaping of the specimen. Highly sulfated glycosaminoglycans within the cartilage matrix provide structural rigidity to the tissue through extensive ionic-bonding networks; this matrix is highly permselective for cations. Our studies indicate that EMR results from electrochemical generation of localized, low-pH gradients within the tissue: fixed negative charges in the proteoglycan matrix are protonated, resulting in chemically induced stress relaxation of the tissue. Re-equilibration to physiological pH restores the fixed negative charges, and yields remodeled cartilage that retains a new shape approximated by the geometry of the reshaping jig. PMID:27059655

  2. Clinical Effect of Microfracture Combined with Hyaluronic Acid Injection to Repair Knee Joint Cartilage Injury%微骨折术联合玻璃酸钠注射修复膝关节软骨损伤

    Institute of Scientific and Technical Information of China (English)

    付昌马; 钱春生; 章有才

    2013-01-01

    目的 研究关节镜下微骨折术(microfracture,MF)联合玻璃酸钠(hyaluronic acid,HA)注射修复膝关节软骨损伤患者的治疗效果.方法 收集2011年4月至2012年9月在合肥市第三人民医院关节镜手术治疗的40例膝关节软骨损伤患者,其中外伤导致的软骨损伤9例,骨关节炎(退变)导致的软骨损伤31例.对40例膝关节软骨损伤患者采用关节镜下微骨折术,缺损面积0.5~9 cm2,平均3.3 cm2;术后立即注射玻璃酸钠20 mg,术后第1周,第2周均注射HA 20 mg;术后8周膝关节功能Lysholm得分采用两样本均数t检验;采用Tegner运动评级进行膝关节功能评价.结果 纳入研究的40例膝关节软骨损伤患者均进入结果分析.40例膝关节软骨损伤患者手术前后膝关节功能Lysholm得分有差异(P<0.05).40例膝关节软骨损伤患者手术后Tegner运动评级优15例,良20例,差5例,优良率87.5%.结论 微骨折术联合玻璃酸钠注射修复膝关节软骨损伤取得满意的治疗效果.关节镜下微骨折术联合玻璃酸钠注射修复操作方便,方法简单.不管是退变的膝关节软骨损伤还是外伤的软骨损伤,均可明显改善患者的关节功能和减轻疼痛症状.%Objective To explore the clinical effect of arthroscopic microfracture surgery combined sodium hyaluronate injection to repair knee cartilage damage. Methods 40 patients who accept arthroscopic surgery in the Third People's Hospital of Hefei 2011-04/2012-09 were analyzed. There were 9 cases with traumatic cartilage injury. And 31 cases with knee cartilage damage caused by osteoarthritis. The defect area ranged from 0. 5 cm2 to 9 cm2,with an average of 3. 3 cm2. Sodium hyaluronate (HA) 20 mg was injected immediately after surgery,one week,two weeks and eight weeks after surgery. Knee function Lysholm score and Tegner movement rating were analyzed. Results The Lysholm score improved after surgery (P<0. 05). According to Tegner movement rating,there were

  3. Comprehensive profiling of cartilage extracellular matrix formation and maturation using sequential extraction and label-free quantitative proteomics.

    Science.gov (United States)

    Wilson, Richard; Diseberg, Anders F; Gordon, Lavinia; Zivkovic, Snezana; Tatarczuch, Liliana; Mackie, Eleanor J; Gorman, Jeffrey J; Bateman, John F

    2010-06-01

    Articular cartilage is indispensable for joint function but has limited capacity for self-repair. Engineering of neocartilage in vitro is therefore a major target for autologous cartilage repair in arthritis. Previous analysis of neocartilage has targeted cellular organization and specific molecular components. However, the complexity of extracellular matrix (ECM) development in neocartilage has not been investigated by proteomics. To redress this, we developed a mouse neocartilage culture system that produces a cartilaginous ECM. Differential analysis of the tissue proteome of 3-week neocartilage and 3-day postnatal mouse cartilage using solubility-based protein fractionation targeted components involved in neocartilage development, including ECM maturation. Initially, SDS-PAGE analysis of sequential extracts revealed the transition in protein solubility from a high proportion of readily soluble (NaCl-extracted) proteins in juvenile cartilage to a high proportion of poorly soluble (guanidine hydrochloride-extracted) proteins in neocartilage. Label-free quantitative mass spectrometry (LTQ-Orbitrap) and statistical analysis were then used to filter three significant protein groups: proteins enriched according to extraction condition, proteins differentially abundant between juvenile cartilage and neocartilage, and proteins with differential solubility properties between the two tissue types. Classification of proteins differentially abundant between NaCl and guanidine hydrochloride extracts (n = 403) using bioinformatics revealed effective partitioning of readily soluble components from subunits of larger protein complexes. Proteins significantly enriched in neocartilage (n = 78) included proteins previously not reported or with unknown function in cartilage (integrin-binding protein DEL1; coiled-coil domain-containing protein 80; emilin-1 and pigment epithelium derived factor). Proteins with differential extractability between juvenile cartilage and neocartilage

  4. Preparation and Characterization of Biomimetic Hydroxyapatite-Resorbable Polymer Composites for Hard Tissue Repair

    Science.gov (United States)

    Hiebner, Kristopher Robert

    Autografts are the orthopedic "gold standard" for repairing bone voids. Autografts are osteoconductive and do not elicit an immune response, but they are in short supply and require a second surgery to harvest the bone graft. Allografts are currently the most common materials used for the repair of segmental defects in hard tissue. Unlike autografts, allografts can cause an undesirable immune response and the possibility of disease transmission is a major concern. As an alternative to the above approaches, recent research efforts have focused on the use of composite materials made from hydroxyapatite (HA) and bioresorbable polymers, such as poly-L-lactide (PLLA). Recent results have shown that the surface hydroxides on HA can initiate the ring opening polymerization (ROP) of L-lactide and other lactones creating a composite with superior interfacial strength. This thesis demonstrates that the surface of porous biologically derived HA substrates, such as coralline HA and trabecular bone, can be used to initiate the ROP of L-lactide and other lactones from the vapor phase. This process increases the strength of the porous scaffold through the deposition of a thin, uniform polymer coating, while maintaining the porous structure. The kinetics of the chemical vapor deposition polymerization (CVDP) are described using a quartz crystal microbalance (QCM). The reaction temperature and monomer vapor pressure are found to affect the rate of the polymerization. Also described in this thesis is the preparation of a porous polymer scaffold that mimics the structure of demineralized bone matrix (DBM). This demineralized bone matrix simulant (DBMS) is created using anorganic bovine bone as a template to initiate the polymerization of various lactones, followed by the removal of the HA scaffold. This material retained its shape and exhibits mechanical properties superior to DBM. Finally it is shown that HA can be used to initiate the ROP of a-caprolactam and the biocompatibility

  5. Layer-by-layer assembly of type I collagen and chondroitin sulfate on aminolyzed PU for potential cartilage tissue engineering application

    Energy Technology Data Exchange (ETDEWEB)

    He Xianyun [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 (China); Wang Yingjun, E-mail: imwangyj@163.com [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China) and National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China) and Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 (China); Wu Gang, E-mail: imwugang@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 (China)

    2012-10-01

    Highlights: Black-Right-Pointing-Pointer A novel biodegradable polyurethane (PU) was successfully synthesized. Black-Right-Pointing-Pointer Surface aminolyzing of the PU was performed by reacting it with 1,3-propanediamine. Black-Right-Pointing-Pointer Collagen and chondroitin sulfate were deposited alternately on the PU surface. - Abstract: In this paper, a two-step method was used to synthesize a biodegradable polyurethane (PU) composed of L-lysine ethyl ester diisocyanate (LDI), poly({epsilon}-caprolactone) diols (PCL-diol) and 1,4:3,6-dianhydro-D-sorbitol (isosorbide). Amino groups were introduced onto the surface of the PU membrane by an amination reacting with 1,3-propanediamine to produce polycationic substratum. And then, type I collagen (Col) and chondroitin sulfate (CS) were deposited alternately on the polycationic substratum through layer-by-layer (LBL) assembly technology. The FTIR and {sup 1}H NMR results showed that the polyurethane was successfully synthesized. Rhodamine B isothiocyanate (RBITC) fluorescence spectrum indicated that amino groups were successfully introduced onto the PU surface. The results of quartz-crystal microbalance (QCM) and RBITC-Col fluorescence spectroscopy monitoring the LBL assemble process presented that the Col/CS deposited alternately on the PU surface. X-ray photoelectron spectroscopy (XPS) results displayed that the CS deposited on the PU surface as well. The surface of the assembled PU became even smoother observed from the surface morphology by atomic force microscopy (AFM) imaging. The hydrophilicity of the PU membrane was greatly enhanced though the modification of LBL assembly. The PU modified with the adsorption of Col/CS may be a potential application for cartilage tissue engineering due to its created mimicking chondrogenic environment.

  6. Layer-by-layer assembly of type I collagen and chondroitin sulfate on aminolyzed PU for potential cartilage tissue engineering application

    International Nuclear Information System (INIS)

    Highlights: ► A novel biodegradable polyurethane (PU) was successfully synthesized. ► Surface aminolyzing of the PU was performed by reacting it with 1,3-propanediamine. ► Collagen and chondroitin sulfate were deposited alternately on the PU surface. - Abstract: In this paper, a two-step method was used to synthesize a biodegradable polyurethane (PU) composed of L-lysine ethyl ester diisocyanate (LDI), poly(ε-caprolactone) diols (PCL-diol) and 1,4:3,6-dianhydro-D-sorbitol (isosorbide). Amino groups were introduced onto the surface of the PU membrane by an amination reacting with 1,3-propanediamine to produce polycationic substratum. And then, type I collagen (Col) and chondroitin sulfate (CS) were deposited alternately on the polycationic substratum through layer-by-layer (LBL) assembly technology. The FTIR and 1H NMR results showed that the polyurethane was successfully synthesized. Rhodamine B isothiocyanate (RBITC) fluorescence spectrum indicated that amino groups were successfully introduced onto the PU surface. The results of quartz-crystal microbalance (QCM) and RBITC-Col fluorescence spectroscopy monitoring the LBL assemble process presented that the Col/CS deposited alternately on the PU surface. X-ray photoelectron spectroscopy (XPS) results displayed that the CS deposited on the PU surface as well. The surface of the assembled PU became even smoother observed from the surface morphology by atomic force microscopy (AFM) imaging. The hydrophilicity of the PU membrane was greatly enhanced though the modification of LBL assembly. The PU modified with the adsorption of Col/CS may be a potential application for cartilage tissue engineering due to its created mimicking chondrogenic environment.

  7. Cartilage (Bovine and Shark) (PDQ)

    Science.gov (United States)

    ... Ask about Your Treatment Research Cartilage (Bovine and Shark) (PDQ®)–Patient Version Overview Go to Health Professional ... 8 ). Questions and Answers About Cartilage (Bovine and Shark) What is cartilage? Cartilage is a type of ...

  8. Repair of Segmental Bone Defect Using Totally Vitalized Tissue Engineered Bone Graft by a Combined Perfusion Seeding and Culture System

    OpenAIRE

    Wang, Lin; Ma, Xiang-Yu; Zhang, Yang; Feng, Ya-Fei; Li, Xiang; Hu, Yun-Yu; Wang, Zhen; Ma, Zhen-Sheng; Lei, Wei

    2014-01-01

    Background The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. Methods In this study, we constructed the TV-TEBG with the c...

  9. An international eDelphi study identifying the research and education priorities in wound management and tissue repair.

    OpenAIRE

    Cowman, Seamus; GETHIN, GEORGINA; Clarke, Eric; Moore, Zena; Craig, Gerardine; Jordan-O'Brien, Julie; McLain, Niamh; Strapp, Helen

    2011-01-01

    Aim.  To incorporate an international and multidisciplinary consensus in the determination of the research and education priorities for wound healing and tissue repair. Background.  A compelling reason for the study is the lack of an agreed list of priorities for wound care research and education. Furthermore, there is a growth in the prevalence of chronic wounds, a growth in wound care products and marketing, and an increase in clinician attendance at conferences and education programmes. De...

  10. Microsurgical head and neck tissue repair by visceral mini-autografting

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2015-06-01

    Full Text Available Objective. To minimize surgical trauma in patients with head and neck tumors during microsurgical plasty with visceral autografts.Subjects and methods. Clinical experience has been gained in the treatment of 53 patients with locally advanced craniofascial (n = 27 and oropharyngeal (n = 36 cancers. Abdominal organs were used for plastic closure of extensive defects after surgical resection. Paraumbilical incision allowing for an adequate approach into the abdominal cavity with minimal external trauma in the anterior abdominal wall was chosen as an access procedure. Video-assisted techniques were used to excise the midline aponeurosis. Donor organs, such as the omentum, greater curvature of the stomach, transverse colon, small intestine were taken through a mini-laparotomic incision to the anterior abdominal wall, then the vascular pedicle was exposed and a visceral autograft was made. After forming and cutting off the autograft, organ anastomoses were created extracorporeally.Results. Mini-access surgery could be completed in 50 of the 53 cases (4 patients had previously undergone abdominal interventions. Omental (n = 26, colo-omental (n = 15, gastro-omental (n = 7, and entero-omental (n = 5 flaps were made and prepared for autografting. No intra- or postoperative abdominal complications were found.Conclusion. Minimally invasive technologies used to create visceral authografts for head and neck tissue repair can minimize surgical trauma and reduce treatment duration. The indications for this access are the debilitating state of a cancer patient or the young age of a patient who does not wish to have an additional scar in the donor region.

  11. Neo-Epitopes—Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis

    Science.gov (United States)

    Karsdal, Morten Asser; Gerlag, Daniëlle M.; Tak, Paul Peter; Bay-Jensen, Anne Christine

    2016-01-01

    Objective Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-degraded vimentin and MMP degraded C-reactive protein. We evaluated if biomarkers measuring serum levels of specific sequences of the mentioned fragments would provide further information of diagnostic and/or prognostic processes in early arthritis. Methods Ninety-two early arthritis patients (arthritis duration<1 year, DMARD naïve) were enrolled. Patients either fulfilled the ACR/EULAR2010 criteria for RA (n = 60) or had unclassified arthritis (UA) (n = 32). Patients fulfilling the RA criteria after 2 years follow-up were classified into non-erosive (n = 25), or erosive disease (n = 13). Concentrations of the biomarkers: C1M, C2M, C3M, VICM and CRPM were measured in baseline serum. Results C1M, C3M and CRPM were able to discriminate between the UA and RA baseline diagnosis in 92 patients with an AUROC of 0.64 (95%CI 0.517 to 0.762), 0.73 (95%CI 0.622 to 0.838) and 0.68 (95%CI 0.570 to 0.795). C2M showed a potential for discrimination between non-erosive and erosive disease in 38 patients with an AUROC of 0.75 (95%CI 0.597 to 0.910). All of the applied biomarkers correlated with one or more of the disease activity parameters: DAS28, ESR, CRP, SJC66, TJC68 and/or HAQ. Conclusion This is the first study evaluating the applied biomarkers at this early stage of arthritis. C1M, C3M, CRPM might be the best diagnostic marker, whereas high levels of C2M indicated progression of disease at follow-up in early RA patients. PMID:27019199

  12. Self-Assembled Infrapatellar Fat-Pad Progenitor Cells on a Poly-ε-Caprolactone Film For Cartilage Regeneration.

    Science.gov (United States)

    Prabhakar, Alisha; Lynch, Amy P; Ahearne, Mark

    2016-04-01

    Cartilage defects resulting from osteoarthritis (OA) or physical injury can severely reduce the quality of life for sufferers. Current treatment options are costly and not always effective in producing stable hyaline cartilage. Here we investigated a new treatment option that could potentially repair and regenerate damaged cartilage tissue. This novel approach involves the application of infrapatellar fat-pad derived chondroprogenitor cells onto a mechanically stable biodegradable polymer film that can be easily implanted into a defect site. Poly-ε-caprolactone (PCL) films were fabricated via solvent casting in either acetone or chloroform. The hydrophobicity, mechanical properties, and surface morphology of the films were examined. Progenitor cells from infrapatellar fat-pad were isolated, expanded, and then seeded onto the films. The cells were allowed to self-assemble on films, and these were then cultured in a chemically defined chondrogenic media for 28 days. The self-assembled tissue was characterized via histological staining, gene expression analysis, immunohistochemistry, and biochemical analysis. Chondrogenic differentiation was induced to generate a cartilaginous matrix upon the films. Despite differences between in the appearance, surface morphology, and mechanical properties of the films cast in chloroform or acetone, both methods produced tissues rich in sulfated glycosaminoglycan and collagen, although the extracellular matrix produced on chloroform-cast films appeared to contain more collagen type II and less collagen type I than acetone-cast films. These self-assembled constructs have the potential to be implanted into defect sites as a potential treatment for cartilage defect regeneration. PMID:26516689

  13. The potential of 3-dimensional construct engineered from poly(lactic-co-glycolic acid)/fibrin hybrid scaffold seeded with bone marrow mesenchymal stem cells for in vitro cartilage tissue engineering.

    Science.gov (United States)

    Abdul Rahman, Rozlin; Mohamad Sukri, Norhamiza; Md Nazir, Noorhidayah; Ahmad Radzi, Muhammad Aa'zamuddin; Zulkifly, Ahmad Hafiz; Che Ahmad, Aminudin; Hashi, Abdurezak Abdulahi; Abdul Rahman, Suzanah; Sha'ban, Munirah

    2015-08-01

    Articular cartilage is well known for its simple uniqueness of avascular and aneural structure that has limited capacity to heal itself when injured. The use of three dimensional construct in tissue engineering holds great potential in regenerating cartilage defects. This study evaluated the in vitro cartilaginous tissue formation using rabbit's bone marrow mesenchymal stem cells (BMSCs)-seeded onto poly(lactic-co-glycolic acid) PLGA/fibrin and PLGA scaffolds. The in vitro cartilaginous engineered constructs were evaluated by gross inspection, histology, cell proliferation, gene expression and sulphated glycosaminoglycan (sGAG) production at week 1, 2 and 3. After 3 weeks of culture, the PLGA/fibrin construct demonstrated gross features similar to the native tissue with smooth, firm and glistening appearance, superior histoarchitectural and better cartilaginous extracellular matrix compound in concert with the positive glycosaminoglycan accumulation on Alcian blue. Significantly higher cell proliferation in PLGA/fibrin construct was noted at day-7, day-14 and day-21 (p<0.05 respectively). Both constructs expressed the accumulation of collagen type II, collagen type IX, aggrecan and sox9, showed down-regulation of collagen type I as well as produced relative sGAG content with PLGA/fibrin construct exhibited better gene expression in all profiles and showed significantly higher relative sGAG content at each time point (p<0.05). This study suggested that with optimum in vitro manipulation, PLGA/fibrin when seeded with pluripotent non-committed BMSCs has the capability to differentiate into chondrogenic lineage and may serve as a prospective construct to be developed as functional tissue engineered cartilage. PMID:26100682

  14. 微载体培养技术在骨与软骨组织工程研究中的应用%Application of microcarrier culture techniques in bone and cartilage tissue engineering

    Institute of Scientific and Technical Information of China (English)

    宁斌; 田周斌; 贾堂宏

    2012-01-01

    BACKGROUND: Proliferation and specific phenotype maintaining of seed cells are the difficulties in bone and cartilage tissueengineering. The microcarrier bioreactor culture system provides a good method to solve this problem.OBJECTIVE: To analyze the domestic and international development of microcarrier culture of bone and cartilage cells, and toprovide the theoretical basis for microcarrier culture of bone and cartilage cells and researches in tissue engineering.METHODS: A computer-based online search of articles published from 1967 to 2011 was performed at November 2010 inPubMed database (http://www.ncbi.nlm.gov/PubMed) and Wanfang database (http://www.wanfangdata.com.cn) using the keywords of "microcarrier, cartilage, tissue engineering" in English and in Chinese, respectively. Articles irrelative to this paper,antiquated or repeated literatures were excluded. Totally 32 articles were chosen for further analysis.RESULTS AND CONCLUSION: Culture conditions of bone and cartilage cells in microcarrier bioreactor culture system can bewell regulated to achieve a large number of proliferation and phenotype maintaining of the cells, or even achieve an enhancementof phenotype. This technology has a good potential application in bone and cartilage tissue engineering and clinical work.%背景 骨与软骨组织工程学中增殖种子细胞和保持细胞特定表型是其难点,微载体生物反应器培养系统提供了很好的条件来解决这个问题.目的 分析近年来国内外骨、软骨细胞微载体培养的研究进展,为骨与软骨细胞微载体培养技术和组织工程研究提供理论基础.方法 由第一作者在2010-11 进行检索.检索数据库:PubMed 数据库(网址http://www.ncbi.nlm.gov/PubMed);万方数据库(网址http://www.wanfangdata.com.cn),资料的检索时间范围为1967/2011.英文检索词为"microcarrier,cartilage,tissue engineering",中文检索词为"微载体,软骨,组织工程学".排除与本文无关及陈

  15. Comparison of novel clinically applicable methodology for sensitive diagnostics of cartilage degeneration

    Directory of Open Access Journals (Sweden)

    P Kiviranta

    2007-04-01

    Full Text Available In order efficiently to target therapies intending to stop or reverse degenerative processes of articular cartilage, it would be crucial to diagnose osteoarthritis (OA earlier and more sensitively than is possible with the existing clinical methods. Unfortunately, current clinical methods for OA diagnostics are insensitive for detecting the early degenerative changes, e.g., arising from collagen network damage or proteoglycan depletion. We have recently investigated several novel quantitative biophysical methods, including ultrasound indentation, quantitative ultrasound techniques and magnetic resonance imaging, for diagnosing the degenerative changes of articular cartilage, typical for OA. In this study, the combined results of these novel diagnostic methods were compared with histological (Mankin score, MS, compositional (proteoglycan, collagen and water content and mechanical (dynamic and equilibrium moduli reference measurements of the same bovine cartilage samples. Receiver operating characteristics (ROC analysis was conducted to judge the diagnostic performance of each technique. Indentation and ultrasound techniques provided the most sensitive measures to differentiate samples of intact appearance (MS=0 from early (13 degeneration. Furthermore, these techniques were good predictors of tissue composition and mechanical properties. The specificity and sensitivity analyses revealed that the mechano-acoustic methods, when further developed for in vivo use, may provide more sensitive probes for OA diagnostics than the prevailing qualitative X-ray and arthroscopic techniques. Noninvasive quantitative MRI measurements showed slightly lower diagnostic performance than mechano-acoustic techniques. The compared methods could possibly also be used for the quantitative monitoring of success of cartilage repair.

  16. He-Ne Laser Irradiation Encourages reparative Processes After cartilage loss in New Zealand rabbits

    International Nuclear Information System (INIS)

    Many therapeutic methods used to encourage reparative processes of cartilage and accelerate their healing such as drugs, magneto-laser and so on.Twenty four adult New Zealand rabbits used in this study.They were divided in to two groups; control and treaded with He-Ne laser.A square skin flap done on the medial aspect of both auricles followed by pealing a square piece of cartilage from the auricle then the flaps sutured.The site of the operation in the rabbits of the treatedgroup were irradiated with He-Ne laser 5mw power for seven days began after the operation directly.3 rabbits from each group used for collection of specimens for histopathological examination at the 1, 2, 4 & 6 weeks post the operation.Significantly well developed cartilage growth, chondroblasts and chondrocytes invade the area of the operation.High increase in the thickness of connective tissue in the same area contain mainly collagen fibers and lesser amount of elastic fibers.He-Ne laser irradiation raised the mitotic activity of the cartilage cells, activated the reproduction processes in addition to the intra and extra regenerative repair

  17. Effects of chronic severe pulmonary regurgitation and percutaneous valve repair on right ventricular geometry and contractility assessed by tissue Doppler echocardiography

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; Iversen, Kasper K; Vejlstrup, Niels G;

    2010-01-01

    Pulmonary regurgitation (PR) following repair of right ventricular (RV) outflow obstruction is related to slowly progressive RV dilatation and heart failure and will eventually require surgical intervention, but optimal timing of pulmonary valve replacement is challenging. Tissue Doppler based...

  18. A simple measuring device for laboratory indentation tests on cartilage.

    Science.gov (United States)

    Koeller, Wolfgang; Kunow, Julius; Ostermeyer, Oliver; Stomberg, Peter; Boos, Carsten; Russlies, Martin

    2008-04-01

    Mechanical testing of articular cartilage and repair tissue enables judgment of their capacity in withstanding mechanical loading. In the past, different methods have been developed requiring a complex technical setup and extensive data analysis. Therefore, the aim of the present project was to build up a simple measuring apparatus for laboratory indentation tests. The device consists of an incremental optical displacement transducer with a sleeve bearing guided plunger and a spherical tip made of polished steel (radius: 0.75 or 1.5 mm), a sensitive load cell and a stiff frame. The indentation force results from the plunger's gravity plus the force of the spring inside the displacement transducer and levels at 0.170 N or 0.765 N. The displacement transducer is fixed to the frame via the load cell that enables one to detect the initial contact of the tip with the tissue. The load cell has a standard uncertainty of 2 mN and the displacement transducer of 1 microm. From indentation-creep tests, a "0.25-s elastic modulus" is calculated. Measurements on thin rubber sheets were carried out to determine the quality of the measuring device. Compression tests on cylinders made of these rubber sheets yielded control data, and a good agreement with the "0.25-s elastic modulus" was found. Indentation tests on cartilage at different sites of sheep femoral condyles yielded a very good repeatability of the measurement results (+/-7.5%). PMID:18979621

  19. The structure and function of cartilage proteoglycans

    Directory of Open Access Journals (Sweden)

    P J Roughley

    2006-11-01

    Full Text Available Cartilage contains a variety of proteoglycans that are essential for its normal function. These include aggrecan, decorin, biglycan, fibromodulin and lumican. Each proteoglycan serves several functions that are determined by both its core protein and its glycosaminoglycan chains. This review discusses the structure/function relationships of the cartilage proteoglycans, and the manner in which perturbations in proteoglycan structure or abundance can adversely affect tissue function.

  20. Repair of bile duct defect with degradable stent and autologous tissue in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Yue-Long Liang; Yi-Chen Yu; Kun Liu; Wei-Jia Wang; Jiang-Bo Ying; Yi-Fan Wang; Xiu-Jun Cai

    2012-01-01

    AIM:To introduce and evaluate a new method to repair bile duct defect with a degradable stent and autologous tissues.METHODS:Eight Ba-Ma mini-pigs were used in this study.Experimental models with common bile duct (CBD) defect (0.5-1.0 cm segment of CBD resected) were established and then CBD was reconstructed by duct to duct anastomosis with a novel degradable stent made of poly [sebacic acid-co-(1,3-propanediol)-co-(1,2-propanediol)].In addition,a vascularized greater omentum was placed around the stent and both ends of CBD.Cholangiography via gall bladder was performed for each pig at postoperative months 1 and 3 to rule out stent translocation and bile duct stricture.Complete blood count was examined pre-and post-operatively to estimate the inflammatory reaction.Liver enzymes and serum bilirubin were examined pre-and post-operatively to evaluate the liver function.Five pigs were sacrificed at month 3 to evaluate the healing of anastomosis.The other three pigs were raised for one year for long-term observation.RESULTS:All the animals underwent surgery successfully.There was no intraoperative mortality and no bile leakage during the observation period.The white blood cell counts were only slightly increased on day 14 and month 3 postoperatively compared with that before operation,the difference was not statistically significant (P =0.652).The plasma level of alanine aminotransferase on day 14 and month 3 postoperatively was also not significantly elevated compared with that before operation (P =0.810).Nevertheless,the plasma level of γ-glutamyl transferase was increased after operation in both groups (P =0.004),especially 2 wk after operation.The level of serum total bilirubin after operation was not significantly elevated compared with that before operation (P =0.227),so did the serum direct bilirubin (P =0.759).By cholangiography via gall bladder,we found that the stent maintained its integrity of shape and was still in situ at month 1,and it disappeared

  1. Disrupted G1 to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

    International Nuclear Information System (INIS)

    Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G0 to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G1 to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes

  2. Impaired antioxidant enzyme activity and increased DNA repair enzyme expression in hamster liver tissues related to cholangiocarcinoma development.

    Science.gov (United States)

    Loilome, Watcharin; Kadsanit, Sasithorn; Namwat, Nisana; Techasen, Anchalee; Puapairoj, Anucha; Dechakhamphu, Ananya; Pinitsoontorn, Chadamas; Yongvanit, Puangrat

    2012-01-01

    A possible mechanism of liver fluke (Opisthorchis viverrini; Ov) -associated cholangiocarcinoma (CCA) genesis may be imbalance in responses of antioxidant enzymes and/or DNA repair enzymes which are the consequence of oxidative/nitrative stress, arising from inflammatory processes. This study aimed to investigate changes in the expression patterns of antioxidant enzymes, including superoxide dismutase 2 (SOD2) and catalase (CAT), as well as their activities in Ov-associated hamster CCA tissues. Expression of DNA repair enzymes including apurinic endonuclease (APE) and DNA polymerase beta (DNA pol β) was also investigated. Our results showed that SOD2 and CAT levels were increased in CCA-induced liver hamster tissues at every time point during cholangiocarcinogenesis. However, once tumors were well established, activities of both enzymes were significantly decreased. Expression of APE and DNA pol β was increased in the acute phase of Ov infection and this persisted until tumors developed. These findings suggest that a reduction in antioxidant enzymes and an increase in DNA repair enzymes may contribute to DNA translesion-mediated CCA in liver fluke-associated cholangiocarcinogenesis in the hamster model. PMID:23480773

  3. Image processing techniques for noise removal, enhancement and segmentation of cartilage OCT images

    International Nuclear Information System (INIS)

    Osteoarthritis, whose hallmark is the progressive loss of joint cartilage, is a major cause of morbidity worldwide. Recently, optical coherence tomography (OCT) has demonstrated considerable promise for the assessment of articular cartilage. Among the most important parameters to be assessed is cartilage width. However, detection of the bone cartilage interface is critical for the assessment of cartilage width. At present, the quantitative evaluations of cartilage thickness are being done using manual tracing of cartilage-bone borders. Since data is being obtained near video rate with OCT, automated identification of the bone-cartilage interface is critical. In order to automate the process of boundary detection on OCT images, there is a need for developing new image processing techniques. In this paper we describe the image processing techniques for speckle removal, image enhancement and segmentation of cartilage OCT images. In particular, this paper focuses on rabbit cartilage since this is an important animal model for testing both chondroprotective agents and cartilage repair techniques. In this study, a variety of techniques were examined. Ultimately, by combining an adaptive filtering technique with edge detection (vertical gradient, Sobel edge detection), cartilage edges can be detected. The procedure requires several steps and can be automated. Once the cartilage edges are outlined, the cartilage thickness can be measured. (author)

  4. Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zonggang, E-mail: chenzg@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Kang, Lingzhi [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Meng, Qing-Yuan [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Liu, Huanye [Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China); Wang, Zhaoliang [Jinan Military General Hospital of PLA, Jinan 250031 (China); Guo, Zhongwu, E-mail: zwguo@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Cui, Fu-Zhai, E-mail: cuifz@mail.tsinghua.edu.cn [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2014-12-01

    The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites. - Highlights: • The nHAC/CSH composite can be as an injectable bone repair material. • The L/S ratio and nHAC content have a significant effect on material degradability. • The degradability of bone materials can be regulated to match tissue repair. • The regulable degradability will further improve the workability of bone materials.

  5. Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration

    International Nuclear Information System (INIS)

    The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites. - Highlights: • The nHAC/CSH composite can be as an injectable bone repair material. • The L/S ratio and nHAC content have a significant effect on material degradability. • The degradability of bone materials can be regulated to match tissue repair. • The regulable degradability will further improve the workability of bone materials

  6. 肢体创伤性软组织缺损修复面面观%General view on the repair of traumatic soft tissue defects of extremities

    Institute of Scientific and Technical Information of China (English)

    柴益民; 陆晟迪; 曾炳芳

    2015-01-01

    Repir of soft tissue defects takes an important role in the ifeld of traumatic repairative surgery, including repair of the injuries and accidents resulted acute wounds, reconstruction for chronic wounds caused by diabetes and vascular diseases, salvage and functional reconstruction of the injured limbs. The repair of traumatic soft tissue defects of the extremities needs overall considerations on the evaluation, methods, principle, decision making and timing. The evaluation consists of the local condition of the injured limb, as well as the general condition, expectation value to the treatment, and the economic and psychological endurance capacity to the multiple reconstructive operations of the patients. Clinically available methods include VAC ( vacuum assisted closure ) technique, skin substitutes, skin graft, plasty of local skin lfap, skin expender, pedicled transposition or transplantation of axial tissue lfaps, neurofasciocutaneous or perforator lfaps. The principles of repair of soft tissue defects are to use the like tissues to repair the defects, to reduce the damage to the donor sites, to reach the goals in both the functional and cosmetic outcome, to plan the operation carefully and comprehensively. The decision making can be done following the concept of “reconstruction ladder”, by which the surgical procedures are selected gradually from “the simple” to “the complex”. However, with the advanced technique in hands, the surgeons may start with “the best” rather than “the simplest” to repair the soft tissue defects, as long as it is indicated no matter how dififcult it might be. As to the timing, the soft tissue defect is repaired the earlier the better, of cause safety and effectiveness are the prerequisite to do this. A successful microsurgical repair can make full use of the tissues spared from the injury to save the injured limb and to reconstruct its function thus to shorten the treatment process, to relieve the pain of the

  7. The bone-cartilage unit in osteoarthritis.

    Science.gov (United States)

    Lories, Rik J; Luyten, Frank P

    2011-01-01

    Osteoarthritis (OA) refers to a group of mechanically-induced joint disorders to which both genetic and acquired factors contribute. Current pathophysiological concepts focus on OA as a disease of the whole joint. Within these models, the functional unit formed by the articular cartilage and the subchondral bone seems to be of particular interest. Cartilage and bone receive and dissipate the stress associated with movement and loading, and are therefore continuously challenged biomechanically. Recent data support the view that cartilage and bone can communicate over the calcified tissue barrier; vessels reach out from bone into the cartilage zone, patches of uncalcified cartilage are in contact with bone, and microcracks and fissures further facilitate transfer of molecules. Several molecular signaling pathways such as bone morphogenetic proteins and Wnts are hypothesized to have a role in OA and can activate cellular and molecular processes in both cartilage and bone cells. In addition, intracellular activation of different kinase cascades seems to be involved in the molecular crosstalk between cartilage and bone cells. Further research is required to integrate these different elements into a comprehensive approach that will increase our understanding of the disease processes in OA, and that could lead to the development of specific therapeutics or treatment strategies. PMID:21135881

  8. Repair of giant omphalocele in a premature neonate with non-cross-linked porcine acellular dermal matrix (Strattice Tissue Matrix

    Directory of Open Access Journals (Sweden)

    Helene Engstrand Lilja

    2016-09-01

    Full Text Available The management of giant omphalocele (GO is a major challenge in pediatric surgery and there are many different surgical strategies described. Here we report a complicated case in which the abdominal wall in a premature neonate (gestational age 33 + 2 weeks and 1700 g with GO was reconstructed with a non-cross-linked acellular porcine dermal matrix (Strattice™ combined with vacuum therapy. This strategy can be an alternative method in the repair of GO in premature neonates with high risk of infection, underdeveloped abdominal cavity and insufficient native tissue.

  9. Additive manufacturing for in situ repair of osteochondral defects

    International Nuclear Information System (INIS)

    Tissue engineering holds great promise for injury repair and replacement of defective body parts. While a number of techniques exist for creating living biological constructs in vitro, none have been demonstrated for in situ repair. Using novel geometric feedback-based approaches and through development of appropriate printing-material combinations, we demonstrate the in situ repair of both chondral and osteochondral defects that mimic naturally occurring pathologies. A calf femur was mounted in a custom jig and held within a robocasting-based additive manufacturing (AM) system. Two defects were induced: one a cartilage-only representation of a grade IV chondral lesion and the other a two-material bone and cartilage fracture of the femoral condyle. Alginate hydrogel was used for the repair of cartilage; a novel formulation of demineralized bone matrix was used for bone repair. Repair prints for both defects had mean surface errors less than 0.1 mm. For the chondral defect, 42.8 ± 2.6% of the surface points had errors that were within a clinically acceptable error range; however, with 1 mm path planning shift, an estimated ∼75% of surface points could likely fall within the benchmark envelope. For the osteochondral defect, 83.6 ± 2.7% of surface points had errors that were within clinically acceptable limits. In addition to implications for minimally invasive AM-based clinical treatments, these proof-of-concept prints are some of the only in situ demonstrations to-date, wherein the substrate geometry was unknown a priori. The work presented herein demonstrates in situ AM, suggests potential biomedical applications and also explores in situ-specific issues, including geometric feedback, material selection and novel path planning techniques.

  10. Additive manufacturing for in situ repair of osteochondral defects

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Daniel L; Lipton, Jeffrey I; Bonassar, Lawrence J; Lipson, Hod, E-mail: dlc44@cornell.ed, E-mail: jil26@cornell.ed, E-mail: lb244@cornell.ed, E-mail: hod.lipson@cornell.ed [Cornell University, Mechanical and Aerospace Engineering, Ithaca, NY (United States)

    2010-09-15

    Tissue engineering holds great promise for injury repair and replacement of defective body parts. While a number of techniques exist for creating living biological constructs in vitro, none have been demonstrated for in situ repair. Using novel geometric feedback-based approaches and through development of appropriate printing-material combinations, we demonstrate the in situ repair of both chondral and osteochondral defects that mimic naturally occurring pathologies. A calf femur was mounted in a custom jig and held within a robocasting-based additive manufacturing (AM) system. Two defects were induced: one a cartilage-only representation of a grade IV chondral lesion and the other a two-material bone and cartilage fracture of the femoral condyle. Alginate hydrogel was used for the repair of cartilage; a novel formulation of demineralized bone matrix was used for bone repair. Repair prints for both defects had mean surface errors less than 0.1 mm. For the chondral defect, 42.8 {+-} 2.6% of the surface points had errors that were within a clinically acceptable error range; however, with 1 mm path planning shift, an estimated {approx}75% of surface points could likely fall within the benchmark envelope. For the osteochondral defect, 83.6 {+-} 2.7% of surface points had errors that were within clinically acceptable limits. In addition to implications for minimally invasive AM-based clinical treatments, these proof-of-concept prints are some of the only in situ demonstrations to-date, wherein the substrate geometry was unknown a priori. The work presented herein demonstrates in situ AM, suggests potential biomedical applications and also explores in situ-specific issues, including geometric feedback, material selection and novel path planning techniques.

  11. 膝关节周围皮肤软组织缺损的修复%Repair of skin and soft tissue defects around the knee joints

    Institute of Scientific and Technical Information of China (English)

    谭谦; 许澎

    2015-01-01

    Skin and soft tissue defects around the knee joints are often accompanied by popliteal artery injury, patellar ligament injury, patellar fracture, and other deep tissue damage or exposure, making them challenging to repair.The principle is to repair the wound, reconstruct anatomical structure of the knee joint, and recover the knee joint function.At present the reconstruction with skin flap or myocutaneous flap is our priority.Local flap or myocutaneous flap can be used for repairing minor defects around the knee joints.Repairing with perforator flap, fascia flap, and free flap are main alternatives for covering larger and complex defects around the knee joints.During the treatment, a joint effort is mandatory, not only to repair the wound, but also to reconstruct vasculature, fix fracture, repair ligament, and finally recover the knee joint function.Therefore, the importance of multidisciplinary cooperation must be emphasized.Moreover, along with the development of new technologies, new methods, and new materials, perforator flap plays an important role in repairing skin and soft tissue defects around the knee joints.

  12. Biochemical effects on long-term frozen human costal cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Santin, Stefany P.; Martinho Junior, Antonio C.; Yoshito, Daniele; Soares, Fernando A.N.; Mathor, Monica B., E-mail: mathor@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Currently, the progresses on treatment of musculoskeletal diseases with the evolving of artificial implants and the success of tissue transplantation between genetically different individuals have conducted to an increase in radiosterilization. Regarding to tissue transplantation, it is essential to have sterile tissue and many tissue banks use radiosterilization as an effective method to sterilize these tissues. However, high doses of ionizing radiation and the preservation method may induce structural modifications in the tissues, as degradation of structural scaffold, decreasing its mechanical properties. Particularly, cartilage have been preserved in high concentrations of glycerol or deep-frozen at -70 degree C for storage after radiosterilization. Therefore, it is important to study the modifications induced in cartilage by preservation methods and by radiosterilization to determine the appropriated parameters for high quality of human allografts. Costal cartilages were obtained from cadaveric donors and were frozen at -20 degree C for 2 years long in order to compare with previous studies for fresh, deep-frozen and glycerolised cartilages. The mechanical tests were carried out in a universal testing machine until sample failure. According our results, there is no significant statistical difference between stress at break of fresh, long-term - 20 degree C frozen cartilages and deep-frozen cartilage. This early result suggests, regarding to tensile property, that long-term - 20 degree C frozen cartilages corresponds to glycerolised costal cartilages irradiated with 25 kGy or deep-frozen cartilages irradiated with 25 and 50 kGy. Thus, this long-term frozen cartilages may be used for tissue banks, but more studies about effects of ionizing radiation are necessary. (author)

  13. Biochemical effects on long-term frozen human costal cartilage

    International Nuclear Information System (INIS)

    Currently, the progresses on treatment of musculoskeletal diseases with the evolving of artificial implants and the success of tissue transplantation between genetically different individuals have conducted to an increase in radiosterilization. Regarding to tissue transplantation, it is essential to have sterile tissue and many tissue banks use radiosterilization as an effective method to sterilize these tissues. However, high doses of ionizing radiation and the preservation method may induce structural modifications in the tissues, as degradation of structural scaffold, decreasing its mechanical properties. Particularly, cartilage have been preserved in high concentrations of glycerol or deep-frozen at -70 degree C for storage after radiosterilization. Therefore, it is important to study the modifications induced in cartilage by preservation methods and by radiosterilization to determine the appropriated parameters for high quality of human allografts. Costal cartilages were obtained from cadaveric donors and were frozen at -20 degree C for 2 years long in order to compare with previous studies for fresh, deep-frozen and glycerolised cartilages. The mechanical tests were carried out in a universal testing machine until sample failure. According our results, there is no significant statistical difference between stress at break of fresh, long-term - 20 degree C frozen cartilages and deep-frozen cartilage. This early result suggests, regarding to tensile property, that long-term - 20 degree C frozen cartilages corresponds to glycerolised costal cartilages irradiated with 25 kGy or deep-frozen cartilages irradiated with 25 and 50 kGy. Thus, this long-term frozen cartilages may be used for tissue banks, but more studies about effects of ionizing radiation are necessary. (author)

  14. Low power laser irradiation stimulates cell proliferation via proliferating cell nuclear antigen and Ki-67 expression during tissue repair

    Science.gov (United States)

    Prabhu, Vijendra; Rao, Bola Sadashiva Satish; Mahato, Krishna Kishore

    2015-03-01

    Low power laser irradiation (LPLI) is becoming an increasingly popular and fast growing therapeutic modality in dermatology to treat various ailments without any reported side effects. In the present study an attempt was made to investigate the proliferative potential of red laser light during tissue repair in Swiss albino mice. To this end, full thickness excisional wounds of diameter 15 mm created on mice were exposed to single dose of Helium-Neon laser (632.8 nm; 7 mW; 4.02 mWcm-2; Linear polarization) at 2 Jcm-2 and 10 Jcm-2 along with un-illuminated controls. The granulation tissues from all the respective experimental groups were harvested on day 10 post-wounding following euthanization. Subsequently, tissue regeneration potential of these laser doses under study were evaluated by monitoring proliferating cell nuclear antigen and Ki-67 following the laser treatment and comparing it with the un-illuminated controls. The percentages of Ki-67 or PCNA positive cells were determined by counting positive nuclei (Ki-67/PCNA) and total nuclei in five random fields per tissue sections. Animal wounds treated with single exposure of the 2 Jcm-2 indicated significant elevation in PCNA (Ptested experimental groups as evidenced by the microscopy results in the study. In summary, the findings of the present study have clearly demonstrated the regulation of cell proliferation by LPLI via PCNA and Ki-67 expression during tissue regeneration.

  15. Low power laser irradiation stimulates cell proliferation via proliferating cell nuclear antigen and Ki-67 expression during tissue repair

    Science.gov (United States)

    Prabhu, Vijendra; Rao, Bola Sadashiva Satish; Mahato, Krishna Kishore

    2015-03-01

    Low power laser irradiation (LPLI) is becoming an increasingly popular and fast growing therapeutic modality in dermatology to treat various ailments without any reported side effects. In the present study an attempt was made to investigate the proliferative potential of red laser light during tissue repair in Swiss albino mice. To this end, full thickness excisional wounds of diameter 15 mm created on mice were exposed to single dose of Helium-Neon laser (632.8 nm; 7 mW; 4.02 mWcm-2; Linear polarization) at 2 Jcm-2 and 10 Jcm-2 along with un-illuminated controls. The granulation tissues from all the respective experimental groups were harvested on day 10 post-wounding following euthanization. Subsequently, tissue regeneration potential of these laser doses under study were evaluated by monitoring proliferating cell nuclear antigen and Ki-67 following the laser treatment and comparing it with the un-illuminated controls. The percentages of Ki-67 or PCNA positive cells were determined by counting positive nuclei (Ki-67/PCNA) and total nuclei in five random fields per tissue sections. Animal wounds treated with single exposure of the 2 Jcm-2 indicated significant elevation in PCNA (PJcm-2) expression as compared to other tested experimental groups as evidenced by the microscopy results in the study. In summary, the findings of the present study have clearly demonstrated the regulation of cell proliferation by LPLI via PCNA and Ki-67 expression during tissue regeneration.

  16. An ovine in vitro model for chondrocyte-based scaffold-assisted cartilage grafts

    Directory of Open Access Journals (Sweden)

    Endres Michaela

    2012-11-01

    Full Text Available Abstract Background Scaffold-assisted autologous chondrocyte implantation is an effective clinical procedure for cartilage repair. From the regulatory point of view, the ovine model is one of the suggested large animal models for pre-clinical studies. The aim of our study was to evaluate the in vitro re-differentiation capacity of expanded ovine chondrocytes in biomechanically characterized polyglycolic acid (PGA/fibrin biomaterials for scaffold-assisted cartilage repair. Methods Ovine chondrocytes harvested from adult articular cartilage were expanded in monolayer and re-assembled three-dimensionally in PGA-fibrin scaffolds. De- and re-differentiation of ovine chondrocytes in PGA-fibrin scaffolds was assessed by histological and immuno-histochemical staining as well as by real-time gene expression analysis of typical cartilage marker molecules and the matrix-remodelling enzymes matrix metalloproteinases (MMP -1, -2 and −13 as well as their inhibitors. PGA scaffolds characteristics including degradation and stiffness were analysed by electron microscopy and biomechanical testing. Results Histological, immuno-histochemical and gene expression analysis showed that dedifferentiated chondrocytes re-differentiate in PGA-fibrin scaffolds and form a cartilaginous matrix. Re-differentiation was accompanied by the induction of type II collagen and aggrecan, while MMP expression decreased in prolonged tissue culture. Electron microscopy and biomechanical tests revealed that the non-woven PGA scaffold shows a textile structure with high tensile strength of 3.6 N/mm2 and a stiffness of up to 0.44 N/mm2, when combined with gel-like fibrin. Conclusion These data suggest that PGA-fibrin is suited as a mechanically stable support structure for scaffold-assisted chondrocyte grafts, initiating chondrogenic re-differentiation of expanded chondrocytes.

  17. Acute lung injury: How macrophages orchestrate resolution of inflammation and tissue repair

    Directory of Open Access Journals (Sweden)

    Susanne eHerold

    2011-11-01

    Full Text Available Lung macrophages are long living cells with broad differentiation potential, which reside in the lung interstitium and alveoli or are organ-recruited upon inflammatory stimuli. A role of resident and recruited macrophages in initiating and maintaining pulmonary inflammation in lung infection or injury has been convincingly demonstrated. More recent reports suggest that lung macrophages are main orchestrators of termination and resolution of inflammation and initiators of parenchymal repair processes that are essential for return to homeostasis with normal gas exchange. In this review we will discuss cellular cross-talk mechanisms and molecular pathways of macrophage plasticity which define their role in inflammation resolution and in initiation of lung barrier repair following lung injury.

  18. Validity of T2 mapping in characterization of the regeneration tissue by bone marrow derived cell transplantation in osteochondral lesions of the ankle

    International Nuclear Information System (INIS)

    Objective: Bone marrow derived cell transplantation (BMDCT) has been recently suggested as a possible surgical technique to repair osteochondral lesions. To date, no qualitative MRI studies have evaluated its efficacy. The aim of our study is to investigate the validity of MRI T2-mapping sequence in characterizing the reparative tissue obtained and its ability to correlate with clinical results. Methods and materials: 20 patients with an osteochondral lesion of the talus underwent BMDCT and were evaluated at 2 years follow up using MRI T2-mapping sequence. 20 healthy volunteers were recruited as controls. MRI images were acquired using a protocol suggested by the International Cartilage Repair Society, MOCART scoring system and T2 mapping. Results were then correlated with AOFAS clinical score. Results: AOFAS score increased from 66.8 ± 14.5 pre-operatively to 91.2 ± 8.3 (p < 0.0005) at 2 years follow-up. T2-relaxation time value of 35-45 ms was derived from healthy ankles evaluation and assumed as normal hyaline cartilage value and used as a control. Regenerated tissue with a T2-relaxation time value comparable to hyaline cartilage was found in all the cases treated, covering a mean of 78% of the repaired lesion area. A high clinical score was related directly to isointense signal in DPFSE fat sat (p = 0.05), and percentage of regenerated hyaline cartilage (p = 0.05), inversely to the percentage of regenerated fibrocartilage. Lesion's depth negatively related to the integrity of the repaired tissue's surface (tau = -0.523, p = 0.007), and to the percentage of regenerated hyaline cartilage (rho = -0.546, p = 0.013). Conclusions: Because of its ability to detect cartilage's quality and to correlate to the clinical score, MRI T2-mapping sequence integrated with Mocart score represent a valid, non-invasive technique for qualitative cartilage assessment after regenerative surgical procedures.

  19. Validity of T2 mapping in characterization of the regeneration tissue by bone marrow derived cell transplantation in osteochondral lesions of the ankle

    Energy Technology Data Exchange (ETDEWEB)

    Battaglia, M., E-mail: milva.battaglia@ior.it [Service of Ecography and Radiology, Rizzoli Orthopaedic Institute, via Pupilli n. 1, 40136 Bologna (Italy); Rimondi, E. [Service of Ecography and Radiology, Rizzoli Orthopaedic Institute, via Pupilli n. 1, 40136 Bologna (Italy); Monti, C. [Service of CT and MRI, Casa di Cura Madre Fortunata Toniolo, Bologna (Italy); Guaraldi, F. [Department of Pathology, The Johns Hopkins University, School of Medicine, Baltimore, MD (United States); Sant' Andrea, A. [Service of CT and MRI, Casa di Cura Madre Fortunata Toniolo, Bologna (Italy); Buda, R.; Cavallo, M.; Giannini, S.; Vannini, F. [Clinical Orthopaedic and Traumatology Unit II, Rizzoli Orthopaedic Institute, Bologna (Italy)

    2011-11-15

    Objective: Bone marrow derived cell transplantation (BMDCT) has been recently suggested as a possible surgical technique to repair osteochondral lesions. To date, no qualitative MRI studies have evaluated its efficacy. The aim of our study is to investigate the validity of MRI T2-mapping sequence in characterizing the reparative tissue obtained and its ability to correlate with clinical results. Methods and materials: 20 patients with an osteochondral lesion of the talus underwent BMDCT and were evaluated at 2 years follow up using MRI T2-mapping sequence. 20 healthy volunteers were recruited as controls. MRI images were acquired using a protocol suggested by the International Cartilage Repair Society, MOCART scoring system and T2 mapping. Results were then correlated with AOFAS clinical score. Results: AOFAS score increased from 66.8 {+-} 14.5 pre-operatively to 91.2 {+-} 8.3 (p < 0.0005) at 2 years follow-up. T2-relaxation time value of 35-45 ms was derived from healthy ankles evaluation and assumed as normal hyaline cartilage value and used as a control. Regenerated tissue with a T2-relaxation time value comparable to hyaline cartilage was found in all the cases treated, covering a mean of 78% of the repaired lesion area. A high clinical score was related directly to isointense signal in DPFSE fat sat (p = 0.05), and percentage of regenerated hyaline cartilage (p = 0.05), inversely to the percentage of regenerated fibrocartilage. Lesion's depth negatively related to the integrity of the repaired tissue's surface (tau = -0.523, p = 0.007), and to the percentage of regenerated hyaline cartilage (rho = -0.546, p = 0.013). Conclusions: Because of its ability to detect cartilage's quality and to correlate to the clinical score, MRI T2-mapping sequence integrated with Mocart score represent a valid, non-invasive technique for qualitative cartilage assessment after regenerative surgical procedures.

  20. Transplanted Bone Marrow Cells Repair Heart Tissue and Reduce Myocarditis in Chronic Chagasic Mice

    OpenAIRE

    MILENA B. P. SOARES; Lima, Ricardo S.; Rocha, Leonardo L.; Takyia, Christina M; Pontes-de-Carvalho, Lain; Campos de Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo

    2004-01-01

    A progressive destruction of the myocardium occurs in ∼30% of Trypanosoma cruzi-infected individuals, causing chronic chagasic cardiomyopathy, a disease so far without effective treatment. Syngeneic bone marrow cell transplantation has been shown to cause repair and improvement of heart function in a number of studies in patients and animal models of ischemic cardiopathy. The effects of bone marrow transplant in a mouse model of chronic chagasic cardiomyopathy, in the presence of the disease ...

  1. Cartilage-Specific Near-Infrared Fluorophores for Biomedical Imaging.

    Science.gov (United States)

    Hyun, Hoon; Owens, Eric A; Wada, Hideyuki; Levitz, Andrew; Park, GwangLi; Park, Min Ho; Frangioni, John V; Henary, Maged; Choi, Hak Soo

    2015-07-20

    A novel class of near-infrared fluorescent contrast agents was developed. These agents target cartilage with high specificity and this property is inherent to the chemical structure of the fluorophore. After a single low-dose intravenous injection and a clearance time of approximately 4 h, these agents bind to all three major types of cartilage (hyaline, elastic, and fibrocartilage) and perform equally well across species. Analysis of the chemical structure similarities revealed a potential pharmacophore for cartilage targeting. Our results lay the foundation for future improvements in tissue engineering, joint surgery, and cartilage-specific drug development. PMID:26095685

  2. Cutaneous Squamous Cell Carcinoma with Invasion through Ear Cartilage

    Directory of Open Access Journals (Sweden)

    Julie Boisen

    2016-01-01

    Full Text Available Cutaneous squamous cell carcinoma of the ear represents a high-risk tumor location with an increased risk of metastasis and local tissue invasion. However, it is uncommon for these cancers to invade through nearby cartilage. Cartilage invasion is facilitated by matrix metalloproteases, specifically collagenase 3. We present the unusual case of a 76-year-old man with an auricular squamous cell carcinoma that exhibited full-thickness perforation of the scapha cartilage. Permanent sections through the eroded cartilage confirmed tumor invasion extending to the posterior ear skin.

  3. Electrospun gelatin/polycaprolactone nanofibrous membranes combined with a coculture of bone marrow stromal cells and chondrocytes for cartilage engineering

    Directory of Open Access Journals (Sweden)

    He X

    2015-03-01

    Full Text Available Xiaomin He,1,* Bei Feng,1,2,* Chuanpei Huang,1 Hao Wang,1 Yang Ge,1 Renjie Hu,1 Meng Yin,1 Zhiwei Xu,1 Wei Wang,1 Wei Fu,1,2 Jinghao Zheng1 1Department of Pediatric Cardiothoracic Surgery, 2Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Electrospinning has recently received considerable attention, showing notable potential as a novel method of scaffold fabrication for cartilage engineering. The aim of this study was to use a coculture strategy of chondrocytes combined with electrospun gelatin/polycaprolactone (GT/PCL membranes, instead of pure chondrocytes, to evaluate the formation of cartilaginous tissue. We prepared the GT/PCL membranes, seeded bone marrow stromal cell (BMSC/chondrocyte cocultures (75% BMSCs and 25% chondrocytes in a sandwich model in vitro, and then implanted the constructs subcutaneously into nude mice for 12 weeks. Gross observation, histological and immunohistological evaluation, glycosaminoglycan analyses, Young’s modulus measurement, and immunofluorescence staining were performed postimplantation. We found that the coculture group formed mature cartilage-like tissue, with no statistically significant difference from the chondrocyte group, and labeled BMSCs could differentiate into chondrocyte-like cells under the chondrogenic niche of chondrocytes. This entire strategy indicates that GT/PCL membranes are also a suitable scaffold for stem cell-based cartilage engineering and may provide a potentially clinically feasible approach for cartilage repairs. Keywords: electrospinning, nanocomposite, cartilage tissue engineering, nanomaterials, stem cells

  4. Chondroitin sulphate and heparan sulphate sulphation motifs and their proteoglycans are involved in articular cartilage formation during human foetal knee joint development.

    Science.gov (United States)

    Melrose, James; Isaacs, Marc D; Smith, Susan M; Hughes, Clare E; Little, Christopher B; Caterson, Bruce; Hayes, Anthony J

    2012-09-01

    Novel sulphation motifs within the glycosaminoglycan chain structure of chondroitin sulphate (CS) containing proteoglycans (PGs) are associated with sites of growth, differentiation and repair in many biological systems and there is compelling evidence that they function as molecular recognition sites that are involved in the binding, sequestration or presentation of soluble signalling molecules (e.g. morphogens, growth factors and cytokines). Here, using monoclonal antibodies 3B3(-), 4C3 and 7D4, we examine the distribution of native CS sulphation motifs within the developing connective tissues of the human foetal knee joint, both during and after joint cavitation. We show that the CS motifs have broad, overlapping distributions within the differentiating connective tissues before the joint has fully cavitated; however, after cavitation, they all localise very specifically to the presumptive articular cartilage tissue. Comparisons with the labelling patterns of heparan sulphate (HS), HS-PGs (perlecan, syndecan-4 and glypican-6) and FGF-2, molecules with known signalling roles in development, indicate that these also become localised to the future articular cartilage tissue after joint cavitation. Furthermore, they display interesting, overlapping distributions with the CS motifs, reflective of early tissue zonation. The overlapping expression patterns of these molecules at this site suggests they are involved, or co-participate, in early morphogenetic events underlying articular cartilage formation; thus having potential clinical relevance to mechanisms involved in its repair/regeneration. We propose that these CS sulphation motifs are involved in modulating the signalling gradients responsible for the cellular behaviours (proliferation, differentiation, matrix turnover) that shape the zonal tissue architecture present in mature articular cartilage. PMID:22617995

  5. Secondary cartilage revealed in a non-avian dinosaur embryo.

    Science.gov (United States)

    Bailleul, Alida M; Hall, Brian K; Horner, John R

    2013-01-01

    The skull and jaws of extant birds possess secondary cartilage, a tissue that arises after bone formation during embryonic development at articulations, ligamentous and muscular insertions. Using histological analysis, we discovered secondary cartilage in a non-avian dinosaur embryo, Hypacrosaurus stebingeri (Ornithischia, Lambeosaurinae). This finding extends our previous report of secondary cartilage in post-hatching specimens of the same dinosaur species. It provides the first information on the ontogeny of avian and dinosaurian secondary cartilages, and further stresses their developmental similarities. Secondary cartilage was found in an embryonic dentary within a tooth socket where it is hypothesized to have arisen due to mechanical stresses generated during tooth formation. Two patterns were discerned: secondary cartilage is more restricted in location in this Hypacrosaurus embryo, than it is in Hypacrosaurus post-hatchlings; secondary cartilage occurs at far more sites in bird embryos and nestlings than in Hypacrosaurus. This suggests an increase in the number of sites of secondary cartilage during the evolution of birds. We hypothesize that secondary cartilage provided advantages in the fine manipulation of food and was selected over other types of tissues/articulations during the evolution of the highly specialized avian beak from the jaws of their dinosaurian ancestors. PMID:23418610

  6. Secondary cartilage revealed in a non-avian dinosaur embryo.

    Directory of Open Access Journals (Sweden)

    Alida M Bailleul

    Full Text Available The skull and jaws of extant birds possess secondary cartilage, a tissue that arises after bone formation during embryonic development at articulations, ligamentous and muscular insertions. Using histological analysis, we discovered secondary cartilage in a non-avian dinosaur embryo, Hypacrosaurus stebingeri (Ornithischia, Lambeosaurinae. This finding extends our previous report of secondary cartilage in post-hatching specimens of the same dinosaur species. It provides the first information on the ontogeny of avian and dinosaurian secondary cartilages, and further stresses their developmental similarities. Secondary cartilage was found in an embryonic dentary within a tooth socket where it is hypothesized to have arisen due to mechanical stresses generated during tooth formation. Two patterns were discerned: secondary cartilage is more restricted in location in this Hypacrosaurus embryo, than it is in Hypacrosaurus post-hatchlings; secondary cartilage occurs at far more sites in bird embryos and nestlings than in Hypacrosaurus. This suggests an increase in the number of sites of secondary cartilage during the evolution of birds. We hypothesize that secondary cartilage provided advantages in the fine manipulation of food and was selected over other types of tissues/articulations during the evolution of the highly specialized avian beak from the jaws of their dinosaurian ancestors.

  7. Multilayered Scaffolds for Osteochondral Tissue Engineering Based on Bioactive Glass and Biodegradable Polymers

    OpenAIRE

    Nooeaid, Patcharakamon

    2014-01-01

    Injuries of the articular cartilage may penetrate to the underlying subchondral bone, forming osteochondral defects which have a limited capacity of self-regeneration. Accompanied with limited surgical treatments and the fact that the causes are not understood well, an approach based in tissue engineering becomes a promising strategy for osteochondral repair. Such tissue engineering approaches are based on the combination of synthetic scaffolds, suitable cell sources and active molecules or g...

  8. Delayed gadolinium-enhanced MRI of cartilage of the ankle joint: Results after autologous matrix-induced chondrogenesis (AMIC)-aided reconstruction of osteochondral lesions of the talus

    International Nuclear Information System (INIS)

    Aim: To assess cartilage quality using delayed gadolinium-enhanced magnetic resonance imaging after repair of osteochondral lesions of the talus using autologous matrix-induced chondrogenesis (AMIC). Materials and methods: A three-dimensional (3D) spoiled gradient-echo (SGE) sequence at 3 T was used to obtain quantitative T1 relaxation times before and after Gd-DTPA2 (Magnevist, 0.2 mM/kg bod weight) administration to assess 23 cases of AMIC-aided repair of osteochondral lesions of the talus. Delta relaxation rates (ΔR1) for reference cartilage (RC) and repair tissue (RT), and the relative delta relaxation rate (rΔR1) were calculated. The morphological appearance of the cartilage RT was graded on sagittal dual-echo steady-state (DESS) views according to the “magnetic resonance observation of cartilage repair tissue” (MOCART) protocol. The study was approved by the institutional review board and written consent from each patient was obtained. Results: The AMIC cases had a mean T1 relaxation time of 1.194 s (SD 0.207 s) in RC and 1.470 s (SD 0.384 s) in RT before contrast medium administration. The contrast-enhanced T1 relaxation time decreased to 0.480 s (SD 0.114 s) in RC and 0.411 s (SD 0.096 s) in RT. There was a significant difference (p > 0.05) between the ΔR1 in RC (1.372 × 10−3/s, range 0.526–3.201 × 10−3/s, SD 0.666 × 10−3/s) and RT (1.856 × 10−3/s, range 0.93–3.336 × 10−3/s, SD 0.609 × 10−3/s). The mean rΔR1 was 1.49, SD 0.45). The mean MOCART score at follow-up was 62.6 points (range 30–95, SD 15.3). Conclusion: The results of the present study suggest that repair cartilage resulting from AMIC-aided repair of osteochondral lesions of the talus has a significantly lower glycosaminoglycan (GAG) content than normal hyaline cartilage, but can be regarded as having hyaline-like properties

  9. In vivo and in vitro evaluation of an Acetobacter xylinum synthesized microbial cellulose membrane intended for guided tissue repair

    Directory of Open Access Journals (Sweden)

    de Lima-Neto João

    2009-03-01

    Full Text Available Abstract Background Barrier materials as cellulose membranes are used for guided tissue repair. However, it is essential that the surrounding tissues accept the device. The present study histologically evaluated tissue reaction to a microbial cellulose membrane after subcutaneous implantation in mice. Furthermore, the interaction between mesenchymal stem cells and the biomaterial was studied in vitro to evaluate its ability to act as cellular scaffold for tissue engineering. Methods Twenty-five Swiss Albino mice were used. A 10 × 10 mm cellulose membrane obtained through biosynthesis using Acetobacter xylinum bacteria was implanted into the lumbar subcutaneous tissue of each mouse. The mice were euthanatized at seven, 15, 30, 60, and 90 days, and the membrane and surrounding tissues were collected and examined by histology. Results A mild inflammatory response without foreign body reaction was observed until 30 days post-surgery around the implanted membrane. Polarized microscopy revealed that the membrane remained intact at all evaluation points. Scanning electron microscopy of the cellulose membrane surface showed absence of pores. The in vitro evaluation of the interaction between cells and biomaterial was performed through viability staining analysis of the cells over the biomaterial, which showed that 95% of the mesenchymal stem cells aggregating to the cellulose membrane were alive and that 5% were necrotic. Scanning electron microscopy showed mesenchymal stem cells with normal morphology and attached to the cellulose membrane surface. Conclusion The microbial cellulose membrane evaluated was found to be nonresorbable, induced a mild inflammatory response and may prove useful as a scaffold for mesenchymal stem cells.

  10. Non-invasive monitoring of cytokine-based regenerative treatment of cartilage by hyperspectral unmixing (Conference Presentation)

    Science.gov (United States)

    Mahbub, Saabah B.; Succer, Peter; Gosnell, Martin E.; Anwaer, Ayad G.; Herbert, Benjamin; Vesey, Graham; Goldys, Ewa M.

    2016-03-01

    Extracting biochemical information from tissue autofluorescence is a promising approach to non-invasively monitor disease treatments at a cellular level, without using any external biomarkers. Our recently developed unsupervised hyperspectral unmixing by Dependent Component Analysis (DECA) provides robust and detailed metabolic information with proper account of intrinsic cellular heterogeneity. Moreover this method is compatible with established methods of fluorescent biomarker labelling. Recently adipose-derived stem cell (ADSC) - based therapies have been introduced for treating different diseases in animals and humans. ADSC have been shown promise in regenerative treatments for osteoarthritis and other bone and joint disorders. One of the mechanism of their action is their anti-inflammatory effects within osteoarthritic joints which aid the regeneration of cartilage. These therapeutic effects are known to be driven by secretions of different cytokines from the ADSCs. We have been using the hyperspectral unmixing techniques to study in-vitro the effects of ADSC-derived cytokine-rich secretions with the cartilage chip in both human and bovine samples. The study of metabolic effects of different cytokine treatment on different cartilage layers makes it possible to compare the merits of those treatments for repairing cartilage.

  11. In vitro and In vivo Evaluation of the Developed PLGA/HAp/Zein Scaffolds for Bone-Cartilage Interface Regeneration

    Institute of Scientific and Technical Information of China (English)

    LIN Yong Xin; DING Zhi Yong; ZHOU Xiao Bin; LI Si Tao; XIE De Ming; LI Zhi Zhong; SUN Guo Dong

    2015-01-01

    Objective To investigate the effect of electronspun PLGA/HAp/Zein scaffolds on the repair of cartilage defects. Methods The PLGA/HAp/Zein composite scaffolds were fabricated by electrospinning method. The physiochemical properties and biocompatibility of the scaffolds were separately characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), and fourier transform infrared spectroscopy (FTIR), human umbilical cord mesenchymal stem cells (hUC-MSCs) culture and animal experiments. Results The prepared PLGA/HAp/Zein scaffolds showed fibrous structure with homogenous distribution. hUC-MSCs could attach to and grow well on PLGA/HAp/Zein scaffolds, and there was no significant difference between cell proliferation on scaffolds and that without scaffolds (P>0.05). The PLGA/HAp/Zein scaffolds possessed excellent ability to promote in vivo cartilage formation. Moreover, there was a large amount of immature chondrocytes and matrix with cartilage lacuna on PLGA/HAp/Zein scaffolds. Conclusion The data suggest that the PLGA/HAp/Zein scaffolds possess good biocompatibility, which are anticipated to be potentially applied in cartilage tissue engineering and reconstruction.

  12. Optical methods for diagnostics and feedback control in laser-induced regeneration of spine disc and joint cartilages

    Science.gov (United States)

    Sobol, Emil; Sviridov, Alexander; Omeltchenko, Alexander; Baum, Olga; Baskov, Andrey; Borchshenko, Igor; Golubev, Vladimir; Baskov, Vladimir

    2011-03-01

    In 1999 we have introduced a new approach for treatment of spine diseases based on the mechanical effect of nondestructive laser radiation on the nucleus pulposus of the intervertebral disc. Laser reconstruction of spine discs (LRD) involves puncture of the disc and non-destructive laser irradiation of the nucleus pulposus to activate reparative processes in the disc tissues. In vivo animal study has shown that LRD allows activate the growth of hyaline type cartilage in laser affected zone. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reparation in cartilages of spine and joints. The results of laser reconstruction of intervertebral discs for 510 patients have shown substantial relief of back pain for 90% of patients. Laser technology has been experimentally tested for reparation of traumatic and degenerative diseases in joint cartilage of 20 minipigs. It is shown that laser regeneration of cartilage allows feeling large (more than 5 mm) defects which usually never repair on one's own. Optical techniques have been used to promote safety and efficacy of the laser procedures.

  13. Combining rhinoplasty with septal perforation repair.

    Science.gov (United States)

    Foda, Hossam M T; Magdy, Emad A

    2006-11-01

    A combined septal perforation repair and rhinoplasty was performed in 80 patients presenting with septal perforations (size 1 to 5 cm) and external nasal deformities. The external rhinoplasty approach was used for all cases and the perforation was repaired using bilateral intranasal mucosal advancement flaps with a connective tissue interposition graft in between. Complete closure of the perforation was achieved in 90% of perforations of size up to 3.5 cm and in only 70% of perforations that were larger than 3.5 cm. Cosmetically, 95% were very satisfied with their aesthetic result. The external rhinoplasty approach proved to be very helpful in the process of septal perforation repair especially in large and posteriorly located perforations and in cases where the caudal septal cartilage was previously resected. Our results show that septal perforation repair can be safely combined with rhinoplasty and that some of the routine rhinoplasty maneuvers, such as medial osteotomies and dorsal lowering, could even facilitate the process of septal perforation repair. PMID:17131270

  14. 松质骨基质复合生物蛋白胶构建组织工程软骨的研究%Construction Tissue-Engineered Cartilage Using Bone Matrix Gelatin and Biological Fibrin Glue

    Institute of Scientific and Technical Information of China (English)

    王正辉; 常会敏; 吴宝俊; 杨壮群; Kamal Mustafa; 卢晓云

    2012-01-01

    目的 尝试采用松质骨基质与生物蛋白胶复合材料构建组织工程软骨.方法 体外培养大鼠软骨细胞,接种于松质骨基质/生物蛋白胶材料上行体外培养、采用HE、甲苯胺蓝染色免疫学检测、扫描电镜观察等方法观察所构建的组织工程软骨的特性.结果 松质骨基质/生物蛋白胶组的组织学结构更接近于软骨样组织,其Ⅱ型胶原、蛋白多糖基因表达量及蛋白多糖含量明显高于松质骨基质组.结论 松质骨基质/生物蛋白胶复合材料可用于构建组织工程软骨, 是一种较理想的支架材料.%Objective To explore the feasibility of the construction of tissue-engineered cartilage using hybrid scaffolds of demineralized bone matrix gelatin (BMG) and fibrin glue. Methods Rattus chottdroeytes were cultured on hybrid BMG/ fibrin glue scaffolds (BMG/fibrin glue group) and BMG scaffolds (HMG group) in vitro. Engineered cartilage-like tissue grown on the scaffolds was characterized by histological observation, immunological examination, scanning electron microscopy, hinchemioiil assays and unatysis of gene expression. Results The presence of proteoglycan was confirmed by positive (oluidiiie blue in BMG/fibrin glue group, compared with BMG group. Collagen type Ⅱ exhibited intense immuno-positivity at the peri-cellular matrices in BMC/fibrin glue group, compared with BMG group. The expression of collagen type Ⅱ had no signifiranl difference between BMG/fibrin glue group and BMG group (p>0.05), while the expression of aggrecan core protein in BMG/fibrin glue group was higher than that in BMG group (P<0.05). The glyrusamlnog]yean production and hycjroxyproline content of BMG/fibrin glue group were higher than that of BMG group (P<0.05). Conclusion The fibrin/BMG hybrid scaffolds may serve as a potential celt delivery vehicle and a ^trurtural basis for cartilage tissue engineering.

  15. Cartilage conduction hearing.

    Science.gov (United States)

    Shimokura, Ryota; Hosoi, Hiroshi; Nishimura, Tadashi; Yamanaka, Toshiaki; Levitt, Harry

    2014-04-01

    Sound information is known to travel to the cochlea via either air or bone conduction. However, a vibration signal, delivered to the aural cartilage via a transducer, can also produce a clearly audible sound. This type of conduction has been termed "cartilage conduction." The aural cartilage forms the outer ear and is distributed around the exterior half of the external auditory canal. In cartilage conduction, the cartilage and transducer play the roles of a diaphragm and voice coil of a loudspeaker, respectively. There is a large gap between the impedances of cartilage and skull bone, such that cartilage vibrations are not easily transmitted through bone. Thus, these methods of conduction are distinct. In this study, force was used to apply a transducer to aural cartilage, and it was found that the sound in the auditory canal was amplified, especially for frequencies below 2 kHz. This effect was most pronounced at an application force of 1 N, which is low enough to ensure comfort in the design of hearing aids. The possibility of using force adjustments to vary amplification may also have applications for cell phone design. PMID:25234994

  16. Transplantation of human adipose tissue-derived stem cells for repair of injured spiral ganglion neurons in deaf guinea pigs

    Science.gov (United States)

    Jang, Sujeong; Cho, Hyong-Ho; Kim, Song-Hee; Lee, Kyung-Hwa; Cho, Yong-Bum; Park, Jong-Seong; Jeong, Han-Seong

    2016-01-01

    Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be able to differentiate into spiral ganglion neurons. Little has been reported on adipose tissue-derived stem cells (ADSCs) for repair of injured spiral ganglion neurons. In this study, we hypothesized that transplantation of neural induced-human ADSCs (NI-hADSCs) can repair the injured spiral ganglion neurons in guinea pigs with neomycin-induced sensorineural hearing loss. NI-hADSCs were induced with culture medium containing basic fibroblast growth factor and forskolin and then injected to the injured cochleae. Guinea pigs that received injection of Hanks’ balanced salt solution into the cochleae were used as controls. Hematoxylin-eosin staining showed that at 8 weeks after cell transplantation, the number of surviving spiral ganglion neurons in the cell transplantation group was significantly increased than that in the control group. Also at 8 weeks after cell transplantation, immunohistochemical staining showed that a greater number of NI-hADSCs in the spiral ganglions were detected in the cell transplantation group than in the control group, and these NI-hADSCs expressed neuronal markers neurofilament protein and microtubule-associated protein 2. Within 8 weeks after cell transplantation, the guinea pigs in the cell transplantation group had a gradually decreased auditory brainstem response threshold, while those in the control group had almost no response to 80 dB of clicks or pure tone burst. These findings suggest that a large amount of NI-hADSCs migrated to the spiral ganglions, survived for a period of time, repaired the injured spiral ganglion cells, and thereby contributed to the recovery of sensorineural hearing loss in guinea pigs. PMID:27482231

  17. Transplantation of human adipose tissue-derived stem cells for repair of injured spiral ganglion neurons in deaf guinea pigs.

    Science.gov (United States)

    Jang, Sujeong; Cho, Hyong-Ho; Kim, Song-Hee; Lee, Kyung-Hwa; Cho, Yong-Bum; Park, Jong-Seong; Jeong, Han-Seong

    2016-06-01

    Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be able to differentiate into spiral ganglion neurons. Little has been reported on adipose tissue-derived stem cells (ADSCs) for repair of injured spiral ganglion neurons. In this study, we hypothesized that transplantation of neural induced-human ADSCs (NI-hADSCs) can repair the injured spiral ganglion neurons in guinea pigs with neomycin-induced sensorineural hearing loss. NI-hADSCs were induced with culture medium containing basic fibroblast growth factor and forskolin and then injected to the injured cochleae. Guinea pigs that received injection of Hanks' balanced salt solution into the cochleae were used as controls. Hematoxylin-eosin staining showed that at 8 weeks after cell transplantation, the number of surviving spiral ganglion neurons in the cell transplantation group was significantly increased than that in the control group. Also at 8 weeks after cell transplantation, immunohistochemical staining showed that a greater number of NI-hADSCs in the spiral ganglions were detected in the cell transplantation group than in the control group, and these NI-hADSCs expressed neuronal markers neurofilament protein and microtubule-associated protein 2. Within 8 weeks after cell transplantation, the guinea pigs in the cell transplantation group had a gradually decreased auditory brainstem response threshold, while those in the control group had almost no response to 80 dB of clicks or pure tone burst. These findings suggest that a large amount of NI-hADSCs migrated to the spiral ganglions, survived for a period of time, repaired the injured spiral ganglion cells, and thereby contributed to the recovery of sensorineural hearing loss in guinea pigs. PMID:27482231

  18. Critical temperature transitions in laser-mediated cartilage reshaping

    Science.gov (United States)

    Wong, Brian J.; Milner, Thomas E.; Kim, Hong H.; Telenkov, Sergey A.; Chew, Clifford; Kuo, Timothy C.; Smithies, Derek J.; Sobol, Emil N.; Nelson, J. Stuart

    1998-07-01

    In this study, we attempted to determine the critical temperature [Tc] at which accelerated stress relaxation occurred during laser mediated cartilage reshaping. During laser irradiation, mechanically deformed cartilage tissue undergoes a temperature dependent phase transformation which results in accelerated stress relaxation. When a critical temperature is attained, cartilage becomes malleable and may be molded into complex new shapes that harden as the tissue cools. Clinically, reshaped cartilage tissue can be used to recreate the underlying cartilaginous framework of structures such as the ear, larynx, trachea, and nose. The principal advantages of using laser radiation for the generation of thermal energy in tissue are precise control of both the space-time temperature distribution and time- dependent thermal denaturation kinetics. Optimization of the reshaping process requires identification of the temperature dependence of this phase transformation and its relationship to observed changes in cartilage optical, mechanical, and thermodynamic properties. Light scattering, infrared radiometry, and modulated differential scanning calorimetry (MDSC) were used to measure temperature dependent changes in the biophysical properties of cartilage tissue during fast (laser mediated) and slow (conventional calorimetric) heating. Our studies using MDSC and laser probe techniques have identified changes in cartilage thermodynamic and optical properties suggestive of a phase transformation occurring near 60 degrees Celsius.

  19. Allograft AlloDerm® tissue for laparoscopic transabdominal preperitoneal groin hernia repair: A case report

    OpenAIRE

    Amirlak, Bardia; Gerdes, Jodi; Puri, Varun; Fitzgibbons, Robert J.

    2014-01-01

    INTRODUCTION Synthetic mesh is the prosthetic material used for most inguinal hernioplasties. However, when left in contact with intra-abdominal viscera, it often becomes associated with infection and migration, particularly in irradiated tissues, contaminated fields, immunosuppressed individuals, and patients with intestinal obstruction or fistula. AlloDerm® Regenerative Tissue Matrix (LifeCell Corporation, Branchburg, NJ) is derived from human cadaver skin and may be associated with fewer v...

  20. APC is required for muscle stem cell proliferation and skeletal muscle tissue repair

    OpenAIRE

    Parisi, Alice; Lacour, Floriane; Giordani, Lorenzo; Colnot, Sabine; Maire, Pascal; Le Grand, Fabien

    2015-01-01

    The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle ste...

  1. Human Blood-Vessel-Derived Stem Cells for Tissue Repair and Regeneration

    OpenAIRE

    Chien-Wen Chen; Mirko Corselli; Bruno Péault; Johnny Huard

    2012-01-01

    Multipotent stem/progenitor cells with similar developmental potentials have been independently identified from diverse human tissue/organ cultures. The increasing recognition of the vascular/perivascular origin of mesenchymal precursors suggested blood vessels being a systemic source of adult stem/progenitor cells. Our group and other laboratories recently isolated multiple stem/progenitor cell subsets from blood vessels of adult human tissues. Each of the three structural layers of blood ve...

  2. A new mechanistic scenario for the origin and evolution of vertebrate cartilage.

    Directory of Open Access Journals (Sweden)

    Maria Cattell

    Full Text Available The appearance of cellular cartilage was a defining event in vertebrate evolution because it made possible the physical expansion of the vertebrate "new head". Despite its central role in vertebrate evolution, the origin of cellular cartilage has been difficult to understand. This is largely due to a lack of informative evolutionary intermediates linking vertebrate cellular cartilage to the acellular cartilage of invertebrate chordates. The basal jawless vertebrate, lamprey, has long been considered key to understanding the evolution of vertebrate cartilage. However, histological analyses of the lamprey head skeleton suggest it is composed of modern cellular cartilage and a putatively unrelated connective tissue called mucocartilage, with no obvious transitional tissue. Here we take a molecular approach to better understand the evolutionary relationships between lamprey cellular cartilage, gnathostome cellular cartilage, and lamprey mucocartilage. We find that despite overt histological similarity, lamprey and gnathostome cellular cartilage utilize divergent gene regulatory networks (GRNs. While the gnathostome cellular cartilage GRN broadly incorporates Runx, Barx, and Alx transcription factors, lamprey cellular cartilage does not express Runx or Barx, and only deploys Alx genes in certain regions. Furthermore, we find that lamprey mucocartilage, despite its distinctive mesenchymal morphology, deploys every component of the gnathostome cartilage GRN, albeit in different domains. Based on these findings, and previous work, we propose a stepwise model for the evolution of vertebrate cellular cartilage in which the appearance of a generic neural crest-derived skeletal tissue was followed by a phase of skeletal tissue diversification in early agnathans. In the gnathostome lineage, a single type of rigid cellular cartilage became dominant, replacing other skeletal tissues and evolving via gene cooption to become the definitive cellular cartilage of

  3. Tissue engineering and cell based therapies, from the bench to the clinic: The potential to replace, repair and regenerate

    Directory of Open Access Journals (Sweden)

    Fodor William L

    2003-11-01

    Full Text Available Abstract The field of Regenerative Biology as it applies to Regenerative Medicine is an increasingly expanding area of research with hopes of providing therapeutic treatments for diseases and/or injuries that conventional medicines and even new biologic drug therapies cannot effectively treat. Extensive research in the area of Regenerative Medicine is focused on the development of cells, tissues and organs for the purpose of restoring function through transplantation. The general belief is that replacement, repair and restoration of function is best accomplished by cells, tissues or organs that can perform the appropriate physiologic/metabolic duties better than any mechanical device, recombinant protein therapeutic or chemical compound. Several strategies are currently being investigated and include, cell therapies derived from autologous primary cell isolates, cell therapies derived from established cell lines, cell therapies derived from a variety of stem cells, including bone marrow/mesenchymal stem cells, cord blood stem cells, embryonic stem cells, as well as cells tissues and organs from genetically modified animals. This mini-review is not meant to be exhaustive, but aims to highlight clinical applications for the four areas of research listed above and will address a few key advances and a few of the hurdles yet to be overcome as the technology and science improve the likelihood that Regenerative Medicine will become clinically routine.

  4. The use of PLDLA/PCL-T scaffold to repair osteochondral defects in vivo

    Directory of Open Access Journals (Sweden)

    Andrea Rodrigues Esposito

    2013-02-01

    Full Text Available The physiological repair of osteochondral lesions requires the development of a scaffold that is compatible with the structure of the damaged tissue, cartilage and bone. The aim of this study was to evaluate the biological performance of a PLDLA/PCL-T (90/10 scaffold for repairing osteochondral defects in rabbits. Polymeric scaffolds containing saccharose (75% w/v were obtained by solvent casting and then implanted in the medial knee condyles of 12 New Zealand rabbits after osteochondral damage with a trephine metallic drill (diameter: 3.3 mm in both medial femoral condyles. Each rabbit received the same treatment, i.e., the polymeric scaffold was implanted on the right side while no material was implanted on the left side (control. Four and 12 weeks later histological examination revealed bone neoformation in the implant group, with the presence of hyaline cartilage and mesenchymal tissue. In contrast, the control group showed bone neoformation with necrosis, exacerbated superficial fibrosis, inflammation and cracks in the neoformed tissue. These findings indicate that the PLDLA/PCL-T scaffold was biocompatible and protected the condyles by stabilizing the lesion and allowing subchondral bone tissue and hyaline cartilage formation.

  5. The use of PLDLA/PCL-T scaffold to repair osteochondral defects in vivo

    Directory of Open Access Journals (Sweden)

    Andrea Rodrigues Esposito

    2012-01-01

    Full Text Available The physiological repair of osteochondral lesions requires the development of a scaffold that is compatible with the structure of the damaged tissue, cartilage and bone. The aim of this study was to evaluate the biological performance of a PLDLA/PCL-T (90/10 scaffold for repairing osteochondral defects in rabbits. Polymeric scaffolds containing saccharose (75% w/v were obtained by solvent casting and then implanted in the medial knee condyles of 12 New Zealand rabbits after osteochondral damage with a trephine metallic drill (diameter: 3.3 mm in both medial femoral condyles. Each rabbit received the same treatment, i.e., the polymeric scaffold was implanted on the right side while no material was implanted on the left side (control. Four and 12 weeks later histological examination revealed bone neoformation in the implant group, with the presence of hyaline cartilage and mesenchymal tissue. In contrast, the control group showed bone neoformation with necrosis, exacerbated superficial fibrosis, inflammation and cracks in the neoformed tissue. These findings indicate that the PLDLA/PCL-T scaffold was biocompatible and protected the condyles by stabilizing the lesion and allowing subchondral bone tissue and hyaline cartilage formation.

  6. Bacterial cellulose scaffolds for cartilage repair

    Directory of Open Access Journals (Sweden)

    Andrew Lloyd

    2004-11-01

    Full Text Available With the growth in the aged population and the need to extend average individual healthspan, biomaterials have an increasingly important role in the development of new generation medical devices, drug delivery systems, and medical diagnostic technologies. This column seeks to provide an insight into the latest developments in biomedical materials and related technologies through brief synopses and expert commentaries of recent presentations, publications, and patents. Andrew Lloyd, University of Brighton.

  7. Pivotal role for skin transendothelial radio-resistant anti-inflammatory macrophages in tissue repair

    Science.gov (United States)

    Barreiro, Olga; Cibrian, Danay; Clemente, Cristina; Alvarez, David; Moreno, Vanessa; Valiente, Íñigo; Bernad, Antonio; Vestweber, Dietmar; Arroyo, Alicia G; Martín, Pilar; von Andrian, Ulrich H; Sánchez Madrid, Francisco

    2016-01-01

    Heterogeneity and functional specialization among skin-resident macrophages are incompletely understood. In this study, we describe a novel subset of murine dermal perivascular macrophages that extend protrusions across the endothelial junctions in steady-state and capture blood-borne macromolecules. Unlike other skin-resident macrophages that are reconstituted by bone marrow-derived progenitors after a genotoxic insult, these cells are replenished by an extramedullary radio-resistant and UV-sensitive Bmi1+ progenitor. Furthermore, they possess a distinctive anti-inflammatory transcriptional profile, which cannot be polarized under inflammatory conditions, and are involved in repair and remodeling functions for which other skin-resident macrophages appear dispensable. Based on all their properties, we define these macrophages as Skin Transendothelial Radio-resistant Anti-inflammatory Macrophages (STREAM) and postulate that their preservation is important for skin homeostasis. DOI: http://dx.doi.org/10.7554/eLife.15251.001 PMID:27304075

  8. Mechanical properties of mesh materials used for hernia repair and soft tissue augmentation.

    Directory of Open Access Journals (Sweden)

    Peter P Pott

    Full Text Available BACKGROUND: Hernia repair is the most common surgical procedure in the world. Augmentation with synthetic meshes has gained importance in recent decades. Most of the published work about hernia meshes focuses on the surgical technique, outcome in terms of mortality and morbidity and the recurrence rate. Appropriate biomechanical and engineering terminology is frequently absent. Meshes are under continuous development but there is little knowledge in the public domain about their mechanical properties. In the presented experimental study we investigated the mechanical properties of several widely available meshes according to German Industrial Standards (DIN ISO. METHODOLOGY/PRINCIPAL FINDINGS: Six different meshes were assessed considering longitudinal and transverse direction in a uni-axial tensile test. Based on the force/displacement curve, the maximum force, breaking strain, and stiffness were computed. According to the maximum force the values were assigned to the groups weak and strong to determine a base for comparison. We discovered differences in the maximum force (11.1±6.4 to 100.9±9.4 N/cm, stiffness (0.3±0.1 to 4.6±0.5 N/mm, and breaking strain (150±6% to 340±20% considering the direction of tension. CONCLUSIONS/SIGNIFICANCE: The measured stiffness and breaking strength vary widely among available mesh materials for hernia repair, and most of the materials show significant anisotropy in their mechanical behavior. Considering the forces present in the abdominal wall, our results suggest that some meshes should be implanted in an appropriate orientation, and that information regarding the directionality of their mechanical properties should be provided by the manufacturers.

  9. Photographic-Based Optical Evaluation of Tissues and Biomaterials Used for Corneal Surface Repair: A New Easy-Applied Method.

    Directory of Open Access Journals (Sweden)

    Miguel Gonzalez-Andrades

    Full Text Available Tissues and biomaterials used for corneal surface repair require fulfilling specific optical standards prior to implantation in the patient. However, there is not a feasible evaluation method to be applied in clinical or Good Manufacturing Practice settings. In this study, we describe and assess an innovative easy-applied photographic-based method (PBM for measuring functional optical blurring and transparency in corneal surface grafts.Plastic compressed collagen scaffolds (PCCS and multilayered amniotic membranes (AM samples were optically and histologically evaluated. Transparency and image blurring measures were obtained by PBM, analyzing photographic images of a standardized band pattern taken through the samples. These measures were compared and correlated to those obtained applying the Inverse Adding-Doubling (IAD technique, which is the gold standard method.All the samples used for optical evaluation by PBM or IAD were histological suitable. PCCS samples presented transmittance values higher than 60%, values that increased with increasing wavelength as determined by IAD. The PBM indicated that PCCS had a transparency ratio (TR value of 80.3 ± 2.8%, with a blurring index (BI of 50.6 ± 4.2%. TR and BI obtained from the PBM showed a high correlation (ρ>|0.6| with the diffuse transmittance and the diffuse reflectance, both determined using the IAD (p<0.005. The AM optical properties showed that there was a largely linear relationship between the blurring and the number of amnion layers, with more layers producing greater blurring.This innovative proposed method represents an easy-applied technique for evaluating transparency and blurriness of tissues and biomaterials used for corneal surface repair.

  10. Minced Tissue in Compressed Collagen: A Cell-containing Biotransplant for Single-staged Reconstructive Repair.

    Science.gov (United States)

    Chamorro, Clara I; Zeiai, Said; Reinfeldt Engberg, Gisela; Fossum, Magdalena

    2016-01-01

    Conventional techniques for cell expansion and transplantation of autologous cells for tissue engineering purposes can take place in specially equipped human cell culture facilities. These methods include isolation of cells in single cell suspension and several laborious and time-consuming events before transplantation back to the patient. Previous studies suggest that the body itself could be used as a bioreactor for cell expansion and regeneration of tissue in order to minimize ex vivo manipulations of tissues and cells before transplanting to the patient. The aim of this study was to demonstrate a method for tissue harvesting, isolation of continuous epithelium, mincing of the epithelium into small pieces and incorporating them into a three-layered biomaterial. The three-layered biomaterial then served as a delivery vehicle, to allow surgical handling, exchange of nutrition across the transplant, and a controlled degradation. The biomaterial consisted of two outer layers of collagen and a core of a mechanically stable and slowly degradable polymer. The minced epithelium was incorporated into one of the collagen layers before transplantation. By mincing the epithelial tissue into small pieces, the pieces could be spread and thereby the propagation of cells was stimulated. After the initial take of the transplants, cell expansion and reorganization would take place and extracellular matrix mature to allow ingrowth of capillaries and nerves and further maturation of the extracellular matrix. The technique minimizes ex vivo manipulations and allow cell harvesting, preparation of autograft, and transplantation to the patient as a simple one-stage intervention. In the future, tissue expansion could be initiated around a 3D mold inside the body itself, according to the specific needs of the patient. Additionally, the technique could be performed in an ordinary surgical setting without the need for sophisticated cell culturing facilities. PMID:26967119

  11. The role of Wnt regulation in heart development, cardiac repair and disease: A tissue engineering perspective.

    Science.gov (United States)

    Pahnke, Aric; Conant, Genna; Huyer, Locke Davenport; Zhao, Yimu; Feric, Nicole; Radisic, Milica

    2016-05-01

    Wingless-related integration site (Wnt) signaling has proven to be a fundamental mechanism in cardiovascular development as well as disease. Understanding its particular role in heart formation has helped to develop pluripotent stem cell differentiation protocols that produce relatively pure cardiomyocyte populations. The resultant cardiomyocytes have been used to generate heart tissue for pharmaceutical testing, and to study physiological and disease states. Such protocols in combination with induced pluripotent stem cell technology have yielded patient-derived cardiomyocytes that exhibit some of the hallmarks of cardiovascular disease and are therefore being used to model disease states. While FDA approval of new treatments typically requires animal experiments, the burgeoning field of tissue engineering could act as a replacement. This would necessitate the generation of reproducible three-dimensional cardiac tissues in a well-controlled environment, which exhibit native heart properties, such as cellular density, composition, extracellular matrix composition, and structure-function. Such tissues could also enable the further study of Wnt signaling. Furthermore, as Wnt signaling has been found to have a mechanistic role in cardiac pathophysiology, e.g. heart attack, hypertrophy, atherosclerosis, and aortic stenosis, its strategic manipulation could provide a means of generating reproducible and specific, physiological and pathological cardiac models. PMID:26626076

  12. MRI of the cartilage

    International Nuclear Information System (INIS)

    With the introduction of fat-suppressed gradient-echo and fast spin-echo (FSE) sequences in clinical routine MR visualization of the hyaline articular cartilage is routinely possible in the larger joints. While 3D gradient-echo with fat suppression allows exact depiction of the thickness and surface of cartilage, FSE outlines the normal and abnormal internal structures of the hyaline cartilage; therefore, both sequences seem to be necessary in a standard MRI protocol for cartilage visualization. In diagnostically ambiguous cases, in which important therapeutic decisions are required, direct MR arthrography is the established imaging standard as an add-on procedure. Despite the social impact and prevalence, until recent years there was a paucity of knowledge about the pathogenesis of cartilage damage. With the introduction of high-resolution MRI with powerful surface coils and fat-suppression techniques, visualization of the articular cartilage is now routinely possible in many joints. After a short summary of the anatomy and physiology of the hyaline cartilage, the different MR imaging methods are discussed and recommended standards are suggested. (orig.)

  13. Development of tissue engineered strategies combining stem cells and scaffolds aimed to regenerate bone and osteochondral interfaces

    OpenAIRE

    Márcia T Rodrigues

    2011-01-01

    Bone is a specialized tissue characterized by its rigidity and hardness, yet light weighed to fulfill diverse functions as mineral storage, organ protection or body support and locomotion. Despite its extraordinary healing ability, bone response may be unsuccessful to repair severe damage caused by injury or degenerative diseases. Furthermore, when bone is affected, other tissues and interfaces might be quite distressed as well. Cartilage and bone interface of the joints (osteo...

  14. 含自体富集骨髓干细胞松质骨移植修复兔关节软骨大面积缺损的实验研究%Large Area Articular Cartilage Defect Repaired with Cancellous Bone Enriching Bone Marrow Stem Cells

    Institute of Scientific and Technical Information of China (English)

    胡德新; 朱博; 应小樟; 石仕元

    2014-01-01

    目的:探讨含自体富集骨髓干细胞松质骨移植修复兔关节软骨大面积缺损的生物学特性和效果。方法30只新西兰大白兔用利刀切除股骨髁全层关节软骨达关节软骨表面积的20%以上,制成关节软骨大面积缺损模型。实验组30条膝关节取含自体富集骨髓干细胞松质骨移植修复关节软骨缺损;对照组30条膝关节软骨缺损不作任何处理。于术后4、8、12周分批处死动物取材,分别进行膝关节活动度测定、大体观察、光镜观察,并对观察指标进行统计学分析。结果各观察节点实验组兔膝关节活动度均优于对照组(P<0.01),于术后12周膝关节活动度已基本接近正常。实验组兔膝关节再生软骨的表面积已基本完全填充造模缺损区,而对照组造模区缺损依然严重,仅修复20%左右,两组差异有统计学意义(P<0.01);实验组再生软骨与周边软骨愈合良好,再生软骨的厚度为周边正常软骨的三分之二左右,表面较光滑平整,无凹陷。电镜下,造模缺损区被再生软骨组织覆盖,表面光滑平整,周围和正常软骨组织接合较好,基质染色变深,软骨细胞数量增多,且大多为透明软骨细胞,可见潮线。结论含自体富集骨髓干细胞松质骨移植能以类透明软骨形式修复兔关节软骨的大面积缺损。%Objective To evaluate the therapeutic efficacy of cancellous bone enriching bone marrow stem cells in treatment of large area defects of articular cartilage in weight-bearing joints. Methods Sixty knees from 30 adult rabbits were randomly divided into experimental and control groups (n=30 in each). Full-thickness articular cartilage defects in the femoral condyle of the knees were created. Cancellous bone enriching bone marrow stem cells was implanted for repair of the defects in experimental group. Spontaneous evolution occurred in control group. Rabbits were sacrificed in both

  15. Efeitos sobre o tecido ósseo e cartilagem articular provocados pela imobilização e remobilização em ratos Wistar Effects of immobilization and remobilization on bone tissue and cartilage in Wistar rats

    Directory of Open Access Journals (Sweden)

    Danielle Portinho

    2008-10-01

    animais remobilizados.Long immobilization periods lead to bone and properties loss, and its recovery depends on many factors. Besides that, immobilization can cause ulcerations in the articular cartilage tissue due to alterations, such as loss of proteoglycans and total cartilage mass and volume. The aim of this study was to verify histological alterations of the periarticular bone tissue and articular cartilage caused by immobilization as well as remobilization of hinder limbs of Wistar rats. Twelve Wistar rats were divided in two groups: GI - (n=6: 15 days with the left hinder limb immobilized at plantiflexion, with the right limb being the control; GR - (n=6: used a 15 day-period of free remobilization in the cage, associated with 3 daily stretching bouts of the left soleus muscle for 30 seconds. The measures of the cortical bone thickness, diameter of the medular channel and number of condrocites were evaluated; in the cartilage tissue, the cartilage mean thickness and the number of condrocites were measured. The results showed that for GI there were no significant alterations in the bone thickness (p=0.1156, nor in the medular channel diameter (p=0.5698, but there was significant decrease of the osteocytes compared with the counter-lateral side (p=0.0005; in GR decrease in the number of osteocytes (p=0.0001 was also observed, but the differences in thickness (p=0.1343 and medular channel diameter (p=0.6456 remained non-significant. There were no significant differences for the articular cartilage data for the samples, neither in the cartilage thickness for GI (p=0.6640 and GR (p=0.1633; concerning the number of condrocites in GI (p=0.9429 and GR (p=0.1634. It is concluded hence that two weeks of immobilization and remobilization produced only significant decrease in the number of osteocytes in the immobilized rats and continued to decrease even in the remobilized animals.

  16. Evaluation of influence of proteoglycans on hydration of articular cartilage with the use of ultrasound

    Directory of Open Access Journals (Sweden)

    Yi-yi YANG

    2015-04-01

    Full Text Available Objective To monitor the changes in hydration behaviour of articular cartilage induced by degradation of proteoglycans, and to explore the effect of proteoglycans on hydration behaviour of articular cartilage by using high-frequency ultrasound. Methods Twelve porcine patellae with smooth cartilage surface were prepared and equally divided into two groups: normal group without any enzyme treatment, and trypsin group they were treated with 0.25% trypsin for 8h to digest proteoglycan in the cartilage. The hydration behaviour of the cartilage tissue was scanned by high-frequency ultrasound system with a central frequency of 25MHz. Parameters including cartilage hydration strain and cartilage thickness were measured. The histopathological changes in the articular cartilage were observed under a light microscope. Results It took approximately 20min to reach equilibrium during the hydration process in the normal cartilages, while proteoglycan-degraded cartilage took only about 5min to achieve equilibrium. The equilibrium strain of normal cartilage was 3.5%±0.5%. The degradation of proteoglycans induced a significant decrease in equilibrium strain (1.8%±0.2%, P0.05. Conclusion Proteoglycans play an important role in hydration behaviour of articular cartilage. The degradation of proteoglycans could induce degeneration of cartilage structure and decrease in hydration behaviour after dehydration. DOI: 10.11855/j.issn.0577-7402.2015.03.03

  17. Application potential of bone marrow mesenchymal stem cell (BMSCs) based tissue-engineering for spinal cord defect repair in rat fetuses with spina bifida aperta

    OpenAIRE

    Li, Xiaoshuai; Yuan, Zhengwei; Wei, Xiaowei; LI Hui; Zhao, Guifeng; Miao, Jiaoning; Wu, Di; Liu, Bo; Cao, Songying; An, Dong; Ma, Wei; Zhang, Henan; Wang, Weilin; WANG, Qiushi; Gu, Hui

    2016-01-01

    Spina bifida aperta are complex congenital malformations resulting from failure of fusion in the spinal neural tube during embryogenesis. Despite surgical repair of the defect, most patients who survive with spina bifida aperta have a multiple system handicap due to neuron deficiency of the defective spinal cord. Tissue engineering has emerged as a novel treatment for replacement of lost tissue. This study evaluated the prenatal surgical approach of transplanting a chitosan–gelatin scaffold s...

  18. Analysis of friction between articular cartilage and polyvinyl alcohol hydrogel artificial cartilage.

    Science.gov (United States)

    Li, Feng; Wang, Anmin; Wang, Chengtao

    2016-05-01

    Many biomaterials are being used to repair damaged articular cartilage. In particular, poly vinyl alcohol hydrogel has similar mechanical properties to natural cartilage under compressive and shearing loading. Here, three-factor and two-level friction experiments and long-term tests were conducted to better evaluate its tribological properties. The friction coefficient between articular cartilage and the poly vinyl alcohol hydrogel depended primarily on the three factors of load, speed, and lubrication. When the speed increased from 10 to 20 mm/s under a load of 10 N, the friction coefficient increased from 0.12 to 0.147. When the lubricant was changed from Ringer's solution to a hyaluronic acid solution, the friction coefficient decreased to 0.084 with loads as high as 22 N. The poly vinyl alcohol hydrogel was severely damaged and lost its top surface layers, which were transferred to the articular cartilage surface. Wear was observed in the surface morphologies, which indicated the occurrence of surface adhesion of bovine cartilage. Surface fatigue and adhesive wear was the dominant wear mechanism. PMID:26970769

  19. Using Stem Cells to Grow Artificial Tissue for Peripheral Nerve Repair

    Science.gov (United States)

    Bhangra, Kulraj Singh; Busuttil, Francesca

    2016-01-01

    Peripheral nerve injury continues to pose a clinical hurdle despite its frequency and advances in treatment. Unlike the central nervous system, neurons of the peripheral nervous system have a greater ability to regenerate. However, due to a number of confounding factors, this is often both incomplete and inadequate. The lack of supportive Schwann cells or their inability to maintain a regenerative phenotype is a major factor. Advances in nervous system tissue engineering technology have led to efforts to build Schwann cell scaffolds to overcome this and enhance the regenerative capacity of neurons following injury. Stem cells that can differentiate along a neural lineage represent an essential resource and starting material for this process. In this review, we discuss the different stem cell types that are showing promise for nervous system tissue engineering in the context of peripheral nerve injury. We also discuss some of the biological, practical, ethical, and commercial considerations in using these different stem cells for future clinical application.

  20. Electrospun Microfiber Scaffolds with Anti-Inflammatory Tributanoylated N-Acetyl-d-Glucosamine Promote Cartilage Regeneration.

    Science.gov (United States)

    Kim, Chaekyu; Shores, Lucas; Guo, Qiongyu; Aly, Ahmed; Jeon, Ok Hee; Kim, Do Hun; Bernstein, Nicholas; Bhattacharya, Rahul; Chae, Jemin Jeremy; Yarema, Kevin J; Elisseeff, Jennifer H

    2016-04-01

    Tissue-engineering strategies offer promising tools for repairing cartilage damage; however, these strategies suffer from limitations under pathological conditions. As a model disease for these types of nonideal systems, the inflammatory environment in an osteoarthritic (OA) joint limits the efficacy of engineered therapeutics by disrupting joint homeostasis and reducing its capacity for regeneration. In this work, we investigated a sugar-based drug candidate, a tributanoylated N-acetyl-d-glucosamine analogue, called 3,4,6-O-Bu3GlcNAc, that is known to reduce nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in osteoarthritis. 3,4,6-O-Bu3GlcNAc not only inhibited NFκB signaling but also exerted chondrogenic and anti-inflammatory effects on chondrocytes isolated from patients with osteoarthritis. 3,4,6-O-Bu3GlcNAc also increased the expression of extracellular matrix proteins and induced cartilage tissue production in three-dimensional in vitro hydrogel culture systems. To translate these chondrogenic and anti-inflammatory properties to tissue regeneration in osteoarthritis, we implanted 3,4,6-O-Bu3GlcNAc-loaded poly(lactic-co-glycolic acid) microfiber scaffolds into rats. The drug-laden scaffolds were biocompatible, and when seeded with human OA chondrocytes, similarly promoted cartilage tissue formation. 3,4,6-O-Bu3GlcNAc combined with the appropriate structural environment could be a promising therapeutic approach for osteoarthritis. PMID:27019285

  1. Cyanoacrylate tissue glue for wound repair in early posttrabeculectomy conjunctival bleb leak: a case series

    OpenAIRE

    Haslinda AR; Azhany Y; Noor-Khairul R; Zunaina E; Liza-Sharmini AT

    2015-01-01

    Abdul-Rahim Haslinda, Yaakub Azhany, Rasid Noor-Khairul, Embong Zunaina, Ahmad-Tajudin Liza-Sharmini Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia Abstract: We demonstrated a noninvasive management of early bleb leak following trabeculectomy using cyanoacrylate tissue glue (CATG). Three patients who underwent augmented trabeculectomy with mitomycin C with early bleb leak between January 2009 and June 2010 ...

  2. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.

    OpenAIRE

    Igarashi, A; Okochi, H; Bradham, D M; Grotendorst, G R

    1993-01-01

    Connective tissue growth factor (CTGF) is a cysteine-rich peptide that exhibits platelet-derived growth factor (PDGF)-like biological and immunological activities. CTGF is a member of a family of peptides that include serum-induced immediate early gene products, a v-src-induced peptide, and a putative avian transforming gene, nov. In the present study, we demonstrate that human foreskin fibroblasts produce high levels of CTGF mRNA and protein after activation with transforming growth factor b...

  3. A Reservoir of Mature Cavity Macrophages that Can Rapidly Invade Visceral Organs to Affect Tissue Repair.

    Science.gov (United States)

    Wang, Jing; Kubes, Paul

    2016-04-21

    A key feature of inflammation is the timely recruitment of leukocytes, including monocytes, from blood into tissues, the latter maturing into macrophages over a period of 2-3 days. Using multi-channel spinning disk microscopy, we identified a rapid pathway of macrophage recruitment into an injured organ via a non-vascular route requiring no maturation from monocytes. In response to a sterile injury in liver, a reservoir of fully mature F4/80(hi)GATA6(+) peritoneal cavity macrophages rapidly invaded into afflicted tissue via direct recruitment across the mesothelium. The invasion was dependent on CD44 and DAMP molecule ATP and resulted in rapid replication and switching of macrophage toward an alternatively activated phenotype. These macrophages dismantled the nuclei of necrotic cells releasing DNA and forming a cover across the injury site. Rapid invasion of mature macrophages from body cavity with capacity for induction of reparative phenotype may impact altered tissues ranging from trauma to infections to cancer. VIDEO ABSTRACT. PMID:27062926

  4. Mechanical behavior of colonic anastomosis in experimental settings as a measure of wound repair and tissue integrity

    Institute of Scientific and Technical Information of China (English)

    Konstantinos A Ekmektzoglou; Georgios C Zografos; Stavros K Kourkoulis; Ismene A Dontas; Panagiotis K Giannopoulos; Katerina A Marinou; Maria V Poulakou; Despina N Perrea

    2006-01-01

    AIM: To determine the mechanical properties of anastomotic colonic tissue in experimental settings and therefore give a measure of wound healing.METHODS: Thirty-six male Wistar rats were used as experimental models of anastomotic tissue integrity. On the 5th post-operative day, the tensile strength was measured by application of an axial force, providing a quantitative measure of anastomotic dehiscence and leakage.RESULTS: Diagrams of the load as a function of the time [P = P (t)] and of the displacement also as a function of time [△s = △s (t)] were recorded for each test,permitting the design of the load versus the displacement diagram and thus providing significant data about the critical values of anastomotic failure. Quantitative data were obtained concerning the anastomotic strength of both control specimens (healthy rats), as well as specimens from non-healthy rats for comparison.CONCLUSION: This experimental model provides an excellent method of measuring anastomotic strength.Despite the relative small number of specimens used,this method provides an accurate way of measuring wound repair. More experimental measurements need to be performed to correlate emerging tensile strength values to anastomotic failure.

  5. Namaste (counterbalancing technique: Overcoming warping in costal cartilage

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    Kapil S Agrawal

    2015-01-01

    Full Text Available Background: Indian noses are broader and lack projection as compared to other populations, hence very often need augmentation, that too by large volume. Costal cartilage remains the material of choice in large volume augmentations and repair of complex primary and secondary nasal deformities. One major disadvantage of costal cartilage grafts (CCG which offsets all other advantages is the tendency to warp and become distorted over a period of time. We propose a simple technique to overcome this menace of warping. Materials and Methods: We present the data of 51 patients of rhinoplasty done using CCG with counterbalancing technique over a period of 4 years. Results: No evidence of warping was found in any patient up to a maximum follow-up period of 4 years. Conclusion: Counterbalancing is a useful technique to overcome the problem of warping. It gives liberty to utilize even unbalanced cartilage safely to provide desired shape and use the cartilage without any wastage.

  6. Study on the Microstructure of Human Articular Cartilage/Bone Interface

    Institute of Scientific and Technical Information of China (English)

    Yaxiong Liu; Qin Lian; Jiankang He; Jinna Zhao; Zhongmin Jin; Dichen Li

    2011-01-01

    For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope (SEM), histological sections and MicroCT were used to observe, measure and model the microstructure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified cartilage and subchondral bone are in the manner of"protrusion-pore" with average diameter of 17.0 μm and 34.1 μm respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.

  7. The integrin-collagen connection--a glue for tissue repair?

    Science.gov (United States)

    Zeltz, Cédric; Gullberg, Donald

    2016-02-15

    The α1β1, α2β1, α10β1 and α11β1 integrins constitute a subset of the integrin family with affinity for GFOGER-like sequences in collagens. Integrins α1β1 and α2β1 were originally identified on a subset of activated T-cells, and have since been found to be expressed on a number of cell types including platelets (α2β1), vascular cells (α1β1, α2β1), epithelial cells (α1β1, α2β1) and fibroblasts (α1β1, α2β1). Integrin α10β1 shows a distribution that is restricted to mesenchymal stem cells and chondrocytes, whereas integrin α11β1 appears restricted to mesenchymal stem cells and subsets of fibroblasts. The bulk of the current literature suggests that collagen-binding integrins only have a limited role in adult connective tissue homeostasis, partly due to a limited availability of cell-binding sites in the mature fibrillar collagen matrices. However, some recent data suggest that, instead, they are more crucial for dynamic connective tissue remodeling events--such as wound healing--where they might act specifically to remodel and restore the tissue architecture. This Commentary discusses the recent development in the field of collagen-binding integrins, their roles in physiological and pathological settings with special emphasis on wound healing, fibrosis and tumor-stroma interactions, and include a discussion of the most recently identified newcomers to this subfamily--integrins α10β1 and α11β1. PMID:26857815

  8. Repair of segmental bone defect using Totally Vitalized tissue engineered bone graft by a combined perfusion seeding and culture system.

    Directory of Open Access Journals (Sweden)

    Lin Wang

    Full Text Available BACKGROUND: The basic strategy to construct tissue engineered bone graft (TEBG is to combine osteoblastic cells with three dimensional (3D scaffold. Based on this strategy, we proposed the "Totally Vitalized TEBG" (TV-TEBG which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. METHODS: In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP scaffold fabricated by Rapid Prototyping (RP technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC method, static seeding and perfusion culture (SSPC method, and static seeding and static culture (SSSC method for their in vitro performance and bone defect healing efficacy with a rabbit model. RESULTS: Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. CONCLUSION: This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and

  9. Zn deposition at the bone cartilage interface in equine articular cartilage

    Science.gov (United States)

    Bradley, D. A.; Moger, C. J.; Winlove, C. P.

    2007-09-01

    In articular cartilage metalloproteinases, a family of enzymes whose function relies on the presence of divalent cations such as Zn and Ca plays a central role in the normal processes of growth and remodelling and in the degenerative and inflammatory processes of arthritis. Another important enzyme, alkaline phosphatase, involved in cartilage mineralisation also relies on metallic cofactors. The local concentration of divalent cations is therefore of considerable interest in cartilage pathophysiology and several authors have used synchrotron X-ray fluorescence (XRF) to map metal ion distributions in bone and cartilage. We report use of a bench-top XRF analytical microscope, providing spatial resolution of 10 μm and applicable to histological sections, facilitating correlation of the distribution with structural features. The study seeks to establish the elemental distribution in normal tissue as a precursor to investigation of changes in disease. For six samples prepared from equine metacarpophalangeal joint, we observed increased concentration of Zn and Sr ions around the tidemark between normal and mineralised cartilage. This is believed to be an active site of remodelling but its composition has hitherto lacked detailed characterization. We also report preliminary results on two of the samples using Proton-Induced X-ray Emission (PIXE). This confirms our previous observations using synchrotron-based XRF of enhanced deposition of Sr and Zn at the surface of the subchondral bone and in articular cartilage.

  10. Zn deposition at the bone-cartilage interface in equine articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, D.A. [Department of Physics, University of Surrey, Guildford, GU2 7XH (United Kingdom)], E-mail: D.A.Bradley@surrey.ac.uk; Moger, C.J.; Winlove, C.P. [School of Physics, University of Exeter, Exeter, EX4 4QL (United Kingdom)

    2007-09-21

    In articular cartilage metalloproteinases, a family of enzymes whose function relies on the presence of divalent cations such as Zn and Ca plays a central role in the normal processes of growth and remodelling and in the degenerative and inflammatory processes of arthritis. Another important enzyme, alkaline phosphatase, involved in cartilage mineralisation also relies on metallic cofactors. The local concentration of divalent cations is therefore of considerable interest in cartilage pathophysiology and several authors have used synchrotron X-ray fluorescence (XRF) to map metal ion distributions in bone and cartilage. We report use of a bench-top XRF analytical microscope, providing spatial resolution of 10 {mu}m and applicable to histological sections, facilitating correlation of the distribution with structural features. The study seeks to establish the elemental distribution in normal tissue as a precursor to investigation of changes in disease. For six samples prepared from equine metacarpophalangeal joint, we observed increased concentration of Zn and Sr ions around the tidemark between normal and mineralised cartilage. This is believed to be an active site of remodelling but its composition has hitherto lacked detailed characterization. We also report preliminary results on two of the samples using Proton-Induced X-ray Emission (PIXE). This confirms our previous observations using synchrotron-based XRF of enhanced deposition of Sr and Zn at the surface of the subchondral bone and in articular cartilage.

  11. Zn deposition at the bone-cartilage interface in equine articular cartilage

    International Nuclear Information System (INIS)

    In articular cartilage metalloproteinases, a family of enzymes whose function relies on the presence of divalent cations such as Zn and Ca plays a central role in the normal processes of growth and remodelling and in the degenerative and inflammatory processes of arthritis. Another important enzyme, alkaline phosphatase, involved in cartilage mineralisation also relies on metallic cofactors. The local concentration of divalent cations is therefore of considerable interest in cartilage pathophysiology and several authors have used synchrotron X-ray fluorescence (XRF) to map metal ion distributions in bone and cartilage. We report use of a bench-top XRF analytical microscope, providing spatial resolution of 10 μm and applicable to histological sections, facilitating correlation of the distribution with structural features. The study seeks to establish the elemental distribution in normal tissue as a precursor to investigation of changes in disease. For six samples prepared from equine metacarpophalangeal joint, we observed increased concentration of Zn and Sr ions around the tidemark between normal and mineralised cartilage. This is believed to be an active site of remodelling but its composition has hitherto lacked detailed characterization. We also report preliminary results on two of the samples using Proton-Induced X-ray Emission (PIXE). This confirms our previous observations using synchrotron-based XRF of enhanced deposition of Sr and Zn at the surface of the subchondral bone and in articular cartilage

  12. Simultaneous Magnetic Resonance Imaging and Consolidation Measurement of Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Robert Mark Wellard

    2014-05-01

    Full Text Available Magnetic resonance imaging (MRI offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP. MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer.

  13. Cyanoacrylate tissue glue for wound repair in early posttrabeculectomy conjunctival bleb leak: a case series

    Directory of Open Access Journals (Sweden)

    Haslinda AR

    2015-07-01

    Full Text Available Abdul-Rahim Haslinda, Yaakub Azhany, Rasid Noor-Khairul, Embong Zunaina, Ahmad-Tajudin Liza-Sharmini Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia Abstract: We demonstrated a noninvasive management of early bleb leak following trabeculectomy using cyanoacrylate tissue glue (CATG. Three patients who underwent augmented trabeculectomy with mitomycin C with early bleb leak between January 2009 and June 2010 were reviewed. Case 1 and Case 2 exhibited bleb leak on postoperative Day 1 and Case 3 showed leak on follow-up at postoperative Day 7. Case 1 was successfully sealed with CATG at postoperative Day 3, after failed pressure padding and bandage contact lens. Case 2 was successfully sealed with CATG at postoperative Day 3, after failed pressure padding and conjunctiva flap resuturing. In Case 3, the leaking conjunctival flap was managed with combined techniques of resuturing and applying CATG at postoperative Day 9, after failed pressure padding. During leakage, the intraocular pressure was low (6–8 mmHg in all three cases, with shallow anterior chamber depth and absence of other complications such as choroidal detachment, hypotony maculopathy, or endophthalmitis. Foreign body sensation was the main complaint following the procedure. No clinical allergy reaction was documented. CATG may serve as a potential adjunctive and effective method in the management of posttrabeculectomy early bleb leak. Keywords: cyanoacrylate tissue glue, bleb leak, trabeculectomy, mitomycin C

  14. The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth

    Directory of Open Access Journals (Sweden)

    Han Zhipeng

    2012-03-01

    Full Text Available Abstract Mesenchymal stem cells (MSCs have acquired great interests for their potential use in the clinical therapy of many diseases because of their functions including multiple lineage differentiation, low immunogenicity and immunosuppression. Many studies suggest that MSCs are strongly immunosuppressive in vitro and in vivo. MSCs exert a profound inhibitory effect on the proliferation of T cells, B cells, dendritic cells and natural killer cells. In addition, several soluble factors have been reported to involved in the immunosuppressive effects by MSCs such as TGF-β, HGF, PGE2, IDO and iNOS. These results suggest that MSCs can be used in the therapy of immune disorder diseases, prevention of organ transplantation rejection and tissue injury. In recent study, we demonstrated that MSCs in tumor inflammatory microenvironment might be elicited of immunosuppressive function. Thus, the application of MSCs in cancer therapy might have negative effect by helping tumor cells escaping from the immune surveillance.

  15. DNA double strand break repair pathway plays a significant role in determining the radiotherapy induced normal tissue toxicity among head-and-neck and breast cancer

    International Nuclear Information System (INIS)

    The ability to predict individual risk of radiotherapy induced normal tissue complications prior to the therapy may give an opportunity to personalize the treatment aiming improved therapeutic effect and quality of life. Therefore, predicting the risk of developing acute reactions before the initiation of radiation therapy may serve as a potential biomarker. DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of Head-and-Neck (n = 183) and Breast cancer (n = 132) patients undergoing chemoradiation or radiation therapy alone were analyzed by performing γ-H2AX foci, neutral comet and a modified neutral filter elution assay. Candidate radioresponsive genes like DNA repair, antioxidant pathway, profibrotic cytokine genes were screened for the common variants for their association with normal tissue toxicity outcome. Patients were stratified as non-over responders (NOR) and over responders (OR) based on their Radiation Therapy Oncology Group grading for normal tissue adverse reactions. Our results suggest that DSB repair plays a major role in the development of normal tissue a