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Sample records for cartilage repair tissue

  1. Repairing articular cartilage defects with tissue-engineering cartilage in rabbits

    Institute of Scientific and Technical Information of China (English)

    SONG Hong-xing; LI Fo-bao; SHEN Hui-liang; LIAO Wei-ming; LIU Miao; WANG Min; CAO Jun-ling

    2006-01-01

    Objective: To investigate the effect of cancellous bone matrix gelatin (BMG) engineered with allogeneic chondrocytes in repairing articular cartilage defects in rabbits.Methods: Chondrocytes were seeded onto three-dimensional cancellous BMG and cultured in vitro for 12 days to prepare BMG-chondrocyte complexes. Under anesthesia with 2.5% pentobarbital sodium (1 ml/kg body weight), articular cartilage defects were made on the right knee joints of 38 healthy New Zealand white rabbits (regardless of sex, aged 4-5 months and weighing 2.5-3 kg) and the defects were then treated with 2.5 % trypsin.Then BMG-chondrocyte complex (Group A, n=18 ),BMG ( Group B, n=10), and nothing ( Group C, n=10)were implanted into the cartilage defects, respectively. The repairing effects were assessed by macroscopic, histologic,transmission electron microscopic (TEM) observation,immunohistochemical examination and in situ hybridization detection, respectively, at 2, 4, 8, 12 and 24 weeks after operation.Results: Cancellous BMG was degraded within 8 weeks after operation. In Group A, lymphocyte infiltration was observed around the graft. At 24 weeks after operation, the cartilage defects were repaired by cartilage tissues and the articular cartilage and subchondral bone were soundly healed. Proteoglycan and type Ⅱ collagen were detected in the matrix of the repaired tissues by Safranin-O staining and immunohistochemical staining,respectively. In situ hybridization proved gene expression of type Ⅱ collagen in the cytoplasm of chondrocytes in the repaired tissues. TEM observation showed that chondrocytes and cartilage matrix in repaired tissues were almost same as those in the normal articular cartilage. In Group B, the defects were repaired by cartilage-fibrous tissues. In Group C, the defects were repaired only by fibrous tissues.Conclusions : Cancellous BMG can be regarded as the natural cell scaffolds for cartilage tissue engineering.Articular cartilage defects can be repaired by

  2. 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...

  3. 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.

  4. 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...

  5. Quantitative assessment of optical properties in healthy cartilage and repair tissue by optical coherence tomography and histology (Conference Presentation)

    Science.gov (United States)

    Jansen, Sanne M. A.; Cernohorsky, Paul; de Bruin, Daniel M.; van der Pol, Edwin; Savci-Heijink, Cemile D.; Strackee, Simon D.; Faber, Dirk J.; van Leeuwen, Ton G.

    2016-02-01

    Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, repair tissue, bone and layers within repair tissue in a controlled setting. OCT and histology was used to assess goat talus articular surfaces in which central osteochondral defects were created. Exact matches of OCT and histology were selected for research. μOCT measurements were taken from healthy cartilage, repair tissue and bone. Measured μOCT in healthy cartilage was higher compared to both repair tissue and bone tissue. Two possible mechanisms for the difference in attenuation were investigated. We studied morphological parameters in terms of nucleus count, nucleus size and inter-nucleus distance. Collagen content in healthy cartilage and repair tissue was assessed using polarization microscopy. Quantitative analysis of the nuclei did not demonstrate a difference in nucleus size and count between healthy cartilage and repair tissue. In healthy cartilage, cells were spaced farther apart and had a lower variation in local nuclear density compared to repair tissue. Polarization microscopy suggested higher collagen content in healthy cartilage compared to repair tissue. μOCT measurements can distinguish between healthy cartilage, repair tissue and bone. Results suggest that cartilage OCT attenuation measurements could be of great impact in clinical diagnostics of osteoarthritis.

  6. 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...

  7. 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.

  8. Biomaterial and Cell Based Cartilage Repair

    NARCIS (Netherlands)

    Zhao, X

    2015-01-01

    Injuries to human native cartilage tissue are particularly troublesome because cartilage has little ability to heal or regenerate itself. The reconstruction, repair, and regeneration of cartilage tissue continue to be one of the greatest clinical challenges, especially in orthopaedic and plastic sur

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

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    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.

  10. 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.

  11. 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

  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. Cartilage Repair Surgery: Outcome Evaluation by Using Noninvasive Cartilage Biomarkers Based on Quantitative MRI Techniques?

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    Pia M. Jungmann

    2014-01-01

    Full Text Available Background. New quantitative magnetic resonance imaging (MRI techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC, and diffusion weighted imaging (DWI are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair.

  14. 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...

  15. Cartilage repair: Generations of autologous chondrocyte transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Marlovits, Stefan [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail: stefan.marlovits@meduniwien.ac.at; Zeller, Philip [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Singer, Philipp [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Resinger, Christoph [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Vecsei, Vilmos [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-01-15

    Articular cartilage in adults has a limited capacity for self-repair after a substantial injury. Surgical therapeutic efforts to treat cartilage defects have focused on delivering new cells capable of chondrogenesis into the lesions. Autologous chondrocyte transplantation (ACT) is an advanced cell-based orthobiologic technology used for the treatment of chondral defects of the knee that has been in clinical use since 1987 and has been performed on 12,000 patients internationally. With ACT, good to excellent clinical results are seen in isolated post-traumatic lesions of the knee joint in the younger patient, with the formation of hyaline or hyaline-like repair tissue. In the classic ACT technique, chondrocytes are isolated from small slices of cartilage harvested arthroscopically from a minor weight-bearing area of the injured knee. The extracellular matrix is removed by enzymatic digestion, and the cells are then expanded in monolayer culture. Once a sufficient number of cells has been obtained, the chondrocytes are implanted into the cartilage defect, using a periosteal patch over the defect as a method of cell containment. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. Further improvements in tissue engineering have contributed to the next generation of ACT techniques, where cells are combined with resorbable biomaterials, as in matrix-associated autologous chondrocyte transplantation (MACT). These biomaterials secure the cells in the defect area and enhance their proliferation and differentiation.

  16. Tissue engineering strategies to study cartilage development, degeneration and regeneration.

    Science.gov (United States)

    Bhattacharjee, Maumita; Coburn, Jeannine; Centola, Matteo; Murab, Sumit; Barbero, Andrea; Kaplan, David L; Martin, Ivan; Ghosh, Sourabh

    2015-04-01

    Cartilage tissue engineering has primarily focused on the generation of grafts to repair cartilage defects due to traumatic injury and disease. However engineered cartilage tissues have also a strong scientific value as advanced 3D culture models. Here we first describe key aspects of embryonic chondrogenesis and possible cell sources/culture systems for in vitro cartilage generation. We then review how a tissue engineering approach has been and could be further exploited to investigate different aspects of cartilage development and degeneration. The generated knowledge is expected to inform new cartilage regeneration strategies, beyond a classical tissue engineering paradigm.

  17. Stem Cell-assisted Approaches for Cartilage Tissue Engineering

    OpenAIRE

    Park, In-Kyu; Cho, Chong-Su

    2010-01-01

    The regeneration of damaged articular cartilage remains challenging due to its poor intrinsic capacity for repair. Tissue engineering of articular cartilage is believed to overcome the current limitations of surgical treatment by offering functional regeneration in the defect region. Selection of proper cell sources and ECM-based scaffolds, and incorporation of growth factors or mechanical stimuli are of primary importance to successfully produce artificial cartilage for tissue repair. When d...

  18. Connective tissue growth factor and articular cartilage repair%结缔组织生长因子与关节软骨的修复

    Institute of Scientific and Technical Information of China (English)

    张世松; 张志峰; 黄健

    2015-01-01

    BACKGROUND:Connective tissue growth factor has the potential to stimulate the differentiation of mesenchymal cels into chondrocytes, can promote the proliferation and differentiation of chondrocytes, and also can promote the expression of type II colagen and proteoglycan in the articular cartilage. So, the connective tissue growth factor plays an important role in the articular cartilage repair along with other growth factors. OBJECTIVE: To focus on the structure of connective tissue growth factor, its function in articular cartilage repair and the interactions with other factors. METHODS: A search across the databases of PubMed (January 1980 to July 2014) was performed, with the key words of “connective tissue growth factor, connective tissue growth factor and articular cartilage, articular cartilage damage, articular cartilage repairment” in English and “articular cartilage injury” in Chinese. Studies with the obsolete, repetitive or unrelated content were excluded. A total of 32 papers were included in thi study. RESULTS AND CONCLUSION: Connective tissue growth factor has the potential to stimulate the differentiation of mesenchymal cels into chondrocytes, can promote the proliferation, differentiation and maturity of chondrocytes, can maintain the extracelular matrix synthesis and balance, and also can promote the expression of type II colagen and proteoglycan in the articular cartilage. Along with other growth factors, connective tissue growth factor exerts an important role in the articular cartilage repair. Connective tissue growth factor is the key factor of chondrocyte growth, proliferation and differentiation, which is throughout the process of cartilage repair. Studies have shown that articular chondrocytes from patients with osteoarthritis show an increase in the number positively correlated with the expressions of fibroblast growth factor 1 and connective tissue growth factor. Connective tissue growth factor interacts with articular cartilage

  19. 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.

  20. 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

  1. Stem Cell-assisted Approaches for Cartilage Tissue Engineering.

    Science.gov (United States)

    Park, In-Kyu; Cho, Chong-Su

    2010-05-01

    The regeneration of damaged articular cartilage remains challenging due to its poor intrinsic capacity for repair. Tissue engineering of articular cartilage is believed to overcome the current limitations of surgical treatment by offering functional regeneration in the defect region. Selection of proper cell sources and ECM-based scaffolds, and incorporation of growth factors or mechanical stimuli are of primary importance to successfully produce artificial cartilage for tissue repair. When designing materials for cartilage tissue engineering, biodegradability and biocompatibility are the key factors in selecting material candidates, for either synthetic or natural polymers. The unique environment of cartilage makes it suitable to use a hydrogel with high water content in the cross-linked or thermosensitive (injectable) form. Moreover, design of composite scaffolds from two polymers with complementary physicochemical and biological properties has been explored to provide residing chondrocytes with a combination of the merits that each component contributes.

  2. 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

  3. The Application of Sheet Technology in Cartilage Tissue Engineering.

    Science.gov (United States)

    Ge, Yang; Gong, Yi Yi; Xu, Zhiwei; Lu, Yanan; Fu, Wei

    2016-04-01

    Cartilage tissue engineering started to act as a promising, even essential alternative method in the process of cartilage repair and regeneration, considering adult avascular structure has very limited self-renewal capacity of cartilage tissue in adults and a bottle-neck existed in conventional surgical treatment methods. Recent progressions in tissue engineering realized the development of more feasible strategies to treat cartilage disorders. Of these strategies, cell sheet technology has shown great clinical potentials in the regenerative areas such as cornea and esophagus and is increasingly considered as a potential way to reconstruct cartilage tissues for its non-use of scaffolds and no destruction of matrix secreted by cultured cells. Acellular matrix sheet technologies utilized in cartilage tissue engineering, with a sandwich model, can ingeniously overcome the drawbacks that occurred in a conventional acellular block, where cells are often blocked from migrating because of the non-nanoporous structure. Electrospun-based sheets with nanostructures that mimic the natural cartilage matrix offer a level of control as well as manipulation and make them appealing and widely used in cartilage tissue engineering. In this review, we focus on the utilization of these novel and promising sheet technologies to construct cartilage tissues with practical and beneficial functions. PMID:26414455

  4. 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

  5. Lineage plasticity and cell biology of fibrocartilage and hyaline cartilage: Its significance in cartilage repair and replacement

    Energy Technology Data Exchange (ETDEWEB)

    Freemont, Anthony J. [Regenerative Medicine Research Group, University of Manchester, England (United Kingdom)]. E-mail: Tony.freemont@man.ac.uk; Hoyland, Judith [Regenerative Medicine Research Group, University of Manchester, England (United Kingdom)

    2006-01-15

    Cartilage repair is a major goal of modern tissue engineering. To produce novel engineered implants requires a knowledge of the basic biology of the tissues that are to be replaced or reproduced. Hyaline articular cartilage and meniscal fibrocartilage are two tissues that have excited attention because of the frequency with which they are damaged. A basic strategy is to re-engineer these tissues ex vivo by stimulating stem cells to differentiate into the cells of the mature tissue capable of producing an intact functional matrix. In this brief review, the sources of cells for tissue engineering cartilage and the culture conditions that have promoted differentiation are discussed within the context of natural cartilage repair. In particular, the role of cell density, cytokines, load, matrices and oxygen tension are discussed.

  6. Mechanobiology and Cartilage Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Céline; HUSELSTEIN; Natalia; de; ISLA; Sylvaine; MULLER; Jean-Franois; STOLTZ

    2005-01-01

    1 IntroductionThe cartilage is a hydrated connective tissue in joints that withstands and distributes mechanical forces. Chondrocytes utilize mechanical signals to maintain tissue homeostasis. They regulate their metabolic activity through complex biological and biophysical interactions with the extracellular matrix (ECM). Although some of the mechanisms of mechanotransduction are known today, there are certainly many others left unrevealed. Different topics of chondrocytes mechanobiology have led to the de...

  7. Composite scaffolds for cartilage tissue engineering.

    Science.gov (United States)

    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 functions 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 crucial role in determining the functional properties of engineered tissues, including biomechanical characteristics such as inhomogeneity, anisotropy, nonlinearity or viscoelasticity. While single-phase, homogeneous materials have been used extensively to create numerous types of tissue constructs, there continue to be significant challenges in the development of scaffolds that can provide the functional properties of load-bearing tissues such as articular cartilage. In an attempt to create more complex scaffolds that promote the regeneration of functional engineered tissues, composite scaffolds comprising two or more distinct materials have been developed. This paper reviews various studies on the development and testing of composite scaffolds for the tissue engineering of articular cartilage, using techniques such as embedded fibers and textiles for reinforcement, embedded solid structures, multi-layered designs, or three-dimensionally woven composite materials. In many cases, the use of composite scaffolds can provide unique biomechanical and biological properties for the development of functional tissue engineering scaffolds.

  8. Spectrocolorimetric evaluation of repaired articular cartilage after a microfracture

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    Dohi Yoshihiro

    2008-09-01

    Full Text Available Abstract Background In clinical practice, surgeons differentiate color changes in repaired cartilage compared with surrounding intact cartilage, but cannot quantify these color changes. Objective assessments are required. A spectrocolorimeter was used to evaluate whether intact and repaired cartilage can be quantified. Findings We investigated the use of a spectrocolorimeter and the application of two color models (L* a* b* colorimetric system and spectral reflectance distribution to describe and quantify articular cartilage. In this study, we measured the colors of intact and repaired cartilage after a microfracture. Histologically, the repaired cartilage was a mixture of fibrocartilage and hyaline cartilage. In the L* a* b* colorimetric system, the L* and a* values recovered to close to the values of intact cartilage, whereas the b* value decreased over time after the operation. Regarding the spectral reflectance distribution at 12 weeks after the operation, the repaired cartilage had a higher spectral reflectance ratio than intact cartilage between wavelengths of 400 to 470 nm. Conclusion This study reports the first results regarding the relationship between spectrocolorimetric evaluation and the histological findings of repair cartilage after a microfracture. Our findings demonstrate the ability of spectrocolorimetric measurement to judge the repair cartilage after treatment on the basis of objective data such as the L*, a* and b* values and the SRP as a coincidence index of the spectral reflectance curve.

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

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    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.

  10. Evidence of cartilage repair by joint distraction in a canine model of osteoarthritis

    NARCIS (Netherlands)

    Wiegant, Karen; Intema, Femke; Van Roermund, Peter M.; Barten-Van Rijbroek, Angelique D.; Doornebal, Arie; Hazewinkel, Herman A W; Lafeber, Floris P J G; Mastbergen, Simon C.

    2015-01-01

    Objective. Knee osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage, bone, and synovial tissue changes that lead to pain and functional impairment. Joint distraction is a treatment that provides long-term improvement in pain and function accompanied by cartilage repair, a

  11. 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...

  12. 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.

  13. 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

  14. 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

  15. Cartilage change after arthroscopic repair for an isolated meniscal tear.

    Science.gov (United States)

    Soejima, Takashi; Murakami, Hidetaka; Inoue, Takashi; Kanazawa, Tomonoshin; Katouda, Michihiro; Nagata, Kensei

    2005-01-01

    To investigate the direct effect to the cartilage caused by the meniscal repair, we examined patients who underwent an isolated meniscal repair without any other abnormalities by arthroscopic examination. A total of 17 patients were examined by second-look arthroscopy after an average interval of 9 months from the meniscal repair, and have been evaluated the status of the repaired meniscus and of the relative femoral condylar cartilage. Changes in the severity of the cartilage lesion between at the time of meniscal repair and the time of the second-look arthroscopy were considered based on the status of the repaired meniscus. Regardless of the healing status of the repair site, it was possible to prevent degeneration in the cartilage in 9 of the 10 patients who demonstrated no degeneration in the meniscal body. Of the 7 patients who demonstrated degeneration in the meniscal body, progression in cartilage degeneration was noted as 1 grade in 2 patients and 2 grades in another 3 patients. Even in those in which stable fusion of the repair site was achieved, the condition of the inner meniscal body was not necessarily maintained favorably in all cases, indicating that degeneration in the meniscal body was a risk factor for cartilage degeneration. It was concluded that recovery could not be expected even at 9 months after the repair if the lesion had already demonstrated degeneration in the meniscal body at the time of repair.

  16. Experimental articular cartilage repair in the Göttingen minipig

    DEFF Research Database (Denmark)

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

    2015-01-01

    repair techniques and evaluating the use of two defects per knee. METHODS: Sixteen fully mature Göttingen minipigs were used. The minipigs received bilateral trochlear osteochondral drill-hole defects or chondral defects (Ø 6 mm), either one defect per knee or two defects per knee. The defects were...... treated with one of the following: Matrix-induced autologous chondrocyte implantation (MACI), microfracture (MFx), autologous-dual-tissue transplantation (ADTT), autologous bone graft, autologous cartilage chips. Empty chondral and osteochondral defects were used as controls. MRI and CT were performed 3...

  17. 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...

  18. Repair of articular cartilage defects in rabbits through tissue-engineered cartilage constructed with chitosan hydrogel and chondrocytes%新型壳聚糖水凝胶结合软骨细胞修复兔关节软骨缺损的实验研究

    Institute of Scientific and Technical Information of China (English)

    Ming ZHAO; Zhu CHEN; Kang LIU; Yu-qing WAN; Xu-dong LI; Xu-wei LUO; Yi-guang BAI; Ze-long YANG; Gang FENG

    2015-01-01

    Objective: In our previous work, we prepared a type of chitosan hydrogel with excelent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Methods: Chitosan hydrogels were prepared with a crosslinker formed by com-bining 1,6-disocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondro-cytes that had been cultured for one weekin vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups: the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologicaly and immuno-histochemicaly. The repairs were scored according to the international cartilage repair society (ICRS) standard. Results: The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups (P  创新点:利用自主研发的具有良好生物相容性和稳定性的壳聚糖水凝胶与软骨细胞,在体外初步构建组织工程软骨,并尝试利用其修复缺损的关节软骨,从而为关节软骨缺损的修复提供了一种新的治疗方法。  方法:取兔肋软骨体外培养扩增,获得P2代软骨细胞,将其种植到冻干的壳聚糖水凝胶上,体

  19. 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.)

  20. A high throughput mechanical screening device for cartilage tissue engineering.

    Science.gov (United States)

    Mohanraj, Bhavana; Hou, Chieh; Meloni, Gregory R; Cosgrove, Brian D; Dodge, George R; Mauck, Robert L

    2014-06-27

    Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome, given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying 'hits', or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput.

  1. Uninduced adipose-derived stem cells repair the defect of full-thickness hyaline cartilage

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hai-ning; LI Lei; LENG Ping; WANG Ying-zhen; Lü Cheng-yu

    2009-01-01

    Objective: To testify the effect of the stem cells derived from the widely distributed fat tissue on repairing full-thickness hyaline cartilage defects.Methods: Adipose-derived stem cells (ADSCs) were derived from adipose tissue and cultured in vitro.Twentyseven New Zealand white rabbits were divided into three groups randomly.The cultured ADSCs mixed with calcium alginate gel were used to fill the full-thickness hyaline cartilage defects created at the patellafemoral joint,and the defects repaired with gel or without treatment served as control groups.After 4,8 and 12 weeks,the reconstructed tissue was evaluated macroscopically and microscopically.Histological analysis and qualitative scoring were also performed to detect the outcome.Results: Full thickness hyaline cartilage defects were repaired completely with ADSCs-derived dssue.The result was better in ADSCs group than the control ones.The microstructure of reconstructed tissue with ADSCs was similar to that of hvaline cartilage and contained more cells and regular matrix fibers,being better than other groups.Plenty of collagen fibers around cells could be seen under transmission electron microscopy.Statistical analysis revealed a significant difference in comparison with other groups at each time point(t=4.360,P<0.01).Conclusion: Thcse results indicate that stem cells derived from mature adipose without induction possess the ability to repair cartilage defects

  2. Nanofibrous poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate) scaffolds provide a functional microenvironment for cartilage repair.

    Science.gov (United States)

    Ching, Kuan Y; Andriotis, Orestis G; Li, Siwei; Basnett, Pooja; Su, Bo; Roy, Ipsita; Tare, Rahul S; Sengers, Bram G; Stolz, Martin

    2016-07-01

    Articular cartilage defects, when repaired ineffectively, often lead to further deterioration of the tissue, secondary osteoarthritis and, ultimately, joint replacement. Unfortunately, current surgical procedures are unable to restore normal cartilage function. Tissue engineering of cartilage provides promising strategies for the regeneration of damaged articular cartilage. As yet, there are still significant challenges that need to be overcome to match the long-term mechanical stability and durability of native cartilage. Using electrospinning of different blends of biodegradable poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate), we produced polymer scaffolds and optimised their structure, stiffness, degradation rates and biocompatibility. Scaffolds with a poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate) ratio of 1:0.25 exhibit randomly oriented fibres that closely mimic the collagen fibrillar meshwork of native cartilage and match the stiffness of native articular cartilage. Degradation of the scaffolds into products that could be easily removed from the body was indicated by changes in fibre structure, loss of molecular weight and a decrease in scaffold stiffness after one and four months. Histological and immunohistochemical analysis after three weeks of culture with human articular chondrocytes revealed a hyaline-like cartilage matrix. The ability to fine tune the ultrastructure and mechanical properties using different blends of poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate) allows to produce a cartilage repair kit for clinical use to reduce the risk of developing secondary osteoarthritis. We further suggest the development of a toolbox with tailor-made scaffolds for the repair of other tissues that require a 'guiding' structure to support the body's self-healing process.

  3. Advances in mesenchymal stem cell-based strategies for cartilage repair and regeneration.

    Science.gov (United States)

    Toh, Wei Seong; Foldager, Casper Bindzus; Pei, Ming; Hui, James Hoi Po

    2014-10-01

    Significant research efforts have been undertaken in the last decade in the development of stem cell-based therapies for cartilage repair. Among the various stem cell sources, mesenchymal stem cells (MSCs) demonstrate great promise and clinical efficacy in cartilage regeneration. With a deeper understanding of stem cell biology, new therapeutics and new bioengineering approaches have emerged and showed potential for further developments. Of note, there has been a paradigm shift in applying MSCs for tissue regeneration from the use of stem cells for transplantation to the use of stem cell-derived matrix and secretome components as therapeutic tools and agents for cartilage regeneration. In this review, we will discuss the emerging role of MSCs in cartilage regeneration and the most recent advances in development of stem cell-based therapeutics for cartilage regeneration.

  4. Is the repair of articular cartilage lesion by costal chondrocyte transplantation donor age-dependent? An experimental study in rabbits.

    Directory of Open Access Journals (Sweden)

    Janusz Popko

    2006-09-01

    Full Text Available The repair of chondral injuries is a very important problem and a subject of many experimental and clinical studies. Different techniques to induce articular cartilage repair are under investigation. In the present study, we have investigated whether the repair of articular cartilage folowing costal chondrocyte transplantation is donor age-dependent. Transplantation of costal chondrocytes from 4- and 24-week old donors, with artificially induced femoral cartilage lesion, was performed on fourteen 20-week-old New Zealand White male rabbits. In the control group, the lesion was left without chondrocyte transplantation. The evaluation of the cartilage repair was performed after 12 weeks of transplantation. We analyzed the macroscopic and histological appearance of the newly formed tissue. Immunohistochemistry was also performed using monoclonal antibodies against rabbit collagen type II. The newly formed tissue had a hyaline-like appearance in most of the lesions after chondrocyte transplantation. Positive immunohistochemical reaction for collagen II was also observed in both groups with transplanted chondrocytes. Cartilage from adult donors required longer isolation time and induced slightly poorer repair. However, hyaline-like cartilage was observed in most specimens from this group, in contrast to the control group, where fibrous connective tissue filled the lesions. Rabbit costal chondrocytes seem to be a potentially useful material for inducing articular cartilage repair and, even more important, they can also be derived from adult, sexually mature animals.

  5. Differentiating the extent of cartilage repair in rabbit ears using nonlinear optical microscopy.

    Science.gov (United States)

    Zhu, X Q; Xu, Y H; Liao, C X; Liu, W G; Cheng, K K; Chen, J X

    2015-11-01

    Nonlinear optical microscopy (NLOM) was used as a noninvasive and label-free tool to detect and quantify the extent of the cartilage recovery. Two cartilage injury models were established in the outer ears of rabbits that created a different extent of cartilage recovery based on the presence or absence of the perichondrium. High-resolution NLOM images were used to measure cartilage repair, specifically through spectral analysis and image texture. In contrast to a wound lacking a perichondrium, wounds with intact perichondria demonstrated significantly larger TPEF signals from cells and matrix, coarser texture indicating the more deposition of type I collagen. Spectral analysis of cells and matrix can reveal the matrix properties and cell growth. In addition, texture analysis of NLOM images showed significant differences in the distribution of cells and matrix of repaired tissues with or without perichondrium. Specifically, the decay length of autocorrelation coefficient based on TPEF images is 11.2 ± 1.1 in Wound 2 (with perichondrium) and 7.5 ± 2.0 in Wound 1 (without perichondrium), indicating coarser image texture and faster growth of cells in repaired tissues with perichondrium (p < 0.05). Moreover, the decay length of autocorrelation coefficient based on collagen SHG images also showed significant difference between Wound 2 and 1 (16.2 ± 1.2 vs. 12.2 ± 2.1, p < 0.05), indicating coarser image texture and faster deposition of collagen in repaired tissues with perichondrium (Wound 2). These findings suggest that NLOM is an ideal tool for studying cartilage repair, with potential applications in clinical medicine. NLOM can capture macromolecular details and distinguish between different extents of cartilage repair without the need for labelling agents.

  6. 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.

  7. Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury.

    Science.gov (United States)

    Man, Zhentao; Hu, Xiaoqing; Liu, Zhenlong; Huang, Hongjie; Meng, Qingyang; Zhang, Xin; Dai, Linghui; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Zhou, Chunyan; Ao, Yingfang

    2016-11-01

    Cartilage tissue engineering is the hotspot of cartilage repair. The allogenic chondrocytes appear to be a promising source of seed cells in cartilage tissue engineering. In this study, we aimed to transplant allogenic chondrocytes with chitosan hydrogel (CS)-demineralized bone matrix (DBM) hybrid scaffold (CS/DBM) to repair rabbit cartilage injury with one-step operation. After the CS/DBM scaffold was successfully fabricated, it showed that the porous CS filled the large pores of DBM, which improved the distribution of seed cells in the CS/DBM scaffold. The allogenic chondrocytes at second passage were transplanted with different scaffolds to repair rabbit cartilage injury. Twenty-four weeks after surgery, the cartilage defect in the CS/DBM group was successfully filled as shown by MRI. Moreover, the histological score of CS/DBM group was significantly higher than that of the other groups. On the aspect of biomechanical property, the regenerated cartilage in the CS/DBM group were superior to those in the other groups as determined by nanoindentation. Meanwhile, no obvious inflammatory response was observed after the transplantation of allogenic chondrocytes at 24 weeks post-surgery. Furtherly, gene expression profile for cells within the repair tissue was compared with the allogenic chondrocytes before transplantation using Agilent microarray and RT-qPCR. The results showed that some genes beneficial to cartilage regeneration, such as BMP-7, HGF, and IGF-1, were upregulated one month after transplantation. Consequently, our study demonstrated that the transplantation of allogenic chondrocytes with CS/DBM scaffold successfully repaired rabbit cartilage injury with only one-step operation, thereby providing new insights into cartilage tissue engineering. PMID:27636153

  8. Tissue engineering technology and biomaterials for repair of sports articular cartilage injury%组织工程技术及生物材料修复运动性关节软骨损伤

    Institute of Scientific and Technical Information of China (English)

    马金玉; 薛媛; 杨洪武

    2011-01-01

    January 1993 to October 2010 was performed for related articles, using "articular cartilage, tissue engineering technology, biomaterials" for the Chinese key words and "tissue engineering, articular cartilage, scaffold material" for the English key words, duplicated research or Meta analysis were eliminated. Twenty-three papers mainly discuss seed cells,scaffolds, cytokines and their properties in the repair of sports articular cartilage injury.RESULTS : Totally 104 studies were screened out by computer search, according to inclusion and exclusion criteria, studies regarding the seed cells and bio-scaffolds for cartilage tissue engineering, as well as cytokines for tissue engineering were summarized and analyzed. Seed cells are the primary factor restricting clinical application of tissue engineered cartilage, the common seed cells include cartilage cells, bone marrow stromal stem cells and embryonic stem cells; bio-scaffold materials includes natural materials and synthetic biodegradable polymers; the growth factors for cartilage tissue engineering include transforming growth factor, bone morphogenetic protein, fibroblast growth factor, insulin-like growth factor and so on.CONCLUSION: So far, there is no ideal materials for the seed cells and scaffold materials of engineered cartilage, as well as culture environment, the focus of future research is a kind of tissue engineered articular cartilage with good performance.However, many studies are still in the experimental stage, and some problems need to be solved, especially after tissue engineering scaffolds are implanted, whether the material degradation is synchronized with cell functioning, thus altering genetic materials, gene expression or gene mutation, their clinical application requires relevant scholars and experts to constantly practice and explore.

  9. Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.

    Science.gov (United States)

    Xiao, Yinghua; Friis, Elizabeth A; Gehrke, Stevin H; Detamore, Michael S

    2013-10-01

    Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.

  10. Repair of the superior sulcus deformity using autogenous costal cartilage.

    Science.gov (United States)

    Sutula, F C; Thomas, O

    1982-05-01

    Superior sulcus deformity is a late sequela of surgical anophthalmos. Many methods have been proposed to treat this difficult problem. A technique using autogenous costal cartilage that has resulted in satisfactory repair is presented. In addition to standard photographs and exophthalmometry measurements to follow these patients, a specific device to accurately measure orbital volume gain after operation was fashioned. PMID:7099560

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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...

  16. 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...

  17. 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.

  18. 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

  19. Tissue-engineering strategies to repair joint tissue in osteoarthritis: nonviral gene-transfer approaches.

    Science.gov (United States)

    Madry, Henning; Cucchiarini, Magali

    2014-10-01

    Loss of articular cartilage is a common clinical consequence of osteoarthritis (OA). In the past decade, substantial progress in tissue engineering, nonviral gene transfer, and cell transplantation have provided the scientific foundation for generating cartilaginous constructs from genetically modified cells. Combining tissue engineering with overexpression of therapeutic genes enables immediate filling of a cartilage defect with an engineered construct that actively supports chondrogenesis. Several pioneering studies have proved that spatially defined nonviral overexpression of growth-factor genes in constructs of solid biomaterials or hydrogels is advantageous compared with gene transfer or scaffold alone, both in vitro and in vivo. Notably, these investigations were performed in models of focal cartilage defects, because advanced cartilage-repair strategies based on the principles of tissue engineering have not advanced sufficiently to enable resurfacing of extensively degraded cartilage as therapy for OA. These studies serve as prototypes for future technological developments, because they raise the possibility that cartilage constructs engineered from genetically modified chondrocytes providing autocrine and paracrine stimuli could similarly compensate for the loss of articular cartilage in OA. Because cartilage-tissue-engineering strategies are already used in the clinic, combining tissue engineering and nonviral gene transfer could prove a powerful approach to treat OA.

  20. Effect of Human Adipose Tissue Mesenchymal Stem Cells on the Regeneration of Ovine Articular Cartilage.

    Science.gov (United States)

    Zorzi, Alessandro R; Amstalden, Eliane M I; Plepis, Ana Maria G; Martins, Virginia C A; Ferretti, Mario; Antonioli, Eliane; Duarte, Adriana S S; Luzo, Angela C M; Miranda, João B

    2015-11-09

    Cell therapy is a promising approach to improve cartilage healing. Adipose tissue is an abundant and readily accessible cell source. Previous studies have demonstrated good cartilage repair results with adipose tissue mesenchymal stem cells in small animal experiments. This study aimed to examine these cells in a large animal model. Thirty knees of adult sheep were randomly allocated to three treatment groups: CELLS (scaffold seeded with human adipose tissue mesenchymal stem cells), SCAFFOLD (scaffold without cells), or EMPTY (untreated lesions). A partial thickness defect was created in the medial femoral condyle. After six months, the knees were examined according to an adaptation of the International Cartilage Repair Society (ICRS 1) score, in addition to a new Partial Thickness Model scale and the ICRS macroscopic score. All of the animals completed the follow-up period. The CELLS group presented with the highest ICRS 1 score (8.3 ± 3.1), followed by the SCAFFOLD group (5.6 ± 2.2) and the EMPTY group (5.2 ± 2.4) (p = 0.033). Other scores were not significantly different. These results suggest that human adipose tissue mesenchymal stem cells promoted satisfactory cartilage repair in the ovine model.

  1. Chondroitin sulfate and glucosamine in the cartilage and subchondral bone repair of dogs - Histological findings

    Directory of Open Access Journals (Sweden)

    R.B. Eleotério

    2015-04-01

    Full Text Available Chondroitin and glucosamine sulfate nutraceuticals are commonly used in the management of degenerative articular disease in veterinary routine. However, there are controversies on the contribution of these substances to articular cartilage. The purpose of this study was to evaluate the efficiency of a chondroitin and glucosamine sulfate-based veterinary nutraceutical on the repair of an induced osteochondral defect in a dog femoral condyle, by macroscopic, histological and histomorphometric analyses. The nutraceutical was orally administered the day following injury induction, every 24 hours (treated group, TG, n=24, compared with animals that did not receive the product (control group, CG, n=24. Six animals per group were anaesthetized for sample collection at 15, 30, 60 and 90 days after surgery. At 15 days, defects were macroscopically filled with red-pinkish tissue. After 30 days, whitish color tissue was observed, both in TG and CG animals, with firmer consistency to touch at 60 and 90 postoperative days. Histological analysis demonstrated that, in both groups, there was initial blood clot formation, which was subsequently substituted by a fibrin net, with capillary proliferation from the adjacent bone marrow and infiltration of mesenchymal cells in clot periphery. As cellular differentiation developed, repair tissue presented a fibrocartilage aspect most of the time, and new subchondral bone formation occurred in the deepest area corresponding to the defect. Histomorphometry suggested that the nutraceutical did not favor the articular cartilage repair process. It was concluded that nutraceutical did not significantly influence chondrocytes proliferation or hyaline architecture restoration.

  2. 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.

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

    Science.gov (United States)

    Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

    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.

  4. 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

  5. Articular Cartilage Repair Using Marrow Stimulation Augmented with a Viable Chondral Allograft: 9-Month Postoperative Histological Evaluation

    Directory of Open Access Journals (Sweden)

    James K. Hoffman

    2015-01-01

    Full Text Available Marrow stimulation is frequently employed to treat focal chondral defects of the knee. However, marrow stimulation typically results in fibrocartilage repair tissue rather than healthy hyaline cartilage, which, over time, predisposes the repair to failure. Recently, a cryopreserved viable chondral allograft was developed to augment marrow stimulation. The chondral allograft is comprised of native viable chondrocytes, chondrogenic growth factors, and extracellular matrix proteins within the superficial, transitional, and radial zones of hyaline cartilage. Therefore, host mesenchymal stem cells that infiltrate the graft from the underlying bone marrow following marrow stimulation are provided with the optimal microenvironment to undergo chondrogenesis. The present report describes treatment of a trochlear defect with marrow stimulation augmented with this novel chondral allograft, along with nine month postoperative histological results. At nine months, the patient demonstrated complete resolution of pain and improvement in function, and the repair tissue consisted of 85% hyaline cartilage. For comparison, a biopsy obtained from a patient 8.2 months after treatment with marrow stimulation alone contained only 5% hyaline cartilage. These outcomes suggest that augmenting marrow stimulation with the viable chondral allograft can eliminate pain and improve outcomes, compared with marrow stimulation alone.

  6. 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...

  7. Dry Arthroscopy With a Retraction System for Matrix-Aided Cartilage Repair of Patellar Lesions

    OpenAIRE

    Sadlik, Boguslaw; Wiewiorski, Martin

    2014-01-01

    Several commercially available cartilage repair techniques use a natural or synthetic matrix to aid cartilage regeneration (e.g., autologous matrix–induced chondrogenesis or matrix-induced cartilage implantation). However, the use of matrix-aided techniques during conventional knee joint arthroscopy under continuous irrigation is challenging. Insertion and fixation of the matrix can be complicated by the presence of fluid and the confined patellofemoral joint space with limited access to the ...

  8. Tissue Engineering Cartilage with a Composite Electrospun and Hydrogel Scaffold

    OpenAIRE

    Wright, Lee David

    2011-01-01

    Osteoarthritis is the most prevalent musculoskeletal disease in humans, severely reducing the standard of living of millions of people. Osteoarthritis is characterized by degeneration and loss of articular cartilage which leads to pain, and loss of joint motility and function. Individuals suffering from severe osteoarthritis are commonly treated with full knee replacements. The procedure does eliminate the problem of degrading cartilage tissue; however, it does not fully restore function a...

  9. Computational aspects in mechanical modeling of the articular cartilage tissue.

    Science.gov (United States)

    Mohammadi, Hadi; Mequanint, Kibret; Herzog, Walter

    2013-04-01

    This review focuses on the modeling of articular cartilage (at the tissue level), chondrocyte mechanobiology (at the cell level) and a combination of both in a multiscale computation scheme. The primary objective is to evaluate the advantages and disadvantages of conventional models implemented to study the mechanics of the articular cartilage tissue and chondrocytes. From monophasic material models as the simplest form to more complicated multiscale theories, these approaches have been frequently used to model articular cartilage and have contributed significantly to modeling joint mechanics, addressing and resolving numerous issues regarding cartilage mechanics and function. It should be noted that attentiveness is important when using different modeling approaches, as the choice of the model limits the applications available. In this review, we discuss the conventional models applicable to some of the mechanical aspects of articular cartilage such as lubrication, swelling pressure and chondrocyte mechanics and address some of the issues associated with the current modeling approaches. We then suggest future pathways for a more realistic modeling strategy as applied for the simulation of the mechanics of the cartilage tissue using multiscale and parallelized finite element method.

  10. A comparative Study between the Structure of Cartilage Tissue Produced from Murine MSCs Differentiation and Hyaline Costal Cartilage

    Directory of Open Access Journals (Sweden)

    M.R. Baghban Eslaminezhad, Ph.D.

    2007-09-01

    Full Text Available Background and purpose: Vitro cartilage differentiation of mesenchymal stem cells (MSCs has been noticed in several investigations. In this regard, almost always molecular differentiation of the cells has been examined, while structural and morphological differentiation of them has been ignored. Therefore, the present study examines the structure and ultrastructure of the cartilage differentiated from murine MSCs compared with that of costal cartilage.Materials and Methods: 2× 105 MSCs isolated from the bone marrow of NMRI mice were pleted by centrifugation and cultured for 21 days in chondrogenic medium. At the end of cultivation period, occurrence of chondrogenic differentiation was confirmed by reverse transcriptase–polymerase chain reaction (RT-PCR analysis for some cartilage-specific genes. To compare the structure of differentiated tissue with that of natural cartilage, the cartilage was differentiated from MSCs and the cartilage obtained from the same murine rib was prepared for transmission electron microscopy (TEM.Results: Structural studies indicated that similar to the costal cartilage, the cartilage produced from differentiation of perichondrium-like layer was formed. According to the microscopic images, in contrast to costal chondrocytes, the differentiated cells had euchromatic nucleus and their cytoplasm contained plenty of the organelles involved in active cell secretion. Furthermore, intercellular matrix in differentiated cartilage had a fibrillar appearance. Conclusion: Our results indicated that the structure of cartilage produced in micro mass culture system is somewhat different from that of costal cartilage. The cells from differentiated tissue seemed to be more active than those from costal cartilage. .

  11. 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...

  12. Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair.

    Science.gov (United States)

    Wang, Jianhua; Yang, Qiu; Cheng, Niangmei; Tao, Xiaojun; Zhang, Zhihua; Sun, Xiaomin; Zhang, Qiqing

    2016-04-01

    For cartilage repair, ideal scaffolds should mimic natural extracellular matrix (ECM) exhibiting excellent characteristics, such as biocompatibility, suitable porosity, and good cell affinity. This study aimed to prepare a collagen/silk fibroin composite scaffold incorporated with poly-lactic-co-glycolic acid (PLGA) microsphere that can be applied in repairing cartilage. To obtain optimum conditions for manufacturing a composite scaffold, a scaffold composed of different collagen-to-silk fibroin ratios was evaluated by determining porosity, water absorption, loss rate in hot water, and cell proliferation. Results suggested that the optimal ratio of collagen and silk fibroin composite scaffold was 7:3. The microstructure and morphological characteristics of the obtained scaffold were also examined through scanning electron microscopy and Fourier transform infrared spectroscopy. The results of in vitro fluorescence staining of bone marrow stromal cells revealed that collagen/silk fibroin composite scaffold enhanced cell proliferation without eliciting side effects. The prepared composite scaffold incorporated with PLGA microsphere was implanted in fully thick articular cartilage defects in rabbits. Collagen/silk fibroin composite scaffold with PLGA microspheres could enhance articular cartilage regeneration and integration between the repaired cartilage and the surrounding cartilage. Therefore, this composite will be a promising material for cartilage repair and regeneration.

  13. 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.

  14. Cartilage repair and subchondral bone migration using 3D printing osteochondral composites: a one-year-period study in rabbit trochlea.

    Science.gov (United States)

    Zhang, Weijie; Lian, Qin; Li, Dichen; Wang, Kunzheng; Hao, Dingjun; Bian, Weiguo; He, Jiankang; Jin, Zhongmin

    2014-01-01

    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.

  15. 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...

  16. 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

  17. 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

  18. Local Morphological Response of the Distal Femoral Articular–Epiphyseal Cartilage Complex of Young Foals to Surgical Stab Incision and Potential Relevance to Cartilage Injury and Repair in Children

    Science.gov (United States)

    Hendrickson, Eli H.S.; Ekman, Stina; Carlson, Cathy S.; Dolvik, Nils I.

    2013-01-01

    Objective: Describe the local morphological response of the articular–epiphyseal cartilage complex to surgical stab incision in the distal femur of foals, with emphasis on the relationship between growth cartilage injury, enchondral ossification, and repair. Design: Nine foals were induced into general anesthesia at the age of 13 to 15 days. Four full-thickness stab incision defects were created in the cartilage on the lateral aspect of the lateral trochlear ridge of the left distal femur. Follow-up examination was carried out from 1 to 49 days postoperatively, including examination of intact bones, sawed slabs, and histological sections. Results: Incision defects filled with cells displaying fibroblast-, chondrocyte-, and osteoblast-like characteristics, potentially validating the rationale behind the drilling of stable juvenile osteochondritis dissecans lesions in children. Incisions induced necrosis within the cartilage on the margins at all depths of the defects. Sharp dissection may therefore be contraindicated in cartilage repair in young individuals. Incisions caused a focal delay in enchondral ossification in 2 foals, apparently related to the orientation of the incision defect relative to the direction of ossification. Defects became progressively surrounded by subchondral bone, in which granulation tissue containing clasts and foci of osteoblast-like cells was observed. Continued enchondral ossification was therefore likely to result in healing of uncomplicated defects to morphologically normal bone. Conclusions: Epiphyseal growth cartilage injury had the potential to exert a negative effect on enchondral ossification. Enchondral ossification exerted a beneficial effect on repair. This relationship warrants consideration in future studies of cartilage injury and repair within the articular–epiphyseal cartilage complex of all species. PMID:26069670

  19. Transforming growth factor beta signaling is essential for the autonomous formation of cartilage-like tissue by expanded chondrocytes.

    Directory of Open Access Journals (Sweden)

    Adel Tekari

    Full Text Available Cartilage is a tissue with limited self-healing potential. Hence, cartilage defects require surgical attention to prevent or postpone the development of osteoarthritis. For cell-based cartilage repair strategies, in particular autologous chondrocyte implantation, articular chondrocytes are isolated from cartilage and expanded in vitro to increase the number of cells required for therapy. During expansion, the cells lose the competence to autonomously form a cartilage-like tissue, that is in the absence of exogenously added chondrogenic growth factors, such as TGF-βs. We hypothesized that signaling elicited by autocrine and/or paracrine TGF-β is essential for the formation of cartilage-like tissue and that alterations within the TGF-β signaling pathway during expansion interfere with this process. Primary bovine articular chondrocytes were harvested and expanded in monolayer culture up to passage six and the formation of cartilage tissue was investigated in high density pellet cultures grown for three weeks. Chondrocytes expanded for up to three passages maintained the potential for autonomous cartilage-like tissue formation. After three passages, however, exogenous TGF-β1 was required to induce the formation of cartilage-like tissue. When TGF-β signaling was blocked by inhibiting the TGF-β receptor 1 kinase, the autonomous formation of cartilage-like tissue was abrogated. At the initiation of pellet culture, chondrocytes from passage three and later showed levels of transcripts coding for TGF-β receptors 1 and 2 and TGF-β2 to be three-, five- and five-fold decreased, respectively, as compared to primary chondrocytes. In conclusion, the autonomous formation of cartilage-like tissue by expanded chondrocytes is dependent on signaling induced by autocrine and/or paracrine TGF-β. We propose that a decrease in the expression of the chondrogenic growth factor TGF-β2 and of the TGF-β receptors in expanded chondrocytes accounts for a decrease

  20. Porous polymers for repair and replacement of the knee joint meniscus and articular cartilage

    NARCIS (Netherlands)

    Klompmaker, Jan

    1992-01-01

    The studies presented here were initiated to answer a variety of questions concerning firstly the repair and replacement of the knee joint meniscus and, secondly, the repair of full-thickness defects of articular cartilage. AIMS OF THE STUDIES I To assess the effect of implantation of a porous polym

  1. Tissue engineering of cartilages using biomatrices

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...... 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 widely...

  2. Dry arthroscopy with a retraction system for matrix-aided cartilage repair of patellar lesions.

    Science.gov (United States)

    Sadlik, Boguslaw; Wiewiorski, Martin

    2014-02-01

    Several commercially available cartilage repair techniques use a natural or synthetic matrix to aid cartilage regeneration (e.g., autologous matrix-induced chondrogenesis or matrix-induced cartilage implantation). However, the use of matrix-aided techniques during conventional knee joint arthroscopy under continuous irrigation is challenging. Insertion and fixation of the matrix can be complicated by the presence of fluid and the confined patellofemoral joint space with limited access to the lesion. To overcome these issues, we developed a novel arthroscopic approach for matrix-aided cartilage repair of patellar lesions. This technical note describes the use of dry arthroscopy assisted by a minimally invasive retraction system. An autologous matrix-induced chondrogenesis procedure is used to illustrate this novel approach.

  3. Devitalisation of human cartilage by high hydrostatic pressure treatment: Subsequent cultivation of chondrocytes and mesenchymal stem cells on the devitalised tissue

    Science.gov (United States)

    Hiemer, B.; Genz, B.; Jonitz-Heincke, A.; Pasold, J.; Wree, A.; Dommerich, S.; Bader, R.

    2016-01-01

    The regeneration of cartilage lesions still represents a major challenge. Cartilage has a tissue-specific architecture, complicating recreation by synthetic biomaterials. A novel approach for reconstruction is the use of devitalised cartilage. Treatment with high hydrostatic pressure (HHP) achieves devitalisation while biomechanical properties are remained. Therefore, in the present study, cartilage was devitalised using HHP treatment and the potential for revitalisation with chondrocytes and mesenchymal stem cells (MSCs) was investigated. The devitalisation of cartilage was performed by application of 480 MPa over 10 minutes. Effective cellular inactivation was demonstrated by the trypan blue exclusion test and DNA quantification. Histology and electron microscopy examinations showed undamaged cartilage structure after HHP treatment. For revitalisation chondrocytes and MSCs were cultured on devitalised cartilage without supplementation of chondrogenic growth factors. Both chondrocytes and MSCs significantly increased expression of cartilage-specific genes. ECM stainings showed neocartilage-like structure with positive AZAN staining as well as collagen type II and aggrecan deposition after three weeks of cultivation. Our results showed that HHP treatment caused devitalisation of cartilage tissue. ECM proteins were not influenced, thus, providing a scaffold for chondrogenic differentiation of MSCs and chondrocytes. Therefore, using HHP-treated tissue might be a promising approach for cartilage repair. PMID:27671122

  4. Development of hybrid scaffolds using ceramic and hydrogel for articular cartilage tissue regeneration.

    Science.gov (United States)

    Seol, Young-Joon; Park, Ju Young; Jeong, Wonju; Kim, Tae-Ho; Kim, Shin-Yoon; Cho, Dong-Woo

    2015-04-01

    The regeneration of articular cartilage consisting of hyaline cartilage and hydrogel scaffolds has been generally used in tissue engineering. However, success in in vivo studies has been rarely reported. The hydrogel scaffolds implanted into articular cartilage defects are mechanically unstable and it is difficult for them to integrate with the surrounding native cartilage tissue. Therefore, it is needed to regenerate cartilage and bone tissue simultaneously. We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were press-fitted into osteochondral tissue defects in a rabbit knee joints and the cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds was compared. In 12th week after implantation, the histological and immunohistochemical analyses were conducted to evaluate the cartilage tissue regeneration. In the blank and hydrogel scaffold groups, the defects were filled with fibrous tissues and the implanted hydrogel scaffolds could not maintain their initial position; in the hybrid scaffold group, newly generated cartilage tissues were morphologically similar to native cartilage tissues and were smoothly connected to the surrounding native tissues. This study demonstrates hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the defect site.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. In vitro cartilage tissue engineering using cancellous bone matrix gelatin as a biodegradable scaffold.

    Science.gov (United States)

    Yang, Bo; Yin, Zhanhai; Cao, Junling; Shi, Zhongli; Zhang, Zengtie; Song, Hongxing; Liu, Fuqiang; Caterson, Bruce

    2010-08-01

    In this study, we constructed tissue-engineered cartilage using allogeneic cancellous bone matrix gelatin (BMG) as a scaffold. Allogeneic BMG was prepared by sequential defatting, demineralization and denaturation. Isolated rabbit chondrocytes were seeded onto allogeneic cancellous BMG, and cell-BMG constructs were harvested after 1, 3 and 6 weeks for evaluation by hematoxylin and eosin staining for overall morphology, toluidine blue for extracellular matrix (ECM) proteoglycans, immunohistochemical staining for collagen type II and a transmission electron microscope for examining cellular microstructure on BMG. The prepared BMG was highly porous with mechanical strength adjustable by duration of demineralization and was easily trimmed for tissue repair. Cancellous BMG showed favorable porosity for cell habitation and metabolism material exchange with larger pore sizes (100-500 microm) than in cortical BMG (5-15 microm), allowing cell penetration. Cancellous BMG also showed good biocompatibility, which supported chondrocyte proliferation and sustained their differentiated phenotype in culture for up to 6 weeks. Rich and evenly distributed cartilage ECM proteoglycans and collagen type II were observed around chondrocytes on the surface and inside the pores throughout the cancellous BMG. Considering the large supply of banked bone allografts and relatively convenient preparation, our study suggests that allogeneic cancellous BMG is a promising scaffold for cartilage tissue engineering.

  12. In vitro cartilage tissue engineering using cancellous bone matrix gelatin as a biodegradable scaffold

    Energy Technology Data Exchange (ETDEWEB)

    Yang Bo; Yin Zhanhai; Cao Junling; Shi Zhongli; Zhang Zengtie; Liu Fuqiang [College of Medicine, Xi' an Jiaotong University, Yanta West Road, No 76, Yanta District, Xi' an, Shaanxi Province 710061 (China); Song Hongxing [Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Caterson, Bruce, E-mail: caojl@mail.xjtu.edu.c [Connective Tissue Biology Laboratories, Cardiff School of Biosciences, Cardiff University, Biomedical Building, Museum Avenue, Cardiff, CF10 3US (United Kingdom)

    2010-08-01

    In this study, we constructed tissue-engineered cartilage using allogeneic cancellous bone matrix gelatin (BMG) as a scaffold. Allogeneic BMG was prepared by sequential defatting, demineralization and denaturation. Isolated rabbit chondrocytes were seeded onto allogeneic cancellous BMG, and cell-BMG constructs were harvested after 1, 3 and 6 weeks for evaluation by hematoxylin and eosin staining for overall morphology, toluidine blue for extracellular matrix (ECM) proteoglycans, immunohistochemical staining for collagen type II and a transmission electron microscope for examining cellular microstructure on BMG. The prepared BMG was highly porous with mechanical strength adjustable by duration of demineralization and was easily trimmed for tissue repair. Cancellous BMG showed favorable porosity for cell habitation and metabolism material exchange with larger pore sizes (100-500 {mu}m) than in cortical BMG (5-15 {mu}m), allowing cell penetration. Cancellous BMG also showed good biocompatibility, which supported chondrocyte proliferation and sustained their differentiated phenotype in culture for up to 6 weeks. Rich and evenly distributed cartilage ECM proteoglycans and collagen type II were observed around chondrocytes on the surface and inside the pores throughout the cancellous BMG. Considering the large supply of banked bone allografts and relatively convenient preparation, our study suggests that allogeneic cancellous BMG is a promising scaffold for cartilage tissue engineering.

  13. 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.

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

    Science.gov (United States)

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

    2016-05-27

    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.

  15. 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

  16. 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

  17. Use of NASA Bioreactor in Engineering Tissue for Bone Repair

    Science.gov (United States)

    Duke, Pauline

    1998-01-01

    This study was proposed in search for a new alternative for bone replacement or repair. Because the systems commonly used in repair of bony defects form bone by going through a cartilaginous phase, implantation of a piece of cartilage could enhance the healing process by having a more advanced starting point. However, cartilage has seldom been used to replace bone due, in part, to the limitations in conventional culture systems that did not allow production of enough tissue for implants. The NASA-developed bioreactors known as STLV (Slow Turning Lateral Vessel) provide homogeneous distribution of cells, nutrients, and waste products, with less damaging turbulence and shear forces than conventional systems. Cultures under these conditions have higher growth rates, viability, and longevity, allowing larger "tissue-like" aggregates to form, thus opening the possibilities of producing enough tissue for implantation, along with the inherent advantages of in vitro manipulations. To assure large numbers of cells and to eliminate the use of timed embryos, we proposed to use an immortalized mouse limb bud cell line as the source of cells.

  18. Chondrocyte Generation of Cartilage-Like Tissue Following Photoencapsulation in Methacrylated Polysaccharide Solution Blends.

    Science.gov (United States)

    Hayami, James W S; Waldman, Stephen D; Amsden, Brian G

    2016-07-01

    Chondrocyte-seeded, photo-cross-linked hydrogels prepared from solutions containing 50% mass fractions of methacrylated glycol chitosan or methacrylated hyaluronic acid (MHA) with methacrylated chondroitin sulfate (MCS) are cultured in vitro under static conditions over 35 d to assess their suitability for load-bearing soft tissue repair. The photo-cross-linked hydrogels have initial equilibrium moduli between 100 and 300 kPa, but only the MHAMCS hydrogels retain an approximately constant modulus (264 ± 5 kPa) throughout the culture period. Visually, the seeded chondrocytes in the MHAMCS hydrogels are well distributed with an apparent constant viability in culture. Multicellular aggregates are surrounded by cartilaginous matrix, which contain aggrecan and collagen II. Thus, co-cross-linked MCS and MHA hydrogels may be suited for use in an articular cartilage or nucleus pulposus repair applications. PMID:27061241

  19. 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 ...

  20. Influence of tissue- and cell-scale extracellular matrix distribution on the mechanical properties of tissue-engineered cartilage

    NARCIS (Netherlands)

    Khoshgoftar, M.; Wilson, W.; Ito, K.; Donkelaar, C.C. van

    2013-01-01

    The insufficient load-bearing capacity of today's tissue- engineered (TE) cartilage limits its clinical application. Generally, cartilage TE studies aim to increase the extracellular matrix (ECM) content, as this is thought to determine the load-bearing properties of the cartilage. However, there ar

  1. 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

  2. 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

  3. 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

  4. Allogeneic Bone Marrow Transplant from MRL/MpJ Super-Healer Mice Does Not Improve Articular Cartilage Repair in the C57Bl/6 Strain.

    Directory of Open Access Journals (Sweden)

    Catherine A Leonard

    Full Text Available Articular cartilage has been the focus of multiple strategies to improve its regenerative/ repair capacity. The Murphy Roths Large (MRL/MpJ "super-healer" mouse demonstrates an unusual enhanced regenerative capacity in many tissues and provides an opportunity to further study endogenous cartilage repair. The objective of this study was to test whether the super-healer phenotype could be transferred from MRL/MpJ to non-healer C57Bl/6 mice by allogeneic bone marrow transplant.The healing of 2mm ear punches and full thickness cartilage defects was measured 4 and 8 weeks after injury in control C57Bl/6 and MRL/MpJ "super-healer" mice, and in radiation chimeras reconstituted with bone marrow from the other mouse strain. Healing was assessed using ear hole diameter measurement, a 14 point histological scoring scale for the cartilage defect and an adapted version of the Osteoarthritis Research Society International scale for assessment of osteoarthritis in mouse knee joints.Normal and chimeric MRL mice showed significantly better healing of articular cartilage and ear wounds along with less severe signs of osteoarthritis after cartilage injury than the control strain. Contrary to our hypothesis, however, bone marrow transplant from MRL mice did not confer improved healing on the C57Bl/6 chimeras, either in regards to ear wound healing or cartilage repair.The elusive cellular basis for the MRL regenerative phenotype still requires additional study and may possibly be dependent on additional cell types external to the bone marrow.

  5. Scaffold-based Drug Delivery for Cartilage Tissue Regeneration.

    Science.gov (United States)

    Shalumon, K T; Chen, Jyh-Ping

    2015-01-01

    Regenerative engineering is an advanced field comprising the collective benefit of biodegradable polymers with cells and tissue inducing factors. Current method of replacing the defective organ is through transplantation, but is limited due to immune rejection and availability. As a solution, new polymeric biomaterial-based three-dimensional (3D) scaffolds in combination with cells and inducing factors were aroused to fulfil the existing demands. These scaffolds apply material science, biomedical technology and translational medicine to develop functional tissue engineering constructs. Presence of small molecules and growth factors guides the cell phenotypes to specific organ development. The 3D scaffold thus could also be favorably used as carriers for various types of drugs and genes, with the release profile fine-tuned by modulation of the scaffold's morphology, porosity, and composition. An increasing trend was observed in recent years toward the combination of scaffolds and growth factors to fabricate a bioactive system, which not only provide a biomimetic biodegradable physical support for tissue growth but also explores biological signals to modulate tissue regeneration. In this review, along with general aspects of tissue engineering, we also discuss the importance of various scaffold architectures like nanofibers, hydrogels, beads, meshes, microspheres etc. in combination with specific drugs, growth factors and small molecules for cartilage regeneration. Growth factors may be incorporated into scaffolds by direct blending, physical adsorption, drop casting, surface grafting, covalent bonding, chemical immobilization, coaxial electrospinning, microparticle incorporation etc. This offers new possibilities for the development of biomimetic scaffolds that are endowed with a hierarchical architecture and sophisticated release kinetics of the growth factors. This review portrait the fundamentals of tissue engineering with emphasis on the role of inducing factors

  6. 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)

  7. 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.

  8. 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

  9. Macrophages in Tissue Repair, Regeneration, and Fibrosis.

    Science.gov (United States)

    Wynn, Thomas A; Vannella, Kevin M

    2016-03-15

    Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled production of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.

  10. 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

  11. Method of tissue repair using a composite material

    Science.gov (United States)

    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.

  12. 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.

  13. 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.

  14. 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...

  15. Use of magnetic forces to promote stem cell aggregation during differentiation, and cartilage tissue modeling.

    Science.gov (United States)

    Fayol, D; Frasca, G; Le Visage, C; Gazeau, F; Luciani, N; Wilhelm, C

    2013-05-14

    Magnetic forces induce cell condensation necessary for stem cell differentiation into cartilage and elicit the formation of a tissue-like structure: Magnetically driven fusion of aggregates assembled by micromagnets results in the formation of a continuous tissue layer containing abundant cartilage matrix. PMID:23526452

  16. 3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration.

    Science.gov (United States)

    Rosenzweig, Derek H; Carelli, Eric; Steffen, Thomas; Jarzem, Peter; Haglund, Lisbet

    2015-07-03

    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.

  17. 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.

  18. 3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration

    Science.gov (United States)

    Rosenzweig, Derek H.; Carelli, Eric; Steffen, Thomas; Jarzem, Peter; Haglund, Lisbet

    2015-01-01

    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. PMID:26151846

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Cartilage tissue engineering using pre-aggregated human articular chondrocytes

    Directory of Open Access Journals (Sweden)

    F Wolf

    2008-12-01

    Full Text Available In this study, we first aimed at determining whether human articular chondrocytes (HAC proliferate in aggregates in the presence of strong chondrocyte mitogens. We then investigated if the aggregated cells have an enhanced chondrogenic capacity as compared to cells cultured in monolayer. HAC from four donors were cultured in tissue culture dishes either untreated or coated with 1% agarose in the presence of TGFb-1, FGF-2 and PDGF-BB. Proliferation and stage of differentiation were assessed by measuring respectively DNA contents and type II collagen mRNA. Expanded cells were induced to differentiate in pellets or in Hyaff®-11 meshes and the formed tissues were analysed biochemically for glycosaminoglycans (GAG and DNA, and histologically by Safranin O staining. The amount of DNA in aggregate cultures increased significantly from day 2 to day 6 (by 3.2-fold, but did not further increase with additional culture time. Expression of type II collagen mRNA was about two orders of magnitude higher in aggregated HAC as compared to monolayer expanded cells. Pellets generated by aggregated HAC were generally more intensely stained for GAG than those generated by monolayer-expanded cells. Scaffolds seeded with aggregates accumulated more GAG (1.3-fold than scaffolds seeded with monolayer expanded HAC. In conclusion, this study showed that HAC culture in aggregates does not support a relevant degree of expansion. However, aggregation of expanded HAC prior to loading into a porous scaffold enhances the quality of the resulting tissues and could thus be introduced as an intermediate culture phase in the manufacture of engineered cartilage grafts.

  11. Strategies for cell engineering in tissue repair.

    Science.gov (United States)

    Brown, R A; Smith, K D; Angus McGrouther, D

    1997-01-01

    Cellular and tissue engineering are new areas of research, currently attracting considerable interest because of the remarkable potential they have for clinical application. Some claims have indeed been dramatic, including the possibility of growing complete, artificial organs, such as the liver. However, amid such long-term aspirations there is the very real possibility that small tissues (artificial grafts) may be fabricated in the near future for use in reconstructive surgery. Logically, we should focus on how it is possible to produce modest, engineered tissues for tissue repair. It is evident that strategies to date either depend on innate information within implanted cells, to reform the target tissue or aim to provide appropriate environmental cues or guidance to direct cell behavior. It is argued here that present knowledge of tissue repair biology points us toward the latter approach, providing external cues which will direct how cells should organize the new tissue. This will be particularly true where we need to reproduce microscopic and ultrastructural features of the original tissue architecture. A number of such cues have been identified, and methods are already available, including substrate chemistry, substrate contact guidance, mechanical loading, and biochemical mediators to provide these cues. Examples of these are already being used with some success to control the formation of tissue structures.

  12. 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...

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Advancement of the Subchondral Bone Plate in Translational Models of Osteochondral Repair: Implications for Tissue Engineering Approaches.

    Science.gov (United States)

    Orth, Patrick; Madry, Henning

    2015-12-01

    Subchondral bone plate advancement is of increasing relevance for translational models of osteochondral repair in tissue engineering (TE). Especially for therapeutic TE approaches, a basic scientific knowledge of its chronological sequence, possible etiopathogenesis, and clinical implications are indispensable. This review summarizes the knowledge on this topic gained from a total of 31 translational investigations, including 1009 small and large animals. Experimental data indicate that the advancement of the subchondral bone plate frequently occurs during the spontaneous repair of osteochondral defects and following established articular cartilage repair approaches for chondral lesions such as marrow stimulation and TE-based strategies such as autologous chondrocyte implantation. Importantly, this subchondral bone reaction proceeds in a defined chronological and spatial pattern, reflecting both endochondral ossification and intramembranous bone formation. Subchondral bone plate advancement arises earlier in small animals and defects, but is more pronounced at the long term in large animals. Possible etiopathologies comprise a disturbed subchondral bone/articular cartilage crosstalk and altered biomechanical conditions or neovascularization. Of note, no significant correlation was found so far between subchondral bone plate advancement and articular cartilage repair. This evidence from translational animal models adverts to an increasing awareness of this previously underestimated pathology. Future research will shed more light on the advancement of the subchondral bone plate in TE models of cartilage repair. PMID:26066580

  18. Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model.

    Science.gov (United States)

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

    2015-11-01

    This study was carried out to assess the feasibility of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in articular cartilage repair and to further determine a suitable delivering hydrogel in a rat model. Critical sized full thickness cartilage defects were created. The hUCB-MSCs and three different hydrogel composites (hydrogel A; 4% hyaluronic acid/30% pluronic (1:1, v/v), hydrogel B; 4% hyaluronic acid, and hydrogel C; 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v)) were implanted into the experimental knee (right knee) and hydrogels without hUCB-MSCs were implanted into the control knee (left knee). Defects were evaluated after 8 weeks. The hUCB-MSCs with hydrogels composites resulted in a better repair as seen by gross and histological evaluation compared with hydrogels without hUCB-MSCs. Among the three different hydrogels, the 4% hyaluronic acid hydrogel composite (hydrogel B) showed the best result in cartilage repair as seen by the histological evaluation compared with the other hydrogel composites (hydrogel A and C). The results of this study suggest that hUCB-MSCs may be a promising cell source in combination with 4% hyaluronic acid hydrogels in the in vivo repair of cartilage defects.

  19. 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.

  20. 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 ...

  1. Use of bone morphogenetic proteins in mesenchymal stemcell stimulation of cartilage and bone repair

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    The extracellular matrix-associated bone morphogeneticproteins (BMPs) govern a plethora of biological processes.The BMPs are members of the transforming growthfactor-β protein superfamily, and they actively participateto kidney development, digit and limb formation,angiogenesis, tissue fibrosis and tumor development.Since their discovery, they have attracted attentionfor their fascinating perspectives in the regenerativemedicine and tissue engineering fields. BMPs havebeen employed in many preclinical and clinical studiesexploring their chondrogenic or osteoinductive potentialin several animal model defects and in human diseases.During years of research in particular two BMPs, BMP2and BMP7 have gained the podium for their use inthe treatment of various cartilage and bone defects.In particular they have been recently approved foremployment in non-union fractures as adjunct therapies.On the other hand, thanks to their potentialities inbiomedical applications, there is a growing interest instudying the biology of mesenchymal stem cell (MSC),the rules underneath their differentiation abilities, andto test their true abilities in tissue engineering. In fact,the specific differentiation of MSCs into targeted celltypelineages for transplantation is a primary goal of theregenerative medicine. This review provides an overviewon the current knowledge of BMP roles and signaling inMSC biology and differentiation capacities. In particularthe article focuses on the potential clinical use of BMPsand MSCs concomitantly, in cartilage and bone tissuerepair.

  2. Decellularized cartilage may be a chondroinductive material for osteochondral tissue engineering.

    Directory of Open Access Journals (Sweden)

    Amanda J Sutherland

    Full Text Available Extracellular matrix (ECM-based materials are attractive for regenerative medicine in their ability to potentially aid in stem cell recruitment, infiltration, and differentiation without added biological factors. In musculoskeletal tissue engineering, demineralized bone matrix is widely used, but recently cartilage matrix has been attracting attention as a potentially chondroinductive material. The aim of this study was thus to establish a chemical decellularization method for use with articular cartilage to quantify removal of cells and analyze the cartilage biochemical content at various stages during the decellularization process, which included a physically devitalization step. To study the cellular response to the cartilage matrix, rat bone marrow-derived mesenchymal stem cells (rBMSCs were cultured in cell pellets containing cells only (control, chondrogenic differentiation medium (TGF-β, chemically decellularized cartilage particles (DCC, or physically devitalized cartilage particles (DVC. The chemical decellularization process removed the vast majority of DNA and about half of the glycosaminoglycans (GAG within the matrix, but had no significant effect on the amount of hydroxyproline. Most notably, the DCC group significantly outperformed TGF-β in chondroinduction of rBMSCs, with collagen II gene expression an order of magnitude or more higher. While DVC did not exhibit a chondrogenic response to the extent that DCC did, DVC had a greater down regulation of collagen I, collagen X and Runx2. A new protocol has been introduced for cartilage devitalization and decellularization in the current study, with evidence of chondroinductivity. Such bioactivity along with providing the 'raw material' building blocks of regenerating cartilage may suggest a promising role for DCC in biomaterials that rely on recruiting endogenous cell recruitment and differentiation for cartilage regeneration.

  3. 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

  4. 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

  5. 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...

  6. 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.

  7. 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

  8. [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

  9. Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

    Science.gov (United States)

    Gaut, Carrie; Sugaya, Kiminobu

    2015-01-01

    Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

  10. 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...

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Niina Hopper

    Full Text Available 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 (<1%, p = 0.006. However, the adherent PBMC population expressed mesenchymal stem cell markers in hypoxic culture and lacked CD34/45 positive cells (<0.2%. This finding demonstrated that the adherent 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

  14. Multilayered Short Peptide-Alginate Blends as New Materials for Potential Applications in Cartilage Tissue Regeneration.

    Science.gov (United States)

    Knoll, Grant A; Romanelli, Steven M; Brown, Alexandra M; Sortino, Rachel M; Banerjee, Ipsita A

    2016-03-01

    Peptide based nanomaterials have been gaining increased prominence due to their ability to form permeable scaffolds that promote growth and regeneration of new tissue. In this work for the first time a short hexapeptide motif VQIVYK, derived from the Tau protein family was conjugated with an organic polyamine linker, putrescine and utilized as a template for developing new materials for cartilage tissue regeneration. Our results showed that the conjugate formed extensive nanofibrous assemblies upon self-assembly under aqueous conditions. We then employed the layer-by-layer (LBL) approach to design the scaffold by first incorporating a short segment of the dentin sialophosphoprotein motif GDASYNSDESK followed by integration with the peptide sequence GSGAGAGSGAGAGSGAGA. This sequence mimics Ala, Gly, Ser repeats seen in the spider silk protein. We then incorporated the polysaccharide alginate which served as a hydrogel. To further enhance binding interactions with chondrocytes, and promote the formation of cartilage in vitro, the bionanocomposites were then attached to the chondrocyte binding peptide sequence HDSQLEALIKFM. The thermal properties as well as biodegradability of the scaffold was examined. To confirm biocompatibility, we examined cell viability, attachment and morphology in the presence of bovine chondrocytes. The cells were found to efficiently adhere to the scaffolds which formed an intricate mesh mimicking the extracellular matrix of cartilage tissue. To evaluate if differentiation occurred in the presence of the scaffolds, we examined in vitro deposition of proteoglycans. Thus, we have developed a new family of nanoscale scaffolds that may be utilized for cartilage tissue regeneration.

  15. 运动性关节软骨损伤修复材料的选择及其生物力学特征%Selection and biomechanical features of repair materials for exercise-induced articular cartilage injury

    Institute of Scientific and Technical Information of China (English)

    王洪博; 刘东兴; 任志杰; 尹树仁

    2011-01-01

    背景:关节软骨是无血管、淋巴管和神经的组织,通常情况下软骨细胞不能进行有丝分裂,这导致自身修复能力有限.生理负荷下,关节软骨经常处在应力环境中.根据软骨自身的结构和特点,作为人工软骨的替代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的应用进展及其生物替代材料的生物力学特征.方法:以"关节软骨,生物材料,生物力学"为中文关键词,以" tissue enginneering,articular cartilage,scaffold material,biomechanics" 为英文关键词,采用计算机检索中国期刊全文数据库、PubMed数据库1993-01/2010-10相关文章.纳入与运动有关的关节软骨损伤修复、目前常用于修复关节软骨损伤的生物材料以及生物替代材料的生物力学特征研究文章;排除重复研究或Meta分析类文章.以20篇文献为主重点对运动性关节软骨缺损修复材料的生物力学特征进行讨论.结果与结论:关节软骨是一种各向异性、非均质、具有黏弹性并充满液体的可渗透物质,具有独特的力学性能.损伤的关节软骨在生物力学方面均与原来的软骨不同,且极易退变.骨软骨柱移植力学性能近期效果最佳;脱细胞软骨基质、小肠黏膜下基质具有一定的力学强度;普通聚乙烯醇水凝胶的最大缺陷是力学性能的不足;聚乙烯醇材料其良好的柔韧性和高弹性能,具有与人关节软骨相似的力学性能;n-HA浆料与聚酰胺66在溶剂中复合,无论在力学性能还是化学组成上都与自然骨相似.提示在众多关节软骨替代材料中,无论是人工合成材料、天然材料、复合材料其生物力学性能各有不同,且目前还无法再造与天然生成的软骨具有相同力学性能的软骨组织.%BACKGROUND: Articular cartilage is non-vascular, lymphatic and nerve tissue, cartilage cells usually can not perform mitosis,resulting in limited ability to repair

  16. A dual flow bioreactor with controlled mechanical stimulation for cartilage tissue engineering.

    Science.gov (United States)

    Spitters, Tim W G M; Leijten, Jeroen C H; Deus, Filipe D; Costa, Ines B F; van Apeldoorn, Aart A; van Blitterswijk, Clemens A; Karperien, Marcel

    2013-10-01

    In cartilage, tissue engineering bioreactors can create a controlled environment to study chondrocyte behavior under mechanical stimulation or produce chondrogenic grafts of clinically relevant size. Here we present a novel bioreactor that combines mechanical stimulation with a two compartment system through which nutrients can be supplied solely by diffusion from opposite sides of a tissue-engineered construct. This design is based on the hypothesis that creating gradients of nutrients, growth factors, and growth factor antagonists can aid in the generation of zonal tissue-engineered cartilage. Computational modeling predicted that the design facilitates the creation of a biologically relevant glucose gradient. This was confirmed by quantitative glucose measurements in cartilage explants. In this system, it is not only possible to create gradients of nutrients, but also of anabolic or catabolic factors. Therefore, the bioreactor design allows control over nutrient supply and mechanical stimulation useful for in vitro generation of cartilage constructs that can be used for the resurfacing of articulated joints or as a model for studying osteoarthritis disease progression.

  17. The effect of tissue-engineered cartilage biomechanical and biochemical properties on its post-implantation mechanical behavior

    NARCIS (Netherlands)

    Khoshgoftar, M.; Wilson, W.; Ito, K.; Donkelaar, C.C. van

    2013-01-01

    The insufficient load-bearing capacity of today's tissue-engineered (TE) cartilage limits its clinical application. Focus has been on engineering cartilage with enhanced mechanical stiffness by reproducing native biochemical compositions. More recently, depth dependency of the biochemical content an

  18. Influence of the temporal deposition of extracellular matrix on the mechanical properties of tissue-engineered cartilage

    NARCIS (Netherlands)

    Khoshgoftar, M.; Wilson, W.; Ito, K.; Donkelaar, C.C. van

    2014-01-01

    Enhancement of the load-bearing capacity of tissue-engineered (TE) cartilage is expected to improve the clinical outcome of implantations. Generally, cartilage TE studies aim to increase the total extracellular matrix (ECM) content to improve implant mechanical properties. Besides the ECM content, h

  19. 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)

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

    Science.gov (United States)

    Chen, Chih-Hao; Shyu, Victor Bong-Hang; Chen, Jyh-Ping; Lee, Ming-Yih

    2014-03-01

    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.

  1. REPAIR OF SHEEP ARTICULAR-CARTILAGE DEFECTS WITH A RABBIT COSTAL PERICHONDRIAL GRAFT

    NARCIS (Netherlands)

    HOMMINGA, GN; BULSTRA, SK; KUIJER, R; VANDERLINDEN, AJ

    1991-01-01

    A xenograft of costal rabbit perichondrium was transplanted to an articular cartilage defect in a sheep knee. After 12 weeks, cartilage was formed with increased calcification of the basal layer and a mean of 74 percent collagen type 11. The synovium did not show any infiltration, indicating the abs

  2. 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

  3. 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

  4. Ⅱ型胶原海绵填充材料修复兔关节软骨缺损%Repair of articular cartilage defect in rabbit with type Ⅱ collagen sponge filling material

    Institute of Scientific and Technical Information of China (English)

    贺敬义; 龙瑞芳

    2005-01-01

    of cartilage have been used previously; however, the source of the donor is limited, the fixation is difficult as well as the occurrence of endochondrial ossification and delamination between the inferior cartilage and reparative cartilage, etc. Type Ⅱ collagen, the main component of cartilage matrix, has certain effects in the repair of articular cartilage defect.OBJECTIVE: To investigate the effects of type Ⅱ collagen sponge filling on the repair of articular cartilage defect.DESIGN: A randomized controlled trial.SETTING and MATERIALS: The study was conducted in the Guangzhou Institute of Traumatic Surgery. Materials were 24 adult male purebred New Zealand Rabbits(48 knees), ordinary grade, with a body mass of (2.29 ±0. 25) kg. Animals were fed with standard feeding in separate cage.INTERVENTIONS: A full-thickness defect in articular cartilage was made on the femoral trochlear surface by a drill of 5 mm in diameter and 3 mm in depth. Rabbits were allocated into filling group(type Ⅱ collagen sponge was grafted into left keen joint defect) and control group(right knee joint defect site was set as control) according to random number table.MAIN OUTCOME MEASURES: Gross morphological and histological observation of the defect repair in each dual week within 12 weeks after operation.RESULTS: During 10 - 12 weeks, in cuntrol group: The defect area was repaired by white and soft tissue that had no resistance to press. The repaired tissue was still lower than the surrounding articular surface with clear boundary. By histological observation, it was found that the defect was repaired by the mechanism similar to inflammatory reaction and the defect is ultimately filled by the hyperplasia of hyaline degenerative fibrous tissues. In filling group: the defect was repaired by semi-transparent, smooth, textured tissues with polish that had resistance to press as well as elasticity. The repaired tissue was almost similar to the shape of the surrounding cartilage,difficult to

  5. 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 ...

  6. Farnesol-modified biodegradable polyurethanes for cartilage tissue engineering.

    Science.gov (United States)

    Eglin, David; Grad, Sibylle; Gogolewski, Sylwester; Alini, Mauro

    2010-01-01

    A bifunctionalized 3,7,11-trimethyl-2,6,10-dodecatrien-1-diaminobutane amide (isoprenoid) was obtained from 3,7,11-trimethyl-2,6,10-dodecatrien-1-ol (farnesol) in a three-step synthesis. The bifunctionalized isoprenoid was characterized using infrared spectroscopy and (1)H and (13)C nuclear magnetic resonance spectroscopy and was covalently incorporated (0.12 mmol x g(-1)) into the biodegradable aliphatic polyurethane formed on the polycondensation reaction of poly(epsilon-caprolactone) diol, 1,4,3,6-dianhydro-D-sorbitol and 1,6-hexamethylene diisocyanate. Although the covalent incorporation of the isoprenoid molecule into the polyurethane chain modified the surface chemistry of the polymer, it did not affect the viability of attached chondrocytes. Porous 3D scaffolds were produced from the modified and unmodified biodegradable segmented polyurethanes by a salt leaching-phase-inverse technique. The scaffolds were seeded with bovine chondrocytes encapsulated in fibrin gel and cultured in vitro for 14 days. The incorporation of bifunctional isoprenoid into the polyurethane affected the morphology of the scaffolds produced, when compared with the morphology of the scaffolds produced using the same technique from the unmodified polyurethane. As a consequence, there was more uniform cell seeding and more homogeneous distribution of the synthesized extracellular matrix throughout the scaffold resulting in a reduced cell/tissue layer at the edges of the constructs. However, glycosaminoglycan (GAG), DNA content, and chondrocytes phenotype in the scaffolds produced from these two polyurethane formulations did not vary significantly. The findings suggest that the change of surface characteristics and the more open pore structure of the scaffolds produced from the isoprenoid-modified polyurethane are beneficial for the seeding efficiency and the homogeneity of the tissue engineered constructs. PMID:19191318

  7. 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.

  8. 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...

  9. 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

  10. Hydrogels as a Replacement Material for Damaged Articular Hyaline Cartilage

    Directory of Open Access Journals (Sweden)

    Charlotte M. Beddoes

    2016-06-01

    Full Text Available Hyaline cartilage is a strong durable material that lubricates joint movement. Due to its avascular structure, cartilage has a poor self-healing ability, thus, a challenge in joint recovery. When severely damaged, cartilage may need to be replaced. However, currently we are unable to replicate the hyaline cartilage, and as such, alternative materials with considerably different properties are used. This results in undesirable side effects, including inadequate lubrication, wear debris, wear of the opposing articular cartilage, and weakening of the surrounding tissue. With the number of surgeries for cartilage repair increasing, a need for materials that can better mimic cartilage, and support the surrounding material in its typical function, is becoming evident. Here, we present a brief overview of the structure and properties of the hyaline cartilage and the current methods for cartilage repair. We then highlight some of the alternative materials under development as potential methods of repair; this is followed by an overview of the development of tough hydrogels. In particular, double network (DN hydrogels are a promising replacement material, with continually improving physical properties. These hydrogels are coming closer to replicating the strength and toughness of the hyaline cartilage, while offering excellent lubrication. We conclude by highlighting several different methods of integrating replacement materials with the native joint to ensure stability and optimal behaviour.

  11. 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

  12. 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

  13. Online monitoring of cartilage tissue in a novel bioreactor

    Science.gov (United States)

    von der Burg, E.; von Buttlar, M.; Grill, W.

    2011-04-01

    Standard techniques for the analysis of biological tissues like immunohistochemical staining are typically invasive and lead to mortification of cells. Non-invasive monitoring is an important element of regenerative medicine because implants and components of implants should be 100% quality-checked with non-invasive and therefore also marker-free methods. We report on a new bioreactor for the production of collagen scaffolds seeded with Mesenchymal Stem Cells (MSCs). It contains a computer controlled mechanical activation and ultrasonic online monitoring and has been constructed for the in situ determination of ultrasonic and rheological parameters. During the cultivation period of about two weeks the scaffold is periodically compressed by two movable pistons for improved differentiation of the MSCs. This periodic compression beneficially ensures the supply with nutrition even inside the sample. During the physiological stimuli, rheological properties are measured by means of highly sensitive load cells. In addition measurements of the speed of sound in the sample and in the culture medium, with frequencies up to 16 MHz, are performed continuously. Therefore piezoceramic transducers are attached to the pistons and emit and detect ultrasonic waves, travelling through the pistons, the sample and the culture medium. The time-of-flight (TOF) of the ultrasonic signals is determined in real time with the aid of chirped excitation and correlation procedures with a resolution of at least 10 ps. The implemented ultrasonic measurement scheme allows beside the speed of sound measurements the detection of the distance between the pistons with a resolution better than 100 nm. The developed monitoring delivers information on rigidity, fluid dynamics and velocity of sound in the sample and in the culture medium. The hermetically sealed bioreactor with its life support system provides a biocompatible environment for MSCs for long time cultivation.

  14. Cartilage tissue engineering of nasal septal chondrocyte-macroaggregates in human demineralized bone matrix.

    Science.gov (United States)

    Liese, Juliane; Marzahn, Ulrike; El Sayed, Karym; Pruss, Axel; Haisch, Andreas; Stoelzel, Katharina

    2013-06-01

    Tissue Engineering is an important method for generating cartilage tissue with isolated autologous cells and the support of biomaterials. In contrast to various gel-like biomaterials, human demineralized bone matrix (DBM) guarantees some biomechanical stability for an application in biomechanically loaded regions. The present study combined for the first time the method of seeding chondrocyte-macroaggregates in DBM for the purpose of cartilage tissue engineering. After isolating human nasal chondrocytes and creating a three-dimensional macroaggregate arrangement, the DBM was cultivated in vitro with the macroaggregates. The interaction of the cells within the DBM was analyzed with respect to cell differentiation and the inhibitory effects of chondrocyte proliferation. In contrast to chondrocyte-macroaggregates in the cell-DBM constructs, morphologically modified cells expressing type I collagen dominated. The redifferentiation of chondrocytes, characterized by the expression of type II collagen, was only found in low amounts in the cell-DBM constructs. Furthermore, caspase 3, a marker for apoptosis, was detected in the chondrocyte-DBM constructs. In another experimental setting, the vitality of chondrocytes as related to culture time and the amount of DBM was analyzed with the BrdU assay. Higher amounts of DBM tended to result in significantly higher proliferation rates of the cells within the first 48 h. After 96 h, the vitality decreased in a dose-dependent fashion. In conclusion, this study provides the proof of concept of chondrocyte-macroaggregates with DBM as an interesting method for the tissue engineering of cartilage. The as-yet insufficient redifferentiation of the chondrocytes and the sporadic initiation of apoptosis will require further investigations.

  15. Regulation of tissue repair and regeneration by electric fields

    Institute of Scientific and Technical Information of China (English)

    WANG En-tong; ZHAO Min

    2010-01-01

    Endogenous electric fields(Efs)have been detected at wounds and damaged tissues.The potential roles of Efs in tissue repair and regeneration have been an intriguing topic for centuries.Recent researches have provided significant insights into how naturally occurring Efs may participate in the control of tissue repair and regeneration.Applied Efs equivalent to the size of fields measured in vivo direct cell migration,cell proliferation and nerve sprouting at wounds.More remarkably,physiological Efs are a guidance cue that directs cell migration which overrides other well accepted directional signals including initial injury stimulation,wound void,contact inhibition release,population pressure and chemotaxis.Efs activate many intracellular signaling pathways in a directional manner.Modulation of endogenous wound Efs affects epithelial cell migration,cell proliferation,and nerve growth at cornea wounds in vivo.Electric stimulation is being tested clinically for the treatments of bone fracture,wound healing and spinal cord injury.Efs thus may represent a novel type of signaling paradigm in tissue repair and regeneration.Combination of the electric stimulation and other well understood biochemical regulatory mechanisms may offer powerful and effective therapies for tissue repair and regeneration.This review introduces experimental evidence for the existence of endogenous Efs and discusses their roles in tissue repair and regeneration.

  16. 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.

  17. An additive manufacturing-based PCL-alginate-chondrocyte bioprinted scaffold for cartilage tissue engineering.

    Science.gov (United States)

    Kundu, Joydip; Shim, Jin-Hyung; Jang, Jinah; Kim, Sung-Won; Cho, Dong-Woo

    2015-11-01

    Regenerative medicine is targeted to improve, restore or replace damaged tissues or organs using a combination of cells, materials and growth factors. Both tissue engineering and developmental biology currently deal with the process of tissue self-assembly and extracellular matrix (ECM) deposition. In this investigation, additive manufacturing (AM) with a multihead deposition system (MHDS) was used to fabricate three-dimensional (3D) cell-printed scaffolds using layer-by-layer (LBL) deposition of polycaprolactone (PCL) and chondrocyte cell-encapsulated alginate hydrogel. Appropriate cell dispensing conditions and optimum alginate concentrations for maintaining cell viability were determined. In vitro cell-based biochemical assays were performed to determine glycosaminoglycans (GAGs), DNA and total collagen contents from different PCL-alginate gel constructs. PCL-alginate gels containing transforming growth factor-β (TGFβ) showed higher ECM formation. The 3D cell-printed scaffolds of PCL-alginate gel were implanted in the dorsal subcutaneous spaces of female nude mice. Histochemical [Alcian blue and haematoxylin and eosin (H&E) staining] and immunohistochemical (type II collagen) analyses of the retrieved implants after 4 weeks revealed enhanced cartilage tissue and type II collagen fibril formation in the PCL-alginate gel (+TGFβ) hybrid scaffold. In conclusion, we present an innovative cell-printed scaffold for cartilage regeneration fabricated by an advanced bioprinting technology. PMID:23349081

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

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    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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. Experimental study on tissue engineering resurfacing of articular cartilage defect%组织工程修复关节软骨缺损的实验研究

    Institute of Scientific and Technical Information of China (English)

    胡怀建; 雍宜民; 沈惠良

    2001-01-01

    目的用组织工程的方法,将新生关节软骨细胞先在高分子聚乳酸材料上进行体外培养,然后移植于关节软骨缺损处,以达到修复关节软骨缺损的目的。方法取新生新西兰兔关节软骨细胞培养于高分子聚乳酸材料支架上。将16只兔的32个膝关节股骨髁处人工造成一4mm×6mm大小缺损,并随机分为二组。Ⅰ组10只兔,20个关节缺损,用软骨细胞-高分子聚乳酸移植修复。Ⅱ组6只兔,左膝用软骨细胞-高分子聚乳酸移植体修复,表面覆盖单层软骨细胞;右膝仅用高分子聚乳酸材料修复。术后分别于4、8、12、24周取标本进行大体、光镜、组织化学的方法进行结果评估。结果用软骨细胞-高分子聚乳酸移植体能修复关节软骨缺损,且为透明软骨。新生软骨组织胶原定型为Ⅱ型胶原。结论用软骨细胞-高分子聚乳酸移植体移植,关节软骨缺损能获得透明软骨修复。%Objective Tissue engineering by chondrocyte transplantation with biodegradable polylactic acid scaffolds and new cartilage formation after in vitro culture is developed as a new attempt to repair articular cartilage defects.Methods Chondrocytes from newborn New Zealand rabbits were cultured on polylactic acid implants in vitro.4mm×6mm defects were created artificially at 32 knee joints of 16 rabbits and were randomized into 2 groups.20 joint defects of 10 rabbits in Group 1 were repaired by chondrocyte-seeded polylactic acid implants.In group 2,the left knee joint defects were repaired by chondrocyte-seeded polylactic acid implants while the right knee defects were repaired by polylactic acid implants only.Specimens were collected and assessed grossly,by light microscopy and histochemically at the 4,8,12 and 24th week after operation.Results Joint defects were repaired by chondrocyte-seeded polylactic acid implants and the new cartilages were hyalinic.The collagen component in the new

  7. 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.

  8. 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%Polyhydroxyalkanoate polymer carrying chondrocytes for repair of allogeneic laryngeal cartilage defects

    Institute of Scientific and Technical Information of China (English)

    吴延平; 吴方

    2015-01-01

    BACKGROUND:Laryngeal cartilage defect has a higher incidence, mainly presenting with pain, sweling, and dysfunction after onset. Currently, surgical treatment is the most used in clinical treatment of laryngeal cartilage defect. Although conventional materials can effectively improve symptoms, there is a poor long-term efficacy. In recent years, there are many clinical studies on cartilage tissue engineering, but less about the actual use in the otorhinolaryngology department. OBJECTIVE:To investigate the effect of polyhydroxyalkanoate polymer carrying chondrocytes on the repair of alogeneic laryngeal cartilage defects. METHODS:Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHH) served as the extracelular matrix. Tissue engineering technology was used to prepare cel-material composite. Primary tissue-engineered cartilage tissue was transplanted directly into rabbit thyroid cartilage defect (experimental group A), or implanted into a more mature tissue-engineered cartilage for the repair of thyroid cartilage defect (experimental group B). In the experiment, PHBHH group and simple chondrocyte group were set as controls. Repairing effects on thyroid cartilage defect were evaluated through gross and histological observation. RESULTS AND CONCLUSION:Chondrocytes in the primary tissue-engineered cartilage tissues were beaded under scanning electron microscope, and after 4 weeks of culture, a large amount of jely-shaped substrates were visible. Findings from electron microscope observation showed that the cels were distributed on the surface of composite material and cavernous voids, displaying a plurality of smal round projections. Surgical treatment was successful in al the rabbits, and there was no dyspnea and eating difficulties after surgery. One rabbit appeared to have brief wheezing in the experimental group A, two rabbits died of diarrhea in the experimental B group at 2 weeks after surgery. PHBHH composite carrying chondrocytes had certain hardness. At 4 weeks

  9. Autologous, allogeneic, induced pluripotent stem cell or a combination stem cell therapy? Where are we headed in cartilage repair and why: a concise review

    NARCIS (Netherlands)

    Vonk, L.A.; Windt, de T.S.; Slaper-Cortenbach, Ineke C.M.; Saris, D.B.F.

    2015-01-01

    The evolution of articular cartilage repair procedures has resulted in a variety of cell-based therapies that use both autologous and allogeneic mesenchymal stromal cells (MSCs). As these cells are increasingly available and show promising results both in vitro and in vivo, cell-based strategies, wh

  10. Autologous, allogeneic, induced pluripotent stem cell or a combination stem cell therapy? Where are we headed in cartilage repair and why : A concise review

    NARCIS (Netherlands)

    Vonk, Lucienne A.; De Windt, Tommy S.; Slaper-Cortenbach, Ineke C M; Saris, Daniël B F

    2015-01-01

    The evolution of articular cartilage repair procedures has resulted in a variety of cell-based therapies that use both autologous and allogeneic mesenchymal stromal cells (MSCs). As these cells are increasingly available and show promising results both in vitro and in vivo, cell-based strategies, wh

  11. miRNA control of tissue repair and regeneration.

    Science.gov (United States)

    Sen, Chandan K; Ghatak, Subhadip

    2015-10-01

    Tissue repair and regeneration rely on the function of miRNA, molecular silencers that enact post-transcriptional gene silencing of coding genes. Disruption of miRNA homeostasis is developmentally lethal, indicating that fetal tissue development is tightly controlled by miRNAs. Multiple critical facets of adult tissue repair are subject to control by miRNAs, as well. Sources of cell pool for tissue repair and regeneration are diverse and provided by processes including cellular dedifferentiation, transdifferentiation, and reprogramming. Each of these processes is regulated by miRNAs. Furthermore, induced pluripotency may be achieved by miRNA-based strategies independent of transcription factor manipulation. The observation that miRNA does not integrate into the genome makes miRNA-based therapeutic strategies translationally valuable. Tools to manipulate cellular and tissue miRNA levels include mimics and inhibitors that may be specifically targeted to cells of interest at the injury site. Here, we discuss the extraordinary importance of miRNAs in tissue repair and regeneration based on emergent reports and rapid advances in miRNA-based therapeutics.

  12. Analyzing the Function of Cartilage Replacements: A Laboratory Activity to Teach High School Students Chemical and Tissue Engineering Concepts

    Science.gov (United States)

    Renner, Julie N.; Emady, Heather N.; Galas, Richards J., Jr.; Zhange, Rong; Baertsch, Chelsey D.; Liu, Julie C.

    2013-01-01

    A cartilage tissue engineering laboratory activity was developed as part of the Exciting Discoveries for Girls in Engineering (EDGE) Summer Camp sponsored by the Women In Engineering Program (WIEP) at Purdue University. Our goal was to increase awareness of chemical engineering and tissue engineering in female high school students through a…

  13. 聚乳酸-乙醇酸共聚物/羟基磷灰石复合支架修复喉软骨缺损%Polylactic acid-glycolic acid copolymer/hydroxyapatite composite scaffold repairs laryngeal cartilage defect

    Institute of Scientific and Technical Information of China (English)

    刘永刚; 周香桃

    2015-01-01

    BACKGROUND:The traditional repair methods for laryngeal cartilage defect are restricted by donor source, rejection, which are difficult to be popularized. OBJECTIVE:To investigate the effect of polylactic acid-glycolic acid copolymer/hydroxyapatite composite scaffold in repair of laryngeal cartilage defect. METHODS: A total of 20 Wistar rats were randomly divided into polylactic acid-glycolic acid copolymer/hydroxyapatite composite scaffold and polylactic acid-glycolic acid copolymer scaffold groups. Polylactic acid-glycolic acid copolymer/hydroxyapatite composite scaffold and polylactic acid-glycolic acid copolymer scaffold were respectively used for repair after the establishment of laryngeal cartilage defect models. RESULTS AND CONCLUSION: The laryngeal cartilage defect diameter of rats at 3, 5 and 7 days after modeling in the polylactic acid-glycolic acid copolymer/hydroxyapatite composite scaffold group was significantly smaler than that in the polylactic acid-glycolic acid copolymer scaffold group. The laryngeal cartilage defect of rats in the polylactic acid-glycolic acid copolymer/hydroxyapatite composite scaffold group was basicaly repaired and presented with a smooth surface, and there were no clear boundaries with surrounding tissues; however, the laryngeal cartilage defect of rats in the polylactic acid-glycolic acid copolymer scaffold group had indentations with a rough surface, and there were obvious boundaries with surrounding tissues. These results demonstrate that polylactic acid-glycolic acid copolymer/hydroxyapatite composite scaffold can promote the repair of laryngeal cartilage defect part, and its repair effect is more ideal.%背景:喉软骨缺损传统的修复方法受到供体来源、排斥反应等限制,因而难以推广。目的:观察聚乳酸-乙醇酸共聚物/羟基磷灰石复合支架修复喉软骨缺损的效果。方法:将20只Wistar 大鼠随机分为聚乳酸-乙醇酸共聚物/羟基磷灰石复合支架组和聚

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

    DEFF Research Database (Denmark)

    Andreasen, Jens O

    2012-01-01

    of 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 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....

  15. The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

    Directory of Open Access Journals (Sweden)

    Betul Kul Babur

    Full Text Available We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix "cartilage dust (CD". Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage

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

    NARCIS (Netherlands)

    Hoff, J.W. Von den; Agren, M.S.; Coulomb, B.; Eming, S.A.; Lataillade, J.J.

    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.

  17. 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.

  18. 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

  19. 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...

  20. Matrix metalloproteinase-8 overexpression prevents proper tissue repair

    DEFF Research Database (Denmark)

    Danielsen, Patricia L; Holst, Anders V; Maltesen, Henrik R;

    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...

  1. 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

  2. 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

  3. 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....

  4. 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.)

  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. Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells.

    Science.gov (United States)

    Pak, Jaewoo; Lee, Jung Hun; Lee, Sang Hee

    2014-01-01

    Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.

  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. 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.

  10. 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...

  11. 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); ...

  12. 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)

  13. 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

  14. New frontiers in biomaterials research for tissue repair and regeneration

    Institute of Scientific and Technical Information of China (English)

    Huiling Liu; Haoran Liu; Aaron Clasky; Huilin Yang; Lei Yang

    2016-01-01

    The field of biomaterials has recently emerged to augment or replace lost or damaged tissues and organs due to the human body’s limited ability to self-heal large defects. Historically, metallic components, polymers, ceramics, and composite materials were utilized as synthetic materials along with natural materials to assist in therapy. Various novel biomaterials were developed to respond to a significant amount of new medical challenges in the past decade. Therefore, there is a need to review these newly developed biomaterials and their potential to improve tissue repair and regeneration in a variety of applications. Here, we briefly review the different strategies and attempts to use novel biomaterials, including self-assembled and macromolecular biomaterials, hydrogels, metamaterials, decellularized tissues, and biomaterials obtained via synthetic biology, used either for tissue repair and regeneration or for therapeutic use by exploiting other mechanisms of healing. All these methods aim to create functional materials, devices, systems, and/or organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. This review details the various methods and introduces the applications of these biomaterials in tissue repair and regeneration, especially for bone, nerve, and skin applications.

  15. 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

  16. 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.

  17. In vitro targeted magnetic delivery and tracking of superparamagnetic iron oxide particles labeled stem cells for articular cartilage defect repair.

    Science.gov (United States)

    Feng, Yong; Jin, Xuhong; Dai, Gang; Liu, Jun; Chen, Jiarong; Yang, Liu

    2011-04-01

    To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles (SPIO) labeled mesenchymal stem cells (MSCs) density at a localized cartilage defect site in an in vitro phantom by applying magnetic force. Meanwhile, non-invasive imaging techniques were use to track SPIO-labeled MSCs by magnetic resonance imaging (MRI). Human bone marrow MSCs were cultured and labeled with SPIO. Fresh degenerated human osteochondral fragments were obtained during total knee arthroplasty and a cartilage defect was created at the center. Then, the osteochondral fragments were attached to the sidewalls of culture flasks filled with phosphate-buffered saline (PBS) to mimic the human joint cavity. The SPIO-labeled MSCs were injected into the culture flasks in the presence of a 0.57 Tesla (T) magnetic force. Before and 90 min after cell targeting, the specimens underwent T2-weighted turbo spin-echo (SET2WI) sequence of 3.0 T MRI. MRI results were compared with histological findings. Macroscopic observation showed that SPIO-labeled MSCs were steered to the target region of cartilage defect. MRI revealed significant changes in signal intensity (P<0.01). HE staining exibited that a great number of MSCs formed a three-dimensional (3D) cell "sheet" structure at the chondral defect site. It was concluded that 0.57 T magnetic force permits spatial delivery of magnetically labeled MSCs to the target region in vitro. High-field MRI can serve as an very sensitive non-invasive technique for the visualization of SPIO-labeled MSCs.

  18. Auricular reconstruction in patients with congenital microtia using homograft costal cartilage prepared by the Iranian Tissue Bank

    Directory of Open Access Journals (Sweden)

    Karimiyazdi A

    2008-12-01

    Full Text Available "nBackground: Several therapeutic modalities have been cited for patients with microtia. Recently there are several reports about using cadaveric homograft cartilage for some other purposes. The aim of this study was to assess the results of auricular reconstruct-tion in 10 patients (12 ears with congenital atresia using homograft rib cartilage from the Iranian Tissue Bank. "nMethods: We enrolled 10 patients with microtia who were referred to the Imam Khomeini Hospital from September 2006 to July 2007 for auricular reconstruction. The reconstruction was performed using a pre-shaped homograft(s of each patient's ear(s made by the Iranian Tissue Bank from the 6th, 7th and 8th costal cartilage according to the method of Marquette. In six patients, the second stage of reconstructive surgery was performed three months after the first stage. The patients were followed regarding the ear appearance, the dimensions of cartilage and tissue reaction. "nResults: The mean age of the patients was 11.08 (SD=5.57 years and the average duration of follow-up was 6.29 (SD=3.12 months. Eight cases had unilateral involvement (six right and two left, in addition to two cases of bilateral involvement. During the follow-up period, the appearance of the helix was satisfactory in 11 ears and the lobule in 10 ears. The height and width of the reconstructed auricles was an average of 1-2 millimeters different from the opposite ear. Erythema was the most common early complication. Late complications, including cartilage exposure and infection, were observed in one patient. "nConclusion: Auricular reconstruction using homograft costal cartilage in patients with microtia has promising results. The short term resorption can be ignored and significant early or late complications are infrequent.

  19. 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...

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

    Science.gov (United States)

    Musumeci, G; Loreto, C; Carnazza, M L; Coppolino, F; Cardile, V; Leonardi, R

    2011-01-01

    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.

  1. Meniscal repair by fibrocartilage in the dog : Characterization of the repair tissue and the role of vascularity

    NARCIS (Netherlands)

    Veth, RPH; Jansen, HWB; Nielsen, HKL; deGroot, JH; Pennings, AJ; Kuijer, R

    1996-01-01

    Lesions in the avascular part of 20 canine menisci were repaired by implantation of a porous polyurethane. Seven menisci were not repaired and served as controls. The repair tissue was characterized by biochemical and immunological analysis. The role of vascularity in healing was studied by perfusio

  2. Tissue Engineering a Biological Repair Strategy for Lumbar Disc Herniation.

    Science.gov (United States)

    O'Connell, Grace D; Leach, J Kent; Klineberg, Eric O

    2015-01-01

    The intervertebral disc is a critical part of the intersegmental soft tissue of the spinal column, providing flexibility and mobility, while absorbing large complex loads. Spinal disease, including disc herniation and degeneration, may be a significant contributor to low back pain. Clinically, disc herniations are treated with both nonoperative and operative methods. Operative treatment for disc herniation includes removal of the herniated material when neural compression occurs. While this strategy may have short-term advantages over nonoperative methods, the remaining disc material is not addressed and surgery for mild degeneration may have limited long-term advantage over nonoperative methods. Furthermore, disc herniation and surgery significantly alter the mechanical function of the disc joint, which may contribute to progression of degeneration in surrounding tissues. We reviewed recent advances in tissue engineering and regenerative medicine strategies that may have a significant impact on disc herniation repair. Our review on tissue engineering strategies focuses on cell-based and inductive methods, each commonly combined with material-based approaches. An ideal clinically relevant biological repair strategy will significantly reduce pain and repair and restore flexibility and motion of the spine. PMID:26634189

  3. 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

  4. The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues

    Science.gov (United States)

    Sherk, Vanessa D.; Carpenter, R. Dana; Weaver, Michael; Crapo, Silvia; Gally, Fabienne; Chatham, Lillian S.; Goldstrohm, David A.; Crapo, James D.; Kohrt, Wendy M.; Bowler, Russell P.; Oberley-Deegan, Rebecca E.; Regan, Elizabeth A.

    2015-01-01

    Osteoarthritis (OA) is associated with increased mechanical damage to joint cartilage. We have previously found that extracellular superoxide dismutase (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage may play a role in OA. We explored the effect of forced running as a surrogate for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding. Transgenic mice heterozygous (Het) for the human ECSOD R213G polymorphism and 129-SvEv (wild-type, WT) mice were exposed to forced running on a treadmill for 45 min/day, 5 days/wk, over 8 wk. At the end of the running protocol, knee joint tissue was obtained for histology, immunohistochemistry, and protein analysis. Sedentary Het and WT mice were maintained for comparison. Whole tibias were studied for bone morphometry, finite element analysis, and mechanical testing. Forced running improved joint histology in WT mice. However, when ECSOD levels were reduced, this beneficial effect with running was lost. Het ECSOD runner mice had significantly worse histology scores compared with WT runner mice. Runner mice for both strains had increased bone strength in response to the running protocol, while Het mice showed evidence of a less robust bone structure in both runners and untrained mice. Reduced levels of ECSOD in cartilage produced joint damage when joints were stressed by forced running. The bone tissues responded to increased loading with hypertrophy, regardless of mouse strain. We conclude that ECSOD plays an important role in protecting cartilage from damage caused by mechanical loading. PMID:25593283

  5. 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

  6. 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...

  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. 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...

  10. rAAV-mediated overexpression of sox9, TGF-β and IGF-I in minipig bone marrow aspirates to enhance the chondrogenic processes for cartilage repair.

    Science.gov (United States)

    Frisch, J; Rey-Rico, A; Venkatesan, J K; Schmitt, G; Madry, H; Cucchiarini, M

    2016-03-01

    Administration of therapeutic gene sequences coding for chondrogenic and chondroreparative factors in bone marrow aspirates using the clinically adapted recombinant adeno-associated virus (rAAV) vector may provide convenient, single-step approaches to improve cartilage repair. Here, we tested the ability of distinct rAAV constructs coding for the potent SOX9, transforming growth factor beta (TGF-β) and insulin-like growth factor I (IGF-I) candidate factors to modify marrow aspirates from minipigs to offer a preclinical large animal model system adapted for a translational evaluation of cartilage repair upon transplantation in sites of injury. Our results demonstrate that high, prolonged rAAV gene transfer efficiencies were achieved in the aspirates (up to 100% for at least 21 days) allowing to produce elevated amounts of the transcription factor SOX9 that led to increased levels of matrix synthesis and chondrogenic differentiation and of the growth factors TGF-β and IGF-I that both increased cell proliferation, matrix synthesis and chondrogenic differentiation (although to a lower level than SOX9) compared with control (lacZ) condition. Remarkably, application of the candidate SOX9 vector also led to reduced levels of hypertrophic differentiation in the aspirates, possibly by modulating the β-catenin, Indian hedgehog and PTHrP pathways. The present findings show the benefits of modifying minipig marrow concentrates via rAAV gene transfer as a future means to develop practical strategies to promote cartilage repair in a large animal model.

  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. Photoresponsive Polysaccharide-Based Hydrogels with Tunable Mechanical Properties for Cartilage Tissue Engineering.

    Science.gov (United States)

    Giammanco, Giuseppe E; Carrion, Bita; Coleman, Rhima M; Ostrowski, Alexis D

    2016-06-15

    Photoresponsive hydrogels were obtained by coordination of alginate-acrylamide hybrid gels (AlgAam) with ferric ions. The photochemistry of Fe(III)-alginate was used to tune the chemical composition, mechanical properties, and microstructure of the materials upon visible light irradiation. The photochemical treatment also induced changes in the swelling properties and transport mechanism in the gels due to the changes in material composition and microstructure. The AlgAam gels were biocompatible and could easily be dried and rehydrated with no change in mechanical properties. These gels showed promise as scaffolds for cartilage tissue engineering, where the photochemical treatment could be used to tune the properties of the material and ultimately change the growth and extracellular matrix production of chondrogenic cells. ATDC5 cells cultured on the hydrogels showed a greater than 2-fold increase in the production of sulfated glycosaminoglycans (sGAG) in the gels irradiated for 90 min compared to the dark controls. Our method provides a simple photochemical tool to postsynthetically control and adjust the chemical and mechanical environment in these gels, as well as the pore microstructure and transport properties. By changing these properties, we could easily access different levels of performance of these materials as substrates for tissue engineering.

  13. Collagen scaffolds with controlled insulin release and controlled pore structure for cartilage tissue engineering.

    Science.gov (United States)

    Nanda, Himansu Sekhar; Chen, Shangwu; Zhang, Qin; Kawazoe, Naoki; Chen, Guoping

    2014-01-01

    Controlled and local release of growth factors and nutrients from porous scaffolds is important for maintenance of cell survival, proliferation, and promotion of tissue regeneration. The purpose of the present research was to design a controlled release porous collagen-microbead hybrid scaffold with controlled pore structure capable of releasing insulin for application to cartilage tissue regeneration. Collagen-microbead hybrid scaffold was prepared by hybridization of insulin loaded PLGA microbeads with collagen using a freeze-drying technique. The pore structure of the hybrid scaffold was controlled by using preprepared ice particulates having a diameter range of 150-250 μ m. Hybrid scaffold had a controlled pore structure with pore size equivalent to ice particulates and good interconnection. The microbeads showed an even spatial distribution throughout the pore walls. In vitro insulin release profile from the hybrid scaffold exhibited a zero order release kinetics up to a period of 4 weeks without initial burst release. Culture of bovine articular chondrocytes in the hybrid scaffold demonstrated high bioactivity of the released insulin. The hybrid scaffold facilitated cell seeding and spatial cell distribution and promoted cell proliferation.

  14. Collagen Scaffolds with Controlled Insulin Release and Controlled Pore Structure for Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Himansu Sekhar Nanda

    2014-01-01

    Full Text Available Controlled and local release of growth factors and nutrients from porous scaffolds is important for maintenance of cell survival, proliferation, and promotion of tissue regeneration. The purpose of the present research was to design a controlled release porous collagen-microbead hybrid scaffold with controlled pore structure capable of releasing insulin for application to cartilage tissue regeneration. Collagen-microbead hybrid scaffold was prepared by hybridization of insulin loaded PLGA microbeads with collagen using a freeze-drying technique. The pore structure of the hybrid scaffold was controlled by using preprepared ice particulates having a diameter range of 150–250 μm. Hybrid scaffold had a controlled pore structure with pore size equivalent to ice particulates and good interconnection. The microbeads showed an even spatial distribution throughout the pore walls. In vitro insulin release profile from the hybrid scaffold exhibited a zero order release kinetics up to a period of 4 weeks without initial burst release. Culture of bovine articular chondrocytes in the hybrid scaffold demonstrated high bioactivity of the released insulin. The hybrid scaffold facilitated cell seeding and spatial cell distribution and promoted cell proliferation.

  15. 单侧唇裂鼻软骨不同程度畸形的个性化整复%Customized repair of unilateral cleft lip nasal deformities based on different degree of nasal cartilage framework deformities

    Institute of Scientific and Technical Information of China (English)

    杜本军; 王生钰

    2012-01-01

    目的 探讨采用不同强度自体组织植入、固定矫正单侧唇裂鼻软骨不同程度畸形的临床应用效果.方法 根据鼻尖及软骨支架畸形的程度和鼻尖偏斜程度,选取鼻中隔软骨、肋软骨及髂骨作为鼻小柱支架材料.对自2006年10月至2010年10月期间收治的30例单侧唇裂鼻畸形患者的临床资料进行回顾性分析.结果 术后创口愈合良好,无并发症发生.平均随访6个月,植入材料固位良好、无移位,效果满意.结论 鼻中隔软骨、肋软骨及髂骨作为单侧唇裂鼻畸形整复术中鼻小柱的支架材料,可对抗不同强度的应力,避免术后复发.%Objective To discuss the application of different autologous tissue graft for the repair of unilateral cleft lip nasal deformities based on different degree of nasal cartilage framework deformities. Methods Autologous septal cartilage, costal cartilage and iliac bone were implanted as the nasal tip framework according to different deformities. A retrospective study on 30 patients with unilateral cleft lip nasal deformity received from October 2006 to October 2010 was performed. Results All cases healed primarily without postoperative complications. After 6 months follow-up on average, satisfactory results were received in all cases without implants shift. Conclusion It can accommodate to varying force by customized repair of unilateral cleft lip nasal deformities by autologous septal cartilage, costal cartilage and iliac bone implant as scaffolds without recurrence.

  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. 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.

  18. Dog sciatic nerve gap repaired by artificial tissue nerve graft

    Institute of Scientific and Technical Information of China (English)

    GU Xiaosong; ZHANG Peiyun; WANG Xiaodong; DING Fei; PENG Luping; CHENG Hongbing

    2003-01-01

    The feasibility of repairing dog sciatic nerve damage by using a biodegradable artificial tissue nerve graft enriched with neuroregenerating factors is investigated. The artificial nerve graft was implanted to a 30 mm gap of the sciatic nerve damage in 7 dogs. The dogs with the same nerve damage that were repaired by interposition of the autologous nerve or were given no treatment served as control group 1 or 2, respectively. The observations include gross and morphological observations, immune reaction, electrophysiological examination, fluorescence tracing of the neuron formation and the number of the neurons at the experimental sites, etc. Results showed that 6 months after the implantation of the graft, the regenerated nerve repaired the damage of the sciatic nerve without occurrence of rejection and obvious inflammatory reaction in all 7 dogs, and the function of the sciatic nerve recovered with the nerve conduction velocity of (23.91±11.35)m/s. The regenerated neurons and the forming of axon could be observed under an electron microscope. This proves that artificial tissue nerve graft transplantation can bridge the damaged nerve ends and promote the nerve regeneration.

  19. 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...

  20. Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering

    Science.gov (United States)

    Silva, Joana M.; Georgi, Nicole; Costa, Rui; Sher, Praveen; Reis, Rui L.; Van Blitterswijk, Clemens A.; Karperien, Marcel; Mano, João F.

    2013-01-01

    Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs. PMID:23437056

  1. 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

  2. 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.

  3. Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

    Science.gov (United States)

    Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

    1994-01-01

    Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. [New challenge of tissue repair and regenerative medicine: to achieve a perfect repair and regeneration of multiple tissues in wound sites].

    Science.gov (United States)

    Fu, X B

    2016-01-01

    Great achievements in the study of tissue repair and regeneration have been made, and many of these successes have been shown to be beneficial to the patients in recent years. However, perfect tissue repair and regeneration of damaged tissues and organs remain to be great challenges in the management of trauma and diseases. Based on the progress in developmental biology in animals and advances in stem cell biology, it is possible to attain the aim of perfect repair and regeneration by means of somatic cell reprogramming and different inducing techniques.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Platelet lysate 3D scaffold supports mesenchymal stem cell chondrogenesis: an improved approach in cartilage tissue engineering.

    Science.gov (United States)

    Moroz, Andrei; Bittencourt, Renata Aparecida Camargo; Almeida, Renan Padron; Felisbino, Sérgio Luis; Deffune, Elenice

    2013-01-01

    Articular lesions are still a major challenge in orthopedics because of cartilage's poor healing properties. A major improvement in therapeutics was the development of autologous chondrocytes implantation (ACI), a biotechnology-derived technique that delivers healthy autologous chondrocytes after in vitro expansion. To obtain cartilage-like tissue, 3D scaffolds are essential to maintain chondrocyte differentiated status. Currently, bioactive 3D scaffolds are promising as they can deliver growth factors, cytokines, and hormones to the cells, giving them a boost to attach, proliferate, induce protein synthesis, and differentiate. Using mesenchymal stem cells (MSCs) differentiated into chondrocytes, one can avoid cartilage harvesting. Thus, we investigated the potential use of a platelet-lysate-based 3D bioactive scaffold to support chondrogenic differentiation and maintenance of MSCs. The MSCs from adult rabbit bone marrow (n = 5) were cultivated and characterized using three antibodies by flow cytometry. MSCs (1 × 10(5)) were than encapsulated inside 60 µl of a rabbit platelet-lysate clot scaffold and maintained in Dulbecco's Modified Eagle Medium Nutrient Mixture F-12 supplemented with chondrogenic inductors. After 21 days, the MSCs-seeded scaffolds were processed for histological analysis and stained with toluidine blue. This scaffold was able to maintain round-shaped cells, typical chondrocyte metachromatic extracellular matrix deposition, and isogenous group formation. Cells accumulated inside lacunae and cytoplasm lipid droplets were other observed typical chondrocyte features. In conclusion, the usage of a platelet-lysate bioactive scaffold, associated with a suitable chondrogenic culture medium, supports MSCs chondrogenesis. As such, it offers an alternative tool for cartilage engineering research and ACI.

  18. Sellar repair with autologous muscle and composite septal cartilage grafts for treatment of cerebrospinal fluid leakage following trans-sphenoidal pituitary surgery

    Science.gov (United States)

    El Shazly, Ayman A.; El Wardany, Mohammed A.; Abo El Ezz, Tamer A.

    2016-01-01

    Context: Many reconstructive techniques have been proposed to prevent postoperative cerebrospinal fluid (CSF) leakage after trans-sphenoidal pituitary surgery. However, no total agreement has been reached to the best technique. Aim: Assessment of the efficacy of sellar repair with autologous muscle and composite septal cartilage grafts for treatment of intraoperative and delayed postoperative CSF leakage following trans-sphenoidal pituitary surgery without the use of postoperative external lumbar CSF drain. Study Design: This is a retrospective case series study, level IV evidence. Materials and Methods : Twenty three patients were involved in this study. Seventeen patients had intraoperative CSF leakage and were treated immediately by our technique. Six patients had postoperative CSF rhinorrhea and had delayed treatment with our technique after failure of conservative measures and external lumbar CSF drainage for more than three days. The technique involved intradural placement of autologous muscle graft supplemented with extradural composite septal cartilage graft, composed of a piece of the posterior cartilaginous septum with its covering mucoperichondrium on one side only to fit into the sellar defect as a double layer button. Results: CSF leak was of grade 1 in 6 patients (26.1%), grade 2 in 10 patients (43.5%) and grade 3 in 7 patients (30.4%). None of the patients in our study had postoperative CSF leak after the use of our technique during the follow up period (mean 24 ± 10.47 standard deviation months). None of the patients developed treatment-related complications. All the patients had well developed mucosal covering of the sellar defect after two months. Conclusion: Our technique of sellar repair by using autologous muscle and composite septal cartilage grafts is effective in treatment of intraoperative and delayed postoperative CSF leakage following trans-sphenoidal pituitary surgery without the use of postoperative external lumbar CSF drain even in

  19. 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...

  20. 腺病毒携带骨形态发生蛋白14基因转染脂肪干细胞修复损伤关节软骨%Adipose-derived stem cells transfected with adenovirus carrying bone morphogenetic protein 14 for repair of articular cartilage injury

    Institute of Scientific and Technical Information of China (English)

    马洪斌; 李运祥; 王铭伦

    2015-01-01

    BACKGROUND:The articular cartilage has weak self-repair ability, mainly due to its lack of trophoblast cels in blood vessels and slow cel metabolism. Current treatment methods cannot restore the original function of the cartilage tissue, and cartilage tissue engineering in recent years has garnered increasing attention. OBJECTIVE:To observe the effect of adipose-derived stem cels transfected with bone morphogenetic protein 14 combined with type I colagen sponge scaffold on the repair of articular cartilage injury in the knee of rabbits. METHODS: Adipose-derived stem cels were isolated and cultured from rabbit subcutaneous adipose tissue, and transfected with Ad-CMV-BMP-14-IRES-hrGFP-1. Type I colagen sponge scaffold with the transfected adipose-derived stem cels was used to repair articular cartilage injury in the knee of rabbits. Twelve weeks after operation, the articular tissue was taken for gross assessment and histological evaluation. RESULTS AND CONCLUSION: The expressions of bone morphogenetic protein 14, type II colagen and Sox-9 were higher in cels transfected with bone morphogenetic protein 14 than untransfected ones. At 12 weeks after operation, adipose-derived stem cels transfected with bone morphogenetic protein 14 combined with type I colagen sponge scaffold had good repair effect on articular cartilage injuries, and the injured cartilage tissues were smooth and had good texture, color and integration junction; adipose-derived stem cels combined with type I colagen sponge scaffold could partialy repair the injured cartilage tissues that had similar color and texture to normal tissues, and there was a remarkable boundary between the repaired tissue and normal cartilage tissue;simple type I colagen sponge scaffold was almost colapsed, and no hyaline cartilage tissue formed. These findings indicate that transfection of bone morphogenetic protein 14 can strengthen the ability of adipose-derived stem cels dramaticaly to repair cartilage injuries.%背景

  1. 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

  2. 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

  3. Tissue nonautonomous effects of fat body methionine metabolism on imaginal disc repair in Drosophila.

    Science.gov (United States)

    Kashio, Soshiro; Obata, Fumiaki; Zhang, Liu; Katsuyama, Tomonori; Chihara, Takahiro; Miura, Masayuki

    2016-02-16

    Regulatory mechanisms for tissue repair and regeneration within damaged tissue have been extensively studied. However, the systemic regulation of tissue repair remains poorly understood. To elucidate tissue nonautonomous control of repair process, it is essential to induce local damage, independent of genetic manipulations in uninjured parts of the body. Herein, we develop a system in Drosophila for spatiotemporal tissue injury using a temperature-sensitive form of diphtheria toxin A domain driven by the Q system to study factors contributing to imaginal disc repair. Using this technique, we demonstrate that methionine metabolism in the fat body, a counterpart of mammalian liver and adipose tissue, supports the repair processes of wing discs. Local injury to wing discs decreases methionine and S-adenosylmethionine, whereas it increases S-adenosylhomocysteine in the fat body. Fat body-specific genetic manipulation of methionine metabolism results in defective disc repair but does not affect normal wing development. Our data indicate the contribution of tissue interactions to tissue repair in Drosophila, as local damage to wing discs influences fat body metabolism, and proper control of methionine metabolism in the fat body, in turn, affects wing regeneration.

  4. Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis.

    Directory of Open Access Journals (Sweden)

    Anne C Bay-Jensen

    Full Text Available Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS. Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions. Type II collagen is the primary structural protein of cartilage and type III collagen of connective tissues, and obvious targets for the collagenalytic, which increase during tissue inflammation. The objective of the study was to investigate the diagnostic and prognostic utility of cartilage, C2M, and synovial, C3M, turnover biomarkers in AS. Serum samples were retrieved from patients suffering from AS (n = 103, RA (n = 47 and healthy controls (n = 56. AS progressors were defined as having new vertebral syndesmophytes or more that 3 unit change in mSASSS over a two-year period. Type II collagen degradation markers in serum were measured by the C2M ELISA, and type III collagen degradation by the C3M ELISA. Logistic regression and dichotomized decision tree were used to analyze the prognostic value of the markers individually or in combination. Both C2M and C3M levels were significantly higher in RA patients than in healthy controls (p<0.0001. Diagnostic utility was analyzed by ROC and areas under the curve (AUCs were 72% and 89% for C2M and C3M, respectively. Both C2M and C3M, were significantly higher in serum samples from AS patient than from healthy controls (p<0.0001. The AUCs of C2M and C3M, respectively, were 70% and 81% for AS. A combination of C2M and C3M, dichotomized according to best cut-offs for individual markers, could correctly identify 80% of the progressors and 61% of the non-progressors. The present study is the first to show that specific biomarkers of cartilage and connective tissue degradation facilitate both diagnosis and prediction of progression of RA and AS.

  5. 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)

  6. 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).

  7. Long-term results of rib perichondrial grafts for repair of cartilage defects in the human knee

    NARCIS (Netherlands)

    Bouwmeester, SJM; Beckers, JMH; Kuijer, R; van der Linden, AJ; Bulstra, SK

    1997-01-01

    Eighty-eight patients with articular cartilage defects in the knee were treated by perichondrial arthroplasty between 1986 and 1992. An autogenous strip of costal perichondrium was fixed in place with fibrin glue, followed by immobilisation, continuous passive motion, and partial weightbearing. The

  8. 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.

  9. 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

  10. Mesenchymal progenitor cells derived from synovium and infrapatellar fat pad as a source for superficial zone cartilage tissue engineering: analysis of superficial zone protein/lubricin expression.

    Science.gov (United States)

    Lee, Sang Yang; Nakagawa, Toshiyuki; Reddi, A Hari

    2010-01-01

    Superficial zone protein (SZP) is a boundary lubricant of articular cartilage in joints. As SZP at the surface of articular cartilage plays an important role in the normal function of synovial joints, the localization of SZP-secreting cells at the surface of tissue-engineered cartilage is prerequisite. The aim of this study was to identify suitable progenitor cell sources for tissue engineering of superficial zone cartilage. We investigated whether mesenchymal progenitor cells (MPCs) from synovium and infrapatellar fat pad (IFP) have the potential for secretion of SZP after chondrogenic differentiation in an aggregate pellet culture system. SZP was immunolocalized in pellets from synovium-MPCs and IFP-MPCs. The enzyme-linked immunosorbent assay analysis of SZP demonstrated that chondrogenically differentiated synovium-MPC and IFP-MPC pellets secreted SZP into media. Real-time polymerase chain reaction analysis showed significant upregulation of SZP mRNA in synovium-MPC and IFP-MPC pellets after chondrogenic differentiation. The synovium-MPCs demonstrated the higher colony-forming, proliferative, and chondrogenic potential, and exhibited greater SZP secretion after chondrogenic induction compared with IFP-MPCs. In conclusion, both synovium and IFP are promising cell sources for tissue engineering of superficial zone cartilage.

  11. Contact models of repaired articular surfaces: influence of loading conditions and the superficial tangential zone.

    Science.gov (United States)

    Owen, John R; Wayne, Jennifer S

    2011-07-01

    The superficial tangential zone (STZ) plays a significant role in normal articular cartilage's ability to support loads and retain fluids. To date, tissue engineering efforts have not replicated normal STZ function in cartilage repairs. This finite element study examined the STZ's role in normal and repaired articular surfaces under different contact conditions. Contact area and pressure distributions were allowed to change with time, tension-compression nonlinearity modeled collagen behavior in the STZ, and nonlinear geometry was incorporated to accommodate finite deformation. Responses to loading via impermeable and permeable rigid surfaces were compared to loading via normal cartilage, a more physiologic condition, anticipating the two rigid loading surfaces would bracket that of normal. For models loaded by normal cartilage, an STZ placed over the inferior repair region reduced the short-term axial compression of the articular surface by 15%, when compared to a repair without an STZ. Covering the repair with a normal STZ shifted the flow patterns and strain levels back toward that of normal cartilage. Additionally, reductions in von Mises stress (21%) and an increase in fluid pressure (13%) occurred in repair tissue under the STZ. This continues to show that STZ properties of sufficient quality are likely critical for the survival of transplanted constructs in vivo. However, response to loading via normal cartilage did not always fall within ranges predicted by the rigid surfaces. Use of more physiologic contact models is recommended for more accurate investigations into properties critical to the success of repair tissues.

  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. Supplementation of exogenous adenosine 5'-triphosphate enhances mechanical properties of 3D cell-agarose constructs for cartilage tissue engineering.

    Science.gov (United States)

    Gadjanski, Ivana; Yodmuang, Supansa; Spiller, Kara; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2013-10-01

    Formation of tissue-engineered cartilage is greatly enhanced by mechanical stimulation. However, direct mechanical stimulation is not always a suitable method, and the utilization of mechanisms underlying mechanotransduction might allow for a highly effective and less aggressive alternate means of stimulation. In particular, the purinergic, adenosine 5'-triphosphate (ATP)-mediated signaling pathway is strongly implicated in mechanotransduction within the articular cartilage. We investigated the effects of transient and continuous exogenous ATP supplementation on mechanical properties of cartilaginous constructs engineered using bovine chondrocytes and human mesenchymal stem cells (hMSCs) encapsulated in an agarose hydrogel. For both cell types, we have observed significant increases in equilibrium and dynamic compressive moduli after transient ATP treatment applied in the fourth week of cultivation. Continuous ATP treatment over 4 weeks of culture only slightly improved the mechanical properties of the constructs, without major changes in the total glycosaminoglycan (GAG) and collagen content. Structure-function analyses showed that transiently ATP-treated constructs, and in particular those based on hMSCs, had the highest level of correlation between compositional and mechanical properties. Transiently treated groups showed intense staining of the territorial matrix for GAGs and collagen type II. These results indicate that transient ATP treatment can improve functional mechanical properties of cartilaginous constructs based on chondrogenic cells and agarose hydrogels, possibly by improving the structural organization of the bulk phase and territorial extracellular matrix (ECM), that is, by increasing correlation slopes between the content of the ECM components (GAG, collagen) and mechanical properties of the construct.

  14. Evaluation of bone matrix gelatin/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering.

    Science.gov (United States)

    Wang, Z H; Zhang, J; Zhang, Q; Gao, Y; Yan, J; Zhao, X Y; Yang, Y Y; Kong, D M; Zhao, J; Shi, Y X; Li, X L

    2016-01-01

    This study was designed to evaluate bone matrix gelatin (BMG)/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering. Chondrocytes were isolated from costal cartilage of Sprague-Dawley rats and seeded on BMG/fibrin glue or chitosan/gelatin composite scaffolds. After different in vitro culture durations, the scaffolds were subjected to hematoxylin and eosin, Masson's trichrome, and toluidine blue staining, anti-collagen II and anti-aggrecan immunohistochemistry, and scanning electronic microscopy (SEM) analysis. After 2 weeks of culture, chondrocytes were distributed evenly on the surfaces of both scaffolds. Cell numbers and the presence of extracellular matrix components were markedly increased after 8 weeks of culture, and to a greater extent on the chitosan/gelatin scaffold. The BMG/fibrin glue scaffold showed signs of degradation after 8 weeks. Immunofluorescence analysis confirmed higher levels of collagen II and aggrecan using the chitosan/gelatin scaffold. SEM revealed that the majority of cells on the surface of the BMG/fibrin glue scaffold demonstrated a round morphology, while those in the chitosan/gelatin group had a spindle-like shape, with pseudopodia. Chitosan/gelatin scaffolds appear to be superior to BMG/ fibrin glue constructs in supporting chondrocyte attachment, proliferation, and biosynthesis of cartilaginous matrix components. PMID:27525846

  15. 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

  16. 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 ...

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Stem cells catalyze cartilage formation by neonatal articular chondrocytes in 3D biomimetic hydrogels

    Science.gov (United States)

    Lai, Janice H.; Kajiyama, Glen; Smith, Robert Lane; Maloney, William; Yang, Fan

    2013-12-01

    Cartilage loss is a leading cause of disability among adults and effective therapy remains elusive. Neonatal chondrocytes (NChons) are an attractive allogeneic cell source for cartilage repair, but their clinical translation has been hindered by scarce donor availability. Here we examine the potential for catalyzing cartilage tissue formation using a minimal number of NChons by co-culturing them with adipose-derived stem cells (ADSCs) in 3D hydrogels. Using three different co-culture models, we demonstrated that the effects of co-culture on cartilage tissue formation are dependent on the intercellular distance and cell distribution in 3D. Unexpectedly, increasing ADSC ratio in mixed co-culture led to increased synergy between NChons and ADSCs, and resulted in the formation of large neocartilage nodules. This work raises the potential of utilizing stem cells to catalyze tissue formation by neonatal chondrocytes via paracrine signaling, and highlights the importance of controlling cell distribution in 3D matrices to achieve optimal synergy.

  4. 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.

  5. 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

    2015-12-11

    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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Complement activation in the context of stem cells and tissue repair

    Institute of Scientific and Technical Information of China (English)

    Ingrid; U; Schraufstatter; Sophia; K; Khaldoyanidi; Richard; G; DiScipio

    2015-01-01

    The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation,to increased survival of various cell types in the presence of split products of complement,and to the production of trophic factors by cells activated by the anaphylatoxins C3 a and C5 a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3 a and C5 a.

  11. 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.

  12. 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

  13. 壳聚糖水凝胶复合脂肪间充质干细胞修复兔关节软骨缺损%Chitosan hydrogel composite with adipose-derived stem cells for repair of rabbit articular cartilage defect

    Institute of Scientific and Technical Information of China (English)

    林涛; 陈竹; 袁德超; 刘康; 向小聪; 周玉川; 冯刚

    2016-01-01

    Objective To fabricate a novel tissue-engineered cartilage with adipose-derived stem cells (ADSCs) seeded on the chitosan hydrogel scaffold to repair articular cartilage defect.Methods Adipose tissue and costal cartilage were harvested from New Zealand rabbits,and ADSCs in passage one and chondrocytes were obtained after the samples were digested and cultured in vitro.ADSCs were digested,suspended,seeded onto the sterile chitosan gel,and cultured in vitro for 1 week to fabricate the tissue-engineered cartilage.The defects were respectively filled with the tissue-engineered cartilage (composite group),chondrocyte suspension (cell group),chitosan gel (material group) and nothing at all (control group).At postoperative 12 weeks,cartilage repair was evaluated using the gross examination,histological staining,immunohistochemical staining and international cartilage repair society (ICRS) histological score.Results Effect of cartilage repair in composite group was significantly better compared to other groups.The regenerated tissue in composite group seemed tightly bound in normal tissue,with similar structure and extracellular matrix secretion.ICRS histological score in composite group was (13.89 ± 0.14) points,which differed significantly from (7.06 ± 0.19) points in control group,(7.14 ± 0.22) points in cell group and (7.46 ± 0.26) points in material group (P <0.01).Conclusion The tissue-engineered cartilage with ADSCs seeded onto the chitosan hydrogel is effective for repair of articular cartilage defect.%目的 探讨利用脂肪间充质干细胞(ADSCs)复合壳聚糖水凝胶支架构建的组织工程软骨修复兔关节软骨缺损的效果. 方法 分别取新西兰大白兔皮下脂肪和肋软骨,消化后体外扩增培养分别得到P1代ADSCs和软骨细胞.将ADSCs消化后制成细胞悬液,并种植于灭菌后的壳聚糖水凝胶上,体外培养1周构建组织工程软骨,将构建的组织工程软骨植入到兔的关节软骨缺损处.实

  14. 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

  15. Repair of rabbit articular cartilage and subchondral defects using porous silk fibroin/hydroxyapatite combined with adipose-derived stromal cells%多孔丝素蛋白/羟基磷灰石复合脂肪间充质干细胞修复兔关节软骨及软骨下骨缺损

    Institute of Scientific and Technical Information of China (English)

    鞠刚; 徐卫袁; 张亚; 张兴祥; 严飞; 沙卫平

    2011-01-01

    BACKGROUND: Silk fibroin/hydroxyapatite (SF/HA) is a good scaffold for three-dimensional culture of cells, and is a common material to repair bone defect with good biocompatibility. Adipose -derived stem cells (ADSCs) which can differentiate into bone and cartilage cells are ideal for repairing cartilage defect.OBJECTIVE: To observe the effects of the repair of articular cartilage and subchondral defects in rabbit knee joints with transforming growth factor-?1 and insulin like growth factor-1 in combination with SF/HA and ADSCs.METHODS: A total of 56 New Zealand rabbits were selected, and 2 were used for cultures of ADSCs, which were seeded onto SF/HA at a concentration of 3×109/L. The remaining 54 rabbits were used to establish model of articular cartilage and subchondral defects and randomly assigned to composite, simple and blank control groups. The composite and simple groups were respectively implanted with SF/HA/ADSCs scaffold and SF/HA scaffold. The blank control group was not implanted any materials. Repair of defects was observed and compared by gross, imaging and histological observations.RESULTS AND CONCLUSION: At 12 weeks, gross observation, CT, MRI and histological observations demonstrated that the articular cartilage and subchondral defects were repaired entirely in composite group. The color of repaired tissues was similar to surrounding cartilage. There was no evidence of the residue of silk fibroin or the infiltration of leukocytes. Defects were repaired partially and repaired with cartilage fibrosa in simple group. However, defects remained unchanged in blank control group.Results showed that SF/HA with ADSCs composite could successfully repair articular cartilage and subchondral defects of a rabbit knee joints and the effect was superior to SF/HA scaffold alone. The method for repairing the full-thickness hyaline cartilage defects and reconstructing anatomical structure and function of joints using SF/HA with ADSCs is feasible and promising to

  16. Autologous tissue repair of large abdominal wall defects.

    NARCIS (Netherlands)

    Vries Reilingh, T.S. de; Bodegom, M.E.; Goor, H. van; Hartman, E.H.M.; Wilt, G.J. van der; Bleichrodt, R.P.

    2007-01-01

    BACKGROUND AND METHOD: Techniques for autologous repair of abdominal wall defects that could not be closed primarily are reviewed. Medline and PubMed were searched for English or German publications using the following keywords: components separation technique (CST), Ramirez, da Silva, fascia lata,

  17. 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

  18. 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...

  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. The Application of Tissue Engineering Procedures to Repair the Larynx

    Science.gov (United States)

    Ringel, Robert L.; Kahane, Joel C.; Hillsamer, Peter J.; Lee, Annie S.; Badylak, Stephen F.

    2006-01-01

    The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice,…

  2. 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

  3. 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

  4. 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.

  5. Solid protein solder-doped biodegradable polymer membranes for laser-assisted tissue repair

    Science.gov (United States)

    Hodges, Diane E.; McNally-Heintzelman, Karen M.; Welch, Ashley J.

    2000-05-01

    Solid protein solder-doped polymer membranes have been developed for laser-assisted tissue repair. Biodegradable polymer films of controlled porosity were fabricated with poly(L-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) using a solvent-casting and particulate-leaching technique. The films provided a porous scaffold that readily absorbed the traditional protein solder mix composed of bovine serum albumin (BSA) and indocyanine green (ICG) dye. In vitro investigations were conducted to assess the influence of various processing parameters on the strength of tissue repairs formed using the new membranes. These parameters included the PLGA copolymer and PLGA/PEG blend ratio, the salt particle size, the initial bovine serum albumin (BSA) weight fraction, and the laser irradiance used to denature the solder. Altering the PLGA copolymer ratio had little effect on repair strength, however, it influenced the membrane degradation rate. Repair strength increased with increased membrane pore size and BSA concentration. The addition of PEG during the film casting stage increased the flexibility of the membranes but not necessarily the repair strength. The repair strength increased with increasing irradiance from 12 W/cm2 to 15 W/cm2. The new solder-doped polymer membranes provide all of the benefits associated with solid protein solders including high repair strength and improved edge coaptation. In addition, the flexible and moldable nature of the new membranes offer the capability of tailoring the membranes to a wide range of tissue geometries, and consequently, improved clinical applicability of laser- assisted tissue repair.

  6. 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...

  7. 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.

  8. Cartilage Wound Healing and Integration

    NARCIS (Netherlands)

    P.K. Bos (Koen)

    2006-01-01

    textabstractThe intrinsic regeneration capacity of articular cartilage following injury is limited. Partialthickness defects are not repaired and full-thickness defects are repaired with fi brocartilage. Untreated, these defects may progress to early osteoarthritis. The goal of surgical treatment

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Microsurgical repair at early stage for soft tissue defect of limbs wounded by modern firearm

    Institute of Scientific and Technical Information of China (English)

    刘晋才; 彭学良; 刘荫秋; 赖西南; 李曙光; 王民刚; 黄海洋; 杜全印; 孙红振

    2002-01-01

    To explore an early stage repair method for soft tissue defect of limbs of modern firearm wound, and to improve treating result. Methods: Defects of the hind limbs of dogs were repaired with skin, muscle and myocutaneous flaps. Results: Wounds healed within 2 weeks in the experimental group except one that healed in 3 weeks because of infection. Limb function was close to normal. The treatment result was better in the experimental group than the control. Conclusions: Skin, muscle and myocutaneous flaps can cover soft tissue defect at an early stage, prevent and reduce infection, promote the healing and recovery of combined injury, reduce the time of treatment and disability rate.

  16. 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.

  17. 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

  18. 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.

  19. 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...

  20. Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering.

    Science.gov (United States)

    Rennerfeldt, Deena A; Renth, Amanda N; Talata, Zsolt; Gehrke, Stevin H; Detamore, Michael S

    2013-11-01

    Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells.

  1. 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.

  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. Nucleotide excision repair is reduced in oral epithelial tissues compared with skin.

    Science.gov (United States)

    Mitchell, David; Paniker, Lakshmi; Godar, Dianne

    2012-01-01

    Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the signature mutations of UVR. Radioimmunoassay was used to quantify the induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in DNA purified from three reconstructed tissues, EpiDerm(TM) , EpiGingival(TM) and EpiOral(TM) . We observed comparable levels of DNA damage in all tissues immediately after UVR exposure. In contrast, repair was significantly reduced in both oral tissues compared with EpiDerm(TM) . Our data suggest that UVR exposure of oral tissues can result in accumulation of DNA damage and increase the risk for carcinoma and melanoma of the mouth. Because NER is a broad-spectrum defense against DNA damage caused by a variety of agents in addition to UVR, our data suggest that the relatively low NER efficiency observed in oral tissues may have wide-ranging consequences in this highly exposed environment.

  4. Nucleotide excision repair is reduced in oral epithelial tissues compared to skin‡

    Science.gov (United States)

    Mitchell, David; Paniker, Lakshmi; Godar, Dianne

    2012-01-01

    Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the signature mutations of UVR. Radioimmunoassay was used to quantify the induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in DNA purified from three reconstructed tissues, EpiDerm™, EpiGingival™, and EpiOral™ (MatTek Corp.). We observed comparable levels of DNA damage in all tissues immediately after UVR exposure. In contrast, repair was significantly reduced in both oral tissues compared to EpiDerm™. Our data suggest that UVR exposure of oral tissues can result in accumulation of DNA damage and increase the risk for carcinoma and melanoma of the mouth. Because NER is a broad-spectrum defense against DNA damage caused by a variety of agents in addition to UVR, our data suggest that the relatively low NER efficiency observed in oral tissues may have wide-ranging consequences in this highly exposed environment. PMID:22519509

  5. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction.

    Science.gov (United States)

    Shah, Nisarg J; Hyder, Md Nasim; Quadir, Mohiuddin A; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J; Nevins, Myron; Spector, Myron; Hammond, Paula T

    2014-09-01

    Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration.

  6. 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

  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. Nucleotide excision repair is reduced in oral epithelial tissues compared to skin‡

    OpenAIRE

    Mitchell, David; Paniker, Lakshmi; Godar, Dianne

    2012-01-01

    Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the ...

  9. 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 ...

  10. Lung tissue flap repairs esophagus defection with an inner chitosan tube stent

    Institute of Scientific and Technical Information of China (English)

    Gang Chen; Wen-Jun Shi

    2009-01-01

    AIM:To repair the partial esophagus defect with a chitosan stent, a new esophageal prosthesis made of pulmonary tissue with vascular pedicle. METHODS:Fifteen Japanese big ear white rabbits were divided into experimental group ( n = 10) and control group ( n = 5). Esophagus defect in rabbits of experimental group was repaired using lung tissue flap with a chitosan tube stent, gross and histological appearance was observed at week 2, 4 and 8 after operation, and barium sulphate X-ray screen was performed at week 10 after operation. Esophagus defect of rabbits in control group was repaired using lung tissue flap with no chitosan tube stent, gross and histological appearance was observed at week 2, 4 and 8 after operation, and barium sulphate X-ray screen was performed at week 10 after operation. RESULTS:In the experimental group, 6 rabbits survived for over two weeks, the lung tissue flap healed esophageal defec t ion, and squamous metaplasia occurred on the surface of lung tissue flap. At week 10 after operation, barium sulphate examination found that barium was fluent through the esophagus with no stricture or back stream, the creeping was good. In the control group, 4 rabbits survived for two weeks, the lung tissue flap healed esophageal defection with fibrous tissue hyperplasia, barium sulphate examination found that barium was fluent through the esophagus with a slight stricture or back stream, and the creeping was not good at week 10 after operation.CONCLUSION:Esophagus defect can be repaired using lung tissue flap with an inner chitosan tube stent.

  11. 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

  12. 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.

  13. 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...

  14. 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

  15. Tissue engineering of cartilage using a mechanobioreactor exerting simultaneous mechanical shear and compression to simulate the rolling action of articular joints.

    Science.gov (United States)

    Shahin, Kifah; Doran, Pauline M

    2012-04-01

    The effect of dynamic mechanical shear and compression on the synthesis of human tissue-engineered cartilage was investigated using a mechanobioreactor capable of simulating the rolling action of articular joints in a mixed fluid environment. Human chondrocytes seeded into polyglycolic acid (PGA) mesh or PGA-alginate scaffolds were precultured in shaking T-flasks or recirculation perfusion bioreactors for 2.5 or 4 weeks prior to mechanical stimulation in the mechanobioreactor. Constructs were subjected to intermittent unconfined shear and compressive loading at a frequency of 0.05 Hz using a peak-to-peak compressive strain amplitude of 2.2% superimposed on a static axial compressive strain of 6.5%. The mechanical treatment was carried out for up to 2.5 weeks using a loading regime of 10 min duration each day with the direction of the shear forces reversed after 5 min and release of all loading at the end of the daily treatment period. Compared with shaking T-flasks and mechanobioreactor control cultures without loading, mechanical treatment improved the amount and quality of cartilage produced. On a per cell basis, synthesis of both major structural components of cartilage, glycosaminoglycan (GAG) and collagen type II, was enhanced substantially by up to 5.3- and 10-fold, respectively, depending on the scaffold type and seeding cell density. Levels of collagen type II as a percentage of total collagen were also increased after mechanical treatment by up to 3.4-fold in PGA constructs. Mechanical treatment had a less pronounced effect on the composition of constructs precultured in perfusion bioreactors compared with perfusion culture controls. This work demonstrates that the quality of tissue-engineered cartilage can be enhanced significantly by application of simultaneous dynamic mechanical shear and compression, with the greatest benefits evident for synthesis of collagen type II.

  16. Bioinspired Nanoparticulate Medical Glues for Minimally Invasive Tissue Repair.

    Science.gov (United States)

    Lee, Yuhan; Xu, Chenjie; Sebastin, Monisha; Lee, Albert; Holwell, Nathan; Xu, Calvin; Miranda Nieves, David; Mu, Luye; Langer, Robert S; Lin, Charles; Karp, Jeffrey M

    2015-11-18

    Delivery of tissue glues through small-bore needles or trocars is critical for sealing holes, affixing medical devices, or attaching tissues together during minimally invasive surgeries. Inspired by the granule-packaged glue delivery system of sandcastle worms, a nanoparticulate formulation of a viscous hydrophobic light-activated adhesive based on poly(glycerol sebacate)-acrylate is developed. Negatively charged alginate is used to stabilize the nanoparticulate surface to significantly reduce its viscosity and to maximize injectability through small-bore needles. The nanoparticulate glues can be concentrated to ≈30 w/v% dispersions in water that remain localized following injection. With the trigger of a positively charged polymer (e.g., protamine), the nanoparticulate glues can quickly assemble into a viscous glue that exhibits rheological, mechanical, and adhesive properties resembling the native poly(glycerol sebacate)-acrylate based glues. This platform should be useful to enable the delivery of viscous glues to augment or replace sutures and staples during minimally invasive procedures.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. The cellular and molecular mechanisms of tissue repair and regeneration as revealed by studies in Xenopus

    Science.gov (United States)

    Li, Jingjing; Zhang, Siwei

    2016-01-01

    Abstract Survival of any living organism critically depends on its ability to repair and regenerate damaged tissues and/or organs during its lifetime following injury, disease, or aging. Various animal models from invertebrates to vertebrates have been used to investigate the molecular and cellular mechanisms of wound healing and tissue regeneration. It is hoped that such studies will form the framework for identifying novel clinical treatments that will improve the healing and regenerative capacity of humans. Amongst these models, Xenopus stands out as a particularly versatile and powerful system. This review summarizes recent findings using this model, which have provided fundamental knowledge of the mechanisms responsible for efficient and perfect tissue repair and regeneration.

  2. 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

  3. 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.

  4. 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

  5. Role of Macrophages in the Repair Process during the Tissue Migrating and Resident Helminth Infections

    Science.gov (United States)

    Faz-López, Berenice

    2016-01-01

    The Th1/Th2/Th17 balance is a fundamental feature in the regulation of the inflammatory microenvironment during helminth infections, and an imbalance in this paradigm greatly contributes to inflammatory disorders. In some cases of helminthiasis, an initial Th1 response could occur during the early phases of infection (acute), followed by a Th2 response that prevails in chronic infections. During the late phase of infection, alternatively activated macrophages (AAMs) are important to counteract the inflammation caused by the Th1/Th17 response and larval migration, limiting damage and repairing the tissue affected. Macrophages are the archetype of phagocytic cells, with the primary role of pathogen destruction and antigen presentation. Nevertheless, other subtypes of macrophages have been described with important roles in tissue repair and immune regulation. These types of macrophages challenge the classical view of macrophages activated by an inflammatory response. The role of these subtypes of macrophages during helminthiasis is a controversial topic in immunoparasitology. Here, we analyze some of the studies regarding the role of AAMs in tissue repair during the tissue migration of helminths. PMID:27648452

  6. 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.

  7. 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.

  8. 应用生物蛋白胶与胚胎软骨细胞混合移植修复兔膝关节实验性软骨缺损区%Repair of experimental defects of articular cartilage in rabbits with homografts of fibrin sealant and embryonic chondrocytes

    Institute of Scientific and Technical Information of China (English)

    陆敏安; 杨渊; 肖增明; 李世德

    2005-01-01

    BACKGROUND:Research about the repair of articular cartilage with heterograft chondrocytes is frequently reported, but the method may cause immune rejection. Since the embryonic cells possess lower antigenicity and stronger proliferation capability, it is hoped that they can be used as a novel carrier substitute in tissue engineering research.DESIGN: A randomized grouping observation and comparative experiment.SETTING: Histological Embryonic Laboratory in Guangxi Medical University.MATERIALS: A big white adult New Zealand rabbit pregnant for 4 weeks was adopted; and another 24 big white adult New Zealand rabbits were selected, with no limitationin whether they were female or male and with a body mass of 2 to 2.5 kg.METHODS: This experiment was carried out at the Histological Embryonic Laboratory in Guangxi Medical University between December 2000and June 2002. The models of defects in articular cartilage were made artificially in femur medial malleolus of the mature rabbits. In the experimental group, defects were repaired by the implantation of Fibrin Sealant and embryonic chondrocytes mixture, but for the control group, only Fibrin Sealant was implanted or nothing was done about the defect. The restoration of articular cartilage defect was then observed 4,8 and 12 weeks after the operation, and was scored according to modified Pineda's method. The standard consists of 5 items, I.e., cellular morphology, matrix staining, surfacing smoothness, cartilage thickness and host union. 0 refers to normal and the higher the score is, the more serious the pathological changes are.MAIN OUTCOME MEASURES: ①The general observation of rabbit knee joint; ② Histological observation of rabbit knee joints; ③ Histological semi-quantitative score of articular cartilage; ④ Appraisal of the curative effect of articular cartilage defects.RESULTS: Totally 24 rabbits were enrolled in this experiment and all entered the stage of result analysis. ① The general observation of rabbit

  9. 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)

  10. 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 ...

  11. 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...

  12. Investigation of Migration and Differentiation of Human Mesenchymal Stem Cells on Five-Layered Collagenous Electrospun Scaffold Mimicking Native Cartilage Structure.

    Science.gov (United States)

    Reboredo, Jenny W; Weigel, Tobias; Steinert, Andre; Rackwitz, Lars; Rudert, Maximilian; Walles, Heike

    2016-09-01

    Cartilage degeneration is the major cause of chronic pain, lost mobility, and reduced quality of life for over estimated 150 million osteoarthritis sufferers worldwide. Despite intensive research, none of the available therapies can restore the hyaline cartilage surface beyond just fibrous repair. To overcome these limitations, numerous cell-based approaches for cartilage repair are being explored that aim to provide an appropriate microenvironment for chondrocyte maintenance and differentiation of multipotent mesenchymal stem cells (MSCs) toward the chondrogenic lineage. Articular cartilage is composed of highly organized collagen network that entails the tissue into four distinct zones and each zone into three different regions based on differences in matrix morphology and biochemistry. Current cartilage implants cannot establish the hierarchical tissue organization that seems critical for normal cartilage function. Therefore, in this study, a structured, multilayered collagen scaffold designed for the replacement of damaged cartilage is presented that allows repopulation by host cells and synthesis of a new natural matrix. By using the electrospinning method, the potential to engineer a scaffold consisting of two different collagen types is obtained. With the developed collagen scaffold, a five-layered biomaterial is created that has the potency to induce the differentiation of human bone marrow derived MSCs toward the chondrogenic lineage. PMID:27185494

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Drug delivery strategies to control macrophages for tissue repair and regeneration.

    Science.gov (United States)

    Garash, Reham; Bajpai, Anamika; Marcinkiewicz, Brandon M; Spiller, Kara L

    2016-05-01

    Tissue repair and regeneration is a complex process. Our bodies have an excellent capacity to regenerate damaged tissues in many situations. However, tissue healing is impaired in injuries that exceed a critical size or are exacerbated by chronic inflammatory diseases like diabetes. In these instances, biomaterials and drug delivery strategies are often required to facilitate tissue regeneration by providing physical and biochemical cues. Inflammation is the body's response to injury. It is critical for wound healing and biomaterial integration and vascularization, as long as the timing is well controlled. For example, chronic inflammation is well known to impair healing in chronic wounds. In this review, we highlight the importance of a well-controlled inflammatory response, primarily mediated by macrophages in tissue repair and regeneration and discuss various strategies designed to promote regeneration by controlling macrophage behavior. These strategies include temporally controlled delivery of anti-inflammatory drugs, delivery of macrophages as cellular therapy, controlled release of cytokines that modulate macrophage phenotype, and the design of nanoparticles that exploit the inherent phagocytic behavior of macrophages. A clear outcome of this review is that a deeper understanding of the role and timing of complex macrophage phenotypes or activation states is required to fully harness their abilities with drug delivery strategies. PMID:27190256

  2. 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

  3. 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.

  4. 慢速梯度降温冷冻保存同种异体骨软骨移植治疗膝关节全层软骨缺损(附三例报告)%Osteochondral allografts of step cooling cryopreservation for repair of full-thickness articular cartilage defect of knee joint (report of 3 cases)

    Institute of Scientific and Technical Information of China (English)

    亓建洪; 赵建莉; 张明; 闫新峰; 张延明

    2012-01-01

    目的 总结冷冻保存同种异体骨软骨移植物治疗3例膝关节全层骨软骨缺损的手术方法及疗效.方法 应用梯度降温冷冻保存的6枚同种异体骨软骨移植物治疗3例膝关节全层骨软骨缺损,2例在关节镜下同种异体骨软骨移植,1例行关节切开移植.膝关节股骨髁关节软骨全层缺损平均面积2.16cm2.所有患者在手术后第1个月、第3个月时进行膝关节MRI检查,了解移植物与周围骨软骨组织的愈合情况.并于门诊复查时进行Brittberg-Peterson膝关节功能评分,了解功能恢复情况.结果 随访4~6个月,平均4.7个月.所有患者术后疼痛消失;无排异反应发生.术后3个月时,MRI 检查示术后移植物与宿主软骨下骨整合良好,移植软骨组织结构与内部信号良好.Brittberg-Peterson评分术后6个月比手术前明显降低.结论 经梯度降温冷冻保存的同种异体骨软骨移植治疗膝关节软骨缺损早期效果满意.%Objective To introduce the repair method of full-thickness articular cartilage of knee join through osteochondral allograft of step cooling cryopresercvation and its early clinical outcome. Methods Three patients who suffered from full-thickness defect of knee articular cartilage were treated by transplantation of osteochondral allograft cryopreserved in step cooling under arthroscopy or arthrectomy. The average cartilage defect was 2.16 cm2. All patients were examined by MRI to display the integrating of allograft with surrounding tissues at 1st month, 3rd month postoperatively, and evaluate the function of operative knee through Brittberg-Peterson score system. Results The average follow-up time was 4.7 months (range: 4-6 months). All patients' pain disappeared. The Brittberg-Peterson score decreased remarkably from 97.5 preoperatively to 10.0 at ? Six months postoperatively. The integration of allograft with subchondral bone surrounding was well, and the structure and internal signal of

  5. Porcine Fetal Bone Marrow Mesenchymal Stem Cells in Cartilage Tissue Engineering%胎猪BMSC体外构建软骨的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘李娜; 何爱娟; 周广东; 曹卫刚

    2013-01-01

    Objective To investigate the optimal seed cell for cartilage engineering by comparing the chondrogenesis capability of porcine fetal bone marrow mesenchymal stem cells (fBMSCs) and adult porcine BMSCs (aBMSCs). Methods Fetal pigs with gestational age of 70 days were obtained by the uterine-incision delivery, and primary fBMSCs were isolated from the bone marrow. Primary aBMSCs were isolated from the bone marrow which was aspirated from iliac. Cell morphology of the two kinds of cells at passage 3 were observed after in vitro proliferation. The two kinds of cells at passages 3 were characterized by their osteogenic, adipogenic and chondrogenic differentiation potential. Then the fBMSCs and aBMSCs were separately seeded onto a polyglycolic acid/polylactic acid (PGA/PLA) scaffold with the concentration of 1 ×108 cells/mL. All specimens were harvested after 8 weeks' culture in vitro. Gross observation, glycosaminoglycan (GAG) quantification, total collagen quantification and histology were used to compare related characteristic differences of engineered cartilage formed by the two kinds of cells. Results fBMSCs had better proliferation and multiple differentiation capacity than aBMSCs. The two kinds of cells both formed mature cartilage after 8 weeks of culture in vitro, and the engineered cartilage of aBMSCs group had better appearance. The GAG content and total collagen content of the cartilage formed by fBMSCs were both higher than the cartilage formed by aBMSCs (P<0.01). Histology and immunohistochemistry demonstrated that the cartilage formed by fBMSCs have more compact tissue structure. The cartilage matrix staining of cartilage formed by fBMSCs were stronger than that of cartilage formed by aBMSCs. Conclusion The fBMSCs seems to be the optimal seed cells for cartilage tissue engineering.%目的比较胎猪骨髓间充质干细胞(Bone Marrow Mesenchymal Stem Cells,BMSCs)和成年猪BMSCs构建软骨能力的差异,寻找合适的同种异体组织工

  6. In vitro mechanical fatigue behavior of poly-ɛ-caprolactone macroporous scaffolds for cartilage tissue engineering: Influence of pore filling by a poly(vinyl alcohol) gel.

    Science.gov (United States)

    Panadero, J A; Vikingsson, L; Gomez Ribelles, J L; Lanceros-Mendez, S; Sencadas, V

    2015-07-01

    Polymeric scaffolds used in regenerative therapies are implanted in the damaged tissue and submitted to repeated loading cycles. In the case of articular cartilage engineering, an implanted scaffold is typically subjected to long-term dynamic compression. The evolution of the mechanical properties of the scaffold during bioresorption has been deeply studied in the past, but the possibility of failure due to mechanical fatigue has not been properly addressed. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading-unloading cycles. In this work fatigue studies of polycaprolactone scaffolds were carried by subjecting the scaffold to repeated compression cycles in conditions simulating the scaffold implanted in the articular cartilage. The behavior of the polycaprolactone sponge with the pores filled with a poly(vinyl alcohol) gel simulating the new formed tissue within the pores was compared with that of the material immersed in water. Results were analyzed with Morrow's criteria for failure and accurate fittings are obtained just up to 200 loading cycles. It is also shown that the presence of poly(vinyl alcohol) increases the elastic modulus of the scaffolds, the effect being more pronounced with increasing the number of freeze/thawing cycles.

  7. Advances in tissue engineering

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Tissue engineering is a newly developed specialty involved in the construction of tissues and organs either in vitro or in vivo. Tremendous progress has been achieved over the past decade in tisse construction as well as in other related areas, such as bone marrow stromal cells, embryonic stem cells and tissue progenitor cells. In our laboratory, tissues of full-thickness skin, bone, cartilage and tendon have been successfully engineered, and the engineered tissues have repaired full-thickness skin wound, cranial bone defects, articular cartilage defects and tendon defects in animals. In basic research areas, bone marrow stromal cells have been induced and transformed into osteoblasts and chondrocytes in vitro. Mouse embryo stem cell lines we established have differentiated into neuron precursor, cardiac muscle cells and epithelial cells. Genetic modifications of seed cells for promoting cell proliferation, delaying cell aging and inducing immune tolerance have also been investigated.

  8. 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...

  9. Proteoglycan concentrations in healthy and diseased articular cartilage by Fourier transform infrared imaging and principal component regression

    Science.gov (United States)

    Yin, Jianhua; Xia, Yang

    2014-12-01

    Fourier transform infrared imaging (FTIRI) combining with principal component regression (PCR) analysis were used to determine the reduction of proteoglycan (PG) in articular cartilage after the transection of the anterior cruciate ligament (ACL). A number of canine knee cartilage sections were harvested from the meniscus-covered and meniscus-uncovered medial tibial locations from the control joints, the ACL joints at three time points after the surgery, and their contralateral joints. The PG loss in the ACL cartilage was related positively to the durations after the surgery. The PG loss in the contralateral knees was less than that of the ACL knees. The PG loss in the meniscus-covered cartilage was less than that of the meniscus-uncovered tissue in both ACL and contralateral knees. The quantitative mapping of PG loss could monitor the disease progression and repair processes in arthritis.

  10. 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.

  11. Femoral hernia repair

    Science.gov (United States)

    Femorocele repair; Herniorrhaphy; Hernioplasty - femoral ... During surgery to repair the hernia, the bulging tissue is pushed back in. The weakened area is sewn closed or strengthened. This repair ...

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Transplant tissue of antilogous cartilage - cartilage membrane complex in tym panoplasty%自体软骨-软骨膜复合物在鼓室成形术中的应用价值

    Institute of Scientific and Technical Information of China (English)

    杨花荣

    2012-01-01

    Objective To investigate the potential applications, effects, and the outcome of transplant tissue of antilogous cartilage - cartilage membrane complex in tympanoplasty. Methods 36 cases of chronic suppurative otitis media patients with antilogous cartilage-cartilage membrane complex in tympanoplasty, follow-up after post-operation 10d, 1, 3, 6 months to 1, 2 years. Results After 10d, 32 cases healed; 1 case gap in the top of the tympanic membrane, 1 case on the bottom, 2 had infection, healed after re-operation; all cases with new tympanic membrane in 3 ~ 6 months, 2 cases the tympanic membrane become thickening and shrink plaque in 6 months to 2 years; follow up two years, all cured. Preoperative mean air conduction was ( 45.76 ±8.30 ) dB HL, bone-air conduction gap (26.15 ±8.05 ) dB HL; 1 month were ( 30.48 ±7.35 ) dB HL and ( 19.51 ±6.31 ) dB HL; 3 months were (26.08 ±7.12) dB HL and ( 12.53 ±7.69 ) dB HL; 6 months were (23.65 ±7.60 ) dB HL and ( 10.89 ±5.42 ) dB HL respectively. Hearing significantly improved after 1 month post-operation, compared with 3 months increased (P0.05 ) . Conclusion Autologous cartilage - cartilage complex is an ideal material, operation supervised by convenience, easy drawing in tympanoplasty; the new tympanic membrane with normal morphology, hearing improved significantly, clinical cure rate is high.%目的 探讨自体软骨-软骨膜在中耳炎鼓室成形术中的应用、效果、移植组织的转归.方法 36例慢性化脓性中耳炎患者行软骨-软骨膜复合物鼓室成形术;术后10d,1、3、6个月,1、2年随访观察.结果 术后10d,愈合32例,鼓膜前上方、前下方出现缝隙各1例,术后感染2例,再次手术痊愈,3~6个月新鼓膜形态完整,6个月~2年2例鼓膜出现增厚、萎缩斑.随访2年成功100%;术前平均气导为(45.76±8.30)dB HL,骨气导差距为(26.15±8.05)dB HL;术后1个月为(30.48±7.35)dB HL和(19.51±6.31)dB HL;3个月为(26.08±7.12)dB HL和(12.53±7

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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...

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Repair of Minor Tissue Defect in Hand by Transfer of Free Tissue Flap from the Toe

    Directory of Open Access Journals (Sweden)

    Haitao Tan

    2014-03-01

    Full Text Available Background:   To introduce our experience of using the free neurovascular flap from great and second toe. Methods:   Thirteen patients (fifteen fingers sought surgical treatment for soft tissue defects of the hand at our medical institutin between March 2006 and September 2009. In two patients, fibular side skin-nail flaps of great toe were applied to cover the dorsal defect of distal thumb. In twelve, in the treatment of pulp defect of finger with fibular side flap of great toe or tibial side flap of second toe. In one, in the treatment of defect of distal middle with composite flap with distal digital bone of second toe. Results:   All flaps were survived. The average subjective satisfaction score was 8.08 (range 4-10. Nine patients (69% experienced cold intolerance, and 2 patients (15% dysesthesia. The Semmes-Weinstein sensitivity score was between 3.47and 4.72 on the flap, and 0-4.18 on the donor site. The mean two-point discrimination was 6.8 mm (range 4-12. Grip strength was 10% less than in the unaffected hand. The proximal interphalangeal mobility loss was less than 15 degrees. Conclusions:   Our results indicated that these free flaps from toe are useful for patients with a small soft-tissue defect in hand.

  11. 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.

  12. Biodegradable synthetic polymer scaffolds for reinforcement of albumin protein solders used for laser-assisted tissue repair.

    Science.gov (United States)

    Hoffman, Grant T; Soller, Eric C; McNally-Heintzelman, Karen M

    2002-01-01

    Laser tissue soldering has been investigated for several years by researchers in our laboratory as an alternative to conventional tissue fasteners, including sutures, staples and clips. Laser tissue soldering is a bonding technique in which protein solder is applied to the tissue surfaces to be joined, and laser energy is used to bond the solder to the tissue surfaces. Over the past four years we have been investigating the use of synthetic polymer membranes as a means for reinforcing the strength of tissue repairs formed using traditional laser tissue soldering techniques. The purpose of this study was to assess the influence of various processing parameters on the strength of tissue repairs formed using the reinforced solder. Biodegradable polymer membranes of specific porosity were fabricated by means of a solvent-casting and particulate-leaching technique, using three different poly(alpha ester)s: polyglycolic acid (PGA), polylactic acid (PLA) and poly(L-lactic-co-glycolic acid) (PLGA). In addition, several membranes were also prepared with poly(ethylene glycol) (PEG). The membranes were then doped with the traditional protein solder mixture of serum albumin and indocyanine green dye. Varied processing parameters included the polymer type, the PLGA copolymer blend ratio, the polymer/PEG blend ratio, the porosity of the polymer membrane and the initial albumin weight fraction. Variation of the polymer type had negligible effect on the strength of the repairs. Although it is known that alteration of the copolymer blend ratio of PLGA influences the degradation rate of the polymer, this variation also had no significant effect on the strength of the repairs formed. Increased membrane flexibility was observed when PEG was added during the casting stage. An increase in the porosity of the polymer membranes led to a subsequent increase in the final concentration of protein contained within the membranes, hence aiding in strengthening the resultant repairs. Likewise

  13. 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.

  14. 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.

  15. The influence of platelet- derived products on angiogenesis and tissue repair: a concise update

    Directory of Open Access Journals (Sweden)

    Constanza E Martínez

    2015-10-01

    Full Text Available Platelet degranulation allows the release of a large amount of soluble mediators, is an essential step for wound healing initiation, and stimulates clotting and angiogenesis. The latter process is one of the most critical biological events observed during tissue repair,increasing the growth of blood vessels in the maturing wound. Angiogenesis requires the action of a variety of growth factors that act in an appropriate physiological ratio to assure functional blood vessel restoration. Platelets release main regulators of angiogenesis: Vascular Endothelial Growth Factors (VEGFs, basic fibroblast growth factor (FGF-2, and Platelet derived growth factors (PDGFs, among others. In order to stimulate tissue repair, platelet derived fractions have been used as an autologous source of growth factors and biomolecules, namely Platelet Rich Plasma (PRP, Platelet Poor Plasma (PPP and Platelet Rich Fibrin(PRF. The continuous release of these growth factors has been proposed to promote angiogenesis both in vitro and in vivo. Considering the existence of clinical trials currently evaluating the efficacy of autologous PRP, the present review analyses fundamental questions regarding the putative role of platelet derived fractions as regulators of angiogenesis and evaluates the possible clinical implications of these formulations.

  16. Hiatal Hernia Repair with Gore Bio-A Tissue Reinforcement: Our Experience

    Directory of Open Access Journals (Sweden)

    Agrusa Antonino

    2014-01-01

    Full Text Available Type I hiatal hernia is associated with gastroesophageal reflux disease (GERD in 50–90% of cases. Several trials strongly support surgery as an effective alternative to medical therapy. Today, laparoscopic fundoplication is considered as the procedure of choice. However, primary laparoscopic hiatal hernia repair is associated with upto 42% recurrence rate. Mesh reinforcement of the crural closure decreases the recurrence but can lead to complications, above all nonabsorbable ones. We experiment a new totally absorbable mesh by Gore. Case. We present a case of a 65-year-old female patient with a 6-year classic history of GERD. Endoscopy revealed a large hiatal hernia and esophagitis. pH study was positive for acid reflux; esophageal manometry revealed LES intrathoracic dislocation. With laparoscopic approach, the hiatal hernia defect was identified and primarily repaired, by crural closure. Gore Bio-A Tissue Reinforcement was trimmed to fit the defect accommodating the esophagus. Nissen fundoplication was performed. Result. Bio-A mesh was easily placed laparoscopically. It has good handling and could be cut and tailored intraoperatively for optimal adaptation. There were no short-term complications. Conclusion. Crural closure reinforcement can be done readily with this new totally absorbable mesh replaced by soft tissue over six months. However, further data and studies are needed to evaluate long-term outcomes.

  17. 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.

  18. PEOT/PBT based scaffolds with low mechanical properties improve cartilage repair tissue formation in osteochondral defects

    NARCIS (Netherlands)

    Jansen, Edwin J. P.; Pieper, Jeroen; Gijbels, Marion J. J.; Guldemond, Nick A.; Riesle, Jens; Van Rhijn, Lodewijk W.; Bulstra, Sjoerd K.; Kuijer, Roel

    2009-01-01

    The aim of our Study was to compare the healing response of biomechanically and biochemically different scaffolds in osteochondral defects created in rabbit medial femoral condyles. A block copolymer comprised of poly(ethylene oxide terephthalate) and poly(butylene terephthalate) was used to prepare

  19. Tensorial electrokinetics in articular cartilage.

    Science.gov (United States)

    Reynaud, Boris; Quinn, Thomas M

    2006-09-15

    Electrokinetic phenomena contribute to biomechanical functions of articular cartilage and underlie promising methods for early detection of osteoarthritic lesions. Although some transport properties, such as hydraulic permeability, are known to become anisotropic with compression, the direction-dependence of cartilage electrokinetic properties remains unknown. Electroosmosis experiments were therefore performed on adult bovine articular cartilage samples, whereby fluid flows were driven by electric currents in directions parallel and perpendicular to the articular surface of statically compressed explants. Magnitudes of electrokinetic coefficients decreased slightly with compression (from approximately -7.5 microL/As in the range of 0-20% compression to -6.0 microL/As in the 35-50% range) consistent with predictions of microstructure-based models of cartilage material properties. However, no significant dependence on direction of the electrokinetic coupling coefficient was detected, even for conditions where the hydraulic permeability tensor is known to be anisotropic. This contrast may also be interpreted using microstructure-based models, and provides insights into structure-function relationships in cartilage extracellular matrix and physical mediators of cell responses to tissue compression. Findings support the use of relatively simple isotropic modeling approaches for electrokinetic phenomena in cartilage and related materials, and indicate that measurement of electrokinetic properties may provide particularly robust means for clinical evaluation of cartilage matrix integrity.

  20. 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

  1. 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.

  2. The application of lesion sterilization and tissue repair 3Mix-MP for treating rat's dental pulp tissue

    Directory of Open Access Journals (Sweden)

    Raditya Nugroho

    2015-03-01

    Full Text Available Background: Lesion sterilization and tissue repair (LSTR 3Mix-MP are three broad-spectrum antibiotics, including metronidazole, ciprofloxacin and minocycline are mixed with propylene glycol or macrogol. There is the possibility ofthe healing process that marked proliferation ofnew blood vessels and proliferation offibroblasts in the treatment ofirreversible pulpitis by pulp capping LSTR 3MixMP because of  the principle of the method LSTR 3Mix-MP is to kill bacteria. Purpose: The purpose of this study to prove the effect of LSTR 3Mix-MP on chronic inflammation and the healing process in rat dental pulp tissue in vivo. Methods: Rattus norvegicus anaesthetized by using ketamine and xylazine dissolved in sterile isotonic saline solution (0.2 ml/50gr mm on the upper right thigh. Cavity preparation class I to perforation by using a low speed tapered diamond round bur. In the treatment group, rats were treated 3Mix-MP at a dose of10 mg and then covered with glass ionomer cement for 7 days on the pulp that has been opened for 3 days. The control group treated with saline irrigation on the pulp that has been opened for 3 days. Rats were killed after seven days, and then made preparations pulp tissue to count the number oflymphocytes, macrophages, plasma cells, blood vessels, and fibroblasts Results: There is an increase in the average number ofmacrophage cells, plasma, and fibroblasts; and decreased lymphocytes and blood vessels in the treated group exposure LSTR 3Mix-MP. Conclusion:LSTR 3Mix-MP can reduce chronic inflammation process and enhance the healing process in rat dental pulp tissue.

  3. 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

  4. Applications of Chondrocyte-Based Cartilage Engineering: An Overview

    Directory of Open Access Journals (Sweden)

    Abdul-Rehman Phull

    2016-01-01

    Full Text Available Chondrocytes are the exclusive cells residing in cartilage and maintain the functionality of cartilage tissue. Series of biocomponents such as different growth factors, cytokines, and transcriptional factors regulate the mesenchymal stem cells (MSCs differentiation to chondrocytes. The number of chondrocytes and dedifferentiation are the key limitations in subsequent clinical application of the chondrocytes. Different culture methods are being developed to overcome such issues. Using tissue engineering and cell based approaches, chondrocytes offer prominent therapeutic option specifically in orthopedics for cartilage repair and to treat ailments such as tracheal defects, facial reconstruction, and urinary incontinence. Matrix-assisted autologous chondrocyte transplantation/implantation is an improved version of traditional autologous chondrocyte transplantation (ACT method. An increasing number of studies show the clinical significance of this technique for the chondral lesions treatment. Literature survey was carried out to address clinical and functional findings by using various ACT procedures. The current study was conducted to study the pharmacological significance and biomedical application of chondrocytes. Furthermore, it is inferred from the present study that long term follow-up studies are required to evaluate the potential of these methods and specific positive outcomes.

  5. Applications of Chondrocyte-Based Cartilage Engineering: An Overview

    Science.gov (United States)

    Eo, Seong-Hui; Abbas, Qamar; Ahmed, Madiha

    2016-01-01

    Chondrocytes are the exclusive cells residing in cartilage and maintain the functionality of cartilage tissue. Series of biocomponents such as different growth factors, cytokines, and transcriptional factors regulate the mesenchymal stem cells (MSCs) differentiation to chondrocytes. The number of chondrocytes and dedifferentiation are the key limitations in subsequent clinical application of the chondrocytes. Different culture methods are being developed to overcome such issues. Using tissue engineering and cell based approaches, chondrocytes offer prominent therapeutic option specifically in orthopedics for cartilage repair and to treat ailments such as tracheal defects, facial reconstruction, and urinary incontinence. Matrix-assisted autologous chondrocyte transplantation/implantation is an improved version of traditional autologous chondrocyte transplantation (ACT) method. An increasing number of studies show the clinical significance of this technique for the chondral lesions treatment. Literature survey was carried out to address clinical and functional findings by using various ACT procedures. The current study was conducted to study the pharmacological significance and biomedical application of chondrocytes. Furthermore, it is inferred from the present study that long term follow-up studies are required to evaluate the potential of these methods and specific positive outcomes. PMID:27631002

  6. Knee cartilage extraction and bone-cartilage interface analysis from 3D MRI data sets

    Science.gov (United States)

    Tamez-Pena, Jose G.; Barbu-McInnis, Monica; Totterman, Saara

    2004-05-01

    This works presents a robust methodology for the analysis of the knee joint cartilage and the knee bone-cartilage interface from fused MRI sets. The proposed approach starts by fusing a set of two 3D MR images the knee. Although the proposed method is not pulse sequence dependent, the first sequence should be programmed to achieve good contrast between bone and cartilage. The recommended second pulse sequence is one that maximizes the contrast between cartilage and surrounding soft tissues. Once both pulse sequences are fused, the proposed bone-cartilage analysis is done in four major steps. First, an unsupervised segmentation algorithm is used to extract the femur, the tibia, and the patella. Second, a knowledge based feature extraction algorithm is used to extract the femoral, tibia and patellar cartilages. Third, a trained user corrects cartilage miss-classifications done by the automated extracted cartilage. Finally, the final segmentation is the revisited using an unsupervised MAP voxel relaxation algorithm. This final segmentation has the property that includes the extracted bone tissue as well as all the cartilage tissue. This is an improvement over previous approaches where only the cartilage was segmented. Furthermore, this approach yields very reproducible segmentation results in a set of scan-rescan experiments. When these segmentations were coupled with a partial volume compensated surface extraction algorithm the volume, area, thickness measurements shows precisions around 2.6%

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Growth factor stimulation improves the structure and properties of scaffold-free engineered auricular cartilage constructs.

    Directory of Open Access Journals (Sweden)

    Renata G Rosa

    Full Text Available The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1 was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm. While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation.

  13. 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.

  14. 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.

  15. 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...

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Oorschot, Bregje van, E-mail: b.vanoorschot@amc.uva.nl [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hovingh, Suzanne E. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Moerland, Perry D. [Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Medema, Jan Paul; Stalpers, Lukas J.A. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Franken, Nicolaas A.P. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  3. 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

  4. Knockdown of the cell cycle inhibitor p21 enhances cartilage formation by induced pluripotent stem cells.

    Science.gov (United States)

    Diekman, Brian O; Thakore, Pratiksha I; O'Connor, Shannon K; Willard, Vincent P; Brunger, Jonathan M; Christoforou, Nicolas; Leong, Kam W; Gersbach, Charles A; Guilak, Farshid

    2015-04-01

    The limited regenerative capacity of articular cartilage contributes to progressive joint dysfunction associated with cartilage injury or osteoarthritis. Cartilage tissue engineering seeks to provide a biological substitute for repairing damaged or diseased cartilage, but requires a cell source with the capacity for extensive expansion without loss of chondrogenic potential. In this study, we hypothesized that decreased expression of the cell cycle inhibitor p21 would enhance the proliferative and chondrogenic potential of differentiated induced pluripotent stem cells (iPSCs). Murine iPSCs were directed to differentiate toward the chondrogenic lineage with an established protocol and then engineered to express a short hairpin RNA (shRNA) to reduce the expression of p21. Cells expressing the p21 shRNA demonstrated higher proliferative potential during monolayer expansion and increased synthesis of glycosaminoglycans (GAGs) in pellet cultures. Furthermore, these cells could be expanded ∼150-fold over three additional passages without a reduction in the subsequent production of GAGs, while control cells showed reduced potential for GAG synthesis with three additional passages. In pellets from extensively passaged cells, knockdown of p21 attenuated the sharp decrease in cell number that occurred in control cells, and immunohistochemical analysis showed that p21 knockdown limited the production of type I and type X collagen while maintaining synthesis of cartilage-specific type II collagen. These findings suggest that manipulating the cell cycle can augment the monolayer expansion and preserve the chondrogenic capacity of differentiated iPSCs, providing a strategy for enhancing iPSC-based cartilage tissue engineering.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. Modifying the Genetic Regulation of Bone and Cartilage Cells and Associated Tissue by EMF Stimulation Fields and Uses Thereof

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor); Shackelford, Linda C. (Inventor)

    2014-01-01

    An apparatus and method to modify the genetic regulation of mammalian tissue, bone, or any combination. The method may be comprised of the steps of tuning at least one predetermined profile associated with at least one time-varying stimulation field thereby resulting in at least one tuned time-varying stimulation field comprised of at least one tuned predetermined profile, wherein said at least one tuned predetermined profile is comprised of a plurality of tuned predetermined figures of merit and is controllable through at least one of said plurality of tuned predetermined figures of merit, wherein said plurality of predetermined tuned figures of merit is comprised of a tuned B-Field magnitude, tuned rising slew rate, tuned rise time, tuned falling slew rate, tuned fall time, tuned frequency, tuned wavelength, and tuned duty cycle; and exposing mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination to said at least one tuned time-varying stimulation field comprised of said at least one tuned predetermined profile for a predetermined tuned exposure time or plurality of tuned exposure time sequences.

  11. 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

  12. 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

  13. 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...

  14. 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.

  15. 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 ...

  16. Bone-Marrow-Derived Mesenchymal Stem Cells for Organ Repair

    Directory of Open Access Journals (Sweden)

    Ming Li

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are prototypical adult stem cells with the capacity for self-renewal and differentiation with a broad tissue distribution. MSCs not only differentiate into types of cells of mesodermal lineage but also into endodermal and ectodermal lineages such as bone, fat, cartilage and cardiomyocytes, endothelial cells, lung epithelial cells, hepatocytes, neurons, and pancreatic islets. MSCs have been identified as an adherent, fibroblast-like population and can be isolated from different adult tissues, including bone marrow (BM, umbilical cord, skeletal muscle, and adipose tissue. MSCs secrete factors, including IL-6, M-CSF, IL-10, HGF, and PGE2, that promote tissue repair, stimulate proliferation and differentiation of endogenous tissue progenitors, and decrease inflammatory and immune reactions. In this paper, we focus on the role of BM-derived MSCs in organ repair.

  17. Handheld-Level Electromechanical Cartilage Reshaping Device.

    Science.gov (United States)

    Kim, Sehwan; Manuel, Cyrus T; Wong, Brian J F; Chung, Phil-Sang; Mo, Ji-Hun

    2015-06-01

    We have developed a handheld-level multichannel electromechanical reshaping (EMR) cartilage device and evaluated the feasibility of providing a means of cartilage reshaping in a clinical outpatient setting. The effect of EMR on pig costal cartilage was evaluated in terms of shape change, tissue heat generation, and cell viability. The pig costal cartilage specimens (23 mm × 6.0 mm × 0.7 mm) were mechanically deformed to 90 degrees and fixed to a plastic jig and applied 5, 6, 7, and 8 V up to 8 minutes to find the optimal dosimetry for the our developed EMR device. The results reveal that bend angle increased with increasing voltage and application time. The maximum bend angle obtained was 70.5 ± 7.3 at 8 V, 5 minutes. The temperature of flat pig costal cartilage specimens were measured, while a constant electric voltage was applied to three pairs of electrodes that were inserted into the cartilages. The nonthermal feature of EMR was validated by a thermal infrared camera; that is, the maximum temperate of the flat cartilages is 20.3°C at 8 V. Cell viability assay showed no significant difference in cell damaged area from 3 to 7 minutes exposure with 7 V. In conclusion, the multichannel EMR device that was developed showed a good feasibility of cartilage shaping with minimal temperature change. PMID:26126226

  18. 骨形态发生蛋白与碱性成纤维细胞生长因子联合修复软骨缺损的效果评价%Effects of recombinant human bone morphogenetic protein combined with basic fibroblast growth factor on the repair of articular cartilage defects

    Institute of Scientific and Technical Information of China (English)

    朱国华; 蔡建平; 郭翠玲; 廖家新; 刘勇; 罗洪涛; 许国华; 胡红涛

    2012-01-01

    背景:多种细胞生长因子在骨软骨代谢过程中的协同作用越来越受到重视,但目前复合细胞生长因子修复软骨缺损报道较少,且修复效果尚无定论.目的:探讨骨形态发生蛋白和碱性成纤维细胞生长因子联合应用修复关节软骨缺损的效果.方法:24 只日本大耳白兔建立骨软骨缺损模型后随机等分为4 组,对照组缺损处仅填塞明胶海绵,其他3 组在对照组基础上,缺损处分别注射骨形态发生蛋白和碱性成纤维细胞生长因子、骨形态发生蛋白、碱性成纤维细胞生长因子.结果与结论:大体观察显示联合应用2 种细胞因子后,软骨缺损面基本修复但稍不平整,单独使用其中1 种细胞因子缺损面未完全修复,对照组无明显修复.联合应用2 种细胞因子缺损部位软骨细胞数多于其他3 组(P < 0.05),且Ⅱ型胶原免疫组化染色深于其他组.提示联合应用骨形态发生蛋白和碱性成纤维细胞生长因子可以促进关节软骨损伤的修复,疗效优于单独应用骨形态发生蛋白或碱性成纤维细胞生长因子.%BACKGROUND: The synergy of various cell growth factors attracts more and more attention in the course of cartilage metabolism.However, there are few reports of repairing cartilage defects with combined cell growth factors, and the effect remains unknown atpresent.OBJECTIVE: To study the repairing effect of recombinant human bone morphogenetic protein (rhBMP) combined with basicfibroblast growth factor (bFGF) on articular cartilage defects.METHODS: After the model of articular cartilage defects was made, 24 Japan big-eared white rabbits were randomly divided intofour groupsforintervention: rhBMP combined with bFGF (group A), single rhBMP (group B), single bFGF (group C), the fourthgroup was without injection and just filled with gelatin sponge (group D).RESULTS AND CONCLUSION: In general observation, articular cartilage defects were basically repaired but slightly

  19. 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.

  20. 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...

  1. Carboxyl-modified single-wall carbon nanotubes improve bone tissue formation in vitro and repair in an in vivo rat model

    Directory of Open Access Journals (Sweden)

    Barrientos-Durán A

    2014-09-01

    combination of demineralized bone matrix or cartilage particles with SWCNTs were implanted into nude rats, and ectopic bone formation was analyzed. Histological analysis of both types of implants showed high permeability and pore connectivity of the carbon nanotube-soaked implants. Numerous vascularization channels appeared in the formed tissue, additional progenitor cells were recruited, and areas of de novo ossification were found 4 weeks post-implantation. Induction of the expression of bone-related genes and the presence of secreted osteopontin protein were also confirmed by quantitative polymerase chain reaction analysis and immunofluorescence, respectively. In summary, these results are in line with prior contributions that highlight the suitability of SWCNTs as scaffolds with high bone-inducing capabilities both in vitro and in vivo, confirming them as alternatives to current bone-repair therapies. Keywords: human allografts, demineralized bone matrix, cartilage particles, bone regeneration

  2. Chondrocyte differentiation for auricular cartilage reconstruction using a chitosan based hydrogel.

    Science.gov (United States)

    García-López, J; Garciadiego-Cázares, D; Melgarejo-Ramírez, Y; Sánchez-Sánchez, R; Solís-Arrieta, L; García-Carvajal, Z; Sánchez-Betancourt, J I; Ibarra, C; Luna-Bárcenas, G; Velasquillo, C

    2015-12-01

    Tissue engineering with the use of biodegradable and biocompatible scaffolds is an interesting option for ear repair. Chitosan-Polyvinyl alcohol-Epichlorohydrine hydrogel (CS-PVA-ECH) is biocompatible and displays appropriate mechanical properties to be used as a scaffold. The present work, studies the potential of CS-PVA-ECH scaffolds seeded with chondrocytes to develop elastic cartilage engineered-neotissues. Chondrocytes isolated from rabbit and swine elastic cartilage were independently cultured onto CS-PVA-ECH scaffolds for 20 days to form the appropriate constructs. Then, in vitro cell viability and morphology were evaluated by calcein AM and EthD-1 assays and Scanning Electron Microscopy (SEM) respectively, and the constructs were implanted in nu/nu mice for four months, in order to evaluate the neotissue formation. Histological analysis of the formed neotissues was performed by Safranin O, Toluidine blue (GAG's), Verhoeff-Van Gieson (elastic fibers), Masson's trichrome (collagen) and Von Kossa (Calcium salts) stains and SEM. Results indicate appropriate cell viability, seeded with rabbit or swine chondrocyte constructs; nevertheless, upon implantation the constructs developed neotissues with different characteristics depending on the animal species from which the seeded chondrocytes came from. Neotissues developed from swine chondrocytes were similar to auricular cartilage, while neotissues from rabbit chondrocytes were similar to hyaline cartilage and eventually they differentiate to bone. This result suggests that neotissue characteristics may be influenced by the animal species source of the chondrocytes isolated. PMID:26119536

  3. 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.

  4. 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

  5. Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3-D constructs for cartilage tissue engineering.

    Science.gov (United States)

    Hilz, Florian M; Ahrens, Philipp; Grad, Sibylle; Stoddart, Martin J; Dahmani, Chiheb; Wilken, Frauke L; Sauerschnig, Martin; Niemeyer, Philipp; Zwingmann, Jörn; Burgkart, Rainer; von Eisenhart-Rothe, Rüdiger; Südkamp, Norbert P; Weyh, Thomas; Imhoff, Andreas B; Alini, Mauro; Salzmann, Gian M

    2014-02-01

    Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production.

  6. 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

  7. Age-Independent Cartilage Generation for Synovium-Based Autologous Chondrocyte Implantation.

    Science.gov (United States)

    Hunziker, Ernst B; Lippuner, Kurt; Keel, Marius J B; Shintani, Nahoko

    2015-07-01

    The articular cartilage layer of synovial joints is commonly lesioned by trauma or by a degenerative joint disease. Attempts to repair the damage frequently involve the performance of autologous chondrocyte implantation (ACI). Healthy cartilage must be first removed from the joint, and then, on a separate occasion, following the isolation of the chondrocytes and their expansion in vitro, implanted within the lesion. The disadvantages of this therapeutic approach include the destruction of healthy cartilage-which may predispose the joint to osteoarthritic degeneration-the necessarily restricted availability of healthy tissue, the limited proliferative capacity of the donor cells-which declines with age-and the need for two surgical interventions. We postulated that it should be possible to induce synovial stem cells, which are characterized by high, age-independent, proliferative and chondrogenic differentiation capacities, to lay down cartilage within the outer juxtasynovial space after the transcutaneous implantation of a carrier bearing BMP-2 in a slow-release system. The chondrocytes could be isolated on-site and immediately used for ACI. To test this hypothesis, Chinchilla rabbits were used as an experimental model. A collagenous patch bearing BMP-2 in a slow-delivery vehicle was sutured to the inner face of the synovial membrane. The neoformed tissue was excised 5, 8, 11 and 14 days postimplantation for histological and histomorphometric analyses. Neoformed tissue was observed within the outer juxtasynovial space already on the 5th postimplantation day. It contained connective and adipose tissues, and a central nugget of growing cartilage. Between days 5 and 14, the absolute volume of cartilage increased, attaining a value of 12 mm(3) at the latter juncture. Bone was deposited in measurable quantities from the 11th day onwards, but owing to resorption, the net volume did not exceed 1.5 mm(3) (14th day). The findings confirm our hypothesis. The quantity of

  8. 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

  9. 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

  10. Nanomechanics of Engineered Articular Cartilage: Synergistic Influences of Transforming Growth Factor-β3 and Oscillating Pressure.

    Science.gov (United States)

    Nazempour, Arshan; Quisenberry, Chrystal R; Van Wie, Bernard J; Abu-Lail, Nehal I

    2016-03-01

    Articular cartilage (AC), tissue with the lowest volumetric cellular density, is not supplied with blood and nerve tissue resulting in limited ability for self-repair upon injury. Because there is no treatment capable of fully restoring damaged AC, tissue engineering is being investigated. The emphasis of this field is to engineer functional tissues in vitro in bioreactors capable of mimicking in vivo envi- ronments required for appropriate cellular growth and differentiation. In a step towards engineering AC, human adipose-derived stem cells were differentiated in a unique centrifugal bioreactor under oscillating hydrostatic pressure (OHP) and supply of transforming growth factor beta 3 (TGF-β3) that mimic in vivo environments. Static micromass and pellet cultures were used as controls. Since withstanding and absorbing loads are among the main functions of an AC, mechanical properties of the engineered AC tissues were assayed using atomic force microscopy (AFM) under a controlled indentation depth of 100 nm. Young's moduli of elasticity were quantified by modeling AFM force-indentation data using the Hertz model of contact mechanics. We found exposure to OHP causes cartilage constructs to have 45-fold higher Young's moduli compared to static cultures. Addition of TGF-β3 further increases Young's moduli in bioreactor samples by 1.9-fold bringing it within 70.6% of the values estimated for native cartilage. Our results imply that OHP and TGF-β3 act synergistically to improve the mechanics of engineered tissues. PMID:27455774

  11. 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.

  12. Isolation, identification and differentiation of human embryonic cartilage stem cells.

    Science.gov (United States)

    Fu, Changhao; Yan, Zi; Xu, Hao; Zhang, Chen; Zhang, Qi; Wei, Anhui; Yang, Xi; Wang, Yi

    2015-07-01

    We isolated human embryonic cartilage stem cells (hECSCs), a novel stem cell population, from the articular cartilage of eight-week-old human embryos. These stem cells demonstrated a marker expression pattern and differentiation potential intermediate to those of human embryonic stem cells (hESCs) and human adult stem cells (hASCs). hECSCs expressed markers associated with both hESCs (OCT4, NANOG, SOX2, SSEA-3 and SSEA-4) and human adult stem cells (hASCs) (CD29, CD44, CD90, CD73 and CD10). These cells also differentiated into adipocytes, osteoblasts, chondrocytes, neurons and islet-like cells under specific inducing conditions. We identified N(6), 2'-O-dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP) as an inducer of chondrogenic differentiation in hECSCs. Similar results using N(6), 2'-O-dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP) were obtained for two other types of human embryonic tissue-derived stem cells, human embryonic hepatic stem cells (hEHSCs) and human embryonic amniotic fluid stem cells (hEASCs), both of which exhibited a marker expression pattern similar to that of hECSCs. The isolation of hECSCs and the discovery that N(6), 2'-O-dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP) induces chondrogenic differentiation in different stem cell populations might aid the development of strategies in tissue engineering and cartilage repair.

  13. 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

  14. 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.

  15. 猪耳廓及关节来源软骨细胞构建组织工程软骨的实验研究%Comparison study of tissue engineered cartilage constructed with chondrocytes derived from porcine auricular and articular cartilage

    Institute of Scientific and Technical Information of China (English)

    康宁; 刘霞; 曹谊林; 肖苒

    2014-01-01

    Objective To compare the tissue engineered cartilage constructed with chondrocytes derived from auricular and articular cartilage.Methods Chondrocytes were isolated from porcine auricular and articular cartilage,and BMSCs were obtained from bone marrow aspirate and cultured.Each kind of chondrocytes were resuspended alone or mixed with BMSCs at a ratio of 1 ∶ 1,and seeded onto PGA/PLA scaffolds to construct tissue engineered cartilage(n =4).The constructs were cultured for 8 weeks in vitro and then subcutaneously implanted into nude mice for 6 weeks.The differences between chondrocytes monoculture from articular and auricular cartilage or between each of them co-cultured with BMSCs were evaluated by gross view,measurement of thickness and wet weight,histological examinations including H&E,Safranin O,type Ⅱ collagen,and Ponceau' s & Victoria blue staining,and gene expression analysis of cartilage related genes.Results No obvious differences were found histologically among the complexes constructed in vitro 8 weeks except for few elastic fibers secreted in the auricular chondrocytes + BMSCs coculture group.Neo-cartilage is thicker in the groups of articular chondrocytes (38.1% than the group of auricular chondrocytes,P < 0.05) and articular chondrocytes + BMSCs co-culture (19.3% than the group of auricular chondrocytes + BMSCs,P < 0.05).However,after 6 weeks in vivo the elastic fibers were found positive in the complexes constructed by auricular chondrocytes,and its staining was even stronger and more homogenous in the group of auricular chondrocytes + BMSCs co-culture.The tissues generated by articular chondrocytes alone and co-cultured with BMSCs both formed the characteristic features of three-layer structure of hyaline cartilage and ossified in vivo with significant up-regulation of COL10A1 and MMP-13.To summarize,auricular chondrocytes formed the elastic cartilage while articular chondrocytes formed the hyaline cartilage during the development of

  16. 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

  17. [Cartilage tumors : Pathology and radiomorphology].

    Science.gov (United States)

    Uhl, M; Herget, G; Kurz, P

    2016-06-01

    Primary cartilage-forming tumors of the bone are frequent entities in the daily work of skeletal radiologists. This article describes the correlation of pathology and radiology in cartilage-forming skeletal tumors, in particular, enchondroma, osteochondroma, periosteal chondromas, chondroblastoma and various forms of chondrosarcoma. After reading, the radiologist should be able to deduce the different patterns of cartilage tumors on radiographs, CT, and MRI from the pathological aspects. Differentiation of enchondroma and chondrosarcoma is a frequent diagnostic challenge. Some imaging parameters, e. g., deep cortical scalloping (more than two thirds of the cortical thickness), cortical destruction, or a soft-tissue mass, are features of a sarcoma. Osteochondromas are bony protrusions with a continuous extension of bone marrow from the parent bone, the host cortical bone runs continuously from the osseous surface of the tumor into the shaft of the osteochondroma and the osteochondroma has a cartilage cap. Chondromyxoid fibromas are well-defined lytic and eccentric lesions of the metaphysis of the long bones, with nonspecific MRI findings. Chondroblastomas have a strong predilection for the epiphysis of long tubular bones and develop an intense perifocal bone marrow edema. Dedifferentiated chondrosarcomas are bimorphic lesions with a low-grade chondrogenic component and a high-grade noncartilaginous component. Most chondrogenic tumors have a predilection with regard to site and age at manifestation. PMID:27233920

  18. Autologous chondrocyte transplantation for the treatment of articular cartilage defects in the knee joint. Techniques and results; Autologe Chondrozytentransplantation zur Behandlung von Knorpeldefekten des Kniegelenks. Techniken und Ergebnisse

    Energy Technology Data Exchange (ETDEWEB)

    Marlovits, S.; Kutscha-Lissberg, F.; Aldrian, S.; Resinger, C.; Singer, P.; Zeller, P.; Vecsei, V. [Universitaetsklinik fuer Unfallchirurgie, Medizinische Universitaet Wien (Austria)

    2004-08-01

    Currently the use of autologous chondrocytes as a cartilage-repair procedure for the repair of injured articular cartilage of the knee joint, is recommended. This review presents the technique of autologous chondrocyte transplantation (ACT) and their modifications as matrix-associated autologous chondrocyte transplantation (MACT). Beside the surgical procedure the experimental and clinical results are discussed. Furthermore the major complications and the indication guidelines are presented. Articular cartilage in adults has a poor ability to self-repair after a substantial injury. Surgical therapeutic efforts in treating cartilage defects have focused on bringing new cells capable of chondrogenesis into the lesions. With ACT good to excellent clinical results are seen in isolated posttraumatic lesions of the knee joint in the younger patient with the formation of hyalinelike repair tissue. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. The current limitations include osteoarthritic defects and higher patient age. With the right indication and operative technique ACT is an effective and save option for the treatment of large full thickness cartilage defect of the knee joint. (orig.) [German] Zur Behandlung umschriebener Defekte des artikulaeren Kniegelenkgelenkknorpels wird der Einsatz autologer Knorpelzellen zunehmend als neue biologische Methode empfohlen. Die Technik der autologen Chondrozytentransplantation (ACT) und deren Modifikationen als matrixassoziierte autologe Chondrozytentransplantation (MACT) werden dargestellt. Es erfolgt ein Ueberblick ueber die experimentellen und klinischen Ergebnisse mit der Darstellung der haeufigsten Komplikationen und den derzeit gueltigen Indikationsrichtlinien. Unter Verwendung qualitativ hochwertiger Zellen zeigen besonders posttraumatische Knorpeldefekte bei juengeren Patienten eine hohe Erfolgsquote mit der Ausbildung eines hyalinartigen

  19. Human stem cells and articular cartilage regeneration.

    Science.gov (United States)

    Inui, Atsuyuki; Iwakura, Takashi; Reddi, A Hari

    2012-11-05

    The regeneration of articular cartilage damaged due to trauma and posttraumatic osteoarthritis is an unmet medical need. Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors. Stem cells, as a source of cells for articular cartilage regeneration, are a critical factor for articular cartilage regeneration. This is because articular cartilage tissue has a low cell turnover and does not heal spontaneously. Adult stem cells have been isolated from various tissues, such as bone marrow, adipose, synovial tissue, muscle and periosteum. Signals of the transforming growth factor beta superfamily play critical roles in chondrogenesis. However, adult stem cells derived from various tissues tend to differ in their chondrogenic potential. Pluripotent stem cells have unlimited proliferative capacity compared to adult stem cells. Chondrogenesis from embryonic stem (ES) cells has been studied for more than a decade. However, establishment of ES cells requires embryos and leads to ethical issues for clinical applications. Induced pluripotent stem (iPS) cells are generated by cellular reprogramming of adult cells by transcription factors. Although iPS cells have chondrogenic potential, optimization, generation and differentiation toward articular chondrocytes are currently under intense investigation.

  20. Human Stem Cells and Articular Cartilage Regeneration

    Directory of Open Access Journals (Sweden)

    A. Hari Reddi

    2012-11-01

    Full Text Available  The regeneration of articular cartilage damaged due to trauma and posttraumatic osteoarthritis is an unmet medical need. Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors. Stem cells, as a source of cells for articular cartilage regeneration, are a critical factor for articular cartilage regeneration. This is because articular cartilage tissue has a low cell turnover and does not heal spontaneously. Adult stem cells have been isolated from various tissues, such as bone marrow, adipose, synovial tissue, muscle and periosteum. Signals of the transforming growth factor beta superfamily play critical roles in chondrogenesis. However, adult stem cells derived from various tissues tend to differ in their chondrogenic potential. Pluripotent stem cells have unlimited proliferative capacity compared to adult stem cells. Chondrogenesis from embryonic stem (ES cells has been studied for more than a decade. However, establishment of ES cells requires embryos and leads to ethical issues for clinical applications. Induced pluripotent stem (iPS cells are generated by cellular reprogramming of adult cells by transcription factors. Although iPS cells have chondrogenic potential, optimization, generation and differentiation toward articular chondrocytes are currently under intense investigation.

  1. Genipin-crosslinked cartilage-derived matrix as a scaffold for human adipose-derived stem cell chondrogenesis.

    Science.gov (United States)

    Cheng, Nai-Chen; Estes, Bradley T; Young, Tai-Horng; Guilak, Farshid

    2013-02-01

    Autologous cell-based tissue