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Sample records for cartilage repair tissue

  1. Magnetization transfer analysis of cartilage repair tissue: a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Palmieri, F. [University ' Federico II' , Department of Radiology, Naples (Italy); Keyzer, F. de [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Maes, F. [Catholic University Leuven, Department of Electrotechnics, Faculty of Engineering, Leuven (Belgium); Breuseghem, I. van [Ghent University Hospital, Department of Radiology, Gent (Belgium)

    2006-12-15

    To evaluate the magnetization transfer ratio (MTR) after two different cartilage repair procedures, and to compare these data with the MTR of normal cartilage. Twenty-seven patients with a proven cartilage defect were recruited: 13 were treated with autologous chondrocyte implantation (ACI) and 14 were treated with the microfracture technique (MFR). All patients underwent MRI examinations with MT-sequences before the surgical treatment, after 12 months (26 patients) and after 24 months (11 patients). Eleven patients received a complete follow-up study at all three time points (five of the ACI group and six of the MFR group). All images were transferred to a workstation to calculate MTR images. For every MT image set, different ROIs were delineated by two radiologists. Means were calculated per ROI type in the different time frames and in both groups of cartilage repair. The data were analyzed with unpaired t- and ANOVA tests, and by calculating Pearson's correlation coefficient. No significant differences were found in the MTR of fatty bone marrow, muscle and normal cartilage in the different time frames. There was a significant but small difference between the MTR of normal cartilage and the cartilage repair area after 12 months for both procedures. After 24 months, the MTR of ACI repaired cartilage (0.31{+-}0.07) was not significantly different from normal cartilage MTR (0.34{+-}0.05). The MTR of MFR repaired cartilage (0.28{+-}0.02), still showed a significant difference from normal cartilage. The differences between damaged and repaired cartilage MTR are too small to enable MT-imaging to be a useful tool for postoperative follow-up of cartilage repair procedures. There is, however, an evolution towards normal MTR-values in the cartilage repair tissue (especially after ACI repair). (orig.)

  2. Magnetization transfer analysis of cartilage repair tissue: a preliminary study

    International Nuclear Information System (INIS)

    Palmieri, F.; Keyzer, F. de; Maes, F.; Breuseghem, I. van

    2006-01-01

    To evaluate the magnetization transfer ratio (MTR) after two different cartilage repair procedures, and to compare these data with the MTR of normal cartilage. Twenty-seven patients with a proven cartilage defect were recruited: 13 were treated with autologous chondrocyte implantation (ACI) and 14 were treated with the microfracture technique (MFR). All patients underwent MRI examinations with MT-sequences before the surgical treatment, after 12 months (26 patients) and after 24 months (11 patients). Eleven patients received a complete follow-up study at all three time points (five of the ACI group and six of the MFR group). All images were transferred to a workstation to calculate MTR images. For every MT image set, different ROIs were delineated by two radiologists. Means were calculated per ROI type in the different time frames and in both groups of cartilage repair. The data were analyzed with unpaired t- and ANOVA tests, and by calculating Pearson's correlation coefficient. No significant differences were found in the MTR of fatty bone marrow, muscle and normal cartilage in the different time frames. There was a significant but small difference between the MTR of normal cartilage and the cartilage repair area after 12 months for both procedures. After 24 months, the MTR of ACI repaired cartilage (0.31±0.07) was not significantly different from normal cartilage MTR (0.34±0.05). The MTR of MFR repaired cartilage (0.28±0.02), still showed a significant difference from normal cartilage. The differences between damaged and repaired cartilage MTR are too small to enable MT-imaging to be a useful tool for postoperative follow-up of cartilage repair procedures. There is, however, an evolution towards normal MTR-values in the cartilage repair tissue (especially after ACI repair). (orig.)

  3. Repair of osteochondral defects with allogeneic tissue engineered cartilage implants.

    Science.gov (United States)

    Schreiber, R E; Ilten-Kirby, B M; Dunkelman, N S; Symons, K T; Rekettye, L M; Willoughby, J; Ratcliffe, A

    1999-10-01

    The objective of this study was to evaluate the effect of allogeneic tissue engineered cartilage implants on healing of osteochondral defects. Rabbit chondrocytes were cultured in monolayer, then seeded onto biodegradable, three-dimensional polyglycolic acid meshes. Cartilage constructs were cultured hydrodynamically to yield tissue with relatively more (mature) or less (immature) hyalinelike cartilage, as compared with adult rabbit articular cartilage. Osteochondral defects in the patellar grooves of both stifle joints either were left untreated or implanted with allogeneic tissue engineered cartilage. Histologic samples from in and around the defect sites were examined 3, 6, 9, and 12, and 24 months after surgery. By 9 months after surgery, defects sites treated with cartilage implants contained significantly greater amounts of hyalinelike cartilage with high levels of proteoglycan, and had a smooth, nonfibrillated articular surface as compared to untreated defects. In contrast, the repair tissue formed in untreated defects had fibrillated articular surfaces, significant amounts of fibrocartilage, and negligible proteoglycan. These differences between treated and untreated defects persisted through 24 months after surgery. The results of this study suggest that the treatment of osteochondral lesions with allogenic tissue engineered cartilage implants may lead to superior repair tissue than that found in untreated osteochondral lesions.

  4. Gene Therapy for Cartilage Repair

    Science.gov (United States)

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists. PMID:26069580

  5. 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...

  6. New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

    Science.gov (United States)

    Musumeci, Giuseppe; Castrogiovanni, Paola; Leonardi, Rosalia; Trovato, Francesca Maria; Szychlinska, Marta Anna; Di Giunta, Angelo; Loreto, Carla; Castorina, Sergio

    2014-01-01

    In this paper review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness. We illustrated the anatomical aspect of the knee joint cartilage, the current state of cartilage tissue engineering, through mesenchymal stem cells and biomaterials, and in conclusion we provide a short overview on the rehabilitation after articular cartilage repair procedures. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, and to date several researchers aim to implement clinical application of cell-based therapies for cartilage repair. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords, examining the current literature on the well-known tissue engineering methods for the treatment of knee osteoarthritis. PMID:24829869

  7. Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration

    Science.gov (United States)

    Mardones, Rodrigo; Jofré, Claudio M.; Minguell, José J.

    2015-01-01

    Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an ‘in situ’ cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed. PMID:26019754

  8. Tissue-Derived Extracellular Matrix Bioscaffolds: Emerging Applications in Cartilage and Meniscus Repair.

    Science.gov (United States)

    Monibi, Farrah A; Cook, James L

    2017-08-01

    Musculoskeletal injuries are a common problem in orthopedic practice. Given the long-term consequences of unaddressed cartilage and meniscal pathology, a number of treatments have been attempted to stimulate repair or to replace the injured tissue. Despite advances in orthopedic surgery, effective treatments for cartilage and meniscus injuries remain a significant clinical challenge. Tissue engineering is a developing field that aims to regenerate injured tissues with a combination of cells, scaffolds, and signals. Many natural and synthetic scaffold materials have been developed and tested for the repair and restoration of a number of musculoskeletal tissues. Among these, biological scaffolds derived from cell and tissue-derived extracellular matrix (ECM) have shown great promise in tissue engineering given the critical role of the ECM for maintaining the biological and biomechanical properties, structure, and function of native tissues. This review article presents emerging applications for tissue-derived ECM scaffolds in cartilage and meniscus repair. We examine normal ECM composition and the current and future methods for potential treatment of articular cartilage and meniscal defects with decellularized scaffolds.

  9. Evaluation of cartilage repair tissue in the knee and ankle joint using sodium magnetic resonance imaging at 7 Tesla

    International Nuclear Information System (INIS)

    Zbyn, S.

    2015-01-01

    Articular cartilage of adults shows no or very limited intrinsic capacity for self-repair. Since untreated chondral defects often progress to osteoarthritis, symptomatic defects should be treated. Different cartilage repair procedures have been developed with the goal to restore joint function and prevent further cartilage degeneration by providing repair tissue of the same structure, composition, and biomechanical properties as native cartilage. Various cartilage repair procedures have been developed; including bone marrow stimulation (BMS) techniques such as microfracture (MFX), cell-based techniques such as matrix-associated autologous chondrocyte transplantation (MACT), and others. Since biopsies of cartilage repair tissue are invasive and cannot be repeated, a noninvasive method is needed that could follow-up the quality of cartilage and repair tissue. Negatively charged glycosaminoglycans (GAG) are very important for cartilage function as they attract positive ions such as sodium. The high concentration of ions in cartilage is responsible for osmotic pressure providing cartilage its resilience to compression. Since GAGs are counterbalanced by sodium ions, sodium magnetic resonance imaging (MRI) was validated as a sensitive method for the in vivo evaluation of GAG concentration in native cartilage but not for repair tissue. Thus, the main goal of this thesis was to optimize and validate sodium 7 Tesla MRI for the evaluation of cartilage repair tissue quality in patients after different cartilage repair surgeries in the knee and ankle joint. In our studies, sodium MRI was used for the first time for the clinical evaluation of cartilage repair tissue. A strong correlation found between sodium imaging and dGEMRIC (another GAG-sensitive technique) in patients after MACT on femoral cartilage proved sensitivity of sodium MRI to GAG changes in native cartilage and repair tissue in vivo. Comparison between BMS and MACT patients showed significantly lower sodium values

  10. Articular Cartilage Repair Through Muscle Cell-Based Tissue Engineering

    Science.gov (United States)

    2011-03-01

    TaqMan probe AAC-CCT-CTT- TTC -GGA-TTA-ACC-CTG-CGA- GTT. Articular cartilage defect model and cell transplanta- tion. All animal experiments were... inhalation mask. The knee joint was exposed by medial parapa- tellar incision, and the trochlear groove was exposed by lateral dislocation of the...least significant difference test. P values less than 0.05 were considered significant. RESULTS In vitro MDSC characterization. Flow cytometric analysis

  11. Current strategies for articular cartilage repair

    OpenAIRE

    Redman S. N.; Oldfield S. F.; Archer C. W.

    2005-01-01

    Defects of articular cartilage that do not penetrate to the subchondral bone fail to heal spontaneously. Defects that penetrate to the subchondral bone elicit an intrinsic repair response that yields a fibrocartilaginous repair tissue which is a poor substitute for hyaline articular cartilage. Many arthroscopic repair strategies employed utilise this intrinsic repair response to induce the formation of a repair tissue within the defect. The goal, however, is to produce a repair tissue that ha...

  12. Repair of Cartilage injuries using in vitro engineered 3D cartilage tissue- Preliminary Results of Our Animal Studies.

    Science.gov (United States)

    Arumugam, S; Manjunath, S; Senthilkumar, R; Rajendiran, S; Yoshioka, H; Mori, Y; Abraham, S

    2011-01-01

    The cartilage injuries demand novel therapeutic approaches as the success rates of the current conventional strategies for the repair of injured articular cartilages are not that encouraging. Earlier we have reported that the Thermoreversible Gelation Polymer (TGP) is an ideal scaffold for human chondrocyte expansion in vitro. In this study, we report the preliminary results of the in vitro expansion, characterization and experimental in vivo transplantation of chondrocytes in a rabbit model of cartilage injury. Nine rabbits were included in this study scheduled for two years, after approval by the ethics committee. In the first animal, Chondrocytes were isolated from the weight bearing area of patellar groove in the left hindlimb and cultured in TGP Scaffold and maintained at 37°C in 5% carbon dioxide incubator for 64 days without growth factors. Then the TGP-Chondrocyte construct was transplanted into an experimental defect created in the knee of the right forelimb of the same rabbit. After a period of 10 weeks, a biopsy was taken from the transplanted region and subjected to morphological analysis, characterization by histopathology (H&E stain) and Immunohistochemistry (S-100 staining). The chondrocytes in the 3D TGP culture had round to oval shaped morphology without any de-differentiation which is otherwise observed in Conventional 2D cultures. A macroscopic structure which resembled cartilage was appreciated in the TGP construct in vitro after 64 days which was then transplanted to the rabbit. The H&E and Immunohistochemistry studies confirmed the presence of chondrocytes in the biopsy tissue. Based on the results, we conclude that the TGP significantly supports the in vitro expansion of chondrocytes for a longer period and the 3D culture using TGP preserves the phenotype of the articular chondrocytes. The tissue thus grown when implanted with the TGP has engrafted well without any adverse reactions and upon confirmation of safety following completion of the

  13. Definition of pertinent parameters for the evaluation of articular cartilage repair tissue with high-resolution magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Marlovits, Stefan E-mail: stefan.marlovits@akh-wien.ac.at; Striessnig, Gabriele; Resinger, Christoph T.; Aldrian, Silke M.; Vecsei, Vilmos; Imhof, Herwig; Trattnig, Siegfried

    2004-12-01

    To evaluate articular cartilage repair tissue after biological cartilage repair, we propose a new technique of non-invasive, high-resolution magnetic resonance imaging (MRI) and define a new classification system. For the definition of pertinent variables the repair tissue of 45 patients treated with three different techniques for cartilage repair (microfracture, autologous osteochondral transplantation, and autologous chondrocyte transplantation) was analyzed 6 and 12 months after the procedure. High-resolution imaging was obtained with a surface phased array coil placed over the knee compartment of interest and adapted sequences were used on a 1 T MRI scanner. The analysis of the repair tissue included the definition and rating of nine pertinent variables: the degree of filling of the defect, the integration to the border zone, the description of the surface and structure, the signal intensity, the status of the subchondral lamina and subchondral bone, the appearance of adhesions and the presence of synovitis. High-resolution MRI, using a surface phased array coil and specific sequences, can be used on every standard 1 or 1.5 T MRI scanner according to the in-house standard protocols for knee imaging in patients who have had cartilage repair procedures without substantially prolonging the total imaging time. The new classification and grading system allows a subtle description and suitable assessment of the articular cartilage repair tissue.

  14. 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

  15. Repair of Cartilage injuries using in vitro engineered 3D cartilage tissue- Preliminary Results of Our Animal Studies

    Directory of Open Access Journals (Sweden)

    Arumugam S

    2011-01-01

    Full Text Available Introduction: The cartilage injuries demand novel therapeutic approaches as the success rates of the current conventional strategies for the repair of injured articular cartilages are not that encouraging. Earlier we have reported that the Thermoreversible Gelation Polymer (TGP is an ideal scaffold for human chondrocyte expansion in vitro. In this study, we report the preliminary results of the in vitro expansion, characterization and experimental in vivo transplantation of chondrocytes in a rabbit model of cartilage injury Materials & Methods: Nine rabbits were included in this study scheduled for two years, after approval by the ethics committee. In the first animal, Chondrocytes were isolated from the weight bearing area of patellar groove in the left hindlimb and cultured in TGP Scaffold and maintained at 37°C in 5% carbon dioxide incubator for 64 days without growth factors. Then the TGP-Chondrocyte construct was transplanted into an experimental defect created in the knee of the right forelimb of the same rabbit. After a period of 10 weeks, a biopsy was taken from the transplanted region and subjected to morphological analysis, characterization by histopathology (H&E stain and Immunohistochemistry (S-100 staining.Results: The chondrocytes in the 3D TGP culture had round to oval shaped morphology without any de-differentiation which is otherwise observed in Conventional 2D cultures. A macroscopic structure which resembled cartilage was appreciated in the TGP construct in vitro after 64 days which was then transplanted to the rabbit. The H&E and Immunohistochemistry studies confirmed the presence of chondrocytes in the biopsy tissue. Conclusion: Based on the results, we conclude that the TGP significantly supports the in vitro expansion of chondrocytes for a longer period and the 3D culture using TGP preserves the phenotype of the articular chondrocytes. The tissue thus grown when implanted with the TGP has engrafted well without any

  16. Low friction hydrogel for articular cartilage repair: evaluation of mechanical and tribological properties in comparison with natural cartilage tissue.

    Science.gov (United States)

    Blum, Michelle M; Ovaert, Timothy C

    2013-10-01

    The mechanical and tribological properties of a novel biomaterial, a boundary lubricant functionalized hydrogel, were investigated and compared to natural cartilage tissue. This low friction hydrogel material was developed for use as a synthetic replacement for focal defects in articular cartilage. The hydrogel was made by functionalizing the biocompatible polymer polyvinyl alcohol with a carboxylic acid derivative boundary lubricant molecule. Two different gel processing techniques were used to create the hydrogels. The first method consisted of initially functionalizing the boundary lubricant to the polyvinyl alcohol and then creating hydrogels by physically crosslinking the reacted polymer. The second method consisted of creating non-functionalized polyvinyl alcohol hydrogels and then performing the functionalization reaction on the fully formed gel. Osteochondral bovine samples were collected and replicate experiments were conducted to compare the mechanical and tribological performance of the boundary lubricant functionalized hydrogels to non-functionalized hydrogels and native cartilage. Friction experiments displayed a maximum decrease in friction coefficient of 70% for the functionalized hydrogels compared to neat polyvinyl alcohol. Indentation investigated the elastic modulus of the hydrogels, demonstrating that stability of the hydrogel was affected by processing method. Hydrogel performance was within the lower ranges of natural cartilage tested under the exact same conditions, showing the potential of the boundary lubricant functionalized hydrogels to perform as a biomimetic synthetic articular cartilage replacement. © 2013.

  17. INJURED ARTICULAR CARTILAGE REPAIR

    Directory of Open Access Journals (Sweden)

    Ariana Barlič

    2008-02-01

    Surveys show that the most frequently used surgical methods are mosaicplasty and bonemarrow stimulation with microfracturing. The efficacy of the autologous chondrocyte implantationmethod should be superior to microfracturing on a long run. Especially when(regeneration of the hyaline cartilage instead of fibrous tissue (fibrocartilage is concerned.However, it has not been scientifically proved yet

  18. 2-year postoperative evaluation of a patient with a symptomatic full-thickness patellar cartilage defect repaired with particulated juvenile cartilage tissue.

    Science.gov (United States)

    Bonner, Kevin F; Daner, William; Yao, Jian Q

    2010-06-01

    This case report describes the early results of a 36-year-old man who underwent repair of a symptomatic full-thickness patellar cartilage defect with transplanted particulated juvenile articular cartilage. At 2 years postoperatively, the patient has experienced substantial clinical improvement in both pain and function when evaluated with both International Knee Documentation Committee subjective evaluation and Knee Injury and Osteoarthritis Outcome Score outcome measures. Two-year postoperative magnetic resonance imaging demonstrates fill of the defect with repair tissue and near complete resolution of preoperative subchondral bone edema. To the best of the authors' knowledge, this case report is the first to report clinical results of this new technique at 2 years postoperatively.

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

    Directory of Open Access Journals (Sweden)

    Juan Antonio Marchal

    2013-03-01

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

  20. Current concepts of articular cartilage repair.

    Science.gov (United States)

    Schindler, Oliver S

    2011-12-01

    Articular cartilage provides a vital function in the homeostasis of the joint environment. It possesses unique mechanical properties, allowing for the maintenance of almost frictionless motion over a lifetime. However, cartilage is vulnerable to traumatic injury and due to its poor vascularity and inability to access mesenchymal stem cells, unable to facilitate a satisfactory healing response. Untreated chondral defects are thus likely to predispose patients to the development of osteoarthritis. Reconstitution and repair of articular cartilage is dependent on the neosynthesis or implantation of cartilage matrix elements, a goal which can be achieved through a variety of surgical means. Commonly used repair techniques include marrow stimulation, structural osteo-articular autografts or chondrocyte implantation. Despite substantial differences in the complexity and technical application of each method, all are united in the endeavour to restore joint function and prevent joint degeneration. Anyone attempting to treat cartilage defects must possess a basic understanding of the physiology of cartilage growth, and relevant factors affecting cartilage healing and repair. Furthermore, knowledge of the biomechanics and kinematics of the knee are essential in order to appreciate the forces acting on joint surfaces and repair tissues. Although clinical success is dependent on appropriate patient selection, accurate clinical assessment, definition of root causes and application of the right choice of treatment modality, the ultimate outcome of any intervention remains heavily reliant on the surgeon's proficiency in the technical aspects of the chosen surgical procedure.

  1. The Application of Polysaccharide Biocomposites to Repair Cartilage Defects

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. Principles of cartilage repair

    CERN Document Server

    Erggelet, Christoph; Mandelbaum, Bert R

    2008-01-01

    Cartilage defects affect patients of all age groups. Surgeons, teamdoctors, general practitioners and physiotherapists alike are expected to provide adequate care. Only individual treatment plans combining a well balanced choice of various options will be successful. Background knowledge, operative and non-operative therapies are described in concise chapters: Articular cartilage biology - Diagnostics - Surgical techniques - Symptomatic and alternative medications - Physiotherapy. Diagnostic findings and surgical procedures are generously illustrated by aquarelles and colour photographs. Recommendations for additional reading, description of important clinical scoring systems and a listing of analytic tools are added for further information.

  4. Intraarticular Hyaluronic Acid Injection after Microfracture Technique for the Management of Full-Thickness Cartilage Defects Does Not Improve the Quality of Repair Tissue

    Science.gov (United States)

    Bostan, Bora; Erdem, Mehmet; Koseoglu, Resid Dogan; Asci, Murat; Sen, Cengiz

    2012-01-01

    Objective: Tissue repair that occurs after microfracture does not include hyaline-like cartilage. Therefore, other treatment modalities must be combined with microfracture to improve repair tissue quality. In this study, we combined exogenous hyaluronic acid with microfracture. Design: Thirty mature New Zealand rabbits were randomly divided into 3 groups as control, microfracture (MF), and microfracture and hyaluronic acid (MFHA). Four-millimetre full-thickness cartilage defects were created in the medial femoral condyle of each rabbit. Microfracture was performed on defects in the MF and MFHA groups. At 1 week following surgery, 1 mL of saline was injected into the knees of the control and MF groups, whereas 1 mL (15 mg/mL) hyaluronic acid was injected into the knees of the MFHA group 3 times weekly. At 6 months postsurgery, defects were evaluated according to the ICRS (International Cartilage Repair Society) and Wakitani scales. Results: According to the ICRS and Wakitani scales, the quality of repair tissue was improved in MF and MFHA groups as compared the control group (P = 0.001 and 0.001, respectively). No significant difference was observed between the MF and MFHA groups (P = 0.342). Conclusions: According to the model in this study, no beneficial effect was obtained when HA injection was combined with microfracture in the treatment of full-thickness cartilage defects. PMID:26069616

  5. MR imaging of cartilage and its repair in the knee - a review

    Energy Technology Data Exchange (ETDEWEB)

    Trattnig, S.; Welsch, G.W. [Medical University Vienna, MR Centre of Excellence, Department of Radiology, Vienna (Austria); Domayer, S. [Medical University Vienna, MR Centre of Excellence, Department of Radiology, Vienna (Austria); Medical University Vienna, Department of Orthopedics, Vienna (Austria); Mosher, T. [Penn State University, College of Medicine, Department of Radiology and Orthopaedic Surgery, Hershey, PA (United States); Eckstein, F. [Paracelsus Medical University, Institute of Anatomy and Musculoskeletal Research, Salzburg (Austria); Chondrometrics GmbH, Ainring (Germany)

    2009-07-15

    Chondral injuries are common lesions of the knee joint, and many patients could benefit from cartilage repair. Widespread cartilage repair techniques require sophisticated noninvasive follow-up using MRI. In addition to the precise morphological assessment of this area of cartilage repair, the cartilage's biochemical constitution can be determined using biochemical MRI techniques. The combination of the clinical outcome after cartilage repair together with the morphological and biochemical description of the cartilage repair tissue as well as the surrounding cartilage can lead to an optimal follow-up evaluation. The present article on MR imaging techniques of cartilage repair focuses on morphological description and scoring using techniques from conventional 2D through advanced isotropic 3D MRI sequences. Furthermore the ultrastructure of the repair tissue and the surrounding cartilage is evaluated in-vivo by biochemical T1-delayed gadolinium enhanced MRI of cartilage (dGEMRIC), T2 relaxation, and diffusion-weighted imaging techniques. (orig.)

  6. Magnetic resonance imaging of cartilage and cartilage repair

    International Nuclear Information System (INIS)

    Verstraete, K.L.; Almqvist, F.; Verdonk, P.; Vanderschueren, G.; Huysse, W.; Verdonk, R.; Verbrugge, G.

    2004-01-01

    Magnetic resonance (MR) imaging of articular cartilage has assumed increased importance because of the prevalence of cartilage injury and degeneration, as well as the development of new surgical and pharmacological techniques to treat damaged cartilage. This article will review relevant aspects of the structure and biochemistry of cartilage that are important for understanding MR imaging of cartilage, describe optimal MR pulse sequences for its evaluation, and review the role of experimental quantitative MR techniques. These MR aspects are applied to clinical scenarios, including traumatic chondral injury, osteoarthritis, inflammatory arthritis, and cartilage repair procedures

  7. Magnetic resonance imaging of cartilage and cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Verstraete, K.L. E-mail: koenraad.verstraete@ugent.be; Almqvist, F.; Verdonk, P.; Vanderschueren, G.; Huysse, W.; Verdonk, R.; Verbrugge, G

    2004-08-01

    Magnetic resonance (MR) imaging of articular cartilage has assumed increased importance because of the prevalence of cartilage injury and degeneration, as well as the development of new surgical and pharmacological techniques to treat damaged cartilage. This article will review relevant aspects of the structure and biochemistry of cartilage that are important for understanding MR imaging of cartilage, describe optimal MR pulse sequences for its evaluation, and review the role of experimental quantitative MR techniques. These MR aspects are applied to clinical scenarios, including traumatic chondral injury, osteoarthritis, inflammatory arthritis, and cartilage repair procedures.

  8. Cellular reprogramming for clinical cartilage repair

    OpenAIRE

    Driessen, Britta J.H.; Logie, Colin; Vonk, Lucienne A.

    2017-01-01

    The repair of articular cartilage needs a sufficient number of chondrocytes to replace the defect tissue, and therefore, expansion of cells is generally required. Chondrocytes derived by cellular reprogramming may provide a solution to the limitations of current (stem) cell-based therapies. In this article, two distinct approaches?induced pluripotent stem cell (iPSC)-mediated reprogramming and direct lineage conversion?are analysed and compared according to criteria that encompass the qualifi...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. Comparison of international guidelines for regenerative medicine: Knee cartilage repair and replacement using human-derived cells and tissues.

    Science.gov (United States)

    Itoh, Kuni; Kano, Shingo

    2016-07-01

    Regenerative medicine (RM) is an emerging field using human-derived cells and tissues (HCT). Due to the complexity and diversity of HCT products, each country has its own regulations for authorization and no common method has been applied to date. Individual regulations were previously clarified at the level of statutes but no direct comparison has been reported at the level of guidelines. Here, we generated a new analytical framework that allows comparison of guidelines independent from local definitions of RM, using 2 indicators, product type and information type. The guidelines for products for repair and replacement of knee cartilage in Japan, the United States of America, and Europe were compared and differences were detected in both product type and information type by the proposed analytical framework. Those findings will be critical not only for the product developers to determine the region to initiate the clinical trials but also for the regulators to assess and build their regulations. This analytical framework is potentially expandable to other RM guidelines to identify gaps, leading to trigger discussion of global harmonization in RM regulations. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  12. Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: application in cartilage tissue repair.

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    Sophie Portron

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

  13. Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: Determination of interobserver variability and correlation to clinical outcome after 2 years

    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; Singer, Philipp [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Zeller, Philip [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Mandl, Irena [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Haller, Joerg [Department of Radiology, Hanusch Hospital, Heinrich-Collin-Strasse, A-1140 Vienna (Austria); Trattnig, Siegfried [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-01-15

    In an observational study, the validity and reliability of magnetic resonance imaging (MRI) for the assessment of autologous chondrocyte transplantation (ACT) in the knee joint was determined. Two years after implantation, high-resolution MRI was used to analyze the repair tissue with nine pertinent variables. A complete filling of the defect was found in 61.5%, and a complete integration of the border zone to the adjacent cartilage in 76.9%. An intact subchondral lamina was present in 84.6% and an intact subchondral bone was present in 61.5%. Isointense signal intensities of the repair tissue compared to the adjacent native cartilage were seen in 92.3%. To evaluate interobserver variability, a reliability analysis with the determination of the intraclass correlation coefficient (ICC) was calculated. An 'almost perfect' agreement, with an ICC value >0.81, was calculated in 8 of 9 variables. The clinical outcome after 2 years showed the visual analog score (VAS) at 2.62 (S.D. {+-}0.65). The values for the knee injury and osteoarthritis outcome score (KOOS) subgroups were 68.29 ({+-}23.90) for pain, 62.09 ({+-}14.62) for symptoms, 75.45 ({+-}21.91) for ADL function, 52.69 ({+-}28.77) for sport and 70.19 ({+-}22.41) for knee-related quality of life. The clinical scores were correlated with the MRI variables. A statistically significant correlation was found for the variables 'filling of the defect,' 'structure of the repair tissue,' 'changes in the subchondral bone,' and 'signal intensities of the repair issue'. High resolution MRI and well-defined MRI variables are a reliable, reproducible and accurate tool for assessing cartilage repair tissue.

  14. Articular cartilage tissue engineering: the role of signaling molecules

    Science.gov (United States)

    Kwon, Heenam; Paschos, Nikolaos K.; Hu, Jerry C.; Athanasiou, Kyriacos

    2017-01-01

    Effective early disease modifying options for osteoarthritis remain lacking. Tissue engineering approach to generate cartilage in vitro has emerged as a promising option for articular cartilage repair and regeneration. Signaling molecules and matrix modifying agents, derived from knowledge of cartilage development and homeostasis, have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage. Clinical translation of neocartilage faces challenges, such as phenotypic instability of the engineered cartilage, poor integration, inflammation, and catabolic factors in the arthritic environment; these can all contribute to failure of implanted neocartilage. A comprehensive understanding of signaling molecules involved in osteoarthritis pathogenesis and their actions on engineered cartilage will be crucial. Thus, while it is important to continue deriving inspiration from cartilage development and homeostasis, it has become increasing necessary to incorporate knowledge from osteoarthritis pathogenesis into cartilage tissue engineering. PMID:26811234

  15. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    Science.gov (United States)

    Im, Gun-Il

    2016-04-01

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

  16. Tissue engineering techniques to regenerate articular cartilage using polymeric scaffolds.

    OpenAIRE

    PÉREZ OLMEDILLA, MARCOS

    2016-01-01

    [EN] Articular cartilage is a tissue that consists of chondrocytes surrounded by a dense extracellular matrix (ECM). The ECM is mainly composed of type II collagen and proteoglycans. The main function of articular cartilage is to provide a lubricated surface for articulation. Articular cartilage damage is common and may lead to osteoarthritis. Articular cartilage does not have blood vessels, nerves or lymphatic vessels and therefore has limited capacity for intrinsic healing and repair. ...

  17. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant.

    Science.gov (United States)

    Bartz, Christoph; Meixner, Miriam; Giesemann, Petra; Roël, Giulietta; Bulwin, Grit-Carsta; Smink, Jeske J

    2016-11-15

    Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don's chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids) that is in clinical use in Germany. Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids before implantation and a higher regeneration potential

  18. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant

    Directory of Open Access Journals (Sweden)

    Christoph Bartz

    2016-11-01

    Full Text Available Abstract Background Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don’s chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids that is in clinical use in Germany. Methods Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. Results After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids

  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. Recent developments in scaffold-guided cartilage tissue regeneration.

    Science.gov (United States)

    Liao, Jinfeng; Shi, Kun; Ding, Qiuxia; Qu, Ying; Luo, Feng; Qian, Zhiyong

    2014-10-01

    Articular cartilage repair is one of the most challenging problems in biomedical engineering because the regenerative capacity of cartilage is intrinsically poor. The lack of efficient treatment modalities motivates researches into cartilage tissue engineering such as combing cells, scaffolds and growth factors. In this review we summarize the current developments on scaffold systems available for cartilage tissue engineering. The factors that are critical to successfully design an ideal scaffold for cartilage regeneration were discussed. Then we present examples of selected material types (natural polymers and synthetic polymers) and fabricated forms of the scaffolds (three-dimensional scaffolds, micro- or nanoparticles, and their composites). In the end of review, we conclude with an overview of the ways in which biomedical nanotechnology is widely applied in cartilage tissue engineering, especially in the design of composite scaffolds. This review attempts to provide recommendations on the combination of qualities that would produce the ideal scaffold system for cartilage tissue engineering.

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

    Directory of Open Access Journals (Sweden)

    Pieter K Bos

    2010-10-01

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

  2. When is cartilage repair successful?; Wann ist eine Knorpelreparatur erfolgreich

    Energy Technology Data Exchange (ETDEWEB)

    Raudner, M.; Roehrich, S.; Zalaudek, M.; Trattnig, S. [Medizinische Universitaet Wien, Exzellenzzentrum Hochfeld-MR, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria); Schreiner, M.M. [Medizinische Universitaet Wien, Universitaetsklinik fuer Orthopaedie, Wien (Austria)

    2017-11-15

    Focal cartilage lesions are a cause of long-term disability and morbidity. After cartilage repair, it is crucial to evaluate long-term progression or failure in a reproducible, standardized manner. This article provides an overview of the different cartilage repair procedures and important characteristics to look for in cartilage repair imaging. Specifics and pitfalls are pointed out alongside general aspects. After successful cartilage repair, a complete, but not hypertrophic filling of the defect is the primary criterion of treatment success. The repair tissue should also be completely integrated to the surrounding native cartilage. After some months, the transplants signal should be isointense compared to native cartilage. Complications like osteophytes, subchondral defects, cysts, adhesion and chronic bone marrow edema or joint effusion are common and have to be observed via follow-up. Radiological evaluation and interpretation of postoperative changes should always take the repair method into account. (orig.) [German] Die Therapie fokaler Knorpelschaeden ist weiterhin eine klinische Herausforderung. Nach erfolgter Sanierung gilt es daher besonders, Erfolg und Misserfolg zu evaluieren und den Verlauf standardisiert und somit reproduzierbar zu beurteilen. Dieser Artikel bietet einen Ueberblick ueber gaengige Reparaturverfahren und deren Charakteristika in der Magnetresonanztomographie. Nach einer erfolgreichen Knorpelreparatur ist eine vollstaendige, aber nicht hypertrophe Fuellung des Knorpeldefekts das primaere Kriterium. Zum umgebenden Nativknorpel ist ausserdem eine durchgehende Integration des Transplantats vordergruendig. Im weiteren postoperativen Verlauf sollte das Transplantat ausserdem ein im Vergleich zu nativem Knorpel isointenses Signalverhalten zeigen. Haeufig beobachtete Komplikationen sind zentrale Osteophyten, subchondrale Defekte, Zysten, chronifizierte Knochenmarksoedeme, Gelenkserguesse oder Adhaesionen. Die radiologische Beurteilung dieser

  3. Injectable hydrogels for cartilage and bone tissue engineering

    Science.gov (United States)

    Liu, Mei; Zeng, Xin; Ma, Chao; Yi, Huan; Ali, Zeeshan; Mou, Xianbo; Li, Song; Deng, Yan; He, Nongyue

    2017-01-01

    Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed. PMID:28584674

  4. 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.

  5. Mesenchymal stem cells for cartilage repair in osteoarthritis.

    Science.gov (United States)

    Gupta, Pawan K; Das, Anjan K; Chullikana, Anoop; Majumdar, Anish S

    2012-07-09

    Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve. Since the tissue is composed primarily of chondrocytes distributed in a specialized extracellular matrix bed, bone marrow stromal cells (BMSCs), also known as bone marrow-derived 'mesenchymal stem cells' or 'mesenchymal stromal cells', with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. BMSCs can be easily isolated and massively expanded in culture in an undifferentiated state for therapeutic use. Owing to their potential to modulate local microenvironment via anti-inflammatory and immunosuppressive functions, BMSCs have an additional advantage for allogeneic application. Moreover, by secreting various bioactive soluble factors, BMSCs can protect the cartilage from further tissue destruction and facilitate regeneration of the remaining progenitor cells in situ. This review broadly describes the advances made during the last several years in BMSCs and their therapeutic potential for repairing cartilage damage in OA.

  6. Current perspectives in stem cell research for knee cartilage repair

    Directory of Open Access Journals (Sweden)

    Orth P

    2014-01-01

    Full Text Available Patrick Orth,1 Ana Rey-Rico,2 Jagadeesh K Venkatesan,2 Henning Madry,1,2 Magali Cucchiarini2 1Department of Orthopaedic Surgery, 2Center of Experimental Orthopaedics, Saarland University Medical Center, Homburg, Germany Abstract: Protocols based on the delivery of stem cells are currently applied in patients, showing encouraging results for the treatment of articular cartilage lesions (focal defects, osteoarthritis. Yet, restoration of a fully functional cartilage surface (native structural organization and mechanical functions especially in the knee joint has not been reported to date, showing the need for improved designs of clinical trials. Various sources of progenitor cells are now available, originating from adult tissues but also from embryonic or reprogrammed tissues, most of which have already been evaluated for their chondrogenic potential in culture and for their reparative properties in vivo upon implantation in relevant animal models of cartilage lesions. Nevertheless, particular attention will be needed regarding their safe clinical use and their potential to form a cartilaginous repair tissue of proper quality and functionality in the patient. Possible improvements may reside in the use of biological supplements in accordance with regulations, while some challenges remain in establishing standardized, effective procedures in the clinics. Keywords: cartilage repair, knee, focal defects, osteoarthritis, stem cells, clinical trials

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

    Directory of Open Access Journals (Sweden)

    Ashvin K. Dewan

    2014-01-01

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

  8. Effects of mechanical loading on human mesenchymal stem cells for cartilage tissue engineering.

    Science.gov (United States)

    Choi, Jane Ru; Yong, Kar Wey; Choi, Jean Yu

    2018-03-01

    Today, articular cartilage damage is a major health problem, affecting people of all ages. The existing conventional articular cartilage repair techniques, such as autologous chondrocyte implantation (ACI), microfracture, and mosaicplasty, have many shortcomings which negatively affect their clinical outcomes. Therefore, it is essential to develop an alternative and efficient articular repair technique that can address those shortcomings. Cartilage tissue engineering, which aims to create a tissue-engineered cartilage derived from human mesenchymal stem cells (MSCs), shows great promise for improving articular cartilage defect therapy. However, the use of tissue-engineered cartilage for the clinical therapy of articular cartilage defect still remains challenging. Despite the importance of mechanical loading to create a functional cartilage has been well demonstrated, the specific type of mechanical loading and its optimal loading regime is still under investigation. This review summarizes the most recent advances in the effects of mechanical loading on human MSCs. First, the existing conventional articular repair techniques and their shortcomings are highlighted. The important parameters for the evaluation of the tissue-engineered cartilage, including chondrogenic and hypertrophic differentiation of human MSCs are briefly discussed. The influence of mechanical loading on human MSCs is subsequently reviewed and the possible mechanotransduction signaling is highlighted. The development of non-hypertrophic chondrogenesis in response to the changing mechanical microenvironment will aid in the establishment of a tissue-engineered cartilage for efficient articular cartilage repair. © 2017 Wiley Periodicals, Inc.

  9. The Potential for Synovium-derived Stem Cells in Cartilage Repair.

    Science.gov (United States)

    Kubosch, Eva Johanna; Lang, Gernot; Furst, David; Kubosch, David; Izadpanah, Kaywan; Rolauffs, Bernd; Sudkamp, Norbert P; Schmal, Hagen

    2018-02-23

    Articular cartilage defects often result in pain, loss of function and finally osteoarthritis. Developing cell-based therapies for cartilage repair is a major goal of orthopaedic research. Autologous chondrocyte implantation is currently the gold standard cell-based surgical procedure for the treatment of large, isolated, full thickness cartilage defects. Several disadvantages such as the need for two surgical procedures or hypertrophic regenerative cartilage, underline the need for alternative cell sources. Mesenchymal stem cells, particularly synovium-derived mesenchymal stem cells, represent a promising cell source. Synovium-derived mesenchymal stem cells have attracted considerable attention since they display great chondrogenic potential and less hypertrophic differentiation than mesenchymal stem cells derived from bone marrow. The aim of this review was to summarize the current knowledge on the chondrogenic potential for synovial stem cells in regard to cartilage repair purposes. A literature search was carried out identifying 260 articles in the databases up to January 2017. Several in vitro and initial animal in vivo studies of cartilage repair using synovia stem cell application showed encouraging results. Since synvoium-derived stem cells are located in the direct vicinity of cartilage and cartilage lesions these cells might even contribute to natural cartilage regeneration. The only one published human in vivo study with 10 patients revealed good results concerning postoperative outcome, MRI, and histologic features after a two-stage implantation of synovial stem cells into an isolated cartilage defect of the femoral condyle. Synovium-derived stem cells possess great chondrogenic potential and showed encouraging results for cartilage repair purposes. Furthermore, synovial stem cells play an important role in joint homeostasis and possibly in natural cartilage repair. Further studies are needed to elucidate the interplay of synovial stem cells and

  10. Advancing cartilage tissue engineering: the application of stem cell technology.

    Science.gov (United States)

    Raghunath, Joanne; Salacinski, Henryk J; Sales, Kevin M; Butler, Peter E; Seifalian, Alexander M

    2005-10-01

    The treatment of cartilage pathology and trauma face the challenges of poor regenerative potential and inferior repair. Nevertheless, recent advances in tissue engineering indicate that adult stem cells could provide a source of chondrocytes for tissue engineering that the isolation of mature chondrocytes has failed to achieve. Various adjuncts to their propagation and differentiation have been explored, such as biomaterials, bioreactors and growth hormones. To date, all tissue engineered cartilage has been significantly mechanically inferior to its natural counterparts and further problems in vivo relate to poor integration and deterioration of tissue quality over time. However, adult stem cells--with their high rate of proliferation and ease of isolation--are expected to greatly further the development and usefulness of tissue engineered cartilage.

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

    NARCIS (Netherlands)

    Y.M. Bastiaansen-Jenniskens (Yvonne)

    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

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

    Science.gov (United States)

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

    2013-01-01

    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 objectives of this study were to further analyze OCA and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral (ScB) and trabecular (TB) bone structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCA was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCA was lower than Non-Op and other OCA. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCA did not vary compared to Non-Op, but BS/TV was lower. (2) OCA contained “basal” cysts, localized to deeper regions, some “subchondral” cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These

  13. Co-culture systems-based strategies for articular cartilage tissue engineering.

    Science.gov (United States)

    Zhang, Yu; Guo, Weimin; Wang, Mingjie; Hao, Chunxiang; Lu, Liang; Gao, Shuang; Zhang, Xueliang; Li, Xu; Chen, Mingxue; Li, Penghao; Jiang, Peng; Lu, Shibi; Liu, Shuyun; Guo, Quanyi

    2018-03-01

    Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering. © 2017 Wiley Periodicals, Inc.

  14. hWJECM-Derived Oriented Scaffolds with Autologous Chondrocytes for Rabbit Cartilage Defect Repairing.

    Science.gov (United States)

    Zhao, Peng; Liu, Shuyun; Bai, Yuhe; Lu, Shibi; Peng, Jiang; Zhang, Li; Huang, Jingxiang; Zhao, Bin; Xu, Wenjing; Guo, Quanyi

    2018-02-02

    Previously, we synthesized an articular cartilage extracellular matrix (ECM)-derived oriented scaffold for cartilage tissue engineering, which was biomimetic in terms of structure and biochemical composition. However, the limit resource of the cartilage-derived ECM is a hindrance for its application. In this study, we developed a new material for cartilage tissue engineering-human umbilical cord Wharton's jelly-derived ECM (hWJECM). The hWJECM has an abundant resource and similar biochemistry with cartilage ECM, and the use of it is not associated with ethical controversy. We adopted the method previously used in cartilage ECM-derived oriented scaffold preparation to generate the oriented hWJECM-derived scaffold, and the scaffold properties were tested in vitro and in vivo. The three-dimensional scaffold has a porous and well-oriented structure, with a mean pore diameter of ∼104 μm. Scanning electron microscopy and cell viability staining results demonstrated that the oriented scaffold has good biocompatibility and cell alignment. In addition, we used functional autologous chondrocytes to seed the hWJECM-derived oriented scaffold and tested the efficacy of the cell-scaffold constructs to repair the full-thickness articular cartilage defect in a rabbit model. Defects of 4 mm diameter were generated in the patellar grooves of the femurs of both knees and were implanted with chondrocyte-scaffold constructs (group A) or scaffolds alone (group B); rabbits with untreated defects were used as a control (group C). Six months after surgery, all defects in group A were filled completely with repaired tissue, and most of which were hyaline cartilage. In contrast, the defects in group B were filled partially with repaired tissue, and approximately half of these repaired tissues were hyaline cartilage. The defects in group C were only filled with fibrotic tissue. Histological grading score of group A was lower than those of groups B and C. Quantification of

  15. 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.)

  16. Cell-laden hydrogels for osteochondral and cartilage tissue engineering.

    Science.gov (United States)

    Yang, Jingzhou; Zhang, Yu Shrike; Yue, Kan; Khademhosseini, Ali

    2017-07-15

    Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered artificial matrices that can replace the damaged regions and promote tissue regeneration. Hydrogels are emerging as a promising class of biomaterials for both soft and hard tissue regeneration. Many critical properties of hydrogels, such as mechanical stiffness, elasticity, water content, bioactivity, and degradation, can be rationally designed and conveniently tuned by proper selection of the material and chemistry. Particularly, advances in the development of cell-laden hydrogels have opened up new possibilities for cell therapy. In this article, we describe the problems encountered in this field and review recent progress in designing cell-hydrogel hybrid constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel type, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation matrices with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing technologies (e.g. molding, bioprinting, and assembly) for fabrication of hydrogel-based osteochondral and cartilage constructs with complex compositions and microarchitectures to mimic their native counterparts. Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered biomaterials that replace the damaged regions and promote tissue regeneration. Cell-laden hydrogel systems have emerged as a promising tissue

  17. Comparison of chondrocytes produced from adipose tissue-derived stem cells and cartilage tissue.

    Science.gov (United States)

    Meric, Aysenur; Yenigun, Alper; Yenigun, Vildan Betul; Dogan, Remzi; Ozturan, Orhan

    2013-05-01

    Spontaneous cartilage regeneration is poor after a cartilage defect occurs by trauma, surgical, and other reasons. Importance of producing chondrocytes from stem cells and using tissues to repair a defect is getting popular. The aim of this study was to compare the effects of injectable cartilage produced by chondrocytes differentiated from adipose tissue-derived mesenchymal stem cells and chondrocyte cells isolated directly from cartilage tissue. Mesenchymal stem cells were isolated from rat adipose tissue and characterized by cell-surface markers. Then, they were differentiated to chondrocyte cells. The function of differentiated chondrocyte cells was compared with chondrocyte cells directly isolated from cartilage tissue in terms of collagen and glycosaminoglycan secretion. Then, both chondrocyte cell types were injected to rats' left ears in liquid and gel form, and histologic evaluation was done 3 weeks after the injection. Adipose-derived stem cells were strongly positive for the CD44 and CD73 mesenchymal markers. Differentiated chondrocyte cells and chondrocyte cells directly isolated from cartilage tissue had relative collagen and glycosaminoglycan secretion results. However, histologic evaluations did not show any cartilage formation after both chondrocyte cell types were injected to rats. Strong CD44- and CD73-positive expression indicated that adipose-derived cells had the stem cell characters. Collagen and glycosaminoglycan secretion results demonstrated that adipose-derived stem cells were successfully differentiated to chondrocyte cells.

  18. [Tribological assessment of articular cartilage. A system for the analysis of the friction coefficient of cartilage, regenerates and tissue engineering constructs; initial results].

    Science.gov (United States)

    Schwarz, M L R; Schneider-Wald, B; Krase, A; Richter, W; Reisig, G; Kreinest, M; Heute, S; Pott, P P; Brade, J; Schütte, A

    2012-10-01

    Values for the friction coefficient of articular cartilage are given in ranges of percentage and lower and are calculated as a quotient of the friction force and the perpendicular loading force acting on it. Thus, a sophisticated system has to be provided for analysing the friction coefficient under different conditions in particular when cartilage should be coupled as friction partner. It is possible to deep-freeze articular cartilage before measuring the friction coefficient as the procedure has no influence on the results. The presented tribological system was able to distinguish between altered and native cartilage. Furthermore, tissue engineered constructs for cartilage repair were differentiated from native cartilage probes by their friction coefficient. In conclusion a tribological equipment is presented to analyze the friction coefficient of articular cartilage, in vivo generated cartilage regenerates and in vitro tissue engineered constructs regarding their biomechanical properties for quality assessment.

  19. Three-dimensional magnetic resonance observation of cartilage repair tissue (MOCART) score assessed with an isotropic three-dimensional true fast imaging with steady-state precession sequence at 3.0 Tesla.

    Science.gov (United States)

    Welsch, Goetz H; Zak, Lukas; Mamisch, Tallal C; Resinger, Christoph; Marlovits, Stefan; Trattnig, Siegfried

    2009-09-01

    Cartilage defects are common pathologies and surgical cartilage repair shows promising results. In its postoperative evaluation, the magnetic resonance observation of cartilage repair tissue (MOCART) score, using different variables to describe the constitution of the cartilage repair tissue and the surrounding structures, is widely used. High-field magnetic resonance imaging (MRI) and 3-dimensional (3D) isotropic sequences may combine ideal preconditions to enhance the diagnostic performance of cartilage imaging.Aim of this study was to introduce an improved 3D MOCART score using the possibilities of an isotropic 3D true fast imaging with steady-state precession (True-FISP) sequence in the postoperative evaluation of patients after matrix-associated autologous chondrocyte transplantation (MACT) as well as to compare the results to the conventional 2D MOCART score using standard MR sequences. The study had approval by the local ethics commission. One hundred consecutive MR scans in 60 patients at standard follow-up intervals of 1, 3, 6, 12, 24, and 60 months after MACT of the knee joint were prospectively included. The mean follow-up interval of this cross-sectional evaluation was 21.4 +/- 20.6 months; the mean age of the patients was 35.8 +/- 9.4 years. MRI was performed at a 3.0 Tesla unit. All variables of the standard 2D MOCART score where part of the new 3D MOCART score. Furthermore, additional variables and options were included with the aims to use the capabilities of isotropic MRI, to include the results of recent studies, and to adapt to the needs of patients and physician in a clinical routine examination. A proton-density turbo spin-echo sequence, a T2-weighted dual fast spin-echo (dual-FSE) sequence, and a T1-weighted turbo inversion recovery magnitude (TIRM) sequence were used to assess the standard 2D MOCART score; an isotropic 3D-TrueFISP sequence was prepared to evaluate the new 3D MOCART score. All 9 variables of the 2D MOCART score were compared

  20. Experimental Study on 3D Chi - Hap Scaffolds for Thyroid Cartilage Repairing

    Science.gov (United States)

    Sun, Nannan; Shi, Tingchun; Fan, Yuan; Hu, Binbin

    2018-01-01

    Due to the limitation of self-repairing capability for cartilage injury, the construction of tissue engineering in vitro has been an ideal treatment to repair tissue injury. In this paper, hydroxyapatite (Hap) and chitosan (Chi) were selected to fabricate the scaffold through low temperature deposition manufacturing (LDM) technique. The scaffold was characterized with interconnected structure and high porosity, as well as lower toxicity to cells (TDC-5-EGPE). Animal experiment was performed, Twelve white New Zealand rabbits were randomly divided into two groups, the side of the thyroid cartilage was removed, Chi-HAP composite scaffold was implanted into the cartilage defect as the experimental group A. Group B was treated for thyroid cartilage defects without any treatment. After 10 weeks, hematoxylin-eosin (HE) staining and S-O staining were carried out on the injured tissues. The result showed that newborn chondrocytes were found in repaired areas for group A, and there are no new cells found for group B. Therefore, Chi-HAP composite scaffolds formed by LDM possess biological activity for repairing injury cartilage.

  1. Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments.

    Science.gov (United States)

    Vinatier, C; Guicheux, J

    2016-06-01

    Articular cartilage is a non-vascularized and poorly cellularized connective tissue that is frequently damaged as a result of trauma and degenerative joint diseases such as osteoarthrtis. Because of the absence of vascularization, articular cartilage has low capacity for spontaneous repair. Today, and despite a large number of preclinical data, no therapy capable of restoring the healthy structure and function of damaged articular cartilage is clinically available. Tissue-engineering strategies involving the combination of cells, scaffolding biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. During the last 30 years, cartilage tissue engineering has evolved from the treatment of focal lesions of articular cartilage to the development of strategies targeting the osteoarthritis process. In this review, we focus on the different aspects of tissue engineering applied to cartilage engineering. We first discuss cells, biomaterials and biological or environmental factors instrumental to the development of cartilage tissue engineering, then review the potential development of cartilage engineering strategies targeting new emerging pathogenic mechanisms of osteoarthritis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    International Nuclear Information System (INIS)

    Hasegawa, Yoshimichi; Saijo, Hideto; Yonehara, Yoshiyuki; Takato, Tsuyoshi; Nakatuka, Takashi

    2008-01-01

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

  3. 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. © 2013 Published by Elsevier Ltd.

  4. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. 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.

  6. Articular cartilage tissue engineering with plasma-rich in growth factors and stem cells with nano scaffolds

    Science.gov (United States)

    Montaser, Laila M.; Abbassy, Hadeer A.; Fawzy, Sherin M.

    2016-09-01

    The ability to heal soft tissue injuries and regenerate cartilage is the Holy Grail of musculoskeletal medicine. Articular cartilage repair and regeneration is considered to be largely intractable due to the poor regenerative properties of this tissue. Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or continue hypertrophic cartilage. The lack of efficient modalities of treatment has prompted research into tissue engineering combining stem cells, scaffold materials and environmental factors. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased cartilage functionality, has evoked intense interest and holds great potential for improving cartilage therapy. Plasma-rich in growth factors (PRGF) and/or stem cells may be effective for tissue repair as well as cartilage regenerative processes. There is a great promise to advance current cartilage therapies toward achieving a consistently successful approach for addressing cartilage afflictions. Tissue engineering may be the best way to reach this objective via the use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology. In this paper, current and emergent approach in the field of cartilage tissue engineering is presented for specific application. In the next years, the development of new strategies using stem cells, in scaffolds, with supplementation of culture medium could improve the quality of new formed cartilage.

  7. 3D Printing of Cytocompatible Water-Based Light-Cured Polyurethane with Hyaluronic Acid for Cartilage Tissue Engineering Applications

    Science.gov (United States)

    Shie, Ming-You; Chang, Wen-Ching; Wei, Li-Ju; Huang, Yu-Hsin; Chen, Chien-Han; Shih, Cheng-Ting; Chen, Yi-Wen; Shen, Yu-Fang

    2017-01-01

    Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is a limitation in the self-repair ability of the cartilage. Therefore, developing strategies for cartilage repair is very important. Here, we report on a new liquid resin preparation process of water-based polyurethane based photosensitive materials with hyaluronic acid with application of the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton’s jelly mesenchymal stem cells (hWJMSCs) and the cells in this case showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and also facilitate the development of cartilage tissue engineering. PMID:28772498

  8. 3D Printing of Cytocompatible Water-Based Light-Cured Polyurethane with Hyaluronic Acid for Cartilage Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Ming-You Shie

    2017-02-01

    Full Text Available Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is a limitation in the self-repair ability of the cartilage. Therefore, developing strategies for cartilage repair is very important. Here, we report on a new liquid resin preparation process of water-based polyurethane based photosensitive materials with hyaluronic acid with application of the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton’s jelly mesenchymal stem cells (hWJMSCs and the cells in this case showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and also facilitate the development of cartilage tissue engineering.

  9. 3D Printing of Cytocompatible Water-Based Light-Cured Polyurethane with Hyaluronic Acid for Cartilage Tissue Engineering Applications.

    Science.gov (United States)

    Shie, Ming-You; Chang, Wen-Ching; Wei, Li-Ju; Huang, Yu-Hsin; Chen, Chien-Han; Shih, Cheng-Ting; Chen, Yi-Wen; Shen, Yu-Fang

    2017-02-08

    Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is a limitation in the self-repair ability of the cartilage. Therefore, developing strategies for cartilage repair is very important. Here, we report on a new liquid resin preparation process of water-based polyurethane based photosensitive materials with hyaluronic acid with application of the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton's jelly mesenchymal stem cells (hWJMSCs) and the cells in this case showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and also facilitate the development of cartilage tissue engineering.

  10. Repair of cartilage defects in osteoarthritis rats with induced pluripotent stem cell derived chondrocytes.

    Science.gov (United States)

    Zhu, Yanxia; Wu, Xiaomin; Liang, Yuhong; Gu, Hongsheng; Song, Kedong; Zou, Xuenong; Zhou, Guangqian

    2016-11-09

    The incapacity of articular cartilage (AC) for self-repair after damage ultimately leads to the development of osteoarthritis. Stem cell-based therapy has been proposed for the treatment of osteoarthritis (OA) and induced pluripotent stem cells (iPSCs) are becoming a promising stem cell source. Three steps were developed to differentiate human iPSCs into chondrocytes which were transplanted into rat OA models induced by monosodium iodoacetate (MIA). After 6 days embryonic body (EB) formation and 2 weeks differentiation, the gene and protein expression of Col2A1, GAG and Sox9 has significantly increased compare to undifferentiated hiPSCs. After 15 weeks transplantation, no immune responses were observed, micro-CT showed gradual engraftment and the improvement of subchondrol plate integrity, and histological examinations demonstrated articular cartilage matrix production. hiPSC could be an efficient and clinically translatable approach for cartilage tissue regeneration in OA cartilages.

  11. [Cartilage repair and subchondral bone reconstruction based on three-dimensional printing technique].

    Science.gov (United States)

    Zhang, Weijie; Lian, Qin; Li, Dichen; Wang, Kunzheng; Jin, Zhongmin; Bian, Weiguo; Liu, Yaxiong; He, Jiankang; Wang, Ling

    2014-03-01

    To investigate whether subchondral bone microstructural parameters are related to cartilage repair during large osteochondral defect repairing based on three-dimensional (3-D) printing technique. Biomimetic biphasic osteochondral composite scaffolds were fabricated by using 3-D printing technique. The right trochlea critical sized defects (4.8 mm in diameter, 7.5 mm in depth) were created in 40 New Zealand white rabbits (aged 6 months, weighing 2.5-3.5 kg). Biomimetic biphasic osteochondral composite scaffolds were implanted into the defects in the experimental group (n = 35), and no composite scaffolds implantation served as control group (n = 5); the left side had no defect as sham-operation group. Animals of experimental and sham-operation groups were euthanized at 1, 2, 4, 8, 16, 24, and 52 weeks after operation, while animals of control group were sampled at 24 weeks. Subchondral bone microstructural parameters and cartilage repair were quantitatively analyzed using Micro-CT and Wayne scoring system. Correlation analysis and regression analysis were applied to reveal the relationship between subchondral bone parameters and cartilage repair. The subchondral bone parameters included bone volume fraction (BV/TV), bone surface area fraction (BSA/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular spacing (Tb.Sp). In the experimental group, articular cartilage repair was significantly improved at 52 weeks postoperatively, which was dominated by hyaline cartilage tissue, and tidal line formed. Wayne scores at 24 and 52 weeks were significantly higher than that at 16 weeks in the experimental group (P 0.05); the scores of experimental group were significantly lower than those of sham-operation group at all time points (P twin peaks" like discipline to which BV/TV, BSA/BV, and Tb.N increased at 2 and 16 weeks, and then they returned to normal level. The Tb.Sp showed reversed discipline compared to the former 3 parameters, no significant change

  12. 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...... therefore involves a melange of approaches encompassing developmental biology, tissue mechanics, medicine, cell differentiation and survival biology, mechanostransduction and nano-fabrication technology. The central tissue of interest in this review is cartilage. Traumatic injuries, congenital abnormalities...... 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...

  13. Glycogen storage in tissue-engineered cartilage.

    Science.gov (United States)

    Suits, Jocelyne M T; Khan, Aasma A; Waldman, Stephen D

    2008-08-01

    Recent focus in cartilage tissue engineering has been to develop functional tissue that can survive after implantation. One such determinant is the ability of the engineered tissue to be able to sustain its metabolic activity post-implantation. In vivo, chondrocytes contain stores of intracellular glycogen to support metabolism and it is unknown whether these cells can store glycogen during tissue growth in vitro. Thus, the purpose of this study was to determine the appropriate nutrient conditions to elicit glycogen storage in tissue-engineered cartilage. Isolated bovine articular chondrocytes were seeded in scaffold-free, 3D culture and grown under different nutrient conditions (glucose concentrations and media volumes) for 4 weeks. Intracellular glycogen storage, glucose utilization and extracellular matrix (ECM) accumulation of the engineered tissues were then evaluated. Glucose concentration (5-10 mM) and media volume (1-4 ml) had no apparent effect on cartilaginous tissue formation. However, glucose consumption by the cells increased in proportion to the volume of medium provided. Lactate production was similarly affected but in direct proportion to the glucose consumed, indicating a change in glucose utilization. Similarly, under elevated medium volume, engineered tissues stained positive for intracellular glycogen, which was also confirmed biochemically (1 ml, 1 +/- 2; 2 ml, 13 +/- 4; 4 ml, 13 +/- 3 microg/construct). The storage of intracellular glycogen in engineered cartilage can be elicited by culturing the constructs in elevated volumes of medium (>or=1 ml medium/million cells), which might help to ensure appropriate metabolic function after implantation. (c) 2008 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    Baugé, Catherine; Boumédiene, Karim

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Catherine Baugé

    2015-01-01

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

  16. 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.

  17. Advances in cartilage tissue engineering : in vitro

    NARCIS (Netherlands)

    E.W. Mandl (Erik)

    2004-01-01

    textabstractWithin the body three subtypes of cartilage can be distinguished: hyaline cartilage, elastic cartilage and fibrocartilage. Hyaline cartilage is the predominant subtype and is mainly located in articular joints and in less extent in the nasal septum and cricoid. Elastic cartilage can be

  18. 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

  19. Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering.

    OpenAIRE

    Duval , Elise; Baugé , Catherine; Andriamanalijaona , Rina; Bénateau , Hervé; Leclercq , Sylvain; Dutoit , Soizic; Poulain , Laurent; Galéra , Philippe; Boumédiene , Karim

    2012-01-01

    International audience; Cartilage engineering is one of the most challenging issue in regenerative medicine, due to its limited self-ability to repair. Here, we assessed engineering of cartilage tissue starting from human bone marrow (hBM) stem cells under hypoxic environment and delineated the mechanism whereby chondrogenesis could be conducted without addition of exogenous growth factors. hBM stem cells were cultured in alginate beads and chondrogenesis was monitored by chondrocyte phenotyp...

  20. Clinical potential and challenges of using genetically modified cells for articular cartilage repair

    Science.gov (United States)

    Madry, Henning; Cucchiarini, Magali

    2011-01-01

    Articular cartilage defects do not regenerate. Transplantation of autologous articular chondrocytes, which is clinically being performed since several decades, laid the foundation for the transplantation of genetically modified cells, which may serve the dual role of providing a cell population capable of chondrogenesis and an additional stimulus for targeted articular cartilage repair. Experimental data generated so far have shown that genetically modified articular chondrocytes and mesenchymal stem cells (MSC) allow for sustained transgene expression when transplanted into articular cartilage defects in vivo. Overexpression of therapeutic factors enhances the structural features of the cartilaginous repair tissue. Combined overexpression of genes with complementary mechanisms of action is also feasible, holding promises for further enhancement of articular cartilage repair. Significant benefits have been also observed in preclinical animal models that are, in principle, more appropriate to the clinical situation. Finally, there is convincing proof of concept based on a phase I clinical gene therapy study in which transduced fibroblasts were injected into the metacarpophalangeal joints of patients without adverse events. To realize the full clinical potential of this approach, issues that need to be addressed include its safety, the choice of the ideal gene vector system allowing for a long-term transgene expression, the identification of the optimal therapeutic gene(s), the transplantation without or with supportive biomaterials, and the establishment of the optimal dose of modified cells. As safe techniques for generating genetically engineered articular chondrocytes and MSCs are available, they may eventually represent new avenues for improved cell-based therapies for articular cartilage repair. This, in turn, may provide an important step toward the unanswered question of articular cartilage regeneration. PMID:21674822

  1. Cartilage repair by mesenchymal stem cells: Clinical trial update and perspectives

    Directory of Open Access Journals (Sweden)

    Wayne Yuk-wai Lee

    2017-04-01

    The translational potential of this article: This review summarises recent MSC-related clinical research that focuses on cartilage repair. We also propose a novel possible translational direction for hyaline cartilage formation and a new paradigm making use of extra-cellular signalling and epigenetic regulation in the application of MSCs for cartilage repair.

  2. Gelatin Scaffolds with Controlled Pore Structure and Mechanical Property for Cartilage Tissue Engineering.

    Science.gov (United States)

    Chen, Shangwu; Zhang, Qin; Nakamoto, Tomoko; Kawazoe, Naoki; Chen, Guoping

    2016-03-01

    Engineering of cartilage tissue in vitro using porous scaffolds and chondrocytes provides a promising approach for cartilage repair. However, nonuniform cell distribution and heterogeneous tissue formation together with weak mechanical property of in vitro engineered cartilage limit their clinical application. In this study, gelatin porous scaffolds with homogeneous and open pores were prepared using ice particulates and freeze-drying. The scaffolds were used to culture bovine articular chondrocytes to engineer cartilage tissue in vitro. The pore structure and mechanical property of gelatin scaffolds could be well controlled by using different ratios of ice particulates to gelatin solution and different concentrations of gelatin. Gelatin scaffolds prepared from ≥70% ice particulates enabled homogeneous seeding of bovine articular chondrocytes throughout the scaffolds and formation of homogeneous cartilage extracellular matrix. While soft scaffolds underwent cellular contraction, stiff scaffolds resisted cellular contraction and had significantly higher cell proliferation and synthesis of sulfated glycosaminoglycan. Compared with the gelatin scaffolds prepared without ice particulates, the gelatin scaffolds prepared with ice particulates facilitated formation of homogeneous cartilage tissue with significantly higher compressive modulus. The gelatin scaffolds with highly open pore structure and good mechanical property can be used to improve in vitro tissue-engineered cartilage.

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

    Science.gov (United States)

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

    2016-05-01

    In the present study, we aimed at evaluating the ability of novel PLGA-P188-PLGA-based microspheres to induce the differentiation of mesenchymal stem/stromal cells (MSC) into chondrocytes. To this aim, we tested microspheres releasing TGFβ3 (PAM-T) in vitro and in situ, in a pathological osteoarthritic (OA) environment. We first evaluated the chondrogenic differentiation of human MSCs seeded onto PAM-T in vitro and confirmed the up-regulation of chondrogenic markers while the secretome of the cells was not changed by the 3D environment. We then injected human MSC seeded onto PAM-T in the knee joints of mice with collagenase-induced OA. After 6 weeks, histological analysis revealed that formation of a cartilage-like tissue occurred at the vicinity of PAM-T that was not observed when MSCs were seeded onto PAM. We also noticed that the endogenous articular cartilage was less degraded. The extent of cartilage protection was further analysed by confocal laser microscopy. When MSCs seeded onto PAM-T were injected early after OA induction, protection of cartilage against degradation was evidenced and this effect was associated to a higher survival of MSCs in presence of TGFβ3. This study points to the interest of using MSCs seeded onto PAM for cartilage repair and stimulation of endogenous cartilage regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis.

    Science.gov (United States)

    McGonagle, Dennis; Baboolal, Thomas G; Jones, Elena

    2017-12-01

    The role of native (not culture-expanded) joint-resident mesenchymal stem cells (MSCs) in the repair of joint damage in osteoarthritis (OA) is poorly understood. MSCs differ from bone marrow-residing haematopoietic stem cells in that they are present in multiple niches in the joint, including subchondral bone, cartilage, synovial fluid, synovium and adipose tissue. Research in experimental models suggests that the migration of MSCs adjacent to the joint cavity is crucial for chonodrogenesis during embryogenesis, and also shows that synovium-derived MSCs might be the primary drivers of cartilage repair in adulthood. In this Review, the available data is synthesized to produce a proposed model in which joint-resident MSCs with access to superficial cartilage are key cells in adult cartilage repair and represent important targets for manipulation in 'chondrogenic' OA, especially in the context of biomechanical correction of joints in early disease. Growing evidence links the expression of CD271, a nerve growth factor (NGF) receptor by native bone marrow-resident MSCs to a wider role for neurotrophins in OA pathobiology, the implications of which require exploration since anti-NGF therapy might worsen OA. Recognizing that joint-resident MSCs are comparatively abundant in vivo and occupy multiple niches will enable the optimization of single-stage therapeutic interventions for OA.

  5. Repair of articular cartilage lesions in aged chickens by allogeneic transplantation of fresh embryonic epiphyses.

    Science.gov (United States)

    Cohen, Ilan; Melamed, Eitan; Robinson, Dror; Nevo, Zvi

    2007-11-01

    The potential of fresh whole chick epiphyses of embryonic origin to serve as implant material for cartilage defects of aged chicken was tested. Fresh epiphyses of 11-day-old embryos were collected from 24 animals and transplanted into defects created in the weight-bearing areas of tibiotarsal joint cartilage of 2-year-old chicks. Upon sacrifice, samples were examined macroscopically and microsections were prepared for histology. Macroscopically, control defects remained empty at all the time intervals. Defects of the experimental group were, on the other hand, filled with cartilaginous tissue as early as 2 weeks posttransplantation, although individual epiphyses could still be noted in the implant tissue. At 4 weeks and later, defects were filled with cartilaginous material indistinguishable from hyaline cartilage. Histologically, all grafts remained within the defect's pits, showing mitotic and metabolic activity typical to proliferating hyaline cartilage. The engrafted epiphyses showed a partial incorporation and integration with the surrounding host tissues already at 2 weeks. At 4 weeks and later, the integration was complete. It is concluded that a chick embryonic epiphyseal cartilage is suitable as a graft source for articular cartilage transplantation. The embryonic epiphyses provide immediate inherent stability to the graft and supply a good mix of mesenchymal progenitor cells responsible for the high rate of cell proliferation and adhesion to the differentiated committed chondrocytes of the host that create the typical favorable chondrogenic milieu. Based on the present findings, it is postulated that human embryonic epiphyses may, in the future, represent an alternative source to the commonly used techniques of hyaline cartilage repair.

  6. An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair

    Science.gov (United States)

    Tang, Cheng; Jin, Chengzhe; Du, Xiaotao; Yan, Chao; Min, Byoung-Hyun; Xu, Yan

    2014-01-01

    Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds risks of pathogen transmission, undesirable inflammation, and other immunological reactions, as well as ethical issues in clinical practice. The current study was undertaken to evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem cell–derived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage repair. Methods: Full osteochondral defects were performed on the trochlear groove of both knees in 24 rabbits. One group underwent BMS only in the right knee (the BMS group), and the other group was treated by implantation of the aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group). Results: Better repair of cartilage defects was observed in the aBMSC-dECM scaffold group than in the BMS group according to gross observation, histological assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and DNA content, the distribution of proteoglycan, and the distribution and arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC-dECM scaffold group at 12 weeks after surgery were similar to that surrounding normal hyaline cartilage. Conclusions: Implanting aBMSC-dECM scaffolds can enhance the therapeutic effect of BMS on articular cartilage repair, and this combination treatment is a potential method for successful articular cartilage repair. PMID:24666429

  7. Experimental articular cartilage repair in the Göttingen minipig

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  8. Advances in Application of Mechanical Stimuli in Bioreactors for Cartilage Tissue Engineering.

    Science.gov (United States)

    Li, Ke; Zhang, Chunqiu; Qiu, Lulu; Gao, Lilan; Zhang, Xizheng

    2017-08-01

    Articular cartilage (AC) is the weight-bearing tissue in diarthroses. It lacks the capacity for self-healing once there are injuries or diseases due to its avascularity. With the development of tissue engineering, repairing cartilage defects through transplantation of engineered cartilage that closely matches properties of native cartilage has become a new option for curing cartilage diseases. The main hurdle for clinical application of engineered cartilage is how to develop functional cartilage constructs for mass production in a credible way. Recently, impressive hyaline cartilage that may have the potential to provide capabilities for treating large cartilage lesions in the future has been produced in laboratories. The key to functional cartilage construction in vitro is to identify appropriate mechanical stimuli. First, they should ensure the function of metabolism because mechanical stimuli play the role of blood vessels in the metabolism of AC, for example, acquiring nutrition and removing wastes. Second, they should mimic the movement of synovial joints and produce phenotypically correct tissues to achieve the adaptive development between the micro- and macrostructure and function. In this article, we divide mechanical stimuli into three types according to forces transmitted by different media in bioreactors, namely forces transmitted through the liquid medium, solid medium, or other media, then we review and summarize the research status of bioreactors for cartilage tissue engineering (CTE), mainly focusing on the effects of diverse mechanical stimuli on engineered cartilage. Based on current researches, there are several motion patterns in knee joints; but compression, tension, shear, fluid shear, or hydrostatic pressure each only partially reflects the mechanical condition in vivo. In this study, we propose that rolling-sliding-compression load consists of various stimuli that will represent better mechanical environment in CTE. In addition, engineers

  9. 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.

  10. Mechanical stimulation of mesenchymal stem cells: Implications for cartilage tissue engineering.

    Science.gov (United States)

    Fahy, Niamh; Alini, Mauro; Stoddart, Martin J

    2018-01-01

    Articular cartilage is a load-bearing tissue playing a crucial mechanical role in diarthrodial joints, facilitating joint articulation, and minimizing wear. The significance of biomechanical stimuli in the development of cartilage and maintenance of chondrocyte phenotype in adult tissues has been well documented. Furthermore, dysregulated loading is associated with cartilage pathology highlighting the importance of mechanical cues in cartilage homeostasis. The repair of damaged articular cartilage resulting from trauma or degenerative joint disease poses a major challenge due to a low intrinsic capacity of cartilage for self-renewal, attributable to its avascular nature. Bone marrow-derived mesenchymal stem cells (MSCs) are considered a promising cell type for cartilage replacement strategies due to their chondrogenic differentiation potential. Chondrogenesis of MSCs is influenced not only by biological factors but also by the environment itself, and various efforts to date have focused on harnessing biomechanics to enhance chondrogenic differentiation of MSCs. Furthermore, recapitulating mechanical cues associated with cartilage development and homeostasis in vivo, may facilitate the development of a cellular phenotype resembling native articular cartilage. The goal of this review is to summarize current literature examining the effect of mechanical cues on cartilage homeostasis, disease, and MSC chondrogenesis. The role of biological factors produced by MSCs in response to mechanical loading will also be examined. An in-depth understanding of the impact of mechanical stimulation on the chondrogenic differentiation of MSCs in terms of endogenous bioactive factor production and signaling pathways involved, may identify therapeutic targets and facilitate the development of more robust strategies for cartilage replacement using MSCs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:52-63, 2018. © 2017 Orthopaedic Research

  11. Cartilage regeneration and repair testing in a surrogate large animal model.

    Science.gov (United States)

    Simon, Timothy M; Aberman, Harold M

    2010-02-01

    The aging human population is experiencing increasing numbers of symptoms related to its degenerative articular cartilage (AC), which has stimulated the investigation of methods to regenerate or repair AC. However, the seemingly inherent limited capacity for AC to regenerate persists to confound the various repair treatment strategies proposed or studied. Animal models for testing AC implant devices and reparative materials are an important and required part of the Food and Drug Administration approval process. Although final testing is ultimately performed in humans, animal testing allows for a wider range of parameters and combinations of test materials subjected to all the biological interactions of a living system. We review here considerations, evaluations, and experiences with selection and use of animal models and describe two untreated lesion models useful for testing AC repair strategies. These created lesion models, one deep (6 mm and through the subchondral plate) the other shallow (to the level of the subchondral bone plate) were placed in the middle one-third of the medial femoral condyle of the knee joints of goats. At 1-year neither the deep nor the shallow full-thickness chondral defects generated a repair that duplicated natural AC. Moreover, progressive deleterious changes occurred in the AC surrounding the defects. There are challenges in translation from animals to humans as anatomy and structures are different and immobilization to protect delicate repairs can be difficult. The tissues potentially generated by proposed cartilage repair strategies must be compared with the spontaneous changes that occur in similarly created untreated lesions. The prevention of the secondary changes in the surrounding cartilage and subchondral bone described in this article should be addressed with the introduction of treatments for repairs of the articulating surface.

  12. High Throughput and Mechano-Active Platforms to Promote Cartilage Regeneration and Repair

    Science.gov (United States)

    Mohanraj, Bhavana

    Traumatic joint injuries initiate acute degenerative changes in articular cartilage that can lead to progressive loss of load-bearing function. As a result, patients often develop post-traumatic osteoarthritis (PTOA), a condition for which there currently exists no biologic interventions. To address this need, tissue engineering aims to mimic the structure and function of healthy, native counterparts. These constructs can be used to not only replace degenerated tissue, but also build in vitro, pre-clinical models of disease. Towards this latter goal, this thesis focuses on the design of a high throughput system to screen new therapeutics in a micro-engineered model of PTOA, and the development of a mechanically-responsive drug delivery system to augment tissue-engineered approaches for cartilage repair. High throughput screening is a powerful tool for drug discovery that can be adapted to include 3D tissue constructs. To facilitate this process for cartilage repair, we built a high throughput mechanical injury platform to create an engineered cartilage model of PTOA. Compressive injury of functionally mature constructs increased cell death and proteoglycan loss, two hallmarks of injury observed in vivo. Comparison of this response to that of native cartilage explants, and evaluation of putative therapeutics, validated this model for subsequent use in small molecule screens. A primary screen of 118 compounds identified a number of 'hits' and relevant pathways that may modulate pathologic signaling post-injury. To complement this process of therapeutic discovery, a stimuli-responsive delivery system was designed that used mechanical inputs as the 'trigger' mechanism for controlled release. The failure thresholds of these mechanically-activated microcapsules (MAMCs) were influenced by physical properties and composition, as well as matrix mechanical properties in 3D environments. TGF-beta released from the system upon mechano-activation stimulated stem cell

  13. SIS with tissue-cultured allogenic cartilages patch tracheoplasty in a rabbit model for tracheal defect.

    Science.gov (United States)

    Zhang, Longfang; Liu, Zhi; Cui, Pengcheng; Zhao, Daqing; Chen, Wenxian

    2007-06-01

    In the rabbit model, small intestinal submucosa (SIS) compounded with tissue-cultured allogenic cartilages appeared to be an efficacious method for the patch repair of partial circumferential tracheal defects instead of autologous grafts. SIS appears to be a safe and promising means of facilitating neovascularization and tissue regeneration. The long-term use of SIS and tissue-cultured allogenic cartilages warrants further investigation. Tracheal defect reparation remains a challenging surgical problem that can require reconstruction using autologous grafts or artificial stents. This study was performed to evaluate the efficacy of SIS, a biocompatible, acellular matrix, compounded with different tissue-cultured allogenic cartilages, in the repair of a critical-size tracheal defect. A full-thickness defect (4 x 8 mm) was created in tracheal rings four to six in adult rabbits. A piece of 8-ply SIS sandwiched in thyroid cartilage, auricular cartilage, or without cartilage, respectively (designated experiment 1, 2, or 3, respectively), was sutured to the edges of the defect with interrupted 4-0 polypropylene sutures. In control animals, the defect was closed with lamina praetrachealis. All animals were followed until signs of dyspnea became apparent or for 4 or 12 weeks. After follow-up and euthanasia, the trachea was harvested and prepared for histologic evaluation using conventional techniques. All animals tolerated the procedure well but two animals in group 1 (n=5), three in group 2 (n=5), and one in group 3 (n=5) had stridor after operation and expired within 1 month. Histologically, neovascularization of the patch was noted with moderate inflammation. The surface of the SIS patch was covered with a lining of ciliated epithelial cells. The tissue-cultured allogenic cartilages degraded to some extent.

  14. Semi-automated International Cartilage Repair Society scoring of equine articular cartilage lesions in optical coherence tomography images.

    Science.gov (United States)

    Te Moller, N C R; Pitkänen, M; Sarin, J K; Väänänen, S; Liukkonen, J; Afara, I O; Puhakka, P H; Brommer, H; Niemelä, T; Tulamo, R-M; Argüelles Capilla, D; Töyräs, J

    2017-07-01

    Arthroscopic optical coherence tomography (OCT) is a promising tool for the detailed evaluation of articular cartilage injuries. However, OCT-based articular cartilage scoring still relies on the operator's visual estimation. To test the hypothesis that semi-automated International Cartilage Repair Society (ICRS) scoring of chondral lesions seen in OCT images could enhance intra- and interobserver agreement of scoring and its accuracy. Validation study using equine cadaver tissue. Osteochondral samples (n = 99) were prepared from 18 equine metacarpophalangeal joints and imaged using OCT. Custom-made software was developed for semi-automated ICRS scoring of cartilage lesions on OCT images. Scoring was performed visually and semi-automatically by five observers, and levels of inter- and intraobserver agreement were calculated. Subsequently, OCT-based scores were compared with ICRS scores based on light microscopy images of the histological sections of matching locations (n = 82). When semi-automated scoring of the OCT images was performed by multiple observers, mean levels of intraobserver and interobserver agreement were higher than those achieved with visual OCT scoring (83% vs. 77% and 74% vs. 33%, respectively). Histology-based scores from matching regions of interest agreed better with visual OCT-based scoring than with semi-automated OCT scoring; however, the accuracy of the software was improved by optimising the threshold combinations used to determine the ICRS score. Images were obtained from cadavers. Semi-automated scoring software improved the reproducibility of ICRS scoring of chondral lesions in OCT images and made scoring less observer-dependent. The image analysis and segmentation techniques adopted in this study warrant further optimisation to achieve better accuracy with semi-automated ICRS scoring. In addition, studies on in vivo applications are required. © 2016 EVJ Ltd.

  15. 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.

  16. Chondrogenic Differentiation of Defined Equine Mesenchymal Stem Cells Derived from Umbilical Cord Blood for Use in Cartilage Repair Therapy

    Directory of Open Access Journals (Sweden)

    Mélanie Desancé

    2018-02-01

    Full Text Available Cartilage engineering is a new strategy for the treatment of cartilage damage due to osteoarthritis or trauma in humans. Racehorses are exposed to the same type of cartilage damage and the anatomical, cellular, and biochemical properties of their cartilage are comparable to those of human cartilage, making the horse an excellent model for the development of cartilage engineering. Human mesenchymal stem cells (MSCs differentiated into chondrocytes with chondrogenic factors in a biomaterial appears to be a promising therapeutic approach for direct implantation and cartilage repair. Here, we characterized equine umbilical cord blood-derived MSCs (eUCB-MSCs and evaluated their potential for chondrocyte differentiation for use in cartilage repair therapy. Our results show that isolated eUCB-MSCs had high proliferative capacity and differentiated easily into osteoblasts and chondrocytes, but not into adipocytes. A three-dimensional (3D culture approach with the chondrogenic factors BMP-2 and TGF-β1 potentiated chondrogenic differentiation with a significant increase in cartilage-specific markers at the mRNA level (Col2a1, Acan, Snorc and the protein level (type II and IIB collagen without an increase in hypertrophic chondrocyte markers (Col10a1 and Mmp13 in normoxia and in hypoxia. However, these chondrogenic factors caused an increase in type I collagen, which can be reduced using small interfering RNA targeting Col1a2. This study provides robust data on MSCs characterization and demonstrates that eUCB-MSCs have a great potential for cartilage tissue engineering.

  17. 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.

  18. POSSIBILITIES OF CURRENT CELLULAR TECHNOLOGIES FOR ARTICULAR CARTILAGE REPAIR (ANALYTICAL REVIEW

    Directory of Open Access Journals (Sweden)

    M. S. Bozhokin

    2016-01-01

    Full Text Available Despite a wide variety of surgical procedures utilized in clinical practice for treatment of articular cartilage lesions, the search for other options of articular reconstruction remains a relevant and open issue at the current stage of medicine and biotechnologies development. The recent years demonstrated a strong belief in cellular methods of hyaline cartilage repair such as implantation of autologous chondrocytes (ACI or cultures of mesenchymal stem cells (MSC including techniques for genetic modification of cells.The purpose of presented review is to summarize the published scientific data on up to date results of perspective cellular technologies for articular cartilage repair that are being developed. Autologous chondrocyte transplantation originally performed by Swedish researchers in 1987 is considered the first clinically applied technique for restoration of hyaline cartilage using cellular technologies. However, the transplanted cell culture featured low proliferative capacity and inability to form a regenerate resistant to high physical activity. Another generation of methods originated at the turn of the century utilized mesenchymal stem cells instead of autologous chondrocytes. Preparation of MSCs is a less invasive procedure compared to chondrocytes harvesting and the culture is featured by a higher proliferative ability. Researchers use various biodegradable carriers (matrices to secure cell fixation. Despite good clinical mid-term outcomes the transplanted tissue-engineering structures deteriorate with time due to cellular de-differentiation. Next generation of techniques being currently under pre-clinical studies is featured by the preliminary chondrogenic modification of transplanted cell culture. Usage of various growth factors, modified cell product and gene-activated matrices allow to gain a stable regulatory and key proteins synthesis and achieve a focused influence on regenerate's chondrogenic proliferation and in result

  19. Revision Surgery After Cartilage Repair: Data From the German Cartilage Registry (KnorpelRegister DGOU).

    Science.gov (United States)

    Pestka, Jan M; Luu, Nam H; Südkamp, Norbert P; Angele, Peter; Spahn, Gunther; Zinser, Wolfgang; Niemeyer, Philipp

    2018-02-01

    Various operative strategies have been introduced to restore the integrity of articular cartilage when injured. The frequency of revision surgery after cartilage regenerative surgery remains incompletely understood. The purpose of this study was to identify the reasons for revision surgery after cartilage regenerative surgery of the knee. We hypothesized that in a large patient cohort, revision rates would differ from those in the current literature. Case-control study; Level of evidence, 3. A total of 2659 complete data sets from the German Cartilage Registry were available for analyses. In brief, baseline data were provided by the attending physician at the time of index surgery. Follow-up data were collected using a web-based questionnaire inquiring whether patients had needed revision surgery during follow-up, which was defined as the endpoint of the present analysis. A total of 88 patients (3.3%) reported the need for revision surgery as early as 12 months postoperatively. Among the most common causes were arthrofibrosis (n = 27) and infection (n = 10). Female patients showed a significantly greater complication rate (4.5%) when compared with male patients (2.6%; P = .0071). The majority of cartilage lesions were located at the medial femoral condyle (40.2%), with a mean defect size of 3.5 ± 2.1 cm 2 . Neither the location nor defect size appeared to lead to an increased revision rate, which was greatest after osteochondral autografts (5.2%) and autologous chondrocyte implantation (4.6%). Revision rates did not differ significantly among surgical techniques. Chi-square analysis revealed significant correlations between the number of previous joint surgeries and the need for revision surgery ( P = .0203). Multivariate regression analysis further confirmed sex and the number of previous surgeries as variables predicting the need for early revision surgery. The low early revision rates found in this study underline that today's cartilage repair surgeries are

  20. Acrylamide Polymer Double-Network Hydrogels: Candidate Cartilage Repair Materials with Cartilage-Like Dynamic Stiffness and Attractive Surgery-Related Attachment Mechanics.

    Science.gov (United States)

    Arnold, Markus P; Daniels, Alma U; Ronken, Sarah; García, Helena Ardura; Friederich, Niklaus F; Kurokawa, Takayuki; Gong, Jian P; Wirz, Dieter

    2011-10-01

    In focal repair of joint cartilage and meniscus, initial stiffness and strength of repairs are generally much less than surrounding tissue. This increases early failure potential. Secure primary fixation of the repair material is also a problem. Acrylamide polymer double-network (DN) hydrogels are candidate-improved repair materials. DN gels have exceptional strength and toughness compared to ordinary gels. This stems from the double-network structure in which there is a high molar ratio of the second network to the first network, with the first network highly crosslinked and the second loosely crosslinked. Previous studies of acrylic PAMPS/PDMAAm and PAMPS/PAAm DN gels demonstrated physicochemical stability and tissue compatibility as well as the ability to foster cartilage formation. Mechanical properties related to surgical use were tested in 2 types of DN gels. Remarkably, these >90%-water DN gels exhibited dynamic impact stiffness (E*) values (~1.1 and ~1.5 MPa) approaching swine meniscus (~2.9 MPa). Dynamic impact energy-absorbing capability was much lower (median loss angles of ~2°) than swine meniscus (>10°), but it is intriguing that >90%-water materials can efficiently store energy. Also, fine 4/0 suture tear-out strength approached cartilage (~2.1 and ~7.1 N v. ~13.5 N). Initial strength of attachment of DN gels to cartilage with acrylic tissue adhesive was also high (~0.20 and ~0.15 N/mm(2)). DN gel strength and toughness properties stem from optimized entanglement of the 2 network components. DN gels thus have obvious structural parallels with cartilaginous tissues, and their surgical handling properties make them ideal candidates for clinical use.

  1. The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

    Science.gov (United States)

    Goldberg, Andy; Mitchell, Katrina; Soans, Julian; Kim, Louise; Zaidi, Razi

    2017-03-09

    The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre

  2. MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Dhollander, A.A.M., E-mail: Aad.Dhollander@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Huysse, W.C.J., E-mail: Wouter.Huysse@Ugent.b [Department of Radiology, Ghent University Hospital, De Pintelaan 185, -1K12 IB, B9000 Gent (Belgium); Verdonk, P.C.M., E-mail: pverdonk@yahoo.co [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Verstraete, K.L., E-mail: Koenraad.Verstraete@Ugent.b [Department of Radiology, Ghent University Hospital, De Pintelaan 185, -1K12 IB, B9000 Gent (Belgium); Verdonk, R., E-mail: Rene.Verdonk@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Verbruggen, G., E-mail: Gust.Verbruggen@Ugent.b [Laboratory of Connective Tissue Biology, Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium); Almqvist, K.F., E-mail: Fredrik.Almqvist@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium)

    2010-07-15

    Aim: The present study was designed to evaluate the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of symptomatic cartilage defects of the knee. MRI was used for the morphological analysis of cartilage repair. The correlation between MRI findings and clinical outcome was also studied. Methods: A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of symptomatic chondral and osteochondral lesions in the knee. Twenty-one patients were prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale (VAS) for pain preoperatively and at 3, 6, 9 and 12 months of follow-up. Of the 21 patients, 12 had consented to follow the postoperative MRI evaluation protocol. MRI data were analyzed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. The correlation between the clinical outcome and MRI findings was evaluated. Results: A statistically significant clinical improvement became apparent after 6 months and patients continued to improve during the 12 months of follow-up. One of the two MRI scoring systems that were used, showed a statistically significant deterioration of the repair tissue at 1 year of follow-up. Twelve months after the operation complete filling or hypertrophy was found in 41.6%. Bone-marrow edema and effusion were seen in 41.7% and 25% of the study patients, respectively. We did not find a consistent correlation between the MRI criteria and the clinical results. Discussion: The present study confirmed the primary role of MRI in the evaluation of cartilage repair. Two MOCART-based scoring systems were used in a longitudinal fashion and allowed a practical and morphological evaluation of the repair tissue. However, the correlation between clinical outcome and MRI findings was poor. Further

  3. MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for cartilage repair

    International Nuclear Information System (INIS)

    Dhollander, A.A.M.; Huysse, W.C.J.; Verdonk, P.C.M.; Verstraete, K.L.; Verdonk, R.; Verbruggen, G.; Almqvist, K.F.

    2010-01-01

    Aim: The present study was designed to evaluate the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of symptomatic cartilage defects of the knee. MRI was used for the morphological analysis of cartilage repair. The correlation between MRI findings and clinical outcome was also studied. Methods: A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of symptomatic chondral and osteochondral lesions in the knee. Twenty-one patients were prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale (VAS) for pain preoperatively and at 3, 6, 9 and 12 months of follow-up. Of the 21 patients, 12 had consented to follow the postoperative MRI evaluation protocol. MRI data were analyzed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. The correlation between the clinical outcome and MRI findings was evaluated. Results: A statistically significant clinical improvement became apparent after 6 months and patients continued to improve during the 12 months of follow-up. One of the two MRI scoring systems that were used, showed a statistically significant deterioration of the repair tissue at 1 year of follow-up. Twelve months after the operation complete filling or hypertrophy was found in 41.6%. Bone-marrow edema and effusion were seen in 41.7% and 25% of the study patients, respectively. We did not find a consistent correlation between the MRI criteria and the clinical results. Discussion: The present study confirmed the primary role of MRI in the evaluation of cartilage repair. Two MOCART-based scoring systems were used in a longitudinal fashion and allowed a practical and morphological evaluation of the repair tissue. However, the correlation between clinical outcome and MRI findings was poor. Further

  4. Osteoarthritis-derived chondrocytes are a potential source of multipotent progenitor cells for cartilage tissue engineering.

    Science.gov (United States)

    Oda, Tomoyuki; Sakai, Tadahiro; Hiraiwa, Hideki; Hamada, Takashi; Ono, Yohei; Nakashima, Motoshige; Ishizuka, Shinya; Matsukawa, Tetsuya; Yamashita, Satoshi; Tsuchiya, Saho; Ishiguro, Naoki

    2016-10-21

    The natural healing capacity of damaged articular cartilage is poor, rendering joint surface injuries a prime target for regenerative medicine. While autologous chondrocyte or mesenchymal stem cell (MSC) implantation can be applied to repair cartilage defects in young patients, no appropriate long-lasting treatment alternative is available for elderly patients with osteoarthritis (OA). Multipotent progenitor cells are reported to present in adult human articular cartilage, with a preponderance in OA cartilage. These facts led us to hypothesize the possible use of osteoarthritis-derived chondrocytes as a cell source for cartilage tissue engineering. We therefore analyzed chondrocyte- and stem cell-related markers, cell growth rate, and multipotency in OA chondrocytes (OACs) and bone marrow-derived MSCs, along with normal articular chondrocytes (ACs) as a control. OACs demonstrated similar phenotype and proliferation rate to MSCs. Furthermore, OACs exhibited multilineage differentiation ability with a greater chondrogenic differentiation ability than MSCs, which was equivalent to ACs. We conclude that chondrogenic capacity is not significantly affected by OA, and OACs could be a potential source of multipotent progenitor cells for cartilage tissue engineering. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Calcium/Cobalt Alginate Beads as Functional Scaffolds for Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Stefano Focaroli

    2016-01-01

    Full Text Available Articular cartilage is a highly organized tissue with complex biomechanical properties. However, injuries to the cartilage usually lead to numerous health concerns and often culminate in disabling symptoms, due to the poor intrinsic capacity of this tissue for self-healing. Although various approaches are proposed for the regeneration of cartilage, its repair still represents an enormous challenge for orthopedic surgeons. The field of tissue engineering currently offers some of the most promising strategies for cartilage restoration, in which assorted biomaterials and cell-based therapies are combined to develop new therapeutic regimens for tissue replacement. The current study describes the in vitro behavior of human adipose-derived mesenchymal stem cells (hADSCs encapsulated within calcium/cobalt (Ca/Co alginate beads. These novel chondrogenesis-promoting scaffolds take advantage of the synergy between the alginate matrix and Co+2 ions, without employing costly growth factors (e.g., transforming growth factor betas (TGF-βs or bone morphogenetic proteins (BMPs to direct hADSC differentiation into cartilage-producing chondrocytes.

  6. Extraction of aggrecan-peptide from cartilage by tissue autolysis.

    Science.gov (United States)

    Nakano, Takuo; Srichamroen, Anchalee; Ozimek, Lech

    2014-01-01

    Aggrecan is a cartilage specific proteoglycan containing chondroitin sulfate (CS) and keratan sulfate (KS). CS is an acidic polysaccharide having wide range of applications in pharmaceutical, cosmetic, and food industries. CS is extracted from cartilage by tissue proteolysis with an exogenous proteinase or by activating endogenous proteinases (autolysis) to release aggrecan-peptides from the tissue. This review is focused on the latter technique. Bovine nasal and tracheal cartilages, and broiler chicken sternum cartilage have been used for autolysis studies. To extract aggrecan-peptide, cartilage tissues are cut into small pieces, and incubated in a monovalent or divalent salt solution (e.g., 0.1 M sodium or calcium acetate) at pH 4.5 and 37 °C for 7 - 24 h. Most (~80% or more) of total tissue uronic acid, a constituent sugar of aggrecan, is extracted and released into the salt solution during incubation. Reextraction of the tissue residue results in release of a small amount of uronic acid. Aggrecan-peptides purified using anion exchange chromatography are large compounds containing CS and KS. On gel chromatography, they are excluded from the column of Sephacryl S-300. Chemical composition analysis demonstrated that aggrecan-peptides from either bovine or chicken cartilage contain >90% CS with small amount (autolysis has been used as a plate coating antigen in enzyme- linked immunosorbent assay (ELISA) to determine KS.

  7. Significance of cartilage endplate within herniated disc tissue.

    Science.gov (United States)

    Lama, Polly; Zehra, Uruj; Balkovec, Christian; Claireaux, Henry A; Flower, Luke; Harding, Ian J; Dolan, Patricia; Adams, Michael A

    2014-09-01

    Disc herniations sometimes contain hyaline cartilage fragments, but their origins and significance are uncertain. Herniations were removed surgically from 21 patients (aged 35-74 years) whose main symptom was sciatica (10 patients) or back pain (11 patients). Frozen sections, 5 µm thick, were examined histologically, and antibodies were used to label the matrix-degrading enzyme MMP 1, pro-inflammatory mediator TNFα, and cell proliferation marker Ki-67. Proportions of each tissue type were quantified by image analysis. Cartilage and bone components of the endplate were examined in 7-µm frozen sections from 16 cadaveric spines, aged 61-98 years. Cartilage fragments were found in 10/21 herniations. They averaged 5.0 mm in length, comprised 25 % of the herniation area, and two had some bone attached. Hyaline cartilage was more common in herniations from patients with sciatica (7/10) than with back pain (3/11, P = 0.050), and the area (%) of the herniation occupied by the cartilage was greater in sciatica patients (P Disc herniations often include hyaline cartilage pulled from the vertebral endplates. Cartilage fragments show little swelling or proteoglycan loss, and may be slow to resorb, increasing the risk of persisting sciatica. Loss of cartilage will increase endplate permeability, facilitating endplate inflammation and disc infection.

  8. [Experimental study of repairing full-thickness articular cartilage defect with chondrocyte-sodium alginate hydrogel-SIS complex].

    Science.gov (United States)

    Mo, Xiangtao; Deng, Li; Li, Xiuqun; Xie, Huiqi; Luo, Jingcong; Guo, Shangchun; Yang, Zhiming

    2009-08-01

    To explore the effect of tissue engineered cartilage reconstructed by using sodium alginate hydrogel and SIS complex as scaffold material and chondrocyte as seed cell on the repair of full-thickness articular cartilage defects. SIS was prepared by custom-made machine and detergent-enzyme treatment. Full-thickness articular cartilage of loading surface of the humeral head and the femoral condyle obtained from 8 New Zealand white rabbits (2-3 weeks old) was used to culture chondrocytes in vitro. Rabbit chondrocytes at passage 4 cultured by conventional multiplication method were diluted by sodium alginate to (5-7) x 10(7) cells/mL, and then were coated on SIS to prepare chondrocyte-sodium alginate hydrogel-SIS complex. Forty 6-month-old clean grade New Zealand white rabbits weighing 3.0-3.5 kg were randomized into two groups according to different operative methods (n = 20 rabbits per group), and full-thickness cartilage defect model of the unilateral knee joint (right or left) was established in every rabbit. In experimental group, the complex was implanted into the defect layer by layer to construct tissue engineered cartilage, and SIS membrane was coated on the surface to fill the defect completely. While in control group, the cartilage defect was filled by sodium alginate hydrogel and was sutured after being coated with SIS membrane without seeding of chondrocyte. General condition of the rabbits after operation was observed. The rabbits in two groups were killed 1, 3, 5, 7, and 9 months after operation, and underwent gross and histology observation. Eight rabbits were excluded due to anesthesia death, wound infection and diarrhea death. Sixteen rabbits per group were included in the experiment, and 3, 3, 3, 3, and 4 rabbits from each group were randomly selected and killed 1, 3, 5, 7, and 9 months after operation, respectively. Gross observation and histology Masson trichrome staining: in the experimental group, SIS on the surface of the implant was fused with

  9. [Nasal septum cartilage-silica gel complex for repairing nasal deformities of unilateral cleft lip].

    Science.gov (United States)

    Li, Qingwei; Sheng, Zunqi; Tang, Shengjian; Yang, Biaobing; Yu, Xiaohua

    2009-07-01

    To evaluate the operative methods and therapeutic effects of nasal septum cartilage-silica gel complex for two-stage repair of nasal deformities of unilateral cleft lip. From June 2001 to June 2007, 38 cases of secondary nasal deformity and septum deviation of cleft lip were treated with transplanting nasal septum cartilage-silica gel complex. Among of them, there were 21 males and 17 females, aging 14-23 years with an average of 17.6 years. All cases were with nasal deformities of unilateral cleft lip, including 21 cases of complete cleft lip and 17 cases of incomplete cleft lip. The locations were left side in 26 cases and right side in 12 cases. Nasal deformities were columella nasi deflexion, flattened nasal tip, pteleorrhine and alanasi collapse. The patients received 1-4 times operations, and the interval of two operations was 3-10 years (mean 5.5 years). According to nasal deformity, the nasal septum cartilage of 1.8 cm x 1.2 cm was cut, and transplanted into the nose point phantom surface forming "the shield" to extend nose column and to raise the tip of the nose. At the same time the nasal tip fat-connective tissue flap graft with fat knot was given. After fixation, the nasal alar cartilage and soft tissues were reduced to normal position. Primary healing of the incisions was achieved in all cases. The nasal deformity was corrected. The postoperative follow-up period was 12-18 months with an average of 15.6 months. All the patients of regional cartilage scars had no complication. The figure of nose was slinky, the height of apex of nose and the shape of nose was natural, the apex of nose, nasal ala, nostrils and nasal columella were satisfactory [(the results were satisfactory in 30 cases (78.9%), general in 8 cases (21.1%)]. The nose department overall esthetics shape was improved in all the patients, no complications of the phantom sliding, shifting and exposure, hemorrhage and infection occurred. The nasal septum cartilage-silica gel complex to repair

  10. 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. © 2013.

  11. In situ repair of bone and cartilage defects using 3D scanning and 3D printing.

    Science.gov (United States)

    Li, Lan; Yu, Fei; Shi, Jianping; Shen, Sheng; Teng, Huajian; Yang, Jiquan; Wang, Xingsong; Jiang, Qing

    2017-08-25

    Three-dimensional (3D) printing is a rapidly emerging technology that promises to transform tissue engineering into a commercially successful biomedical industry. However, the use of robotic bioprinters alone is not sufficient for disease treatment. This study aimed to report the combined application of 3D scanning and 3D printing for treating bone and cartilage defects. Three different kinds of defect models were created to mimic three orthopedic diseases: large segmental defects of long bones, free-form fracture of femoral condyle, and International Cartilage Repair Society grade IV chondral lesion. Feasibility of in situ 3D bioprinting for these diseases was explored. The 3D digital models of samples with defects and corresponding healthy parts were obtained using high-resolution 3D scanning. The Boolean operation was used to achieve the shape of the defects, and then the target geometries were imported in a 3D bioprinter. Two kinds of photopolymerized hydrogels were synthesized as bioinks. Finally, the defects of bone and cartilage were restored perfectly in situ using 3D bioprinting. The results of this study suggested that 3D scanning and 3D bioprinting could provide another strategy for tissue engineering and regenerative medicine.

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

    OpenAIRE

    Catherine Baugé; Karim Boumédiene

    2015-01-01

    Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. So, in recent years, researchers and surgeons have been working hard to elaborate cartilage repair interventions for patients who suffer from cartilage damage. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or hypertrophic cartil...

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jianhua; Yang, Qiu; Cheng, Niangmei [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Tao, Xiaojun [Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, Hunan (China); Zhang, Zhihua; Sun, Xiaomin [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Zhang, Qiqing, E-mail: zhangqiq@126.com [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Key Laboratory of Biomedical Materials of Tianjin, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192 (China)

    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. - Highlights: • Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere proposed for cartilage repair was created. • In vivo, scaffold could enhance cartilage regeneration and integration between the repaired and surrounding cartilage. • In vitro, scaffold exhibits excellent characteristics, such as, improved porosity water absorption and good cell affinity.

  14. Repair of osteochondral defects in rabbits with ectopically produced cartilage

    NARCIS (Netherlands)

    Emans, PJ; Hulsbosch, M; Wetzels, GMR; Bulstra, SK; Kuijer, R

    2005-01-01

    Cartilage has poor regenerative capacity. Donor site morbidity and interference with joint homeostasis should be considered when applying the autologous chondrocyte transplantation technique. The use of ectopically produced cartilage, derived from periosteum, might be a novel method to heal

  15. Microfluidic-based screening of resveratrol and drug-loading PLA/Gelatine nano-scaffold for the repair of cartilage defect.

    Science.gov (United States)

    Ming, Li; Zhipeng, Yuan; Fei, Yu; Feng, Rao; Jian, Weng; Baoguo, Jiang; Yongqiang, Wen; Peixun, Zhang

    2018-03-26

    Cartilage defect is common in clinical but notoriously difficult to treat for low regenerative and migratory capacity of chondrocytes. Biodegradable tissue engineering nano-scaffold with a lot of advantages has been the direction of material to repair cartilage defect in recent years. The objective of our study is to establish a biodegradable drug-loading synthetic polymer (PLA) and biopolymer (Gelatine) composite 3D nano-scaffold to support the treatment of cartilage defect. We designed a microfluidic chip-based drug-screening device to select the optimum concentration of resveratrol, which has strong protective capability for chondrocyte. Then biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds were fabricated and used to repair the cartilage defects. As a result, we successfully cultured primary chondrocytes and screened the appropriate concentrations of resveratrol by the microfluidic device. We also smoothly obtained superior biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds and compared the properties and therapeutic effects of cartilage defect in rats. In summary, our microfluidic device is a simple but efficient platform for drug screening and resveratrol-loading PLA/Gelatine 3D nano-scaffolds could greatly promote the cartilage formation. It would be possible for materials and medical researchers to explore individualized pharmacotherapy and drug-loading synthetic polymer and biopolymer composite tissue engineering scaffolds for the repair of cartilage defect in future.

  16. Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites

    NARCIS (Netherlands)

    Lu, S.; Lam, J.; Trachtenberg, J.E.; Lee, E.J.; Seyednejad, H.; Beucken, J.J.J.P van den; Tabata, Y.; Kasper, F.K.; Scott, D.W.; Wong, M.E.; Jansen, J.A.; Mikos, A.G.

    2015-01-01

    The present work investigated correlations between cartilage and subchondral bone repair, facilitated by a growth factor-delivering scaffold, in a rabbit osteochondral defect model. Histological scoring indices and microcomputed tomography morphological parameters were used to evaluate cartilage and

  17. Rehabilitation after Articular Cartilage Repair of the Knee in the Football (Soccer) Player.

    Science.gov (United States)

    Hambly, Karen; Silvers, Holly Jacinda; Steinwachs, Matthias

    2012-01-01

    Participation in football can put both male and female players at an increased risk for knee osteoarthritis. There is a higher prevalence of focal chondral defects in the knee of athletes compared to nonathletes. The management of chondral defects in the football player is complex and multifactorial. The aim of this study is to provide an overview of the current strategies for rehabilitation after articular cartilage repair of the knee in the football player. A review of current literature and the scientific evidence for rehabilitation after articular cartilage repair of the knee. Articular cartilage repair has been shown to allow return to sport but rehabilitation timescales are lengthy. Successful rehabilitation for a return to football after articular cartilage repair of the knee requires the player to be able to accept the load of the sport. This necessitates a multidisciplinary approach to rehabilitation, especially in the transition from therapy to performance care. It should be recognized that not all players will return to football after articular cartilage repair. The evidence base for rehabilitative practice after articular cartilage repair is increasing but remains sparse in areas.

  18. Rehabilitation after Articular Cartilage Repair of the Knee in the Football (Soccer) Player

    Science.gov (United States)

    Silvers, Holly Jacinda; Steinwachs, Matthias

    2012-01-01

    Background: Participation in football can put both male and female players at an increased risk for knee osteoarthritis. There is a higher prevalence of focal chondral defects in the knee of athletes compared to nonathletes. The management of chondral defects in the football player is complex and multifactorial. Objective: The aim of this study is to provide an overview of the current strategies for rehabilitation after articular cartilage repair of the knee in the football player. Design: A review of current literature and the scientific evidence for rehabilitation after articular cartilage repair of the knee. Conclusions: Articular cartilage repair has been shown to allow return to sport but rehabilitation timescales are lengthy. Successful rehabilitation for a return to football after articular cartilage repair of the knee requires the player to be able to accept the load of the sport. This necessitates a multidisciplinary approach to rehabilitation, especially in the transition from therapy to performance care. It should be recognized that not all players will return to football after articular cartilage repair. The evidence base for rehabilitative practice after articular cartilage repair is increasing but remains sparse in areas. PMID:26069608

  19. Mesenchymal stem cell therapy in osteoarthritis: advanced tissue repair or intervention with smouldering synovial activation?

    OpenAIRE

    van Lent, Peter LEM; van den Berg, Wim B

    2013-01-01

    Although it is generally accepted that osteoarthritis is a degenerative condition of the cartilage, other tissues such as synovium in which immunological and inflammatory reactions occur contribute to the development of joint pathology. This sheds new light on the potential mechanism of action of mesenchymal stem cell therapy in osteoarthritis. Rather than tissue repair due to local transformation of injected mesenchymal stem cells to chondrocytes and filling defects in cartilage, such treatm...

  20. Evaluation of chondrocyte behavior in a new equine collagen scaffold useful for cartilage repair.

    Science.gov (United States)

    Grigolo, B; Desando, G; Cavallo, C; Zini, N; Ghisu, S; Facchini, A

    2011-01-01

    Association of biomaterials with autologous cells can provide a new generation of implantable devices for cartilage repair. An ideal scaffold should possess a preformed three-dimensional shape, fix the cells to the damaged area and prevent their migration into the articular cavity. Furthermore, the constructs should have sufficient mechanical strength to facilitate handling in a clinical setting and stimulate the uniform spreading of cells and a phenotype re-differentiation process. The aim of this study was to verify the ability of an equine collagen membrane to support the growth of human chondrocytes and to allow the re-expression of their original phenotype. This ability was assessed by the evaluation of collagen type I, II and aggrecan mRNA expression by Real-Time PCR. Immunohistochemical analyses were performed to evaluate collagen type I, II and proteoglycans synthesis. Electron microscopy was utilized to highlight the structure of the biomaterial and its interactions with the cells. Our data indicate that human chondrocytes seeded onto a collagen membrane express and produce collagen type II and aggrecan and downregulate the production of collagen type I during the experimental times analyzed. These results provide an in vitro demonstration for the therapeutic potential of autologous chondrocyte transplantation by an equine collagen membrane as a delivery vehicle in a tissue-engineered approach towards the repair of articular cartilage defects.

  1. Piezoelectric smart biomaterials for bone and cartilage tissue engineering.

    Science.gov (United States)

    Jacob, Jaicy; More, Namdev; Kalia, Kiran; Kapusetti, Govinda

    2018-01-01

    Tissues like bone and cartilage are remodeled dynamically for their functional requirements by signaling pathways. The signals are controlled by the cells and extracellular matrix and transmitted through an electrical and chemical synapse. Scaffold-based tissue engineering therapies largely disturb the natural signaling pathways, due to their rigidity towards signal conduction, despite their therapeutic advantages. Thus, there is a high need of smart biomaterials, which can conveniently generate and transfer the bioelectric signals analogous to native tissues for appropriate physiological functions. Piezoelectric materials can generate electrical signals in response to the applied stress. Furthermore, they can stimulate the signaling pathways and thereby enhance the tissue regeneration at the impaired site. The piezoelectric scaffolds can act as sensitive mechanoelectrical transduction systems. Hence, it is applicable to the regions, where mechanical loads are predominant. The present review is mainly concentrated on the mechanism related to the electrical stimulation in a biological system and the different piezoelectric materials suitable for bone and cartilage tissue engineering.

  2. Platelet-rich plasma enhances the integration of bioengineered cartilage with native tissue in an in vitro model.

    Science.gov (United States)

    Sermer, Corey; Kandel, Rita; Anderson, Jesse; Hurtig, Mark; Theodoropoulos, John

    2018-02-01

    Current therapies for cartilage repair can be limited by an inability of the repair tissue to integrate with host tissue. Thus, there is interest in developing approaches to enhance integration. We have previously shown that platelet-rich plasma (PRP) improves cartilage tissue formation. This raised the question as to whether PRP could promote cartilage integration. Chondrocytes were isolated from cartilage harvested from bovine joints, seeded on a porous bone substitute and grown in vitro to form an osteochondral-like implant. After 7 days, the biphasic construct was soaked in PRP for 30 min before implantation into the core of a donut-shaped biphasic explant of native cartilage and bone. Controls were not soaked in PRP. The implant-explant construct was cultured for 2-4 weeks. PRP-soaked bioengineered implants integrated with host tissue in 73% of samples, whereas controls only integrated in 19% of samples. The integration strength, as determined by a push-out test, was significantly increased in the PRP-soaked implant group (219 ± 35.4 kPa) compared with controls (72.0 ± 28.5 kPa). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP-treated implant group, compared with untreated controls. Immunohistochemical studies revealed that the integration zone contained collagen type II and aggrecan. The cells at the zone of integration in the PRP-soaked group had a 3.5-fold increase in matrix metalloproteinase-13 gene expression compared with controls. These results suggest that PRP-soaked bioengineered cartilage implants may be a better approach for cartilage repair due to enhanced integration. Copyright © 2017 John Wiley & Sons, Ltd.

  3. AMIC Cartilage Repair in a Professional Soccer Player

    OpenAIRE

    Bark, S.; Riepenhof, H.; Gille, J.

    2012-01-01

    We report a case of a professional soccer player suffering from a traumatic cartilage lesion grade IV according to the Outerbridge classification at the femoral condyle treated with an enhanced microfracture technique (AMIC). Autologous Matrix-Induced Chondrogenesis (AMIC) is an innovative treatment for localized full-thickness cartilage defects combining the well-known microfracturing with collagen scaffold and fibrin glue. Because of the cartilage lesion (3 cm2), an AMIC procedure was perfo...

  4. Gene therapy for cartilage and bone tissue engineering

    CERN Document Server

    Hu, Yu-Chen

    2014-01-01

    "Gene Therapy for Cartilage and Bone Tissue Engineering" outlines the tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery, specifically for cartilage and bone engineering. It is intended for tissue engineers, cell therapists, regenerative medicine scientists and engineers, gene therapist and virologists. Dr. Yu-Chen Hu is a Distinguished Professor at the Department of Chemical Engineering, National Tsing Hua University and has received the Outstanding Research Award (National Science Council), Asia Research Award (Society of Chemical Engineers, Japan) and Professor Tsai-Teh Lai Award (Taiwan Institute of Chemical Engineers). He is also a fellow of the American Institute for Medical and Biological Engineering (AIMBE) and a member of the Tissue Engineering International & Regenerative Medicine Society (TERMIS)-Asia Pacific Council.

  5. 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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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

  7. Bone morphogenetic protein-induced cartilage development in tissue culture

    Energy Technology Data Exchange (ETDEWEB)

    Sato, K.; Urist, M.R.

    1984-03-01

    Outgrowths of mesenchyme-type cells from explants of allogeneic rat muscle onto a substratum of bone matrix containing bone morphogenetic protein (BMP) differentiate into cartilage. When BMP is chemically extracted from the bone matrix, the explanted cells develop only into fibrous tissue. When exogenous bovine BMP is introduced into the culture medium, either as a microsuspension or as a layer of particles between the matrix and the muscle cell tissue, cartilage develops at the interface between the matrix and the mesenchymal cell outgrowth. The chondrogenetic response is induced by as little as 2 micrograms of BMP; the optimum dose is 10 micrograms/40 mg (wet weight) of explant. The endogenous BMP equivalent for a comparable chondrogenetic response is about 0.6 micrograms/mg of allogeneic matrix. The minimum time for transfer of BMP to mesenchymal cell receptors is 1.0 hour, adequate time is 2.5 hours, and optimum time is approximately 5.0 hours. Measured in terms of incorporation of /sup 3/H-thymidine into DNA and of /sup 35/S sulfate into glycosaminoglycan, there is a latent period of one to three days preceeding the differentiation of mesenchyme-type cells into cartilage. During this latent period BMP-modulated mesenchymal cells disaggregate, migrate, reaggregate, and proliferate on new surfaces and constitute the morphogenetic phase of bone development. By the fourth day cells simultaneously undergo mitotic division, synthesize extracellular cartilage matrix, and establish the cytodifferentiation phase of development.

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

    Directory of Open Access Journals (Sweden)

    M Pei

    2011-11-01

    Full Text Available 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 decreased cell proliferation capacity. This is a significant challenge for cartilage tissue engineering and regeneration. Despite much progress having been made in cell expansion, there are still concerns over expanded cell size and quality for cell transplantation applications. Recently, in vivo investigations in stem cell niches have suggested the importance of developing an in vitro stem cell microenvironment for cell expansion and tissue-specific differentiation. Our and other investigators’ work indicates that a decellularized stem cell matrix (DSCM may provide such an expansion system to yield large-quantity and high-quality cells for cartilage tissue engineering and regeneration. This review briefly introduces key parameters in an in vivo stem cell niche and focuses on our recent work on DSCM for its rejuvenating or reprograming effect on various adult stem cells and chondrocytes. Since research in DSCM is still in its infancy, we are only able to discuss some potential mechanisms of DSCM on cell proliferation and chondrogenic potential. Further investigations of the underlying mechanism and in vivo regeneration capacity will allow this approach to be used in clinics.

  9. Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine.

    Science.gov (United States)

    Wu, Ling; Cai, Xiaoxiao; Zhang, Shu; Karperien, Marcel; Lin, Yunfeng

    2013-05-01

    Adipose-derived stem cells (ASCs) have been discovered for more than a decade. Due to the large numbers of cells that can be harvested with relatively little donor morbidity, they are considered to be an attractive alternative to bone marrow derived mesenchymal stem cells. Consequently, isolation and differentiation of ASCs draw great attention in the research of tissue engineering and regenerative medicine. Cartilage defects cause big therapeutic problems because of their low self-repair capacity. Application of ASCs in cartilage regeneration gives hope to treat cartilage defects with autologous stem cells. In recent years, a lot of studies have been performed to test the possibility of using ASCs to re-construct damaged cartilage tissue. In this article, we have reviewed the most up-to-date articles utilizing ASCs for cartilage regeneration in basic and translational research. Our topic covers differentiation of adipose tissue derived mesenchymal stem cells into chondrocytes, increased cartilage formation by co-culture of ASCs with chondrocytes and enhancing chondrogenic differentiation of ASCs by gene manipulation. Copyright © 2012 Wiley Periodicals, Inc.

  10. 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.

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

    Science.gov (United States)

    Paetzold, H; Goepfert, C; Huber, G; Hoenig, E; Pörtner, R; Schilling, A F; Meenen, N M; Morlock, M M

    2012-04-05

    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.

  12. Repair of rabbit cartilage defect based on the fusion of rabbit bone marrow stromal cells and Nano-HA/PLLA composite material.

    Science.gov (United States)

    Zhu, Weimin; Guo, Daiqi; Peng, Liangquan; Chen, Yun Fang; Cui, Jiaming; Xiong, Jianyi; Lu, Wei; Duan, Li; Chen, Kang; Zeng, Yanjun; Wang, Daping

    2017-02-01

    Objective To assess the effect of the fusion of rabbit bone marrow stromal cells (rBMSCs) and Nano-hydroxyapatite/poly (l-lactic acid) (Nano-HA/PLLA) in repairing the rabbit knee joint with full-thickness cartilage defect. Method The rBMSCs were isolated and cultured in vitro, and the third generation of rBMSCs was co-cultured with the Nano-HA/PLLA to construct the tissue-engineered cartilage (TEC). Eighteen New Zealand white rabbits were selected and randomly divided into three groups, namely, TEC group, Nano-HA/PLLA group, and control group. A cartilage defect model with the diameter of 4.5 mm and depth of 5 mm was constructed on the articular surface of medial malleolus of rabbit femur. General observation, histological observation, and Wakitani's histological scoring were conducted in the 12th and 24th week postoperatively. Results The results of TEC group indicated that new cartilage tissue was formed on the defect site and subchondral bone achieved physiological integration basically. Histological and immunohistochemical analyses indicated the generation of massive extracellular matrix. In contrast, limited regeneration and reconstruction of cartilage was achieved in the Nano-HA/PLLA group and control group, with a significant difference from the TEC group (p Nano-HA/PLLA combined with BMSCs promoted the repair of weight-bearing bone of adult rabbit's knee joint with cartilage defect.

  13. Matrix-based autologous chondrocyte implantation for cartilage repair with Hyalograft{sup (R)}C: Two-year follow-up by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Trattnig, S. [Department of Radiology, University Hospital of Vienna, Medical University of Vienna, Vienna (Austria)]. E-mail: siegfried.trattnig@meduniwien.ac.at; Pinker, K. [Department of Radiology, University Hospital of Vienna, Medical University of Vienna, Vienna (Austria); Krestan, C. [Department of Radiology, University Hospital of Vienna, Medical University of Vienna, Vienna (Austria); Plank, C. [Department of Radiology, University Hospital of Vienna, Medical University of Vienna, Vienna (Austria); Millington, S. [Department of Radiology, University Hospital of Vienna, Medical University of Vienna, Vienna (Austria); Marlovits, S. [Department of Radiology, University Hospital of Vienna, Medical University of Vienna, Vienna (Austria)

    2006-01-15

    Objective: Monitoring of articular cartilage repair after matrix-associated autologous chondrocyte implantation with Hyalograft{sup (R)}C by a new grading system based on non-invasive high-resolution magnetic resonance imaging. Patients and methods: In 23 patients, postoperative magnetic resonance imaging (MRI) was performed between 76 and 120 weeks. In nine of these patients, five MRI examinations were performed at 4, 12, 24, 52 and 104 weeks after Hyalograft{sup (R)}C implant. The repair tissue was described with separate variables: degree of defect repair in width and length, signal intensity of the repair tissue and status of the subchondral bone. For these variables a grading system with point scale evaluation was applied. Results: A complete filling of the defect by repair tissue was found in 15 patients. A moderate hypertrophy of the repair tissue was found in two patients. An underfilling of the defect by repair tissue was observed in four patients. In one patient, a partial detachment of the implant with associated subchondral cyst and edema was seen, and in one patient, a complete detachment of the graft was observed. The filling of the defect parallel to cartilage surface (integration) was complete in 18 cases. A split-like incomplete integration was present in one patient. Incomplete integration was found in four patients. The signal intensity of the implant on FSE and on 3D-GRE+FS was isointense compared to native normal cartilage in all cases after 12 months. The subchondral bone was normal in 14 patients. An edema-like signal alteration was found in three cases. In six patients, a non-edema abnormality of the subchondral bone (granulation tissue, cysts or sclerosis) was present. On follow-up exams performed in nine patients at the same postoperative intervals dynamic processes such as filling of partial defects, vanishing of hypertrophies and change of signal intensity of implant to isointensity with native articular cartilage were observed. A

  14. Repair of full-thickness articular cartilage defects by cultured mesenchymal stem cells transfected with the transforming growth factor β1 gene

    International Nuclear Information System (INIS)

    Guo Xiaodong; Zheng Qixin; Yang Shuhua; Shao Zengwu; Yuan Quan; Pan Zhengqi; Tang Shuo; Liu Kai; Quan Daping

    2006-01-01

    Articular cartilage repair remains a clinical and scientific challenge with increasing interest focused on the combined techniques of gene transfer and tissue engineering. Transforming growth factor beta 1 (TGF-β 1 ) is a multifunctional molecule that plays a central role in promotion of cartilage repair, and inhibition of inflammatory and alloreactive immune response. Cell mediated gene therapy can allow a sustained expression of TGF-β 1 that may circumvent difficulties associated with growth factor delivery. The objective of this study was to investigate whether TGF-β 1 gene modified mesenchymal stem cells (MSCs) could enhance the repair of full-thickness articular cartilage defects in allogeneic rabbits. The pcDNA 3 -TGF-β 1 gene transfected MSCs were seeded onto biodegradable poly-L-lysine coated polylactide (PLA) biomimetic scaffolds in vitro and allografted into full-thickness articular cartilage defects in 18 New Zealand rabbits. The pcDNA 3 gene transfected MSCs/biomimetic scaffold composites and the cell-free scaffolds were taken as control groups I and II, respectively. The follow-up times were 2, 4, 12 and 24 weeks. Macroscopical, histological and ultrastructural studies were performed. In vitro SEM studies found that abundant cartilaginous matrices were generated and completely covered the interconnected pores of the scaffolds two weeks post-seeding in the experimental groups. In vivo, the quality of regenerated tissue improved over time with hyaline cartilage filling the chondral region and a mixture of trabecular and compact bone filling the subchondral region at 24 weeks post-implantation. Joint repair in the experimental groups was better than that of either control group I or II, with respect to: (1) synthesis of hyaline cartilage specific extracellular matrix at the upper portion of the defect; (2) reconstitution of the subchondral bone at the lower portion of the defect and (3) inhibition of inflammatory and alloreactive immune responses. The

  15. AMIC Cartilage Repair in a Professional Soccer Player

    Directory of Open Access Journals (Sweden)

    S. Bark

    2012-01-01

    Full Text Available We report a case of a professional soccer player suffering from a traumatic cartilage lesion grade IV according to the Outerbridge classification at the femoral condyle treated with an enhanced microfracture technique (AMIC. Autologous Matrix-Induced Chondrogenesis (AMIC is an innovative treatment for localized full-thickness cartilage defects combining the well-known microfracturing with collagen scaffold and fibrin glue. Because of the cartilage lesion (3 cm2, an AMIC procedure was performed followed by a rehabilitation program according to the protocols in the literature, (Steadman et al.; 2003. After 8 months of rehabilitation, the player returned to team training and after 10 months to competition. Altogether he returned to the same skill level for almost one year after the index operation. He is very satisfied with the clinical results after AMIC, which corresponds with the Lysholm score of 90 points at 12 months.

  16. AMIC Cartilage Repair in a Professional Soccer Player.

    Science.gov (United States)

    Bark, S; Riepenhof, H; Gille, J

    2012-01-01

    We report a case of a professional soccer player suffering from a traumatic cartilage lesion grade IV according to the Outerbridge classification at the femoral condyle treated with an enhanced microfracture technique (AMIC). Autologous Matrix-Induced Chondrogenesis (AMIC) is an innovative treatment for localized full-thickness cartilage defects combining the well-known microfracturing with collagen scaffold and fibrin glue. Because of the cartilage lesion (3 cm(2)), an AMIC procedure was performed followed by a rehabilitation program according to the protocols in the literature, (Steadman et al.; 2003). After 8 months of rehabilitation, the player returned to team training and after 10 months to competition. Altogether he returned to the same skill level for almost one year after the index operation. He is very satisfied with the clinical results after AMIC, which corresponds with the Lysholm score of 90 points at 12 months.

  17. Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering.

    Science.gov (United States)

    Duval, Elise; Baugé, Catherine; Andriamanalijaona, Rina; Bénateau, Hervé; Leclercq, Sylvain; Dutoit, Soizic; Poulain, Laurent; Galéra, Philippe; Boumédiene, Karim

    2012-09-01

    Cartilage engineering is one of the most challenging issue in regenerative medicine, due to its limited self-ability to repair. Here, we assessed engineering of cartilage tissue starting from human bone marrow (hBM) stem cells under hypoxic environment and delineated the mechanism whereby chondrogenesis could be conducted without addition of exogenous growth factors. hBM stem cells were cultured in alginate beads and chondrogenesis was monitored by chondrocyte phenotypic markers. Activities and roles of Sox and HIF-1α transcription factors were investigated with complementary approaches of gain and loss of function and provided evidences that HIF-1α is essential for hypoxic induction of chondrogenesis. Thereafter, hBM cells and human articular chondrocytes (HAC) underwent chondrogenesis by 3D and hypoxic culture for 7 days or by ectopic expression of HIF-1α. After subcutaneous implantation of 3 weeks into athymic mice, tissue analysis showed that hypoxia or HIF-1α overexpression is effective and sufficient to induce chondrocyte phenotype in hBM cells, without use of exogenous growth factors. Therefore, this study brings interesting data for a simple and affordable system in biotechnology of cartilage engineering. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditions.

    Science.gov (United States)

    Mobasheri, Ali; Kalamegam, Gauthaman; Musumeci, Giuseppe; Batt, Mark E

    2014-07-01

    Osteoarthritis (OA) represents a final and common pathway for all major traumatic insults to synovial joints. OA is the most common form of degenerative joint disease and a major cause of pain and disability. Despite the global increase in the incidence of OA, there are no effective pharmacotherapies capable of restoring the original structure and function of damaged articular cartilage. Consequently cell-based and biological therapies for osteoarthritis (OA) and related orthopaedic disorders have become thriving areas of research and development. Autologous chondrocyte implantation (ACI) has been used for treatment of osteoarticular lesions for over two decades. Although chondrocyte-based therapy has the capacity to slow down the progression of OA and delay partial or total joint replacement surgery, currently used procedures are associated with the risk of serious adverse events. Complications of ACI include hypertrophy, disturbed fusion, delamination, and graft failure. Therefore there is significant interest in improving the success rate of ACI by improving surgical techniques and preserving the phenotype of the primary chondrocytes used in the procedure. Future tissue-engineering approaches for cartilage repair will also benefit from advances in chondrocyte-based repair strategies. This review article focuses on the structure and function of articular cartilage and the pathogenesis of OA in the context of the rising global burden of musculoskeletal disease. We explore the challenges associated with cartilage repair and regeneration using cell-based therapies that use chondrocytes and mesenchymal stem cells (MSCs). This paper also explores common misconceptions associated with cell-based therapy and highlights a few areas for future investigation. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Translational Application of Microfluidics and Bioprinting for Stem Cell-Based Cartilage Repair

    Directory of Open Access Journals (Sweden)

    Silvia Lopa

    2018-01-01

    Full Text Available Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells. Here, we discuss the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics. In particular, we will focus on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D bioprinting applications, on the screening of biochemical and biophysical factors through microfluidic devices to enhance stem cell chondrogenesis, and on the use of microfluidic technology to generate implantable constructs with a complex geometry. Finally, we will describe some new bioprinting applications that pave the way to the clinical use of stem cell-based therapies, such as scaffold-free bioprinting and the development of a 3D handheld device for the in situ repair of cartilage defects.

  20. The Potential for Synovium-derived Stem Cells in Cartilage Repair

    DEFF Research Database (Denmark)

    Kubosch, Eva Johanna; Lang, Gernot Michael; Fürst, David

    2018-01-01

    BACKGROUND: Articular cartilage defects often result in pain, loss of function and finally osteoarthritis. Developing cell-based therapies for cartilage repair is a major goal of orthopaedic research. Autologous chondrocyte implantation is currently the gold standard cell-based surgical procedure...... for the treatment of large, isolated, full thickness cartilage defects. Several disadvantages such as the need for two surgical procedures or hypertrophic regenerative cartilage, underline the need for alternative cell sources. OBJECTIVE: Mesenchymal stem cells, particularly synovium-derived mesenchymal stem cells......, represent a promising cell source. Synovium-derived mesenchymal stem cells have attracted considerable attention since they display great chondrogenic potential and less hypertrophic differentiation than mesenchymal stem cells derived from bone marrow. The aim of this review was to summarize the current...

  1. Similar properties of chondrocytes from osteoarthritis joints and mesenchymal stem cells from healthy donors for tissue engineering of articular cartilage.

    Directory of Open Access Journals (Sweden)

    Amilton M Fernandes

    Full Text Available Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM derived mesenchymal stem cells (MSCs from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin, ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage.

  2. Similar properties of chondrocytes from osteoarthritis joints and mesenchymal stem cells from healthy donors for tissue engineering of articular cartilage.

    Science.gov (United States)

    Fernandes, Amilton M; Herlofsen, Sarah R; Karlsen, Tommy A; Küchler, Axel M; Fløisand, Yngvar; Brinchmann, Jan E

    2013-01-01

    Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA) may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM) derived mesenchymal stem cells (MSCs) from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin), ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage.

  3. The comparison of acellular dermal matric (Alloderm), Dacron, Gore-Tex, and autologous cartilage graft materials in an experimental animal model for nasal septal repair surgery.

    Science.gov (United States)

    Mola, Ferhat; Keskin, Gurkan; Ozturk, Murat; Muezzinoglu, Bahar

    2007-01-01

    The aim of this study was to compare the compatibility of Alloderm, Dacron, Gore-Tex, and autologous cartilage graft materials with host tissues in nasal septal perforation repair surgery. The materials were placed into the nasal septum of 16 New Zealand rabbits. At the end of the 3rd month, septums of the rabbits were removed totally and reactions, such as inflammation;foreign body giant cell; or fibrosis that developed in the surrounding tissue against the implant material were evaluated. Acute inflammation reactions occurred mostly with Gore-Tex. There were no differences between groups according to chronic inflammation. When the number of reactions and tissue compatibility were taken into consideration, cartilage performed the best followed by Alloderm. There were more reactions with Dacron, but it still showed compatibility. Cartilage was found to be the best material followed by Alloderm and Dacron, but Gore-Tex was found unsuitable.

  4. 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.

  5. Sodium magnetic resonance imaging of ankle joint in cadaver specimens, volunteers, and patients after different cartilage repair techniques at 7 T: initial results.

    Science.gov (United States)

    Zbýň, Štefan; Brix, Martin O; Juras, Vladimir; Domayer, Stephan E; Walzer, Sonja M; Mlynarik, Vladimir; Apprich, Sebastian; Buckenmaier, Kai; Windhager, Reinhard; Trattnig, Siegfried

    2015-04-01

    The goal of cartilage repair techniques such as microfracture (MFX) or matrix-associated autologous chondrocyte transplantation (MACT) is to produce repair tissue (RT) with sufficient glycosaminoglycan (GAG) content. Sodium magnetic resonance imaging (MRI) offers a direct and noninvasive evaluation of the GAG content in native cartilage and RT. In the femoral cartilage, this method was able to distinguish between RTs produced by MFX and MACT having different GAG contents. However, it needs to be clarified whether sodium MRI can be useful for evaluating RT in thin ankle cartilage. Thus, the aims of this 7-T study were (1) to validate our sodium MRI protocol in cadaver ankle samples, (2) to evaluate the sodium corrected signal intensities (cSI) in cartilage of volunteers, (3) and to compare sodium values in RT between patients after MFX and MACT treatment. Five human cadaver ankle samples as well as ankles of 9 asymptomatic volunteers, 6 MFX patients and 6 MACT patients were measured in this 7-T study. Sodium values from the ankle samples were compared with histochemically evaluated GAG content. In the volunteers, sodium cSI values were calculated in the cartilages of ankle and subtalar joint. In the patients, sodium cSI in RT and reference cartilage were measured, morphological appearance of RT was evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system, and clinical outcome before and after surgery was assessed using the American Orthopaedic Foot and Ankle Society score and Modified Cincinnati Knee Scale. All regions of interest were defined on morphological images and subsequently transferred to the corresponding sodium images. Analysis of variance, t tests, and Pearson correlation coefficients were evaluated. In the patients, significantly lower sodium cSI values were found in RT than in reference cartilage for the MFX (P = 0.007) and MACT patients (P = 0.008). Sodium cSI and MOCART scores in RT did not differ between

  6. Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites.

    Science.gov (United States)

    Lu, Steven; Lam, Johnny; Trachtenberg, Jordan E; Lee, Esther J; Seyednejad, Hajar; van den Beucken, Jeroen J J P; Tabata, Yasuhiko; Kasper, F Kurtis; Scott, David W; Wong, Mark E; Jansen, John A; Mikos, Antonios G

    2015-12-01

    The present work investigated correlations between cartilage and subchondral bone repair, facilitated by a growth factor-delivering scaffold, in a rabbit osteochondral defect model. Histological scoring indices and microcomputed tomography morphological parameters were used to evaluate cartilage and bone repair, respectively, at 6 and 12 weeks. Correlation analysis revealed significant associations between specific cartilage indices and subchondral bone parameters that varied with location in the defect (cortical vs. trabecular region), time point (6 vs. 12 weeks), and experimental group (insulin-like growth factor-1 only, bone morphogenetic protein-2 only, or both growth factors). In particular, significant correlations consistently existed between cartilage surface regularity and bone quantity parameters. Overall, correlation analysis between cartilage and bone repair provided a fuller understanding of osteochondral repair and can help drive informed studies for future osteochondral regeneration strategies.

  7. One-stage vs two-stage cartilage repair: a current review

    Directory of Open Access Journals (Sweden)

    Daniel Meyerkort

    2010-10-01

    Full Text Available Daniel Meyerkort, David Wood, Ming-Hao ZhengCenter for Orthopaedic Research, School of Surgery and Pathology, University of Western Australia, Perth, AustraliaIntroduction: Articular cartilage has a poor capacity for regeneration if damaged. Various methods have been used to restore the articular surface, improve pain, function, and slow progression to osteoarthritis.Method: A PubMed review was performed on 18 March, 2010. Search terms included “autologous chondrocyte implantation (ACI” and “microfracture” or “mosaicplasty”. The aim of this review was to determine if 1-stage or 2-stage procedures for cartilage repair produced different functional outcomes.Results: The main procedures currently used are ACI and microfracture. Both first-generation ACI and microfracture result in clinical and functional improvement with no significant differences. A significant increase in functional outcome has been observed in second-generation procedures such as Hyalograft C, matrix-induced ACI, and ChondroCelect compared with microfracture. ACI results in a higher percentage of patients with clinical improvement than mosaicplasty; however, these results may take longer to achieve.Conclusion: Clinical and functional improvements have been demonstrated with ACI, microfracture, mosaicplasty, and synthetic cartilage constructs. Heterogeneous products and lack of good-quality randomized-control trials make product comparison difficult. Future developments involve scaffolds, gene therapy, growth factors, and stem cells to create a single-stage procedure that results in hyaline articular cartilage.Keywords: autologous chondrocyte implantation, microfracture, cartilage repair

  8. 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.

  9. Collagen-alginate as bioink for three-dimensional (3D) cell printing based cartilage tissue engineering.

    Science.gov (United States)

    Yang, Xingchen; Lu, Zhenhui; Wu, Huayu; Li, Wei; Zheng, Li; Zhao, Jinmin

    2018-02-01

    Articular cartilage repair is still a huge challenge for researchers and clinicians. 3D bioprinting could be an innovative technology for cartilage tissue engineering. In this study, we used collagen type I (COL) or agarose (AG) mixed with sodium alginate (SA) to serve as 3D bioprinting bioinks and incorporated chondrocytes to construct in vitro 3D printed cartilage tissue. Swelling ratio, mechanical properties, scanning electron microscopy (SEM), cell viability and cytoskeleton, biochemistry analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to investigate the function of different bioinks in 3D printing cartilage tissue engineering applications. The results showed that the mechanical strength was improved in both SA/COL and SA/AG groups compared to SA alone. Besides, the addition of COL or AG has little impact on gelling behavior, demonstrating the advantage as bioinks for 3D printing. Among the three scaffolds, SA/COL could distinctly facilitated cell adhesion, accelerated cell proliferation and enhanced the expression of cartilage specific genes such as Acan, Col2al and Sox9 than the other two groups. Lower expression of Col1a1, the fibrocartilage marker, was present in SA/COL group than that in both of SA and SA/AG groups. The results indicated that SA/COL effectively suppressed dedifferentiation of chondrocytes and preserved the phenotype. In summary, 3D bioprinted SA/COL with favorable mechanical strength and biological functionality is promising in cartilage tissue engineering. Copyright © 2017. Published by Elsevier B.V.

  10. 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.

  11. Chondrogenesis and cartilage tissue engineering: the longer road to technology development.

    Science.gov (United States)

    Mahmoudifar, Nastaran; Doran, Pauline M

    2012-03-01

    Joint injury and disease are painful and debilitating conditions affecting a substantial proportion of the population. The idea that damaged cartilage in articulating joints might be replaced seamlessly with tissue-engineered cartilage is of obvious commercial interest because the market for such treatments is large. Recently, a wealth of new information about the complex biology of chondrogenesis and cartilage has emerged from stem cell research, including increasing evidence of the role of physical stimuli in directing differentiation. The challenge for the next generation of tissue engineers is to identify the key elements in this new body of knowledge that can be applied to overcome current limitations affecting cartilage synthesis in vitro. Here we review the status of cartilage tissue engineering and examine the contribution of stem cell research to technology development for cartilage production. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. 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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Engineered cartilage regeneration from adipose tissue derived-mesenchymal stem cells: A morphomolecular study on osteoblast, chondrocyte and apoptosis evaluation.

    Science.gov (United States)

    Szychlinska, Marta Anna; Castrogiovanni, Paola; Nsir, Houda; Di Rosa, Michelino; Guglielmino, Claudia; Parenti, Rosalba; Calabrese, Giovanna; Pricoco, Elisabetta; Salvatorelli, Lucia; Magro, Gaetano; Imbesi, Rosa; Mobasheri, Ali; Musumeci, Giuseppe

    2017-08-15

    The poor self-repair capacity of cartilage tissue in degenerative conditions, such as osteoarthritis (OA), has prompted the development of a variety of therapeutic approaches, such as cellular therapies and tissue engineering based on the use of mesenchymal stem cells (MSCs). The aim of this study is to demonstrate, for the first time, that the chondrocytes differentiated from rat adipose tissue derived-MSCs (AMSCs), are able to constitute a morphologically and biochemically healthy hyaline cartilage after 6 weeks of culture on a Collagen Cell Carrier (CCC) scaffold. In this study we evaluated the expression of some osteoblasts (Runt-related transcription factor 2 (RUNX2) and osteocalcin), chondrocytes (collagen I, II and lubricin) and apoptosis (caspase-3) biomarkers in undifferentiated AMSCs, differentiated AMSCs in chondrocytes cultured in monolayer and AMSCs-derived chondrocytes seeded on CCC scaffolds, by different techniques such as immunohistochemistry, ELISA, Western blot and gene expression analyses. Our results showed the increased expression of collagen II and lubricin in AMSCs-derived chondrocytes cultured on CCC scaffolds, whereas the expression of collagen I, RUNX2, osteocalcin and caspase-3 resulted decreased, when compared to the controls. In conclusion, this innovative basic study could be a possible key for future therapeutic strategies for articular cartilage restoration through the use of CCC scaffolds, to reduce the morbidity from acute cartilage injuries and degenerative joint diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Development and characterization of decellularized human nasoseptal cartilage matrix for use in tissue engineering.

    Science.gov (United States)

    Graham, M Elise; Gratzer, Paul F; Bezuhly, Michael; Hong, Paul

    2016-10-01

    Reconstruction of cartilage defects in the head and neck can require harvesting of autologous cartilage grafts, which can be associated with donor site morbidity. To overcome this limitation, tissue-engineering approaches may be used to generate cartilage grafts. The objective of this study was to decellularize and characterize human nasoseptal cartilage with the aim of generating a biological scaffold for cartilage tissue engineering. Laboratory study using nasoseptal cartilage. Remnant human nasoseptal cartilage specimens were collected and subjected to a novel decellularization treatment. The decellularization process involved several cycles of enzymatic detergent treatments. For characterization, decellularized and fresh (control) specimens underwent histological, biochemical, and mechanical analyses. Scanning electron microscopy and biocompatibility assay were also performed. The decellularization process had minimal effect on glycosaminoglycan content of the cartilage extracellular matrix. Deoxyribonucleic acid (DNA) analysis revealed the near-complete removal of genomic DNA from decellularized tissues. The effectiveness of the decellularization process was also confirmed on histological and scanning electron microscopic analyses. Mechanical testing results showed that the structural integrity of the decellularized tissue was maintained, and biocompatibility was confirmed. Overall, the current decellularization treatment resulted in significant reduction of genetic/cellular material with preservation of the underlying extracellular matrix structure. This decellularized material may serve as a potential scaffold for cartilage tissue engineering. N/A. Laryngoscope, 126:2226-2231, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  15. 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.

  16. 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.

  17. 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.

  18. Cartilage repair in an osteochondral defect in a rabbit model

    NARCIS (Netherlands)

    Barron, V.; Merghani, K.; Nandakumar, A.; van Blitterswijk, Clemens; Habibovic, Pamela; Shaw, G.; Coleman, C.; Hayes, J.; Moroni, Lorenzo; Barry, F.; Murphy, M.

    2013-01-01

    Despite the fact that mesenchymal stem cells (MSC) offer clinical potential for osteoarthritis applications, retaining sufficient numbers of functional MSC at the site of injury for optimal repair still continues to be a major challenge. One method of overcoming this limitation is to create an

  19. Chitosan adhesive for laser tissue repair

    Science.gov (United States)

    Lauto, A.; Stoodley, M.; Avolio, A.; Foster, L. J. R.

    2006-02-01

    Background. Laser tissue repair usually relies on haemoderivate solders, based on serum albumin. These solders have intrinsic limitations that impair their widespread use, such as limited repair strength, high solubility, brittleness and viral transmission. Furthermore, the solder activation temperature (65-70 °C) can induce significant damage to tissue. In this study, a new laser-activated biomaterial for tissue repair was developed and tested in vitro and in vivo to overcome some of the shortcomings of traditional solders. Materials and Methods. Flexible and insoluble strips of chitosan adhesive (surface area ~34 mm2, thickness ~20 μm) were developed and bonded on sheep intestine with a laser fluence and irradiance of 52 +/- 2 J/cm2 and ~15 W/cm2 respectively. The temperature between tissue and adhesive was measured using small thermocouples. The strength of repaired tissue was tested by a calibrated tensiometer. The adhesive was also bonded in vivo to the sciatic nerve of rats to assess the thermal damage induced by the laser (fluence = 65 +/- 11 J/cm2, irradiance = 15 W/cm2) four days post-operatively. Results. Chitosan adhesives successfully repaired intestine tissue, achieving a repair strength of 0.50 +/- 0.15 N (shear stress = 14.7 +/- 4.7 KPa, n=30) at a temperature of 60-65 °C. The laser caused demyelination of axons at the operated site; nevertheless, the myelinated axons retained their normal morphology proximally and distally.

  20. 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

  1. A new biotechnology for articular cartilage repair: subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2).

    Science.gov (United States)

    Tamai, Noriyuki; Myoui, Akira; Hirao, Makoto; Kaito, Takashi; Ochi, Takahiro; Tanaka, Junzo; Takaoka, Kunio; Yoshikawa, Hideki

    2005-05-01

    Articular cartilage repair remains a major obstacle in tissue engineering. We recently developed a novel tool for articular cartilage repair, consisting of a triple composite of an interconnected porous hydroxyapatite (IP-CHA), recombinant human bone morphogenetic protein-2 (rhBMP-2), and a synthetic biodegradable polymer [poly-d,l-lactic acid/polyethylene glycol (PLA-PEG)] as a carrier for rhBMP-2. In the present study, we evaluated the capacity of the triple composite to induce the regeneration of articular cartilage. Full-thickness cartilage defects were created in the trochlear groove of 52 New Zealand White rabbits. Sixteen defects were filled with the bone morphogenetic protein (BMP)/PLA-PEG/IP-CHA composite (group I), 12 with PLA-PEG/IP-CHA (group II), 12 with IP-CHA alone (group III), and 12 were left empty (group IV). The animals were killed 1, 3, and 6 weeks after surgery, and the gross appearance of the defect sites was assessed. The harvested tissues were examined radiographically and histologically. One week after implantation with the BMP/PLA-PEG/IP-CHA composite (group I), vigorous repair had occurred in the subchondral defect. It contained an agglomeration of mesenchymal cells which had migrated from the surrounding bone marrow either directly, or indirectly via the interconnecting pores of the IP-CHA scaffold. At 6 weeks, these defects were completely repaired. The regenerated cartilage manifested a hyaline-like appearance, with a mature matrix and a columnar organization of chondrocytes. The triple composite of rhBMP-2, PLA-PEG, and IP-CHA promotes the repair of full-thickness articular cartilage defects within as short a period as 3 weeks in the rabbit model. Hence, this novel cell-free implant biotechnology could mark a new development in the field of articular cartilage repair.

  2. Biocompatible nanocomposite of TiO2 incorporated bi-polymer for articular cartilage tissue regeneration: A facile material.

    Science.gov (United States)

    Cao, Lei; Wu, Xiaofeng; Wang, Qiugen; Wang, Jiandong

    2018-01-01

    The development and design of polymeric hydrogels for articular cartilage tissue engineering have been a vital biomedical research for recent days. Organic/inorganic combined hydrogels with improved surface activity have shown potential for the repair and regeneration of hard tissues, but have not been broadly studied for articular cartilage tissue engineering applications. In this work, bi-polymeric hydrogel composite was designed with the incorporation some quantities of stick-like TiO 2 nanostructures for favorable surface behavior and enhancement of osteoblast adhesions. The microscopic investigations clearly exhibited that the stick-like TiO 2 nanostructured materials are highly inserted into the PVA/PVP bi-polymeric matrix, due to the long-chain PVA molecules are promoted to physical crosslinking density in hydrogel network. The results of improved surface topography of hydrogel matrixes show that more flatted cell morphologies and enhanced osteoblast attachment on the synthesized nanocomposites. The crystalline bone and stick-like TiO 2 nanocomposites significantly improved the bioactivity via lamellipodia and filopodia extension of osteoblast cells, due to its excellent intercellular connection and regulated cell responses. Consequently, these hydrogel has been enhanced the antibacterial activity against Staphylococcus aureus and Escherichia coli bacterial pathogens. Hence it is concluded that these hydrogel nanocomposite with improved morphology, osteoblast behavior and bactericidal activity have highly potential candidates for articular cartilage tissue regeneration applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Effects of microcurrent stimulation on Hyaline cartilage repair in immature male rats (Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    de Campos Ciccone Carla

    2013-01-01

    Full Text Available Abstract Background In this study, we investigate the effects of microcurrent stimulation on the repair process of xiphoid cartilage in 45-days-old rats. Methods Twenty male rats were divided into a control group and a treated group. A 3-mm defect was then created with a punch in anesthetized animals. In the treated group, animals were submitted to daily applications of a biphasic square pulse microgalvanic continuous electrical current during 5 min. In each application, it was used a frequency of 0.3 Hz and intensity of 20 μA. The animals were sacrificed at 7, 21 and 35 days after injury for structural analysis. Results Basophilia increased gradually in control animals during the experimental period. In treated animals, newly formed cartilage was observed on days 21 and 35. No statistically significant differences in birefringent collagen fibers were seen between groups at any of the time points. Treated animals presented a statistically larger number of chondroblasts. Calcification points were observed in treated animals on day 35. Ultrastructural analysis revealed differences in cell and matrix characteristics between the two groups. Chondrocyte-like cells were seen in control animals only after 35 days, whereas they were present in treated animals as early as by day 21. The number of cuprolinic blue-stained proteoglycans was statistically higher in treated animals on days 21 and 35. Conclusion We conclude that microcurrent stimulation accelerates the cartilage repair in non-articular site from prepuberal animals.

  4. Emergence of scaffold-free approaches for tissue engineering musculoskeletal cartilages.

    Science.gov (United States)

    DuRaine, Grayson D; Brown, Wendy E; Hu, Jerry C; Athanasiou, Kyriacos A

    2015-03-01

    This review explores scaffold-free methods as an additional paradigm for tissue engineering. Musculoskeletal cartilages-for example articular cartilage, meniscus, temporomandibular joint disc, and intervertebral disc-are characterized by low vascularity and cellularity, and are amenable to scaffold-free tissue engineering approaches. Scaffold-free approaches, particularly the self-assembling process, mimic elements of developmental processes underlying these tissues. Discussed are various scaffold-free approaches for musculoskeletal cartilage tissue engineering, such as cell sheet engineering, aggregation, and the self-assembling process, as well as the availability and variety of cells used. Immunological considerations are of particular importance as engineered tissues are frequently of allogeneic, if not xenogeneic, origin. Factors that enhance the matrix production and mechanical properties of these engineered cartilages are also reviewed, as the fabrication of biomimetically suitable tissues is necessary to replicate function and ensure graft survival in vivo. The concept of combining scaffold-free and scaffold-based tissue engineering methods to address clinical needs is also discussed. Inasmuch as scaffold-based musculoskeletal tissue engineering approaches have been employed as a paradigm to generate engineered cartilages with appropriate functional properties, scaffold-free approaches are emerging as promising elements of a translational pathway not only for musculoskeletal cartilages but for other tissues as well.

  5. Imaging stem cell differentiation for cell-based tissue repair.

    Science.gov (United States)

    Lee, Zhenghong; Dennis, James; Alsberg, Eben; Krebs, Melissa D; Welter, Jean; Caplan, Arnold

    2012-01-01

    Mesenchymal stem cells (MSCs) can differentiate into a number of tissue lineages and possess great potential in tissue regeneration and cell-based therapy. For bone fracture or cartilage wear and tear, stem cells need to be delivered to the injury site for repair. Assessing engraftment of the delivered cells and their differentiation status is crucial for the optimization of novel cell-based therapy. A longitudinal and quantitative method is needed to track stem cells transplanted/implanted to advance our understanding of their therapeutic effects and facilitate improvements in cell-based therapy. Currently, there are very few effective noninvasive ways to track the differentiation of infused stem cells. A brief review of a few existing approaches, mostly using transgenic animals, is given first, followed by newly developed in vivo imaging strategies that are intended to track implanted MSCs using a reporter gene system. Specifically, marker genes are selected to track whether MSCs differentiate along the osteogenic lineage for bone regeneration or the chondrogenic lineage for cartilage repair. The general strategy is to use the promoter of a differentiation-specific marker gene to drive the expression of an established reporter gene for noninvasive and repeated imaging of stem cell differentiation. The reporter gene system is introduced into MSCs by way of a lenti-viral vector, which allows the use of human cells and thus offers more flexibility than the transgenic animal approach. Imaging osteogenic differentiation of implanted MSCs is used as a demonstration of the proof-of-principle of this differentiation-specific reporter gene approach. This framework can be easily extended to other cell types and for differentiation into any other cell lineage for which a specific marker gene (promoter) can be identified. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. 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.

  7. Application of cell and biomaterial-based tissue engineering methods in the treatment of cartilage, menisci and ligament injuries.

    Science.gov (United States)

    Trzeciak, Tomasz; Richter, Magdalena; Suchorska, Wiktoria; Augustyniak, Ewelina; Lach, Michał; Kaczmarek, Małgorzata; Kaczmarczyk, Jacek

    2016-03-01

    Over 20 years ago it was realized that the traditional methods of the treatment of injuries to joint components: cartilage, menisci and ligaments, did not give satisfactory results and so there is a need of employing novel, more effective therapeutic techniques. Recent advances in molecular biology, biotechnology and polymer science have led to both the experimental and clinical application of various cell types, adapting their culture conditions in order to ensure a directed differentiation of the cells into a desired cell type, and employing non-toxic and non-immunogenic biomaterial in the treatment of knee joint injuries. In the present review the current state of knowledge regarding novel cell sources, in vitro conditions of cell culture and major important biomaterials, both natural and synthetic, used in cartilage, meniscus and ligament repair by tissue engineering techniques are described, and the assets and drawbacks of their clinical application are critically evaluated.

  8. 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

  9. Reduction of sample size requirements by bilateral versus unilateral research designs in animal models for cartilage tissue engineering.

    Science.gov (United States)

    Orth, Patrick; Zurakowski, David; Alini, Mauro; Cucchiarini, Magali; Madry, Henning

    2013-11-01

    Advanced tissue engineering approaches for articular cartilage repair in the knee joint rely on translational animal models. In these investigations, cartilage defects may be established either in one joint (unilateral design) or in both joints of the same animal (bilateral design). We hypothesized that a lower intraindividual variability following the bilateral strategy would reduce the number of required joints. Standardized osteochondral defects were created in the trochlear groove of 18 rabbits. In 12 animals, defects were produced unilaterally (unilateral design; n=12 defects), while defects were created bilaterally in 6 animals (bilateral design; n=12 defects). After 3 weeks, osteochondral repair was evaluated histologically applying an established grading system. Based on intra- and interindividual variabilities, required sample sizes for the detection of discrete differences in the histological score were determined for both study designs (α=0.05, β=0.20). Coefficients of variation (%CV) of the total histological score values were 1.9-fold increased following the unilateral design when compared with the bilateral approach (26 versus 14%CV). The resulting numbers of joints needed to treat were always higher for the unilateral design, resulting in an up to 3.9-fold increase in the required number of experimental animals. This effect was most pronounced for the detection of small-effect sizes and estimating large standard deviations. The data underline the possible benefit of bilateral study designs for the decrease of sample size requirements for certain investigations in articular cartilage research. These findings might also be transferred to other scoring systems, defect types, or translational animal models in the field of cartilage tissue engineering.

  10. Rehabilitation after Articular Cartilage Repair of the Knee in the Football (Soccer) Player

    OpenAIRE

    Hambly, Karen; Silvers, Holly Jacinda; Steinwachs, Matthias

    2012-01-01

    BACKGROUND\\ud \\ud Participation in football can put both male and female players at an increased risk for knee osteoarthritis. There is a higher prevalence of focal chondral defects in the knee of athletes compared to nonathletes. The management of chondral defects in the football player is complex and multifactorial.\\ud \\ud OBJECTIVE\\ud \\ud The aim of this study is to provide an overview of the current strategies for rehabilitation after articular cartilage repair of the knee in the football...

  11. Autologous Bone Marrow Concentrate in a Sheep Model of Osteoarthritis: New Perspectives for Cartilage and Meniscus Repair.

    Science.gov (United States)

    Desando, Giovanna; Giavaresi, Gianluca; Cavallo, Carola; Bartolotti, Isabella; Sartoni, Federica; Nicoli Aldini, Nicolò; Martini, Lucia; Parrilli, Annapaola; Mariani, Erminia; Fini, Milena; Grigolo, Brunella

    2016-06-01

    Cell-based therapies are becoming a valuable tool to treat osteoarthritis (OA). This study investigated and compared the regenerative potential of bone marrow concentrate (BMC) and mesenchymal stem cells (MSC), both engineered with Hyaff(®)-11 (HA) for OA treatment in a sheep model. OA was induced via unilateral medial meniscectomy. Bone marrow was aspirated from the iliac crest, followed by concentration processes or cell isolation and expansion to obtain BMC and MSC, respectively. Treatments consisted of autologous BMC and MSC seeded onto HA. The regenerative potential of bone, cartilage, menisci, and synovia was monitored using macroscopy, histology, immunohistochemistry, and micro-computed tomography at 12 weeks post-op. Data were analyzed using the general linear model with adjusted Sidak's multiple comparison and Spearman's tests. BMC-HA treatment showed a greater repair ability in inhibiting OA progression compared to MSC-HA, leading to a reduction of inflammation in cartilage, meniscus, and synovium. Indeed, the decrease of inflammation positively contributed to counteract the progression of fibrotic and hypertrophic processes, known to be involved in tissue failure. Moreover, the treatment with BMC-HA showed the best results in allowing meniscus regeneration. Minor healing effects were noticed at bone level for both cell strategies; however, a downregulation of subchondral bone thickness (Cs.Th) was found in both cell treatments compared to the OA group in the femur. The transplantation of BMC-HA provided the best effects in supporting regenerative processes in cartilage, meniscus, and synovium and at less extent in bone. On the whole, both MSC and BMC combined with HA reduced inflammation and contributed to switch off fibrotic and hypertrophic processes. The observed regenerative potential by BMC-HA on meniscus could open new perspectives, suggesting its use not only for OA care but also for the treatment of meniscal lesions, even if further analyses are

  12. In situ repair of bone and cartilage defects using 3D scanning and 3D printing

    OpenAIRE

    Li, Lan; Yu, Fei; Shi, Jianping; Shen, Sheng; Teng, Huajian; Yang, Jiquan; Wang, Xingsong; Jiang, Qing

    2017-01-01

    Three-dimensional (3D) printing is a rapidly emerging technology that promises to transform tissue engineering into a commercially successful biomedical industry. However, the use of robotic bioprinters alone is not sufficient for disease treatment. This study aimed to report the combined application of 3D scanning and 3D printing for treating bone and cartilage defects. Three different kinds of defect models were created to mimic three orthopedic diseases: large segmental defects of long bon...

  13. Tissue repair capacity and repair kinetics deduced from multifractionated or continuous irradiation regimens with incomplete repair

    International Nuclear Information System (INIS)

    Thames, H.D. Jr.; Peters, L.J.

    1984-01-01

    A model is proposed for cell survival after multiple doses, when the interfraction interval is insufficient for complete Elkind repair. In the limit of ever-increasing number of ever-smaller fractional doses, the model transforms into the accumulation model of survival after continuous irradiation. When adapted to describe tissue responses to isoeffective multifractionated regimens, wherein repair is incomplete, a generalization of the usually linear plot of reciprocal total dose versus dose per fraction is obtained, in which downward curvature is evident. There is an advantage in studying tissue responses to multifractionated regimens with incomplete repair in the interfraction intervals, or continuous exposures at various dose rates since, in addition to determination of repair capacity, there is an estimate of repair kinetics. Results of analyses of previously published data are presented as illustration. Estimated from the response of three acutely responding normal tissues in the mouse (jejunum, colon and bone marrow), repair halftimes ranged from 0.3-0.9 h and values of β/delta were approximately 0.1 Gy -1 . From the response of mouse lung (LD50 for pneumonitis) to multifractionated regimens with incomplete repair, the repair halftime was estimated at 1.5 h and β/delta was 0.27 Gy -1 . In the rat spinal cord β/delta was 0.7 Gy -1 and Tsub(1/2) was 1.5 h. (U.K.)

  14. Cell factory-derived bioactive molecules with polymeric cryogel scaffold enhance the repair of subchondral cartilage defect in rabbits.

    Science.gov (United States)

    Gupta, Ankur; Bhat, Sumrita; Chaudhari, Bhushan P; Gupta, Kailash C; Tägil, Magnus; Zheng, Ming Hao; Kumar, Ashok; Lidgren, Lars

    2017-06-01

    We have explored the potential of cell factory-derived bioactive molecules, isolated from conditioned media of primary goat chondrocytes, for the repair of subchondral cartilage defects. Enzyme-linked immunosorbent assay (ELISA) confirms the presence of transforming growth factor-β1 in an isolated protein fraction (12.56 ± 1.15 ng/mg protein fraction). These bioactive molecules were used alone or with chitosan-agarose-gelatin cryogel scaffolds, with and without chondrocytes, to check whether combined approaches further enhance cartilage repair. To evaluate this, an in vivo study was conducted on New Zealand rabbits in which a subchondral defect (4.5 mm wide × 4.5 mm deep) was surgically created. Starting after the operation, bioactive molecules were injected at the defect site at regular intervals of 14 days. Histopathological analysis showed that rabbits treated with bioactive molecules alone had cartilage regeneration after 4 weeks. However, rabbits treated with bioactive molecules along with scaffolds, with or without cells, showed cartilage formation after 3 weeks; 6 weeks after surgery, the cartilage regenerated in rabbits treated with either bioactive molecules alone or in combinations showed morphological similarities to native cartilage. No systemic cytotoxicity or inflammatory response was induced by any of the treatments. Further, ELISA was done to determine systemic toxicity, which showed no difference in concentration of tumour necrosis factor-α in blood serum, before or after surgery. In conclusion, intra-articular injection with bioactive molecules alone may be used for the repair of subchondral cartilage defects, and bioactive molecules along with chondrocyte-seeded scaffolds further enhance the repair. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Numerical Simulation of Mass Transfer and Three-Dimensional Fabrication of Tissue-Engineered Cartilages Based on Chitosan/Gelatin Hybrid Hydrogel Scaffold in a Rotating Bioreactor.

    Science.gov (United States)

    Zhu, Yanxia; Song, Kedong; Jiang, Siyu; Chen, Jinglian; Tang, Lingzhi; Li, Siyuan; Fan, Jiangli; Wang, Yiwei; Zhao, Jiaquan; Liu, Tianqing

    2017-01-01

    Cartilage tissue engineering is believed to provide effective cartilage repair post-injuries or diseases. Biomedical materials play a key role in achieving successful culture and fabrication of cartilage. The physical properties of a chitosan/gelatin hybrid hydrogel scaffold make it an ideal cartilage biomimetic material. In this study, a chitosan/gelatin hybrid hydrogel was chosen to fabricate a tissue-engineered cartilage in vitro by inoculating human adipose-derived stem cells (ADSCs) at both dynamic and traditional static culture conditions. A bioreactor that provides a dynamic culture condition has received greater applications in tissue engineering due to its optimal mass transfer efficiency and its ability to simulate an equivalent physical environment compared to human body. In this study, prior to cell-scaffold fabrication experiment, mathematical simulations were confirmed with a mass transfer of glucose and TGF-β2 both in rotating wall vessel bioreactor (RWVB) and static culture conditions in early stage of culture via computational fluid dynamic (CFD) method. To further investigate the feasibility of the mass transfer efficiency of the bioreactor, this RWVB was adopted to fabricate three-dimensional cell-hydrogel cartilage constructs in a dynamic environment. The results showed that the mass transfer efficiency of RWVB was faster in achieving a final equilibrium compared to culture in static culture conditions. ADSCs culturing in RWVB expanded three times more compared to that in static condition over 10 days. Induced cell cultivation in a dynamic RWVB showed extensive expression of extracellular matrix, while the cell distribution was found much more uniformly distributing with full infiltration of extracellular matrix inside the porous scaffold. The increased mass transfer efficiency of glucose and TGF-β2 from RWVB promoted cellular proliferation and chondrogenic differentiation of ADSCs inside chitosan/gelatin hybrid hydrogel scaffolds. The

  16. Tissue Engineering Based Therapy for Articular Cartilage Defects - A New Approach

    Directory of Open Access Journals (Sweden)

    Abraham S

    2007-01-01

    Full Text Available Background: Articular cartilage, the load-bearing tissue in diarthrodial joints, when damaged due to trauma could lead to osteoarthritis. At present Autologous Cartilage Implantation is an established method in which patients own chondrocytes are isolated and then implanted after in vitro expansion over the affected area with bovine or porcine collagen matrix. This procedure results in more of Collagen Type I during in vitro expansion, which eventually becomes fibrocartilage. Also it requires growth factors. We have in this study tried growing human Chondrocytes without growth factors using synthetic scaffolds to grow more Collagen Type II Materials and Methods: Human cartilage specimens were harvested through arthroscopy from the non-weight bearing area of the knee joint from 13 patients who underwent surgical procedures of the knee joint after getting their informed consent. The tissues were transported in saline taking 1 hour to laboratory and subjected to digestion with Collagenase type II for 16~18 Hrs. The chondrocyte cells obtained after dissociation were divided into two groups for culture. Gr. I were embedded in a Thermogelation polymer (TGP and Gr. II in basal culture media (DMEM + Ascorbic Acid without using any growth factors. The Group II cells were viable only for 4 weeks and then started degenerating. The TGP-Chondrocytes scaffolds were grown for 16 weeks and the specimens were harvested at 4, 8, 12 and 16-week intervals and their morphology and molecular characteristics were studied by H&E staining, S-100 protein analysis and RT-PCR.Results: Human chondrocytes could be cultured in both TGP (group I and Basal culture media (group II. The Gr. I cells were viable upto the 16th week while the Group II chondrocytes started degenerating after the 4 week. Both the groups were proven positive for S-100 protein, a Chondrocyte specific marker protein; Gr. II specimens after 4 weeks, and Gr. I specimens after 4, 8, 12 and 16 weeks. RT

  17. 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.

  18. The formation of human auricular cartilage from microtic tissue: An in vivo study.

    Science.gov (United States)

    Ishak, Mohamad Fikeri bin; See, Goh Bee; Hui, Chua Kien; Abdullah, Asma bt; Saim, Lokman bin; Saim, Aminuddin bin; Idrus, Ruszymah bt Haji

    2015-10-01

    This study aimed to isolate, culture-expand and characterize the chondrocytes isolated from microtic cartilage and evaluate its potential as a cell source for ear cartilage reconstruction. Specific attention was to construct the auricular cartilage tissue by using fibrin as scaffold. Cell culture experiment with the use of microtic chondrocytes. Cell culture experiment with the use of microtic chondrocytes. After ear reconstructive surgery at the Universiti Kebangsaan Malaysia Medical Center, chondrocytes were isolated from microtic cartilage. Chondrocytes isolated from the tissue were cultured expanded until passage 4 (P4). Upon confluency at P4, chondrocytes were harvested and tissue engineered constructs were made with human plasma polymerized to fibrin. Constructs formed later is implanted at the dorsal part of nude mice for 8 weeks, followed by post-implantation evaluation with histology staining (Hematoxylin and Eosin (H&E) and Safranin O), immunohistochemistry and RT-PCR for chondrogenic associated genes expression level. Under gross assessment, the construct after 8 weeks of implantation showed similar physical characteristics that of cartilage. Histological staining showed abundant lacunae cells embedded in extracellular matrix similar to that of native cartilage. Safranin O staining showed positive staining which indicates the presence of proteoglycan-rich matrix. Immunohistochemistry analysis showed the strong positive staining for collagen type II, the specific collagen type in the cartilage. Gene expression quantification showed no significant differences in the expression of chondrogenic gene used which is collagen type I, collagen type II, aggrecan core protein (ACP), elastin and sox9 genes when compared to construct formed from normal auricular tissue. Chondrocytes isolated from microtia cartilage has the potential to be used as an alternative cell source for external ear reconstruction in future clinical application. Copyright © 2015 Elsevier

  19. USE OF GENETICALLY MODIFIED MUSCLE AND FAT GRAFTS TO REPAIR DEFECTS IN BONE AND CARTILAGE

    Science.gov (United States)

    Evans, C.H.; Liu, F.-J.; Glatt, V.; Hoyland, J.A.; Kirker-Head, C.; Walsh, A.; Betz, O.; Wells, J.W.; Betz, V.; Porter, R.M.; Saad, F.A.; Gerstenfeld, L.C.; Einhorn, T.A.; Harris, M.B.; Vrahas, M.S.

    2015-01-01

    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. PMID:20073015

  20. High resolution MRI imaging at 9.4 Tesla of the osteochondral unit in a translational model of articular cartilage repair.

    Science.gov (United States)

    Goebel, Lars; Müller, Andreas; Bücker, Arno; Madry, Henning

    2015-04-16

    Non-destructive structural evaluation of the osteochondral unit is challenging. Here, the capability of high-field magnetic resonance imaging (μMRI) at 9.4 Tesla (T) was explored to examine osteochondral repair ex vivo in a preclinical large animal model. A specific aim of this study was to detect recently described alterations of the subchondral bone associated with cartilage repair. Osteochondral samples of medial femoral condyles from adult ewes containing full-thickness articular cartilage defects treated with marrow stimulation were obtained after 6 month in vivo and scanned in a 9.4 T μMRI. Ex vivo imaging of small osteochondral samples (typical volume: 1-2 cm(3)) at μMRI was optimised by variation of repetition time (TR), time echo (TE), flip angle (FA), spatial resolution and number of excitations (NEX) from standard MultiSliceMultiEcho (MSME) and three-dimensional (3D) spoiled GradientEcho (SGE) sequences. A 3D SGE sequence with the parameters: TR = 10 ms, TE = 3 ms, FA = 10°, voxel size = 120 × 120 × 120 μm(3) and NEX = 10 resulted in the best fitting for sample size, image quality, scanning time and artifacts. An isovolumetric voxel shape allowed for multiplanar reconstructions. Within the osteochondral unit articular cartilage, cartilaginous repair tissue and bone marrow could clearly be distinguished from the subchondral bone plate and subarticular spongiosa. Specific alterations of the osteochondral unit associated with cartilage repair such as persistent drill holes, subchondral bone cysts, sclerosis of the subchondral bone plate and of the subarticular spongiosa and intralesional osteophytes were precisely detected. High resolution, non-destructive ex vivo analysis of the entire osteochondral unit in a preclinical large animal model that is sufficient for further analyses is possible using μMRI at 9.4 T. In particular, 9.4 T is capable of accurately depicting alterations of the subchondral bone that are associated with

  1. Adipokines induce catabolism of newly synthesized matrix in cartilage and meniscus tissues.

    Science.gov (United States)

    Nishimuta, James F; Levenston, Marc E

    Altered synovial levels of various adipokines (factors secreted by fat as well as other tissues) have been associated with osteoarthritis (OA) onset and progression. However, the metabolic effects of adipokines on joint tissues, in particular the fibrocartilaginous menisci, are not well understood. This study investigated effects of several adipokines on release of recently synthesized extracellular matrix in bovine cartilage and meniscus tissue explants. After labeling newly synthesized proteins and sulfated glycosaminoglycans (sGAGs) with 3 H-proline and 35 S-sulfate, respectively; bovine cartilage and meniscus tissue explants were cultured for 6 days in basal medium (control) or media supplemented with adipokines (1 µg/ml of leptin, visfatin, adiponectin, or resistin) or 20 ng/ml interleukin-1 (IL-1). Release of radiolabel and sGAG to the media during culture and the final explant water, DNA, sGAG, and retained radiolabel were measured. Matrix metalloproteinase (MMP-2) and MMP-3 activities were assessed using gelatin and casein zymography, respectively. Water and DNA contents were not significantly altered by any treatment. Visfatin, adiponectin, resistin, and IL-1 stimulated sGAG release from meniscus, whereas only IL-1 stimulated sGAG release from cartilage. Release of 3 H and 35 S was stimulated not only by resistin and IL-1 in meniscus but also by IL-1 in cartilage. Retained 3 H was unaltered by any treatment, while retained 35 S was reduced by visfatin, resistin, and IL-1 in meniscus and by only IL-1 in cartilage. Resistin and IL-1 elevated active MMP-2 and total MMP-3 in meniscus, whereas cartilage MMP-3 activity was elevated by only IL-1. Resistin stimulated rapid and extensive catabolism of meniscus tissue, similar to IL-1, whereas adipokines minimally affected cartilage. Release of newly synthesized matrix was similar to overall release in both tissues. These observations provide further indications that meniscal tissue is more sensitive to pro

  2. 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.

  3. Mesenchymal Stem Cells in Tissue Repair

    Directory of Open Access Journals (Sweden)

    Amy M DiMarino

    2013-09-01

    Full Text Available The advent of mesenchymal stem cell (MSC based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage and subsequent regeneration and repair. Application-based ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the preparation as well as quality control (QC and quality assurance (QA are only as good as the assays that are developed. In vivo measures of efficacy and potency require an appreciation of the overall pathophysiology of the model and standardization of outcome measures. The new concepts of how MSC’s participate in the tissue regeneration and wound repair process and further, how this is impacted by estimates of efficacy and potency Are important new topics. In this regard,,, this chapter will review some of the in vitro and in vivo assays for MSC function and activity and their application to the clinical arena.

  4. 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.

  5. Mechanical Characterization of Tissue-Engineered Cartilage Using Microscopic Magnetic Resonance Elastography

    Science.gov (United States)

    Yin, Ziying; Schmid, Thomas M.; Yasar, Temel K.; Liu, Yifei; Royston, Thomas J.

    2014-01-01

    Knowledge of mechanical properties of tissue-engineered cartilage is essential for the optimization of cartilage tissue engineering strategies. Microscopic magnetic resonance elastography (μMRE) is a recently developed MR-based technique that can nondestructively visualize shear wave motion. From the observed wave pattern in MR phase images the tissue mechanical properties (e.g., shear modulus or stiffness) can be extracted. For quantification of the dynamic shear properties of small and stiff tissue-engineered cartilage, μMRE needs to be performed at frequencies in the kilohertz range. However, at frequencies greater than 1 kHz shear waves are rapidly attenuated in soft tissues. In this study μMRE, with geometric focusing, was used to overcome the rapid wave attenuation at high frequencies, enabling the measurement of the shear modulus of tissue-engineered cartilage. This methodology was first tested at a frequency of 5 kHz using a model system composed of alginate beads embedded in agarose, and then applied to evaluate extracellular matrix development in a chondrocyte pellet over a 3-week culture period. The shear stiffness in the pellet was found to increase over time (from 6.4 to 16.4 kPa), and the increase was correlated with both the proteoglycan content and the collagen content of the chondrocyte pellets (R2=0.776 and 0.724, respectively). Our study demonstrates that μMRE when performed with geometric focusing can be used to calculate and map the shear properties within tissue-engineered cartilage during its development. PMID:24266395

  6. A Novel Through-Thickness Perfusion Bioreactor for the Generation of Scaffold-Free Tissue Engineered Cartilage

    Directory of Open Access Journals (Sweden)

    Eric Gilbert

    2014-08-01

    Full Text Available The objective of this study was to characterize our designed through-thickness perfusion bioreactor which could generate large scaffold-free tissue engineered cartilage constructs. The hypothesis being that through-thickness perfusion could accelerate maturation of scaffold-free tissue engineered cartilage, grown in transwell culture inserts large enough to repair typical size chondral lesions in the human knee. Internal cell culture media temperature and pH were examined over time, upon implementation of the bioreactor perfusion system inside a CO2 incubator, to ensure adequate regulation conducive to cell viability. Results indicate that temperature and pH both equilibrate within approximately 3 h. The bioreactor was tested for its efficacy to support formation of 4.5 cm2 constructs by porcine neonatal chondrocytes. Tests were conducted under three conditions: immediate perfusion with flow from bottom to top, immediate perfusion with media flow from top to bottom, and bottom to top perfusion after four weeks of static culture, giving the cells time to self-aggregate into a consolidated construct prior to perfusion. The best cell culture results were obtained when perfusion was delayed for four weeks relative to the immediate perfusion of the other methods, and this should be further investigated.

  7. 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

    2016-02-06

    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.

  8. Bio-inspired design of a magnetically active trilayered scaffold for cartilage tissue engineering.

    Science.gov (United States)

    Brady, Mariea A; Talvard, Lucien; Vella, Alain; Ethier, C Ross

    2017-04-01

    An important topic in cartilage tissue engineering is the development of biomimetic scaffolds which mimic the depth-dependent material properties of the native tissue. We describe an advanced trilayered nanocomposite hydrogel (ferrogel) with a gradient in compressive modulus from the top to the bottom layers (p elastic, depth-dependent strain gradient. When bovine chondrocytes were seeded into the ferrogels and cultured for up to 14 days, there was good cell viability and a biochemical gradient was measured with sulphated glycosaminoglycan increasing with depth from the surface. This novel construct provides tremendous scope for tailoring location-specific cartilage replacement tissue; by varying the density of magnetic nanoparticles, concentration of base hydrogel and number of cells, physiologically relevant depth-dependent gradients may be attained. © 2015 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. © 2015 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

  9. Recent advances on gradient hydrogels in biomimetic cartilage tissue engineering [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Ivana Gadjanski

    2017-12-01

    Full Text Available Articular cartilage (AC is a seemingly simple tissue that has only one type of constituting cell and no blood vessels and nerves. In the early days of tissue engineering, cartilage appeared to be an easy and promising target for reconstruction and this was especially motivating because of widespread AC pathologies such as osteoarthritis and frequent sports-induced injuries. However, AC has proven to be anything but simple. Recreating the varying properties of its zonal structure is a challenge that has not yet been fully answered. This caused the shift in tissue engineering strategies toward bioinspired or biomimetic approaches that attempt to mimic and simulate as much as possible the structure and function of the native tissues. Hydrogels, particularly gradient hydrogels, have shown great potential as components of the biomimetic engineering of the cartilaginous tissue.

  10. Tissue expansion in burn sequelae repair.

    Science.gov (United States)

    Tavares Filho, João Medeiros; Belerique, Manoel; Franco, Diogo; Porchat, Carlos Alberto; Franco, Talita

    2007-03-01

    Burns may cause emotional, aesthetic and functional sequelae. Extended or hypertrophic scars are usually difficult to repair using local tissues, and the use of skin grafts may cause further injuries to the donor sites. The use of tissue expanders may offer a better option in the treatment of burn sequelae. This is a report on our experience using tissue expanders in 54 cases (23 patients) of burn sequelae located in different anatomical areas. Fourteen of the patients were female and nine male ranging in age between 5 and 48. The expanders were placed in the subgaleal, submuscular, subfascial or subcutaneous planes. Skin expansion was completed in 50 cases (92.5%). The injured area was removed by advancement flaps in 44 cases and by transposition flaps in 6 of them. Primary expansion was performed in 42 cases and reexpansion in 12. The rate of complications was 24.07%, of which 30.8% were considered to be absolute and 69.2% relative. Tissue expansion is an excellent option for burn sequelae treatment because it provides skin of similar local characteristics and does not damage the donor site. The procedure can be repeated in the event of major sequelae (reexpansion).

  11. Association between expression of the bone morphogenetic proteins 2 and 7 in the repair of circumscribed cartilage lesions with clinical outcome

    DEFF Research Database (Denmark)

    Schmal, Hagen; Niemeyer, Philipp; Zwingmann, Jörn

    2010-01-01

    BACKGROUND: Although there is much known about the role of BMPs in cartilage metabolism reliable data about the in vivo regulation in natural and surgically induced cartilage repair are still missing. METHODS: Lavage fluids of knee joints of 47 patients were collected during surgical therapy. 5...

  12. Autologous osteochondral mosaicplasty or TruFit plugs for cartilage repair.

    Science.gov (United States)

    Hindle, Paul; Hendry, Jane L; Keating, John F; Biant, Leela C

    2014-06-01

    Autologous osteochondral mosaicplasty and TruFit Bone graft substitute plugs are methods used to repair symptomatic articular cartilage defects in the adult knee. There have been no comparative studies of the two techniques. This retrospective study assessed functional outcome of patients using the EQ-5D, Knee Injury and Osteoarthritis Outcome Score (KOOS) and Modified Cincinnati scores at follow-up of 1-5 years. There were 66 patients in the study (35 TruFit and 31 Mosaicplasty): 44 males and 22 females with a mean age of 37.3 years (SD 12.6). The mean BMI was 26.8. Thirty-six articular cartilage lesions were due to trauma, twenty-six due to osteochondritis dissecans and three due to non-specific degenerative change or unknown. There was no difference between the two groups age (n.s.), sex (n.s.), BMI (n.s.), defect location (n.s.) or aetiology (n.s.). The median follow-up was 22 months for the TruFit cohort and 30 months for the mosaicplasty group. There was no significant difference in the requirement for re-operation (n.s). Patients undergoing autologous mosaicplasty had a higher rate of returning to sport (p = 0.006), lower EQ-5D pain scores (p = 0.048) and higher KOOS activities of daily living (p = 0.029) scores. Sub-group analysis showed no difference related to the number of cases the surgeon performed. Patients requiring re-operation had lower outcome scores regardless of their initial procedure. This study demonstrated significantly better outcomes using two validated outcome scores (KOOS, EQ-5D), and an ability to return to sport in those undergoing autologous mosaicplasty compared to those receiving TruFit plugs. IV.

  13. Biomimetically Reinforced Polyvinyl Alcohol-Based Hybrid Scaffolds for Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Hwan D. Kim

    2017-11-01

    Full Text Available Articular cartilage has a very limited regeneration capacity. Therefore, injury or degeneration of articular cartilage results in an inferior mechanical stability, load-bearing capacity, and lubrication capability. Here, we developed a biomimetic scaffold consisting of macroporous polyvinyl alcohol (PVA sponges as a platform material for the incorporation of cell-embedded photocrosslinkable poly(ethylene glycol diacrylate (PEGDA, PEGDA-methacrylated chondroitin sulfate (PEGDA-MeCS; PCS, or PEGDA-methacrylated hyaluronic acid (PEGDA-MeHA; PHA within its pores to improve in vitro chondrocyte functions and subsequent in vivo ectopic cartilage tissue formation. Our findings demonstrated that chondrocytes encapsulated in PCS or PHA and loaded into macroporous PVA hybrid scaffolds maintained their physiological phenotypes during in vitro culture, as shown by the upregulation of various chondrogenic genes. Further, the cell-secreted extracellular matrix (ECM improved the mechanical properties of the PVA-PCS and PVA-PHA hybrid scaffolds by 83.30% and 73.76%, respectively, compared to their acellular counterparts. After subcutaneous transplantation in vivo, chondrocytes on both PVA-PCS and PVA-PHA hybrid scaffolds significantly promoted ectopic cartilage tissue formation, which was confirmed by detecting cells positively stained with Safranin-O and for type II collagen. Consequently, the mechanical properties of the hybrid scaffolds were biomimetically reinforced by 80.53% and 210.74%, respectively, compared to their acellular counterparts. By enabling the recapitulation of biomimetically relevant structural and functional properties of articular cartilage and the regulation of in vivo mechanical reinforcement mediated by cell–matrix interactions, this biomimetic material offers an opportunity to control the desired mechanical properties of cell-laden scaffolds for cartilage tissue regeneration.

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

    OpenAIRE

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

    2016-01-01

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

  15. 3D Printing and Electrospinning of Composite Hydrogels for Cartilage and Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Arianna De Mori

    2018-03-01

    Full Text Available Injuries of bone and cartilage constitute important health issues costing the National Health Service billions of pounds annually, in the UK only. Moreover, these damages can become cause of disability and loss of function for the patients with associated social costs and diminished quality of life. The biomechanical properties of these two tissues are massively different from each other and they are not uniform within the same tissue due to the specific anatomic location and function. In this perspective, tissue engineering (TE has emerged as a promising approach to address the complexities associated with bone and cartilage regeneration. Tissue engineering aims at developing temporary three-dimensional multicomponent constructs to promote the natural healing process. Biomaterials, such as hydrogels, are currently extensively studied for their ability to reproduce both the ideal 3D extracellular environment for tissue growth and to have adequate mechanical properties for load bearing. This review will focus on the use of two manufacturing techniques, namely electrospinning and 3D printing, that present promise in the fabrication of complex composite gels for cartilage and bone tissue engineering applications.

  16. Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells: From In Vitro Optimization to a First‐in‐Human Study

    Science.gov (United States)

    Whitehouse, Michael R.; Howells, Nicholas R.; Parry, Michael C.; Austin, Eric; Kafienah, Wael; Brady, Kyla; Goodship, Allen E.; Eldridge, Jonathan D.; Blom, Ashley W.

    2016-01-01

    Abstract Meniscal cartilage tears are common and predispose to osteoarthritis (OA). Most occur in the avascular portion of the meniscus where current repair techniques usually fail. We described previously the use of undifferentiated autologous mesenchymal stem cells (MSCs) seeded onto a collagen scaffold (MSC/collagen‐scaffold) to integrate meniscal tissues in vitro. Our objective was to translate this method into a cell therapy for patients with torn meniscus, with the long‐term goal of delaying or preventing the onset of OA. After in vitro optimization, we tested an ovine‐MSC/collagen‐scaffold in a sheep meniscal cartilage tear model with promising results after 13 weeks, although repair was not sustained over 6 months. We then conducted a single center, prospective, open‐label first‐in‐human safety study of patients with an avascular meniscal tear. Autologous MSCs were isolated from an iliac crest bone marrow biopsy, expanded and seeded into the collagen scaffold. The resulting human‐MSC/collagen‐scaffold implant was placed into the meniscal tear prior to repair with vertical mattress sutures and the patients were followed for 2 years. Five patients were treated and there was significant clinical improvement on repeated measures analysis. Three were asymptomatic at 24 months with no magnetic resonance imaging evidence of recurrent tear and clinical improvement in knee function scores. Two required subsequent meniscectomy due to retear or nonhealing of the meniscal tear at approximately 15 months after implantation. No other adverse events occurred. We conclude that undifferentiated MSCs could provide a safe way to augment avascular meniscal repair in some patients. Registration: EU Clinical Trials Register, 2010‐024162‐22. Stem Cells Translational Medicine 2017;6:1237–1248 PMID:28186682

  17. 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.

    Science.gov (United States)

    Tao, Hongyue; Shang, Xiliang; Lu, Rong; Li, Hong; Hua, Yinghui; Feng, Xiaoyuan; Chen, Shuang

    2014-08-01

    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. • Patients with unstable ankle OCD had satisfactory clinical outcome after MF. • Quantitative MRI correlates with clinical outcome after MF for ankle OCD. • The reduction of subchondral BME will improve the patient's clinical outcome. • Quantitative MRI can monitor the process of cartilage repair over time.

  18. Optical projection tomography can be used to investigate spatial distribution of chondrocytes in three-dimensional biomaterial scaffolds for cartilage tissue engineering.

    Science.gov (United States)

    Järvinen, Elina; Muhonen, Virpi; Haaparanta, Anne-Marie; Kellomäki, Minna; Kiviranta, Ilkka

    2014-01-01

    Biomaterial scaffolds have been used in autologous chondrocyte implantation to facilitate the repair of large lesions and to advance the formation of articular cartilage [Exp. Biol. Med. (Maywood) 237(1) (2012), 10-17]. Biomaterial scaffolds are usually three-dimensional (3-D) porous structures consisting of biodegradable materials to support articular cartilage formation. Adequate porosity of the scaffold is necessary for uniform cell distribution and cell attachment, and the density of the cells in the scaffold should be appropriate for cartilage formation [Cartilage 3(2) (2012), 108-117]. There have been only a restricted number of studies on the spatial distribution of cells in scaffolds, and on the role of this to cartilage formation [J. Biotechnol. 129 (2007), 516-531; Biotechnol. Progr. 14 (1998), 193-202; Biotechnol. Bioeng. 84 (2003), 205-214]. This may be due to the limited availability of appropriate visualization methods. Acquiring 3-D images throughout the scaffold by histology or confocal methods are not applicable to all types of scaffolds, and moreover, they are time consuming, laborious and thus not very feasible for a large scale analysis. To make the visualization of the spatial distribution of the cells easier in biomaterial scaffolds we have applied optical projection tomography (OPT). OPT microscope produces high-resolution 3-D images of both fluorescent and non-fluorescent specimens [Science 296(5567) (2002), 541-545]. Here we demonstrate that the OPT method can be used for the evaluation and visualization of the cell seeding method, spatial distribution and density of cells in biomaterial scaffolds and thus establish the OPT as a valid tool for analysis of cell distribution in cartilage tissue engineering samples.

  19. [Experimental study on collagen hydrogel scaffolds for cartilage tissue engineering].

    Science.gov (United States)

    Li, Kuifeng; Guo, Likun; Fan, Yujiang; Zhang, Xingdong

    2012-11-01

    /mL, showing significant differences among 3 groups (P < 0.05). Increasing the concentration of collagen hydrogels leads to better mechanical properties and higher shrink-resistance, but it may induce the up-regulation of cartilage fibrosis and hypertrophy related gene expression.

  20. Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles.

    Science.gov (United States)

    Yin, Heyong; Wang, Yu; Sun, Zhen; Sun, Xun; Xu, Yichi; Li, Pan; Meng, Haoye; Yu, Xiaoming; Xiao, Bo; Fan, Tian; Wang, Yiguo; Xu, Wenjing; Wang, Aiyuan; Guo, Quanyi; Peng, Jiang; Lu, Shibi

    2016-03-01

    We propose a method of preparing a novel cell carrier derived from natural cartilage extracellular matrix (ECM), designated cartilage ECM-derived particles (CEDPs). Through a series of processes involving pulverization, sieving, and decellularization, fresh cartilage was made into CEDPs with a median diameter of 263 ± 48 μm. Under microgravity culture conditions in a rotary cell culture system (RCCS), bone marrow stromal cells (BMSCs) can proliferate rapidly on the surface of CEDPs with high viability. Histological evaluation and gene expression analysis indicated that BMSCs were differentiated into mature chondrocytes after 21 days of culture without the use of exogenous growth factors. Functional cartilage microtissue aggregates of BMSC-laden CEDPs formed as time in culture increased. Further, the microtissue aggregates were directly implanted into trochlear cartilage defects in a rat model (CEDP+MSC group). Gait analysis and histological results indicated that the CEDP+MSC group obtained better and more rapid joint function recovery and superior cartilage repair compared to the control groups, in which defects were treated with CEDPs alone or only fibrin glue, at both 6 and 12 weeks after surgery. In conclusion, the innovative cell carrier derived from cartilage ECM could promote chondrogenic differentiation of BMSCs, and the direct use of functional cartilage microtissue facilitated cartilage regeneration. This strategy for cell culture, stem cell differentiation and one-step surgery using cartilage microtissue for cartilage repair provides novel prospects for cartilage tissue engineering and may have further broad clinical applications. We proposed a method to prepare a novel cell carrier derived from natural cartilage ECM, termed cartilage ECM-derived particles (CEDPs), which can support proliferation of MSCs and facilitate their chondrogenic differentiation. Further, the direct use of functional cartilage microtissue of MSC-laden CEDP aggregates for

  1. Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair.

    Science.gov (United States)

    Hindle, Paul; Baily, James; Khan, Nusrat; Biant, Leela C; Simpson, A Hamish R; Péault, Bruno

    2016-11-01

    Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti-human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34 - CD45 - CD146 + ) and adventitial cells (CD34 + CD45 - CD146 - ). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair.

  2. Collagen-PVA aligned nanofiber on collagen sponge as bi-layered scaffold for surface cartilage repair.

    Science.gov (United States)

    Lin, Hsin-Yi; Tsai, Wen-Chi; Chang, Shih-Hsing

    2017-05-01

    Researchers have made bi-layered scaffolds but mostly for osteochondral repairs. The anatomic structure of human cartilage has different zones and that each has varying matrix morphology and mechanical properties is often overlooked. Two bi-layered collagen-based composites were made to replicate the superficial and transitional zones of an articular cartilage. Aligned and random collagen-PVA nanofibers were electrospun onto a freeze-dried collagen sponge to make the aligned and random composites, respectively. The morphology, swelling ratio, degradation and tensile properties of the two composites were examined. Primary porcine chondrocytes were cultured on the composites for three weeks and their proliferation and secretion of glycosaminoglycan (GAG) and type II collagen were measured. The influences of the cell culture on the tensile properties of the composites were studied. The nanofiber layer remained adhered to the sponge after three weeks of cell culture. Both composites lost 30-35% of their total weight in a saline buffer after three weeks. The tensile strength and Young's modulus of both composites increased after three weeks of chondrocyte culture (p collagen. They were seen embedded in lacunae after three weeks. The aligned composite may be more suitable for articular cartilage repair because of the higher tensile strength from the aligned nanofibers on the surface that can better resist wear.

  3. Tissue Engineering of Cartilage on Ground-Based Facilities

    DEFF Research Database (Denmark)

    Aleshcheva, Ganna; Bauer, Johann; Hemmersbach, Ruth

    2016-01-01

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

  4. Application of Extrusion-Based Hydrogel Bioprinting for Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Fu You

    2017-07-01

    Full Text Available Extrusion-based bioprinting (EBB is a rapidly developing technique that has made substantial progress in the fabrication of constructs for cartilage tissue engineering (CTE over the past decade. With this technique, cell-laden hydrogels or bio-inks have been extruded onto printing stages, layer-by-layer, to form three-dimensional (3D constructs with varying sizes, shapes, and resolutions. This paper reviews the cell sources and hydrogels that can be used for bio-ink formulations in CTE application. Additionally, this paper discusses the important properties of bio-inks to be applied in the EBB technique, including biocompatibility, printability, as well as mechanical properties. The printability of a bio-ink is associated with the formation of first layer, ink rheological properties, and crosslinking mechanisms. Further, this paper discusses two bioprinting approaches to build up cartilage constructs, i.e., self-supporting hydrogel bioprinting and hybrid bioprinting, along with their applications in fabricating chondral, osteochondral, and zonally organized cartilage regenerative constructs. Lastly, current limitations and future opportunities of EBB in printing cartilage regenerative constructs are reviewed.

  5. Signaling pathways effecting crosstalk between cartilage and adjacent tissues: Seminars in cell and developmental biology: The biology and pathology of cartilage.

    Science.gov (United States)

    Maes, Christa

    2017-02-01

    Endochondral ossification, the mechanism responsible for the development of the long bones, is dependent on an extremely stringent coordination between the processes of chondrocyte maturation in the growth plate, vascular expansion in the surrounding tissues, and osteoblast differentiation and osteogenesis in the perichondrium and the developing bone center. The synchronization of these processes occurring in adjacent tissues is regulated through vigorous crosstalk between chondrocytes, endothelial cells and osteoblast lineage cells. Our knowledge about the molecular constituents of these bidirectional communications is undoubtedly incomplete, but certainly some signaling pathways effective in cartilage have been recognized to play key roles in steering vascularization and osteogenesis in the perichondrial tissues. These include hypoxia-driven signaling pathways, governed by the hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF), which are absolutely essential for the survival and functioning of chondrocytes in the avascular growth plate, at least in part by regulating the oxygenation of developing cartilage through the stimulation of angiogenesis in the surrounding tissues. A second coordinating signal emanating from cartilage and regulating developmental processes in the adjacent perichondrium is Indian Hedgehog (IHH). IHH, produced by pre-hypertrophic and early hypertrophic chondrocytes in the growth plate, induces the differentiation of adjacent perichondrial progenitor cells into osteoblasts, thereby harmonizing the site and time of bone formation with the developmental progression of chondrogenesis. Both signaling pathways represent vital mediators of the tightly organized conversion of avascular cartilage into vascularized and mineralized bone during endochondral ossification. Copyright © 2016. Published by Elsevier Ltd.

  6. Mesenchymal Stem Cells for Treating Articular Cartilage Defects and Osteoarthritis.

    Science.gov (United States)

    Wang, Yu; Yuan, Mei; Guo, Quan-yi; Lu, Shi-bi; Peng, Jiang

    2015-01-01

    Articular cartilage damage and osteoarthritis are the most common joint diseases. Joints are prone to damage caused by sports injuries or aging, and such damage regularly progresses to more serious joint disorders, including osteoarthritis, which is a degenerative disease characterized by the thinning and eventual wearing out of articular cartilage, ultimately leading to joint destruction. Osteoarthritis affects millions of people worldwide. Current approaches to repair of articular cartilage damage include mosaicplasty, microfracture, and injection of autologous chondrocytes. These treatments relieve pain and improve joint function, but the long-term results are unsatisfactory. The long-term success of cartilage repair depends on development of regenerative methodologies that restore articular cartilage to a near-native state. Two promising approaches are (i) implantation of engineered constructs of mesenchymal stem cell (MSC)-seeded scaffolds, and (ii) delivery of an appropriate population of MSCs by direct intra-articular injection. MSCs may be used as trophic producers of bioactive factors initiating regenerative activities in a defective joint. Current challenges in MSC therapy are the need to overcome current limitations in cartilage cell purity and to in vitro engineer tissue structures exhibiting the required biomechanical properties. This review outlines the current status of MSCs used in cartilage tissue engineering and in cell therapy seeking to repair articular cartilage defects and related problems. MSC-based technologies show promise when used to repair cartilage defects in joints.

  7. Immunohistochemical detection of interstitial collagens in bone and cartilage tissue remnants in an infant Peruvian mummy.

    Science.gov (United States)

    Nerlich, A G; Parsche, F; Kirsch, T; Wiest, I; von der Mark, K

    1993-07-01

    We investigated the immunohistochemical presence of various collagen types in bone and cartilage tissue from an infant Peruvian mummy dating between 500 and 1000 A.D. which had been excavated at the necropolis of Las Trancas in the Nazca region in Peru. Following careful rehydration and decalcification of the tissue, the mummy tissue showed morphologically good preservation of the matrix, which could be shown to be composed of various collagen types in a typical pattern. Bone consisted of a collagen I matrix with a small rim of collagen III and V at the endosteal lining and a pericellular collagen V staining around osteocytic holes. In the hypertrophic cartilage of the epiphyseal growth plate, a typical pattern of collagen types II and X could be found. These observations provide evidence that in well-preserved mummy tissue the antigenic determinants of major matrix components are still adequately preserved for an immunohistochemical analysis. This technique may thus be a very helpful tool for the analysis of pathologic processes of historic bone tissue. It may also allow in certain circumstances a distinction between pseudopathologic tissue destruction and pathologic tissue alteration.

  8. Scaffold-free cartilage tissue engineering with a small population of human nasoseptal chondrocytes.

    Science.gov (United States)

    Chiu, Loraine L Y; To, William T H; Lee, John M; Waldman, Stephen D

    2017-03-01

    Cartilage tissue engineering is a promising approach to provide suitable materials for nasal reconstruction; however, it typically requires large numbers of cells. We have previously shown that a small number of chondrocytes cultivated within a continuous flow bioreactor can elicit substantial tissue growth, but translation to human chondrocytes is not trivial. Here, we aimed to demonstrate the application of the bioreactor to generate large-sized tissues from a small population of primary human nasoseptal chondrocytes. Experimental study. Chondrocytes were cultured in the bioreactor using different medium compositions, with varying amounts of serum and with or without growth factors. Resulting engineered tissues were analyzed for physical properties, biochemical composition, tissue microstructure, and protein localization. Bioreactor-cultivated constructs grown with serum and growth factors (basic fibroblast growth factor and transforming growth factor beta 2) had greater thickness, as well as DNA and glycosaminoglycan (GAG) contents, compared to low serum and no growth factor controls. These constructs also showed the most intense proteoglycan and collagen II staining. The combination of bioreactor conditions, serum, and growth factors allowed the generation of large, thick scaffold-free human cartilaginous tissues that resembled the native nasoseptal cartilage. There also may be implications for patient selection in future clinical applications of these engineered tissues because their GAG content decreased with donor age. NA. Laryngoscope, 127:E91-E99, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Sliding motion modulates stiffness and friction coefficient at the surface of tissue engineered cartilage.

    Science.gov (United States)

    Grad, S; Loparic, M; Peter, R; Stolz, M; Aebi, U; Alini, M

    2012-04-01

    Functional cartilage tissue engineering aims to generate grafts with a functional surface, similar to that of authentic cartilage. Bioreactors that stimulate cell-scaffold constructs by simulating natural joint movements hold great potential to generate cartilage with adequate surface properties. In this study two methods based on atomic force microscopy (AFM) were applied to obtain information about the quality of engineered graft surfaces. For better understanding of the molecule-function relationships, AFM was complemented with immunohistochemistry. Bovine chondrocytes were seeded into polyurethane scaffolds and subjected to dynamic compression, applied by a ceramic ball, for 1h daily [loading group 1 (LG1)]. In loading group 2 (LG2), the ball additionally oscillated over the scaffold, generating sliding surface motion. After 3 weeks, the surfaces of the engineered constructs were analyzed by friction force and indentation-type AFM (IT-AFM). Results were complemented and compared to immunohistochemical analyses. The loading type significantly influenced the mechanical and histological outcomes. Constructs of LG2 exhibited lowest friction coefficient and highest micro- and nanostiffness. Collagen type II and aggrecan staining were readily observed in all constructs and appeared to reach deeper areas in loaded (LG1, LG2) compared to unloaded scaffolds. Lubricin was specifically detected at the top surface of LG2. This study proposes a quantitative AFM-based functional analysis at the micrometer- and nanometer scale to evaluate the quality of cartilage surfaces. Mechanical testing (load-bearing) combined with friction analysis (gliding) can provide important information. Notably, sliding-type biomechanical stimuli may favor (re-)generation and maintenance of functional articular surfaces and support the development of mechanically competent engineered cartilage. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights

  10. Transforming growth factor-beta1 inhibits tissue engineering cartilage absorption via inducing the generation of regulatory T cells.

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    Li, Chichi; Bi, Wei; Gong, Yiming; Ding, Xiaojun; Guo, Xuehua; Sun, Jian; Cui, Lei; Yu, Youcheng

    2016-02-01

    The objective of the present study was to explore the mechanisms of transforming growth factor (TGF)-β1 inhibiting the absorption of tissue engineering cartilage. We transfected TGF-β1 gene into bone marrow mesenchymal stem cells (BMMSCs) and co-cultured with interferon (IFN)-γ and tumour necrosis factor (TNF)-α and CD4(+) CD25(-) T lymphocytes. We then characterized the morphological changes, apoptosis and characterization of chondrogenic-committed cells from TGF-β1(+) BMMSCs and explored their mechanisms. Results showed that BMMSCs apoptosis and tissue engineering cartilage absorption in the group with added IFN-γ and TNF-α were greater than in the control group. In contrast, there was little BMMSC apoptosis and absorption by tissue engineering cartilage in the group with added CD4(+) CD25(-) T lymphocytes; Foxp3(+) T cells and CD25(+) CD39(+) T cells were found. In contrast, no type II collagen or Foxp3(+) T cells or CD25(+) CD39(+) T cells was found in the TGF-β1(-) BMMSC group. The data suggest that IFN-γ and TNF-α induced BMMSCs apoptosis and absorption of tissue engineering cartilage, but the newborn regulatory T (Treg) cells inhibited the function of IFN-γ and TNF-α and protected BMMSCs and tissue engineering cartilage. TGF-β1not only played a cartilage inductive role, but also inhibited the absorption of tissue engineering cartilage. The pathway proposed in our study may simulate the actual reaction procedure after implantation of BMMSCs and tissue engineering cartilage in vivo. Copyright © 2013 John Wiley & Sons, Ltd.

  11. Tissue-engineering strategies to repair chondral and osteochondral tissue in osteoarthritis: use of mesenchymal stem cells.

    Science.gov (United States)

    Grässel, Susanne; Lorenz, Julia

    2014-10-01

    Focal chondral or osteochondral lesions can be painful and disabling because they have insufficient intrinsic repair potential, and constitute one of the major extrinsic risk factors for osteoarthritis (OA). Attention has, therefore, been paid to regenerative therapeutic procedures for the early treatment of cartilaginous defects. Current treatments for OA are not regenerative and have little effect on the progressive degeneration of joint tissue. One major reason for this underrepresentation of regenerative therapy is that approaches to treating OA with cell-based strategies have to take into consideration the larger sizes of the defects, as compared with isolated focal articular-cartilage defects, and the underlying disease process. Here, we review current treatment strategies using mesenchymal stem cells (MSCs) for chondral and osteochondral tissue repair in trauma and OA-affected joints. We discuss tissue-engineering approaches, in preclinical large-animal models and clinical studies in humans, which use crude bone-marrow aspirates and MSCs from different tissue sources in combination with bioactive agents and materials.

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

    International Nuclear Information System (INIS)

    Tao, Hongyue; Lu, Rong; Feng, Xiaoyuan; Chen, Shuang; Shang, Xiliang; Li, Hong; Hua, Yinghui

    2014-01-01

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

  13. 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.

  14. A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology.

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    Wang, Chen-Chie; Yang, Kai-Chiang; Lin, Keng-Hui; Liu, Hwa-Chang; Lin, Feng-Huei

    2011-10-01

    Osteoarthritis is a degenerative disease and frequently involves the knee, hip and phalangeal joints. Current treatments used in small cartilage defects including multiple drilling, abrasion arthroplasty, mosaicplasty, and autogenous chondrocyte transplantation, however, there are problems needed to be solved. The standard treatment for severe osteoarthritis is total joint arthroplasty. The disadvantages of this surgery are the possibility of implant loosening. Therefore, tissue engineering for cartilage regeneration has become a promising topic. We have developed a new method to produce a highly organized single polymer (alginate) scaffold using microfluidic device. Scanning electron microscope and confocal fluoroscope examinations showed that the scaffold has a regular interconnected porous structure in the scale of 250 μm and high porosity. The scaffold is effective in chondrocyte culture; the cell viability test (WST-1 assay), cell toxicity (lactate dehydrogenase assay), cell survival rate, extracellular matrix production (glycosaminoglycans contents), cell proliferation (DNA quantification), and gene expression (real-time PCR) all revealed good results for chondrocyte culture. The chondrocytes can maintain normal phenotypes, highly express aggrecan and type II collagen, and secrete a great deal of extracellular matrix when seeded in the alginate scaffold. This study demonstrated that a highly organized alginate scaffold can be prepared with an economical microfluidic device, and this scaffold is effective in cartilage tissue engineering. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  15. Validation of a diffusion chamber as in vitro system for the analysis of compound diffusibility through cartilage tissue.

    Science.gov (United States)

    Kreiselmeier, Alexander; Ulmer, Wolfgang; Stöve, Johannes; Wieland, Heike A; Gerwin, Nicole; Bartnik, Eckart; Schudok, Manfred; Heute, Steffen; Breitenfelder, Michael; Scharf, Hanns-Peter; Schwarz, Markus L R

    2005-08-01

    The validation of a diffusion chamber comprising a donor and a receptor side separated by a cartilage membrane was undertaken according to the basic principles described by Peng et al. (1998). The study had three targets: first to evaluate the chamber as in vitro system by the examination of the diffusibility of compound through bovine cartilage samples; second the analysis of the affinity of compound (RS-130830) to cartilage; third to test the influence of two pre-incubation periods (one or three nights) of the cartilage samples. The validation of the chamber as in vitro system for the analysis of compound diffusibility and affinity to cartilage was performed using membrane slices of fresh bovine cartilage and a hydroxamic acid derivative (RS-130830) known as matrix metalloproteinase inhibitor (MMPI). The influence of the pre-incubation of cartilage was also examined. Compound concentrations in donor, receptor and membrane were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS). Diffusion could be demonstrated after 6 h and finally 24 h incubation: the compound concentration in the receptor increased from 0 to 35 microM (mean) while it decreased in the donor from 200 to 144 microM (mean). We also found compound in the cartilage membrane (approximately 1.2 nmol (mean)). Pre-incubation of cartilage samples in culture buffer is suitable as a storage procedure, since the results on the donor side only were influenced significantly but not for the receptor and the cartilage affinity. Thus, the system could clearly reflect relevant properties of the tested compound with regard to its diffusibility and affinity to cartilage tissue.

  16. [Experimental study of tissue engineered cartilage construction using oriented scaffold combined with bone marrow mesenchymal stem cells in vivo].

    Science.gov (United States)

    Duan, Wei; Da, Hu; Wang, Wentao; Lü, Shangjun; Xiong, Zhuo; Liu, Jian

    2013-05-01

    To investigate the feasibility of fabricating an oriented scaffold combined with chondrogenic-induced bone marrow mesenchymal stem cells (BMSCs) for enhancement of the biomechanical property of tissue engineered cartilage in vivo. Temperature gradient-guided thermal-induced phase separation was used to fabricate an oriented cartilage extracellular matrix-derived scaffold composed of microtubules arranged in parallel in vertical section. No-oriented scaffold was fabricated by simple freeze-drying. Mechanical property of oriented and non-oriented scaffold was determined by measurement of compressive modulus. Oriented and non-oriented scaffolds were seeded with chondrogenic-induced BMSCs, which were obtained from the New Zealand white rabbits. Proliferation, morphological characteristics, and the distribution of the cells on the scaffolds were analyzed by MTT assay and scanning electron microscope. Then cell-scaffold composites were implanted subcutaneously in the dorsa of nude mice. At 2 and 4 weeks after implantation, the samples were harvested for evaluating biochemical, histological, and biomechanical properties. The compressive modulus of oriented scaffold was significantly higher than that of non-oriented scaffold (t=201.099, P=0.000). The cell proliferation on the oriented scaffold was significantly higher than that on the non-oriented scaffold from 3 to 9 days (P fibers with chondrocyte-like cells on the oriented-structure constructs. Total DNA, glycosaminoglycan (GAG), and collagen contents increased with time, and no significant difference was found between 2 groups (P > 0.05). The compressive modulus of the oriented tissue engineered cartilage was significantly higher than that of the non-oriented tissue engineered cartilage at 2 and 4 weeks after implantation (P < 0.05). Total DNA, GAG, collagen contents, and compressive modulus in the 2 tissue engineered cartilages were significantly lower than those in normal cartilage (P < 0.05). Oriented extracellular

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

    Science.gov (United States)

    Babur, Betul Kul; Kabiri, Mahboubeh; Klein, Travis Jacob; Lott, William B; Doran, Michael Robert

    2015-01-01

    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 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 tissues; the incorporation of CD enhanced tissue size and matrix content, but did not enhance chondrogenic gene expression.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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

  19. 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.

  20. Preparation and characterization of collagen/PLA, chitosan/PLA, and collagen/chitosan/PLA hybrid scaffolds for cartilage tissue engineering.

    Science.gov (United States)

    Haaparanta, Anne-Marie; Järvinen, Elina; Cengiz, Ibrahim Fatih; Ellä, Ville; Kokkonen, Harri T; Kiviranta, Ilkka; Kellomäki, Minna

    2014-04-01

    In this study, three-dimensional (3D) porous scaffolds were developed for the repair of articular cartilage defects. Novel collagen/polylactide (PLA), chitosan/PLA, and collagen/chitosan/PLA hybrid scaffolds were fabricated by combining freeze-dried natural components and synthetic PLA mesh, where the 3D PLA mesh gives mechanical strength, and the natural polymers, collagen and/or chitosan, mimic the natural cartilage tissue environment of chondrocytes. In total, eight scaffold types were studied: four hybrid structures containing collagen and/or chitosan with PLA, and four parallel plain scaffolds with only collagen and/or chitosan. The potential of these types of scaffolds for cartilage tissue engineering applications were determined by the analysis of the microstructure, water uptake, mechanical strength, and the viability and attachment of adult bovine chondrocytes to the scaffolds. The manufacturing method used was found to be applicable for the manufacturing of hybrid scaffolds with highly porous 3D structures. All the hybrid scaffolds showed a highly porous structure with open pores throughout the scaffold. Collagen was found to bind water inside the structure in all collagen-containing scaffolds better than the chitosan-containing scaffolds, and the plain collagen scaffolds had the highest water absorption. The stiffness of the scaffold was improved by the hybrid structure compared to plain scaffolds. The cell viability and attachment was good in all scaffolds, however, the collagen hybrid scaffolds showed the best penetration of cells into the scaffold. Our results show that from the studied scaffolds the collagen/PLA hybrids are the most promising scaffolds from this group for cartilage tissue engineering.

  1. Human Suprapatellar Fat Pad-Derived Mesenchymal Stem Cells Induce Chondrogenesis and Cartilage Repair in a Model of Severe Osteoarthritis

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    Ignacio Muñoz-Criado

    2017-01-01

    Full Text Available Cartilage degeneration is associated with degenerative bone and joint processes in severe osteoarthritis (OA. Spontaneous cartilage regeneration is extremely limited. Often the treatment consists of a partial or complete joint implant. Adipose-derived stem cell (ASC transplantation has been shown to restore degenerated cartilage; however, regenerative differences of ASC would depend on the source of adipose tissue. The infra- and suprapatellar fat pads surrounding the knee offer a potential autologous source of ASC for patients after complete joint substitution. When infrapatellar- and suprapatellar-derived stromal vascular fractions (SVF were compared, a significantly higher CD105 (+ population was found in the suprapatellar fat. In addition, the suprapatellar SVF exhibited increased numbers of colony formation units and a higher population doubling in culture compared to the infrapatellar fraction. Both the suprapatellar- and infrapatellar-derived ASC were differentiated in vitro into mature adipocytes, osteocytes, and chondrocytes. However, the suprapatellar-derived ASC showed higher osteogenic and chondrogenic efficiency. Suprapatellar-derived ASC transplantation in a severe OA mouse model significantly diminished the OA-associated knee inflammation and cartilage degenerative grade, significantly increasing the production of glycosaminoglycan and inducing endogenous chondrogenesis in comparison with the control group. Overall, suprapatellar-derived ASC offer a potential autologous regenerative treatment for patients with multiple degenerative OA.

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

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    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.

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

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    Diego Correa

    2002-01-01

    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.

  4. 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. Copyright © 2013 John Wiley & Sons, Ltd.

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

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    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.

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

    Science.gov (United States)

    Chen, Chih-Hao; Liu, Jolene Mei-Jun; Chua, Chee-Kai; Chou, Siaw-Meng; Shyu, Victor Bong-Hang; Chen, Jyh-Ping

    2014-03-13

    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.

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

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    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.

  8. Fibroblast growth factors: key players in regeneration and tissue repair.

    Science.gov (United States)

    Maddaluno, Luigi; Urwyler, Corinne; Werner, Sabine

    2017-11-15

    Tissue injury initiates a complex repair process, which in some organisms can lead to the complete regeneration of a tissue. In mammals, however, the repair of most organs is imperfect and results in scar formation. Both regeneration and repair are orchestrated by a highly coordinated interplay of different growth factors and cytokines. Among the key players are the fibroblast growth factors (FGFs), which control the migration, proliferation, differentiation and survival of different cell types. In addition, FGFs influence the expression of other factors involved in the regenerative response. Here, we summarize current knowledge on the roles of endogenous FGFs in regeneration and repair in different organisms and in different tissues and organs. Gaining a better understanding of these FGF activities is important for appropriate modulation of FGF signaling after injury to prevent impaired healing and to promote organ regeneration in humans. © 2017. Published by The Company of Biologists Ltd.

  9. Do Cartilage Repair Procedures Prevent Degenerative Meniscus Changes? Longitudinal T1ρ and Morphological Evaluation at 3.0T

    Science.gov (United States)

    Jungmann, Pia M.; Li, Xiaojuan; Nardo, Lorenzo; Subburaj, Karupppasamy; Lin, Wilson; Ma, C. Benjamin; Majumdar, Sharmila; Link, Thomas M.

    2014-01-01

    Background Cartilage repair (CR) procedures are widely accepted for treatment of isolated cartilage defects at the knee joint. However, it is not well known whether these procedures prevent degenerative joint disease. Hypothesis/Purpose CR procedures prevent accelerated qualitative and quantitative progression of meniscus degeneration in individuals with focal cartilage defects. Study Design Cohort Study; Level of evidence 2b Methods A total of 94 subjects were studied. CR procedures were performed on 34 patients (n=16 osteochondral transplantation, n=18 microfracture); 34 controls were matched. An additional 13 patients received CR and anterior cruciate ligament (ACL) reconstruction (CR&ACL) and 13 patients received only ACL reconstruction. 3.0T MRI with T1ρ mapping and sagittal fat-saturated intermediate-weighted fast spin echo (FSE) sequences was performed to analyze menisci quantitatively and qualitatively (Whole-Organ Magnetic Resonance Imaging Score, WORMS). CR and CR&ACL patients were examined 4 months (n=34; n=13), 1 (n=21; n=8) and 2 (n=9; n=5) years post CR. Control subjects were scanned at baseline and after 1 and 2 years, ACL patients after 1 and 2 years. Results At baseline, global meniscus T1ρ values were higher in individuals with CR (14.2±0.6ms; P=0.004) and in individuals with CR&ACL (17.1±0.9ms; Pmeniscus above cartilage defects (16.4±1.0ms) and T1ρ of the subgroup of control knees without cartilage defects (12.1±0.8ms; Pmeniscus tears at the overlying meniscus; 10% of CR subjects showed an increase of WORMS meniscus score within the first year, none progressed in the second year. Control subjects with (without) cartilage defects showed meniscus tears in 30% (5%) at baseline; 38% (19%) increased within the first, and 15% (10%) within the second year. Conclusions This study identified more severe meniscus degeneration after CR surgery compared to controls. However, progression of T1ρ values was not observed from 1 to 2 years after surgery

  10. Reconstruction of Alar Nasal Cartilage Defects Using a Tissue Engineering Technique Based on a Combined Use of Autologous Chondrocyte Micrografts and Platelet-rich Plasma: Preliminary Clinical and Instrumental Evaluation

    Science.gov (United States)

    Scioli, Maria G.; Bielli, Alessandra; Orlandi, Augusto; Cervelli, Valerio

    2016-01-01

    Background: Developing cartilage constructs with injectability, appropriate matrix composition, and persistent cartilaginous phenotype remains an enduring challenge in cartilage repair. The combined use of autologous chondrocyte micrografts and platelet-rich plasma (PRP) is an alternative that opens a new era in this field. Methods: At the Department of Plastic and Reconstructive Surgery, University of Rome Tor Vergata, Italy, 11 patients underwent nasal alar reconstruction with chondrocyte micrografts gently poured onto PRP in solid form. A computed tomographic scan control was performed after 12 months. Pearson’s Chi-square test was used to investigate difference in cartilage density between native and newly formed cartilages. Results: The constructs of chondrocyte micrografts–PRP that were subcutaneously injected resulted in a persistent cartilage tissue with appropriate morphology, adequate central nutritional perfusion without central necrosis or ossification, and further augmented nasal dorsum without obvious contraction and deformation. Conclusion: This report demonstrated that chondrocyte micrografts derived from nasal septum poured onto PRP in solid form are useful for cartilage regeneration in patients with external nasal valve collapse. PMID:27826462

  11. 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

  12. A Systematic Review And Meta-Analysis of Clinical Trials of Mesenchymal Stem Cell Therapy for Cartilage Repair.

    Science.gov (United States)

    Borakati, Aditya; Mafi, Reza; Mafi, Pouya; Khan, Wasim S

    2018-02-23

    Osteoarthritis (OA) is a major global burden creating significant morbidity worldwide. Current curative therapies are expensive, challenging to access and have significant risks, making them infeasible and difficult in many cases. Mesenchymal stem cells (MSCs) can be applied to joints and may regenerate the cartilage damaged in OA, this therapy may be advantageous to existing treatments. We systematically reviewed clinical trials of MSCs for cartilage repair and provide an overview of the literature in this area here. MEDLINE, Embase, CENTRAL, clinicaltrials.gov and Open- Grey were searched for controlled trials and case series with >5 patents involving MSC therapy for cartilage repair. The controlled trials were meta-analysed and the primary outcome measure was improvement in pain over the control group. A narrative synthesis was composed for the case series. A significant reduction in pain was found with the use of MSCs over controls: Standardised mean difference=-1.27 (95% Confidence intervals -1.95 to -0.58). However, the data was extremely heterogeneous with I2=95%, this may be attributed to differing therapies, clinical indication for treatment and joints treated amongst others. Case series showed improvements in treated patients with a variety of differing treatments and by many outcomes. There were no severe adverse outcomes found across all studies that could be attributed to MSCs, implying their safety. We conclude that MSCs have significant potential for the treatment of OA, however, larger, more consistent trials are needed for conclusive analysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. [Research on preparation and characters of decellularized cartilage matrix for tissue engineering].

    Science.gov (United States)

    Yang, Ziquan; He, Junren; Li, Gang; Yang, Shuhua; Wei, Xiaochun

    2008-10-01

    To produce a decellularized cartilage matrix (DCM) and investigate its possibility to be used as a scaffold for tissue engineering. Fresh bovine articular cartilage from knee joints was sliced, freeze-dried and freeze-ground into fine powder, and then was treated sequentially with Trypsin, Triton X-100 and hypotonic solution for decellularization. The decellularized matrix was freeze-dried for shaping and cross-linked by UV radiation. Histological, immunohistological, SEM, porosity assays and biomechanical assays were used to characterize the DCM. BMSCs were isolated from rabbit bone marrow aspirate and cultured in DCM extraction medium of different concentration (100%, 10% and 1%) for 0, 24, 48 and 72 hours, respectively, to detect the release rate of the lactate dehydrogenase (LDH). The DMEM medium (5% FBS) served as the control. Biocompatibility was evaluated using BMSCs (1 x 10(7)/mL) cultured with DCM. The DCM showed white spongy appearances, and histological analysis showed that the material was constructed by cartilage particles without any cells or cell fragments left in the matrix. Immunohistology staining and alcian blue staining showed that DCM retained the collagen and glycosaminoglycan components of cartilaginous matrix. SEM scanning showed that DCM had a porous spongy-like structure with the aperture ranging 30-150 microm. The porosity assay showed that the average porosity was 89.37% and the average aperture was 90.8 microm. The mechanical assay showed that there was no difference for the compress module before and after the decellularization process, which was (17.91 +/- 0.98) MPa and (15.12 +/- 0.77) MPa, respectively (P > 0.05), but were both statistical different from normal articular cartilage [(26.30 +/- 1.98) MPa, P 0.05). The cell adhesion test showed BMSCs grew well on DCM without any signs of growth inhibition. Articular cartilage can be decellularized and fabricated into a scaffold which retains the major components of cartilaginous matrix

  14. In vivo construction of tissue-engineered cartilage using adipose-derived stem cells and bioreactor technology.

    Science.gov (United States)

    Kang, Hongjun; Lu, Shibi; Peng, Jiang; Yang, Qiang; Liu, Shuyun; Zhang, Li; Huang, Jingxiang; Sui, Xiang; Zhao, Bin; Wang, Aiyuan; Xu, Wenjing; Guo, Quanyi; Song, Qing

    2015-03-01

    The present study aims to investigate the feasibility of tissue-engineered cartilage constructed in vivo and in vitro by dynamically culturing adipose-derived stem cells (ADSCs) with an articular cartilage acellular matrix in a bioreactor and subsequently implanting the cartilage in nude mice. ADSCs were proliferated, combined with three dimensional scaffolds (cell density: 5 × 10(7)/mL) and subsequently placed in a bioreactor and culture plate for 3 weeks. In the in vivo study, complexes cultured for 1 week under dynamic or static states were subcutaneously implanted into nude mice and collected after 3 weeks. Indicators such as gross morphology, histochemistry and immunohistochemistry were examined. In the in vitro study, histological observation showed that most scaffolds in the dynamic group were absorbed, and cell proliferation and matrix secretion were significant. Positive staining of safranin-O and alcian blue II collagen stain in the dynamic group was significantly stronger than that in the static culture group. In the in vivo study, cartilage-like tissues formed in the specimens of the two groups. Histological examination showed that cell distribution in the dynamic group was relatively more uniform than in the static group, and matrix secretion was relatively stronger. Bioreactor culturing can promote ADSC proliferation and cartilage differentiation and is thus a suitable method for constructing tissue-engineered cartilage in vivo.

  15. Regulation of tissue repair and regeneration by electric fields.

    Science.gov (United States)

    Wang, En-tong; Zhao, Min

    2010-02-01

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Design and validation of a biomechanical bioreactor for cartilage tissue culture.

    Science.gov (United States)

    Correia, V; Panadero, J A; Ribeiro, C; Sencadas, V; Rocha, J G; Gomez Ribelles, J L; Lanceros-Méndez, S

    2016-04-01

    Specific tissues, such as cartilage, undergo mechanical solicitation under their normal performance in human body. In this sense, it seems necessary that proper tissue engineering strategies of these tissues should incorporate mechanical solicitations during cell culture, in order to properly evaluate the influence of the mechanical stimulus. This work reports on a user-friendly bioreactor suitable for applying controlled mechanical stimulation--amplitude and frequency--to three-dimensional scaffolds. Its design and main components are described, as well as its operation characteristics. The modular design allows easy cleaning and operating under laminar hood. Different protocols for the sterilization of the hermetic enclosure are tested and ensure lack of observable contaminations, complying with the requirements to be used for cell culture. The cell viability study was performed with KUM5 cells.

  18. 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.

  19. 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…

  20. Potential of Agarose/Silk Fibroin Blended Hydrogel for in Vitro Cartilage Tissue Engineering.

    Science.gov (United States)

    Singh, Yogendra Pratap; Bhardwaj, Nandana; Mandal, Biman B

    2016-08-24

    An osteoarthritis pandemic has accelerated exploration of various biomaterials for cartilage reconstruction with a special emphasis on silk fibroin from mulberry (Bombyx mori) and non-mulberry (Antheraea assamensis) silk worms. Retention of positive attributes of the agarose standard and nullification of its negatives are central to the current agarose/silk fibroin hydrogel design. In this study, hydrogels of mulberry and non-mulberry silk fibroin blended with agarose were fabricated and evaluated in vitro for two weeks for cartilaginous tissue formation. The fabricated hydrogels were physicochemically characterized and analyzed for cell viability, proliferation, and extra cellular matrix deposition. The amalgamation of silk fibroin with agarose impacted the pore size, as illustrated by field emission scanning electron microscopy studies, swelling behavior, and in vitro degradation of the hydrogels. Fourier transform infrared spectroscopy results indicated the blend formation and confirmed the presence of both components in the fabricated hydrogels. Rheological studies demonstrated enhanced elasticity of blended hydrogels with G' > G″. Biochemical analysis revealed significantly higher levels of sulfated glycosaminoglycans (sGAGs) and collagen (p ≤ 0.01) in blended hydrogels. More specifically, the non-mulberry silk fibroin blend showed sGAG and collagen content (∼1.5-fold) higher than that of the mulberry blend (p ≤ 0.05). Histological and immunohistochemical analyses further validated the enhanced deposition of sGAG and collagen, indicating maintenance of chondrogenic phenotype within constructs after two weeks of culture. Real-time PCR analysis further confirmed up-regulation of cartilage-specific aggrecan, sox-9 (∼1.5-fold) and collagen type II (∼2-fold) marker genes (p ≤ 0.01) in blended hydrogels. The hydrogels demonstrated immunocompatibility, which was evidenced by minimal in vitro secretion of tumor necrosis factor-α (TNF-α) by murine

  1. Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

    Science.gov (United States)

    Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

    2017-01-01

    Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. HR007: a family of biomaterials based on glycosaminoglycans for tissue repair.

    Science.gov (United States)

    Herrero-Mendez, A; Palomares, T; Castro, B; Herrero, J; Granado, M H; Bejar, J M; Alonso-Varona, A

    2017-04-01

    Most new advances in tissue engineering (TE) focus on the creation of adequate microenvironments that may accelerate the repair processes of damaged tissues. Extracellular matrix (ECM) of Wharton's jelly (WJ) from umbilical cords is very rich in sulphated GAGs (sGAGs) and hyaluronic acid (HA), components which have special properties that could positively influence the regeneration of several types of tissue. Previously, we described the methodology for the extraction and purification of GAGs from WJ and, importantly, the separation of sGAGs and HA to develop various scaffolds for regenerative medicine. In this new study we hypothesized that the biomaterials obtained, called HR007s, would be excellent candidates for two different applications, chondral and dermal repair. First, we have confirmed that the GAGs obtained are biocompatible, as they do not cause cytotoxicity, haemolysis or an inflammatory response. Second, we have developed three-dimensional (3D) structures through the combination of different ratios of GAGs and their subsequent stabilization, which can be properly adapted to target tissues, cartilage or skin. Finally, we have combined these scaffolds with adipose mesenchymal stem cells (ASCs) or fibroblasts for application to chondral or dermal defects, respectively, with the goal of promoting fast reparative processes. The results show that HR007 scaffolds induce cell proliferation, enhance the expression of specific gene markers, increase the production of tissue ECM proteins and have chemotactic effects over the studied cells. In summary, the bioactive properties of HR007 scaffolds make them promising candidates for use in regenerative medicine, at least for chondral and dermal repair. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Preparation and properties of polyvinyl alcohol (PVA) and hydroxylapatite (HA) hydrogels for cartilage tissue engineering.

    Science.gov (United States)

    Yuan, F; Ma, M; Lu, L; Pan, Z; Zhou, W; Cai, J; Luo, S; Zeng, W; Yin, F

    2017-05-20

    A novel bioactive hydrogel for cartilage tissue based on polyvinyl alcohol (PVA) and hydroxylapatite (HA) were prepared, the effects of its component contents on the mechanical properties and microstructure of the hydrogel were investigated. The important properties of the scaffold composites, such as density, porosity, compressive modulus and microstructure were studied and analyzed through various measurements and methods. The biodegradability of hydrogel was evaluated by soaking the samples into artificial degradation solution at body temperature (36 - 37 oC) in vitro. Experimental results showed that the PVA/HA hydrogels had a density of 0.572 - 0.683 g/cm3, a porosity of 63.25 - 96.14% and a compressive modulus of 5.62 - 8.24 MP. The HA compound in the hydrogels enhanced the biodegradation significantly and linearly increased the rate of biodegradation by 2.3 - 8.5 %. The compressive modulus of PVA/HA exhibited a linear reduce to 0.86 - 1.53 MP with the time of degradation. The scaffold composites PVA/HA possess a high porosity, decent compressive modulus and good biodegradability. After further optimizing the structure and properties, this composite might be considered as novel hydrogel biomaterials to be applied in the field of cartilage tissue engineering.

  4. Novel electrospun nanofibers of modified gelatin-tyrosine in cartilage tissue engineering

    International Nuclear Information System (INIS)

    Agheb, Maria; Dinari, Mohammad; Rafienia, Mohammad; Salehi, Hossein

    2017-01-01

    In natural cartilage tissues, chondrocytes are linked to extracellular matrix (ECM) through cell-surface binding proteins. Surface modification of gelatin can provide a new generation of biopolymers and fibrous scaffolds with chemical, mechanical, and biological properties. In this study tyrosine protein and 1,2,3-triazole ring were utilized to functionalize gelatin without Cu catalyst. Their molecular structure was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ( 1 HNMR). Chemical cross-linkers such as glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysulfosuccinimide (NHS) were used to electrospin the modified gelatin. The modification of gelatin and cross-linking effects were confirmed by scanning electron microscopy (SEM), contact angle measurement, and mechanical tests. MTT assay using chondrocyte cells showed cell viability of electrospun modified gelatin scaffolds. In vitro cell culture studies showed that electrospun engineered protein scaffolds would support the attachment and growth of cells. The results also showed that cross-linked nanofibers with EDC/NHS could be considered excellent matrices in cell adhesion and proliferation before electrospinning process and their potential substrate in tissue engineering applications, especially in the field of cartilage engineering.

  5. 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.; de Windt, T.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,

  6. 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,

  7. Key Role of DAMP in Inflammation, Cancer, and Tissue Repair.

    Science.gov (United States)

    Pandolfi, Franco; Altamura, Simona; Frosali, Simona; Conti, Pio

    2016-05-01

    This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known DAMP molecules and have been primarily associated with inflammation. However, as we shall see, recent data have linked these molecules to tissue repair. HMGB1 is associated with cancer-related inflammation. It activates nuclear factor kB, which is involved in cancer regulation via its receptor for advanced glycation end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and Toll like receptor 2 and 4 role in inflammation and by increasing their concentration in tissue repair, respectively. We conducted a MEDLINE search for articles pertaining to the various issues related to DAMP, and we discuss the most relevant articles especially (ie, not only those published in journals with a higher impact factor). A cluster of remarkable articles on DAMP have appeared in the literature in recent years. Regarding inflammation, several strategies have been proposed to target HMGB1, from antibodies to recombinant box A, which interacts with RAGE, competing with the full molecule. In tissue repair, it was reported that the overexpression of HMGB1 or the administration of exogenous HMGB1 significantly increased the number of vessels and promoted recovery in skin-wound, ischemic injury. Due to the bivalent nature of DAMP, it is often difficult to explain the relative role of DAMP in inflammation versus its role in tissue repair. However, this point is crucial as DAMP-related treatments move into clinical practice. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  8. 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.

  9. 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...

  10. MR imaging of canine osteoarthritis shows sustained hypertrophic repair of articular cartilage

    International Nuclear Information System (INIS)

    Braunstein, E.M.; Albrecht, M.; Brandt, K.D.

    1989-01-01

    This paper reports MR imaging used to evaluate cartilage abnormalities in three dogs in which the anterior cruciate ligament (ACL) of one hind limb had been transected to produce osteoarthritis. In this model changes mirror those in human osteoarthritis, but they are not progressive after a few months. The authors performed serial plain radiography and MR imaging of the osteoarthritic knee and control knee 3 years after ACL transection. Coronal T1- weighted images and sagittal multiecho and field echo summed images were obtained. Radiographs showed osteophytes, geodes, and subchondral sclerosis of the operated knees, with no progression between 2 and 3 years. Contralateral knees were normal. On MR images in each case there was indistinctness and thickening of articular cartilage in the abnormal knee compared with the contralateral knee

  11. 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.)

  12. The use of a prosthetic inlay resurfacing as a salvage procedure for a failed cartilage repair.

    Science.gov (United States)

    Dhollander, Aad Alfons Maria; Almqvist, Karl Fredrik; Moens, Kris; Vandekerckhove, Pieter-Jan; Verdonk, René; Verdonk, Peter; Victor, Jan

    2015-08-01

    This study was designed to describe the clinical and radiographical outcome of the HemiCAP(®) resurfacing system as a salvage treatment for a failed index cartilage procedure. Fourteen patients were treated consecutively and clinically prospectively followed for a mean period of 26.1 ± 12.8 months. All patients were previously treated for their cartilage lesion. Radiographical data were analysed based on the Kellgren and Lawrence system. The patients involved in this study demonstrated a gradual clinical improvement in time. However, radiographically significant osteoarthritic changes were observed during the follow-up period. The position of the HemiCAP(®) resurfacing system was adequate in all cases, and no signs of loosening were observed during the follow-up period. The HemiCAP(®) resurfacing system is feasible as a salvage treatment for a failed index cartilage procedure and resulted in a gradual clinical improvement. However, the favourable clinical outcome was not confirmed by the radiographical findings. IV.

  13. Chondroitin sulfate immobilization at the surface of electrospun nanofiber meshes for cartilage tissue regeneration approaches

    Science.gov (United States)

    Piai, Juliana Francis; da Silva, Marta Alves; Martins, Albino; Torres, Ana Bela; Faria, Susana; Reis, Rui L.; Muniz, Edvani Curti; Neves, Nuno M.

    2017-05-01

    Aiming at improving the biocompatibility of biomaterial scaffolds, surface modification presents a way to preserve their mechanical properties and to improve the surface bioactivity. In this work, chondroitin sulfate (CS) was immobilized at the surface of electrospun poly(caprolactone) nanofiber meshes (PCL NFMs), previously functionalized by UV/O3 exposure and aminolysis. Contact angle, SEM, optical profilometry, FTIR, X-ray photoelectron spectroscopy techniques confirmed the success of CS-immobilization in PCL NFMs. Furthermore, CS-immobilized PCL NFMs showed lower roughness and higher hydrophilicity than the samples without CS. Human articular chondrocytes (hACs) were cultured on electrospun PCL NFMs with or without CS immobilization. It was observed that hACs proliferated through the entire time course of the experiment in both types of nanofibrous scaffolds, as well as for the production of glycosaminoglycans. Quantitative-PCR results demonstrated over-expression of cartilage-related genes such as Aggrecan, Collagen type II, COMP and Sox9 on both types of nanofibrous scaffolds. Morphological observations from SEM and LSCM revealed that hACs maintained their characteristic round shape and cellular agglomeration exclusively on PCL NFMs with CS immobilization. In conclusion, CS immobilization at the surface of PCL NFMs was achieved successfully and provides a valid platform enabling further surface functionalization methods in scaffolds to be developed for cartilage tissue engineering.

  14. Noninvasive evaluation of tissue-engineered cartilage with time-resolved laser-induced fluorescence spectroscopy.

    Science.gov (United States)

    Kutsuna, Toshiharu; Sato, Masato; Ishihara, Miya; Furukawa, Katsuko S; Nagai, Toshihiro; Kikuchi, Makoto; Ushida, Takashi; Mochida, Joji

    2010-06-01

    Regenerative medicine requires noninvasive evaluation. Our objective is to investigate the application of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) using a nano-second-pulsed laser for evaluation of tissue-engineered cartilage (TEC). To prepare scaffold-free TEC, articular chondrocytes from 4-week-old Japanese white rabbits were harvested, and were inoculated at a high density in a mold. Cells were cultured for 5 weeks by rotating culture (RC) or static culture (SC). The RC group and SC group at each week (n = 5), as well as normal articular cartilage and purified collagen type II (as controls), were analyzed by TR-LIFS. The peak wavelength was compared with those of type II collagen immunostaining and type II collagen quantification by enzyme-linked immunosorbent assay and tensile testing. The fluorescence peak wavelength of the TEC analyzed by this method shifted significantly in the RC group at 3 weeks, and in the SC group at 5 weeks (p TEC.

  15. A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties.

    Science.gov (United States)

    Salinas, Evelia Y; Hu, Jerry C; Athanasiou, Kyriacos A

    2018-03-21

    The use of tissue-engineered articular cartilage (AC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in-vivo use have yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC. This review focuses on the use of mechanical stimulation to attain and enhance the properties of AC constructs needed to translate these implants to the clinic. In-vivo, mechanical loading at maximal and supramaximal physiological levels has been shown to be detrimental to AC through the development of degenerative changes. In contrast, multiple studies have revealed that during culture, mechanical stimulation within narrow ranges of magnitude and duration can produce anisotropic, mechanically robust AC constructs with high cellular viability. Significant progress has been made in evaluating a variety of mechanical stimulation techniques on tissue-engineered AC, either alone or in combination with other stimuli. These advancements include determining and optimizing efficacious loading parameters (e.g., duration and frequency) to yield improvements in construct design criteria, such as collagen II content, compressive stiffness, cell viability, and fiber organization. With the advancement of mechanical stimulation as a potent strategy in AC tissue-engineering, a compendium detailing the results achievable by various stimulus regimens would be of great use for researchers in academia and industry. The objective is to list the qualitative and quantitative effects that can be attained when direct compression, hydrostatic pressure, shear

  16. Recombinant Gelatin Microspheres : Novel Formulations for Tissue Repair?

    NARCIS (Netherlands)

    Tuin, Annemarie; Kluijtmans, Sebastiaan G.; Bouwstra, Jan B.; Harmsen, Martin C.; Van Luyn, Marja J. A.

    Microspheres (MSs) can function as multifunctional scaffolds in different approaches of tissue repair (TR), as a filler, a slow-release depot for growth factors, or a delivery vehicle for cells. Natural cell adhesion-supporting extracellular matrix components like gelatin are good materials for

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

    Directory of Open Access Journals (Sweden)

    A Basiri

    2014-08-01

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

  18. Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials.

    Science.gov (United States)

    Reddi, A H

    2000-08-01

    Morphogenesis is the developmental cascade of pattern formation, body plan establishment, and the architecture of mirror-image bilateral symmetry of many structures and asymmetry of some, culminating in the adult form. Tissue engineering is the emerging discipline of design and construction of spare parts for the human body to restore function based on principles of molecular developmental biology and morphogenesis governed by bioengineering. The three key ingredients for both morphogenesis and tissue engineering are inductive signals, responding stem cells, and the extracellular matrix. Among the many tissues in the human body, bone has considerable powers for regeneration and is a prototype model for tissue engineering based on morphogenesis. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and permitted the isolation of bone morphogens. Although it is traditional to study morphogenetic signals in embryos, bone morphogenetic proteins (BMPs), the inductive signals for bone, were isolated from demineralized bone matrix from adults. BMPs and related cartilage-derived morphogenetic proteins (CDMPs) initiate, promote, and maintain chondrogenesis and osteogenesis and have actions beyond bone. The symbiosis of bone inductive and conductive strategies are critical for tissue engineering, and is in turn governed by the context and biomechanics. The context is the microenvironment, consisting of extracellular matrix, which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion proteins including fibronectins. Thus, the rules of architecture for tissue engineering are an imitation of the laws of developmental biology and morphogenesis, and thus may be universal for all tissues, including bones and joints.

  19. 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

    2015-09-28

    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.

  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. PMID:22073377

  1. 3D Bioprinting Human Chondrocytes with Nanocellulose-Alginate Bioink for Cartilage Tissue Engineering Applications.

    Science.gov (United States)

    Markstedt, Kajsa; Mantas, Athanasios; Tournier, Ivan; Martínez Ávila, Héctor; Hägg, Daniel; Gatenholm, Paul

    2015-05-11

    The introduction of 3D bioprinting is expected to revolutionize the field of tissue engineering and regenerative medicine. The 3D bioprinter is able to dispense materials while moving in X, Y, and Z directions, which enables the engineering of complex structures from the bottom up. In this study, a bioink that combines the outstanding shear thinning properties of nanofibrillated cellulose (NFC) with the fast cross-linking ability of alginate was formulated for the 3D bioprinting of living soft tissue with cells. Printability was evaluated with concern to printer parameters and shape fidelity. The shear thinning behavior of the tested bioinks enabled printing of both 2D gridlike structures as well as 3D constructs. Furthermore, anatomically shaped cartilage structures, such as a human ear and sheep meniscus, were 3D printed using MRI and CT images as blueprints. Human chondrocytes bioprinted in the noncytotoxic, nanocellulose-based bioink exhibited a cell viability of 73% and 86% after 1 and 7 days of 3D culture, respectively. On the basis of these results, we can conclude that the nanocellulose-based bioink is a suitable hydrogel for 3D bioprinting with living cells. This study demonstrates the potential use of nanocellulose for 3D bioprinting of living tissues and organs.

  2. Reinforcement of articular cartilage with a tissue-interpenetrating polymer network reduces friction and modulates interstitial fluid load support.

    Science.gov (United States)

    Cooper, B G; Lawson, T B; Snyder, B D; Grinstaff, M W

    2017-07-01

    Osteoarthritis (OA) is associated with increased articular cartilage hydraulic permeability and decreased maintenance of high interstitial fluid load support (IFLS) during articulation, resulting in increased friction on the cartilage solid matrix. This study assesses frictional response following in situ synthesis of an interpenetrating polymer network (IPN) designed to mimic glycosaminoglycans (GAGs) depleted during OA. Cylindrical osteochondral explants containing various interpenetrating polymer concentrations were subjected to a torsional friction test under unconfined creep compression. Time-varying coefficient of friction, compressive engineering strain, and normalized strain values (ε/ε eq ) were calculated and analyzed. The polymer network reduced friction coefficient over the duration of the friction test, with statistically significantly reduced friction coefficients (95% confidence interval 14-34% reduced) at equilibrium compressive strain upon completion of the test (P = 0.015). A positive trend was observed relating polymer network concentration with magnitude of friction reduction compared to non-treated tissue. The cartilage-interpenetrating polymer treatment improves lubrication by augmenting the biphasic tissue's interstitial fluid phase, and additionally improves the friction dissipation of the tissue's solid matrix. This technique demonstrates potential as a therapy to augment tribological function of articular cartilage. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  3. Allogeneic Mesenchymal Stem Cells Stimulate Cartilage Regeneration and Are Safe for Single-Stage Cartilage Repair in Humans upon Mixture with Recycled Autologous Chondrons

    NARCIS (Netherlands)

    de Windt, Tommy S; Vonk, Lucienne A; Slaper-Cortenbach, Ineke C M; van den Broek, Marcel P H; Nizak, Razmara; van Rijen, Mattie H P; de Weger, Roel A; Dhert, Wouter J A; Saris, Daniel B F

    Traditionally, mesenchymal stem cells (MSCs) isolated from adult bone marrow were described as being capable of differentiating to various lineages including cartilage. Despite increasing interest in these MSCs, concerns regarding their safety, in vivo behavior and clinical effectiveness have

  4. 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

  5. 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

    Abstract 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

  6. Treatment of human cartilage defects by means of Nd:YAG Laser Therapy.

    Science.gov (United States)

    Zati, A; Desando, G; Cavallo, C; Buda, R; Giannini, S; Fortuna, D; Facchini, A; Grigolo, B

    2012-01-01

    Articular cartilage lesions represent a challenging problem for orthopaedic surgeons. The purpose of this study was to evaluate the effect of a new pulsed Nd:YAG High Intensity Laser Therapy on the regeneration of cartilage tissue in patients with traumatic lesions. Clinical, histological and immunohistochemical evaluations were performed. Ten patients affected by chondral lesions scheduled for ACI procedure, were enrolled into the study. During the chondrocyte expansion for ACI procedure, cartilage from five patients was treated by Nd:YAG High Intensity Laser Therapy (HILT group). No laser treatment was performed in the remaining patients, who were used as controls. Cartilage repair was assessed by clinicians using two different scores: Cartilage Repair Assessment (CRA) and Overall Repair Assessment (ORA). Cartilage biopsy specimens were harvested to perform histological and immunohistochemical analyses at T0 (before laser treatment) and T1 (at the end of the treatment). A significant decrease in cartilage depth was noticed in the HILT group at T1. Histological and immunohistochemical evaluations showed some regenerative processes in cartilaginous tissue in terms of high amount of proteoglycans, integration with adjacent articular cartilage and good cellular arrangement in the HILT group. By contrast, a not well organized cartilaginous tissue with various fibrous features in the control group at T0 and T1 was observed. In conclusion, the use of this new pulsed Nd:YAG HILT resulted promising in the treatment of moderate cartilage lesions markedly in the young patients.

  7. Reprogramming of blood cells into induced pluripotent stem cells as a new cell source for cartilage repair.

    Science.gov (United States)

    Li, Yueying; Liu, Tie; Van Halm-Lutterodt, Nicholas; Chen, JiaYu; Su, Qingjun; Hai, Yong

    2016-02-17

    An attempt was made to reprogram peripheral blood cells into human induced pluripotent stem cell (hiPSCs) as a new cell source for cartilage repair. We generated chondrogenic lineage from human peripheral blood via hiPSCs using an integration-free method. Peripheral blood cells were either obtained from a human blood bank or freshly collected from volunteers. After transforming peripheral blood cells into iPSCs, the newly derived iPSCs were further characterized through karyotype analysis, pluripotency gene expression and cell differentiation ability. iPSCs were differentiated through multiple steps, including embryoid body formation, hiPSC-mesenchymal stem cell (MSC)-like cell expansion, and chondrogenic induction for 21 days. Chondrocyte phenotype was then assessed by morphological, histological and biochemical analysis, as well as the chondrogenic expression. hiPSCs derived from peripheral blood cells were successfully generated, and were characterized by fluorescent immunostaining of pluripotent markers and teratoma formation in vivo. Flow cytometric analysis showed that MSC markers CD73 and CD105 were present in monolayer cultured hiPSC-MSC-like cells. Both alcian blue and toluidine blue staining of hiPSC-MSC-chondrogenic pellets showed as positive. Immunohistochemistry of collagen II and X staining of the pellets were also positive. The sulfated glycosaminoglycan content was significantly increased, and the expression levels of the chondrogenic markers COL2, COL10, COL9 and AGGRECAN were significantly higher in chondrogenic pellets than in undifferentiated cells. These results indicated that peripheral blood cells could be a potential source for differentiation into chondrogenic lineage in vitro via generation of mesenchymal progenitor cells. This study supports the potential applications of utilizing peripheral blood cells in generating seed cells for cartilage regenerative medicine in a patient-specific and cost-effective approach.

  8. Chondroitin sulfate immobilization at the surface of electrospun nanofiber meshes for cartilage tissue regeneration approaches

    Energy Technology Data Exchange (ETDEWEB)

    Piai, Juliana Francis [3B’s Research Group − Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães (Portugal); ICVS/3B’s − PT Government Associate Laboratory, Braga/Guimarães (Portugal); Grupo de Materiais Poliméricos e Compósitos, GMPC – Departamento de Química- Universidade Estadual de Maringá, Av. Colombo 5790, 87020-900, Maringá, Paraná (Brazil); Alves da Silva, Marta; Martins, Albino; Torres, Ana Bela [3B’s Research Group − Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães (Portugal); ICVS/3B’s − PT Government Associate Laboratory, Braga/Guimarães (Portugal); Faria, Susana [Research Center Officinal Mathematical, Department of Mathematics for Science and Technology, University of Minho, Campus de Azurém, 4800-058 Guimarães (Portugal); and others

    2017-05-01

    Highlights: • Chemical immobilization of chondroitin sulfate at the surface of nanofiber meshes. • CS-immobilized NFMs showed lower roughness and higher hydrophilicity. • CS-immobilized NFMs offer a highly effective substrate for hACs phenotypic stability. - Abstract: Aiming at improving the biocompatibility of biomaterial scaffolds, surface modification presents a way to preserve their mechanical properties and to improve the surface bioactivity. In this work, chondroitin sulfate (CS) was immobilized at the surface of electrospun poly(caprolactone) nanofiber meshes (PCL NFMs), previously functionalized by UV/O{sub 3} exposure and aminolysis. Contact angle, SEM, optical profilometry, FTIR, X-ray photoelectron spectroscopy techniques confirmed the success of CS-immobilization in PCL NFMs. Furthermore, CS-immobilized PCL NFMs showed lower roughness and higher hydrophilicity than the samples without CS. Human articular chondrocytes (hACs) were cultured on electrospun PCL NFMs with or without CS immobilization. It was observed that hACs proliferated through the entire time course of the experiment in both types of nanofibrous scaffolds, as well as for the production of glycosaminoglycans. Quantitative-PCR results demonstrated over-expression of cartilage-related genes such as Aggrecan, Collagen type II, COMP and Sox9 on both types of nanofibrous scaffolds. Morphological observations from SEM and LSCM revealed that hACs maintained their characteristic round shape and cellular agglomeration exclusively on PCL NFMs with CS immobilization. In conclusion, CS immobilization at the surface of PCL NFMs was achieved successfully and provides a valid platform enabling further surface functionalization methods in scaffolds to be developed for cartilage tissue engineering.

  9. 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

    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

  10. Extracellular vesicles in cartilage homeostasis and osteoarthritis.

    Science.gov (United States)

    Miyaki, Shigeru; Lotz, Martin K

    2018-01-01

    Extracellular vesicles carry bioactive molecules that can be transferred between cells and tissues. The purpose of this review is to describe how extracellular vesicles regulate functions of cells in cartilage and other joint tissues. The potential application of extracellular vesicles in the treatment of osteoarthritis and as biomarkers will also be discussed. Extracellular vesicles are found in synovial fluid, in articular cartilage and in the supernatants of synoviocytes and chondrocytes. Extracellular vesicles in cartilage have been proposed to be involved in cross talk between cells in joint tissues and to affect extracellular matrix turnover and inflammation. Extracellular vesicles from arthritic joints can promote abnormal gene expression and changes in cartilage extracellular matrix, including abnormal mineralization. Promising results were obtained in the therapeutic application of mesenchymal stem cell-derived extracellular vesicles for cartilage repair and experimental osteoarthritis. Extracellular vesicles have emerged as vehicles for the exchange of bioactive signaling molecules within cartilage and between joint tissues to promote joint homeostasis and arthritis pathogenesis. As the molecular content of extracellular vesicles can be customized, they offer utility in therapeutic applications.

  11. Fractures of the distal phalanx and associated soft tissue and osseous abnormalities in 22 horses with ossified sclerotic ungual cartilages diagnosed with magnetic resonance imaging.

    Science.gov (United States)

    Selberg, Kurt; Werpy, Natasha

    2011-01-01

    Ungual cartilage ossification in the forelimb is a common finding in horses. Subtle abnormalities associated with the ungual cartilages can be difficult to identify on radiographs. Magnetic resonance (MR) imaging findings of 22 horses (23 forelimbs) with a fracture of the distal phalanx and ossified ungual cartilage were characterized and graded. All horses had a forelimb fracture. Eleven involved a left forelimb (seven medial; four lateral), and 12 involved a right forelimb (five medial; seven lateral). All fractures were nonarticular, simple in configuration, and nondisplaced. The fractures were oriented in an axial proximal to abaxial distal and palmar to dorsal direction, and extended from the base of the ossified ungual cartilage into the distal phalanx. The fracture involved the fossa of the collateral ligament on the distal phalanx in 17 of 23 limbs. The palmar process and ossified ungual cartilage was abnormally mineralized in all horses. Ligaments and soft tissues adjacent to the ossified ungual cartilages were affected in all horses. The routine site of fracture in this study at the base of the ossified ungual cartilage extending into the distal phalanx suggests a biomechanical cause or focal stress point from cycling. The ligamentous structures associated with the ungual cartilages were often affected, showed altered signal intensity as well as enlargement and were thought to be contributing to the lameness. In conclusion, ossified ungual cartilages may lead to fracture of the palmar process of the distal phalanx and injury of the ungual cartilage ligaments. © 2011 Veterinary Radiology & Ultrasound.

  12. Changes in tissue morphology and collagen composition during the repair of cortical bone in the adult chicken.

    Science.gov (United States)

    Glimcher, M J; Shapiro, F; Ellis, R D; Eyre, D R

    1980-09-01

    An animal model was developed to study the histology and collagen chemistry of healing cortical bone. A hole was cut through the cortex of the mid-shaft of the humerus of the adult chicken, which allowed for repair at a mechanically stable site. After one to two weeks the collagen of the repair tissue, which consisted principally of woven bone, contained almost three times as much hydroxylysine as the collagen of normal adult bone and thus resembled the collagen of embryonic long bones. By eight weeks, when lamellar one predominated, the hydroxylysine content had fallen to normal levels. Type I was the major genetic type of collagen present throughout. No type-II collagen, characteristic of cartilage, was detected; this was consistent with the histological findings. The results established that hydroxylysine-rich type-I collagen can be made by osteoblasts of adult animals as well as by those of embryos and early postnates. In order to understand the biological characteristics of fracture healing, it is vital to study not only the macroscopic organization of the repair tissue but also the chemical properties of its molecular components. The strength of healing fractured bone, and indeed of normal bone, depends largely on the properties of the structural protein collagen. To date, it is not known whether the collagen in healing fractures is the same as that in normal bone, or whether it has distinct chemical features that may suit it for bone repair.

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

    Directory of Open Access Journals (Sweden)

    Hemanth Akkiraju

    2015-12-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Biomaterials/scaffolds. Design of bioactive, multiphasic PCL/collagen type I and type II-PCL-TCP/collagen composite scaffolds for functional tissue engineering of osteochondral repair tissue by using electrospinning and FDM techniques.

    Science.gov (United States)

    Schumann, Detlef; Ekaputra, Andrew K; Lam, Christopher X F; Hutmacher, Dietmar W

    2007-01-01

    Current clinical therapies for traumatic or chronic injuries involving osteochondral tissue result in temporary pain reduction and filling of the defect but with biomechanically inferior repair tissue. Tissue engineering of osteochondral repair tissue using autologous cells and bioactive biomaterials has the potential to overcome the current limitations and results in native-like repair tissue with good integration capabilities. For this reason, we applied two modem biomaterial design techniques, namely, electrospinning and fused deposition modeling (FDM), to produce bioactive poly(epsilon-caprolactone)/collagen (PCL/Col) type I and type II-PCL-tri-calcium phosphate (TCP)/Col composites for precursor cell-based osteochondral repair. The application of these two design techniques (electrospinning and FDM) allowed us to specifically produce the a suitable three-dimensional (3D) environment for the cells to grow into a particular tissue (cartilage and bone) in vitro prior to in vivo implantation. We hypothesize that our new designed biomaterials, seeded with autologous bone marrow-derived precursor cells, in combination with bioreactor-stimulated cell-culture techniques can be used to produce clinically relevant osteochondral repair tissue.

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

    NARCIS (Netherlands)

    R.H.J. Das (Ruud)

    2014-01-01

    markdownabstract__Abstract__ Articular cartilage enables friction-free, and thus painless, joint movement, while also functioning as a shock absorber. Although articular cartilage is made up of only few main components, natural healing fails to re-establish the native organization of the

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

    Directory of Open Access Journals (Sweden)

    Wang ZH

    2014-05-01

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

  18. Epithelial-mesenchymal transition in tissue repair and fibrosis.

    Science.gov (United States)

    Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana

    2016-09-01

    The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

  19. Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model

    Directory of Open Access Journals (Sweden)

    Weimin Guo

    2018-01-01

    Full Text Available Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM- based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects.

  20. Irradiation by pulsed Nd:YAG laser induces the production of extracellular matrix molecules by cells of the connective tissues: a tool for tissue repair

    Science.gov (United States)

    Monici, Monica; Basile, Venere; Cialdai, Francesca; Romano, Giovanni; Fusi, Franco; Conti, Antonio

    2008-04-01

    Many studies demonstrated that mechanical stress is a key factor for tissue homeostasis, while unloading induce loss of mass and impairment of function. Because of their physiological function, muscle, connective tissue, bone and cartilage dynamically interact with mechanical and gravitational stress, modifying their properties through the continuous modification of their composition. Indeed, it is known that mechanical stress increases the production of extracellular matrix (ECM) components by cells, but the mechanotransduction mechanisms and the optimal loading conditions required for an optimal tissue homeostasis are still unknown. Considering the importance of cell activation and ECM production in tissue regeneration, a proper use of mechanical stimulation could be a powerful tool in tissue repair and tissue engineering. Studies exploring advanced modalities for supplying mechanical stimuli are needed to increase our knowledge on mechanobiology and to develop effective clinical applications. Here we describe the effect of photomechanical stress, supplied by a pulsed Nd:YAG laser on ECM production by cells of connective tissues. Cell morphology, production of ECM molecules (collagens, fibronectin, mucopolysaccharides), cell adhesion and cell energy metabolism have been studied by using immunofluorescence and autofluorescence microscopy. The results show that photomechanical stress induces cytoskeleton remodelling, redistribution of membrane integrins, increase in production of ECM molecules. These results could be of consequence for developing clinical protocols for the treatment of connective tissue dideases by pulsed Nd:YAG laser.

  1. Construction of bionic tissue engineering cartilage scaffold based on three-dimensional printing and oriented frozen technology.

    Science.gov (United States)

    Xu, Yuanyuan; Guo, Xiao; Yang, Shuaitao; Li, Long; Zhang, Peng; Sun, Wei; Liu, Changyong; Mi, Shengli

    2018-02-20

    Articular cartilage (AC) has gradient features in both mechanics and histology as well as a poor regeneration ability. The repair of AC poses difficulties in both research and the clinic. In this paper, a gradient scaffold based on poly(lactic-co-glycolic acid) (PLGA)-extracellular matrix was proposed. Cartilage scaffolds with a three-layer gradient structure were fabricated by PLGA through three-dimensional printing, and the microstructure orientation and pore fabrication were made by decellularized extracellular matrix injection and directional freezing. The manufactured scaffold has a mechanical strength close to that of real cartilage. A quantitative optimization of the Young's modulus and shear modulus was achieved by material mechanics formulas, which achieved a more accurate mechanical bionic and a more stable interface performance because of the one-time molding process. At the same time, the scaffolds have a bionic and gradient microstructure orientation and pore size, and the stratification ratio can be quantitatively optimized by design of the freeze box and temperature simulation. In general, this paper provides a method to optimize AC scaffolds by both mechanics and histology as well as a bionic multimaterial scaffold. This paper is of significance for cell culture and clinical transplantation experiments. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

  2. Differentiation of human mesenchymal stromal cells cultured on collagen sponges for cartilage repair.

    Science.gov (United States)

    Sanjurjo-Rodríguez, Clara; Martínez-Sánchez, Adela Helvia; Hermida-Gómez, Tamara; Fuentes-Boquete, Isaac; Díaz-Prado, Silvia; Blanco, Francisco J

    2016-11-01

    The aim of this study was to evaluate proliferation and chondrogenic differentiation of human bone-marrow mesenchymal stromal cells (hBMSCs) cultured on collagen biomaterials. hBMSCs were seeded on five different collagen (Col) sponges: C1C2 (types I and II Col), C1C2HS (types I and II Col plus heparan sulphate (HS)), C1C2CHS (types I and II Col plus chondroitin sulphate (CHS)), C1-OLH3 (type I Col plus low molecular weight heparin) and C1CHS (type I Col plus CHS). The resulting constructs were analyzed by histological and immunohistochemical staining, molecular biology and electron microscopy. Col released into culture media was measured by a dye-binding method Results: hBMSCs on biomaterials C1C2, C1C2HS and C1C2CHS had more capacity to attach, proliferate and synthesize Col II and proteoglycans in the extracellular matrix (ECM) than on C1-OLH3 and C1CHS. The presence of aggrecan was detected only at the gene level. Total Col liberated by the cells in the supernatants in all scaffold cultures was detected. The level of Col I in the ECM was lower in C1-OLH3 and that of Col II was highest in C1C2 and C1C2HS. Electron microscopy showed differently shaped cells, from rounded to flattened, in all constructs. Col fibers in bundles were observed in C1C2CHS by transmission electron microscopy. The results show that Col I and Col II (C1C2, C1C2HS and C1C2CHS) biomaterials allowed cell proliferation and chondrogenic-like differentiation of hBMSCs at an early stage. Constructs cultured on C1C2HS and C1C2CHS showed better cartilage-like phenotype than the other ones.

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

    International Nuclear Information System (INIS)

    Srinivasan, Padma P; McCoy, Sarah Y; Yang Weidong; Farach-Carson, Mary C; Kirn-Safran, Catherine B; Jha, Amit K; Jia Xinqiao

    2012-01-01

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

  4. Hierarchical Structure of Articular Bone-Cartilage Interface and Its Potential Application for Osteochondral Tissue Engineering

    Science.gov (United States)

    Bian, Weiguo; Qin, Lian; Li, Dichen; Wang, Jin; Jin, Zhongmin

    2010-09-01

    The artificial biodegradable osteochondral construct is one of mostly promising lifetime substitute in the joint replacement. And the complex hierarchical structure of natural joint is important in developing the osteochondral construct. However, the architecture features of the interface between cartilage and bone, in particular those at the micro-and nano-structural level, remain poorly understood. This paper investigates these structural data of the cartilage-bone interface by micro computerized tomography (μCT) and Scanning Electron Microscope (SEM). The result of μCT shows that important bone parameters and the density of articular cartilage are all related to the position in the hierarchical structure. The conjunctions of bone and cartilage were defined by SEM. All of the study results would be useful for the design of osteochondral construct further manufactured by nano-tech. A three-dimensional model with gradient porous structure is constructed in the environment of Pro/ENGINEERING software.

  5. Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Dixin Cui

    2017-01-01

    Full Text Available Temporomandibular joint osteoarthritis (TMJ OA is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs, derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering.

  6. Modern cartilage imaging of the ankle

    International Nuclear Information System (INIS)

    Weber, Marc-Andre; Wuennemann, Felix; Rehnitz, Christoph; Jungmann, Pia M.; Kuni, Benita

    2017-01-01

    Talar osteochondral lesions are an important risk factor for the development of talar osteoarthritis. Furthermore, osteochondral lesions might explain persistent ankle pain. Early diagnosis of accompanying chondral defects is important to establish the optimal therapy strategy and thereby delaying or preventing the onset of osteoarthritis. The purpose of this review is to explain modern cartilage imaging with emphasis of MR imaging as well as the discussion of more sophisticated imaging studies like CT-arthrography or functional MR imaging. Pubmed literature search concerning: osteochondral lesions, cartilage damage, ankle joint, talus, 2 D MR imaging, 3 D MR imaging, cartilage MR imaging, CT-arthrography, cartilage repair, microfracture, OATS, MACT. Dedicated MR imaging protocols to delineate talar cartilage and the appearance of acute and chronic osteochondral lesions were discussed. Recent developments of MR imaging, such as isotropic 3 D imaging that has a higher signal-to noise ratio when compared to 2 D imaging, and specialized imaging methods such as CT-arthrography as well as functional MR imaging were introduced. Several classifications schemes and imaging findings of osteochondral lesions that influence the conservative or surgical therapy strategy were discussed. MRI enables after surgery the non-invasive assessment of the repair tissue and the success of implantation. Key points: Modern MRI allows for highly resolved visualization of the articular cartilage of the ankle joint and of subchondral pathologies. Recent advances in MRI include 3 D isotropic ankle joint imaging, which deliver higher signal-to-noise ratios of the cartilage and less partial volume artifacts when compared with standard 2 D sequences. In case of osteochondral lesions MRI is beneficial for assessing the stability of the osteochondral fragment and for this discontinuity of the cartilage layer is an important factor. CT-arthrography can be used in case of contraindications of MRI and

  7. Angiogenic peptide nanofibers repair cardiac tissue defect after myocardial infarction.

    Science.gov (United States)

    Rufaihah, Abdul Jalil; Yasa, I Ceren; Ramanujam, Vaibavi Srirangam; Arularasu, Suganya Cheyyatraivendran; Kofidis, Theo; Guler, Mustafa O; Tekinay, Ayse B

    2017-08-01

    Myocardial infarction remains one of the top leading causes of death in the world and the damage sustained in the heart eventually develops into heart failure. Limited conventional treatment options due to the inability of the myocardium to regenerate after injury and shortage of organ donors require the development of alternative therapies to repair the damaged myocardium. Current efforts in repairing damage after myocardial infarction concentrates on using biologically derived molecules such as growth factors or stem cells, which carry risks of serious side effects including the formation of teratomas. Here, we demonstrate that synthetic glycosaminoglycan (GAG) mimetic peptide nanofiber scaffolds induce neovascularization in cardiovascular tissue after myocardial infarction, without the addition of any biologically derived factors or stem cells. When the GAG mimetic nanofiber gels were injected in the infarct site of rodent myocardial infarct model, increased VEGF-A expression and recruitment of vascular cells was observed. This was accompanied with significant degree of neovascularization and better cardiac performance when compared to the control saline group. The results demonstrate the potential of future clinical applications of these bioactive peptide nanofibers as a promising strategy for cardiovascular repair. We present a synthetic bioactive peptide nanofiber system can enhance cardiac function and enhance cardiovascular regeneration after myocardial infarction (MI) without the addition of growth factors, stem cells or other biologically derived molecules. Current state of the art in cardiac repair after MI utilize at least one of the above mentioned biologically derived molecules, thus our approach is ground-breaking for cardiovascular therapy after MI. In this work, we showed that synthetic glycosaminoglycan (GAG) mimetic peptide nanofiber scaffolds induce neovascularization and cardiomyocyte differentiation for the regeneration of cardiovascular

  8. 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.

  9. Cartilage Tissue Engineering by the 3D Bioprinting of iPS Cells in a Nanocellulose/Alginate Bioink.

    Science.gov (United States)

    Nguyen, Duong; Hägg, Daniel A; Forsman, Alma; Ekholm, Josefine; Nimkingratana, Puwapong; Brantsing, Camilla; Kalogeropoulos, Theodoros; Zaunz, Samantha; Concaro, Sebastian; Brittberg, Mats; Lindahl, Anders; Gatenholm, Paul; Enejder, Annika; Simonsson, Stina

    2017-04-06

    Cartilage lesions can progress into secondary osteoarthritis and cause severe clinical problems in numerous patients. As a prospective treatment of such lesions, human-derived induced pluripotent stem cells (iPSCs) were shown to be 3D bioprinted into cartilage mimics using a nanofibrillated cellulose (NFC) composite bioink when co-printed with irradiated human chondrocytes. Two bioinks were investigated: NFC with alginate (NFC/A) or hyaluronic acid (NFC/HA). Low proliferation and phenotypic changes away from pluripotency were seen in the case of NFC/HA. However, in the case of the 3D-bioprinted NFC/A (60/40, dry weight % ratio) constructs, pluripotency was initially maintained, and after five weeks, hyaline-like cartilaginous tissue with collagen type II expression and lacking tumorigenic Oct4 expression was observed in 3D -bioprinted NFC/A (60/40, dry weight % relation) constructs. Moreover, a marked increase in cell number within the cartilaginous tissue was detected by 2-photon fluorescence microscopy, indicating the importance of high cell densities in the pursuit of achieving good survival after printing. We conclude that NFC/A bioink is suitable for bioprinting iPSCs to support cartilage production in co-cultures with irradiated chondrocytes.

  10. 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

  11. Is there health inequity in Europe today? The ‘strange case’ of the application of an European regulation to cartilage repair

    Directory of Open Access Journals (Sweden)

    Roberto Beretta

    2016-03-01

    Full Text Available An important regulation, issued by the European Community in 2008, regulates the authorisation and supervision of advanced therapy medicinal products (ATMP and subsequent follow up in Europe. This law contains a Hospital Exemption clause, under which some hospitals in some countries can be exempted from the regulations governing ATMPs. The application of this regulation in Europe has resulted in differences in the costs of cell therapy for cartilage injuries in Germany compared with the costs in other European countries and in the U.S. The present paper argues on the real impact of political decisions on the health of citizens, on economy of healthcare systems, and highlights a possible case of inequality among European citizens with respect to cartilage repair procedures.

  12. Fibroblast growth factors as tissue repair and regeneration therapeutics

    Directory of Open Access Journals (Sweden)

    Quentin M. Nunes

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    Andreasen, Jens O

    2012-01-01

    Healing subsequent to dental trauma is known to be very complex, a result explained by the variability of the types of dental trauma (six luxations, nine fracture types, and their combinations). On top of that, at least 16 different cellular systems get involved in more severe trauma types each...... 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....

  14. Quantification of collagen distributions in rat hyaline and fibro cartilages based on second harmonic generation imaging

    Science.gov (United States)

    Zhu, Xiaoqin; Liao, Chenxi; Wang, Zhenyu; Zhuo, Shuangmu; Liu, Wenge; Chen, Jianxin

    2016-10-01

    Hyaline cartilage is a semitransparent tissue composed of proteoglycan and thicker type II collagen fibers, while fibro cartilage large bundles of type I collagen besides other territorial matrix and chondrocytes. It is reported that the meniscus (fibro cartilage) has a greater capacity to regenerate and close a wound compared to articular cartilage (hyaline cartilage). And fibro cartilage often replaces the type II collagen-rich hyaline following trauma, leading to scar tissue that is composed of rigid type I collagen. The visualization and quantification of the collagen fibrillar meshwork is important for understanding the role of fibril reorganization during the healing process and how different types of cartilage contribute to wound closure. In this study, second harmonic generation (SHG) microscope was applied to image the articular and meniscus cartilage, and textural analysis were developed to quantify the collagen distribution. High-resolution images were achieved based on the SHG signal from collagen within fresh specimens, and detailed observations of tissue morphology and microstructural distribution were obtained without shrinkage or distortion. Textural analysis of SHG images was performed to confirm that collagen in fibrocartilage showed significantly coarser compared to collagen in hyaline cartilage (p wound repair following cartilage injury.

  15. 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.

  16. 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.

  17. Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

    Science.gov (United States)

    Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

    2014-10-01

    Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

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

    Science.gov (United States)

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

    2015-05-15

    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, which aim to improve ease of use and cost-effectiveness, are progressively explored. The use of MSCs in cartilage repair makes it possible to develop single-stage cell-based therapies. However, true single-stage procedures rely on one intervention, which will limit cell sources to fraction concentrates containing autologous MSCs or culture-expanded allogeneic MSCs. So far, it seems both autologous and allogeneic cells can safely be applied, but clinical studies are still ongoing and little information on clinical outcome is available. Further development of cell-based therapies may lead to clinical-grade, standardized, off-the-shelf products with easy handling for orthopedic surgeons. Although as of yet no preclinical or clinical studies are ongoing which explore the use of induced pluripotent stem cells for cartilage repair, a good manufacturing practice-grade induced pluripotent stem cell line might become the basis for such a product in the future, providing that cell fate can be controlled. The use of stem cells in clinical trials brings along new ethical issues, such as proper controls and selecting primary outcome measures. More clinical trials are needed to estimate detailed risk-benefit ratios and trials must be carefully designed to minimize risks and burdens for patients while choosing outcome measures that allow for adequate comparison with results from similar trials. In this review, we discuss the different aspects of new stem cell-based treatments, including safety and ethical issues, as well as provide an overview of current clinical trials exploring these approaches and future perspectives.

  19. 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

  20. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Jaewoo Pak

    2016-08-01

    Full Text Available This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs and homogenized extracellular matrix (ECM in the form of adipose stromal vascular fraction (SVF, along with hyaluronic acid (HA and platelet-rich plasma (PRP activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI data, functional rating index, range of motion (ROM, and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees.

  1. Advances and Perspectives on Tissue Repair and Healing

    Science.gov (United States)

    Pinheiro, Antonio L. B.; Marques, Aparecida M. C.; de Sousa, Ana Paula C.; Aciole, Jouber M. S.; Soares, Luiz G. P.

    2011-08-01

    Wound healing involves local and systemic responses that reflect the etiology of the lesion, type of tissue, systemic condition and others. Despite being essentially the same for different wounds, the pattern of healing may change due to intrinsic and/or extrinsic factors. The type of tissue has also to be considered. Several therapeutic approaches have been used to improve healing including phototherapies such as Laser, LEDs and Lamps. Their effects on soft and mineralized tissues are well reported. The choice of appropriated parameters is essential for the results of the treatment and includes wavelength, power density, energy, duration and frequency of application and others. We studied the effects of different types of light on the healing of both soft and mineralized tissues using different models. We found that the use of Laser and polarized light are effective on improving the healing of diabetic and undernourished animals. We also found that Laser light is capable of improving the healing of drug-induced impairment and on increasing the survival rate of flaps on both diabetic and non-diabetic animals. We have also studied and shown the influence of the laser parameters on the healing of surgical and laser wounds. Lately we verified the positive effect of LEDs on healing. We used Laser/LED light for improving bone healing in conditions such as in dental implants, autologous grafts, biomaterials and fractures. From these reports and our own experience we have no doubt whatsoever that the use of phototherapies, carried out with appropriate parameters, promotes quicker tissue repair.

  2. The composition of engineered cartilage at the time of implantation determines the likelihood of regenerating tissue with a normal collagen architecture.

    Science.gov (United States)

    Nagel, Thomas; Kelly, Daniel J

    2013-04-01

    The biomechanical functionality of articular cartilage is derived from both its biochemical composition and the architecture of the collagen network. Failure to replicate this normal Benninghoff architecture in regenerating articular cartilage may in turn predispose the tissue to failure. In this article, the influence of the maturity (or functionality) of a tissue-engineered construct at the time of implantation into a tibial chondral defect on the likelihood of recapitulating a normal Benninghoff architecture was investigated using a computational model featuring a collagen remodeling algorithm. Such a normal tissue architecture was predicted to form in the intact tibial plateau due to the interplay between the depth-dependent extracellular matrix properties, foremost swelling pressures, and external mechanical loading. In the presence of even small empty defects in the articular surface, the collagen architecture in the surrounding cartilage was predicted to deviate significantly from the native state, indicating a possible predisposition for osteoarthritic changes. These negative alterations were alleviated by the implantation of tissue-engineered cartilage, where a mature implant was predicted to result in the formation of a more native-like collagen architecture than immature implants. The results of this study highlight the importance of cartilage graft functionality to maintain and/or re-establish joint function and suggest that engineering a tissue with a native depth-dependent composition may facilitate the establishment of a normal Benninghoff collagen architecture after implantation into load-bearing defects.

  3. Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing

    Energy Technology Data Exchange (ETDEWEB)

    Sobol, Emil [Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, RussiabFederal Scientific Research Centre “Crystallography and Photonics” of the Russian Academy of Sciences, Institute of Photonic Technologies, Moscow, Russia; Baum, Olga [Federal Scientific Research Centre “Crystallography and Photonics” of the Russian Academy of Sciences, Institute of Photonic Technologies, Moscow, Russia; Shekhter, Anatoly [Sechenov First Medical University of Moscow, Institute of Regenerative Medicine, Moscow, Russia; Wachsmann-Hogiu, Sebastian [University of California, Center for Biophotonics, Department of Pathology and Laboratory Medicine, Sacramento, California, United StateseMcGill University, Department of Bioengineering, Montreal, Canada; Shnirelman, Alexander [Concordia University, Department of Mathematics and Statistics, Montreal, Canada; Alexandrovskaya, Yulia [Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, RussiabFederal Scientific Research Centre “Crystallography and Photonics” of the Russian Academy of Sciences, Institute of Photonic Technologies, Moscow, Russia; Sadovskyy, Ivan [Argonne National Laboratory, Materials Science Division, Argonne, Illinois, United States; Vinokur, Valerii [Argonne National Laboratory, Materials Science Division, Argonne, Illinois, United States

    2017-05-31

    Pores are vital for functioning of avascular tissues. Laser-induced pores play an important role in the process of cartilage regeneration. The aim of any treatment for osteoarthritis is to repair hyaline-type cartilage. The aims of this study are to answer two questions: (1) How do laser-assisted pores affect the cartilaginous cells to synthesize hyaline cartilage (HC)? and (2) How can the size distribution of pores arising in the course of laser radiation be controlled? We have shown that in cartilage, the pores arise predominately near chondrocytes, which promote nutrition of cells and signal molecular transfer that activates regeneration of cartilage. In vivo laser treatment of damaged cartilage of miniature pig joints provides cellular transformation and formation of HC. We propose a simple model of pore formation in biopolymers that paves the way for going beyond the trial-anderror approach when choosing an optimal laser treatment regime. Our findings support the approach toward laser healing of osteoarthritis.

  4. Detection of Repair of the Zone of Calcified Cartilage with Osteoarthritis through Mesenchymal Stem Cells by Ultrashort Echo Time Magnetic Resonance Imaging.

    Science.gov (United States)

    Zhou, Quan; Li, Shao-Lin; Ma, Ya-Jun; de Tal, Vicki; Li, Wei; Zhao, Ying-Hua

    2018-02-05

    Currently, magnetic resonance imaging (MRI) is the most commonly used imaging modality for observing the growth and development of mesenchymal stem cells (MSCs) after in vivo transplantation to treat osteoarthritis (OA). However, it is a challenge to accurately monitor the treatment effects of MSCs in the zone of calcified cartilage (ZCC) with OA. This is especially true in the physiological and biochemical views that are not accurately detected by MRI contrast agents. In contrast, ultrashort time echo (UTE) MRI has been shown to be sensitive to the presence of the ZCC, creating the potential for more effectively observing the repair of the ZCC in OA by MSCs. A special focus is given to the outlook of the use of UTE MRI to detect repair of the ZCC with OA through MSCs. The limitations of the current techniques for clinical applications and future directions are also discussed. Using the combined keywords: "osteoarthritis", "mesenchymal stem cells", "calcified cartilage", and "magnetic resonance imaging", the PubMed/MEDLINE literature search was conducted up to June 1, 2017. A total of 132 published articles were initially identified citations. Of the 132 articles, 48 articles were selected after further detailed review. This study referred to all the important English literature in full. In contrast, UTE MRI has been shown to be sensitive to the presence of the ZCC, creating the potential for more effectively observing the repair of the ZCC in OA by MSCs. The current studies showed that the ZCC could be described in terms of its histomorphology and biochemistry by UTE MRI. We prospected that UTE MRI has been shown the potential for more effectively observing the repair of the ZCC in OA by MSCs in vivo.

  5. The importance of bicarbonate and nonbicarbonate buffer systems in batch and continuous flow bioreactors for articular cartilage tissue engineering.

    Science.gov (United States)

    Khan, Aasma A; Surrao, Denver C

    2012-05-01

    In cartilage tissue engineering an optimized culture system, maintaining an appropriate extracellular environment (e.g., pH of media), can increase cell proliferation and extracellular matrix (ECM) accumulation. We have previously reported on a continuous-flow bioreactor that improves tissue growth by supplying the cells with a near infinite supply of medium. Previous studies have observed that acidic environments reduce ECM synthesis and chondrocyte proliferation. Hence, in this study we investigated the combined effects of a continuous culture system (bioreactor) together with additional buffering agents (e.g., sodium bicarbonate [NaHCO₃]) on cartilaginous tissue growth in vitro. Isolated bovine chondrocytes were grown in three-dimensional cultures, either in static conditions or in a continuous-flow bioreactor, in media with or without NaHCO₃. Tissue constructs cultivated in the bioreactor with NaHCO₃-supplemented media were characterized with significantly increased (p<0.05) ECM accumulation (glycosaminoglycans a 98-fold increase; collagen a 25-fold increase) and a 13-fold increase in cell proliferation, in comparison with static cultures. Additionally, constructs grown in the bioreactor with NaHCO₃-supplemented media were significantly thicker than all other constructs (p<0.05). Further, the chondrocytes from the primary construct expanded and synthesized ECM, forming a secondary construct without a separate expansion phase, with a diameter and thickness of 4 mm and 0.72 mm respectively. Tissue outgrowth was negligible in all other culturing conditions. Thus this study demonstrates the advantage of employing a continuous flow bioreactor coupled with NaHCO₃ supplemented media for articular cartilage tissue engineering.

  6. Cartilage imaging: motivation, techniques, current and future significance

    International Nuclear Information System (INIS)

    Link, Thomas M.; Stahl, Robert; Woertler, Klaus

    2007-01-01

    Cartilage repair techniques and pharmacological therapies are currently areas of major clinical interest and research, in particular to prevent and treat osteoarthritis. MR imaging-based techniques to visualize cartilage are prerequisites to guide and monitor these therapies. In this review article, standard MR imaging sequences are described, including proton density-weighted fast spin echo, spoiled gradient echo and dual echo steady state sequences. In addition, new sequences that have been developed and are currently being investigated are presented, including driven equilibrium Fourier transform and steady-state free precession-based imaging. Using high-field MR imaging at 3.0-T, visualization of cartilage and the related pathology has been improved. Volumetric quantitative cartilage MR imaging was developed as a tool to monitor the progression of osteoarthritis and to evaluate new pharmacological cartilage protective therapies. The most exciting developments, however, are in the field of cartilage matrix assessment with quantitative dGEMRIC, T2 and T1rho mapping techniques. These techniques aim at detecting cartilage damage at a stage when changes are potentially still reversible, before cartilage tissue is lost. There is currently substantial interest in these techniques from rheumatologists and orthopedists; radiologists therefore need to keep up with these developments. (orig.)

  7. Viability and Tissue Quality of Cartilage Flaps From Patients With Femoroacetabular Hip Impingement: A Matched-Control Comparison

    Science.gov (United States)

    Rodriguez-Fontan, Francisco; Payne, Karin A.; Chahla, Jorge; Mei-Dan, Omer; Richards, Abigail; Uchida, Soshi; Pascual-Garrido, Cecilia

    2017-01-01

    Background: Chondrolabral damage is commonly observed in patients with cam-type femoroacetabular impingement (FAI). Chondral flap reattachment has recently been proposed as a possible preservation technique. Purpose/Hypothesis: The purpose of this study was to determine the viability and tissue quality of chondral flaps from patients with FAI at the time of arthroscopy. It was hypothesized that chondral flaps from patients with cam lesions of the hip would exhibit less viability and greater tissue degeneration than would those of a matched control group. Study Design: Cohort study; Level of evidence, 2. Methods: Patients with cam-type FAI who were treated with hip arthroscopy between 2014 and 2016 were asked to participate in this study. The cartilage lesions were localized and classified intraoperatively according to Beck classification. A chondral flap (study group) and a cartilage sample (control group) were obtained from each patient for histologic evaluation. Cellular viability and tissue quality were examined and compared in both groups. Cellular viability was determined with live/dead staining, and tissue quality was evaluated using safranin O/fast green, hematoxylin and eosin (H&E) staining, and immunohistochemistry for collagen II. Osteoarthritis Research Society International (OARSI) grading was used for quality assessment, and Image J software was used to calculate the percentage of tissue viability and Col II stain. Results: A total of 10 male patients with a mean age of 38.4 years (range, 30-55 years) were enrolled. All chondral flaps were classified as Beck grade 4. The mean cellular viability of the chondral flaps was reduced (54.6% ± 25.6%), and they were found to be degenerated (OARSI grade, 4 ± 1.27). Control samples also had reduced viability (38.8% ± 30.3%) and were degenerative (OARSI grade, 3.5 ± 1.38). There was no statistically significant intergroup difference for viability (P = .203) or OARSI grade (P = .645), nor was there an

  8. Tissue-specific endothelial cells: a promising approach for augmentation of soft tissue repair in orthopedics.

    Science.gov (United States)

    Lebaschi, Amir; Nakagawa, Yusuke; Wada, Susumu; Cong, Guang-Ting; Rodeo, Scott A

    2017-12-01

    Biologics are playing an increasingly significant role in the practice of modern medicine and surgery in general and orthopedics in particular. Cell-based approaches are among the most important and widely used modalities in orthopedic biologics, with mesenchymal stem cells and other multi/pluripotent cells undergoing evaluation in numerous preclinical and clinical studies. On the other hand, fully differentiated endothelial cells (ECs) have been found to perform critical roles in homeostasis of visceral tissues through production of an adaptive panel of so-called "angiocrine factors." This newly discovered function of ECs renders them excellent candidates for novel approaches in cell-based biologics. Here, we present a review of the role of ECs and angiocrine factors in some visceral tissues, followed by an overview of current cell-based approaches and a discussion of the potential applications of ECs in soft tissue repair. © 2017 New York Academy of Sciences.

  9. Histochemistry as a unique approach for investigating normal and osteoarthritic cartilage

    Directory of Open Access Journals (Sweden)

    G. Musumeci

    2014-04-01

    Full Text Available In this review article, we describe benefits and disadvantages of the established histochemical methods for studying articular cartilage tissue under normal, pathological and experimental conditions. We illustrate the current knowledge on cartilage tissue based on histological and immunohistochemical aspects, and in conclusion we provide a short overview on the degeneration of cartilage, such as osteoarthritis. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to implement the knowledge in the study of cartilage in the last years, and histochemistry proved to be an especially powerful tool to this aim.

  10. Nanotechnology Biomimetic Cartilage Regenerative Scaffolds

    Science.gov (United States)

    Sardinha, Jose Paulo; Myers, Simon

    2014-01-01

    Cartilage has a limited regenerative capacity. Faced with the clinical challenge of reconstruction of cartilage defects, the field of cartilage engineering has evolved. This article reviews current concepts and strategies in cartilage engineering with an emphasis on the application of nanotechnology in the production of biomimetic cartilage regenerative scaffolds. The structural architecture and composition of the cartilage extracellular matrix and the evolution of tissue engineering concepts and scaffold technology over the last two decades are outlined. Current advances in biomimetic techniques to produce nanoscaled fibrous scaffolds, together with innovative methods to improve scaffold biofunctionality with bioactive cues are highlighted. To date, the majority of research into cartilage regeneration has been focused on articular cartilage due to the high prevalence of large joint osteoarthritis in an increasingly aging population. Nevertheless, the principles and advances are applicable to cartilage engineering for plastic and reconstructive surgery. PMID:24883273

  11. Advances in electrospun nanofibers for bone and cartilage regeneration.

    Science.gov (United States)

    Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P; Balasubramanian, Preethi; Jin, Guorui; Valipouri, Afsaneh; Ramakrishna, Seeram

    2013-07-01

    Regeneration of bone and cartilage tissues has been an important issue for biological repair in the field of regenerative medicine. The rapidly emerging field of tissue engineering holds great promise for repair and generation of functional bone and cartilage substitutes with a combination of biomaterials, cells, drugs and growth factors. Scaffolds play a pivotal role in tissue engineering as they mimic the natural extracellular matrix (ECM) and play an important role in guiding cell adhesion and proliferation, and maintaining the normal phenotype of the tissues. The use of tissue-engineered grafts based on scaffolds has found to be a more effective method than conventional implantations of autograft, allograft, xenograft. In recent years much attention has been given to electrospinning as a feasible and versatile technique for fabrication of nanofibrous scaffolds, with large surface area to volume ratio, high porosity, mechanical properties and physical dimension similar to the ECM of natural tissues. Extensive research has been carried out for fabrication polymeric nanofibrous substrates with incorporation of hydroxyapatite nanoparticles or bone morphogenetic protein molecules for efficient tissue repair. Here we review on the literature of electrospun nanofibrous scaffolds, their modifications, and advances aimed towards the rapid regeneration of bone and cartilage.

  12. 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.

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

    Science.gov (United States)

    Jeong, Claire G; Hollister, Scott J

    2010-05-01

    The goal of this study was to determine material effects on cartilage regeneration for scaffolds with the same controlled architecture. The 3D polycaprolactone (PCL), poly (glycerol sebacate) (PGS), and poly (1,8 octanediol-co-citrate) (POC) scaffolds of the same design were physically characterized and tissue regeneration in terms of cell phenotype, cellular proliferation and differentiation, and matrix production were compared to find which material would be most optimal for cartilage regeneration in vitro. POC provided the best support for cartilage regeneration in terms of tissue ingrowth, matrix production, and relative mRNA expressions for chondrocyte differentiation (Col2/Col1). PGS was seen as the least favorable material for cartilage based on its relatively high de-differentiation (Col1), hypertrophic mRNA expression (Col10) and high matrix degradation (MMP13, MMP3) results. PCL still provided microenvironments suitable for cells to be active yet it seemed to cause de-differentiation (Col1) of chondrocytes inside the scaffold while many cells migrated out, growing cartilage outside the scaffold. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  14. Postnatal administration of 2-oxoglutaric acid improves articular and growth plate cartilages and bone tissue morphology in pigs prenatally treated with dexamethasone.

    Science.gov (United States)

    Tomaszewska, E; Dobrowolski, P; Wydrych, J

    2012-10-01

    The potential effects of prenatal administration of dexamethasone (DEX) and postnatal treatment with 2-oxoglutaric acid (2-Ox) on postnatal development of connective tissue of farm animals were not examined experimentally. The aim of this study was to establish changes in morphological parameters of bone and articular and growth plate cartilages damaged by the prenatal action of DEX in piglets supplemented with 2-Ox. The 3 mg of DEX was administered by intramuscular route every second day from day 70 of pregnancy to parturition and then piglets were supplemented with 2-Ox during 35 days of postnatal life (0.4 g/kg body weight). The mechanical properties, BMD and BMC of bones, and histomorphometry of articular and growth plate cartilages were determined. Maternal treatment with DEX decreased the weight by 48%, BMD by 50% and BMC by 61% of the tibia in male piglets while such action of DEX in female piglets was not observed. DEX led to thinning of articular and growth plate cartilages and trabeculae thickness and reduced the serum GH concentration in male piglets. The administration of 2-Ox prevented the reduction of trabeculae thickness, the width of articular and growth plate cartilages in male piglets connected with higher growth hormone concentration compared with non-supplemented male piglets. The result showed that the presence of 2-Ox in the diet had a positive effect on the development of connective tissue in pigs during suckling and induced a complete recovery from bone and cartilage damage caused by prenatal DEX action.

  15. Hematopoietic tissue repair under chronic low daily dose irradiation

    Science.gov (United States)

    Seed, T. M.

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

  16. 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.

  17. The use of fibrin and poly(lactic-co-glycolic acid hybrid scaffold for articular cartilage tissue engineering: an in vivo analysis

    Directory of Open Access Journals (Sweden)

    S Munirah

    2008-02-01

    Full Text Available Our preliminary results indicated that fibrin and poly(lactic-co-glycolic acid (PLGA hybrid scaffold promoted early chondrogenesis of articular cartilage constructs in vitro. The aim of this study was to evaluate in vivo cartilaginous tissue formation by chondrocyte-seeded fibrin/PLGA hybrid scaffolds. PLGA scaffolds were soaked carefully, in chondrocyte-fibrin suspension, and polymerized by dropping thrombin-calcium chloride (CaCl2 solution. PLGA-seeded chondrocytes were used as a control. Resulting constructs were implanted subcutaneously, at the dorsum of nude mice, for 4 weeks. Macroscopic observation, histological evaluation, gene expression and sulphated-glycosaminoglycan (sGAG analyses were performed at each time point of 1, 2 and 4 weeks post-implantation. Cartilaginous tissue formation in fibrin/PLGA hybrid construct was confirmed by the presence of lacunae and cartilage-isolated cells embedded within basophilic ground substance. Presence of proteoglycan and glycosaminoglycan (GAG in fibrin/PLGA hybrid constructs was confirmed by positive Safranin O and Alcian Blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrices. Chondrogenic properties were further demonstrated by the expression of gene encoded cartilage-specific markers, collagen type II and aggrecan core protein. The sGAG production in fibrin/PLGA hybrid constructs was higher than in the PLGA group. In conclusion, fibrin/PLGA hybrid scaffold promotes cartilaginous tissue formation in vivo and may serve as a potential cell delivery vehicle and a structural basis for articular cartilage tissue-engineering.

  18. Self assembling bioactive materials for cell adhesion in tissue repair

    Science.gov (United States)

    Hwang, Julia J.

    This work involved the study of biodegradable and biocompatible materials that have the potential to modify tissue engineering scaffolds through self assembly, generating multiple layers that deliver bioactivity. Diblock biomaterials containing cholesteryl moieties and oligomers of lactic acid units were found to form single crystals when precipitated from hot ethanol and smectic liquid crystalline phases when cast as a film. Cell culture experiments on these films with 3T3 and 3T6 fibroblasts indicated that these ordered materials form surfaces with specific chemistries that favored cell adhesion, spreading, and proliferation suggesting the potential of mediating human tissue repair. The author believes the cholesteryl moieties found on the surface play a key role in determining cell behavior. Cholesteryl-(L-lactic acid) diblock molecules were then functionalized with moieties including vitamin Bx, cholesterol, and the anti-inflammatory drug indomethacin. An unstable activated ester between indomethacin and the diblock molecule resulted in the release of indomethacin into the culture medium which inhibited the proliferation of 3T3 fibroblasts. Finally, a series of molecules were designed to incorporate dendrons based on amino acids at the termini of the diblock structures. It was determined that lysine, a basic amino acid, covalently coupled to cholesteryl-(L-lactic acid) can promote cell adhesion and spreading while negatively charged and zwitterionic 2nd generation dendrons based on aspartic acid do not. Incorporation of the well known arginine-glycine-aspartic acid (RGD) sequence, which is found in many adhesive proteins, to the dendrons imparted integrin-mediated cell adhesion as evidenced by the formation of stress fibers. We also explored the capacity of integrin receptors to bind to ligands that are not the linear form of RGD, but have R, G, and D spatially positioned to mimic the linear RGD environments. For this purpose, the arms of the 2 nd generation

  19. 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.

  20. 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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

    Bonakdar, Shahin; Emami, Shahriar Hojjati; Shokrgozar, Mohammad Ali; Farhadi, Afshin; Ahmadi, Seyed Amir Hoshiar; Amanzadeh, Amir

    2010-01-01

    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.

  2. Delayed gadolinium-enhanced MRI of cartilage and T2 mapping for evaluation of reparative cartilage-like tissue after autologous chondrocyte implantation associated with Atelocollagen-based scaffold in the knee

    Energy Technology Data Exchange (ETDEWEB)

    Tadenuma, Taku; Uchio, Yuji; Kumahashi, Nobuyuki; Iwasa, Junji [Shimane University School of Medicine, Department of Orthopaedic Surgery, Izumo-shi, Shimane-ken (Japan); Fukuba, Eiji; Kitagaki, Hajime [Shimane University School of Medicine, Department of Radiology, Izumo-shi, Shimane-ken (Japan); Ochi, Mitsuo [Hiroshima University, Department of Orthopaedic Surgery, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Minami-ku, Hiroshima (Japan)

    2016-10-15

    To elucidate the quality of tissue-engineered cartilage after an autologous chondrocyte implantation (ACI) technique with Atelocollagen gel as a scaffold in the knee in the short- to midterm postoperatively, we assessed delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and T2 mapping and clarified the relationship between T1 and T2 values and clinical results. In this cross-sectional study, T1 and T2 mapping were performed on 11 knees of 8 patients (mean age at ACI, 37.2 years) with a 3.0-T MRI scanner. T1{sub implant} and T2{sub implant} values were compared with those of the control cartilage region (T1{sub control} and T2{sub control}). Lysholm scores were also assessed for clinical evaluation. The relationships between the T1 and T2 values and the clinical Lysholm score were also assessed. There were no significant differences in the T1 values between the T1{sub implant} (386.64 ± 101.78 ms) and T1{sub control} (375.82 ± 62.89 ms) at the final follow-up. The implants showed significantly longer T2 values compared to the control cartilage (53.83 ± 13.89 vs. 38.21 ± 4.43 ms). The postoperative Lysholm scores were significantly higher than the preoperative scores. A significant correlation was observed between T1{sub implant} and clinical outcomes, but not between T2{sub implant} and clinical outcomes. Third-generation ACI implants might have obtained an almost equivalent glycosaminoglycan concentration compared to the normal cartilage, but they had lower collagen density at least 3 years after transplantation. The T1{sub implant} value, but not the T2 value, might be a predictor of clinical outcome after ACI. (orig.)

  3. Engineering Lubrication in Articular Cartilage

    Science.gov (United States)

    McNary, Sean M.; Athanasiou, Kyriacos A.

    2012-01-01

    Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional

  4. Hematopoietic tissue repair under chronic low daily dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.

    1994-12-01

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

  5. Hematopoietic tissue repair under chronic low daily dose irradiation

    International Nuclear Information System (INIS)

    Seed, T.M.

    1994-01-01

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

  6. 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.

  7. Tissue repair genes: the TiRe database and its implication for skin wound healing

    OpenAIRE

    Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E.

    2016-01-01

    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 ...

  8. Cartilage Repair with Mesenchymal Stem Cells (MSCs) Delivered in a Novel Chondroitin Sulfate / Polyethylene Glycol Hydrogel in a Rabbit Animal Model”

    Science.gov (United States)

    Pascual-Garrido, Cecilia; Fontan, Francisco Rodriguez; Chahla, Jorge; Payne, Karin; Aisenbrey, Elizabeth; Bryant, Stephanie J.; LaPrade, Robert F.; Clohisy, John C.; Goodrich, Laurie R.

    2017-01-01

    Objectives: To determine whether rabbit bone marrow-derived MSCs embedded in a chondroitin sulfate (ChS)/ poly (ethylene glycol) (PEG) biodegradable hydrogel display enhanced in vivo chondrogenesis as compared to ChS/PEG hydrogel alone, in a critical sized osteochondral defect in a rabbit animal model. Methods: Allogenic MSCs were harvested from bone marrow and expanded in specific media (20% fetal bovine serum, 50 U ml-1 penicillin, 50 mg ml-1 streptomycin, 20 mg ml-1 gentamicin, and 5 ng ml-1 bFGF (fibroblast growth factor) in low glucose Dulbecco’s modified Eagle media) under standard cell culture conditions (37o C with 5% CO2). Surgery was carried out in 10 mature New Zealand white rabbits (8 months old). A critical sized chondral defect (3mm) was performed bilaterally in the trochlear groove of the femoropatellar joint in all ten rabbits. Three treatment groups were established as follows: 1- hydrogel alone (5N), 2- hydrogel with MSCs (3 x 106 cell/ml) (5N), and 3- control defect with no treatment (10N). Animals were left to ambulate freely after surgery. At 6 months postoperative, euthanasia was performed. Macroscopic evaluation of defect repair was performed by four observers unaware of treatment groups using ICRS (International Cartilage Repair Society) scoring. Microscopic evaluation was performed using the O’Driscoll grading system. Using SigmaPlot 11.0 statistical software (Systat Software, San Jose, CA, USA), comparison between groups was performed with an ANOVA test to see if differences existed between treatment groups. Tukey’s correction was used to adjust for multiple group comparisons, and two independent t-tests: 1- between rabbits receiving hydrogel alone vs. their respective controls; 2- between rabbits receiving hydrogel / MSCs vs. their respective controls; for both ICRS and O’Driscoll scores, being a total of six statistical analyses. Results: At time of euthanasia, all hydrogels remained in place. There was no synovial reaction or

  9. Modern cartilage imaging of the ankle; Moderne Knorpelbildgebung des Sprunggelenks

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Marc-Andre; Wuennemann, Felix; Rehnitz, Christoph [University Hospital Heidelberg (Germany). Diagnostic and Interventional Radiology; Jungmann, Pia M. [Technical Univ. Munich (Germany). Radiology; Kuni, Benita [Ortho-Zentrum Karlsruhe (Germany). Orthopedics and Trauma Surgery

    2017-10-15

    Talar osteochondral lesions are an important risk factor for the development of talar osteoarthritis. Furthermore, osteochondral lesions might explain persistent ankle pain. Early diagnosis of accompanying chondral defects is important to establish the optimal therapy strategy and thereby delaying or preventing the onset of osteoarthritis. The purpose of this review is to explain modern cartilage imaging with emphasis of MR imaging as well as the discussion of more sophisticated imaging studies like CT-arthrography or functional MR imaging. Pubmed literature search concerning: osteochondral lesions, cartilage damage, ankle joint, talus, 2 D MR imaging, 3 D MR imaging, cartilage MR imaging, CT-arthrography, cartilage repair, microfracture, OATS, MACT. Dedicated MR imaging protocols to delineate talar cartilage and the appearance of acute and chronic osteochondral lesions were discussed. Recent developments of MR imaging, such as isotropic 3 D imaging that has a higher signal-to noise ratio when compared to 2 D imaging, and specialized imaging methods such as CT-arthrography as well as functional MR imaging were introduced. Several classifications schemes and imaging findings of osteochondral lesions that influence the conservative or surgical therapy strategy were discussed. MRI enables after surgery the non-invasive assessment of the repair tissue and the success of implantation. Key points: Modern MRI allows for highly resolved visualization of the articular cartilage of the ankle joint and of subchondral pathologies. Recent advances in MRI include 3 D isotropic ankle joint imaging, which deliver higher signal-to-noise ratios of the cartilage and less partial volume artifacts when compared with standard 2 D sequences. In case of osteochondral lesions MRI is beneficial for assessing the stability of the osteochondral fragment and for this discontinuity of the cartilage layer is an important factor. CT-arthrography can be used in case of contraindications of MRI and

  10. Extracellular Vesicles: Immunomodulatory messengers in the context of tissue repair/regeneration.

    Science.gov (United States)

    Silva, Andreia M; Teixeira, José H; Almeida, Maria Ines; Gonçalves, Raquel M; Barbosa, Mário A; Santos, Susana G

    2017-02-15

    Inflammation is a complex and highly regulated biological process, crucial for a variety of functions in the human body, from host response against infectious agents to initiation of repair/regeneration of injured tissues. In the context of tissue repair, the action of different immune cell populations and their interplay with tissue specific cells, including stem cells, is still being uncovered. Extracellular Vesicles (EV) are small membrane vesicles secreted by cells in a controlled manner, which can act locally and systemically. The ability of EV to influence tissue repair and regeneration has been proposed as a physiologically intelligent and targeted strategy of cell communication. Herein, the role of EV in tissue repair is reviewed, summarising first their contribution to the regulation of immune cell function, and discussing the implications for the resolution of inflammation during repair. Next, the impact of EV on cell proliferation and differentiation, and on extracellular matrix remodelling, key aspects of the subsequent phases of tissue repair, is addressed. Finally, EV-based therapies are discussed, focusing on the application of naturally produced EV, and the use of EV as delivery vehicles. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Amir Sotoudeh

    2013-05-01

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

  13. Predictive value of in vitro and in vivo assays in bone and cartilage repair - What do they really tell us about the clinical performance?

    NARCIS (Netherlands)

    Habibovic, Pamela; Fisher, John P.; Woodfield, T.B.F.; de Groot, K.; van Blitterswijk, Clemens

    2006-01-01

    The continuous increase of life expectancy leads to an expanding demand for repair and replacement of damaged and degraded organs and tissues. Recent completion of a first version of the human genome sequence is a great breakthrough for the field of pharmaceutics. It is conceivable that new

  14. Non-invasive monitoring of in vivo hydrogel degradation and cartilage regeneration by multiparametric MR imaging

    Science.gov (United States)

    Chen, Zelong; Yan, Chenggong; Yan, Shina; Liu, Qin; Hou, Meirong; Xu, Yikai; Guo, Rui

    2018-01-01

    Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering. However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging. Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months. Results: USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate. Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling in vitro. CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends in vivo. The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations. Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration. PMID:29464005

  15. In vitro culture increases mechanical stability of human tissue engineered cartilage constructs by prevention of microscale scaffold buckling.

    Science.gov (United States)

    Middendorf, Jill M; Shortkroff, Sonya; Dugopolski, Caroline; Kennedy, Stephen; Siemiatkoski, Joseph; Bartell, Lena R; Cohen, Itai; Bonassar, Lawrence J

    2017-11-07

    Many studies have measured the global compressive properties of tissue engineered (TE) cartilage grown on porous scaffolds. Such scaffolds are known to exhibit strain softening due to local buckling under loading. As matrix is deposited onto these scaffolds, the global compressive properties increase. However the relationship between the amount and distribution of matrix in the scaffold and local buckling is unknown. To address this knowledge gap, we studied how local strain and construct buckling in human TE constructs changes over culture times and GAG content. Confocal elastography techniques and digital image correlation (DIC) were used to measure and record buckling modes and local strains. Receiver operating characteristic (ROC) curves were used to quantify construct buckling. The results from the ROC analysis were placed into Kaplan-Meier survival function curves to establish the probability that any point in a construct buckled. These analysis techniques revealed the presence of buckling at early time points, but bending at later time points. An inverse correlation was observed between the probability of buckling and the total GAG content of each construct. This data suggests that increased GAG content prevents the onset of construct buckling and improves the microscale compressive tissue properties. This increase in GAG deposition leads to enhanced global compressive properties by prevention of microscale buckling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Inverse Regulation of Early and Late Chondrogenic Differentiation by Oxygen Tension Provides Cues for Stem Cell-Based Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Sophie Portron

    2015-01-01

    Full Text Available Background/Aims: Multipotent stem/stromal cells (MSC are considered promising for cartilage tissue engineering. However, chondrogenic differentiation of MSC can ultimately lead to the formation of hypertrophic chondrocytes responsible for the calcification of cartilage. To prevent the production of this calcified matrix at the articular site, the late hypertrophic differentiation of MSCs must be carefully controlled. Given that articular cartilage is avascular, we hypothesized that in addition to its stimulatory role in the early differentiation of chondrogenic cells, hypoxia may prevent their late hypertrophic conversion. Methods: Early and late chondrogenic differentiation were evaluated using human adipose MSC and murine ATDC5 cells cultured under either normoxic (21%O2 or hypoxic (5%O2 conditions. To investigate the effect of hypoxia on late chondrogenic differentiation, the transcriptional activity of hypoxia-inducible factor-1alpha (HIF-1α and HIF-2α were evaluated using the NoShift DNA-binding assay and through modulation of their activity (chemical inhibitor, RNA interference. Results: Our data demonstrate that low oxygen tension not only stimulates the early chondrogenic commitment of two complementary models of chondrogenic cells, but also inhibits their hypertrophic differentiation. Conclusion: These results suggest that hypoxia can be used as an instrumental tool to prevent the formation of a calcified matrix in MSC-based cartilage tissue engineering.

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

    Science.gov (United States)

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

    2012-03-22

    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.

  18. 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,…

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

    Energy Technology Data Exchange (ETDEWEB)

    Quirbach, Sebastian; Trattnig, Siegfried [Vienna General Hospital, MR Center - High-Field MR, Department of Radiology, Medical University of Vienna, Vienna (Austria); Marlovits, Stefan; Zimmermann, Valentin [Medical University of Vienna, Center for Joint and Cartilage, Department of Trauma Surgery, Vienna (Austria); Domayer, Stephan; Dorotka, Ronald [Medical University of Vienna, Department of Orthopedic Surgery, Vienna (Austria); Mamisch, Tallal C. [University of Berne, Department of Orthopedic Surgery, Berne (Switzerland); Bohndorf, Klaus [Klinikum Augsburg, Department of Radiology, Augsburg (Germany); Welsch, Goetz H. [Vienna General Hospital, MR Center - High-Field MR, Department of Radiology, Medical University of Vienna, Vienna (Austria); University of Erlangen, Department of Trauma Surgery, Erlangen (Germany)

    2009-08-15

    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 ({proportional_to}50 ms), T2* relaxation times ({proportional_to}16 ms), and the diffusion constant for DWI ({proportional_to}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 ({proportional_to}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

  20. Three-Dimensional Bioprinting and Its Potential in the Field of Articular Cartilage Regeneration

    NARCIS (Netherlands)

    Mouser, Vivian H M; Levato, Riccardo; Bonassar, Lawrence J; D'Lima, Darryl D; Grande, Daniel A; Klein, Travis J; Saris, Daniel B F; Zenobi-Wong, Marcy; Gawlitta, Debby; Malda, Jos

    2017-01-01

    Three-dimensional (3D) bioprinting techniques can be used for the fabrication of personalized, regenerative constructs for tissue repair. The current article provides insight into the potential and opportunities of 3D bioprinting for the fabrication of cartilage regenerative constructs. Although 3D

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

    OpenAIRE

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

    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...

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

    Science.gov (United States)

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

    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 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. PMID:28817062

  3. 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.

  4. A new source of mesenchymal stem cells for articular cartilage repair: MSCs derived from mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model.

    Science.gov (United States)

    Fu, Wei-Li; Zhou, Chun-Yan; Yu, Jia-Kuo

    2014-03-01

    Bone marrow (BM) has been considered as a major source of mesenchymal stem cells (MSCs), but it has many disadvantages in clinical application. However, MSCs from peripheral blood (PB) could be obtained by a less invasive method and be more beneficial for autologous transplantation than BM MSCs, which makes PB a promising source for articular cartilage repair in clinical use. To assess whether MSCs from mobilized PB of New Zealand White rabbits have similar biological characteristics in vitro and chondrogenesis in vivo as BM MSCs. Controlled laboratory study. A combined method of drug administration containing granulocyte colony stimulating factor (G-CSF) plus CXCR4 antagonist AMD3100 was adopted to mobilize the PB stem cells of adult New Zealand White rabbits in vitro. The isolated cells were identified as MSCs by morphological characteristics, surface markers, and differentiation potentials. A comparison between PB MSCs and BM MSCs was made in terms of biological characteristics in vitro and chondrogenesis in vivo. This issue was investigated from the aspects of morphology, immune phenotype, multiple differentiation capacity, expansion potential, antiapoptotic capacity, and ability to repair cartilage defects in vivo of PB MSCs compared with BM MSCs. Peripheral blood MSCs were successfully mobilized by the method of combined drug administration, then isolated, expanded, and identified in vitro. No significant difference was found concerning the morphology, immune phenotype, and antiapoptotic capacity between PB MSCs and BM MSCs. Significantly, MSCs from both sources compounded with decalcified bone matrix showed the same ability to repair cartilage defects in vivo. For multipluripotency, BM MSCs exhibited a more osteogenic potential and higher proliferation capacity than PB MSCs, whereas PB MSCs possessed a stronger adipogenic and chondrogenic differentiation potential than BM MSCs in vitro. Although there are some differences in the proliferation and

  5. The effect of PEGT/PBT scaffold architecture on the composition of tissue engineered cartilage

    NARCIS (Netherlands)

    Malda, J.; Woodfield, T.B.F.; van der Vloodt, F.; Wilson, C.; Wilson, C.E.; Martens, D.E.; Tramper, J.; van Blitterswijk, Clemens; Riesle, J.U.

    2005-01-01

    A highly interconnecting and accessible pore network has been suggested as one of a number of prerequisites in the design of scaffolds for tissue engineering. In the present study, two processing techniques, compression-molding/particulate-leaching (CM), and 3D fiber deposition (3DF), were used to

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

    International Nuclear Information System (INIS)

    Huang Sha; Wang Yijuan; Liang Tang; Jin Fang; Liu Shouxin; Jin Yan

    2009-01-01

    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.

  7. 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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Tissue engineered devices for ligament repair, replacement and ...

    African Journals Online (AJOL)

    potential, severe damage warrants surgical intervention including complete replacement. Ligaments are longitudinally arranged, complex tissues; the mechanical properties of ligaments are a direct result of their components and the arrangement of these components in the tissue. It is these mechanics that have made ...

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

    Directory of Open Access Journals (Sweden)

    Nicola Maffulli

    2012-01-01

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

  10. Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model.

    Directory of Open Access Journals (Sweden)

    Li Mei

    Full Text Available Mesenchymal stem cell (MSC-based cell therapy is a promising avenue for osteoarthritis (OA treatment. In the present study, we evaluated the efficacy of intra-articular injections of culture-expanded allogenic adipose tissue-derived stem cells (ADSCs for the treatment of anterior cruciate ligament transection (ACLT induced rat OA model. The paracrine effects of major histocompatibility complex (MHC-unmatched ADSCs on chondrocytes were investigated in vitro. Rats were divided into an OA group that underwent ACLT surgery and a sham-operated group that did not undergo ACLT surgery. Four weeks after surgery mild OA was induced in the OA group. Subsequently, the OA rats were randomly divided into ADSC and control groups. A single dose of 1 × 106 ADSCs suspended in 60 μL phosphate-buffered saline (PBS was intra-articularly injected into the rats of the ADSC group. The control group received only 60 μL PBS. OA progression was evaluated macroscopically and histologically at 8 and 12 weeks after surgery. ADSC treatment did not cause any adverse local or systemic reactions. The degeneration of articular cartilage was significantly weaker in the ADSC group compared to that in the control group at both 8 and 12 weeks. Chondrocytes were co-cultured with MHC-unmatched ADSCs in trans-wells to assess the paracrine effects of ADSCs on chondrocytes. Co-culture with ADSCs counteracted the IL-1β-induced mRNA upregulation of the extracellular matrix-degrading enzymes MMP-3 and MMP-13 and the pro-inflammatory cytokines TNF-α and IL-6 in chondrocytes. Importantly, ADSCs increased the expression of the anti-inflammatory cytokine IL-10 in chondrocytes. The results of this study indicated that the intra-articular injection of culture-expanded allogenic ADSCs attenuated cartilage degeneration in an experimental rat OA model without inducing any adverse reactions. MHC-unmatched ADSCs protected chondrocytes from inflammatory factor-induced damage. The paracrine effects

  11. Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model.

    Science.gov (United States)

    Mei, Li; Shen, Bojiang; Ling, Peixue; Liu, Shaoying; Xue, Jiajun; Liu, Fuyan; Shao, Huarong; Chen, Jianying; Ma, Aibin; Liu, Xia

    2017-01-01

    Mesenchymal stem cell (MSC)-based cell therapy is a promising avenue for osteoarthritis (OA) treatment. In the present study, we evaluated the efficacy of intra-articular injections of culture-expanded allogenic adipose tissue-derived stem cells (ADSCs) for the treatment of anterior cruciate ligament transection (ACLT) induced rat OA model. The paracrine effects of major histocompatibility complex (MHC)-unmatched ADSCs on chondrocytes were investigated in vitro. Rats were divided into an OA group that underwent ACLT surgery and a sham-operated group that did not undergo ACLT surgery. Four weeks after surgery mild OA was induced in the OA group. Subsequently, the OA rats were randomly divided into ADSC and control groups. A single dose of 1 × 106 ADSCs suspended in 60 μL phosphate-buffered saline (PBS) was intra-articularly injected into the rats of the ADSC group. The control group received only 60 μL PBS. OA progression was evaluated macroscopically and histologically at 8 and 12 weeks after surgery. ADSC treatment did not cause any adverse local or systemic reactions. The degeneration of articular cartilage was significantly weaker in the ADSC group compared to that in the control group at both 8 and 12 weeks. Chondrocytes were co-cultured with MHC-unmatched ADSCs in trans-wells to assess the paracrine effects of ADSCs on chondrocytes. Co-culture with ADSCs counteracted the IL-1β-induced mRNA upregulation of the extracellular matrix-degrading enzymes MMP-3 and MMP-13 and the pro-inflammatory cytokines TNF-α and IL-6 in chondrocytes. Importantly, ADSCs increased the expression of the anti-inflammatory cytokine IL-10 in chondrocytes. The results of this study indicated that the intra-articular injection of culture-expanded allogenic ADSCs attenuated cartilage degeneration in an experimental rat OA model without inducing any adverse reactions. MHC-unmatched ADSCs protected chondrocytes from inflammatory factor-induced damage. The paracrine effects of ADSCs on

  12. Mesenchymal stem cell interaction with a non-woven hyaluronan-based scaffold suitable for tissue repair.

    Science.gov (United States)

    Pasquinelli, G; Orrico, C; Foroni, L; Bonafè, F; Carboni, M; Guarnieri, C; Raimondo, S; Penna, C; Geuna, S; Pagliaro, P; Freyrie, A; Stella, A; Caldarera, C M; Muscari, C

    2008-11-01

    fine modality of interaction with the substrate suggest that such scaffolds could be potentially useful when wide tissue defects are to be repaired as in the case of cartilage repair, wound healing and large vessel replacement.

  13. Protein based devices for oral tissue repair and regeneration

    Directory of Open Access Journals (Sweden)

    Iriczalli Cruz-Maya

    2018-03-01

    Full Text Available In the last decades, a goal of tissue engineering has been devoted to the design of devices with multiple micro- or nano-structures and loaded with bioactive molecules, to mimic the extracellular matrix (ECM so generating a conducive microenvironment for new tissue replacement/regeneration. The ECM, naturally, is composed of fibrous proteins which provide structural support for tissues, mainly regulating cells behavior in terms of proliferation, growth, survival, shape, migration and differentiation by cell-matrix interactions. Several studies have been just investigated the fabrication of different platforms for the regeneration of teeth, oral mucosa, salivary glands, bone, and periodontium. In this context, many proteins—from a natural or biological source—have been used as instructive substances to in vitro guide tissue organization and functions. In particular, new advances in the definition of protein-based formulations currently represent a great challenge to promote a more effective regeneration of dental tissues to be transplanted into patients to replace damaged, diseased or missing tissues. Hence, the purpose of this review is to discuss the use of protein-based systems for the regeneration of oral tissues.

  14. 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. © 2013 Elsevier Ltd. All rights reserved.

  15. Roles of microglia in brain development, tissue maintenance and repair.

    Science.gov (United States)

    Michell-Robinson, Mackenzie A; Touil, Hanane; Healy, Luke M; Owen, David R; Durafourt, Bryce A; Bar-Or, Amit; Antel, Jack P; Moore, Craig S

    2015-05-01

    The emerging roles of microglia are currently being investigated in the healthy and diseased brain with a growing interest in their diverse functions. In recent years, it has been demonstrated that microglia are not only immunocentric, but also neurobiological and can impact neural development and the maintenance of neuronal cell function in both healthy and pathological contexts. In the disease context, there is widespread consensus that microglia are dynamic cells with a potential to contribute to both central nervous system damage and repair. Indeed, a number of studies have found that microenvironmental conditions can selectively modify unique microglia phenotypes and functions. One novel mechanism that has garnered interest involves the regulation of microglial function by microRNAs, which has therapeutic implications such as enhancing microglia-mediated suppression of brain injury and promoting repair following inflammatory injury. Furthermore, recently published articles have identified molecular signatures of myeloid cells, suggesting that microglia are a distinct cell population compared to other cells of myeloid lineage that access the central nervous system under pathological conditions. Thus, new opportunities exist to help distinguish microglia in the brain and permit the study of their unique functions in health and disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. [Application of the xenogenic acellular dermal matrix membrane application used in the postoperative tissue shortage repair].

    Science.gov (United States)

    Bai, Yanxia; Yan, Liying; Zhang, Shaoqiang; Shao, Yuan; Yao, Xiaobao; Li, Honghui; Zhao, Ruimin; Zhao, Qian; Zhang, Pengfei; Yang, Qi

    2014-09-01

    To observe the short-term and long-term curative effect of the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer) application used in the 82 cases postoperative tissue shortage repair that after the head neck carcinoma resection. To held the 82 cases head neck carcinoma postoperative mucosa shortage repaired after resection by the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer), 65 cases mucosa shortage wound be directly covered by the repair membrane and the other 17 cases mucosa shortage wound be repaired by the tranfered muscle tissue flap with the repair membrane covered; 53 cases underwent additional postoperative radiotherapy between 2-4 weeks and follow-up in 1, 3, 6, 12, 18, 24, 30, 36, 48, 60 months and observed the operation site repair process through the electronic laryngoscope, observed the patients respiration, swallow, phonation function. Seventy-seven cases patients operation incision reached I phase healing standard, another 5 cases patients operation incision reached II phase healing standard because of the wound infection and fully-recovered through the local wound drainage,dressing process. All the patients tracheal cannula,the stomach tube be extubated successfully and without the local cicatricial constriction occurred. Seventy-eight cases follow up period reached 1 year including 53 cases who underwent postoperative radiotherapy, 49 cases follow up period reached 3 years including 32 cases who underwent postoperative radiotherapy, 14 cases follow up period reached 5 years including 12 cases who underwent postoperative radiotherapy. The patients with static local lesions discovered no reaction such as exclusion, allergy. The application of xenogenic acellular dermal matrix membrane (or joint muscle flap transfer used in in the postoperative tissue shortage repair that after the head neck carcinoma resection have several advantage such as comparatively easily implementation, operation safety

  17. Tissue engineering approaches for bone repair: concepts and evidence.

    Science.gov (United States)

    Schroeder, Josh E; Mosheiff, Rami

    2011-06-01

    Over the last decades, the medical world has advanced dramatically in the understanding of fracture repair. The three components needed for fracture healing are osteoconduction, osteoinduction and osteogenesis. With newly designed scaffolds, ex vivo produced growth factors and isolated stem cells, most of the challenges of critical size bone defects have been resolved in vitro, and in some cases in animal models as well. However, there are still challenges needed to be overcome before these technologies can be fully converted from the bench to the bedside. These technological and biological advancements need to be converted to mass production of affordable products that can be used in every part of the world. Vascularity, full substation of scaffolds by native bone, and bio-safety are the three most critical steps to be challenged before reaching the clinical setting. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. IL-17A-Induced PLET1 Expression Contributes to Tissue Repair and Colon Tumorigenesis.

    Science.gov (United States)

    Zepp, Jarod A; Zhao, Junjie; Liu, Caini; Bulek, Katazyna; Wu, Ling; Chen, Xing; Hao, Yujun; Wang, Zhenghe; Wang, Xinxin; Ouyang, Wenjun; Kalady, Matthew F; Carman, Julie; Yang, Wen-Pin; Zhu, Jun; Blackburn, Clare; Huang, Yina H; Hamilton, Thomas A; Su, Bing; Li, Xiaoxia

    2017-12-01

    This study identifies a novel mechanism linking IL-17A with colon tissue repair and tumor development. Abrogation of IL-17A signaling in mice attenuated tissue repair of dextran sulfate sodium (DSS)-induced damage in colon epithelium and markedly reduced tumor development in an azoxymethane/DSS model of colitis-associated cancer. A novel IL-17A target gene, PLET1 (a progenitor cell marker involved in wound healing), was highly induced in DSS-treated colon tissues and tumors in an IL-17RC-dependent manner. PLET1 expression was induced in LGR5 + colon epithelial cells after DSS treatment. LGR5 + PLET1 + marks a highly proliferative cell population with enhanced expression of IL-17A target genes. PLET1 deficiency impaired tissue repair of DSS-induced damage in colon epithelium and reduced tumor formation in an azoxymethane/DSS model of colitis-associated cancer. Our results suggest that IL-17A-induced PLET1 expression contributes to tissue repair and colon tumorigenesis. Copyright © 2017 by The American Association of Immunologists, Inc.

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

    Science.gov (United States)

    Nam, Jin

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth and diffe......Mesenchymal stem cells (MSC) are stem cell populations present among the bone marrow stroma and a number of other tissues that are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. MSC provide supportive stroma for growth...

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

    NARCIS (Netherlands)

    Klotz, Barbara J|info:eu-repo/dai/nl/411265938; Gawlitta, Debby; Rosenberg, Antoine J W P; Malda, Jos|info:eu-repo/dai/nl/412461099; Melchels, Ferry P W

    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,

  3. Tissue engineered devices for ligament repair, replacement and ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-29

    Dec 29, 2009 ... composed of types I, III, and V collagen, elastin, proteo- glycans, water ..... Rejection of the foreign tissue is another very serious risk of xenografts. ... Blood samples were analyzed for the presence of anti-Gal and anti–non-Gal antibodies, including antibodies to proteins present in the porcine grafts. Serum ...

  4. 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

  5. Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design.

    Science.gov (United States)

    Ogle, Molly E; Segar, Claire E; Sridhar, Sraeyes; Botchwey, Edward A

    2016-05-01

    Monocytes and macrophages play a critical role in tissue development, homeostasis, and injury repair. These innate immune cells participate in guiding vascular remodeling, stimulation of local stem and progenitor cells, and structural repair of tissues such as muscle and bone. Therefore, there is a great interest in harnessing this powerful endogenous cell source for therapeutic regeneration through immunoregenerative biomaterial engineering. These materials seek to harness specific subpopulations of monocytes/macrophages to promote repair by influencing their recruitment, positioning, differentiation, and function within a damaged tissue. Monocyte and macrophage phenotypes span a continuum of inflammatory (M1) to anti-inflammatory or pro-regenerative cells (M2), and their heterogeneous functions are highly dependent on microenvironmental cues within the injury niche. Increasing evidence suggests that division of labor among subpopulations of monocytes and macrophages could allow for harnessing regenerative functions over inflammatory functions of myeloid cells; however, the complex balance between necessary functions of inflammatory versus regenerative myeloid cells remains to be fully elucidated. Historically, biomaterial-based therapies for promoting tissue regeneration were designed to minimize the host inflammatory response; although, recent appreciation for the roles that innate immune cells play in tissue repair and material integration has shifted this paradigm. A number of opportunities exist to exploit known signaling systems of specific populations of monocytes/macrophages to promote repair and to better understand the biological and pathological roles of myeloid cells. This review seeks to outline the characteristics of distinct populations of monocytes and macrophages, identify the role of these cells within diverse tissue injury niches, and offer design criteria for immunoregenerative biomaterials given the intrinsic inflammatory response to their

  6. Optimization of Methods for Articular Cartilage Surface Tissue Engineering: Cell Density and Transforming Growth Factor Beta Are Critical for Self-Assembly and Lubricin Secretion.

    Science.gov (United States)

    Iwasa, Kenjiro; Reddi, A Hari

    2017-07-01

    Lubricin/superficial zone protein (SZP)/proteoglycan4 (PRG4) plays an important role in boundary lubrication in articular cartilage. Lubricin is secreted by superficial zone chondrocytes and synoviocytes of the synovium. The specific objective of this investigation is to optimize the methods for tissue engineering of articular cartilage surface. The aim of this study is to investigate the effect of cell density on the self-assembly of superficial zone chondrocytes and lubricin secretion as a functional assessment. Superficial zone chondrocytes were cultivated as a monolayer at low, medium, and high densities. Chondrocytes at the three different densities were treated with transforming growth factor beta (TGF-β)1 twice a week or daily, and the accumulated lubricin in the culture medium was analyzed by immunoblots and quantitated by enzyme-linked immunosorbent assay (ELISA). Cell numbers in low and medium densities were increased by TGF-β1; whereas cell numbers in high-density cell cultures were decreased by twice-a-week treatment of TGF-β1. On the other hand, the cell numbers were maintained by daily TGF-β treatment. Immunoblots and quantitation of lubricin by ELISA analysis indicated that TGF-β1 stimulated lubricin secretion by superficial zone chondrocytes at all densities with twice-a-week TGF-β treatment. It is noteworthy that the daily treatment of TGF-β1 increased lubricin much higher compared with twice-a-week treatment. These data demonstrate that daily treatment is optimal for the TGF-β1 response in a higher density of monolayer cultures. These findings have implications for self-assembly of surface zone chondrocytes of articular cartilage for application in tissue engineering of articular cartilage surface.

  7. 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. Copyright © 2011 Wiley Periodicals, Inc.

  8. Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair

    NARCIS (Netherlands)

    Lu, S.; Lam, J.; Trachtenberg, J.E.; Lee, E.J.; Seyednejad, H.; van den Beucken, J.J.; Tabata, Y.; Wong, M.E.; Jansen, J.A.; Mikos, A.G.; Kasper, F.K.

    2014-01-01

    The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the

  9. Lung ageing and COPD : is there a role for ageing in abnormal tissue repair?

    NARCIS (Netherlands)

    Brandsma, Corry-Anke; de Vries, Maaike; Costa, Rita; Woldhuis, Roy R; Königshoff, Melanie; Timens, Wim

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, with increasing prevalence, in particular in the elderly. COPD is characterised by abnormal tissue repair resulting in (small) airways disease and emphysema. There is accumulating evidence that ageing

  10. 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.

  11. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Origin and function of cartilage stem/progenitor cells in osteoarthritis.

    Science.gov (United States)

    Jiang, Yangzi; Tuan, Rocky S

    2015-04-01

    Articular cartilage is a physiologically non-self-renewing avascular tissue with a singular cell type, the chondrocyte, which functions as the load-bearing surface of the arthrodial joint. Injury to cartilage often progresses spatiotemporally from the articular surface to the subchondral bone, leading to development of degenerative joint diseases such as osteoarthritis (OA). Although lacking intrinsic reparative ability, articular cartilage has been shown to contain a population of stem cells or progenitor cells, similar to those found in many other adult tissues, that are thought to be involved in the maintenance of tissue homeostasis. These so-called cartilage-derived stem/progenitor cells (CSPCs) have been observed in human, equine and bovine articular cartilage, and have been identified, isolated and characterized on the basis of expression of stem-cell-related surface markers, clonogenicity and multilineage differentiation ability. However, the origin and functions of CSPCs are incompletely understood. We review here the current status of CSPC research and discuss the possible origin of these cells, what role they might have in cartilage repair, and their therapeutic potential in OA.

  13. Hypospadias repair using laser tissue soldering (LTS): preliminary results of a prospective randomized study

    Science.gov (United States)

    Kirsch, Andrew J.; Cooper, Christopher S.; Canning, Douglas A.; Snyder, Howard M., III; Zderic, Stephen A.

    1998-07-01

    Purpose: The purpose of this study was to evaluate laser tissue soldering using an 808 nm diode laser and wavelength- matched human albumin solder for urethral surgery in children. Methods: Currently, 30 boys, ages 3 months to 8 years were randomized to standard suturing (n equals 22) or 'sutureless' laser hypospadias repair (n equals 18). Laser soldering was performed with a human albumin solder doped with indocyanine green dye (2.5 mg/ml) using a laser power output of 0.5 W, pulse duration of 0.5 sec, and interval of 0.1 sec. Power density was approximately 16 W/cm2. In the laser group, sutures were used for tissue alignment only. At the time of surgery, neourethral and penile lengths, operative time for urethral repair, and number of sutures/throws were measured. Postoperatively, patients were examined for complications of wound healing, stricture, or fistula formation. Results: Mean age, severity of urethral defect, type of repair, and neourethra length were equivalent between the two groups. Operative time was significantly faster for laser soldering in both simple (1.6 plus or minus 0.21 min, p less than 0.001) and complex (5.4 plus or minus 0.28 min, p less than 0.0001) hypospadias repairs compared to controls (10.6 plus or minus 1.4 min and 27.8 plus or minus 2.9 min, respectively). The mean number of sutures used in the laser group for simple and complex repairs (3.3 plus or minus 0.3 and 8.1 plus or minus 0.64, respectively) were significantly (p less than 0.0001) less than for controls (8.2 plus or minus 0.84 and 20 plus or minus 2.3, respectively). Followup was between 3 months and 14 months. The overall complication rate in the laser group (11%) was lower than the controls (23%). However, statistical significance (p less than 0.05) was achieved only for the subgroup of patients undergoing simple repairs (LTS, 100% success versus suturing, 69% success). Conclusions: These preliminary results indicate that laser tissue soldering for hypospadias repair

  14. Shark Cartilage

    Science.gov (United States)

    ... inflammation of the intestine (enteritis). Some people apply shark cartilage directly to the skin for arthritis and psoriasis. ... ingredients. Additionally, there is no research showing that shark cartilage is absorbed through the skin. Psoriasis. Developing research suggests that a specific shark ...

  15. 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.

  16. A histomorphometric and scanning electron microscopy study of human condylar cartilage and bone tissue changes in relation to age

    DEFF Research Database (Denmark)

    Paulsen, Hans Ulrik; Thomsen, J.S.; Hougen, Hans Petter

    1999-01-01

    . EXPERIMENTAL SETTING AND DESIGN: A histomorphometric and scanning electron microscopic analysis of cartilage characteristics and bone remodelling activity. The Departments of Orthodontics and Cell Biology at Aarhus University, Denmark. An autopsy sample of condyles from 20 individuals, 18-31 years of age...

  17. 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)

  18. ADENOSINE RECEPTOR STIMULATION BY POLYDEOXYRIBONUCLEOTIDE IMPROVES TISSUE REPAIR AND SYMPTOMOLOGY IN EXPERIMENTAL COLITIS.

    Directory of Open Access Journals (Sweden)

    Giovanni Pallio

    2016-08-01

    Full Text Available Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodelling 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 remodelling 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 dinitro-benzene-sulfonic acid (DNBS, 25mg diluted in 0.8ml 50% ethanol. After 6 hrs, animals were randomized to receive either PDRN (8mg/kg/i.p., or PDRN + the A2A antagonist (DMPX; 10mg/kg/i.p., or vehicle (0.8 ml saline solution daily. In the second model, dextran sodium sulphate (DSS was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 hrs 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, myeloperoxydase activity, and malondialdheyde. 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.

  19. Tissue injury and repair following cutaneous exposure of mice to sulfur mustard.

    Science.gov (United States)

    Joseph, Laurie B; Composto, Gabriella M; Heck, Diane E

    2016-08-01

    In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and pro-growth/pro-wound healing mediators, including cyclooxygenase-2, which generates prostanoids, inducible nitric oxide synthase, which generates nitric oxide, fibroblast growth factor receptor 2, and galectin-3. Characterization of the mediators regulating structural changes in the skin during SM-induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. © 2016 New York Academy of Sciences.

  20. Metabolic regulation of macrophages during tissue repair: insights from skeletal muscle regeneration.

    Science.gov (United States)

    Juban, Gaëtan; Chazaud, Bénédicte

    2017-10-01

    Macrophages are highly versatile cells that are involved both in the mounting and the resolution of inflammatory responses. Besides their properties in innate immunity to fight against pathogens, macrophages are essential for tissue repair, during which they adopt sequential inflammatory status. While the acquisition of some canonical polarized inflammatory statuses in vitro (M1/M2) is beginning to be understood at the molecular level, the regulation of macrophage skewing in vivo has been less investigated. Immunometabolism, in particular, is an emerging field, and most of the studies so far have investigated the control of macrophage polarization using in vitro set-ups. In this context, skeletal muscle regeneration is an excellent paradigm to study tissue repair, since the sequential steps of inflammatory response and tissue repair are well characterized. In this Review, after introducing macrophage populations and functions during skeletal muscle regeneration, we present the current knowledge on the metabolic regulation of macrophage inflammatory status, with particular emphasis on the comparison between in vitro and in vivo models of macrophage activation. We also discuss the metabolic regulation of macrophages in vivo during skeletal muscle regeneration. © 2017 Federation of European Biochemical Societies.

  1. Current advances in tissue repair and regeneration: the future is bright.

    Science.gov (United States)

    Ninov, Nikolay; Yun, Maximina H

    2015-04-01

    The fifth EMBO conference on 'The Molecular and Cellular Basis of Regeneration and Repair' took place in the peaceful coastal town of Sant Feliu de Guixols (Spain) on September 2014. The meeting was organised by Emili Saló (U. Barcelona, Spain), Kimberly Mace (U. Manchester, UK), Patrizia Ferretti (University College London, UK) and Michael Brand (Centre for Regenerative Therapies Dresden, Germany) and received the generous support of Society for Developmental Biology, The Company of Biologists, Centre for Regenerative Therapies Dresden, Garland Science and the journals Regeneration and Cell Signalling. The natural surroundings provided an inspiring setting for 185 researchers from all over the world to share their latest findings and views on the field. The conference showcased the great diversity of model organisms used for studying regeneration and tissue repair, including invertebrate and vertebrate species (Fig. 1). Importantly, this diversity in animal models allowed for a global overview of the mechanisms that promote regeneration. In addition, it highlighted some of the unique aspects that confer differences in regenerative capacities among different species. These differences might lie in each of the different steps involved in performing regeneration, including triggering the regenerative response, controlling cellular plasticity, re-stablishing the correct tissue patterns, as well as determining the roles of extrinsic factors, such as the role of inflammation in regeneration. A deeper understanding of these processes in the naturally regenerating species is a prerequisite for advancing the field of regenerative medicine and tissue repair in humans.

  2. 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.

  3. 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. © 2014 Wiley Periodicals, Inc.

  4. Evaluation of structural and mechanical properties of electrospun nano-micro hybrid of poly hydroxybutyrate-chitosan/silk scaffold for cartilage tissue engineering.

    Science.gov (United States)

    Karbasi, Saeed; Fekrat, Farnoosh; Semnani, Daryoush; Razavi, Shahnaz; Zargar, Elham Naghash

    2016-01-01

    One of the new methods of scaffold fabrication is a nano-micro hybrid structure in which the properties of the scaffold are improved by introducing nanometer and micrometer structures. This method could be suitable for scaffold designing if some features improve. In this study, electrospun nanofibers of 9% weight solution of poly (3-hydroxybutyrate) (P3HB) and a 15% weight of chitosan by trifluoroacetic acid were coated on both the surface of a silk knitted substrate in the optimum condition to improve the mechanical properties of scaffolds for cartilage tissue engineering application. These hybrid nano-micro fibrous scaffolds were characterized by structural and mechanical evaluation methods. Scanning electron microscopy values and porosity analysis showed that average diameter of nanofibers was 584.94 nm in electrospinning part and general porosity was more than 80%. Fourier transform infrared spectroscopy results indicated the presence of all elements without pollution. The tensile test also stated that by electrospinning, as well as adding chitosan, both maximum strength and maximum elongation increased to 187 N and 10 mm. It means that the microfibrous part of scaffold could affect mechanical properties of nano part of the hybrid scaffold, significantly. It could be concluded that P3HB-chitosan/silk hybrid scaffolds can be a good candidate for cartilage tissue engineering.

  5. 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.

  6. Amino acids supply in culture media is not a limiting factor in the matrix synthesis of engineered cartilage tissue

    Science.gov (United States)

    Ng, K. W.; DeFrancis, J. G.; Kugler, L. E.; Kelly, T.-A. N.; Ho, M. M.; O’Conor, C. J.; Ateshian, G. A.; Hung, C. T.

    2013-01-01

    Summary Increased amino acid supplementation (0.5×, 1.0×, and 5.0× recommended concentrations or additional proline) was hypothesized to increase the collagen content in engineered cartilage. No significant differences were found between groups in matrix content or dynamic modulus. Control constructs possessed the highest compressive Young’s modulus on day 42. On day 42, compared to controls, decreased type II collagen was found with 0.5×, 1.0×, and 5.0× supplementation and significantly increased DNA content found in 1.0× and 5.0×. No effects were observed on these measures with added proline. These results lead us to reject our hypothesis and indicate that the low collagen synthesis in engineered cartilage is not due to a limited supply of amino acids in media but may require a further stimulatory signal. The results of this study also highlight the impact that culture environment can play on the development of engineered cartilage. PMID:17713744

  7. 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.

  8. Bioactive stratified polymer ceramic-hydrogel scaffold for integrative osteochondral repair.

    Science.gov (United States)

    Jiang, Jie; Tang, Amy; Ateshian, Gerard A; Guo, X Edward; Hung, Clark T; Lu, Helen H

    2010-06-01

    Due to the intrinsically poor repair potential of articular cartilage, injuries to this soft tissue do not heal and require clinical intervention. Tissue engineered osteochondral grafts offer a promising alternative for cartilage repair. The functionality and integration potential of these grafts can be further improved by the regeneration of a stable calcified cartilage interface. This study focuses on the design and optimization of a stratified osteochondral graft with biomimetic multi-tissue regions, including a pre-designed and pre-integrated interface region. Specifically, the scaffold based on agarose hydrogel and composite microspheres of polylactide-co-glycolide (PLGA) and 45S5 bioactive glass (BG) was fabricated and optimized for chondrocyte density and microsphere composition. It was observed that the stratified scaffold supported the region-specific co-culture of chondrocytes and osteoblasts which can lead to the production of three distinct yet continuous regions of cartilage, calcified cartilage and bone-like matrices. Moreover, higher cell density enhanced chondrogenesis and improved graft mechanical property over time. The PLGA-BG phase promoted chondrocyte mineralization potential and is required for the formation of a calcified interface and bone regions on the osteochondral graft. These results demonstrate the potential of the stratified scaffold for integrative cartilage repair and future studies will focus on scaffold optimization and in vivo evaluations.

  9. Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke.

    Science.gov (United States)

    Cook, Douglas J; Nguyen, Cynthia; Chun, Hyun N; L Llorente, Irene; Chiu, Abraham S; Machnicki, Michal; Zarembinski, Thomas I; Carmichael, S Thomas

    2017-03-01

    Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood-brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel + BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate ( Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel + BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2 cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.

  10. [Clinical observation of microsurgial repairing for the treatment of soft tissue defection of heel].

    Science.gov (United States)

    Liu, Jing-sheng; Wang, Yu-liang; Xia, Ya-yi; Hao, Jun-long; Zhou, Hai-yu; Zhao, Lin; Wu, Meng; Wang, Xu

    2014-10-01

    T o summarize the clinical effects of the repairing methods for skin and soft tissue defection of heel. From June 1998 to June 2009,42 patients with skin and soft tissue defection of heel underwent the repairing treatment,including 23 males and 19 females, with an average age of 37 years old ranging from 18 to 65. The causes of injuries included mangled injury in 22 cases, high fall injury in 10 cases, cut injury in 5 cases,melanoma in 3 cases, decubital ulcer in 2 cases. Of the 42 cases, 27 were on left side and 15 on right side. The defect area of skin ranged from 3 cm x 2 cm to 18 cm x 16 cm. The time between the injury and surgery ranged from 8 hours to 10 years. The wounds were repaired separately by medial plantar flap in 13 cases, lesser saphenous sural nerve vascular island flap in 18 cases, saphenous neurocutaneous vascular flap in 11 cases. The patients' outcome were evaluated with appearance,blood supply, texture, resilience and two points discrimination of the flaps. All of the 42 flaps were survived. The distal skin necrosis occurred in 2 flaps, but healing occurred after debridement and intermediate thickness skin grafting. Three patients with sinus formation healed after 5 to 12 months of dressing change. All patients were follow-up for 8 months to 6 years. The flaps of all patients gained a satisfied shape after operation. The patients had a normal gait, the flaps had a good sense and a resistance to wearing,and no ulcer occurred. The two point discrimination of the flap was 4 to 12 mm. It is convenient and effective to repair the heel skin and soft tissue defects using medial plantar island skin flap when the defects is less then 8 cmx6 cm. As reliable blood supply,major artery preservation and high survival, the lesser saphenous sural nerve vascular island flap and saphenous neurocutaneous vascular flap can be transferred to repair the large soft tissue defect of heel.

  11. Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering.

    Science.gov (United States)

    Chen, Chih-Hao; Kuo, Chang-Yi; Wang, Yan-Jie; Chen, Jyh-Ping

    2016-11-23

    Glucosamine (GlcN) fulfills many of the requirements as an ideal component in scaffolds used in cartilage tissue engineering. The incorporation of GlcN in a gelatin/hyaluronic acid (GH) cryogel scaffold could provide biological cues in maintaining the phenotype of chondrocytes. Nonetheless, substituting gelatin with GlcN may also decrease the crosslinking density and modulate the mechanical properties of the cryogel scaffold, which may be beneficial as physical cues for chondrocytes in the scaffold. Thus, we prepared cryogel scaffolds containing 9% GlcN (GH-GlcN9) and 16% GlcN (GH-GlcN16) by carbodiimide-mediated crosslinking reactions at -16 °C. The crosslinking density and the mechanical properties of the cryogel matrix could be tuned by adjusting the content of GlcN used during cryogel preparation. In general, incorporation of GlcN did not influence scaffold pore size and ultimate compressive strain but increased porosity. The GH-GlcN16 cryogel showed the highest swelling ratio and degradation rate in hyaluronidase and collagenase solutions. On the contrary, the Young's modulus, storage modulus, ultimate compressive stress, energy dissipation level, and rate of stress relaxation decreased by increasing the GlcN content in the cryogel. The release of GlcN from the scaffolds in the culture medium of chondrocytes could be sustained for 21 days for GH-GlcN16 in contrast to only 7 days for GH-GlcN9. In vitro cell culture experiments using rabbit articular chondrocytes revealed that GlcN incorporation affected cell proliferation, morphology, and maintenance of chondrogenic phenotype. Overall, GH-GlcN16 showed the best performance in maintaining chondrogenic phenotype with reduced cell proliferation rate but enhanced glycosaminoglycans (GAGs) and type II collagen (COL II) secretion. Quantitative real-time polymerase chain reaction also showed time-dependent up-regulation of cartilage-specific marker genes (COL II, aggrecan and Sox9) for GH-GlcN16. Implantation of

  12. 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.

  13. Mineralization Induction of Gingival Fibroblasts and Construction of a Sandwich Tissue-Engineered Complex for Repairing Periodontal Defects.

    Science.gov (United States)

    Wu, Mingxuan; Wang, Jie; Zhang, Yanning; Liu, Huijuan; Dong, Fusheng

    2018-02-22

    BACKGROUND The ideal healing technique for periodontal tissue defects would involve the functional regeneration of the alveolar bone, cementum, and periodontal ligament, with new periodontal attachment formation. In this study, gingival fibroblasts were induced and a "sandwich" tissue-engineered complex (a tissue-engineered periodontal membrane between 2 tissue-engineered mineralized membranes) was constructed to repair periodontal defects. We evaluated the effects of gingival fibroblasts used as seed cells on the repair of periodontal defects and periodontal regeneration. MATERIAL AND METHODS Primitively cultured gingival fibroblasts were seeded bilaterally on Bio-Gide collagen membrane (a tissue-engineered periodontal membrane) or unilaterally on small intestinal submucosa segments, and their mineralization was induced. A tissue-engineered sandwich was constructed, comprising the tissue-engineered periodontal membrane flanked by 2 mineralized membranes. Periodontal defects in premolar regions of Beagles were repaired using the tissue-engineered sandwich or periodontal membranes. Periodontal reconstruction was compared to normal and trauma controls 10 or 20 days postoperatively. RESULTS Periodontal defects were completely repaired by the sandwich tissue-engineered complex, with intact new alveolar bone and cementum, and a new periodontal ligament, 10 days postoperatively. CONCLUSIONS The sandwich tissue-engineered complex can achieve ideal periodontal reconstruction rapidly.

  14. Development of biodegradable hyper-branched tissue adhesives for the repair of meniscus tears.

    Science.gov (United States)

    Bochyńska, A I; Van Tienen, T G; Hannink, G; Buma, P; Grijpma, D W

    2016-03-01

    Meniscus tears are one of the most commonly occurring injuries of the knee joint. Current meniscus repair techniques are challenging and do not bring fully satisfactory results. Tissue adhesives are a promising alternative, since they are easy to apply and cause minimal tissue trauma. In this study, a series of amphiphilic copolymers based on polyethylene glycol, trimethylene carbonate and citric acid were synthesized and subsequently end-functionalized with hexamethylene diisocyanate to form reactive adhesive materials. The shear adhesive strength of the networks to bovine meniscus tissue measured in a lap-shear adhesion test ranged between 20 and 80 kPa, which was better than for fibrin glue (10 kPa). The elastic modulus of the networks depended on composition and was in the same range as that of human meniscus. Cell compatibility was assessed using Alamar Blue staining after incubation of the bovine meniscus cells with different concentrations of the glues for 7 days. Cell viability was not affected after adding up to 3mg of the adhesive/mL of medium. The proposed materials are suitable candidates to be used as resorbable tissue adhesives for meniscus repair. They have excellent mechanical and adhesive properties that can be adjusted by varying the composition of the copolymers. Meniscal tears often occur and current treatment strategies do not bring fully satisfactory results. Use of biodegradable tissue adhesives would be an interesting option, but currently available adhesives are not suited due to toxicity or poor mechanical properties. Here, we describe the development of novel biodegradable, hyper-branched, adhesive copolymers. These adhesives cure upon contact with water forming flexible networks. Their adhesion to bovine meniscus tissue was significantly better than that of clinically used fibrin glue. The tensile properties of the cured networks were in the same range of values of the human meniscus. When physiologically relevant amounts were added to

  15. Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing

    Science.gov (United States)

    Sobol, Emil; Baum, Olga; Shekhter, Anatoly; Wachsmann-Hogiu, Sebastian; Shnirelman, Alexander; Alexandrovskaya, Yulia; Sadovskyy, Ivan; Vinokur, Valerii

    2017-09-01

    Pores are vital for functioning of avascular tissues. Laser-induced pores play an important role in the process of cartilage regeneration. The aim of any treatment for osteoarthritis is to repair hyaline-type cartilage. The aims of this study are to answer two questions: (1) How do laser-assisted pores affect the cartilaginous cells to synthesize hyaline cartilage (HC)? and (2) How can the size distribution of pores arising in the course of laser radiation be controlled? We have shown that in cartilage, the pores arise predominately near chondrocytes, which promote nutrition of cells and signal molecular transfer that activates regeneration of cartilage. In vivo laser treatment of damaged cartilage of miniature pig joints provides cellular transformation and formation of HC. We propose a simple model of pore formation in biopolymers that paves the way for going beyond the trial-and-error approach when choosing an optimal laser treatment regime. Our findings support the approach toward laser healing of osteoarthritis.

  16. Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models

    Science.gov (United States)

    Halloran, J. P.; Sibole, S.; van Donkelaar, C. C.; van Turnhout, M. C.; Oomens, C. W. J.; Weiss, J. A.; Guilak, F.; Erdemir, A.

    2012-01-01

    Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes. PMID:22648577

  17. SDF-1α peptide tethered polyester facilitates tissue repair by endogenous cell mobilization and recruitment.

    Science.gov (United States)

    Shafiq, Muhammad; Kong, Deling; Kim, Soo Hyun

    2017-10-01

    The design of bioactive scaffolds that can invoke host's own regenerative capabilities and facilitate endogenous tissue repair hold great promise. This study aims to evaluate the potential of stromal cell-derived factor 1 alpha (SDF-1α)-derived peptide and heparin tethered poly(L-lactide-co-ε-caprolactone) (PLCL) copolymers for blood vessel regeneration applications. Amino acid analysis and toluidine blue assays confirm successful conjugation of SDF-1α peptide and heparin with the PLCL copolymers. Assessment of biocompatibility after subcutaneous implantation in rats discloses higher cell infiltration in SDF-1α peptide (SDF-1 group) or SDF-1 peptide and heparin (SDF-1/heparin group) than the control group. SDF-1 and SDF-1/heparin grafts also show more numbers of laminin + blood vessels, CD90 + stem cells, and alpha smooth muscle actin + cells than the control group. However, SDF-1 and SDF-1/heparin groups did not significantly differ in terms of blood vessel regeneration and stem cell recruitment. Evaluation of the inflammatory response reveal less numbers of CD68 + macrophages in SDF-1 and SDF-1/heparin groups compared with the control group; whereas three groups show similar numbers of CD206 + macrophages. These results indicate that completely synthetic, cell-free grafts can attract endogenous cells and enhance tissue repair. Bioactive polyesters can be fabricated into different shapes and structures for various tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomater Res Part A: 105A: 2670-2684, 2017. © 2017 Wiley Periodicals, Inc.

  18. Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair.

    Science.gov (United States)

    Tarish, Firas L; Schultz, Niklas; Tanoglidi, Anna; Hamberg, Hans; Letocha, Henry; Karaszi, Katalin; Hamdy, Freddie C; Granfors, Torvald; Helleday, Thomas

    2015-11-04

    Chemical castration improves responses to radiotherapy in prostate cancer, but the mechanism is unknown. We hypothesized that this radiosensitization is caused by castration-mediated down-regulation of nonhomologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs). To test this, we enrolled 48 patients with localized prostate cancer in two arms of the study: either radiotherapy first or radiotherapy after neoadjuvant castration treatment. We biopsied patients at diagnosis and before and after castration and radiotherapy treatments to monitor androgen receptor, NHEJ, and DSB repair in verified cancer tissue. We show that patients receiving neoadjuvant castration treatment before radiotherapy had reduced amounts of the NHEJ protein Ku70, impaired radiotherapy-induced NHEJ activity, and higher amounts of unrepaired DSBs, measured by γ-H2AX foci in cancer tissues. This study demonstrates that chemical castration impairs NHEJ activity in prostate cancer tissue, explaining the improved response of patients with prostate cancer to radiotherapy after chemical castration. Copyright © 2015, American Association for the Advancement of Science.

  19. Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells.

    Science.gov (United States)

    Weinberger, Florian; Breckwoldt, Kaja; Pecha, Simon; Kelly, Allen; Geertz, Birgit; Starbatty, Jutta; Yorgan, Timur; Cheng, Kai-Hung; Lessmann, Katrin; Stolen, Tomas; Scherrer-Crosbie, Marielle; Smith, Godfrey; Reichenspurner, Hermann; Hansen, Arne; Eschenhagen, Thomas

    2016-11-02

    Myocardial injury results in a loss of contractile tissue mass that, in the absence of efficient regeneration, is essentially irreversible. Transplantation of human pluripotent stem cell-derived cardiomyocytes has beneficial but variable effects. We created human engineered heart tissue (hEHT) strips from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and hiPSC-derived endothelial cells. The hEHTs were transplanted onto large defects (22% of the left ventricular wall, 35% decline in left ventricular function) of guinea pig hearts 7 days after cryoinjury, and the results were compared with those obtained with human endothelial cell patches (hEETs) or cell-free patches. Twenty-eight days after transplantation, the hearts repaired with hEHT strips exhibited, within the scar, human heart muscle grafts, which had remuscularized 12% of the infarct area. These grafts showed cardiomyocyte proliferation, vascularization, and evidence for electrical coupling to the intact heart tissue in a subset of engrafted hearts. hEHT strips improved left ventricular function by 31% compared to that before implantation, whereas the hEET or cell-free patches had no effect. Together, our study demonstrates that three-dimensional human heart muscle constructs can repair the injured heart. Copyright © 2016, American Association for the Advancement of Science.

  20. 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.

  1. A biocompatible hybrid material with simultaneous calcium and strontium release capability for bone tissue repair

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, J. Carlos [CICECO — Aveiro Institute of Materials, Department of Materials and Ceramic Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Wacha, András [Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar Tudósok körútja 2, Budapest 1117 (Hungary); Gomes, Pedro S. [Laboratory for Bone Metabolism and Regeneration, Faculdade de Medicina Dentária, Universidade do Porto (Portugal); Alves, Luís C. [C2TN, Instituto Superior Técnico, Universidade de Lisboa, E.N.10, 2695-066 Bobadela LRS (Portugal); Fernandes, M. Helena Vaz [CICECO — Aveiro Institute of Materials, Department of Materials and Ceramic Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Salvado, Isabel M. Miranda, E-mail: isabelmsalvado@ua.pt [CICECO — Aveiro Institute of Materials, Department of Materials and Ceramic Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Fernandes, M. Helena R. [Laboratory for Bone Metabolism and Regeneration, Faculdade de Medicina Dentária, Universidade do Porto (Portugal)

    2016-05-01

    The increasing interest in the effect of strontium in bone tissue repair has promoted the development of bioactive materials with strontium release capability. According to literature, hybrid materials based on the system PDMS–SiO{sub 2} have been considered a plausible alternative as they present a mechanical behavior similar to the one of the human bone. The main purpose of this study was to obtain a biocompatible hybrid material with simultaneous calcium and strontium release capability. A hybrid material, in the system PDMS–SiO{sub 2}–CaO–SrO, was prepared with the incorporation of 0.05 mol of titanium per mol of SiO{sub 2}. Calcium and strontium were added using the respective acetates as sources, following a sol–gel technique previously developed by the present authors. The obtained samples were characterized by FT-IR, solid-state NMR, and SAXS, and surface roughness was analyzed by 3D optical profilometry. In vitro studies were performed by immersion of the samples in Kokubo's SBF for different periods of time, in order to determine the bioactive potential of these hybrids. Surfaces of the immersed samples were observed by SEM, EDS and PIXE, showing the formation of calcium phosphate precipitates. Supernatants were analyzed by ICP, revealing the capability of the material to simultaneously fix phosphorus ions and to release calcium and strontium, in a concentration range within the values reported as suitable for the induction of the bone tissue repair. The material demonstrated to be cytocompatible when tested with MG63 osteoblastic cells, exhibiting an inductive effect on cell proliferation and alkaline phosphatase activity. - Highlights: • A hybrid PDMS–SiO{sub 2}–CaO–SrO material was prepared with the incorporation of Ti. • Sr was released in concentrations suitable for the induction of bone tissue repair. • The material demonstrated to be cytocompatible when tested with osteoblastic cells.

  2. Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants.

    Science.gov (United States)

    Tan, Lijun; Ren, Yijin; van Kooten, Theo G; Grijpma, Dirk W; Kuijer, Roel

    2015-03-01

    Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage. Explants of porcine cartilage and human osteoarthritic cartilage were cultured for four weeks and subjected to daily LIPUS or PEMF treatments. At one, two, three and four weeks follow-up explants were prepared for histological assessment or gene expression (porcine only). Non-treated porcine explants showed signs of atrophy of the superficial zone starting at one week. Treated explants did not. In LIPUS-treated explants cell clusters were observed. In PEMF-treated explants more hypertrophic-like changes were observed at later follow up. Newly synthesized tissue was present in treated explants. Gene expression profiles did indicate differences between the two methods. Both methods reduced expression of the aggrecan and collagen type II gene compared to the control. LIPUS treatment of human cartilage samples resulted in a reduction of degeneration according to Mankin scoring. PEMF treatment did not. LIPUS or PEMF prevented degenerative changes in pig knee cartilage explants. LIPUS reduced degeneration in human cartilage samples. LIPUS treatment seems to have more potency in the treatment of osteoarthritis than PEMF treatment.

  3. Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage RegenerationIn Vitro.

    Science.gov (United States)

    Vonk, Lucienne A; van Dooremalen, Sanne F J; Liv, Nalan; Klumperman, Judith; Coffer, Paul J; Saris, Daniël B F; Lorenowicz, Magdalena J

    2018-01-01

    Osteoarthritis (OA) is a rheumatic disease leading to chronic pain and disability with no effective treatment available. Recently, allogeneic human mesenchymal stromal/stem cells (MSC) entered clinical trials as a novel therapy for OA. Increasing evidence suggests that therapeutic efficacy of MSC depends on paracrine signalling. Here we investigated the role of extracellular vesicles (EVs) secreted by human bone marrow derived MSC (BMMSC) in human OA cartilage repair. To test the effect of BMMSC-EVs on OA cartilage inflammation, TNF-alpha-stimulated OA chondrocyte monolayer cultures were treated with BMMSC-EVs and pro-inflammatory gene expression was measured by qRT-PCR after 48 h. To assess the impact of BMMSC-EVs on cartilage regeneration, BMMSC-EVs were added to the regeneration cultures of human OA chondrocytes, which were analyzed after 4 weeks for glycosaminoglycan content by 1,9-dimethylmethylene blue (DMMB) assay. Furthermore, paraffin sections of the regenerated tissue were stained for proteoglycans (safranin-O) and type II collagen (immunostaining). We show that BMMSC-EVs inhibit the adverse effects of inflammatory mediators on cartilage homeostasis. When co-cultured with OA chondrocytes, BMMSC-EVs abrogated the TNF-alpha-mediated upregulation of COX2 and pro-inflammatory interleukins and inhibited TNF-alpha-induced collagenase activity. BMMSC-EVs also promoted cartilage regeneration in vitro . Addition of BMMSC-EVs to cultures of chondrocytes isolated from OA patients stimulated production of proteoglycans and type II collagen by these cells. Our data demonstrate that BMMSC-EVs can be important mediators of cartilage repair and hold great promise as a novel therapeutic for cartilage regeneration and osteoarthritis.

  4. 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

  5. Adipose stem cells: biology and clinical applications for tissue repair and regeneration.

    Science.gov (United States)

    Kokai, Lauren E; Marra, Kacey; Rubin, J Peter

    2014-04-01

    There is a clear clinical need for cell therapies to repair or regenerate tissue lost to disease or trauma. Adipose tissue is a renewable source of stem cells, called adipose-derived stem cells (ASCs), that release important growth factors for wound healing, modulate the immune system, decrease inflammation, and home in on injured tissues. Therefore, ASCs may offer great clinical utility in regenerative therapies for afflictions such as Parkinson's disease and Alzheimer's disease, spinal cord injury, heart disease, and rheumatoid arthritis, or for replacing lost tissue from trauma or tumor removal. This article discusses the regenerative properties of ASCs that can be harnessed for clinical applications, and explores current and future challenges for ASC clinical use. Such challenges include knowledge-based deficiencies, hurdles for translating research to the clinic, and barriers to establishing a new paradigm of medical care. Clinical experience with ASCs, ASCs as a portion of the heterogeneous stromal cell population extracted enzymatically from adipose tissue, and stromal vascular fraction are also described. Copyright © 2014 Mosby, Inc. All rights reserved.

  6. 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.

  7. Capturing tissue repair in zebrafish larvae with time-lapse brightfield stereomicroscopy.

    Science.gov (United States)

    Lisse, Thomas S; Brochu, Elizabeth A; Rieger, Sandra

    2015-01-31

    The zebrafish larval tail fin is ideal for studying tissue regeneration due to the simple architecture of the larval fin-fold, which comprises of two layers of skin that enclose undifferentiated mesenchyme, and because the larval tail fin regenerates rapidly within 2-3 days. Using this system, we demonstrate a method for capturing the repair dynamics of the amputated tail fin with time-lapse video brightfield stereomicroscopy. We demonstrate that fin amputation triggers a contraction of the amputation wound and extrusion of cells around the wound margin, leading to their subsequent clearance. Fin regeneration proceeds from proximal to distal direction after a short delay. In addition, developmental growth of the larva can be observed during all stages. The presented method provides an opportunity for observing and analyzing whole tissue-scale behaviors such as fin development and growth in a simple microscope setting, which is easily adaptable to any stereomicroscope with time-lapse capabilities.

  8. Evaluation of reparative cartilage after autologous chondrocyte implantation for osteochondritis dissecans. Histology, biochemistry, and MR imaging

    International Nuclear Information System (INIS)

    Moriya, Takuro; Watanabe, Atsuya; Sasho, Takahisa; Nakagawa, Koichi; Moriya, Hideshige; Wada, Yuichi; Mainil-Varlet, P.

    2007-01-01

    The aim of this study was to investigate the biochemical properties, histological and immunohistochemical appearance, and magnetic resonance (MR) imaging findings of reparative cartilage after autologous chondrocyte implantation (ACI) for osteochondritis dissecans (OCD). Six patients (mean age 20.2±8.8 years; 13-35 years) who underwent ACI for full-thickness cartilage defects of the femoral condyle were studied. One year after the procedure, a second-look arthroscopic operation was performed with biopsy of reparative tissue. The International Cartilage Repair Society (ICRS) visual histological assessment scale was used for histological assessment. Biopsied tissue was immunohistochemically analyzed with the use of monoclonal antihuman collagen type I and monoclonal antihuman collagen type II primary antibodies. Glycosaminoglycan (GAG) concentrations in biopsied reparative cartilage samples were measured by high performance liquid chromatography (HPLC). MR imaging was performed with T 1 and T 2 -weighted imaging and three-dimensional spoiled gradient-recalled (3D-SPGR) MR imaging. Four tissue samples were graded as having a mixed morphology of hyaline and fibrocartilage while the other two were graded as fibrocartilage. Average ICRS scores for each criterion were (I) 1.0±1.5; (II) 1.7±0.5; (III) 0.6±1.0; (IV) 3.0±0.0; (V) 1.8±1.5; and (VI) 2.5±1.2. Average total score was 10.7±2.8. On immunohistochemical analysis, the matrix from deep and middle layers of reparative cartilage stained positive for type II collagen; however, the surface layer did not stain well. The average GAG concentration in reparative cartilage was 76.6±4.2 μg/mg whereas that in normal cartilage was 108±11.2 μg/mg. Common complications observed on 3D-SPGR MR imaging were hypertrophy of grafted periosteum, edema-like signal in bone marrow, and incomplete repair of subchondral bone at the surgical site. Clinically, patients had significant improvements in Lysholm scores. In spite of a

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

    Science.gov (United States)

    Antonino, Agrusa; Giorgio, Romano; Giuseppe, Frazzetta; Giovanni, De Vita; Silvia, Di Giovanni; Daniela, Chianetta; Giuseppe, Di Buono; Vincenzo, Sorce; Gaspare, Gulotta

    2014-01-01

    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. PMID:24864221

  10. Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

    Science.gov (United States)

    Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

    2017-09-01

    The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

  11. 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.

  12. 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.

  13. In Vivo Identification and Induction of Articular Cartilage Stem Cells by Inhibiting NF-κB Signaling in Osteoarthritis.

    Science.gov (United States)

    Tong, Wenxue; Geng, Yiyun; Huang, Yan; Shi, Yu; Xiang, Shengnan; Zhang, Ning; Qin, Ling; Shi, Qin; Chen, Qian; Dai, Kerong; Zhang, Xiaoling

    2015-10-01

    Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder characterized by the degeneration of articular cartilage. However, no effective medical therapy has been found yet for such condition. In this study, we directly confirmed the existence of articular cartilage stem cells (ACSCs) in vivo and in situ for the first time both in normal and OA articular cartilage, and explored their chondrogenesis in Interleukin-1β (IL-1β) induced inflammation environment and disclose whether the inhibition of NF-κB signaling can induce ACSCs activation thus improve the progression of experimental OA. We found an interesting phenomenon that ACSCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for self-repair. During the in vitro mechanism study, we discovered IL-1β can efficiently activate the NF-κB pathway and potently impair the responsiveness of ACSCs, whereas the NF-κB pathway inhibitor rescued the ACSCs chondrogenesis. The final in vivo experiments further confirmed ACSCs' activation were maintained by NF-κB pathway inhibitor, which induced cartilage regeneration, and protected articular cartilage from injury in an OA animal model. Our results provided in vivo evidence of the presence of ACSCs, and disclosed their action in the early OA stage and gradual quiet as OA process, presented a potential mechanism for both cartilage intrinsic repair and its final degradation, and demonstrated the feasibility of inducing endogenous adult tissue-specific mesenchymal stem cells for articular cartilage repair and OA therapy. © 2015 AlphaMed Press.

  14. Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

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    Mouthuy PA

    2017-05-01

    Full Text Available Pierre-Alexis Mouthuy,1,2 Maja Somogyi Škoc,3 Ana Čipak Gašparović,1 Lidija Milković,1 Andrew J Carr,2 Neven Žarković1 1Laboratory for Oxidative Stress, Rudjer Boskovic Institute, Zagreb, Croatia; 2Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Medical Science Division, University of Oxford, Oxford, UK; 3Department of Materials, Fibres and Textile Testing, University of Zagreb, Zagreb, Croatia Abstract: Electrospun filaments represent a new generation of medical textiles with promising applications in soft tissue repair. A potential strategy to improve their design is to combine them with bioactive molecules. Curcumin, a natural compound found in turmeric, is particularly attractive for its antioxidant, anti-inflammatory, and antimicrobial properties. However, investigating the range of relevant doses of curcumin in materials designed for tissue regeneration has remained limited. In this paper, a wide range of curcumin concentrations was explored and the potential of the resulting materials for soft tissue repair applications was assessed. Polydioxanone (PDO filaments were prepared with various amounts of curcumin: 0%, 0.001%, 0.01%, 0.1%, 1%, and 10% (weight to weight ratio. The results from the present study showed that, at low doses (≤0.1%, the addition of curcumin has no influence on the spinning process or on the physicochemical properties of the filaments, whereas higher doses lead to smaller fiber diameters and improved mechanical properties. Moreover, filaments with 0.001% and 0.01% curcumin stimulate the metabolic activity and proliferation of normal human dermal fibroblasts (NHDFs compared with the no-filament control. However, this stimulation is not significant when compared to the control filaments (0%. Highly dosed filaments induce either the inhibition of proliferation (with 1% or cell apoptosis (with 10% as a result of the concentrations of curcumin found in the

  15. Effect of in vitro chondrogenic differentiation of autologous mesenchymal stem cells on cartilage and subchondral cancellous bone repair in osteoarthritis of temporomandibular joint.

    Science.gov (United States)

    Chen, K; Man, C; Zhang, B; Hu, J; Zhu, S S

    2013-02-01

    This study investigated the effects of in vitro chondrogenic differentiated mesenchymal stem cells (MSCs) on cartilage and subchondral cancellous bone in temporomandibular joint osteoarthritis (TMJOA). Four weeks after induction of osteoarthritis (OA), the joints received hylartin solution, non-chondrogenic MSCs or in vitro chondrogenic differentiated MSCs. The changes in cartilage and subchondral cancellous bone were evaluated by histology, reverse transcription polymerase chain reaction and micro-computed tomography (CT). Implanted cells were tracked using Adeno-LacZ labelling. The differentiated MSC-treated group had better histology than the MSC-treated group at 4 and 12 weeks, but no difference at 24 weeks. Increased mRNA expression of collegan II, aggeran, Sox9 and decreased matrix metalloproteinase 13 (MMP13) were observed in differentiated MSC-treated groups compared to the undifferentiated MSC-treated group at 4 weeks. The differentiated MSC-treated group had decreased bone volume fraction, trabecular thickness and bone surface density, and increased trabecular spacing in the subchondral cancellous bone than the undifferentiated MSC-treated group. Transplanted cells were observed at cartilage, subchondral bone, and the synovial membrane lining at 4 weeks. Intra-articular injection of MSCs could delay the progression of TMJOA, and in vitro chondrogenic induction of MSCs could enhance the therapeutic effects. This provides new insights into the role of MSCs in cell-based therapies for TMJOA. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  16. Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects.

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    Lin, Tao; Liu, Sheng; Chen, Shihao; Qiu, Shuai; Rao, Zilong; Liu, Jianghui; Zhu, Shuang; Yan, Liwei; Mao, Haiquan; Zhu, Qingtang; Quan, Daping; Liu, Xiaolin

    2018-04-09

    Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy

  17. Cooperation of Rho family proteins Rac1 and Cdc42 in cartilage development and calcified tissue formation.

    Science.gov (United States)

    Ikehata, Mikiko; Yamada, Atsushi; Fujita, Koji; Yoshida, Yuko; Kato, Tadashi; Sakashita, Akiko; Ogata, Hiroaki; Iijima, Takehiko; Kuroda, Masahiko; Chikazu, Daichi; Kamijo, Ryutaro

    2018-04-20

    Rac1 and Cdc42, Rho family low molecular weight G proteins, are intracellular signaling factors that transmit various information from outside to inside cells. Primarily, they are known to control various biological activities mediated by actin cytoskeleton reorganization, such as cell proliferation, differentiation, and apoptosis. In order to investigate the functions of Rac1 and Cdc42 in bone formation, we prepared cartilage-specific double conditional knockout mice, Rac1 fl/fl ; Cdc42 fl/fl ; Col2-Cre (Rac1: Cdc42 dcKO mice), which died just after birth, similar to Cdc42 fl/fl ; Col2-Cre mice (Cdc42 cKO mice). Our findings showed that the long tubule bone in Rac1: Cdc42 dcKO mice was shorter than that in Rac1 fl/fl ; Col2-Cre mice (Rac1 cKO mice) and Cdc42 cKO mice. Abnormal skeleton formation was also observed and disordered columnar formation in the growth plate of the Rac1: Cdc42 dcKO mice was more severe as compared to the Rac1 cKO and Cdc42 cKO mice. Together, these results suggest that Rac1 and Cdc42 have cooperating roles in regulation of bone development. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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    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.

  19. A functional biphasic biomaterial homing mesenchymal stem cells for in vivo cartilage regeneration.

    Science.gov (United States)

    Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Dai, Linghui; Man, Zhentao; Yuan, Lan; Chen, Haifeng; Zhou, Chunyan; Ao, Yingfang

    2014-12-01

    Cartilage regeneration after trauma is still a great challenge for clinicians and researchers due to many reasons, such as joint load-bearing, synovial movement and the paucity of endogenous repair cells. To overcome these limitations, we constructed a functional biomaterial using a biphasic scaffold platform and a bone-derived mesenchymal stem cells (BMSCs)-specific affinity peptide. The biphasic scaffold platform retains more cells homogeneously within the sol-gel transition of chitosan and provides sufficient solid matrix strength. This biphasic scaffold platform is functionalized with an affinity peptide targeting a cell source of interest, BMSCs. The presence of conjugated peptide gives this system a biological functionality towards BMSC-specific homing both in vitro and in vivo. The functional biomaterial can stimulate stem cell proliferation and chondrogenic differentiation during in vitro culture. Six months after in vivo implantation, compared with routine surgery or control scaffolds, the functional biomaterials induced superior cartilage repair without complications, as indicated by histological observations, magnetic resonance imaging and biomechanical properties. Beyond cartilage repair, this functional biphasic scaffold may provide a biomaterial framework for one-step tissue engineering strategy by homing endogenous cells to stimulate tissue regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Evaluation of the Effects of BioCell Collagen, a Novel Cartilage Extract, on Connective Tissue Support and Functional Recovery From Exercise.

    Science.gov (United States)

    Lopez, Hector L; Ziegenfuss, Tim N; Park, Joosang

    2015-06-01

    Little is known about the effect of nutritional supplementation on metabolic optimization for enhancing adaptation and recovery of the connective tissue elements that support musculoskeletal function. The study aimed to determine the potential effect of supplementation with a novel, hydrolyzed chicken sternal cartilage extract-called BioCell Collagen-on biomarkers and functional indices of recovery from intense exercise. The research team designed a randomized, double-blind, placebo-controlled pilot study. The study was conducted at the Center for Applied Health Sciences in Stow, OH, USA. Participants were 8 healthy, recreationally active individuals, with a mean age of 29.3 y. Participants ingested either 3 g of a novel, hydrolyzed chicken sternal cartilage extract called BioCell Collagen ("supplement") or 3 g of a placebo daily for 6 wk prior to challenge with an upper-body, muscle-damaging resistance exercise (UBC) on day 43 and a rechallenge on day 46 to assess functional recovery. Primary endpoints were levels of 3 blood biomarkers-creatine kinase (CK), lactate dehydrogenase (LDH), and C-reactive protein (CRP)- and scores on a clinical pain scale and a perceived recovery scale (PRS). The extract attenuated the post-UBC increase in serum markers for muscle tissue damage: CK, LDH, and CRP. For the intervention group vs the placebo group, the mean changes were as follows: (1) an increase in CK of 20 U/L vs 4726 U/L, respectively; (2) a decrease in LDH of 3.5 U/L vs an increase of 82.9 U/L, respectively; and (3) an increase in CRP of 0.07 mg/L vs an increase of 0.7 mg/L, respectively. The performance decrement in bench press repetitions to failure was 57.9% on day 43 and 57.8% on day 46 for the intervention group vs 72.2% on day 43 and 65% on day 46 for the placebo group. The overall trend for the performance decrement, together with the results for the PRS, suggested that a more robust muscular recovery and adaptive response occurred with use of the extract. The

  1. Effects of tenoxicam and aspirin on the metabolism of proteoglycans and hyaluronan in normal and osteoarthritic human articular cartilage.

    Science.gov (United States)

    Manicourt, D H; Druetz-Van Egeren, A; Haazen, L; Nagant de Deuxchaisnes, C

    1994-01-01

    1. As nonsteroidal anti-inflammatory drugs may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan (PG) and hyaluronan (HA) molecules produced by tenoxicam and aspirin in human normal cartilage explants and in osteoarthritic (OA) cartilage from age-matched donors. 2. Explants were sampled from the medial femoral condyle and were classified by use of Mankin's histological-histochemical grading system. Cartilage specimens were normal in 10 subjects, exhibited moderate OA (MOA) in 10 and had severe OA (SOA) in 10. 3. Cartilage explants were pulsed with [3H]-glucosamine and chased in the absence and in the presence of either aspirin (190 micrograms ml-1) or tenoxicam (4-16 micrograms ml-1). After papain digestion, the labelled chondroitin sulphate ([3H]-PGs) and HA([3H]-HA) molecules present in the tissue and media were purified by anion-exchange chromatography. 4. In normal cartilage as well as in explants with MOA and SOA aspirin reduced more strongly PG and HA synthesis than the loss of [3H]-HA and [3H]-PGs. 5. In normal cartilage, tenoxicam did not affect PG metabolism whereas it reduced HA synthesis in a dose-dependent manner and did not change or even increased the net loss of [3H]-HA. In contrast, in OA cartilage, tenoxicam produced a stronger reduction in the loss of [3H]-PGs than in PG synthesis and this decrease occurred at lower concentrations in cartilage with SOA (4-8 micrograms ml-1) than in cartilage with MOA (8-16 micrograms ml-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7889262

  2. 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

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

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    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.

  4. Freshly isolated stromal cells from the infrapatellar fat pad are suitable for a one-step surgical procedure to regenerate cartilage tissue

    NARCIS (Netherlands)

    Jurgens, W.J.F.M.; Dijk, van A.; Zandieh Doulabi, B.; Niessen, F.B.; Ritt, M.J.P.F.; Milligen - Kummer, van F.J.; Helder, M.N.

    2009-01-01

    BACKGROUND AIMS: Stem cell therapies are being evaluated as promising alternatives for cartilage regeneration. We investigated whether stromal vascular fraction cells (SVF) from the infrapatellar (Hoffa) fat pad are suitable for a one-step surgical procedure to treat focal cartilage defects.

  5. The Role of Changes in Extracellular Matrix of Cartilage in the Presence of Inflammation on the Pathology of Osteoarthritis

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    Maricela Maldonado

    2013-01-01

    Full Text Available Osteoarthritis (OA is a degenerative disease that affects various tissues surrounding joints such as articular cartilage, subchondral bone, synovial membrane, and ligaments. No therapy is currently available to completely prevent the initiation or progression of the disease partly due to poor understanding of the mechanisms of the disease pathology. Cartilage is the main tissue afflicted by OA, and chondrocytes, the sole cellular component in the tissue, actively participate in the degeneration process. Multiple factors affect the development and progression of OA including inflammation that is sustained during the progression of the disease and alteration in biomechanical conditions due to wear and tear or trauma in cartilage. During the progression of OA, extracellular matrix (ECM of cartilage is actively remodeled by chondrocytes under inflammatory conditions. This alteration of ECM, in turn, changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. The changes in ECM composition and structure also prevent participation of mesenchymal stem cells in the repair process by inhibiting their chondrogenic differentiation. This review focuses on how inflammation-induced ECM remodeling disturbs cellular activities to prevent self-regeneration of cartilage in the pathology of OA.

  6. 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.

  7. The superior regenerative potential of muscle-derived stem cells for articular cartilage repair is attributed to high cell survival and chondrogenic potential

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    Hongshuai Li

    2016-01-01

    Full Text Available Three populations of muscle-derived cells (PP1, PP3, and PP6 were isolated from mouse skeletal muscle using modified preplate technique and retrovirally transduced with BMP4/GFP.  In vitro, the PP1 cells (fibroblasts proliferated significantly slower than the PP3 (myoblasts and PP6 cells (muscle-derived stem cells; the PP1 and PP6 cells showed a superior rate of survival compared with PP3 cells under oxidative stress; and the PP6 cells showed significantly superior chondrogenic capabilities than PP1 and PP3 cells. In vivo, the PP6 cells promoted superior cartilage regeneration compared with the other muscle-derived cell populations. The cartilage defects in the PP6 group had significantly higher histological scores than those of the other muscle-derived cell groups, and GFP detection revealed that the transplanted PP6 cells showed superior in vivo cell survival and chondrogenic capabilities compared with the PP1 and PP3 cells. PP6 cells (