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Sample records for cartilage regeneration age

  1. Towards Regeneration of Articular Cartilage

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    Iwamoto, Masahiro; Ohta, Yoichi; Larmour, Colleen; Enomoto-Iwamoto, Motomi

    2014-01-01

    Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site. PMID:24078496

  2. Cartilage extracellular matrix as a biomaterial for cartilage regeneration.

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    Kiyotake, Emi A; Beck, Emily C; Detamore, Michael S

    2016-11-01

    The extracellular matrix (ECM) of various tissues possesses the model characteristics that biomaterials for tissue engineering strive to mimic; however, owing to the intricate hierarchical nature of the ECM, it has yet to be fully characterized and synthetically fabricated. Cartilage repair remains a challenge because the intrinsic properties that enable its durability and long-lasting function also impede regeneration. In the last decade, cartilage ECM has emerged as a promising biomaterial for regenerating cartilage, partly because of its potentially chondroinductive nature. As this research area of cartilage matrix-based biomaterials emerged, investigators facing similar challenges consequently developed convergent solutions in constructing robust and bioactive scaffolds. This review discusses the challenges, emerging trends, and future directions of cartilage ECM scaffolds, including a comparison between two different forms of cartilage matrix: decellularized cartilage (DCC) and devitalized cartilage (DVC). To overcome the low permeability of cartilage matrix, physical fragmentation greatly enhances decellularization, although the process itself may reduce the chondroinductivity of fabricated scaffolds. The less complex processing of a scaffold composed of DVC, which has not been decellularized, appears to have translational advantages and potential chondroinductive and mechanical advantages over DCC, without detrimental immunogenicity, to ultimately enhance cartilage repair in a clinically relevant way. © 2016 New York Academy of Sciences.

  3. Harnessing biomechanics to develop cartilage regeneration strategies.

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    Athanasiou, Kyriacos A; Responte, Donald J; Brown, Wendy E; Hu, Jerry C

    2015-02-01

    As this review was prepared specifically for the American Society of Mechanical Engineers H.R. Lissner Medal, it primarily discusses work toward cartilage regeneration performed in Dr. Kyriacos A. Athanasiou's laboratory over the past 25 years. The prevalence and severity of degeneration of articular cartilage, a tissue whose main function is largely biomechanical, have motivated the development of cartilage tissue engineering approaches informed by biomechanics. This article provides a review of important steps toward regeneration of articular cartilage with suitable biomechanical properties. As a first step, biomechanical and biochemical characterization studies at the tissue level were used to provide design criteria for engineering neotissues. Extending this work to the single cell and subcellular levels has helped to develop biochemical and mechanical stimuli for tissue engineering studies. This strong mechanobiological foundation guided studies on regenerating hyaline articular cartilage, the knee meniscus, and temporomandibular joint (TMJ) fibrocartilage. Initial tissue engineering efforts centered on developing biodegradable scaffolds for cartilage regeneration. After many years of studying scaffold-based cartilage engineering, scaffoldless approaches were developed to address deficiencies of scaffold-based systems, resulting in the self-assembling process. This process was further improved by employing exogenous stimuli, such as hydrostatic pressure, growth factors, and matrix-modifying and catabolic agents, both singly and in synergistic combination to enhance neocartilage functional properties. Due to the high cell needs for tissue engineering and the limited supply of native articular chondrocytes, costochondral cells are emerging as a suitable cell source. Looking forward, additional cell sources are investigated to render these technologies more translatable. For example, dermis isolated adult stem (DIAS) cells show potential as a source of

  4. Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention

    OpenAIRE

    Tiku, Moti L.; Sabaawy, Hatem E.

    2015-01-01

    Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates c...

  5. Peptide-Based Materials for Cartilage Tissue Regeneration.

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    Hastar, Nurcan; Arslan, Elif; Guler, Mustafa O; Tekinay, Ayse B

    2017-01-01

    Cartilaginous tissue requires structural and metabolic support after traumatic or chronic injuries because of its limited capacity for regeneration. However, current techniques for cartilage regeneration are either invasive or ineffective for long-term repair. Developing alternative approaches to regenerate cartilage tissue is needed. Therefore, versatile scaffolds formed by biomaterials are promising tools for cartilage regeneration. Bioactive scaffolds further enhance the utility in a broad range of applications including the treatment of major cartilage defects. This chapter provides an overview of cartilage tissue, tissue defects, and the methods used for regeneration, with emphasis on peptide scaffold materials that can be used to supplement or replace current medical treatment options.

  6. Mesenchymal stem cells in cartilage regeneration.

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    Savkovic, Vuk; Li, Hanluo; Seon, Jong-Keun; Hacker, Michael; Franz, Sandra; Simon, Jan-Christoph

    2014-01-01

    Articular cartilage provides life-long weight-bearing and mechanical lubrication with extraordinary biomechanical performance and simple structure. However, articular cartilage is apparently vulnerable to multifactorial damage and insufficient to self-repair, isolated in articular capsule without nerves or blood vessels. Osteoarthritis (OA) is known as a degenerative articular cartilage deficiency progressively affecting large proportion of the world population, and restoration of hyaline cartilage is clinical challenge to repair articular cartilage lesion and recreate normal functionality over long period. Mesenchymal stem cells (MSC) are highly proliferative and multipotent somatic cells that are able to differentiate mesoderm-derived cells including chondrocytes and osteoblasts. Continuous endeavors in basic research and preclinical trial have achieved promising outcomes in cartilage regeneration using MSCs. This review focuses on rationale and technologies of MSC-based hyaline cartilage repair involving tissue engineering, 3D biomaterials and growth factors. By comparing conventional treatment and current research progress, we describe insights of advantage and challenge in translation and application of MSC-based chondrogenesis for OA treatment.

  7. Bioactive Scaffolds for Regeneration of Cartilage and Subchondral Bone Interface

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    Deng, Cuijun; Zhu, Huiying; Li, Jiayi; Feng, Chun; Yao, Qingqiang; Wang, Liming; Chang, Jiang; Wu, Chengtie

    2018-01-01

    The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr5(PO4)2SiO4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in osteochondral defect reconstruction. Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method. The SEM and ICPAES were used to investigate the physicochemical properties of SPS scaffolds. The proliferation and maturation of rabbit chondrocytes stimulated by SPS bioactive ceramics were measured in vitro. The stimulatory effect of SPS scaffolds for cartilage and subchondral bone regeneration was investigated in vivo. Results: SPS scaffolds significantly stimulated chondrocyte proliferation, and SPS extracts distinctly enhanced the maturation of chondrocytes and preserved chondrocytes from OA. SPS scaffolds markedly promoted the regeneration of osteochondral defects. The complex interface microstructure between cartilage and subchondral bone was obviously reconstructed. The underlying mechanism may be related to Sr and Si ions stimulating cartilage regeneration by activating HIF pathway and promoting subchondral bone reconstruction through activating Wnt pathway, as well as preserving chondrocytes from OA via inducing autophagy and inhibiting hedgehog pathway. Conclusion: Our findings suggest that SPS scaffolds can help osteochondral defect reconstruction and well reconstruct the complex interface between cartilage and subchondral bone, which represents a promising strategy for osteochondral defect regeneration. PMID:29556366

  8. Which cartilage is regenerated, hyaline cartilage or fibrocartilage? Non-invasive ultrasonic evaluation of tissue-engineered cartilage.

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    Hattori, K; Takakura, Y; Ohgushi, H; Habata, T; Uematsu, K; Takenaka, M; Ikeuchi, K

    2004-09-01

    To investigate ultrasonic evaluation methods for detecting whether the repair tissue is hyaline cartilage or fibrocartilage in new cartilage regeneration therapy. We examined four experimental rabbit models: a spontaneous repair model (group S), a large cartilage defect model (group L), a periosteal graft model (group P) and a tissue-engineered cartilage regeneration model (group T). From the resulting ultrasonic evaluation, we used %MM (the maximum magnitude of the measurement area divided by that of the intact cartilage) as a quantitative index of cartilage regeneration. The results of the ultrasonic evaluation were compared with the histological findings and histological score. The %MM values were 61.1 +/- 16.5% in group S, 29.8 +/- 15.1% in group L, 36.3 +/- 18.3% in group P and 76.5 +/- 18.7% in group T. The results showed a strong similarity to the histological scoring. The ultrasonic examination showed that all the hyaline-like cartilage in groups S and T had a high %MM (more than 60%). Therefore, we could define the borderline between the two types of regenerated cartilage by the %MM.

  9. Transcriptomic signatures in cartilage ageing

    Science.gov (United States)

    2013-01-01

    Introduction Age is an important factor in the development of osteoarthritis. Microarray studies provide insight into cartilage aging but do not reveal the full transcriptomic phenotype of chondrocytes such as small noncoding RNAs, pseudogenes, and microRNAs. RNA-Seq is a powerful technique for the interrogation of large numbers of transcripts including nonprotein coding RNAs. The aim of the study was to characterise molecular mechanisms associated with age-related changes in gene signatures. Methods RNA for gene expression analysis using RNA-Seq and real-time PCR analysis was isolated from macroscopically normal cartilage of the metacarpophalangeal joints of eight horses; four young donors (4 years old) and four old donors (>15 years old). RNA sequence libraries were prepared following ribosomal RNA depletion and sequencing was undertaken using the Illumina HiSeq 2000 platform. Differentially expressed genes were defined using Benjamini-Hochberg false discovery rate correction with a generalised linear model likelihood ratio test (P ageing cartilage. Conclusion There was an age-related dysregulation of matrix, anabolic and catabolic cartilage factors. This study has increased our knowledge of transcriptional networks in cartilage ageing by providing a global view of the transcriptome. PMID:23971731

  10. [Current overview of cartilage regeneration procedures].

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    Schenker, H; Wild, M; Rath, B; Tingart, M; Driessen, A; Quack, V; Betsch, M

    2017-11-01

    Cartilage is an avascular, alymphatic and non-innervated tissue with limited intrinsic repair potential. The high prevalence of cartilage defects and their tremendous clinical importance are a challenge for all treating physicians. This article provides the reader with an overview about current cartilage treatment options and their clinical outcome. Microfracture is still considered the gold standard in the treatment of small cartilage lesions. Small osteochondral defects can be effectively treated with the autologous osteochondral transplantation system. Larger cartilage defects are successfully treated by autologous membrane-induced chondrogenesis (AMIC) or by membrane-assisted autologous chondrocyte implantation (MACI). Despite limitations of current cartilage repair strategies, such procedures can result in short- and mid-term clinical improvement of the patients. Further developments and clinical studies are necessary to improve the long-term outcome following cartilage repair.

  11. Transcriptomic profiling of cartilage ageing

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    Mandy Jayne Peffers

    2014-12-01

    Full Text Available The musculoskeletal system is severely affected by the ageing process, with many tissues undergoing changes that lead to loss of function and frailty. Articular cartilage is susceptible to age related diseases, such as osteoarthritis. Applying RNA-Seq to young and old equine cartilage, we identified an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage from older donors. Here we describe the contents and quality controls in detail for the gene expression and related results published by Peffers and colleagues in Arthritis Research and Therapy 2013 associated with the data uploaded to ArrayExpress (E-MTAB-1386.

  12. Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention

    Science.gov (United States)

    Sabaawy, Hatem E.

    2015-01-01

    Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates chondrocyte activation, expression of proteases and growth factor release from the matrix. This regenerative process results in the local activation of inflammatory response genes in cartilage without migration of inflammatory cells or angiogenesis. The end results are catabolic and anabolic responses, and it is the balance between these two outcomes that controls remodelling of the matrix and regeneration. A tantalizing clinical clue for cartilage regrowth in OA joints has been observed in surgically created joint distraction. We hypothesize that cartilage growth in these distracted joints may have a biological connection with the size of organs and regeneration. Therefore we propose a novel, practical and nonsurgical intervention to validate the role of distraction in cartilage regeneration in OA. The approach permits normal wake-up activity while during sleep; the index knee is subjected to distraction with a pull traction device. Comparison of follow-up magnetic resonance imaging (MRI) at 3 and 6 months of therapy to those taken before therapy will provide much-needed objective evidence for the use of this mode of therapy for OA. We suggest that the paradigm presented here merits investigation for treatment of OA in knee joints. PMID:26029269

  13. Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

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    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.

  14. Animal models used for testing hydrogels in cartilage regeneration.

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    Zhu, Chuntie; Wu, Qiong; Zhang, Xu; Chen, Fubo; Liu, Xiyang; Yang, Qixiang; Zhu, Lei

    2018-05-14

    Focal cartilage or osteochondral lesions can be painful and detrimental. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, rely on the combination of biodegradable scaffolds and specific biological cues, such as growth factors, adhesive factors and genetic materials. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as feasibility of replication of diseases in animals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. The properties of bioengineered chondrocyte sheets for cartilage regeneration

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    Ota Naoshi

    2009-03-01

    Full Text Available Abstract Background Although the clinical results of autologous chondrocyte implantation for articular cartilage defects have recently improved as a result of advanced techniques based on tissue engineering procedures, problems with cell handling and scaffold imperfections remain to be solved. A new cell-sheet technique has been developed, and is potentially able to overcome these obstacles. Chondrocyte sheets applicable to cartilage regeneration can be prepared with this cell-sheet technique using temperature-responsive culture dishes. However, for clinical application, it is necessary to evaluate the characteristics of the cells in these sheets and to identify their similarities to naive cartilage. Results The expression of SOX 9, collagen type 2, 27, integrin α10, and fibronectin genes in triple-layered chondrocyte sheets was significantly increased in comparison to those in conventional monolayer culture and in a single chondrocyte sheet, implying a nature similar to ordinary cartilage. In addition, immunohistochemistry demonstrated that collagen type II, fibronectin, and integrin α10 were present in the triple-layered chondrocyte sheets. Conclusion The results of this study indicate that these chondrocyte sheets with a consistent cartilaginous phenotype and adhesive properties may lead to a new strategy for cartilage regeneration.

  16. Surgical correction of joint deformities and hyaline cartilage regeneration

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    Vyacheslav Alexandrovich Vinokurov

    2015-12-01

    Full Text Available Aim. To determine a method of extra-articular osteochondral fragment formation for the improvement of surgical correction results of joint deformities and optimization of regenerative conditions for hyaline cartilage. Materials and Methods. The method of formation of an articular osteochondral fragment without penetration into the joint cavity was devised experimentally. More than 30 patients with joint deformities underwent the surgery. Results. During the experiments, we postulated that there may potentially be a complete recovery of joint defects because of hyaline cartilage regeneration. By destructing the osteochondral fragment and reforming it extra-articularally, joint defects were recovered in all patients. The results were evaluated as excellent and good in majority of the patients. Conclusion. These findings indicate a novel method in which the complete recovery of joint defects due to dysplastic genesis or osteochondral defects as a result of injuries can be obtained. The devised method can be used in future experiments for objectification and regenerative potential of hyaline cartilage (e.g., rate and volume of the reformed joints that regenerate, detection of cartilage elements, and the regeneration process.

  17. Subchondral chitosan/blood implant-guided bone plate resorption and woven bone repair is coupled to hyaline cartilage regeneration from microdrill holes in aged rabbit knees.

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    Guzmán-Morales, J; Lafantaisie-Favreau, C-H; Chen, G; Hoemann, C D

    2014-02-01

    Little is known of how to routinely elicit hyaline cartilage repair tissue in middle-aged patients. We tested the hypothesis that in skeletally aged rabbit knees, microdrill holes can be stimulated to remodel the bone plate and induce a more integrated, voluminous and hyaline cartilage repair tissue when treated by subchondral chitosan/blood implants. New Zealand White rabbits (13 or 32 months old, N = 7) received two 1.5 mm diameter, 2 mm depth drill holes in each knee, either left to bleed as surgical controls or press-fit with a 10 kDa (distal hole: 10K) or 40 kDa (proximal hole: 40K) chitosan/blood implant with fluorescent chitosan tracer. Post-operative knee effusion was documented. Repair tissues at day 0 (N = 1) and day 70 post-surgery (N = 6) were analyzed by micro-computed tomography, and by histological scoring and histomorphometry (SafO, Col-2, and Col-1) at day 70. All chitosan implants were completely cleared after 70 days, without increasing transient post-operative knee effusion compared to controls. Proximal control holes had worse osteochondral repair than distal holes. Both implant formulations induced bone remodeling and improved lateral integration of the bone plate at the hole edge. The 40K implant inhibited further bone repair inside 50% of the proximal holes, while the 10K implant specifically induced a "wound bloom" reaction, characterized by decreased bone plate density in a limited zone beyond the initial hole edge, and increased woven bone (WB) plate repair inside the initial hole (P = 0.016), which was accompanied by a more voluminous and hyaline cartilage repair (P holes with a biodegradable subchondral implant that elicits bone plate resorption followed by anabolic WB repair within a 70-day repair period. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  18. 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...

  19. Hydrogels for Cartilage Regeneration, from Polysaccharides to Hybrids

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    Daniela Anahí Sánchez-Téllez

    2017-12-01

    Full Text Available The aims of this paper are: (1 to review the current state of the art in the field of cartilage substitution and regeneration; (2 to examine the patented biomaterials being used in preclinical and clinical stages; (3 to explore the potential of polymeric hydrogels for these applications and the reasons that hinder their clinical success. The studies about hydrogels used as potential biomaterials selected for this review are divided into the two major trends in tissue engineering: (1 the use of cell-free biomaterials; and (2 the use of cell seeded biomaterials. Preparation techniques and resulting hydrogel properties are also reviewed. More recent proposals, based on the combination of different polymers and the hybridization process to improve the properties of these materials, are also reviewed. The combination of elements such as scaffolds (cellular solids, matrices (hydrogel-based, growth factors and mechanical stimuli is needed to optimize properties of the required materials in order to facilitate tissue formation, cartilage regeneration and final clinical application. Polymer combinations and hybrids are the most promising materials for this application. Hybrid scaffolds may maximize cell growth and local tissue integration by forming cartilage-like tissue with biomimetic features.

  20. Cartilage repair in the degenerative ageing knee

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    Brittberg, Mats; Gomoll, Andreas H; Canseco, José A; Far, Jack; Lind, Martin; Hui, James

    2016-01-01

    Background and purpose Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints. PMID:27910738

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

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

    2015-04-01

    The regeneration of articular cartilage consisting of hyaline cartilage and hydrogel scaffolds has been generally used in tissue engineering. However, success in in vivo studies has been rarely reported. The hydrogel scaffolds implanted into articular cartilage defects are mechanically unstable and it is difficult for them to integrate with the surrounding native cartilage tissue. Therefore, it is needed to regenerate cartilage and bone tissue simultaneously. We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were press-fitted into osteochondral tissue defects in a rabbit knee joints and the cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds was compared. In 12th week after implantation, the histological and immunohistochemical analyses were conducted to evaluate the cartilage tissue regeneration. In the blank and hydrogel scaffold groups, the defects were filled with fibrous tissues and the implanted hydrogel scaffolds could not maintain their initial position; in the hybrid scaffold group, newly generated cartilage tissues were morphologically similar to native cartilage tissues and were smoothly connected to the surrounding native tissues. This study demonstrates hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the defect site. © 2014 Wiley Periodicals, Inc.

  2. Magnetic resonance imaging of hyaline cartilage regeneration in neocartilage graft implantation.

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    Tan, C F; Ng, K K; Ng, S H; Cheung, Y C

    2003-12-01

    The purpose of this study was to investigate the regenerative potential of hyaline cartilage in a neocartilage graft implant with the aid of MR cartilage imaging using a rabbit model. Surgical osteochondral defects were created in the femoral condyles of 30 mature New Zealand rabbits. The findings of neocartilage in autologous cartilage grafts packed into osteochondral defects were compared with control group of no implant to the osteochondral defect. The outcome of the implantations was correlated with histologic and MR cartilage imaging findings over a 3-month interval. Neocartilage grafts packed into osteochondral defects showed regeneration of hyaline cartilage at the outer layer of the implant using MR cartilage imaging. Fibrosis of fibrocartilage developed at the outer layer of the autologous cartilage graft together with an inflammatory reaction within the osteochondral defect. This animal study provides evidence of the regenerative ability of hyaline cartilage in neocartilage transplants to repair articular cartilage.

  3. Isolation, characterization, and differentiation of stem cells for cartilage regeneration.

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    Beane, Olivia S; Darling, Eric M

    2012-10-01

    The goal of tissue engineering is to create a functional replacement for tissues damaged by injury or disease. In many cases, impaired tissues cannot provide viable cells, leading to the investigation of stem cells as a possible alternative. Cartilage, in particular, may benefit from the use of stem cells since the tissue has low cellularity and cannot effectively repair itself. To address this need, researchers are investigating the chondrogenic capabilities of several multipotent stem cell sources, including adult and extra-embryonic mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Comparative studies indicate that each cell type has advantages and disadvantages, and while direct comparisons are difficult to make, published data suggest some sources may be more promising for cartilage regeneration than others. In this review, we identify current approaches for isolating and chondrogenically differentiating MSCs from bone marrow, fat, synovium, muscle, and peripheral blood, as well as cells from extra-embryonic tissues, ESCs, and iPSCs. Additionally, we assess chondrogenic induction with growth factors, identifying standard cocktails used for each stem cell type. Cell-only (pellet) and scaffold-based studies are also included, as is a discussion of in vivo results.

  4. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.

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    Jones, Brendan A; Pei, Ming

    2012-08-01

    Articular cartilage is difficult to heal once injury or disease occurs. Autologous chondrocyte transplantation is a biological treatment with good prognosis, but donor site morbidity and limited cell source are disadvantages. Currently, mesenchymal stem cells (MSCs) are a promising approach for cartilage regeneration. Despite there being various sources, the best candidate for cartilage regeneration is the one with the greatest chondrogenic potential and the least hypertrophic differentiation. These properties are able to insure that the regenerated tissue is hyaline cartilage of high quality. This review article will summarize relevant literature to justify synovium-derived stem cells (SDSCs) as a tissue-specific stem cell for chondrogenesis by comparing synovium and cartilage with respect to anatomical location and functional structure, comparing the growth characterization and chondrogenic capacity of SDSCs and MSCs, evaluating the application of SDSCs in regenerative medicine and diseases, and discussing potential future directions.

  5. Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced by a novel double-network gel implantation.

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    Arakaki, Kazunobu; Kitamura, Nobuto; Kurokawa, Takayuki; Onodera, Shin; Kanaya, Fuminori; Gong, Jian-Ping; Yasuda, Kazunori

    2011-02-01

    We have recently discovered that spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect in the rabbit, when we implant a novel double-network (DN) gel plug at the bottom of the defect. To clarify whether joint immobilization inhibits the spontaneous hyaline cartilage regeneration, we conducted this study with 20 rabbits. At 4 or 12 weeks after surgery, the defect in the mobile knees was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen, while no cartilage tissues were observed in the defect in the immobilized knees. Type-2 collagen, Aggrecan, and SOX9 mRNAs were expressed only in the mobile knees at each period. This study demonstrated that joint immobilization significantly inhibits the spontaneous hyaline cartilage regeneration induced by the DN gel implantation. This fact suggested that the mechanical environment is one of the significant factors to induce this phenomenon.

  6. Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury

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    Embree, Mildred C.; Chen, Mo; Pylawka, Serhiy; Kong, Danielle; Iwaoka, George M.; Kalajzic, Ivo; Yao, Hai; Shi, Chancheng; Sun, Dongming; Sheu, Tzong-Jen; Koslovsky, David A.; Koch, Alia; Mao, Jeremy J.

    2016-01-01

    Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues. PMID:27721375

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

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    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

  8. 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

  9. The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells.

    Science.gov (United States)

    Levato, Riccardo; Webb, William R; Otto, Iris A; Mensinga, Anneloes; Zhang, Yadan; van Rijen, Mattie; van Weeren, René; Khan, Ilyas M; Malda, Jos

    2017-10-01

    Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models. Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells

  10. Xiphoid Process-Derived Chondrocytes: A Novel Cell Source for Elastic Cartilage Regeneration

    Science.gov (United States)

    Nam, Seungwoo; Cho, Wheemoon; Cho, Hyunji; Lee, Jungsun

    2014-01-01

    Reconstruction of elastic cartilage requires a source of chondrocytes that display a reliable differentiation tendency. Predetermined tissue progenitor cells are ideal candidates for meeting this need; however, it is difficult to obtain donor elastic cartilage tissue because most elastic cartilage serves important functions or forms external structures, making these tissues indispensable. We found vestigial cartilage tissue in xiphoid processes and characterized it as hyaline cartilage in the proximal region and elastic cartilage in the distal region. Xiphoid process-derived chondrocytes (XCs) showed superb in vitro expansion ability based on colony-forming unit fibroblast assays, cell yield, and cumulative cell growth. On induction of differentiation into mesenchymal lineages, XCs showed a strong tendency toward chondrogenic differentiation. An examination of the tissue-specific regeneration capacity of XCs in a subcutaneous-transplantation model and autologous chondrocyte implantation model confirmed reliable regeneration of elastic cartilage regardless of the implantation environment. On the basis of these observations, we conclude that xiphoid process cartilage, the only elastic cartilage tissue source that can be obtained without destroying external shape or function, is a source of elastic chondrocytes that show superb in vitro expansion and reliable differentiation capacity. These findings indicate that XCs could be a valuable cell source for reconstruction of elastic cartilage. PMID:25205841

  11. A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose

    Science.gov (United States)

    2013-01-01

    Introduction Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model. Methods Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material. Results Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures

  12. Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model

    NARCIS (Netherlands)

    Tsuchida, Anika I.; Beekhuizen, Michiel; Rutgers, Marijn; van Osch, Gerjo J.V.M.; Bekkers, Joris E.J.; Bot, Arjan G.J.; Geurts, Bernd; Dhert, Wouter J.A.; Saris, Daniël B.F.; Creemers, Laura B.

    2012-01-01

    Introduction This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.

  13. Biostable scaffolds of polyacrylate polymers implanted in the articular cartilage induce hyaline-like cartilage regeneration in rabbits.

    Science.gov (United States)

    Sancho-Tello, María; Forriol, Francisco; Martín de Llano, José J; Antolinos-Turpin, Carmen; Gómez-Tejedor, José A; Gómez Ribelles, José L; Carda, Carmen

    2017-07-05

    To study the influence of scaffold properties on the organization of in vivo cartilage regeneration. Our hypothesis was that stress transmission to the cells seeded inside the pores of the scaffold or surrounding it, which is highly dependent on the scaffold properties, determines the differentiation of both mesenchymal cells and dedifferentiated autologous chondrocytes. 4 series of porous scaffolds made of different polyacrylate polymers, previously seeded with cultured rabbit chondrocytes or without cells, were implanted in cartilage defects in rabbits. Subchondral bone was injured during the surgery to allow blood to reach the implantation site and fill the scaffold pores. At 3 months after implantation, excellent tissue regeneration was obtained, with a well-organized layer of hyaline-like cartilage at the condylar surface in most cases of the hydrophobic or slightly hydrophilic series. The most hydrophilic material induced the poorest regeneration. However, no statistically significant difference was observed between preseeded and non-preseeded scaffolds. All of the materials used were biocompatible, biostable polymers, so, in contrast to some other studies, our results were not perturbed by possible effects attributable to material degradation products or to the loss of scaffold mechanical properties over time due to degradation. Cartilage regeneration depends mainly on the properties of the scaffold, such as stiffness and hydrophilicity, whereas little difference was observed between preseeded and non-preseeded scaffolds.

  14. Cartilage and bone cells do not participate in skeletal regeneration in Ambystoma mexicanum limbs.

    Science.gov (United States)

    McCusker, Catherine D; Diaz-Castillo, Carlos; Sosnik, Julian; Q Phan, Anne; Gardiner, David M

    2016-08-01

    The Mexican Axolotl is one of the few tetrapod species that is capable of regenerating complete skeletal elements in injured adult limbs. Whether the skeleton (bone and cartilage) plays a role in the patterning and contribution to the skeletal regenerate is currently unresolved. We tested the induction of pattern formation, the effect on cell proliferation, and contributions of skeletal tissues (cartilage, bone, and periosteum) to the regenerating axolotl limb. We found that bone tissue grafts from transgenic donors expressing GFP fail to induce pattern formation and do not contribute to the newly regenerated skeleton. Periosteum tissue grafts, on the other hand, have both of these activities. These observations reveal that skeletal tissue does not contribute to the regeneration of skeletal elements; rather, these structures are patterned by and derived from cells of non-skeletal connective tissue origin. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    NARCIS (Netherlands)

    Pot, M.W.; Kuppevelt, T.H. van; Gonzales, V.K.; Buma, P.; Hout, J. in't; Vries, R.B.M. de; Daamen, W.F.

    2017-01-01

    Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline

  16. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Science.gov (United States)

    Ude, Chinedu C; Sulaiman, Shamsul B; Min-Hwei, Ng; Hui-Cheng, Chen; Ahmad, Johan; Yahaya, Norhamdan M; Saim, Aminuddin B; Idrus, Ruszymah B H

    2014-01-01

    In this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7) autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008). Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan) compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013). Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001). Fluorescence of the tracking dye (PKH26) in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  17. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Directory of Open Access Journals (Sweden)

    Chinedu C Ude

    Full Text Available OBJECTIVES: In this study, Adipose stem cells (ADSC and bone marrow stem cells (BMSC, multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7 autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. RESULTS: The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008. Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013. Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001. Fluorescence of the tracking dye (PKH26 in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. CONCLUSION: Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  18. [Progress in application of 3D bioprinting in cartilage regeneration and reconstruction for tissue engineering].

    Science.gov (United States)

    Liao, Junlin; Wang, Shaohua; Chen, Jia; Xie, Hongju; Zhou, Jianda

    2017-02-28

    Three-dimensional (3D) bioprinting provides an advanced technology for tissue engineering and regenerative medicine because of its ability to produce the models or organs with higher precision and more suitable for human body. It has been successfully used to produce a variety of cartilage scaffold materials. In addition, 3D bioprinter can directly to print tissue and organs with live chondrocytes. In conclusion, 3D bioprinting may have broad prospect for cartilage regeneration and reconstruction in tissue engineering.

  19. Assessment of fixed charge density in regenerated cartilage by Gd-DTPA-enhanced MRI

    International Nuclear Information System (INIS)

    Miyata, Shogo; Homma, Kazuhiro; Numano, Tomokazu; Furukawa, Katsuko; Tateishi, Tetsuya; Ushida, Takashi

    2006-01-01

    Applying regenerated cartilage in a clinical setting requires noninvasive evaluation to detect the maturity of cartilage tissue. Magnetic resonance (MR) imaging of articular cartilage is well accepted and has been applied clinically in recent years. We attempt to establish a noninvasive method to evaluate the maturity of regenerated cartilage tissue using gadolinium-enhanced MR imaging. To reconstruct cartilaginous tissue, we embedded articular chondrocytes harvested from bovine humeral head in agarose gel and cultured the cells in vitro up to 4 weeks. The fixed charge density (FCD) of the cartilage was determined using MRI gadolinium exclusion method. The sulfated glycosaminoglycan (sGAG) content was determined by dimethylmethylene blue dye-binding assay. The sGAG content and FCD of the regenerated cartilage increased with duration of culture. In the T 1 Gd maps, the [Gd-DTPA 2- ] in the specimen decreased, and the boundary between the sample disk and the bath solution of phosphate buffered saline (PBS) became clearer as time in culture increased. In the linear regression analysis, FCD and sGAG content correlated significantly. Gadolinium-enhanced MR imaging measurements can be useful predictors of the degree of cartilaginous tissue formation. (author)

  20. [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.

  1. Articular Cartilage Increases Transition Zone Regeneration in Bone-tendon Junction Healing

    Science.gov (United States)

    Qin, Ling; Lee, Kwong Man; Leung, Kwok Sui

    2008-01-01

    The fibrocartilage transition zone in the direct bone-tendon junction reduces stress concentration and protects the junction from failure. Unfortunately, bone-tendon junctions often heal without fibrocartilage transition zone regeneration. We hypothesized articular cartilage grafts could increase fibrocartilage transition zone regeneration. Using a goat partial patellectomy repair model, autologous articular cartilage was harvested from the excised distal third patella and interposed between the residual proximal two-thirds bone fragment and tendon during repair in 36 knees. We evaluated fibrocartilage transition zone regeneration, bone formation, and mechanical strength after repair at 6, 12, and 24 weeks and compared them with direct repair. Autologous articular cartilage interposition resulted in more fibrocartilage transition zone regeneration (69.10% ± 14.11% [mean ± standard deviation] versus 8.67% ± 7.01% at 24 weeks) than direct repair at all times. There was no difference in the amount of bone formation and mechanical strength achieved. Autologous articular cartilage interposition increases fibrocartilage transition zone regeneration in bone-tendon junction healing, but additional research is required to ascertain the mechanism of stimulation and to establish the clinical applicability. PMID:18987921

  2. Tailored PVA/ECM Scaffolds for Cartilage Regeneration

    Directory of Open Access Journals (Sweden)

    Elena Stocco

    2014-01-01

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

  3. RHEB: a potential regulator of chondrocyte phenotype for cartilage tissue regeneration.

    Science.gov (United States)

    Ashraf, S; Ahn, J; Cha, B-H; Kim, J-S; Han, I; Park, H; Lee, S-H

    2017-09-01

    As articular cartilage has a limited ability to self-repair, successful cartilage regeneration requires clinical-grade chondrocytes with innate characteristics. However, cartilage regeneration via chondrocyte transplantation is challenging, because chondrocytes lose their innate characteristics during in vitro expansion. Here, we investigated the mechanistic underpinning of the gene Ras homologue enriched in brain (RHEB) in the control of senescence and dedifferentiation through the modulation of oxidative stress in chondrocytes, a hallmark of osteoarthritis. Serial expansion of human chondrocytes led to senescence, dedifferentiation and oxidative stress. RHEB maintained the innate characteristics of chondrocytes by regulating senescence, dedifferentiation and oxidative stress, leading to the upregulation of COL2 expression via SOX9 and the downregulation of p27 expression via MCL1. RHEB also decreased the expression of COL10. RHEB knockdown mimics decreased the expression of SOX9, COL2 and MCL1, while abrogating the suppressive function of RHEB on p27 and COL10 in chondrocytes. RHEB-overexpressing chondrocytes successfully formed cartilage tissue in vitro as well as in vivo, with increased expression of GAG matrix and chondrogenic markers. RHEB induces a distinct gene expression signature that maintained the innate chondrogenic properties over a long period. Therefore, RHEB expression represents a potentially useful mechanism in terms of cartilage tissue regeneration from chondrocytes, by which chondrocyte phenotypic and molecular characteristics can be retained through the modulation of senescence, dedifferentiation and oxidative stress. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Stable subcutaneous cartilage regeneration of bone marrow stromal cells directed by chondrocyte sheet.

    Science.gov (United States)

    Li, Dan; Zhu, Lian; Liu, Yu; Yin, Zongqi; Liu, Yi; Liu, Fangjun; He, Aijuan; Feng, Shaoqing; Zhang, Yixin; Zhang, Zhiyong; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

    2017-05-01

    In vivo niche plays an important role in regulating differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. This study explored the feasibility that chondrocyte sheet created chondrogenic niche retained chondrogenic phenotype of BMSC engineered cartilage (BEC) in subcutaneous environments. Porcine BMSCs were seeded into biodegradable scaffolds followed by 4weeks of chondrogenic induction in vitro to form BEC, which were wrapped with chondrocyte sheets (Sheet group), acellular small intestinal submucosa (SIS, SIS group), or nothing (Blank group) respectively and then implanted subcutaneously into nude mice to trace the maintenance of chondrogenic phenotype. The results showed that all the constructs in Sheet group displayed typical cartilaginous features with abundant lacunae and cartilage specific matrices deposition. These samples became more mature with prolonged in vivo implantation, and few signs of ossification were observed at all time points except for one sample that had not been wrapped completely. Cell labeling results in Sheet group further revealed that the implanted BEC directly participated in cartilage formation. Samples in both SIS and Blank groups mainly showed ossified tissue at all time points with partial fibrogenesis in a few samples. These results suggested that chondrocyte sheet could create a chondrogenic niche for retaining chondrogenic phenotype of BEC in subcutaneous environment and thus provide a novel research model for stable ectopic cartilage regeneration based on stem cells. In vivo niche plays an important role in directing differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. The current study demonstrated that chondrocyte sheet generated by

  5. Dental mesenchymal stem cells encapsulated in alginate hydrogel co-delivery microencapsulation system for cartilage regeneration

    Science.gov (United States)

    Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider; Akiyama, Kentaro; Snead, Malcolm L; Shi, Songtao

    2013-01-01

    Dental-derived MSCs are promising candidates for cartilage regeneration, with high chondrogenic differentiation capacity. This property contributes to making dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating Periodontal Ligament Stem Cells (PDLSCs) or Gingival Mesenchymal Stem Cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs, GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSC) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by toluidine blue and safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (Palginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs. PMID:23891740

  6. Polycaprolactone foam functionalized with chitosan microparticles – a suitable scaffold for cartilage regeneration.

    Czech Academy of Sciences Publication Activity Database

    Filová, Eva; Jakubcová, B.; Danilová, I.; Kuželová Košťáková, E.; Jarošíková, T.; Chernyavskiy, Oleksandr; Hejda, J.; Handl, M.; Beznoska, J.; Nečas, A.; Rosina, J.; Amler, Evžen

    2016-01-01

    Roč. 65, č. 1 (2016), s. 121-131 ISSN 0862-8408 Institutional support: RVO:68378041 ; RVO:67985823 Keywords : poly-epsilon-caprolactone * chitosan * cartilage regeneration * foam Subject RIV: FI - Traumatology, Orthopedics Impact factor: 1.461, year: 2016

  7. [Cartilage regeneration surgery on the hip : What is feasible?

    Science.gov (United States)

    Landgraeber, Stefan; Jäger, Marcus; Fickert, Stefan

    2017-11-01

    Localized cartilage defects at the hip are mainly caused by pre-arthritic deformities, particularly by cam-type femoroacetabular impingement (FAI). Timely elimination of symptomatic deformities can prevent further progression such as cartilage defects. As the defects mostly occur in the anterolateral part of the acetabulum, they can be easily treated either by open surgery or by arthroscopy. To date the most effective methods of treatment are bone marrow stimulation, with or without a covering of biomaterials, and autologous chondrocyte transplantation. In selected cases, readaptation of the damaged cartilage can be attempted by biological procedures. In the present article, the findings reported in current studies on these procedures are summarized and discussed in detail. An outlook is given regarding possible future treatment concepts.

  8. 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.

  9. Calcineurin Inhibition at Physiological Osmolarity: Toward improving cartilage regeneration

    NARCIS (Netherlands)

    A.E. van der Windt (Anna)

    2017-01-01

    markdownabstractArticular hyaline cartilage is a white, smooth structure covering the ends of bones in synovial joints, like in the hip and knee. Because of its unique stiff yet flexible properties, it distributes the loads, as a consequence of weight bearing and locomotion, over the surface of the

  10. Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives.

    Science.gov (United States)

    Huang, Yi-Zhou; Xie, Hui-Qi; Silini, Antonietta; Parolini, Ornella; Zhang, Yi; Deng, Li; Huang, Yong-Can

    2017-10-01

    Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are considered ideal sources for cartilage regeneration. In addition to the progress in research and promising preclinical results, many important research questions must be answered before widespread success in cartilage regeneration is achieved. This review outlines the biology of stem/progenitor cells derived from the articular cartilage, the synovial membrane, and the synovial fluid, including their tissue distribution, function and biological characteristics. Furthermore, preclinical and clinical trials focusing on their applications for cartilage regeneration are summarized, and future research perspectives are discussed.

  11. Extracellular matrix scaffolds for cartilage and bone regeneration

    NARCIS (Netherlands)

    Benders, K.E.M.; van Weeren, P.R.; Badylak, S.F.; Saris, Daniël B.F.; Dhert, W.J.A.; Malda, J.

    2013-01-01

    Regenerative medicine approaches based on decellularized extracellular matrix (ECM) scaffolds and tissues are rapidly expanding. The rationale for using ECM as a natural biomaterial is the presence of bioactive molecules that drive tissue homeostasis and regeneration. Moreover, appropriately

  12. Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels.

    Science.gov (United States)

    Meppelink, Amanda M; Zhao, Xing; Griffin, Darvin J; Erali, Richard; Gill, Thomas J; Bonassar, Lawrence J; Redmond, Robert W; Randolph, Mark A

    2016-07-01

    Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.

  13. Regeneration of spine disc and joint cartilages under temporal and space modulated laser radiation

    Science.gov (United States)

    Sobol, E.; Shekhter, A.; Baskov, A.; Baskov, V.; Baum, O.; Borchshenko, I.; Golubev, V.; Guller, A.; Kolyshev, I.; Omeltchenko, A.; Sviridov, A.; Zakharkina, O.

    2009-02-01

    The effect of laser radiation on the generation of hyaline cartilage in spine disc and joints has been demonstrated. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reconstruction of spine discs. Possible mechanisms of laser-induced regeneration include: (1) Space and temporary modulated laser beam induces nonhomogeneous and pulse repetitive thermal expansion and stress in the irradiated zone of cartilage. Mechanical effect due to controllable thermal expansion of the tissue and micro and nano gas bubbles formation in the course of the moderate (up to 45-50 oC) heating of the NP activate biological cells (chondrocytes) and promote cartilage regeneration. (2) Nondestructive laser radiation leads to the formation of nano and micro-pores in cartilage matrix. That promotes water permeability and increases the feeding of biological cells. Results provide the scientific and engineering basis for the novel low-invasive laser procedures to be used in orthopedics for the treatment cartilages of spine and joints. The technology and equipment for laser reconstruction of spine discs have been tested first on animals, and then in a clinical trial. Since 2001 the laser reconstruction of intervertebral discs have been performed for 340 patients with chronic symptoms of low back or neck pain who failed to improve with non-operative care. Substantial relief of back pain was obtained in 90% of patients treated who returned to their daily activities. The experiments on reparation of the defects in articular cartilage of the porcine joints under temporal and spase modulated laser radiation have shown promising results.

  14. Isolation, Characterization, and Differentiation of Stem Cells for Cartilage Regeneration

    OpenAIRE

    Beane, Olivia S.; Darling, Eric M.

    2012-01-01

    The goal of tissue engineering is to create a functional replacement for tissues damaged by injury or disease. In many cases, impaired tissues cannot provide viable cells, leading to the investigation of stem cells as a possible alternative. Cartilage, in particular, may benefit from the use of stem cells since the tissue has low cellularity and cannot effectively repair itself. To address this need, researchers are investigating the chondrogenic capabilities of several multipotent stem cell ...

  15. Original and regenerating lizard tail cartilage contain putative resident stem/progenitor cells.

    Science.gov (United States)

    Alibardi, Lorenzo

    2015-11-01

    Regeneration of cartilaginous tissues is limited in mammals but it occurs with variable extension in lizards (reptiles), including in their vertebrae. The ability of lizard vertebrae to regenerate cartilaginous tissue that is later replaced with bone has been analyzed using tritiated thymidine autoradiography and 5BrdU immunocytochemistry after single pulse or prolonged-pulse and chase experiments. The massive cartilage regeneration that can restore broad vertebral regions and gives rise to a long cartilaginous tube in the regenerating tail, depends from the permanence of some chondrogenic cells within adult vertebrae. Few cells that retain tritiated thymidine or 5-bromodeoxy-uridine for over 35 days are mainly localized in the inter-vertebral cartilage and in sparse chondrogenic regions of the neural arch of the vertebrae, suggesting that they are putative resident stem/progenitor cells. The study supports previous hypothesis indicating that the massive regeneration of the cartilaginous tissue in damaged vertebrae and in the regenerating tail of lizards derive from resident stem cells mainly present in the cartilaginous areas of the vertebrae including in the perichondrium that are retained in adult lizards as growing centers for most of their lifetime. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. In Vitro Analysis of Cartilage Regeneration Using a Collagen Type I Hydrogel (CaReS) in the Bovine Cartilage Punch Model.

    Science.gov (United States)

    Horbert, Victoria; Xin, Long; Foehr, Peter; Brinkmann, Olaf; Bungartz, Matthias; Burgkart, Rainer H; Graeve, T; Kinne, Raimund W

    2018-02-01

    Objective Limitations of matrix-assisted autologous chondrocyte implantation to regenerate functional hyaline cartilage demand a better understanding of the underlying cellular/molecular processes. Thus, the regenerative capacity of a clinically approved hydrogel collagen type I implant was tested in a standardized bovine cartilage punch model. Methods Cartilage rings (outer diameter 6 mm; inner defect diameter 2 mm) were prepared from the bovine trochlear groove. Collagen implants (± bovine chondrocytes) were placed inside the cartilage rings and cultured up to 12 weeks. Cartilage-implant constructs were analyzed by histology (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2), and for protein content, RNA expression, and implant push-out force. Results Cartilage-implant constructs revealed vital morphology, preserved matrix integrity throughout culture, progressive, but slight proteoglycan loss from the "host" cartilage or its surface and decreasing proteoglycan release into the culture supernatant. In contrast, collagen 2 and 1 content of cartilage and cartilage-implant interface was approximately constant over time. Cell-free and cell-loaded implants showed (1) cell migration onto/into the implant, (2) progressive deposition of aggrecan and constant levels of collagens 1 and 2, (3) progressively increased mRNA levels for aggrecan and collagen 2, and (4) significantly augmented push-out forces over time. Cell-loaded implants displayed a significantly earlier and more long-lasting deposition of aggrecan, as well as tendentially higher push-out forces. Conclusion Preserved tissue integrity and progressively increasing cartilage differentiation and push-out forces for up to 12 weeks of cultivation suggest initial cartilage regeneration and lateral bonding of the implant in this in vitro model for cartilage replacement materials.

  17. Patient Profiling in Cartilage Regeneration Prognostic Factors Determining Success of Treatment for Cartilage Defects

    NARCIS (Netherlands)

    de Windt, Tommy S.; Bekkers, Joris E. J.; Creemers, Laura B.; Dhert, Wouter J. A.; Saris, Daniel B. F.

    2009-01-01

    Background: Cartilage therapy for focal articular lesions has been implemented for more than a decade, and it is becoming increasingly available. What is still lacking, however, is analysis of patient characteristics to help improve outcome or select patients for specific treatment. Purpose: To

  18. Cartilage Regeneration in Full-Thickness Patellar Chondral Defects Treated with Particulated Juvenile Articular Allograft Cartilage: An MRI Analysis.

    Science.gov (United States)

    Grawe, Brian; Burge, Alissa; Nguyen, Joseph; Strickland, Sabrina; Warren, Russell; Rodeo, Scott; Shubin Stein, Beth

    2017-10-01

    Background Full-thickness cartilage lesions of the patella represent a common source of pain and dysfunction. Previously reported surgical treatment options include marrow stimulation, cell-based treatments, and osteochondral transfer. Minced juvenile allograft cartilage is a novel treatment option that allows for a single stage approach for these lesions. Hypothesis Particulated juvenile allograft cartilage (PJAC) for the treatment of chondral defects of the patella would offer acceptable lesion fill rates, mature over time, and not be associated with any negative biologic effects on the surrounding tissue. Methods A retrospective chart review of prospectively collected data was conducted to identify consecutive patients who were treated with PJAC for a full thickness symptomatic cartilage lesion. Qualitative (fast spin echo) and quantitative (T2 mapping) magnetic resonance imaging (MRI) was undertaken at the 6-, 12-, and 24-month postoperative mark. Numerous patient, lesion, and graft specific factors were assessed against MRI scores and percent defect fill of the graft. Graft maturation over time was also assessed. Results Forty-five patients total were included in the study. Average age at the time of surgery was 26.5 years (range 13-45 years), average lesion size was 208 mm 2 (range 4-500 mm 2 ), and average donor age was 49.5 months (range 3-120 months). Sixty percent of the patients were female, while 93% of all patients underwent a concomitant procedure at the time of the index operation. Six-month MRI findings revealed that no patient-, graft-, or donor-specific factors correlated with MR scores, and 82% of the knees demonstrated good to excellent fill. Twelve-month MRI findings revealed that T2 relaxation times of deep graft demonstrated negative correlation with patient age ( P = 0.049) and donor age ( P = 0.006), the integration zone showed a negative correlation with donor age ( P = 0.026). In all, 85% of patients at 12 months displayed good to

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

    Science.gov (United States)

    Guo, Weimin; Zheng, Xifu; Zhang, Weiguo; Chen, Mingxue; Wang, Zhenyong; Hao, Chunxiang; Huang, Jingxiang; Yuan, Zhiguo; Zhang, Yu; Wang, Mingjie; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Sui, Xiang; Xu, Wenjing; Liu, Shuyun; Lu, Shibi; Guo, Quanyi

    2018-01-01

    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. In Vitro Mimetic Models for the Bone-Cartilage Interface Regeneration.

    Science.gov (United States)

    Bicho, Diana; Pina, Sandra; Oliveira, J Miguel; Reis, Rui L

    2018-01-01

    In embryonic development, pure cartilage structures are in the basis of bone-cartilage interfaces. Despite this fact, the mature bone and cartilage structures can vary greatly in composition and function. Nevertheless, they collaborate in the osteochondral region to create a smooth transition zone that supports the movements and forces resulting from the daily activities. In this sense, all the hierarchical organization is involved in the maintenance and reestablishment of the equilibrium in case of damage. Therefore, this interface has attracted a great deal of interest in order to understand the mechanisms of regeneration or disease progression in osteoarthritis. With that purpose, in vitro tissue models (either static or dynamic) have been studied. Static in vitro tissue models include monocultures, co-cultures, 3D cultures, and ex vivo cultures, mostly cultivated in flat surfaces, while dynamic models involve the use of bioreactors and microfluidic systems. The latter have emerged as alternatives to study the cellular interactions in a more authentic manner over some disadvantages of the static models. The current alternatives of in vitro mimetic models for bone-cartilage interface regeneration are overviewed and discussed herein.

  1. Fabrication of custom-shaped grafts for cartilage regeneration.

    Science.gov (United States)

    Koo, Seungbum; Hargreaves, Brian A; Gold, Garry E; Dragoo, Jason L

    2010-10-01

    to create a custom-shaped graft through 3D tissue shape reconstruction and rapid-prototype molding methods using MRI data, and to test the accuracy of the custom-shaped graft against the original anatomical defect. An iatrogenic defect on the distal femur was identified with a 1.5 Tesla MRI and its shape was reconstructed into a three-dimensional (3D) computer model by processing the 3D MRI data. First, the accuracy of the MRI-derived 3D model was tested against a laser-scan based 3D model of the defect. A custom-shaped polyurethane graft was fabricated from the laser-scan based 3D model by creating custom molds through computer aided design and rapid-prototyping methods. The polyurethane tissue was laser-scanned again to calculate the accuracy of this process compared to the original defect. The volumes of the defect models from MRI and laser-scan were 537 mm3 and 405 mm3, respectively, implying that the MRI model was 33% larger than the laser-scan model. The average (±SD) distance deviation of the exterior surface of the MRI model from the laser-scan model was 0.4 ± 0.4 mm. The custom-shaped tissue created from the molds was qualitatively very similar to the original shape of the defect. The volume of the custom-shaped cartilage tissue was 463 mm3 which was 15% larger than the laser-scan model. The average (±SD) distance deviation between the two models was 0.04 ± 0.19 mm. This investigation proves the concept that custom-shaped engineered grafts can be fabricated from standard sequence 3-D MRI data with the use of CAD and rapid-prototyping technology. The accuracy of this technology may help solve the interfacial problem between native cartilage and graft, if the grafts are custom made for the specific defect. The major source of error in fabricating a 3D custom-shaped cartilage graft appears to be the accuracy of a MRI data itself; however, the precision of the model is expected to increase by the utilization of advanced MR sequences with higher magnet

  2. Efficient Computational Design of a Scaffold for Cartilage Cell Regeneration

    DEFF Research Database (Denmark)

    Tajsoleiman, Tannaz; Jafar Abdekhodaie, Mohammad; Gernaey, Krist V.

    2018-01-01

    Due to the sensitivity of mammalian cell cultures, understanding the influence of operating conditions during a tissue generation procedure is crucial. In this regard, a detailed study of scaffold based cell culture under a perfusion flow is presented with the aid of mathematical modelling...... and computational fluid dynamics (CFD). With respect to the complexity of the case study, this work focuses solely on the effect of nutrient and metabolite concentrations, and the possible influence of fluid-induced shear stress on a targeted cell (cartilage) culture. The simulation set up gives the possibility...... of predicting the cell culture behavior under various operating conditions and scaffold designs. Thereby, the exploitation of the predictive simulation into a newly developed stochastic routine provides the opportunity of exploring improved scaffold geometry designs. This approach was applied on a common type...

  3. Gallium nitrate: effects on cartilage during limb regeneration in the axolotl, Ambystoma mexicanum.

    Science.gov (United States)

    Tassava, Roy A; Mendenhall, Luciara; Apseloff, Glen; Gerber, Nicholas

    2002-09-01

    Gallium nitrate, a drug shown to have efficacy in Paget's disease of bone, hypercalcemia of malignancy, and a variety of experimental autoimmune diseases, also inhibits the growth of some types of cancer. We examined dose and timing of administration of gallium nitrate on limb regeneration in the Mexican axolotl, Ambystoma mexicanum. Administered by intraperitoneal injection, gallium nitrate inhibited limb regeneration in a dose-dependent manner. Gallium nitrate initially suppressed epithelial wound healing and subsequently distorted both anterior-posterior and proximo-distal chondrogenic patterns. Gallium nitrate given at three days after amputation severely inhibited regeneration at high doses (6.25 mg/axolotl) and altered the normal patterning of the regenerates at low doses (3.75 mg/axolotl). Administration of 6.25 mg of gallium nitrate at four or 14 days prior to amputation also inhibited regeneration. In amputated limbs of gallium-treated axolotls, the chondrocytes were lost from inside the radius/ulna. Limbs that regenerated after gallium treatment was terminated showed blastema formation preferentially over the ulna. New cartilage of the regenerate often attached to the sides of the existing radius/ulna proximally into the stump and less so to the distal cut ends. J. Exp. Zool. 293:384-394, 2002. Copyright 2002 Wiley-Liss, Inc.

  4. Strategies on process engineering of chondrocyte culture for cartilage tissue regeneration.

    Science.gov (United States)

    Mallick, Sarada Prasanna; Rastogi, Amit; Tripathi, Satyavrat; Srivastava, Pradeep

    2017-04-01

    The current work is an attempt to study the strategies for cartilage tissue regeneration using porous scaffold in wavy walled airlift bioreactor (ALBR). Novel chitosan, poly (L-lactide) and hyaluronic acid based composite scaffold were prepared. The scaffolds were cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, N-hydroxysuccinimide and chondroitin sulfate to obtain interconnected 3D microstructure showing excellent biocompatibility, higher cellular differentiation and increased stability. The surface morphology and porosity of the scaffolds were analyzed using scanning electron microscopy (SEM) and mercury intrusion porosimeter and optimized for chondrocyte regeneration. The study shows that the scaffolds were highly porous with pore size ranging from 48 to 180 µm and the porosities in the range 80-92%. Swelling and in vitro degradation studies were performed for the composite scaffolds; by increasing the chitosan: HA ratio in the composite scaffolds, the swelling property increases and stabilizes after 24 h. There was controlled degradation of composite scaffolds for 4 weeks. The uniform chondrocyte distribution in the scaffold using various growth modes in the shake flask and ALBR was studied by glycosaminoglycans (GAG) quantification, MTT assay and mixing time evaluation. The cell culture studies demonstrated that efficient designing of ALBR increases the cartilage regeneration as compared to using a shake flask. The free chondrocyte microscopy and cell attachment were performed by inverted microscope and SEM, and from the study it was confirmed that the cells uniformly attached to the scaffold. This study focuses on optimizing strategies for the culture of chondrocyte using suitable scaffold for improved cartilage tissue regeneration.

  5. [Injectable hydrogel functionalised with thrombocyte-rich solution and microparticles for accelerated cartilage regeneration].

    Science.gov (United States)

    Rampichová, M; Buzgo, M; Křížková, B; Prosecká, E; Pouzar, M; Štrajtová, L

    2013-01-01

    Articular cartilage defects arise due to injury or osteochondral disease such as osteonecrosis or osteochondritis dissecans. In adult patients cartilage has minimal ability to repair itself and the lesions develop into degenerative arthritis. Overcoming the low regenerative capacity of the cartilage cells and the Hayflick limit poses a challenge for the therapy of osteochondral defects. Composite scaffolds with appropriate biomechanical properties combined with a suitable blend of proliferation and differentiation factors could be a solution. The aim of this in vitro study was to develop a novel functionalised hydrogel with an integrated drug delivery system stimulating articular cartilage regeneration. Injectable collagen/ hyaluronic acid/fibrin composite hydrogel was mixed with nanofibre-based microparticles. These were loaded with ascorbic acid and dexamethasone. In addition, the effect of thrombocyte-rich solution (TRS) was studied. The gels seeded with mesenchymal stem cells (MSCs) were cultivated for 14 days. The viability, proliferation and morphology of the cells were evaluated using molecular and microscopic methods. Scaffold degradation was also assessed. The cultivation study showed that MSCs remained viable in all experimental groups, which indicated good biocompatibility of the gel. However, the number of cells in the groups enriched with microparticles was lower than in the other groups. On the other hand, confocal microscopy showed higher cell viability and rounded morphology of the cells, which can be associated with chodrogenic differentiation. The scaffolds containing microparticles showed significantly higher stability during the 14-day experiment. Our results suggest that the addition of microparticles to the scaffold improved cell differentiation into the chondrogenic lineage, resulting in a lower proliferation rate. Cell viability was better in the groups enriched with microparticles that served as an efficient drug delivery system. In

  6. Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration.

    Science.gov (United States)

    Lee, Christopher Sd; Burnsed, Olivia A; Raghuram, Vineeth; Kalisvaart, Jonathan; Boyan, Barbara D; Schwartz, Zvi

    2012-08-24

    Adipose stem cells (ASCs) secrete many trophic factors that can stimulate tissue repair, including angiogenic factors, but little is known about how ASCs and their secreted factors influence cartilage regeneration. Therefore, the aim of this study was to determine the effects ASC-secreted factors have in repairing chondral defects. ASCs isolated from male Sprague Dawley rats were cultured in monolayer or alginate microbeads supplemented with growth (GM) or chondrogenic medium (CM). Subsequent co-culture, conditioned media, and in vivo cartilage defect studies were performed. ASC monolayers and microbeads cultured in CM had decreased FGF-2 gene expression and VEGF-A secretion compared to ASCs cultured in GM. Chondrocytes co-cultured with GM-cultured ASCs for 7 days had decreased mRNAs for col2, comp, and runx2. Chondrocytes treated for 12 or 24 hours with conditioned medium from GM-cultured ASCs had reduced sox9, acan, and col2 mRNAs; reduced proliferation and proteoglycan synthesis; and increased apoptosis. ASC-conditioned medium also increased endothelial cell tube lengthening whereas conditioned medium from CM-cultured ASCs had no effect. Treating ASCs with CM reduced or abolished these deleterious effects while adding a neutralizing antibody for VEGF-A eliminated ASC-conditioned medium induced chondrocyte apoptosis and restored proteoglycan synthesis. FGF-2 also mitigated the deleterious effects VEGF-A had on chondrocyte apoptosis and phenotype. When GM-grown ASC pellets were implanted in 1 mm non-critical hyaline cartilage defects in vivo, cartilage regeneration was inhibited as evaluated by radiographic and equilibrium partitioning of an ionic contrast agent via microCT imaging. Histology revealed that defects with GM-cultured ASCs had no tissue ingrowth from the edges of the defect whereas empty defects and defects with CM-grown ASCs had similar amounts of neocartilage formation. ASCs must be treated to reduce the secretion of VEGF-A and other factors that

  7. Cartilage regeneration using a porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite

    International Nuclear Information System (INIS)

    Ohyabu, Yohimi; Adegawa, Takuro; Yoshioka, Tomohiko; Ikoma, Toshiyuki; Uemura, Toshimasa; Tanaka, Junzo

    2010-01-01

    Because cartilage has limited potential for self-repair, tissue engineering is expected to replace the present therapies for damaged cartilage, such as total knee arthroplasty. However, scaffolds suitable for cartilage tissue engineering have not been established. We synthesized a novel porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite (pCol-HAp/ChS), containing materials which resemble extracellular matrices in bone and cartilage tissues, which needs high compressive strength for clinical use. HAp/ChS had smaller crystals and a larger total surface area than HAp. SEM images showed pCol-HAp/ChS to have the roughest surface compared with pCol and pCol-HAp. The mechanical properties suggest that pCol-HAp/ChS and pCol/HAp are similar, and superior to pCol. Seeding experiments showed a uniform distribution of mesenchymal stem cells (MSCs) in pCol-HAp/ChS and pCol/HAp. Safranin O, Toluidine blue and Alcian blue staining after 2 weeks of culture revealed pCol-HAp/ChS to be the most chondrogenic in each case. In addition, MSCs in pCol-HAp/ChS produced more glycosaminoglycans, a cartilage matrix, than those in pCol-HAp. Further, pCol-HAp/ChS regenerated 15 times more cartilaginous tissue than pCol. From these results, pCol-HAp/ChS is expected to be a candidate for a scaffold for cartilage tissue engineering in place of collagen sponge.

  8. Cartilage regeneration using a porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite

    Energy Technology Data Exchange (ETDEWEB)

    Ohyabu, Yohimi, E-mail: ooyabu.yoshimi@aist.go.jp [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, S7-5 Ookayama, Meguro, Tokyo 152-8550 (Japan); Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), Central-4, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566 (Japan); Adegawa, Takuro; Yoshioka, Tomohiko [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, S7-5 Ookayama, Meguro, Tokyo 152-8550 (Japan); Ikoma, Toshiyuki [Biomaterials Center, National Institute for Materials Science, 1-1 Sengen, Tsukuba, Ibaraki, 305-0047 (Japan); Uemura, Toshimasa [Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), Central-4, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566 (Japan); Tanaka, Junzo [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, S7-5 Ookayama, Meguro, Tokyo 152-8550 (Japan)

    2010-10-15

    Because cartilage has limited potential for self-repair, tissue engineering is expected to replace the present therapies for damaged cartilage, such as total knee arthroplasty. However, scaffolds suitable for cartilage tissue engineering have not been established. We synthesized a novel porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite (pCol-HAp/ChS), containing materials which resemble extracellular matrices in bone and cartilage tissues, which needs high compressive strength for clinical use. HAp/ChS had smaller crystals and a larger total surface area than HAp. SEM images showed pCol-HAp/ChS to have the roughest surface compared with pCol and pCol-HAp. The mechanical properties suggest that pCol-HAp/ChS and pCol/HAp are similar, and superior to pCol. Seeding experiments showed a uniform distribution of mesenchymal stem cells (MSCs) in pCol-HAp/ChS and pCol/HAp. Safranin O, Toluidine blue and Alcian blue staining after 2 weeks of culture revealed pCol-HAp/ChS to be the most chondrogenic in each case. In addition, MSCs in pCol-HAp/ChS produced more glycosaminoglycans, a cartilage matrix, than those in pCol-HAp. Further, pCol-HAp/ChS regenerated 15 times more cartilaginous tissue than pCol. From these results, pCol-HAp/ChS is expected to be a candidate for a scaffold for cartilage tissue engineering in place of collagen sponge.

  9. Effects of osteochondral defect size on cartilage regeneration using a double-network hydrogel.

    Science.gov (United States)

    Higa, Kotaro; Kitamura, Nobuto; Goto, Keiko; Kurokawa, Takayuki; Gong, Jian Ping; Kanaya, Fuminori; Yasuda, Kazunori

    2017-05-22

    There has been increased interest in one-step cell-free procedures to avoid the problems related to cell manipulation and its inherent disadvantages. We have studied the chondrogenic induction ability of a PAMPS/PDMAAm double-network (DN) gel and found it to induce chondrogenesis in animal osteochondral defect models. The purpose of this study was to investigate whether the healing process and the degree of cartilage regeneration induced by the cell-free method using DN gel are influenced by the size of osteochondral defects. A total of 63 mature female Japanese white rabbits were used in this study, randomly divided into 3 groups of 21 rabbits each. A 2.5-mm diameter osteochondral defect was created in the femoral trochlea of the patellofemoral joint of bilateral knees in Group I, a 4.3-mm osteochondral defect in Group II, and a 5.8-mm osteochondral defect in Group III. In the right knee of each animal, a DN gel plug was implanted so that a vacant space of 2-mm depth was left above the plug. In the left knee, we did not conduct any treatment to obtain control data. Animals were sacrificed at 2, 4, and 12 weeks after surgery, and gross and histological evaluations were made. The present study demonstrated that all sizes of the DN gel implanted defects as well as the 2.5mm untreated defects showed cartilage regeneration at 4 and 12 weeks. The 4.3-mm and 5.8-mm untreated defects did not show cartilage regeneration during the 12-week period. The quantitative score reported by O'Driscoll et al. was significantly higher in the 4.3-mm and 5.8-mm DN gel-implanted defects than the untreated defects at 4 and 12 weeks (p regeneration in defects between 2.5 and 5.8 mm, offering a promising device to establish a cell-free cartilage regeneration therapy and applicable to various sizes of osteochondral defects.

  10. Hyaline cartilage regeneration by combined therapy of microfracture and long-term bone morphogenetic protein-2 delivery.

    Science.gov (United States)

    Yang, Hee Seok; La, Wan-Geun; Bhang, Suk Ho; Kim, Hak-Jun; Im, Gun-Il; Lee, Haeshin; Park, Jung-Ho; Kim, Byung-Soo

    2011-07-01

    Microfracture of cartilage induces migration of bone-marrow-derived mesenchymal stem cells. However, this treatment often results in fibrocartilage regeneration. Growth factors such as bone morphogenetic protein (BMP)-2 induce the differentiation of bone-marrow-derived mesenchymal stem cells into chondrocytes, which can be used for hyaline cartilage regeneration. Here, we tested the hypothesis that long-term delivery of BMP-2 to cartilage defects subjected to microfracture results in regeneration of high-quality hyaline-like cartilage, as opposed to short-term delivery of BMP-2 or no BMP-2 delivery. Heparin-conjugated fibrin (HCF) and normal fibrin were used as carriers for the long- and short-term delivery of BMP-2, respectively. Rabbit articular cartilage defects were treated with microfracture combined with one of the following: no treatment, fibrin, short-term delivery of BMP-2, HCF, or long-term delivery of BMP-2. Eight weeks after treatment, histological analysis revealed that the long-term delivery of BMP-2 group (microfracture + HCF + BMP-2) showed the most staining with alcian blue. A biochemical assay, real-time polymerase chain reaction assay and Western blot analysis all revealed that the long-term delivery of BMP-2 group had the highest glucosaminoglycan content as well as the highest expression level of collagen type II. Taken together, the long-term delivery of BMP-2 to cartilage defects subjected to microfracture resulted in regeneration of hyaline-like cartilage, as opposed to short-term delivery or no BMP-2 delivery. Therefore, this method could be more convenient for hyaline cartilage regeneration than autologous chondrocyte implantation due to its less invasive nature and lack of cell implantation.

  11. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Xiaowei Zhang

    Full Text Available Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9 is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP (scSOX9 to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

  12. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Xiaowei; Wu, Shili; Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Chu, Cong-Qiu; Zhu, Yong

    2017-01-01

    Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP) (scSOX9) to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

  13. Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts.

    Science.gov (United States)

    Lee, K H; Song, S U; Hwang, T S; Yi, Y; Oh, I S; Lee, J Y; Choi, K B; Choi, M S; Kim, S J

    2001-09-20

    Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

  14. Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis

    Directory of Open Access Journals (Sweden)

    Sello Lebohang Manoto

    2018-05-01

    Full Text Available Osteoarthritis (OA is the most common degenerative joint disease and a growing health problem affecting more than half of the population over the age of 65. It is characterized by inflammation in the cartilage and synovium, resulting in the loss of joint structure and progressive damage to the cartilage. Many pro-inflammatory mediators are elevated in OA, including reactive oxygen species (ROS such as nitric oxide (NO and hydrogen peroxide (H2O2. Damaged articular cartilage remains a challenge to treat due to the limited self-healing capacity of the tissue and unsuccessful biological interventions. This highlights the need for better therapeutic strategies to heal damaged articular cartilage. Ozone (O3 therapy has been shown to have positive results in the treatment of OA; however the use of O3 therapy as a therapeutic agent is controversial. There is a perception that O3 is always toxic, whereas evidence indicates that when it is applied following a specified method, O3 can be effective in the treatment of degenerative diseases. The mechanism of action of O3 therapy in OA is not fully understood and this review summarizes the use of O3 therapy in the treatment of damaged articular cartilage in OA. Keywords: Osteoarthritis (OA, Articular cartilage, Ozone (O3 therapy, Reactive oxygen species (ROS

  15. Laser-induced activation of regeneration processes in spine disc cartilage

    Science.gov (United States)

    Sobol, Emil N.; Vorobjeva, Natalia N.; Sviridov, Alexander P.; Omelchenko, Alexander I.; Baskov, Andrey V.; Shekhter, Anatoliy B.; Baskov, Vladimir A.; Feldchtein, Felix I.; Kamensky, Vladislav A.; Kuranov, Roman V.

    2000-05-01

    The effect of laser radiation on the regeneration processes in spine disk cartilage has been studied in-vivo. We used rabbits as a model and a Holmium (2.09 micrometer) and an Erbium fiber (1.56 micrometer) lasers for irradiation the discs which were preliminary opened to remove annulus fibrosus and the nucleus pulposus of the intervertebral disc. The irradiated zone has been examined using an optical coherent tomography in one month after the operation and conventional histological technique in two months after the laser operation. It has been shown that laser radiation promotes the growth of the new cartilaginous tissue of fibrous and hyaline types.

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

    Science.gov (United States)

    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

    2016-01-01

    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 printing is already used in the orthopedic clinic, the shift toward 3D bioprinting has not yet occurred. We believe that this shift will provide an important step forward in the field of cartilage regeneration. Three-dimensional bioprinting techniques allow incorporation of cells and biological cues during the manufacturing process, to generate biologically active implants. The outer shape of the construct can be personalized based on clinical images of the patient’s defect. Additionally, by printing with multiple bio-inks, osteochondral or zonally organized constructs can be generated. Relevant mechanical properties can be obtained by hybrid printing with thermoplastic polymers and hydrogels, as well as by the incorporation of electrospun meshes in hydrogels. Finally, bioprinting techniques contribute to the automation of the implant production process, reducing the infection risk. To prompt the shift from nonliving implants toward living 3D bioprinted cartilage constructs in the clinic, some challenges need to be addressed. The bio-inks and required cartilage construct architecture need to be further optimized. The bio-ink and printing process need to meet the sterility requirements for implantation. Finally, standards are essential to ensure a reproducible quality of the 3D printed constructs. Once these challenges are addressed, 3D bioprinted living articular cartilage implants may find their way into daily clinical practice. PMID:28934880

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

    Science.gov (United States)

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

    2015-12-01

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

  18. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Manuel Mata

    2017-01-01

    Full Text Available Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI. The effectiveness of ACI has been shown in vitro and in vivo, but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs to regenerate cartilage in vitro and in vivo. hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

  19. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study.

    Science.gov (United States)

    Mata, Manuel; Milian, Lara; Oliver, Maria; Zurriaga, Javier; Sancho-Tello, Maria; de Llano, Jose Javier Martin; Carda, Carmen

    2017-01-01

    Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI). The effectiveness of ACI has been shown in vitro and in vivo , but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs) to regenerate cartilage in vitro and in vivo . hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

  20. Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates.

    Science.gov (United States)

    Kondo, Shimpei; Muneta, Takeshi; Nakagawa, Yusuke; Koga, Hideyuki; Watanabe, Toshifumi; Tsuji, Kunikazu; Sotome, Shinichi; Okawa, Atsushi; Kiuchi, Shinji; Ono, Hideo; Mizuno, Mitsuru; Sekiya, Ichiro

    2017-06-01

    Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. Solid freeform-fabricated scaffolds designed to carry multicellular mesenchymal stem cell spheroids for cartilage regeneration

    Directory of Open Access Journals (Sweden)

    G-S Huang

    2013-10-01

    Full Text Available Three-dimensional (3D cellular spheroids have recently emerged as a new trend to replace suspended single cells in modern cell-based therapies because of their greater regeneration capacities in vitro. They may lose the 3D structure during a change of microenvironment, which poses challenges to their translation in vivo. Besides, the conventional microporous scaffolds may have difficulty in accommodating these relatively large spheroids. Here we revealed a novel design of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC spheroids were made by solid freeform fabrication (SFF from the solution of poly(D,L-lactide-co-glycolide. Their internal surface was modified with chitosan following air plasma treatment in order to preserve the morphology of the spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds produced a significantly larger amount of cartilage-associated extracellular matrix in vitro and in NOD/SCID mice compared to single cells in the same scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral defects of rabbit knees showed superior cartilage regeneration. This study establishes new perspectives in designing the spheroid-sustaining microenvironment within a tissue engineering scaffold for in vivo applications.

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

    Science.gov (United States)

    Mohanraj, Bhavana

    chondrogenesis, demonstrating the potential of MAMCs to actively deliver therapeutics within demanding mechanical environments. Taken together, this work advances our capacity to identify and deliver new compounds of clinical relevance to modulate disease progression following traumatic injury using state-of-the-art micro-engineered screening tools and a novel mechanically-activated delivery system. These platforms advance strategies for cartilage repair and regeneration in PTOA and provide new options for the treatment of this debilitating condition.

  3. 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.

  4. Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration.

    Science.gov (United States)

    Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider; Akiyama, Kentaro; Snead, Malcolm L; Shi, Songtao

    2013-12-01

    Dental-derived mesenchymal stem cells (MSCs) are promising candidates for cartilage regeneration, with a high capacity for chondrogenic differentiation. This property helps make dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs and GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSCs) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by Toluidine Blue and Safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (palginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs. Copyright © 2013 Acta Materialia Inc. All rights reserved.

  5. Regeneration of hyaline cartilage promoted by xenogeneic mesenchymal stromal cells embedded within elastin-like recombinamer-based bioactive hydrogels.

    Science.gov (United States)

    Pescador, David; Ibáñez-Fonseca, Arturo; Sánchez-Guijo, Fermín; Briñón, Jesús G; Arias, Francisco Javier; Muntión, Sandra; Hernández, Cristina; Girotti, Alessandra; Alonso, Matilde; Del Cañizo, María Consuelo; Rodríguez-Cabello, José Carlos; Blanco, Juan Francisco

    2017-08-01

    Over the last decades, novel therapeutic tools for osteochondral regeneration have arisen from the combination of mesenchymal stromal cells (MSCs) and highly specialized smart biomaterials, such as hydrogel-forming elastin-like recombinamers (ELRs), which could serve as cell-carriers. Herein, we evaluate the delivery of xenogeneic human MSCs (hMSCs) within an injectable ELR-based hydrogel carrier for osteochondral regeneration in rabbits. First, a critical-size osteochondral defect was created in the femora of the animals and subsequently filled with the ELR-based hydrogel alone or with embedded hMSCs. Regeneration outcomes were evaluated after three months by gross assessment, magnetic resonance imaging and computed tomography, showing complete filling of the defect and the de novo formation of hyaline-like cartilage and subchondral bone in the hMSC-treated knees. Furthermore, histological sectioning and staining of every sample confirmed regeneration of the full cartilage thickness and early subchondral bone repair, which was more similar to the native cartilage in the case of the cell-loaded ELR-based hydrogel. Overall histological differences between the two groups were assessed semi-quantitatively using the Wakitani scale and found to be statistically significant (p hyaline cartilage in osteochondral lesions.

  6. Cartilage.

    Science.gov (United States)

    Caplan, Arnold I.

    1984-01-01

    Cartilage is a fundamental biological material that helps to shape the body and then helps to support it. Its fundamental properties of strength and resilience are explained in terms of the tissue's molecular structure. (JN)

  7. Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for Cartilage and Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Sajjad Ashraf

    2017-04-01

    Full Text Available Advances in mesenchymal stem cells (MSCs and cell replacement therapies are promising approaches to treat cartilage and bone defects since substantial differentiation capacities of MSCs match the demands of tissue regeneration. Our understanding of the dynamic process requiring indispensable differentiation of MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched in brain regulating gene signature for differentiation of human adipose derived mesenchymal stem cells (ASCs into chondrogenic, osteogenic, and adipogenic lineages. RHEB-overexpression increases the proliferation of the ASCs. RHEB enhances the chondrogenic differentiation of ASCs in 3D culture via upregulation of SOX9 with concomitant increase in glycosaminoglycans (GAGs, and type II collagen (COL2. RHEB increases the osteogenesis via upregulation of runt related transcription factor 2 (RUNX2 with an increase in the calcium and phosphate contents. RHEB also increases the expression of osteogenic markers, osteonectin and osteopontin. RHEB knockdown ASCs were incapable of expressing sufficient SRY (Sex determining region Y-box 9 (SOX9 and RUNX2, and therefore had decreased chondrogenic and osteogenic differentiation. RHEB-overexpression impaired ASCs differentiation into adipogenic lineage, through downregulation of CCAAT/enhancer binding protein beta (C/EBPβ. Conversely, RHEB knockdown abolished the negative regulation of adipogenesis. We demonstrate that RHEB is a novel regulator, with a critical role in ASCs lineage determination, and RHEB-modulated ASCs may be useful as a cell therapy for cartilage and bone defect treatments.

  8. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    Directory of Open Access Journals (Sweden)

    Michiel W. Pot

    2017-10-01

    Full Text Available Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies. Cartilage regeneration was expressed on an absolute 0–100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

  9. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

    Science.gov (United States)

    Pot, Michiel W; van Kuppevelt, Toin H; Gonzales, Veronica K; Buma, Pieter; IntHout, Joanna; de Vries, Rob B M; Daamen, Willeke F

    2017-01-01

    Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP) were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies). Cartilage regeneration was expressed on an absolute 0-100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

  10. Iodine removal adsorbent histories, aging and regeneration

    International Nuclear Information System (INIS)

    Hunt, J.R.; Rankovic, L.; Lubbers, R.; Kovach, J.L.

    1976-01-01

    The experience of efficiency changes with life under various test conditions is described. The adsorbents were periodically removed from both standby and continuously operating systems and tested under various test methods for residual iodine adsorption efficiency. Adsorbent from several conventional ''sampler'' cartridges versus the bulk adsorbent was also tested showing deficiency in the use of cartridge type sampling. Currently required test conditions were found inadequate to follow the aging of the adsorbent because pre-equilibration of the sample acts as a regenerant and the sample is not tested in the ''as is'' condition. The most stringent test was found to be the ambient temperature, high humidity test to follow the aging of the adsorbent. Several methods were evaluated to regenerate used adsorbents; of these high temperature steaming and partial reimpregnation were found to produce adsorbents with near identical properties of freshly prepared adsorbents

  11. THE FUNCTIONAL EFFECTIVENESS OF A CELL-ENGINEERED CONSTRUCT FOR THE REGENERATION OF ARTICULAR CARTILAGE

    Directory of Open Access Journals (Sweden)

    V. I. Sevastianov

    2015-01-01

    Full Text Available The aim of this study is an analysis of the functional effectiveness of a biomedical cell product consisting of a biopolymer microheterogeneous collagen-containing hydrogel (BMCH, human adipose-derived mesenchymal stromal cells (hADMSCs, and chondrogenic induction medium in the regeneration of articular cartilage. Materials and methods. The test model of the adjuvant arthritis was used (female Soviet Chinchilla rabbits with the further development into osteoarthrosis (OA combined with the clinical, biochemical, radiological, and histochemical trials. Results. On Day 92 of the OA model it has been found that the intra-articular introduction of a BMCH with hADMSCs into the left knee joint (n = 3 30 days after the OA modeling, as opposed to the right joint (negative control, n = 3, stimulates the regenerative processes of the cartilaginous tissue structure characterized by the formation of chondrocyte «columns», the emergence of isogenic groups in the intracellular matrix and the regeneration of its structure. Upon the intra-articular introduction of a BMCH (n = 3 such effects are markedly less pronounced. Conclusions. A significant regenerative potential of a cell-engineered construct of human articular tissue (CEC ATh has been proven. It is possible to presume that biostimulating properties of CEC ATh are due to the activating effect of a biomedical cell product on the stem cell migration processes from the surrounding tissue into the injured area with their subsequent differentiation. 

  12. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration.

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    Qian-Shi Zhang

    Full Text Available Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1, also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5, after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1, the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93, or the downstream target, c-Jun N-terminal kinase (SP600125 also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580 had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

  13. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration

    Science.gov (United States)

    Zhang, Qian-Shi; Kurpad, Deepa S.; Mahoney, My G.; Steinbeck, Marla J.

    2017-01-01

    Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase (SP600125) also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580) had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration. PMID:29045420

  14. Aging histological changes in the cartilages of the cricoarytenoid joint

    Directory of Open Access Journals (Sweden)

    Dedivitis Rogério Aparecido

    2004-01-01

    Full Text Available PURPOSE: Analysis of ossification, bone marrow formation, perichondrium thickness, muscle fibers, collagen fibers and elastic fibers quantities of cricoid and arytenoid cartilages. Design: Correlation morphologic study. METHODS: Twenty-four cricoarytenoid joints were obtained from Caucasian male fresh cadavers divided into three groups with eight specimens in each: group I - adolescents, from 15 to 20; group II - adults, from 25 to 35; and group III - elderly, from 60 to 75. The specimens were stained with H-E; trichrome; Picrosirius; and elastic stain. Histometry was performed for quantitative analysis. Bonferroni Test, Fisher Test and the Variance Analysis were used. RESULTS: At the microscopic analysis, the group I specimens presented typical hyaline cartilage, thin perichondrium, bulky muscle fibers and were surrounded by collagen fibers. In group II, there were ossification in small well defined central areas of four specimens, with lamellar bone tissue. In two of these cases there were central bone cavity full of fat tissue. The other parameters were similar to group I. In group III, most part of hyaline cartilage was replaced by typical lamellar bone tissue with poorly outlined haversian systems. Hematopoietic tissue was noted in six cases and fat tissue in the other two. Perichondrium was thicker. Small muscle fibers were smaller and surrounded by collagen in great quantity. Elastic fibers were present in small quantity in the outer portion of perichondrium in all the groups. CONCLUSIONS: In spite of its lack in adolescence, ossification occurs in cricoid and arytenoid cartilages during adulthood and intensifies with age; bone marrow is formed in ossification tissue with hematopoietic tissue in group III; perichondrium becomes thicker in group III; muscle tissue atrophies in group III and is replaced by collagen fibers; these fibers thicken with age; and elastic fibers is always present in the perichondrium in low quantity.

  15. Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls.

    Science.gov (United States)

    Marchand, Catherine; Chen, Gaoping; Tran-Khanh, Nicolas; Sun, Jun; Chen, Hongmei; Buschmann, Michael D; Hoemann, Caroline D

    2012-03-01

    This study analyzed the long-term cartilage and subchondral bone repair of microdrilled defects treated with chitosan glycerol-phosphate/blood implant, using thrombin (Factor IIa) to accelerate in situ solidification. We also evaluated the cartilage repair response to six smaller microdrill holes compared with two larger holes. Bilateral knee trochlear cartilage defects were created in n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal 0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were analyzed by histological scoring and histomorphometry for hyaline matrix characteristics and osseous integration. Subchondral repair bone was analyzed by 3D microcomputed tomography and compared to acute defects (n=6) and intact trochlea (n=8). Implant-treated cartilage repair tissues had higher structural integrity through the entire defect (p=0.02), twofold higher percent staining for glycosaminoglycan (p=0.0004), and ~24% more collagen type II staining over the smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter had no specific effect on cartilage repair. The subchondral bone plate was partially restored in treated and control defects but less dense than intact trochlea, with evidence of incomplete regeneration of the calcified cartilage layer. More residual drill holes (p=0.054) were detected in control versus treated defects, and control defects with more than 40% residual holes presented abnormally thicker trabeculae compared with treated defects. Low osteoclast numbers after 6.5 months repair suggested that bone was no longer remodeling. The subchondral bone plate surrounding the defects exhibited a significant thickening compared with age-matched intact trochlea. These data suggest that debridement and drilling can lead to long-term subchondral bone changes outside the cartilage defect. Compared with drilled

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

    Science.gov (United States)

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

    2015-12-11

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

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

    Directory of Open Access Journals (Sweden)

    Riccardo A. A. Muzzarelli

    2015-12-01

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

  18. 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

  19. Optical methods for diagnostics and feedback control in laser-induced regeneration of spine disc and joint cartilages

    Science.gov (United States)

    Sobol, Emil; Sviridov, Alexander; Omeltchenko, Alexander; Baum, Olga; Baskov, Andrey; Borchshenko, Igor; Golubev, Vladimir; Baskov, Vladimir

    2011-03-01

    In 1999 we have introduced a new approach for treatment of spine diseases based on the mechanical effect of nondestructive laser radiation on the nucleus pulposus of the intervertebral disc. Laser reconstruction of spine discs (LRD) involves puncture of the disc and non-destructive laser irradiation of the nucleus pulposus to activate reparative processes in the disc tissues. In vivo animal study has shown that LRD allows activate the growth of hyaline type cartilage in laser affected zone. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reparation in cartilages of spine and joints. The results of laser reconstruction of intervertebral discs for 510 patients have shown substantial relief of back pain for 90% of patients. Laser technology has been experimentally tested for reparation of traumatic and degenerative diseases in joint cartilage of 20 minipigs. It is shown that laser regeneration of cartilage allows feeling large (more than 5 mm) defects which usually never repair on one's own. Optical techniques have been used to promote safety and efficacy of the laser procedures.

  20. Induction of spontaneous hyaline cartilage regeneration using a double-network gel: efficacy of a novel therapeutic strategy for an articular cartilage defect.

    Science.gov (United States)

    Kitamura, Nobuto; Yasuda, Kazunori; Ogawa, Munehiro; Arakaki, Kazunobu; Kai, Shuken; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian Ping

    2011-06-01

    A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Controlled laboratory study. A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O'Driscoll et al. The DN gel-implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel-implanted defects compared with the untreated control at each period (P cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel-implanted and normal knees. This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.

  1. 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

  2. Intra-articular injection of synovium-derived mesenchymal stem cells and hyaluronic acid promote regeneration of massive cartilage defects in rabbits

    Directory of Open Access Journals (Sweden)

    Vyacheslav Ogay

    2014-01-01

    Full Text Available Introduction: The purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs with low molecular weight hyaluronic acid (HA could promote regeneration of massive cartilage in rabbits. Material and methods: The SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek. The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml were suspended in 0.5% low molecular weight HA (0.15 ml and injected into the left knee, and HA solution (0.30 ml alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days. Results: On day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC- treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage. Conclusion: Thus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits.

  3. Effect of gradual weight-bearing on regenerated articular cartilage after joint distraction and motion in a rabbit model.

    Science.gov (United States)

    Nishino, Tomofumi; Ishii, Tomoo; Chang, Fei; Yanai, Takaji; Watanabe, Arata; Ogawa, Takeshi; Mishima, Hajime; Nakai, Kenjiro; Ochiai, Naoyuki

    2010-05-01

    The purpose of this study was to clarify the effect of gradual weight bearing (GWB) on regenerating cartilage. We developed a novel external fixation device (EFD) with a controllable weight-bearing system and continuous passive motion (CPM). A full-thickness defect was created by resection of the entire articular surface of the tibial plateau after the EFD was fixed in the rabbit's left knee. In the GWB group (n=6), GWB was started 6 weeks after surgery. In the CPM group (n=6), CPM with EFD was applied in the same manner without GWB. The control group (n=5) received only joint distraction. All rabbits were sacrificed 9 weeks after surgery. The central one-third of the regenerated tissue was assessed and scored blindly using a grading scale modified from the International Cartilage Repair Society visual histological assessment scale. The areas stained by Safranin-O and type II collagen antibody were measured, and the percentage of each area was calculated. There was no significant difference in the histological assessment scale among the groups. The percentage of the type II collagen-positive area was significantly larger in the GWB group than in the CPM group. The present study suggests that optimal mechanical stress, such as GWB, may affect regeneration of cartilage, in vivo. Copyright (c) 2009 Orthopaedic Research Society.

  4. The bio in the ink : cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells

    NARCIS (Netherlands)

    Levato, Riccardo; Webb, William R; Otto, Iris A; Mensinga, Anneloes; Zhang, Yadan; van Rijen, Mattie; van Weeren, P. René; Khan, Ilyas M.; Malda, Jos

    2017-01-01

    Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of

  5. Elastin-like protein-hyaluronic acid (ELP-HA) hydrogels with decoupled mechanical and biochemical cues for cartilage regeneration.

    Science.gov (United States)

    Zhu, Danqing; Wang, Huiyuan; Trinh, Pavin; Heilshorn, Sarah C; Yang, Fan

    2017-05-01

    Hyaluronic acid (HA) is a major component of cartilage extracellular matrix and is an attractive material for use as 3D injectable matrices for cartilage regeneration. While previous studies have shown the promise of HA-based hydrogels to support cell-based cartilage formation, varying HA concentration generally led to simultaneous changes in both biochemical cues and stiffness. How cells respond to the change of biochemical content of HA remains largely unknown. Here we report an adaptable elastin-like protein-hyaluronic acid (ELP-HA) hydrogel platform using dynamic covalent chemistry, which allows variation of HA concentration without affecting matrix stiffness. ELP-HA hydrogels were created through dynamic hydrazone bonds via the reaction between hydrazine-modified ELP (ELP-HYD) and aldehyde-modified HA (HA-ALD). By tuning the stoichiometric ratio of aldehyde groups to hydrazine groups while maintaining ELP-HYD concentration constant, hydrogels with variable HA concentration (1.5%, 3%, or 5%) (w/v) were fabricated with comparable stiffness. To evaluate the effects of HA concentration on cell-based cartilage regeneration, chondrocytes were encapsulated within ELP-HA hydrogels with varying HA concentration. Increasing HA concentration led to a dose-dependent increase in cartilage-marker gene expression and enhanced sGAG deposition while minimizing undesirable fibrocartilage phenotype. The use of adaptable protein hydrogels formed via dynamic covalent chemistry may be broadly applicable as 3D scaffolds with decoupled niche properties to guide other desirable cell fates and tissue repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Positive effects of cell-free porous PLGA implants and early loading exercise on hyaline cartilage regeneration in rabbits.

    Science.gov (United States)

    Chang, Nai-Jen; Lin, Chih-Chan; Shie, Ming-You; Yeh, Ming-Long; Li, Chien-Feng; Liang, Peir-In; Lee, Kuan-Wei; Shen, Pei-Hsun; Chu, Chih-Jou

    2015-12-01

    The regeneration of hyaline cartilage remains clinically challenging. Here, we evaluated the therapeutic effects of using cell-free porous poly(lactic-co-glycolic acid) (PLGA) graft implants (PGIs) along with early loading exercise to repair a full-thickness osteochondral defect. Rabbits were randomly allocated to a treadmill exercise (TRE) group or a sedentary (SED) group and were prepared as either a PGI model or an empty defect (ED) model. TRE was performed as a short-term loading exercise; SED was physical inactivity in a free cage. The knees were evaluated at 6 and 12 weeks after surgery. At the end of testing, none of the knees developed synovitis, formed osteophytes, or became infected. Macroscopically, the PGI-TRE group regenerated a smooth articular surface, with transparent new hyaline-like tissue soundly integrated with the neighboring cartilage, but the other groups remained distinct at the margins with fibrous or opaque tissues. In a micro-CT analysis, the synthesized bone volume/tissue volume (BV/TV) was significantly higher in the PGI-TRE group, which also had integrating architecture in the regeneration site. The thickness of the trabecular (subchondral) bone was improved in all groups from 6 to 12 weeks. Histologically, remarkable differences in the cartilage regeneration were visible. At week 6, compared with SED groups, the TRE groups manifested modest inflammatory cells with pro-inflammatory cytokines (i.e., TNF-α and IL-6), improved collagen alignment and higher glycosaminoglycan (GAG) content, particularly in the PGI-TRE group. At week 12, the PGI-TRE group had the best regeneration outcomes, showing the formation of hyaline-like cartilage, the development of columnar rounded chondrocytes that expressed enriched levels of collagen type II and GAG, and functionalized trabecular bone with osteocytes. In summary, the combination of implanting cell-free PLGA and performing an early loading exercise can significantly promote the full

  7. The Age-Related Changes in Cartilage and Osteoarthritis

    Directory of Open Access Journals (Sweden)

    YongPing Li

    2013-01-01

    Full Text Available Osteoarthritis (OA is closely associated with aging, but its underlying mechanism is unclear. Recent publications were reviewed to elucidate the connection between aging and OA. With increasing OA incidence, more senior people are facing heavy financial and social burdens. Age-related OA pathogenesis is not well understood. Recently, it has been realized that age-related changes in other tissues besides articular cartilage may also contribute to OA development. Many factors including senescence-related secretory phenotypes, chondrocytes’ low reactivity to growth factors, mitochondrial dysfunction and oxidative stress, and abnormal accumulation of advanced glycation end products (AGEs may all play key roles in the pathogenesis of age-related OA. Lately, epigenetic regulation of gene expression was recognized for its impact on age-related OA pathogenesis. Up to now, few studies have been reported about the role of miRNA and long-noncoding RNA (lncRNA in age-related OA. Research focusing on this area may provide valuable insights into OA pathogenesis. OA-induced financial and social burdens have become an increasingly severe threat to older population. Age-related changes in noncartilage tissue should be incorporated in the understanding of OA development. Growing attention on oxidative stress and epigenetics will provide more important clues for the better understanding of the age-related OA.

  8. 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.

  9. Histological comparison of patellar cartilage degeneration between chondromalacia in youth and osteoarthritis in aging.

    Science.gov (United States)

    Mori, Y; Kubo, M; Okumo, H; Kuroki, Y

    1995-01-01

    The histological findings of the patellar cartilage were compared between cases of chondromalacia, which occurs predominantly in young persons (22 patients, average age 19.8 years) and cases of osteoarthritis, which is common among the elderly (21 patients, average age 65.4 years). The histological findings of cartilage in the chondromalacia were characterized by increased density and vigorous fibrous metaplasia of chondrocytes. These findings may be considered to represent a reactive change in the chondrocyte. Cartilage degeneration in osteoarthritis, by contrast, is regressive and presents a clearly different histological picture from that of chondromalacia patellae. We conclude that chondromalacia does not easily lead to osteoarthritis. On the other hand, the cartilage was characteristically softened, as observed by gross inspection, and showed rarefaction of the cartilage matrix. It should be noted that the change was not observed in aging, but showed a pattern of cartilage degeneration peculiar to young patients with chondromalacia patellae.

  10. Injectable glycosaminoglycan-protein nano-complex in semi-interpenetrating networks: A biphasic hydrogel for hyaline cartilage regeneration.

    Science.gov (United States)

    Radhakrishnan, Janani; Subramanian, Anuradha; Sethuraman, Swaminathan

    2017-11-01

    Articular hyaline cartilage regeneration remains challenging due to its less intrinsic reparability. The study develops injectable biphasic semi-interpenetrating polymer networks (SIPN) hydrogel impregnated with chondroitin sulfate (ChS) nanoparticles for functional cartilage restoration. ChS loaded zein nanoparticles (∼150nm) prepared by polyelectrolyte-protein complexation were interspersed into injectable SIPNs developed by blending alginate with poly(vinyl alcohol) and calcium crosslinking. The hydrogel exhibited interconnected porous microstructure (39.9±5.8μm pore diameter, 57.7±5.9% porosity), 92% swellability and >350Pa elastic modulus. Primary chondrocytes compatibility, chondrocyte-matrix interaction with cell-cell clustering and spheroidal morphology was demonstrated in ChS loaded hydrogel and long-term (42days) proliferation was also determined. Higher fold expression of cartilage-specific genes sox9, aggrecan and collagen-II was observed in ChS loaded hydrogel while exhibiting poor expression of collagen-I. Immunoblotting of aggregan and collagen II demonstrate favorable positive influence of ChS on chondrocytes. Thus, the injectable biphasic SIPNs could be promising composition-mimetic substitute for cartilage restoration at irregular defects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Mechanical properties of the normal human cartilage-bone complex in relation to age

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Linde, F

    1998-01-01

    OBJECTIVE: This study investigates the age-related variations in the mechanical properties of the normal human tibial cartilage-bone complex and the relationships between cartilage and bone. DESIGN: A novel technique was applied to assess the mechanical properties of the cartilage and bone by mea...... that are of importance for the understanding of the etiology and pathogenesis of degenerative joint diseases, such as arthrosis....

  12. [Regeneration of autologous tissue-engineered cartilage by using basic-fibroblast growth factor in vitro culture].

    Science.gov (United States)

    Ding, Xiao-bang; Cheng, Ning-xin; Chen, Bing; Xia, Wan-yao; Cui, Lei; Liu, Wei; Cao, Yi-lin

    2004-05-01

    To investigate the effect of the basic fibroblast growth factor (b-FGF) to regenerate an autologous tissue-engineered cartilage in vitro. The Cells were harvested from the elastic auricular cartilage of swine,and were plated at the concentration of 1 x 10(4) cells/cm2 , studied in vitro at two different media enviroments: Group I contained Ham's F-12 with supplements and b-FGF, Group II contained Ham's F-12 only with supplements. The passage 2 cells (after 12.75 +/- 1.26 days) were harvested and mixed with 30% pluronic F-127/Ham's F-12 at the concentration of 50 x 10(6) cells/ml. It was injected subcutaneously at 0.5 ml per implant. The implants were harvested 8 weeks after the vivo culture and examined with the histological stains. The chondrocytes displayed morphologically similar to the fibroblasts in the media containing basic-FGF. The number of cell doublings (after 12.75 +/- 1.26 days) in vitro culture was as the following: Group I, 70; Group II, 5.4. Eight 8 weeks after the vivo autologous implantation, the average weight (g) and volume (cm3) in each group was as the following: Group I, 0.371 g/0.370 cm3 Group II, 0.179 g/0.173 cm3 (P < 0.01). With the b-FGF in vitro culture, the cells were expanded by 70 times after 2 weeks. Histologically, all of the engineered cartilage in the two groups were similar to the native elastic cartilage. These results indicate that the basic-FGF could be used positively to enhance the quality and quantity of the seeding cells for the generation of the well-engineered cartilage.

  13. Research studies of aging changes of hyaline cartilage surface by using Raman-scattering spectroscopy

    Science.gov (United States)

    Timchenko, E. V.; Timchenko, P. E.; Dolgushkin, D. A.; Volova, L. T.; Lazarev, V. A.; Tyumchenkova, A. S.; Markova, M. D.

    2017-08-01

    The paper presents the results of a comparative analysis by the method of Raman spectroscopy of the joint hyaline cartilage of adults and children. Differences in the spectral characteristics of the surface of articular cartilage are shown. New optical coefficients have been introduced, which make it possible to evaluate the age-related changes in cartilaginous tissue.

  14. 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.

  15. Pronounced biomaterial dependency in cartilage regeneration using nonexpanded compared with expanded chondrocytes

    NARCIS (Netherlands)

    Tsuchida, A.I.; Bekkers, J.E.J.; Beekhuizen, M.; Vonk, L.A.; Dhert, W.J.A.; Saris, Daniël B.F.; Creemers, L.B.

    2013-01-01

    We aimed to investigate freshly isolated compared with culture-expanded chondrocytes with respect to early regenerative response, cytokine production and cartilage formation in response to four commonly used biomaterials. Materials & methods: Chondrocytes were both directly and after expansion to

  16. Delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) can be effectively applied for longitudinal cohort evaluation of articular cartilage regeneration

    NARCIS (Netherlands)

    Bekkers, J.E.J.; Lambertus, W.B.; Benink, R.J.; Tsuchida, A.I.; Vincken, K.L.; Dhert, W.J.A.; Creemers, L.B.; Saris, Daniël B.F.

    2013-01-01

    Objective Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) facilitates non-invasive evaluation of the glycosaminoglycan content in articular cartilage. The primary aim of this study was to show that the dGEMRIC technique is able to monitor cartilage repair following regenerative cartilage

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

    OpenAIRE

    Goldberg, A.; Mitchell, K.; Soans, J.; Kim, L.; Zaidi, R.

    2017-01-01

    BACKGROUND: 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 ...

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

    OpenAIRE

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

    2017-01-01

    Background 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 e...

  19. Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

    Science.gov (United States)

    Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

    2014-04-01

    Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

  20. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    Directory of Open Access Journals (Sweden)

    Michiel W. Pot

    2016-09-01

    Full Text Available Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found. For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies was assessed and outcome data were collected for meta-analysis (151 studies. Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0–100% scale. Implantation of acellular

  1. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

    Science.gov (United States)

    Pot, Michiel W; Gonzales, Veronica K; Buma, Pieter; IntHout, Joanna; van Kuppevelt, Toin H; de Vries, Rob B M; Daamen, Willeke F

    2016-01-01

    Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling) compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP) using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found). For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies) was assessed and outcome data were collected for meta-analysis (151 studies). Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0-100% scale. Implantation of acellular biomaterials significantly

  2. [Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group "Tissue Regeneration" of the German Society of Orthopaedic Surgery and Traumatology (DGOU)].

    Science.gov (United States)

    Niemeyer, P; Andereya, S; Angele, P; Ateschrang, A; Aurich, M; Baumann, M; Behrens, P; Bosch, U; Erggelet, C; Fickert, S; Fritz, J; Gebhard, H; Gelse, K; Günther, D; Hoburg, A; Kasten, P; Kolombe, T; Madry, H; Marlovits, S; Meenen, N M; Müller, P E; Nöth, U; Petersen, J P; Pietschmann, M; Richter, W; Rolauffs, B; Rhunau, K; Schewe, B; Steinert, A; Steinwachs, M R; Welsch, G H; Zinser, W; Albrecht, D

    2013-02-01

    Autologous chondrocyte transplantation/implantation (ACT/ACI) is an established and recognised procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning potential consequences of primary cartilage lesions and the suitable indication for ACI. Based on current evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than 3-4 cm2; in the case of young and active sports patients at 2.5 cm2. Advanced degenerative joint disease is the single most important contraindication. The review gives a concise overview on important scientific background, the results of clinical studies and discusses advantages and disadvantages of ACI. Georg Thieme Verlag KG Stuttgart · New York.

  3. Ageing is associated with reduction of mechanically-induced activation of Smad2/3P signaling in articular cartilage

    NARCIS (Netherlands)

    Madej, W.M.; Caam, A.P.M. van; Blaney Davidson, E.N.; Hannink, G.J.; Buma, P.; Kraan, P.M. van der

    2016-01-01

    OBJECTIVE: Mechanical signals control key cellular processes in articular cartilage. Previously we have shown that mechanical compression is an important ALK5/Smad2/3P activator in cartilage explants. However, age-related changes in the cartilage are known to affect tissue mechanosensitivity and

  4. Wound healing gene therapy: cartilage regeneration induced by vascular endothelial growth factor plasmid

    Czech Academy of Sciences Publication Activity Database

    Kološtová, K.; Taltynov, O.; Pintérová, D.; Boubelík, M.; Raška, O.; Hozák, Pavel; Jirkovská, M.; Bobek, V.

    2012-01-01

    Roč. 33, č. 1 (2012), s. 68-74 ISSN 0196-0709 Institutional research plan: CEZ:AV0Z50520514 Keywords : BALB/c mouse strain * significant angiogenesis * cartilage repair * phVEGF(165) injection Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.228, year: 2012

  5. 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.

  6. 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

  7. IL-1ß and BMPs - Interactive players of cartilage matrix degradation and regeneration

    Directory of Open Access Journals (Sweden)

    T Aigner

    2006-10-01

    Full Text Available Intact human adult articular cartilage is central for the functioning of the articulating joints. This largely depends on the integrity of its extracellular matrix, given the high loading forces during movements in particular in the weight-bearing joints. Unlike the first impression of a more or less static tissue, articular cartilage shows - albeit in the adult organism a slow - tissue turnover. Thus, one of the most important questions in osteoarthritis research is to understand the balance of catabolic and anabolic factors in articular cartilage as this is the key to understand the biology of cartilage maintenance and degeneration. Anabolic and catabolic pathways are very much intermingled in articular cartilage. The balance between anabolism and catabolism is titrated on numerous levels, starting from the mediator-synthesizing cells which express either catabolic or anabolic factors. Also, on the level of the effector cells (i.e. chondrocytes anabolic and catabolic gene expression compete for a balance of matrix homeostasis, namely the synthesis of matrix components and the expression and activation of matrix-degrading proteases. Also, there are multiple layers of intracellular cross-talks in between the anabolic and catabolic signalling pathways. Maybe the most important lesson from this overview is the notion that the anabolic-catabolic balance as such counts and not so much sufficient net anabolism or limited catabolism alone. Thus, it might be neither the aim of osteoarthritis therapy to foster anabolism nor to knock down catabolism, but the balance of anabolic-catabolic activities as a total might need proper titration and balancing.

  8. 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

  9. Comparative Analysis of Cartilage Marker Gene Expression Patterns during Axolotl and Xenopus Limb Regeneration.

    Directory of Open Access Journals (Sweden)

    Kazumasa Mitogawa

    Full Text Available Axolotls (Ambystoma mexicanum can completely regenerate lost limbs, whereas Xenopus laevis frogs cannot. During limb regeneration, a blastema is first formed at the amputation plane. It is thought that this regeneration blastema forms a limb by mechanisms similar to those of a developing embryonic limb bud. Furthermore, Xenopus laevis frogs can form a blastema after amputation; however, the blastema results in a terminal cone-shaped cartilaginous structure called a "spike." The causes of this patterning defect in Xenopus frog limb regeneration were explored. We hypothesized that differences in chondrogenesis may underlie the patterning defect. Thus, we focused on chondrogenesis. Chondrogenesis marker genes, type I and type II collagen, were compared in regenerative and nonregenerative environments. There were marked differences between axolotls and Xenopus in the expression pattern of these chondrogenesis-associated genes. The relative deficit in the chondrogenic capacity of Xenopus blastema cells may account for the absence of total limb regenerative capacity.

  10. Joint cartilage thickness and automated determination of bone age and bone health in juvenile idiopathic arthritis.

    Science.gov (United States)

    Twilt, Marinka; Pradsgaard, Dan; Spannow, Anne Helene; Horlyck, Arne; Heuck, Carsten; Herlin, Troels

    2017-08-10

    BoneXpert is an automated method to calculate bone maturation and bone health index (BHI) in children with juvenile idiopathic arthritis (JIA). Cartilage thickness can also be seen as an indicator for bone health and arthritis damage. The objective of this study was to evaluate the relation between cartilage thickness, bone maturation and bone health in patients with JIA. Patients with JIA diagnosed according ILAR criteria included in a previous ultrasonography (US) study were eligible if hand radiographs were taken at the same time as the US examination. Of the 95 patients 67 met the inclusion criteria. Decreased cartilage thickness was seen in 27% of the examined joints. Decreased BHI was seen in half of the JIA patient, and delayed bone maturation was seen in 33% of patients. A combination of decreased BHI and bone age was seen in 1 out of 5 JIA patients. Decreased cartilage thickness in the knee, wrist and MCP joint was negatively correlated with delayed bone maturation but not with bone health index. Delayed bone maturation and decreased BHI were not related to a thinner cartilage, but a thicker cartilage. No relation with JADAS 10 was found. The rheumatologist should remain aware of delayed bone maturation and BHI in JIA patients with cartilage changes, even in the biologic era.

  11. [Tissue engineering with mesenchymal stem cells for cartilage and bone regeneration].

    Science.gov (United States)

    Schaefer, D J; Klemt, C; Zhang, X H; Stark, G B

    2000-09-01

    Tissue engineering offers the possibility to fabricate living substitutes for tissues and organs by combining histogenic cells and biocompatible carrier materials. Pluripotent mesenchymal stem cells are isolated and subcultured ex vivo and then their histogenic differentiation is induced by external factors. The fabrication of bone and cartilage constructs, their combinations and gene therapeutic approaches are demonstrated. Advantages and disadvantages of these methods are described by in vitro and in vitro testing. The proof of histotypical function after implantation in vivo is essential. The use of autologous cells and tissue engineering methods offers the possibility to overcome the disadvantages of classical tissue reconstruction--donor site morbidity of autologous grafts, immunogenicity of allogenic grafts and loosening of alloplastic implants. Furthermore, tissue engineering widens the spectrum of surgical indications in bone and cartilage reconstruction.

  12. Platelet-rich plasma loaded in situ-formed hydrogel enhances hyaline cartilage regeneration by CB1 upregulation.

    Science.gov (United States)

    Lee, Hye-Rim; Park, Kyung Min; Joung, Yoon Ki; Park, Ki Dong; Do, Sun Hee

    2012-11-01

    The efficacy of three-dimensional (3D) culture on the proliferation and maturation of chondrocytes seeded into a hydrogel scaffold was assessed. Three types of hydrogel were prepared for the 3D culture of primary isolated chondrocytes. Chondrocyte proliferation was assessed using a live/dead viability/cytotoxicity assay and semiquantitative RT-PCR after 3D culture in hydrogel. Cylindrical defects in the center of rat xyphoids were used for the implantation of platelet-rich plasma (PRP)/hydrogel composites. Rats were killed at day 7 postoperatively and evaluated histochemically and immunohistologically. Xyphoid chondrocytes proliferated well with time in hydrogels. In the PRP-containing hydrogels, xyphoid defects displayed early formation of chondroid matrix with massive peripheral infiltration of spindle cells. These results were consistent with Safranin-O staining for proteoglycans and immunohistochemistry for type II collagen. Gene expression analyses in vitro revealed aggrecan, type II collagen, and ChM-1 and CB1 upregulation by PRP/hydrogel. PRP/hydrogel provided a suitable environment for hyaline cartilaginous regeneration, leading to anti-inflammation by significant increase of CB1 and inhibiting vascular ingrowth via considerable upregulation of ChM-1. The results provide a valuable reference for the clinical application of hydrogel scaffolds for hyaline cartilage regeneration, as well as the use of autologous PRP to improve cellular proliferation and maturation of xyphoid repair. Copyright © 2012 Wiley Periodicals, Inc.

  13. Age-related accumulation of Maillard reaction products in human articular cartilage collagen

    NARCIS (Netherlands)

    Verzijl, N.; Degroot, J.; Oldehinkel, E.; Bank, R. A.; Thorpe, S. R.; Baynes, J. W.; Bayliss, M. T.; Bijlsma, J. W.; Lafeber, F. P.; TeKoppele, J. M.

    2000-01-01

    Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated

  14. 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.

  15. The effect og aging and mechanical loading on the metabolism og articular cartilage

    DEFF Research Database (Denmark)

    Jørgensen, Adam El Mongy; Kjær, Michael; Heinemeier, Katja Maria

    2017-01-01

    Objective. The morphology of articular cartilage (AC) enables painless movement. Aging and mechanical loading are believed to influence development of osteoarthritis (OA), yet the connection remains unclear. Methods. This narrative review describes the current knowledge regarding this area......, with the literature search made on PubMed using appropriate keywords regarding AC, age, and mechanical loading. Results. Following skeletal maturation, chondrocyte numbers decline while increasing senescence occurs. Lower cartilage turnover causes diminished maintenance capacity, which produces accumulation...... collagen network damage and proteoglycan loss, leading to irreversible cartilage destruction because of lack of regenerative capacity. Catabolic pathways involve inflammation and the transcription factor nuclear factor-κB. Thus, age seems to be a predisposing factor for OA, with mechanical overload being...

  16. The Effect of Aging and Mechanical Loading on the Metabolism of Articular Cartilage

    DEFF Research Database (Denmark)

    Jørgensen, Adam El Mongy; Kjaer, Michael; Heinemeier, Katja Maria

    2017-01-01

    Objective. The morphology of articular cartilage (AC) enables painless movement. Aging and mechanical loading are believed to influence development of osteoarthritis (OA), yet the connection remains unclear. Methods. This narrative review describes the current knowledge regarding this area......, with the literature search made on PubMed using appropriate keywords regarding AC, age, and mechanical loading. Results. Following skeletal maturation, chondrocyte numbers decline while increasing senescence occurs. Lower cartilage turnover causes diminished maintenance capacity, which produces accumulation...... collagen network damage and proteoglycan loss, leading to irreversible cartilage destruction because of lack of regenerative capacity. Catabolic pathways involve inflammation and the transcription factor nuclear factor-κB. Thus, age seems to be a predisposing factor for OA, with mechanical overload being...

  17. Mechanical stiffness of TMJ condylar cartilage increases after artificial aging by ribose

    NARCIS (Netherlands)

    Mirahmadi, F.; Koolstra, J.H.; Lobbezoo, F.; van Lenthe, G.H.; Ghazanfari, S.; Snabel, J.; Stoop, R.; Everts, V.

    2018-01-01

    Objective: Aging is accompanied by a series of changes in mature tissues that influence their properties and functions. Collagen, as one of the main extracellular components of cartilage, becomes highly crosslinked during aging. In this study, the aim was to examine whether a correlation exists

  18. Cartilage Regeneration in the Head and Neck Area: Combination of Ear or Nasal Chondrocytes and Mesenchymal Stem Cells Improves Cartilage Production

    NARCIS (Netherlands)

    Pleumeekers, M.M.; Nimeskern, L.M.; Koevoet, W.L.M.; Karperien, Hermanus Bernardus Johannes; Stok, K.S.; van Osch, G.J.V.M.

    2015-01-01

    Background: Cartilage tissue engineering can offer promising solutions for restoring cartilage defects in the head and neck area and has the potential to overcome limitations of current treatments. However, to generate a construct of reasonable size, large numbers of chondrocytes are required, which

  19. Inexhaustible hair-cell regeneration in young and aged zebrafish

    Directory of Open Access Journals (Sweden)

    Filipe Pinto-Teixeira

    2015-07-01

    Full Text Available Animals have evolved two general strategies to counter injury and maintain physiological function. The most prevalent is protection by isolating vital organs into body cavities. However, protection is not optimal for sensory systems because their external components need to be exposed to the environment to fulfill their receptive function. Thus, a common strategy to maintain sensory abilities against persistent environmental insult involves repair and regeneration. However, whether age or frequent injuries affect the regenerative capacity of sensory organs remains unknown. We have found that neuromasts of the zebrafish lateral line regenerate mechanosensory hair cells after recurrent severe injuries and in adulthood. Moreover, neuromasts can reverse transient imbalances of Notch signaling that result in defective organ proportions during repair. Our results reveal inextinguishable hair-cell regeneration in the lateral line, and suggest that the neuromast epithelium is formed by plastic territories that are maintained by continuous intercellular communication.

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

    International Nuclear Information System (INIS)

    Piai, Juliana Francis; Alves da Silva, Marta; Martins, Albino; Torres, Ana Bela; Faria, Susana

    2017-01-01

    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_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.

  1. 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.

  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. In-situ birth of MSCs multicellular spheroids in poly(L-glutamic acid)/chitosan scaffold for hyaline-like cartilage regeneration.

    Science.gov (United States)

    Zhang, Kunxi; Yan, Shifeng; Li, Guifei; Cui, Lei; Yin, Jingbo

    2015-12-01

    The success of mesenchymal stem cells (MSCs) based articular cartilage tissue engineering is limited by the presence of fibrous tissue in generated cartilage, which is associated with the current scaffold strategy that promotes cellular adhesion and spreading. Here we design a non-fouling scaffold based on amide bonded poly(l-glutamic acid) (PLGA) and chitosan (CS) to drive adipose stem cells (ASCs) to aggregate to form multicellular spheroids with diameter of 80-110 μm in-situ. To illustrate the advantage of the present scaffolds, a cellular adhesive scaffold based on the same amide bonded PLGA and CS was created through a combination of air-drying and freeze-drying to limit the hydration effect while also achieving porous structure. Compared to ASCs spreading along the surface of pores within scaffold, the dense mass of aggregated ASCs in PLGA/CS scaffold exhibited enhanced chondrogenic differentiation capacity, as determined by up-regulated GAGs and COL II expression, and greatly decreased COL I deposition during in vitro chondrogenesis. Furthermore, after 12 weeks of implantation, neo-cartilages generated by ASCs adhered on scaffold significantly presented fibrous matrix which was characterized by high levels of COL I deposition. However, neo-cartilage at 12 weeks post-implantation generated by PLGA/CS scaffold carrying ASC spheroids possessed similar high level of GAGs and COL II and low level of COL I as that in normal cartilage. The in vitro and in vivo results indicated the present strategy could not only promote chondrogenesis of ASCs, but also facilitate hyaline-like cartilage regeneration with reduced fibrous tissue formation which may attenuate cartilage degradation in future long-term follow-up. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model.

    Science.gov (United States)

    Luo, Ziwei; Jiang, Li; Xu, Yan; Li, Haibin; Xu, Wei; Wu, Shuangchi; Wang, Yuanliang; Tang, Zhenyu; Lv, Yonggang; Yang, Li

    2015-06-01

    Damaged cartilage has poor self-healing ability and usually progresses to scar or fibrocartilaginous tissue, and finally degenerates to osteoarthritis (OA). Here we demonstrated that one of alternative isoforms of IGF-1, mechano growth factor (MGF) acted synergistically with transforming growth factor β3 (TGF-β3) embedded in silk fibroin scaffolds to induce chemotactic homing and chondrogenic differentiation of mesenchymal stem cells (MSCs). Combination of MGF and TGF-β3 significantly increased cell recruitment up to 1.8 times and 2 times higher than TGF-β3 did in vitro and in vivo. Moreover, MGF increased Collagen II and aggrecan secretion of TGF-β3 induced hMSCs chondrogenesis, but decreased Collagen I in vitro. Silk fibroin (SF) scaffolds have been widely used for tissue engineering, and we showed that methanol treated pured SF scaffolds were porous, similar to compressive module of native cartilage, slow degradation rate and excellent drug released curves. At 7 days after subcutaneous implantation, TGF-β3 and MGF functionalized silk fibroin scaffolds (STM) recruited more CD29+/CD44+cells (Pcartilage-like extracellular matrix and less fibrillar collagen were detected in STM scaffolds than that in TGF-β3 modified scaffolds (ST) at 2 months after subcutaneous implantation. When implanted into articular joints in a rabbit osteochondral defect model, STM scaffolds showed the best integration into host tissues, similar architecture and collagen organization to native hyaline cartilage, as evidenced by immunostaining of aggrecan, collagen II and collagen I, as well as Safranin O and Masson's trichrome staining, and histological evalution based on the modified O'Driscoll histological scoring system (Pcartilage regeneration. This study demonstrated that TGF-β3 and MGF functionalized silk fibroin scaffolds enhanced endogenous stem cell recruitment and facilitated in situ articular cartilage regeneration, thus providing a novel strategy for cartilage repair

  5. 3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Derek H. Rosenzweig

    2015-07-01

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

  6. 3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration.

    Science.gov (United States)

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

    2015-07-03

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

  7. Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.

    Science.gov (United States)

    Chang, N-J; Lam, C-F; Lin, C-C; Chen, W-L; Li, C-F; Lin, Y-T; Yeh, M-L

    2013-10-01

    Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery. EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation. At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-β2 and TGF-β3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th). The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  8. 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|info:eu-repo/dai/nl/10261847X; 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

  9. 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.; den Broek, Marcel P. H; Nizak, Razmara; van Rijen, Mattie H.P.; de Weger, Roel A.; Dhert, Wouter J.A.; Saris, Daniel B.F.

    2017-01-01

    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

  10. Joint cartilage thickness and automated determination of bone age and bone health in juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Twilt, Marinka; Pradsgaard, Dan; Spannow, Anne Helene

    2017-01-01

    BACKGROUND: BoneXpert is an automated method to calculate bone maturation and bone health index (BHI) in children with juvenile idiopathic arthritis (JIA). Cartilage thickness can also be seen as an indicator for bone health and arthritis damage. The objective of this study was to evaluate...... the relation between cartilage thickness, bone maturation and bone health in patients with JIA. METHODS: Patients with JIA diagnosed according ILAR criteria included in a previous ultrasonography (US) study were eligible if hand radiographs were taken at the same time as the US examination. Of the 95 patients...... 67 met the inclusion criteria. RESULTS: Decreased cartilage thickness was seen in 27% of the examined joints. Decreased BHI was seen in half of the JIA patient, and delayed bone maturation was seen in 33% of patients. A combination of decreased BHI and bone age was seen in 1 out of 5 JIA patients...

  11. Biodegradable and injectable cure-on-demand polyurethane scaffolds for regeneration of articular cartilage.

    Science.gov (United States)

    Werkmeister, J A; Adhikari, R; White, J F; Tebb, T A; Le, T P T; Taing, H C; Mayadunne, R; Gunatillake, P A; Danon, S J; Ramshaw, J A M

    2010-09-01

    This paper describes the synthesis and characterization of an injectable methacrylate functionalized urethane-based photopolymerizable prepolymer to form biodegradable hydrogels. The tetramethacrylate prepolymer was based on the reaction between two synthesized compounds, diisocyanato poly(ethylene glycol) and monohydroxy dimethacrylate poly(epsilon-caprolactone) triol. The final prepolymer was hydrated with phosphate-buffered saline (pH 7.4) to yield a biocompatible hydrogel containing up to 86% water. The methacrylate functionalized prepolymer was polymerized using blue light (450 nm) with an initiator, camphorquinone and a photosensitizer, N,N-dimethylaminoethyl methacrylate. The polymer was stable in vitro in culture media over the 28 days tested (1.9% mass loss); in the presence of lipase, around 56% mass loss occurred over the 28 days in vitro. Very little degradation occurred in vivo in rats over the same time period. The polymer was well tolerated with very little capsule formation and a moderate host tissue response. Human chondrocytes, seeded onto Cultispher-S beads, were viable in the tetramethacrylate prepolymer and remained viable during and after polymerization. Chondrocyte-bead-polymer constructs were maintained in static and spinner culture for 8 weeks. During this time, cells remained viable, proliferated and migrated from the beads through the polymer towards the edge of the polymer. New extracellular matrix (ECM) was visualized with Masson's trichrome (collagen) and Alcian blue (glycosaminoglycan) staining. Further, the composition of the ECM was typical for articular cartilage with prominent collagen type II and type VI and moderate keratin sulphate, particularly for tissue constructs cultured under dynamic conditions. 2010. Published by Elsevier Ltd. All rights reserved.

  12. Collagene order of articular cartilage by clinical magnetic resonance images and its age dependency

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, P.; Gruender, W. [Inst. of Medical Physics and Biophysics, Univ. of Leipzig (Germany)

    2005-07-01

    The present papers describes a novel method to obtain information on the degree of order of the collagen network of the knee meniscal cartilage by means of a single clinical MRI. Images were obtained from 34 healthy volunteers aged between 6 and 76 years as well as from one patient with clinically-diagnosed arthrosis at the age of 32 and 37 years. A siemens vision (1.5 T) MRT with TR = 750 ms, TE = 50 ms, FoV = 160 mm, and Matrix 512 x 512 was used for this purpose. The MR signal intensities of the cartilage were read out along slices with constant height above the subchondral bone and plotted versus the actual angle to the external magnetic field. The obtained intensity curves were fitted by a model distribution, and the degree of order of the collagen fibers was calculated. For the knee meniscal cartilage, there was an age-dependency of the degree of order and a significant deviation of the volunteer with arthrosis from the normal curve. The results are discussed in view of the arcade model and of a possible use of non-invasive clinical MRT for the detection of early arthrotic changes of cartilage. (orig.)

  13. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells

    OpenAIRE

    Zhang, Xiaowei; Wu, Shili; Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Chu, Cong-Qiu; Zhu, Yong

    2017-01-01

    Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrat...

  14. Transfection of the IHH gene into rabbit BMSCs in a simulated microgravity environment promotes chondrogenic differentiation and inhibits cartilage aging.

    Science.gov (United States)

    Liu, Peng-Cheng; Liu, Kuan; Liu, Jun-Feng; Xia, Kuo; Chen, Li-Yang; Wu, Xing

    2016-09-27

    The effect of overexpressing the Indian hedgehog (IHH) gene on the chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) was investigated in a simulated microgravity environment. An adenovirus plasmid encoding the rabbit IHH gene was constructed in vitro and transfected into rabbit BMSCs. Two large groups were used: conventional cell culture and induction model group and simulated microgravity environment group. Each large group was further divided into blank control group, GFP transfection group, and IHH transfection group. During differentiation induction, the expression levels of cartilage-related and cartilage hypertrophy-related genes and proteins in each group were determined. In the conventional model, the IHH transfection group expressed high levels of cartilage-related factors (Coll2 and ANCN) at the early stage of differentiation induction and expressed high levels of cartilage hypertrophy-related factors (Coll10, annexin 5, and ALP) at the late stage. Under the simulated microgravity environment, the IHH transfection group expressed high levels of cartilage-related factors and low levels of cartilage hypertrophy-related factors at all stages of differentiation induction. Under the simulated microgravity environment, transfection of the IHH gene into BMSCs effectively promoted the generation of cartilage and inhibited cartilage aging and osteogenesis. Therefore, this technique is suitable for cartilage tissue engineering.

  15. Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel.

    Science.gov (United States)

    Yokota, Masashi; Yasuda, Kazunori; Kitamura, Nobuto; Arakaki, Kazunobu; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian-Ping

    2011-02-22

    Functional repair of articular osteochondral defects remains a major challenge not only in the field of knee surgery but also in tissue regeneration medicine. The purpose is to clarify whether the spontaneous hyaline cartilage regeneration can be induced in a large osteochondral defect created in the femoral condyle by means of implanting a novel double-network (DN) gel at the bottom of the defect. Twenty-five mature rabbits were used in this study. In the bilateral knees of each animal, we created an osteochondral defect having a diameter of 2.4-mm in the medial condyle. Then, in 21 rabbits, we implanted a DN gel plug into a right knee defect so that a vacant space of 1.5-mm depth (in Group I), 2.5-mm depth (in Group II), or 3.5-mm depth (in Group III) was left. In the left knee, we did not apply any treatment to the defect to obtain the control data. All the rabbits were sacrificed at 4 weeks, and the gross and histological evaluations were performed. The remaining 4 rabbits underwent the same treatment as used in Group II, and real-time PCR analysis was performed at 4 weeks. The defect in Group II was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen. The Wayne's gross appearance and histology scores showed that Group II was significantly greater than Group I, III, and Control (p hyaline cartilage regeneration can be induced in vivo in an osteochondral defect created in the femoral condyle by means of implanting the DN gel plug at the bottom of the defect so that an approximately 2-mm deep vacant space was intentionally left in the defect. This fact has prompted us to propose an innovative strategy without cell culture to repair osteochondral lesions in the femoral condyle.

  16. Concise review: unraveling stem cell cocultures in regenerative medicine: which cell interactions steer cartilage regeneration and how?

    NARCIS (Netherlands)

    de Windt, T.S.; Hendriks, J.A.; Zhao, X.; Vonk, L.A.; Creemers, L.B.; Dhert, W.J.A.; Randolph, M.A.; Saris, D.B.F.

    2014-01-01

    Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both young, active patients and older patients disabled and affecting quality of life. In particular, cartilage injury not only imparts acute loss of function but also predisposes to OA. The increase in knowledge

  17. Quantitative evaluation of hyaline articular cartilage T2 maps of knee and determine the relationship of cartilage T2 values with age, gender, articular changes.

    Science.gov (United States)

    Cağlar, E; Şahin, G; Oğur, T; Aktaş, E

    2014-11-01

    To identify changes in knee joint cartilage transverse relaxation values depending on the patient's age and gender and to investigate the relationship between knee joint pathologies and the transverse relaxation time. Knee MRI images of 107 symptomatic patients with various pathologic knee conditions were analyzed retrospectively. T2 values were measured at patellar cartilage, posteromedial and posterolateral femoral cartilage adjacent to the central horn of posterior meniscus. 963 measurements were done for 107 knees MRI. Relationship of T2 values with seven features including subarticular bone marrow edema, subarticular cysts, marginal osteophytes, anterior-posterior cruciate and collateral ligament tears, posterior medial and posterior lateral meniscal tears, synovial thickening and effusion were analyzed. T2 values in all three compartments were evaluated according to age and gender. A T2 value increase correlated with age was present in all three compartments measured in the subgroup with no knee joint pathology and in all patient groups. According to the ROC curve, an increase showing a statistically significant difference was present in the patient group aged over 40 compared to the patient group aged 40 and below in all patient groups. There is a statistically difference at T2 values with and without subarticular cysts, marginal osteophytes, synovial thickening and effusion. T2 relaxation time showed a statistically significant increase in the patients with a medial meniscus tear compared to those without a tear and no statistically significant difference was found in T2 relaxation times of patients with and without a posterior lateral meniscus tear. T2 cartilage mapping on MRI provides opportunity to exhibit biochemical and structural changes related with cartilage extracellular matrix without using invasive diagnostic methods.

  18. Growth activity in human septal cartilage: age-dependent incorporation of labeled sulfate in different anatomic locations

    International Nuclear Information System (INIS)

    Vetter, U.; Pirsig, W.; Heinze, E.

    1983-01-01

    Growth activity in different areas of human septal cartilage was measured by the in vitro incorporation of 35 S-labeled NaSO 4 into chondroitin sulfate. Septal cartilage without perichondrium was obtained during rhinoplasty from 36 patients aged 6 to 35 years. It could be shown that the anterior free end of the septum displays high growth activity in all age groups. The supra-premaxillary area displayed its highest growth activity during prepuberty, showing thereafter a continuous decline during puberty and adulthood. A similar age-dependent pattern in growth activity was found in the caudal prolongation of the septal cartilage. No age-dependent variations could be detected in the posterior area of the septal cartilage

  19. Regeneration

    Science.gov (United States)

    George A. Schier; Wayne D. Shepperd; John R. Jones

    1985-01-01

    There are basically two approaches to regenerating aspen stands-sexual reproduction using seed, or vegetative regeneration by root suckering. In the West, root suckering is the most practical method. The advantage of having an existing, well established root system capable of producing numerous root suckers easily outweighs natural or artificial reforestation in the...

  20. T1ρ and T2 mapping of the proximal tibiofibular joint in relation to aging and cartilage degeneration

    International Nuclear Information System (INIS)

    Hirose, Jun; Nishioka, Hiroaki; Nakamura, Eiichi; Oniki, Yasunari; Yamashita, Yasuyuki; Mizuta, Hiroshi

    2012-01-01

    Objective: To study the effects of aging and cartilage degeneration of the proximal tibiofibular- and femorotibial joint (PTFJ, FTJ) on the cartilage of the PTFJ using T 1 ρ and T 2 mapping. Materials and methods: We performed sagittal T 1 ρ and T 2 mapping of the PTFJ and FTJ on 55 subjects with knee disorders. We placed 3 regions of interest (ROIs) on images of the cartilage in the PTFJ, medial femoral condyle (MFC), and medial tibia plateau (MTP). Correlation analysis was performed for the T 1 ρ and T 2 values of each ROI and the patient age and the osteoarthritic grade of the PTFJ and FTJ. Results: The T 1 ρ and T 2 values of the PTFJ were affected neither by aging nor the osteoarthritic grade of the FTJ. Values of the FTJ normalized to PTFJ values were correlated with the osteoarthritic grade of the FTJ in the MFC (r = 0.851 and 0.779, respectively) and the MTP (r = 0.635 and 0.762, respectively). There was a significant difference in the T 1 ρ but not the T 2 value of the PTFJ and MFC between normal and mildly osteoarthritic cartilage of each joint. Conclusion: We document that the T 1 ρ and T 2 values of PTFJ cartilage were not affected by aging or cartilage degeneration in the FTJ. The T 1 ρ value of the PTFJ may represent a useful internal standard reference for evaluating early degeneration of the FTJ

  1. Experimental study on the role of intra-articular injection of MSCs on cartilage regeneration in haemophilia.

    Science.gov (United States)

    Ravanbod, R; Torkaman, G; Mophid, M; Mohammadali, F

    2015-09-01

    Mesenchymal stem cells (MSCs) therapy is a field in progress in cartilage repair strategies. We tried to investigate the functional properties of the joint and cartilage in experimental haemarthrosis (EH) after MSCs intra-articular (IA) injection. One millilitre of fresh autologous blood was injected twice a week for three consecutive weeks in three groups including control haemophilia 10 days (n = 8), control haemophilia 38 days (n = 8) and MSCs (n = 8) group. In later, 10 days after the end of IA blood injections, MSCs IA injection was performed. Eight animals received no treatment as the normal control group. Thirty-eight days after the end of IA blood injections, animals were sacrificed. Joint friction and stress-relaxation tests were done, inflammatory cytokines of synovial membrane and scanning electron microscopy of the cartilage assessed. Joint friction decreased in MSCs in comparison to other groups and was significant with normal control group, (P = 0.011). The mechanical properties of cartilage showed no significant differences between groups. Tumour necrosis factor alpha and interleukin 1 beta decreased and IL-4 very slightly increased in MSCs in comparison to the time-matched control group. Scanning electron microscopy enabled acquisition of good structural properties of the surface and layers of the cartilage after MSCs injection. The hole induced in the medial plateau of the tibia bones, after inducing haemarthrosis, were covered with cartilage-like structure. The results showed that MSCs IA injection has some beneficial effects on cartilage structure and function in haemarthrosis model and is promising in patients with haemophilia. © 2015 John Wiley & Sons Ltd.

  2. 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

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

    Directory of Open Access Journals (Sweden)

    Janusz Popko

    2006-09-01

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

  4. Asporin stably expressed in the surface layer of mandibular condylar cartilage and augmented in the deeper layer with age.

    Science.gov (United States)

    Miyamoto, Yutaka; Kanzaki, Hiroyuki; Wada, Satoshi; Tsuruoka, Sari; Itohiya, Kanako; Kumagai, Kenichi; Hamada, Yoshiki; Nakamura, Yoshiki

    2017-12-01

    Mandibular condylar cartilage (MCC) exhibits dual roles both articular cartilage and growth center. Of many growth factors, TGF-β has been implicated in the growth of articular cartilage including MCC. Recently, Asporin, decoy to TGF-β, was discovered and it blocks TGF-β signaling. Asporin is expressed in a variety of tissues including osteoarthritic articular cartilage, though there was no report of Asporin expression in MCC. In the present study, we investigated the temporal and spatial expression of Asporin in MCC. Gene expression profile of MCC and epiphyseal cartilage in tibia of 5 weeks old ICR mice were firstly compared with microarray analysis using the laser capture microdissected samples. Variance of gene expression was further confirmed by real-time RT-PCR and immunohistochemical staining at 1,3,10, and 20 weeks old. TGF-β and its signaling molecule, phosphorylated Smad-2/3 (p-Smad2/3), were also examined by immunohistochemical staining. Microarray analysis revealed that Asporin was highly expressed in MCC. Real-time RT-PCR analysis confirmed that the fibrous layer of MCC exhibited stable higher Asporin expression at any time points as compared to epiphyseal cartilage. This was also observed in immunohistochemical staining. Deeper layer in MCC augmented Asporin expression with age. Whereas, TGF-β was stably highly observed in the layer. The fibrous layer of MCC exhibited weak staining of p-Smad2/3, though the proliferating layer of MCC was strongly stained as compared to epiphyseal cartilage of tibia at early time point. Consistent with the increase of Asporin expression in the deeper layer of MCC, the intensity of p-Smad-2/3 staining was decreased with age. In conclusion, we discovered that Asporin was stably expressed at the fibrous layer of MCC, which makes it possible to manage both articular cartilage and growth center at the same time.

  5. Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: short-term results.

    Science.gov (United States)

    Matsuda, Hidetoshi; Kitamura, Nobuto; Kurokawa, Takayuki; Arakaki, Kazunobu; Gong, Jian Ping; Kanaya, Fuminori; Yasuda, Kazunori

    2013-01-31

    A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the defect. The regenerated tissues were evaluated with the Wayne's gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. According to the total Wayne's score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (phyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

  6. Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: Short-term results

    Directory of Open Access Journals (Sweden)

    Matsuda Hidetoshi

    2013-01-01

    Full Text Available Abstract Background A double-network (DN gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid and poly(N,N’-dimethyl acrylamide, can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Methods Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control. Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface in the defect. The regenerated tissues were evaluated with the Wayne’s gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. Results According to the total Wayne’s score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p  Conclusions The 1.0-mm thick DN gel sheet had the same ability to induce hyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

  7. Single-Stage Cell-Based Cartilage Regeneration Using a Combination of Chondrons and Mesenchymal Stromal Cells: Comparison With Microfracture

    NARCIS (Netherlands)

    Bekkers, J.E.J.; Tsuchida, A.I.; van Rijen, M.H.P.; Vonk, L.A.; Dhert, W.J.A.; Saris, Daniël B.F.

    2013-01-01

    Background: Autologous chondrocyte implantation (ACI) is traditionally a 2-step procedure used to repair focal articular cartilage lesions. With use of a combination of chondrons (chondrocytes in their own territorial matrix) and mesenchymal stromal cells (MSCs), ACI could be innovated and performed

  8. A new injectable biphasic hydrogel based on partially hydrolyzed polyacrylamide and nano hydroxyapatite, crosslinked with chromium acetate, as scaffold for cartilage regeneration

    Science.gov (United States)

    Koushki, N.; Tavassoli, H.; Katbab, A. A.; Katbab, P.; Bonakdar, S.

    2015-05-01

    Polymer scaffolds are applied in the field of tissue engineering as three dimensional structures to organize cells and present stimuli to direct generation of a desired damaged tissue. In situ gelling scaffolds have attracted great attentions, as they are structurally similar to the extra cellular matrix (ECM). In the present work, attempts have been made to design and fabricate a new injectable and crosslinkable biphasic hydrogel based on partially hydrolyzed polyacrylamide (HPAM), chromium acetate as crosslink agent and nanocrystalline hydroxyapatite (nHAp) as reinforcing and bioactive agent for repair and regeneration of damaged cartilage. The distinct characteristic of HPAM is the presence of carboxylate anion groups on its backbone which allows to engineer the structure of the hydrogel for the desired bioactivity with appropriate cells differentiation towards both soft and hard (bone) tissues. The synthesized hydrogel exhibited bifunctional behavior which was derived by its biphasic structure in which one phase was loaded with nano hydroxyapatite to provide integration capability by subchondral bones and fix the hydrogel at cartilage defect without a need for suturing. The other phase differentiates the rabbit adipogenic mesenchymal stem cells (MSCs) towards soft tissue. Rheomechanical spectrometry (RMS) was employed to study the kinetic of the gelation including induction time and rate, as well as to measure the ultimate elastic modulus of the optimum crosslinked hydrogel. Surface tension measurement was also performed to tailor the surface characteristics of the gels. In vitro culturing of the cells inside the crosslinked hydrogel revealed high viability and high differentiation of the encapsulated rabbit stem cells, providing that the chromium acetate level was kept below 0.2 wt%. Based on the obtained results, the designed and fabricated biphasic hydrogel exhibited high potential as carrier for the stem cells for cartilage tissue engineering application

  9. Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells as a Potential Source for Cartilage and Bone Regeneration: An In Vitro Study

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    A. Marmotti

    2017-01-01

    Full Text Available Umbilical cord (UC may represent an attractive cell source for allogeneic mesenchymal stem cell (MSC therapy. The aim of this in vitro study is to investigate the chondrogenic and osteogenic potential of UC-MSCs grown onto tridimensional scaffolds, to identify a possible clinical relevance for an allogeneic use in cartilage and bone reconstructive surgery. Chondrogenic differentiation on scaffolds was confirmed at 4 weeks by the expression of sox-9 and type II collagen; low oxygen tension improved the expression of these chondrogenic markers. A similar trend was observed in pellet culture in terms of matrix (proteoglycan production. Osteogenic differentiation on bone-graft-substitute was also confirmed after 30 days of culture by the expression of osteocalcin and RunX-2. Cells grown in the hypertrophic medium showed at 5 weeks safranin o-positive stain and an increased CbFa1 expression, confirming the ability of these cells to undergo hypertrophy. These results suggest that the UC-MSCs isolated from minced umbilical cords may represent a valuable allogeneic cell population, which might have a potential for orthopaedic tissue engineering such as the on-demand cell delivery using chondrogenic, osteogenic, and endochondral scaffold. This study may have a clinical relevance as a future hypothetical option for allogeneic single-stage cartilage repair and bone regeneration.

  10. [Age factor in eye regeneration of the gastropod mollusk Achatina fulica].

    Science.gov (United States)

    Tartakovskaia, O S; Borisenko, S L; Zhukov, V V

    2003-01-01

    The dependence of the ability to regenerate the eye on the age of experimental animals was studied in the snail Achatina fulica. The degree of regeneration was estimated by light-microscopic and electrophysiological methods and by analyzing the motor response to visual stimuli. In older age groups, the number of regenerated eye-bearing tentacles decreased, whereas the period of regeneration increased. The regenerated eyes of the snails operated at the age of more than two months remained smaller than normal eyes even after six months. Regeneration of the distal part of the optic nerve was observed, and the regenerated eyes recovered the ability to respond to stimulation by light. In the electroretinogram, the responses of the regenerated eye, compared to the control, were characterised by a lower amplitude and longer repolarization and refractory periods. Manifestations of the motor response to visual stimuli in the young snails with regenerating eyes could be regarded as evidence for the recovery of connection between the organ of sight and the central ganglia.

  11. The relationship between ultra-short telomeres, aging of articular cartilage and the development of human hip osteoarthritis

    DEFF Research Database (Denmark)

    Harbo, M; Delaisse, J M; Kjaersgaard-Andersen, P

    2013-01-01

    Ultra-short telomeres caused by stress-induced telomere shortening are suggested to induce chondrocyte senescence in human osteoarthritic knees. Here we have further investigated the role of ultra-short telomeres in the development of osteoarthritis (OA) and in aging of articular cartilage in human...

  12. Mechanical stiffness of TMJ condylar cartilage increases after artificial aging by ribose.

    Science.gov (United States)

    Mirahmadi, Fereshteh; Koolstra, Jan Harm; Lobbezoo, Frank; van Lenthe, G Harry; Ghazanfari, Samaneh; Snabel, Jessica; Stoop, Reinout; Everts, Vincent

    2018-03-01

    Aging is accompanied by a series of changes in mature tissues that influence their properties and functions. Collagen, as one of the main extracellular components of cartilage, becomes highly crosslinked during aging. In this study, the aim was to examine whether a correlation exists between collagen crosslinking induced by artificial aging and mechanical properties of the temporomandibular joint (TMJ) condyle. To evaluate this hypothesis, collagen crosslinks were induced using ribose incubation. Porcine TMJ condyles were incubated for 7 days with different concentrations of ribose. The compressive modulus and stiffness ratio (incubated versus control) was determined after loading. Glycosaminoglycan and collagen content, and the number of crosslinks were analyzed. Tissue structure was visualized by microscopy using different staining methods. Concomitant with an increasing concentration of ribose, an increase of collagen crosslinks was found. The number of crosslinks increased almost 50 fold after incubation with the highest concentration of ribose. Simultaneously, the stiffness ratio of the samples showed a significant increase after incubation with the ribose. Pearson correlation analyses showed a significant positive correlation between the overall stiffness ratio and the crosslink level; the higher the number of crosslinks the higher the stiffness. The present model, in which ribose was used to mimic certain aspects of age-related changes, can be employed as an in vitro model to study age-related mechanical changes in the TMJ condyle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. 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.

  14. Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing.

    Science.gov (United States)

    Taylor, Adam M; Hsueh, Ming-Feng; Ranganath, Lakshminarayan R; Gallagher, James A; Dillon, Jane P; Huebner, Janet L; Catterall, Jon B; Kraus, Virginia B

    2017-01-01

    Alkaptonuria (AKU) is a rare autosomal recessive disease resulting from a single enzyme deficiency in tyrosine metabolism. As a result, homogentisic acid cannot be metabolized, causing systemic increases. Over time, homogentisic acid polymerizes and deposits in collagenous tissues, leading to ochronosis. Typically, this occurs in joint cartilages, leading to an early onset, rapidly progressing osteoarthropathy. The aim of this study was to examine tissue turnover in cartilage affected by ochronosis and its role in disease initiation and progression. With informed patient consent, hip and knee cartilages were obtained at surgery for arthropathy due to AKU (n = 6; 2 knees/4 hips) and OA (n = 12; 5 knees/7 hips); healthy non-arthritic (non-OA n = 6; 1 knee/5 hips) cartilages were obtained as waste from trauma surgery. We measured cartilage concentrations (normalized to dry weight) of racemized aspartate, GAG, COMP and deamidated COMP (D-COMP). Unpaired AKU, OA and non-OA samples were compared by non-parametric Mann-Whitney U test. Despite more extractable total protein being obtained from AKU cartilage than from OA or non-OA cartilage, there was significantly less extractable GAG, COMP and D-COMP in AKU samples compared with OA and non-OA comparators. Racemized Asx (aspartate and asparagine) was significantly enriched in AKU cartilage compared with in OA cartilage. These novel data represent the first examination of cartilage matrix components in a sample of patients with AKU, representing almost 10% of the known UK alkaptonuric population. Compared with OA and non-OA, AKU cartilage demonstrates a very low turnover state and has low levels of extractable matrix proteins. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. 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.

  16. Professional ballet dancers have a similar prevalence of articular cartilage defects compared to age- and sex-matched non-dancing athletes.

    Science.gov (United States)

    Mayes, Susan; Ferris, April-Rose; Smith, Peter; Garnham, Andrew; Cook, Jill

    2016-12-01

    Ballet exposes the hip joint to repetitive loading in extreme ranges of movement and may predispose a dancer to pain and osteoarthritis (OA). The aims of this study were to compare the prevalence of cartilage defects in professional ballet dancers and athletes and to determine the relationship of clinical signs and symptoms. Forty-nine male and female, current and retired professional ballet dancers and 49 age- and sex-matched non-dancing athletes completed hip pain questionnaires, including the Copenhagen Hip and Groin Outcome Score (HAGOS), and underwent hip range of movement (ROM) testing and 3-Tesla magnetic resonance imaging to score cartilage defects (no defect, grade 1: focal partial defect and grade 2: diffuse or full thickness defect). Thirty (61 %) dancers and 27 (55 %) athletes had cartilage defects (p = 0.54). The frequency of grade 1 and 2 cartilage defects did not differ between dancers and athletes (p = 0.83). The frequency of cartilage defects was similar in male and female dancers (p = 0.34), and male and female athletes (p = 0.24). Cartilage defects were not related to history of hip pain (p = 0.34), HAGOS pain (p = 0.14), sports/rec (p = 0.15) scores or hip internal rotation ≤20° (p > 0.01). Cartilage defects were related to age in male dancers (p = 0.002). Ballet dancers do not appear to be at a greater risk of cartilage injury compared to non-dancing athletes. Male dancers develop cartilage defects at an earlier age than athletes and female dancers. Cartilage defects were not related to clinical signs and symptoms; thus, prospective studies are required to determine which cartilage defects progress to symptomatic hip OA.

  17. Biocompatibility Assessment of Novel Collagen-Sericin Scaffolds Improved with Hyaluronic Acid and Chondroitin Sulfate for Cartilage Regeneration

    Directory of Open Access Journals (Sweden)

    Sorina Dinescu

    2013-01-01

    Full Text Available Cartilage tissue engineering (CTE applications are focused towards the use of implantable biohybrids consisting of biodegradable scaffolds combined with in vitro cultured cells. Hyaluronic acid (HA and chondroitin sulfate (CS were identified as the most potent prochondrogenic factors used to design new biomaterials for CTE, while human adipose-derived stem cells (ASCs were proved to display high chondrogenic potential. In this context, our aim was not only to build novel 3D porous scaffolds based on natural compounds but also to evaluate their in vitro biological performances. Therefore, for prospective CTE, collagen-sericin (Coll-SS scaffolds improved with HA (5% or 10% and CS (5% or 10% were used as temporary physical supports for ASCs and were analyzed in terms of structural, thermal, morphological, and swelling properties and cytotoxic potential. To complete biocompatibility data, ASCs viability and proliferation potential were also assessed. Our studies revealed that Coll-SS hydrogels improved with 10% HA and 5% CS displayed the best biological performances in terms of cell viability, proliferation, morphology, and distribution. Thus, further work will address a novel 3D system including both HA 10% and CS 5% glycoproteins, which will probably be exposed to prochondrogenic conditions in order to assess its potential use in CTE applications.

  18. T2* Mapping of the Hip in Asymptomatic Volunteers with Normal Cartilage Morphology: An Analysis of Regional and Age-Dependent Distribution.

    Science.gov (United States)

    Hesper, Tobias; Schleich, Christoph; Buchwald, Alexander; Hosalkar, Harish S; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph; Bittersohl, Bernd

    2018-01-01

    Objective To assess age-dependent and regional differences in T2* relaxation measurements in hip joint cartilage of asymptomatic volunteers at 3 T. Design Three age cohorts (cohort 1: age 20-30 years, 15 individuals; cohort 2: age 30-40 years, 17 individuals; cohort 3: age 40-50 years, 15 individuals) were enrolled. T2* values were obtained in the central and peripheral cartilage of the acetabulum and the femoral head in 7 regions (anterior to superior and posterior). Results T2* did not differ among age cohorts in acetabular cartilage (cohort 1: 24.65 ± 6.56 ms, cohort 2: 24.70 ± 4.83 ms, cohort 3: 25.81 ± 5.10 ms, P = 0.10) and femoral head cartilage (cohort 1: 27.08 ± 8.24 ms, cohort 2: 25.90 ± 7.82 ms, cohort 3: 26.50 ± 5.61 ms, P = 0.34). Analysis of the regional T2* distribution pattern indicates increased T2* values in the anterior, anterior-superior, superior-anterior, and the posterior-superior aspects of acetabular and femoral head cartilage. For acetabular cartilage, higher values were observed in the central region (25.90 ± 4.80 ms vs. 24.21 ± 4.05 ms, P cartilage did not reveal such differences (26.62 ± 5.74 ms vs. 26.37 ± 5.89 ms, P = 0.44). Conclusions The T2* analysis of presumably healthy hip joint cartilage does not seem to be stratified according to age in this population. Regional T2* variation throughout hip joint cartilage is apparent in this modality.

  19. Behaviour of telomere and telomerase during aging and regeneration in zebrafish.

    Directory of Open Access Journals (Sweden)

    Monique Anchelin

    Full Text Available Telomere length and telomerase activity are important factors in the pathobiology of human diseases. Age-related diseases and premature aging syndromes are characterized by short telomeres, which can compromise cell viability, whereas tumour cells can prevent telomere loss by aberrantly upregulating telomerase. The zebrafish (Danio rerio offers multiple experimental manipulation advantages over other vertebrate models and, therefore, it has been recently considered as a potential model for aging, cancer, and regeneration studies. However, it has only partially been exploited to shed light on these fundamental biological processes. The aim of this study was, therefore, to investigate telomere length and telomerase expression and activity in different strains of zebrafish obtained from different stock centres to determine whether they undergo any changes during aging and regeneration. We found that although both telomerase expression and telomere length increased from embryo to adulthood stages, they drastically declined in aged fish despite telomerase activity was detected in different tissues of old fish. In addition, we observed a weaker upregulation of telomerase expression in regenerating fins of old fish, which well correlates with their impaired regeneration capacity. Strikingly, telomeres were elongated or maintained during the fin regeneration process at all ages and after repeated amputations, likely to support high cell proliferation rates. We conclude that the expression of telomerase and telomere length are closely related during the entire life cycle of the fish and that these two parameters can be used as biomarkers of aging in zebrafish. Our results also reveal a direct relationship between the expression of telomerase, telomere length and the efficiency of tissue regeneration.

  20. Behaviour of telomere and telomerase during aging and regeneration in zebrafish.

    Science.gov (United States)

    Anchelin, Monique; Murcia, Laura; Alcaraz-Pérez, Francisca; García-Navarro, Esther M; Cayuela, María L

    2011-02-09

    Telomere length and telomerase activity are important factors in the pathobiology of human diseases. Age-related diseases and premature aging syndromes are characterized by short telomeres, which can compromise cell viability, whereas tumour cells can prevent telomere loss by aberrantly upregulating telomerase. The zebrafish (Danio rerio) offers multiple experimental manipulation advantages over other vertebrate models and, therefore, it has been recently considered as a potential model for aging, cancer, and regeneration studies. However, it has only partially been exploited to shed light on these fundamental biological processes. The aim of this study was, therefore, to investigate telomere length and telomerase expression and activity in different strains of zebrafish obtained from different stock centres to determine whether they undergo any changes during aging and regeneration. We found that although both telomerase expression and telomere length increased from embryo to adulthood stages, they drastically declined in aged fish despite telomerase activity was detected in different tissues of old fish. In addition, we observed a weaker upregulation of telomerase expression in regenerating fins of old fish, which well correlates with their impaired regeneration capacity. Strikingly, telomeres were elongated or maintained during the fin regeneration process at all ages and after repeated amputations, likely to support high cell proliferation rates. We conclude that the expression of telomerase and telomere length are closely related during the entire life cycle of the fish and that these two parameters can be used as biomarkers of aging in zebrafish. Our results also reveal a direct relationship between the expression of telomerase, telomere length and the efficiency of tissue regeneration.

  1. 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

  2. Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group.

    Science.gov (United States)

    Nishioka, Hiroaki; Hirose, Jun; Okamoto, Nobukazu; Okada, Tatsuya; Oka, Kiyoshi; Taniwaki, Takuya; Nakamura, Eiichi; Yamashita, Yasuyuki; Mizuta, Hiroshi

    2015-03-01

    The aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Sagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. There were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ=0.737 and ρ=0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. Our study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Comparison of T2* relaxation times of articular cartilage of the knee in elite professional football players and age-and BMI-matched amateur athletes

    Energy Technology Data Exchange (ETDEWEB)

    Behzadi, C., E-mail: c.behzadi@uke.de [Department of Diagnostic and Interventional Radiology and Nuclearmedicine, University Medical Center Hamburg-Eppendorf, Hamburg, 20246 (Germany); Welsch, G.H. [Department of Sports Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, 20246 (Germany); Laqmani, A.; Henes, F.O.; Kaul, M.G. [Department of Diagnostic and Interventional Radiology and Nuclearmedicine, University Medical Center Hamburg-Eppendorf, Hamburg, 20246 (Germany); Schoen, G. [Department of Medical Biometry and Epidemiology, University Medical Center, Hamburg-Eppendorf, Hamburg, 20246 (Germany); Adam, G.; Regier, M. [Department of Diagnostic and Interventional Radiology and Nuclearmedicine, University Medical Center Hamburg-Eppendorf, Hamburg, 20246 (Germany)

    2017-01-15

    Objective: Recent investigation has underlined the potential of quantitative MR imaging to be used as a complementary tool for the diagnosis of cartilage degeneration at an early state. The presented study analyses T2* relaxation times of articular cartilage of the knee in professional athletes and compares the results to age- and BMI (Body Mass Index)-matched healthy amateur athletes. Materials and methods: 22 professional football players and 22 age- and BMI-matched individuals were underwent knee Magnetic Resonance Imaging (MRI) at 3T including qualitative and quantitative analysis. Qualitative analysis included e.g. meniscal tears, joint effusion and bone edema. For quantitative analysis T2* (22 ET: 4.6-53.6 ms) measurements in 3D data acquisition were performed. Deep and superficial layers of 22 predefined cartilage segments were analysed. All data sets were postprocessed using a dedicated software tool. Statistical analysis included Student t-test, confidence intervals and a random effects model. Results: In both groups, T2* relaxation times were significantly higher in the superficial compared to the deep layers (p < 0.001). Professional athletes had significantly higher relaxation times in eight superficial and three deep cartilage layers in the predefined cartilage segments (p < 0.05). Highly significant differences were found in the weight-bearing segments of the lateral superficial femoral condyle (p < 0.001). Conclusion: Elevated T2* values in cartilage layers of professional football players compared to amateur athletes were noted. The effects seem to predominate in superficial cartilage layers.

  4. Comparison of T2* relaxation times of articular cartilage of the knee in elite professional football players and age-and BMI-matched amateur athletes

    International Nuclear Information System (INIS)

    Behzadi, C.; Welsch, G.H.; Laqmani, A.; Henes, F.O.; Kaul, M.G.; Schoen, G.; Adam, G.; Regier, M.

    2017-01-01

    Objective: Recent investigation has underlined the potential of quantitative MR imaging to be used as a complementary tool for the diagnosis of cartilage degeneration at an early state. The presented study analyses T2* relaxation times of articular cartilage of the knee in professional athletes and compares the results to age- and BMI (Body Mass Index)-matched healthy amateur athletes. Materials and methods: 22 professional football players and 22 age- and BMI-matched individuals were underwent knee Magnetic Resonance Imaging (MRI) at 3T including qualitative and quantitative analysis. Qualitative analysis included e.g. meniscal tears, joint effusion and bone edema. For quantitative analysis T2* (22 ET: 4.6-53.6 ms) measurements in 3D data acquisition were performed. Deep and superficial layers of 22 predefined cartilage segments were analysed. All data sets were postprocessed using a dedicated software tool. Statistical analysis included Student t-test, confidence intervals and a random effects model. Results: In both groups, T2* relaxation times were significantly higher in the superficial compared to the deep layers (p < 0.001). Professional athletes had significantly higher relaxation times in eight superficial and three deep cartilage layers in the predefined cartilage segments (p < 0.05). Highly significant differences were found in the weight-bearing segments of the lateral superficial femoral condyle (p < 0.001). Conclusion: Elevated T2* values in cartilage layers of professional football players compared to amateur athletes were noted. The effects seem to predominate in superficial cartilage layers.

  5. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    NARCIS (Netherlands)

    Pot, M.W.; Gonzales, V.K.; Buma, P.; Hout, J. in't; Kuppevelt, T.H. van; Vries, R.B. de; Daamen, W.F.

    2016-01-01

    Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of

  6. Effects of collagen matrix and bioreactor cultivation on cartilage regeneration of a full-thickness critical-size knee joint cartilage defects with subchondral bone damage in a rabbit model.

    Directory of Open Access Journals (Sweden)

    Kuo-Hwa Wang

    Full Text Available Cartilage has limited self-repair ability. The purpose of this study was to investigate the effects of different species of collagen-engineered neocartilage for the treatment of critical-size defects in the articular joint in a rabbit model. Type II and I collagen obtained from rabbits and rats was mixed to form a scaffold. The type II/I collagen scaffold was then mixed with rabbit chondrocytes to biofabricate neocartilage constructs using a rotating cell culture system [three-dimensional (3D-bioreactor]. The rabbit chondrocytes were mixed with rabbit collagen scaffold and rat collagen scaffold to form neoRBT (neo-rabbit cartilage and neoRAT (neo-rat cartilage constructs, respectively. The neocartilage matrix constructs were implanted into surgically created defects in rabbit knee chondyles, and histological examinations were performed after 2 and 3 months. Cartilage-like lacunae formation surrounding the chondrocytes was noted in the cell cultures. After 3 months, both the neoRBT and neoRAT groups showed cartilage-like repair tissue covering the 5-mm circular, 4-mm-deep defects that were created in the rabbit condyle and filled with neocartilage plugs. Reparative chondrocytes were aligned as apparent clusters in both the neoRAT and neoRBT groups. Both neoRBT and neoRAT cartilage repair demonstrated integration with healthy adjacent tissue; however, more integration was obtained using the neoRAT cartilage. Our data indicate that different species of type II/I collagen matrix and 3D bioreactor cultivation can facilitate cartilage engineering in vitro for the repair of critical-size defect.

  7. Establishing even-age northern hardwood regeneration by the shelterwood method--a preliminary guide.

    Science.gov (United States)

    Richard M. Godman; Carl H. Tubbs

    1973-01-01

    The shelterwood system of regeneration with northern hardwoods is a reliable method of obtaining even-age stands of both tolerant and moderately tolerant species. Details of applying the two-cut system are described along with the necessary modifications for encouraging moderately tolerant species.

  8. Effects of strain and age on ear wound healing and regeneration in mice

    Directory of Open Access Journals (Sweden)

    R.A. Costa

    2009-12-01

    Full Text Available Round holes in the ears of MRL mice tend to close with characteristics of regeneration believed to be absent in other mouse strains (e.g., C57BL/6. We evaluated the kinetics and the histopathology of ear wound closure in young (8 weeks old C57BL/6 and BALB/c mice. We also used middle-aged (40 weeks old C57BL/6 mice to evaluate the influence of aging on this process. A circular through-and-through hole was made in the ear, photographs were taken at different times after injury and wound area was measured with digital analysis software. The percentages of closed area measured on day 100 were: 23.57 ± 8.66% for young BALB/c mice, 56.47 ± 7.39% for young C57BL/6 mice, and 75.31 ± 23.65% for middle-aged C57BL/6 mice. Mice were sacrificed on days 1, 3, 5, 25, 44, and 100 for histological evaluation with hematoxylin and eosin, Gomori’s trichrome, periodic acid-Schiff, or picrosirius red staining. In young mice of both strains, healing included re-epithelialization, chondrogenesis, myogenesis, and collagen deposition. Young C57BL/6 and BALB/c mice differed in the organization of collagen fibers visualized using picrosirius-polarization. Sebaceous glands and hair follicles regenerated and chondrogenesis was greater in young C57BL/6 mice. In middle-aged C57BL/6 mice all aspects of regeneration were depressed. The characteristics of regeneration were present during ear wound healing in both young BALB/c and young C57BL/6 mice although they differed in intensity and pattern. Greater ear wound closure in middle-aged C57BL/6 mice was not correlated with regeneration.

  9. Some observations on age relationships in spruce-fir regeneration

    Science.gov (United States)

    Barton M. Blum

    1973-01-01

    Measurement of the ages of seedlings of balsam fir (Abies balsamea (L) Mill.), red spruce (Picea rubens Sarg.), and white spruce (Picea glauca (Moench) Voss) 15 years after the first harvest of a two-cut shelterwood operation revealed that very few potential crop-tree seedlings in the sample occurred as advance...

  10. Transgenic overexpression of ADAM12 suppresses muscle regeneration and aggravates dystrophy in aged mdx mice

    DEFF Research Database (Denmark)

    Jørgensen, Louise Helskov; Jensen, Charlotte Harken; Wewer, Ulla M

    2007-01-01

    mice (ADAM12(+)) after a knife cut lesion and observed that the regeneration process was significantly impaired. ADAM12 seemed to inhibit the satellite cell response and delay myoblast differentiation. These results discourage long-term therapeutic use of ADAM12. They also point to impaired...... effect of ADAM12 was suggested to be mediated via a membrane-stabilizing up-regulation of utrophin, alpha7B integrin, and dystroglycans. Ectopic ADAM12 expression in normal mouse skeletal muscle also improved regeneration after freeze injury, presumably by the same mechanism. Hence, it was suggested...... overexpressing ADAM12 (ADAM12(+)/mdx mice), even though their utrophin levels were mildly elevated compared with age-matched controls. Thus, membrane stabilization was not sufficient to provide protection during prolonged disease. Consequently, we reinvestigated skeletal muscle regeneration in ADAM12 transgenic...

  11. Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group

    International Nuclear Information System (INIS)

    Nishioka, Hiroaki; Hirose, Jun; Okamoto, Nobukazu; Okada, Tatsuya; Oka, Kiyoshi; Taniwaki, Takuya; Nakamura, Eiichi; Yamashita, Yasuyuki; Mizuta, Hiroshi

    2015-01-01

    Highlights: •This prospective cohort study investigated the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. In this study, to the best of our knowledge, this is the first report to compare the T1ρ and T2 values between normal and OA knees within the same age group and to further investigate the relationship between the degree of cartilage degeneration and the T1ρ and T2 values in OA-grading groups of the same age. Our study confirmed that T1ρ and T2 mapping can be used to quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group.. -- Abstract: Objective: The aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Materials and methods: Sagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. Results: There were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ = 0.737 and ρ = 0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. Conclusions: Our study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group

  12. Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group

    Energy Technology Data Exchange (ETDEWEB)

    Nishioka, Hiroaki, E-mail: kinuhnishiok@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 (Japan); Hirose, Jun; Okamoto, Nobukazu; Okada, Tatsuya; Oka, Kiyoshi; Taniwaki, Takuya; Nakamura, Eiichi [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 (Japan); Yamashita, Yasuyuki [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 (Japan); Mizuta, Hiroshi [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 (Japan)

    2015-03-15

    Highlights: •This prospective cohort study investigated the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. In this study, to the best of our knowledge, this is the first report to compare the T1ρ and T2 values between normal and OA knees within the same age group and to further investigate the relationship between the degree of cartilage degeneration and the T1ρ and T2 values in OA-grading groups of the same age. Our study confirmed that T1ρ and T2 mapping can be used to quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group.. -- Abstract: Objective: The aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Materials and methods: Sagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. Results: There were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ = 0.737 and ρ = 0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. Conclusions: Our study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group.

  13. 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

    To determine the possibility for adaptive growth in human condyles, quantifying the thickness of fibrocartilage and the constitution of cells with potential activity, the trabecular bone volume, and the structural parameter: marrow space star volume in a larger sample of human autopsy condyles....... 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...

  14. Beech forests of Azerbaijan: The modern condition, age structure and regeneration

    Directory of Open Access Journals (Sweden)

    Z.M. Hasanov

    2017-12-01

    Full Text Available Azerbaijan is a country with low forest cover, only 11.8% of the territory is covered with forests. All forests perform important water-soil-protection functions. In forests, naturally grow 107 species of trees and 328 shrubs species. Despite the fact that there are many species in dendroflora, only 10 tree species have economic value for the forest sector of the country. Beech (31.68%, oak (27.40% and hornbeam (26.01% are growing in 85.09% of forested areas. Beech forests are spread on 327 thousand hectares from 989,5 of total forest lands of he Republic. Beech forests are a source of high-quality wood and beech nuts. All beech forests grow in mountains at heights of 600–800 and 1600–1800 m above the sea level and performing important ecological functions. Until recently there were no problems with natural renewal of the beech forests, but now the regeneration of beech forests is alarming. In recent years, the productivity and density of beech forests decreased substantially, the natural regeneration proceeds unsatisfactorily and, consequently, reduction of beech forests takes place. We have researched 33,8 thousand hectares of beech forests of the Lesser Caucasus, their natural regeneration and made analysis of age structure of forests. Keywords: Fagus orientalis, Beech forests, Silviculture, Natural regeneration, Age class

  15. Age-dependent Changes in the Articular Cartilage and Subchondral Bone of C57BL/6 Mice after Surgical Destabilization of Medial Meniscus.

    Science.gov (United States)

    Huang, Henry; Skelly, Jordan D; Ayers, David C; Song, Jie

    2017-02-09

    Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. This study investigates how age affects cartilage and subchondral bone changes in mouse joints following DMM. DMM was performed on male C57BL/6 mice at 4 months (4 M), 12 months (12 M) and 19+ months (19 M+) and on females at 12 M and 18 M+. Two months after surgery, operated and unoperated contralateral knees were harvested and evaluated using cartilage histology scores and μCT quantification of subchondral bone plate thickness and osteophyte formation. The 12 M and 19 M+ male mice developed more cartilage erosions and thicker subchondral bone plates after DMM than 4 M males. The size of osteophytes trended up with age, while the bone volume fraction was significantly higher in the 19 M+ group. Furthermore, 12 M females developed milder OA than males as indicated by less cartilage degradation, less subchondral bone plate sclerosis and smaller osteophytes. Our results reveal distinct age/gender-dependent structural changes in joint cartilage and subchondral bone post-DMM, facilitating more thoughtful selection of murine age/gender when using this surgical technique for translational OA research.

  16. Age-dependent Changes in the Articular Cartilage and Subchondral Bone of C57BL/6 Mice after Surgical Destabilization of Medial Meniscus

    Science.gov (United States)

    Huang, Henry; Skelly, Jordan D.; Ayers, David C.; Song, Jie

    2017-01-01

    Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. This study investigates how age affects cartilage and subchondral bone changes in mouse joints following DMM. DMM was performed on male C57BL/6 mice at 4 months (4 M), 12 months (12 M) and 19+ months (19 M+) and on females at 12 M and 18 M+. Two months after surgery, operated and unoperated contralateral knees were harvested and evaluated using cartilage histology scores and μCT quantification of subchondral bone plate thickness and osteophyte formation. The 12 M and 19 M+ male mice developed more cartilage erosions and thicker subchondral bone plates after DMM than 4 M males. The size of osteophytes trended up with age, while the bone volume fraction was significantly higher in the 19 M+ group. Furthermore, 12 M females developed milder OA than males as indicated by less cartilage degradation, less subchondral bone plate sclerosis and smaller osteophytes. Our results reveal distinct age/gender-dependent structural changes in joint cartilage and subchondral bone post-DMM, facilitating more thoughtful selection of murine age/gender when using this surgical technique for translational OA research. PMID:28181577

  17. Age-related changes in the incorporation of [35S]sulfate into two proteoglycan populations from human cartilage

    International Nuclear Information System (INIS)

    Triphaus, G.F.; Schmidt, A.; Buddecke, E.

    1980-01-01

    From human hyaline cartilage (processus xyphoid) preincubated in the presence of [ 35 S] sulfate, proteoglycans were extracted by 4M guanidinium chloride and divided into 6 age groups. Fractionation of proteoglycans by gel filtration under dissociative conditions resulted in two proteoglycan fractions (a and b) with different hydrodynamic volumes. The higher molecular weight fraction a contained chondroitin sulfate, the fraction b keratan sulfate as predominant glycosaminoglycan, the chondroitin sulfate/keratan sulfate ratio decreasing with increasing age in either fraction. The relative portion of proteoglycan fraction b and its 35 S-labelling increased with increasing age. From the specific 35 S radioactivities of the chondroitin sulfate and keratan sulfate preparations, the occurrence of two independent proteoglycan populations is suggested. A precursorproduct relationship between proteoglycan fraction a and b could be excluded. (orig.)

  18. Age-related changes in the incorporation of (/sup 35/S)sulfate into two proteoglycan populations from human cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Triphaus, G.F.; Schmidt, A.; Buddecke, E.

    1980-12-01

    From human hyaline cartilage (processus xyphoid) preincubated in the presence of (/sup 35/S) sulfate, proteoglycans were extracted by 4M guanidinium chloride and divided into 6 age groups. Fractionation of proteoglycans by gel filtration under dissociative conditions resulted in two proteoglycan fractions (a and b) with different hydrodynamic volumes. The higher molecular weight fraction a contained chondroitin sulfate, the fraction b keratan sulfate as predominant glycosaminoglycan, the chondroitin sulfate/keratan sulfate ratio decreasing with increasing age in either fraction. The relative portion of proteoglycan fraction b and its /sup 35/S-labelling increased with increasing age. From the specific /sup 35/S radioactivities of the chondroitin sulfate and keratan sulfate preparations, the occurrence of two independent proteoglycan populations is suggested. A precursorproduct relationship between proteoglycan fraction a and b could be excluded.

  19. Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

    Science.gov (United States)

    Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

    2014-03-01

    In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

  20. Engineering Cartilage

    Science.gov (United States)

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

  1. Shark Cartilage

    Science.gov (United States)

    Shark cartilage (tough elastic tissue that provides support, much as bone does) used for medicine comes primarily from sharks ... Several types of extracts are made from shark cartilage including squalamine lactate, AE-941, and U-995. ...

  2. Evaluation of the potential of rhTGF- β3 encapsulated P(LLA-CL)/collagen nanofibers for tracheal cartilage regeneration using mesenchymal stems cells derived from Wharton's jelly of human umbilical cord

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Sun, Binbin [State Key Laboratory of Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Tian, Lingling [Center for Nanofibers and Nanotechnology, E3-05-14, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); He, Xiaomin [Department of Pediatric Cardiothoracic Surgery, Shanghai Children' s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Gao, Qiang; Wu, Tong [State Key Laboratory of Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Ramakrishna, Seeram [Center for Nanofibers and Nanotechnology, E3-05-14, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou 510632 (China); Zheng, Jinghao, E-mail: zhengjh210@163.com [Department of Pediatric Cardiothoracic Surgery, Shanghai Children' s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Mo, Xiumei, E-mail: xmm@dhu.edu.cn [State Key Laboratory of Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Shandong International Biotechnology Park Development Co., Ltd. (China)

    2017-01-01

    Tracheal injuries are one of major challenging issues in clinical medicine because of the poor intrinsic ability of tracheal cartilage for repair. Tissue engineering provides an alternative method for the treatment of tracheal defects by generating replacement tracheal structures. In this study, core-shell nanofibrous scaffold was fabricated to encapsulate bovine serum albumin & rhTGF-β3 (recombinant human transforming growth factor-β3) into the core of the nanofibers for tracheal cartilage regeneration. Characterization of the core-shell nanofibrous scaffold was carried out by scanning electron microscope (SEM), transmission electron microscope (TEM), laser scanning confocal microscopy (LSCM), and tensile mechanical test. The rhTGF-β3 released from the scaffolds in a sustained and stable manner for about 2 months. The bioactivity of released rhTGF-β3 was evaluated by its effect on the synthesis of type II collagen (COL2) and glycosaminoglycans (GAGs) by chondrocytes. The results suggested that its bioactivity was retained during release process. The proliferation and morphology analyses of mesenchymal stems cells derived from Wharton's jelly of human umbilical cord (WMSCs) indicated the good biocompatibility of the fabricated nanofibrous scaffold. Meanwhile, the chondrogenic differentiation of WMSCs cultured on core-shell nanofibrous scaffold was evaluated by real-time qPCR and histological staining. The results suggested that the core-shell nanofibrous scaffold with rhTGF-β3 could promote the chondrogenic differentiation ability of WMSCs. Therefore, WMSCs could be a promising seed cells in the construction of tissue-engineered tracheal cartilage. Overall, the core-shell nanofibrous scaffold could be an effective delivery system for rhTGF-β3 and served as a promising tissue engineered scaffold for tracheal cartilage regeneration. - Highlights: • rhTGF-β3 could be encapsulated into core-shell nanofibers via electrospinning. • rhTGF-β3 could release

  3. In-vivo study and histological examination of laser reshaping of cartilage

    Science.gov (United States)

    Sviridov, Alexander P.; Sobol, Emil N.; Bagratashvili, Victor N.; Omelchenko, Alexander I.; Ovchinnikov, Yuriy M.; Shekhter, Anatoliy B.; Svistushkin, Valeriy M.; Shinaev, Andrei A.; Nikiforova, G.; Jones, Nicholas

    1999-06-01

    The results of recent study of cartilage reshaping in vivo are reported. The ear cartilage of piglets of 8-12 weeks old have been reshaped in vivo using the radiation of a holmium laser. The stability of the shape and possible side effects have been examined during four months. Histological investigation shown that the healing of irradiated are could accompany by the regeneration of ear cartilage. Finally, elastic type cartilage has been transformed into fibrous cartilage or cartilage of hyaline type.

  4. Fine-tuning Cartilage Tissue Engineering by Applying Principles from Embryonic Development

    OpenAIRE

    Hellingman, Catharine

    2012-01-01

    textabstractCartilage has a very poor capacity for regeneration in vivo. In head and neck surgery cartilage defects are usually reconstructed with autologous cartilage from for instance the external ear or the ribs. Cartilage tissue engineering may be a promising alternative to supply tissue for cartilage reconstructions in otorhinolaryngology as well as in plastic surgery and orthopaedics. The aim of this thesis is to find new tools by which cartilage tissue engineering can be better control...

  5. Skeletal Muscle Regeneration, Repair and Remodelling in Aging: The Importance of Muscle Stem Cells and Vascularization.

    Science.gov (United States)

    Joanisse, Sophie; Nederveen, Joshua P; Snijders, Tim; McKay, Bryon R; Parise, Gianni

    2017-01-01

    Sarcopenia is the age-related loss of skeletal muscle mass and strength. Ultimately, sarcopenia results in the loss of independence, which imposes a large financial burden on healthcare systems worldwide. A critical facet of sarcopenia is the diminished ability for aged muscle to regenerate, repair and remodel. Over the years, research has focused on elucidating underlying mechanisms of sarcopenia and the impaired ability of muscle to respond to stimuli with aging. Muscle-specific stem cells, termed satellite cells (SC), play an important role in maintaining muscle health throughout the lifespan. It is well established that SC are essential in skeletal muscle regeneration, and it has been hypothesized that a reduction and/or dysregulation of the SC pool, may contribute to accelerated loss of skeletal muscle mass that is observed with advancing age. The preservation of skeletal muscle tissue and its ability to respond to stimuli may be impacted by reduced SC content and impaired function observed with aging. Aging is also associated with a reduction in capillarization of skeletal muscle. We have recently demonstrated that the distance between type II fibre-associated SC and capillaries is greater in older compared to younger adults. The greater distance between SC and capillaries in older adults may contribute to the dysregulation in SC activation ultimately impairing muscle's ability to remodel and, in extreme circumstances, regenerate. This viewpoint will highlight the importance of optimal SC activation in addition to skeletal muscle capillarization to maximize the regenerative potential of skeletal muscle in older adults. © 2016 S. Karger AG, Basel.

  6. Slowing of axonal regeneration is correlated with increased axonal viscosity during aging

    Directory of Open Access Journals (Sweden)

    Heidemann Steven R

    2010-10-01

    Full Text Available Abstract Background As we age, the speed of axonal regeneration declines. At the biophysical level, why this occurs is not well understood. Results To investigate we first measured the rate of axonal elongation of sensory neurons cultured from neonatal and adult rats. We found that neonatal axons grew 40% faster than adult axons (11.5 µm/hour vs. 8.2 µm/hour. To determine how the mechanical properties of axons change during maturation, we used force calibrated towing needles to measure the viscosity (stiffness and strength of substrate adhesion of neonatal and adult sensory axons. We found no significant difference in the strength of adhesions, but did find that adult axons were 3 times intrinsically stiffer than neonatal axons. Conclusions Taken together, our results suggest decreasing axonal stiffness may be part of an effective strategy to accelerate the regeneration of axons in the adult peripheral nervous system.

  7. Hyaline cartilage calcification of the first metatarsophalangeal joint is associated with osteoarthritis but independent of age and BMI.

    Science.gov (United States)

    Hubert, Jan; Hawellek, Thelonius; Hischke, Sandra; Bertrand, Jessica; Krause, Matthias; Püschel, Klaus; Rüther, Wolfgang; Niemeier, Andreas

    2016-11-15

    Hyaline cartilage calcification (CC) is associated with osteoarthritis (OA) in hip and knee joints. The first metatarsophalangeal joint (1 st MTPJ) is frequently affected by OA, but it is unclear if CC occurs in the 1 st MTPJ. The aim of the present study was to analyze the prevalence of CC of the 1 st MTPJ in the general population by high-resolution digital contact radiography (DCR) and to determine its association with histological OA severity, age and body mass index (BMI). 168 metatarsal heads of 84 donors (n = 47 male, n = 37 female; mean age 62.73 years, SD ±18.8, range 20-93) were analyzed by DCR for the presence of CC. Histological OA grade (hOA) by OARSI was analyzed in the central load-bearing zone of the first metatarsal head (1 st MH). Structural equation modeling (SEM) was performed to analyze the interrelationship between CC, hOA, age and BMI. The prevalence of CC of 1 st MH was 48.8 % (41/84) (95 %-CI [37.7 %, 60.0 %]), independent of the affected side (p = 0.42), gender (p = 0.41) and BMI (p = 0.51). The mean amount of CC of one MH correlated significantly with that of the contralateral side (r s  = 0.4, 95 %-CI [0.26, 0.52], p cartilage area) of the MH correlated significantly with the severity of hOA (r s  = 0.51, 95 %-CI [0.32, 0.65], p studies.

  8.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  9. The effect of aging on efferent nerve fibers regeneration in mice.

    Science.gov (United States)

    Verdú, E; Butí, M; Navarro, X

    1995-10-23

    This study evaluates the influence of aging on nerve regeneration and reinnervation of target organs in mice aged 2, 6, 9, 12, 18 and 24 months. In animals of each age group the sciatic nerve was subjected to crush, section or section and suture. Reinnervation of plantar muscles and sweat glands (SG) was evaluated over three months after operation by functional methods. Reappearance of SG secretion and motor responses occurred slightly earlier in young than older mice. The degree of motor and sudomotor reinnervation, with respect to preoperative control values, was also significantly higher in young than old animals. The differences were more pronounced after 12 months of age. The degree of recovery progressively decreased with the severity of the lesion, differences being more marked in older mice. Neurorraphy improved recovery, comparatively more in older than in young mice. These results indicate that, after injuries of peripheral nerves, axonal regeneration and reinnervation are maintained throughout life, but tend to be more delayed and slightly less effective with aging.

  10. Fine-tuning Cartilage Tissue Engineering by Applying Principles from Embryonic Development

    NARCIS (Netherlands)

    C.A. Hellingman (Catharine)

    2012-01-01

    textabstractCartilage has a very poor capacity for regeneration in vivo. In head and neck surgery cartilage defects are usually reconstructed with autologous cartilage from for instance the external ear or the ribs. Cartilage tissue engineering may be a promising alternative to supply tissue for

  11. Processes of hydration aging of superconducting ceramics and problem of regeneration of properties

    International Nuclear Information System (INIS)

    Komarov, A.V.; Popov, V.P.; Tikhonov, P.A.

    1989-01-01

    The process of hydration aging (distilled water, saturated water vapors) of YBa 2 Cu 3 O 6.5+x specimens with T s of about 95 K was studied at 55 deg C and water vapors pressure of 119 mmHg. It is established that depending on exposure time and saturated vapors pressure, water affects electric properties of yttrium-barium ceramics with different degree of the effect reversibility. Valuable regeneration of the characteristics can occur only when the hydration process has not led to changes in the phase composition of the material. The mechanism of interaction between cermaics and water is given

  12. Cellular and Acellular Approaches for Cartilage Repair

    Science.gov (United States)

    2015-01-01

    There are several choices of cells to use for cartilage repair. Cells are used as internal or external sources and sometimes in combination. In this article, an analysis of the different cell choices and their use and potential is provided. Embryonic cartilage formation is of importance when finding more about how to be able to perfect cartilage repair. Some suggestions for near future research based on up-to-date knowledge on chondrogenic cells are given to hopefully stimulate more studies on the final goal of cartilage regeneration. PMID:27340516

  13. Polymer Formulations for Cartilage Repair

    Energy Technology Data Exchange (ETDEWEB)

    Gutowska, Anna; Jasionowski, Marek; Morris, J. E.; Chrisler, William B.; An, Yuehuei H.; Mironov, V.

    2001-05-15

    Regeneration of destroyed articular cartilage can be induced by transplantation of cartilage cells into a defect. The best results are obtained with the use of autologus cells. However, obtaining large amounts of autologus cartilage cells causes a problem of creating a large cartilage defect in a donor site. Techniques are currently being developed to harvest a small number of cells and propagate them in vitro. It is a challenging task, however, due to the fact that ordinarily, in a cell culture on flat surfaces, chondrocytes do not maintain their in vivo phenotype and irreversibly diminish or cease the synthesis of aggregating proteoglycans. Therefore, the research is continuing to develop culture conditions for chondrocytes with the preserved phenotype.

  14. In vitro aging of mineralized collagen-based composite as guided tissue regeneration membrane

    Energy Technology Data Exchange (ETDEWEB)

    Pan, S.X. [Department of Prothodontics, School of Stomatology, Peking University, Beijing 100875 (China)]. E-mail: sx_pan@sina.com; Li, Y. [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Feng, H.L. [Department of Prothodontics, School of Stomatology, Peking University, Beijing 100875 (China); Bai, W. [Department of Prothodontics, School of Stomatology, Peking University, Beijing 100875 (China); Gu, Y.Y. [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2006-05-15

    The technique of guided tissue regeneration (GTR) has been developed for the regeneration of periodontal tissues, bone around natural teeth and dental implants. The aim of this study is to investigate the biodegradability and mechanic behavior of a novel mineralized nano-hydroxyapatite/collagen/poly (lactic acid) (nHAC/PLA) composite as GTR membrane in vitro. The elastic modulus and maximum tensile strength of GTR film samples with different nHAC/PLA ratio were measured to get an optimal nHAC/PLA ratio. Thermogravimetric analysis was conducted to evaluate the change of the inorganic component in the samples during the process of in vitro aging. Morphology of samples was checked by using scanning electron microscopy. On the basis of the above results, it can be concluded that the GTR membranes maintained integrity and the original appearance throughout the 1-month in vitro aging. There is an active dissolution and deposition process of crystals which is propitious to the bone formation on the surface of the composite membrane. The optimal nHAC/PLA ratio of the novel membrane is 0.4:1. For a longer period of bone repair, PLA with higher molecular weight should be chosen as the scaffold for the GTR membrane.

  15. Tissue engineering of cartilages using biomatrices

    DEFF Research Database (Denmark)

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

    2008-01-01

    and age-related degenerative diseases can all lead to cartilage loss; however, the low cell density and very limited self-renewal capacity of cartilage necessitate the development of effective therapeutic repair strategies for this tissue. The ontogeny of the chondrocyte, which is the cell that provides...... the biosynthetic machinery for all the component parts of cartilage, is discussed, since an understanding of cartilage development is central to the maintenance of a chondrocytic phenotype in any strategy aiming to produce a replacement cartilage. A plethora of matrices have been developed for cartilage...

  16. Supporting Biomaterials for Articular Cartilage Repair

    Science.gov (United States)

    Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

    2012-01-01

    Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

  17. Age- and gender-related characteristics of the pubic symphysis and triradiate cartilage in pediatric computed tomography

    International Nuclear Information System (INIS)

    Bayer, Joerg; Suedkamp, Norbert P.; Reising, Kilian; Neubauer, Jakob; Saueressig, Ulrich

    2016-01-01

    There is little information on the pubic symphysis' normal CT appearance in children. We sought to generate age-, gender- and maturity-related symphyseal width appearances in CT scans. Pelvic CT scans performed for any reason during a 6-year period in patients younger than 18 years were retrospectively analyzed. The symphysis width was measured in the axial plane and the triradiate cartilage was classified as open or closed. Four hundred twenty-seven CT scans were evaluated and 350 remained for analysis. Age- and gender-related measurements of the symphysis width are illustrated on various centile graphs. When grouping children by age in years 0-6, 7-11, 12-15 and 16-17, mean (standard deviation) symphysis width was 5.4 mm (0.9), 5.3 mm (1.1), 4.1 mm (1.1) and 3.5 mm (1.0), respectively, in girls and 5.9 mm (1.3), 5.4 mm (1.2), 5.2 mm (1.1) and 4.0 mm (1.0), respectively, in boys. Boys and girls were significantly different in the age groups 12-15 years (P<0.001) and 16-17 years (P=0.04). In the mature pelvis, the symphyseal gap is significantly (P<0.001) shorter in both genders, and in girls compared to boys (P=0.04). The pubic symphysis width in children differs according to age, gender and maturity. The reference values published herein may help detect symphyseal injury. (orig.)

  18. Age- and gender-related characteristics of the pubic symphysis and triradiate cartilage in pediatric computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Bayer, Joerg; Suedkamp, Norbert P.; Reising, Kilian [Medical Centre -University of Freiburg, Department of Orthopedics and Trauma Surgery, Freiburg (Germany); Neubauer, Jakob [Medical Centre - University of Freiburg, Department of Radiology, Freiburg (Germany); Saueressig, Ulrich [Kreiskrankenhaus Emmendingen, Department of Radiology, Emmendingen (Germany)

    2016-11-15

    There is little information on the pubic symphysis' normal CT appearance in children. We sought to generate age-, gender- and maturity-related symphyseal width appearances in CT scans. Pelvic CT scans performed for any reason during a 6-year period in patients younger than 18 years were retrospectively analyzed. The symphysis width was measured in the axial plane and the triradiate cartilage was classified as open or closed. Four hundred twenty-seven CT scans were evaluated and 350 remained for analysis. Age- and gender-related measurements of the symphysis width are illustrated on various centile graphs. When grouping children by age in years 0-6, 7-11, 12-15 and 16-17, mean (standard deviation) symphysis width was 5.4 mm (0.9), 5.3 mm (1.1), 4.1 mm (1.1) and 3.5 mm (1.0), respectively, in girls and 5.9 mm (1.3), 5.4 mm (1.2), 5.2 mm (1.1) and 4.0 mm (1.0), respectively, in boys. Boys and girls were significantly different in the age groups 12-15 years (P<0.001) and 16-17 years (P=0.04). In the mature pelvis, the symphyseal gap is significantly (P<0.001) shorter in both genders, and in girls compared to boys (P=0.04). The pubic symphysis width in children differs according to age, gender and maturity. The reference values published herein may help detect symphyseal injury. (orig.)

  19. Financial Performance of Mixed-Age Naturally Regenerated Loblolly-Hardwood Stands in the South Central United States

    Science.gov (United States)

    Ronald Raunikar; Joseph Buongiorno; Jeffrey P. Prestemon; Karen Lee Abt

    2000-01-01

    To estimate the financial performance of a natural mixed species and mixed-age management in the loblolly-pine forest type, we examined 991 FIA plots in the south central states. The plots were of the loblolly pine forest type, mixed-age, and had been regenerated naturally. We gauged the financial performance of each plot from the equivalent annual income (EAI)...

  20. Age variations in the properties of human tibial trabecular bone and cartilage

    DEFF Research Database (Denmark)

    Ding, Ming

    2000-01-01

    , such as apparent, apparent ash and collagen densities of human tibial trabecular bone have significant relationships with age. Tissue density and mineral concentration remain constant throughout life. Trabecular bone is tougher in the younger age, i.e. fracture requires more energy. Collagen density was the single......Initiated and motivated by clinical and scientific problems such as age-related bone fracture, prosthetic loosening, bone remodeling, and degenerative bone diseases, much significant research on the properties of trabecular bone has been carried out over the last two decades. This work has mainly...... focused on the central vertebral trabecular bone, while little is known about age-related changes in the properties of human peripheral (tibial) trabecular bone. Knowledge of the properties of peripheral (tibial) trabecular bone is of major importance for the understanding of degenerative diseases...

  1. β-Cell dedifferentiation, reduced duct cell plasticity, and impaired β-cell mass regeneration in middle-aged rats.

    Science.gov (United States)

    Téllez, Noèlia; Vilaseca, Marina; Martí, Yasmina; Pla, Arturo; Montanya, Eduard

    2016-09-01

    Limitations in β-cell regeneration potential in middle-aged animals could contribute to the increased risk to develop diabetes associated with aging. We investigated β-cell regeneration of middle-aged Wistar rats in response to two different regenerative stimuli: partial pancreatectomy (Px + V) and gastrin administration (Px + G). Pancreatic remnants were analyzed 3 and 14 days after surgery. β-Cell mass increased in young animals after Px and was further increased after gastrin treatment. In contrast, β-cell mass did not change after Px or after gastrin treatment in middle-aged rats. β-Cell replication and individual β-cell size were similarly increased after Px in young and middle-aged animals, and β-cell apoptosis was not modified. Nuclear immunolocalization of neurog3 or nkx6.1 in regenerative duct cells, markers of duct cell plasticity, was increased in young but not in middle-aged Px rats. The pancreatic progenitor-associated transcription factors neurog3 and sox9 were upregulated in islet β-cells of middle-aged rats and further increased after Px. The percentage of chromogranin A+/hormone islet cells was significantly increased in the pancreases of middle-aged Px rats. In summary, the potential for compensatory β-cell hyperplasia and hypertrophy was retained in middle-aged rats, but β-cell dedifferentiation and impaired duct cell plasticity limited β-cell regeneration. Copyright © 2016 the American Physiological Society.

  2. 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.

  3. Distal Regeneration Involves the Age Dependent Activity of Branchial Sac Stem Cells in the Ascidian Ciona intestinalis.

    Science.gov (United States)

    Jeffery, William R

    2015-02-01

    Tunicates have high capacities for regeneration but the underlying mechanisms and their relationship to life cycle progression are not well understood. Here we investigate the regeneration of distal structures in the ascidian tunicate Ciona intestinalis . Analysis of regenerative potential along the proximal-distal body axis indicated that distal organs, such as the siphons, their pigmented sensory organs, and the neural complex, could only be replaced from body fragments containing the branchial sac. Distal regeneration involves the formation of a blastema composed of cells that undergo cell proliferation prior to differentiation and cells that differentiate without cell proliferation. Both cell types originate in the branchial sac and appear in the blastema at different times after distal injury. Whereas the branchial sac stem cells are present in young animals, they are depleted in old animals that have lost their regeneration capacity. Thus Ciona adults contain a population of age-related stem cells located in the branchial sac that are a source of precursors for distal body regeneration.

  4. Biological aspects of tissue-engineered cartilage.

    Science.gov (United States)

    Hoshi, Kazuto; Fujihara, Yuko; Yamawaki, Takanori; Harai, Motohiro; Asawa, Yukiyo; Hikita, Atsuhiko

    2018-04-01

    Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential. In this paper, we reviewed recent trends of cartilage tissue engineering in clinical practice, summarized experimental findings on cellular and matrix changes during the cartilage regeneration, and discussed the importance of further studies on biological aspects of tissue-engineered cartilage, especially by the histological and the morphological methods.

  5. Effect of histone deacetylase inhibitor, trichostatin A, on cartilage ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research June 2017; 16 (6): 1253-1257 ... Conclusion: Treatment with trichostatin A, an HDAC inhibitor, enhances cartilage regeneration in rabbit ..... deacetylase activity in rheumatoid arthritis and asthma.

  6. 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.

  7. Role of Cartilage Forming Cells in Regenerative Medicine for Cartilage Repair

    OpenAIRE

    Sun, Lin; Reagan, Michaela R.; Kaplan, David L.

    2010-01-01

    Lin Sun1, Michaela R Reagan2, David L Kaplan1,21Department of Chemical and Biological Engineering, 2Department of Biomedical Engineering, Tufts University, Medford, MA, USAAbstract: Currently, cartilage repair remains a major challenge for researchers and physicians due to its limited healing capacity. Cartilage regeneration requires suitable cells; these must be easily obtained and expanded, able to produce hyaline matrix with proper mechanical properties, and demonstrate sustained integrati...

  8. Effect of Age-Related Cartilage Turnover on Serum C-Telopeptide of Collagen Type II and Osteocalcin Levels in Growing Rabbits with and without Surgically Induced Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Chung-Cheng Huang

    2014-01-01

    Full Text Available This study aims to determine the effect of age-related cartilage turnover on the serum C-telopeptide of type II collagen (CTX-II and osteocalcin (OC levels in growing rabbits with and without surgically induced osteoarthritis. Twenty-four New Zealand male 3-month-old rabbits were randomized into three operated groups (n = 6 per group, with surgically induced osteroarthritis in the right knee; after blood sampling, the knees were harvested following euthanization at 2, 3, and 6 months after surgery and a control group (n = 6, blood samples were obtained monthly between 3 and 15 months. Histomorphologically, the medial femoral condyles, particularly the central parts, harbored the most severe osteoarthritic changes among the operated rabbits. The serum levels of CTX-II and OC decreased in the controls from 3 to 11 months and then remained stable. No significant differences in the serum CTX-II and OC levels between the osteoarthritic rabbits and controls were observed. The osteoarthritic-to-normal ratios (ONRs, the ratios of serum CTX-II or OC levels in osteoarthritic rabbits to those of the controls at same ages enabled an overall assessment of osteoarthritis and age-related cartilage turnover. Elevated CTX-II ONRs were observed in rabbits with mild to advanced osteoarthritis. However, the OC ONRs were unhelpful in assessing osteoarthritic growing rabbits.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  10. Comparison of friction and wear of articular cartilage on different length scales.

    Science.gov (United States)

    Kienle, Sandra; Boettcher, Kathrin; Wiegleb, Lorenz; Urban, Joanna; Burgkart, Rainer; Lieleg, Oliver; Hugel, Thorsten

    2015-09-18

    The exceptional tribological properties of articular cartilage are still far from being fully understood. Articular cartilage is able to withstand high loads and provide exceptionally low friction. Although the regeneration abilities of the tissue are very limited, it can last for many decades. These biomechanical properties are realized by an interplay of different lubrication and wear protection mechanisms. The deterioration of cartilage due to aging or injury leads to the development of osteoarthritis. A current treatment strategy focuses on supplementing the intra-articular fluid with a saline solution containing hyaluronic acid. In the work presented here, we investigated how changing the lubricating fluid affects friction and wear of articular cartilage, focusing on the boundary and mixed lubrication as well as interstitial fluid pressurization mechanisms. Different length and time scales were probed by atomic force microscopy, tribology and profilometry. We compared aqueous solutions with different NaCl concentrations to a viscosupplement containing hyaluronic acid (HA). In particular, we found that the presence of ions changes the frictional behavior and the wear resistance. In contrast, hyaluronic acid showed no significant impact on the friction coefficient, but considerably reduced wear. This study confirms the previous notion that friction and wear are not necessarily correlated in articular cartilage tribology and that the main role of HA might be to provide wear protection for the articular surface. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. 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

  12. 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

  13. From gristle to chondrocyte transplantation: treatment of cartilage injuries.

    Science.gov (United States)

    Lindahl, Anders

    2015-10-19

    This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. © 2015 The Author(s).

  14. From gristle to chondrocyte transplantation: treatment of cartilage injuries

    Science.gov (United States)

    Lindahl, Anders

    2015-01-01

    This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. PMID:26416680

  15. Allogenic lyophilized cartilage grafts for craniomaxillofacial reconstruction

    International Nuclear Information System (INIS)

    Pill Hoon Choung

    1999-01-01

    Allogenic lyophilized cartilages were made in our clinic after Sailer methods and some modification. In our clinic, we have used allogenic cartilage grafts on 102 defects of craniomaxillofacial area; 1) for defects from cyst or ameloblastoma, 2) for lack of continuity of the mandible, 3) for rhinoplasty, 4) for paranasal augmentation, 5) for augmentation genioplasty, 6) for reconstruction of orbital floor, 7) for oroantral fistula, 8) for temporal augmentation, 9) for TMJ surgery 10) for condyle defect as a costochondral graft, 11) for filling of tooth socket and alveolus augmentation,12) for correction or orbital height and 13) for guided bone regeneration in peripheral implant. The types of lyophilized cartilage used were chip, sheet and block types developed by freeze-dried methods. Some grafts showed change of ossification, in which case we could perform implant on it. We have good results on reconstruction of craniomaxillofacial defects. Allogenic cartilage have advantages such as 1) it has no immune reaction clinically, 2) it is more tolerable to infection than that of autogenous cartilage, 3) it has character of less resorption which require no over correction, 4) it is easy to manipulate contouring, and 5) it has possibility of undergoing ossification. Allogenic cartilage has been considered as good substitutes for bone. The author would like to report the results on 102 allogenic cartilage have

  16. Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

    Science.gov (United States)

    Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

    2015-02-01

    Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. The Akt/mTOR pathway: Data comparing young and aged mice with leucine supplementation at the onset of skeletal muscle regeneration

    Directory of Open Access Journals (Sweden)

    Richard A. Perry, Jr.

    2016-09-01

    Full Text Available The data described herein is related to the article “Differential Effects of Leucine Supplementation in Young and Aged Mice at the Onset of Skeletal Muscle Regeneration” [1]. Aging is associated with a decreased ability of skeletal muscle to regenerate following injury. Leucine supplementation has been extensively shown, in young subjects, to promote protein synthesis during regeneration; however, the effects of leucine supplementation on the Akt/mTOR pathway in aged mice at the onset of muscle regeneration are not fully elucidated. In this article, we present data on the Akt/mTOR protein synthesis pathway at the onset of muscle regeneration in young and aged C57BL/6J mice that are and are not receiving leucine supplementation. More specifically, protein content of total Akt, mTOR, p70S6K and 4EBP-1 are presented. Additionally, we provide relative (phosphorylated:total protein content comparisons of these targets as they present themselves in young and aged mice who have neither been injured nor received leucine supplementation. Lastly, markers of atrophy (FoxO1/O3, MuRF-1, Atrogin-1 are also reported in these young and aged control groups. Keywords: MTOR, Skeletal muscle, Regeneration, Leucine supplementation, Aging

  18. Mechanical properties of hyaline and repair cartilage studied by nanoindentation.

    Science.gov (United States)

    Franke, O; Durst, K; Maier, V; Göken, M; Birkholz, T; Schneider, H; Hennig, F; Gelse, K

    2007-11-01

    Articular cartilage is a highly organized tissue that is well adapted to the functional demands in joints but difficult to replicate via tissue engineering or regeneration. Its viscoelastic properties allow cartilage to adapt to both slow and rapid mechanical loading. Several cartilage repair strategies that aim to restore tissue and protect it from further degeneration have been introduced. The key to their success is the quality of the newly formed tissue. In this study, periosteal cells loaded on a scaffold were used to repair large partial-thickness cartilage defects in the knee joint of miniature pigs. The repair cartilage was analyzed 26 weeks after surgery and compared both morphologically and mechanically with healthy hyaline cartilage. Contact stiffness, reduced modulus and hardness as key mechanical properties were examined in vitro by nanoindentation in phosphate-buffered saline at room temperature. In addition, the influence of tissue fixation with paraformaldehyde on the biomechanical properties was investigated. Although the repair process resulted in the formation of a stable fibrocartilaginous tissue, its contact stiffness was lower than that of hyaline cartilage by a factor of 10. Fixation with paraformaldehyde significantly increased the stiffness of cartilaginous tissue by one order of magnitude, and therefore, should not be used when studying biomechanical properties of cartilage. Our study suggests a sensitive method for measuring the contact stiffness of articular cartilage and demonstrates the importance of mechanical analysis for proper evaluation of the success of cartilage repair strategies.

  19. [Evidence-based therapy for cartilage lesions in the knee - regenerative treatment options].

    Science.gov (United States)

    Proffen, B; von Keudell, A; Vavken, P

    2012-06-01

    The treatment of cartilage defects has seen a shift from replacement to regeneration in the last few years. The rationale behind this development is the improvement in the quality-of-care for the growing segment of young patients who are prone to arthroplasty complications because of their specific characteristics - young age, high level of activity, high demand for functionality. These days, two of the most popular regenerative treatments are microfracture and autologous chondrocyte implantation (ACI). Although these new options show promising results, no final algorithm for the treatment of cartilage lesions has been established as yet. The objective of this review is to describe and compare these two treatment options and to present an evidence-based treatment algorithm for focal cartilage defects. Microfracture is a cost-effective, arthroscopic one-stage procedure, in which by drilling of the subchondral plate, mesenchymal stem cells from the bone marrow migrate into the defect and rebuild the cartilage. ACI is a two-stage procedure in which first chondrocytes are harvested, expanded in cell culture and in a second open procedure reimplanted into the cartilage defect. Microfracture is usually used for focal cartilage defects osteophyte, and for the ACI patient, periosteal hypertrophy and the need for two procedures in ACI. Only a few studies provide detailed and evidence-based information on a comparative assessment. These studies, however, are showing widely similar clinical outcomes but better histological results for ACI, which are likely to translate into better long-term outcomes. Although evidence-based studies comparing microfracture and ACI have not found significant differences in the clinical outcome, the literature does show that choosing the treatment based on the size and characteristics of the osteochondral lesion might be beneficial. The American Association of Orthopedic Surgeons suggest that contained lesions < 4 cm2 should be treated by

  20. Imaging of articular cartilage

    Directory of Open Access Journals (Sweden)

    Bhawan K Paunipagar

    2014-01-01

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

  1. Osteoarthritic cartilage is more homogeneous than healthy cartilage

    DEFF Research Database (Denmark)

    Qazi, Arish A; Dam, Erik B; Nielsen, Mads

    2007-01-01

    it evolves as a consequence to disease and thereby can be used as a progression biomarker. MATERIALS AND METHODS: A total of 283 right and left knees from 159 subjects aged 21 to 81 years were scanned using a Turbo 3D T1 sequence on a 0.18-T MRI Esaote scanner. The medial compartment of the tibial cartilage...... sheet was segmented using a fully automatic voxel classification scheme based on supervised learning. From the segmented cartilage sheet, homogeneity was quantified by measuring entropy from the distribution of signal intensities inside the compartment. Each knee was examined by radiography...... of the region was evaluated by testing for overfitting. Three different regularization techniques were evaluated for reducing overfitting errors. RESULTS: The P values for separating the different groups based on cartilage homogeneity were 2 x 10(-5) (KL 0 versus KL 1) and 1 x 10(-7) (KL 0 versus KL >0). Using...

  2. 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.

  3. Imaging of cartilage repair procedures

    International Nuclear Information System (INIS)

    Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw

    2014-01-01

    The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts

  4. Cartilage constructs from human cord blood stem cells seeded in structurally-graded polycaprolactone scaffolds

    DEFF Research Database (Denmark)

    Munir, Samir; Koch, Thomas Gadegaard; Foldager, Casper Bindzus

    Cartilage is an avascular tissue incapable of regeneration. Current treatment modalities for joint cartilage injuries are inefficient in regenerating hyaline cartilage and often leads to the formation of fibrocartilage with undesirable mechanical properties. There is an increasing interest...... in investigating alternative treatments such as tissue engineering, which combines stem cells with scaffolds to produce cartilage in vitro for subsequent transplant. Previous studies have shown that chondrogenesis of induced stem cells is influenced by various growth factors, oxygen tensions and mechanical...... this novel SGS-PCL scaffold supports the chondrogenic differentiation of MLPCs will be interesting to evaluate since this scaffold possesses mechanical properties absent from other “soft” scaffolds currently being investigated for cartilage regeneration and implantation....

  5. 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.

  6. Articular cartilage explant culture; an appropriate in vitro system to compare osteoarthritic and normal human cartilage

    NARCIS (Netherlands)

    Lafeber, F. P.; Vander Kraan, P. M.; van Roy, J. L.; Huber-Bruning, O.; Bijlsma, J. W.

    1993-01-01

    Proteoglycan metabolism of normal and histologically mild to moderate osteoarthritic cartilage explants were studied. Explants were obtained from the human knee of donors aged over 40 years. Proteoglycan content, synthesis and release were very similar in normal cartilage obtained from donors with

  7. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    OpenAIRE

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain...

  8. Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies.

    Science.gov (United States)

    Veronesi, Francesca; Maglio, Melania; Tschon, Matilde; Aldini, Nicolò Nicoli; Fini, Milena

    2014-07-01

    Several therapeutic approaches have been developed to address hyaline cartilage regeneration, but to date, there is no universal procedure to promote the restoration of mechanical and functional properties of native cartilage, which is one of the most important challenges in orthopedic surgery. For cartilage tissue engineering, adult mesenchymal stem cells (MSCs) are considered as an alternative cell source to chondrocytes. Since little is known about adipose-derived mesenchymal stem cell (ADSC) cartilage regeneration potential, the aim of this review was to give an overview of in vivo studies about the chondrogenic potential and regeneration ability of culture-expanded ADSCs when implanted in heterotopic sites or in osteoarthritic and osteochondral defects. The review compares the different studies in terms of number of implanted cells and animals, cell harvesting sites, in vitro expansion and chondrogenic induction conditions, length of experimental time, defect dimensions, used scaffolds and post-explant analyses of the cartilage regeneration. Despite variability of the in vivo protocols, it seems that good cartilage formation and regeneration were obtained with chondrogenically predifferentiated ADSCs (1 × 10(7) cells for heterotopic cartilage formation and 1 × 10(6) cells/scaffold for cartilage defect regeneration) and polymeric scaffolds, even if many other aspects need to be clarified in future studies. © 2013 Wiley Periodicals, Inc.

  9. Aging impairs long-term hematopoietic regeneration after autologous stem cell transplantation

    NARCIS (Netherlands)

    Woolthuis, Carolien M; Mariani, Niccoló; Verkaik-Schakel, Rikst Nynke; Brouwers-Vos, Annet Z.; Schuringa, Jan Jacob; Vellenga, Edo; de Wolf, Joost T M; Huls, Gerwin

    Most of our knowledge of the effects of aging on the hematopoietic system comes from studies in animal models. In this study, to explore potential effects of aging on human hematopoietic stem and progenitor cells (HSPCs), we evaluated CD34(+) cells derived from young (<35 years) and old (>60 years)

  10. β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions

    NARCIS (Netherlands)

    D. Zwolanek (Daniela); M. Flicker (Magdalena); E. Kirstätter (Elisabeth); F. Zaucke (Frank); G.J.V.M. van Osch (Gerjo); R.G. Erben (Reinhold)

    2015-01-01

    textabstractMesenchymal stem cells (MSC) may have great potential for cell-based therapies of osteoarthritis. However, after injection in the joint, only few cells adhere to defective articular cartilage and contribute to cartilage regeneration. Little is known about the molecular mechanisms of MSC

  11. Nanoparticles for diagnostics and laser medical treatment of cartilage in orthopaedics

    Science.gov (United States)

    Baum, O. I.; Soshnikova, Yu. M.; Omelchenko, A. I.; Sobol, Emil

    2013-02-01

    Laser reconstruction of intervertebral disc (LRD) is a new technique which uses local, non-destructive laser irradiation for the controlled activation of regenerative processes in a targeted zone of damaged disc cartilage. Despite pronounced advancements of LRD, existing treatments may be substantially improved if laser radiation is absorbed near diseased and/or damaged regions in cartilage so that required thermomechanical stress and strain at chondrocytes may be generated and non-specific injury reduced or eliminated. The aims of the work are to study possibility to use nanoparticles (NPs) to provide spatial specificity for laser regeneration of cartilage. Two types of porcine joint cartilage have been impregnated with magnetite NPs: 1) fresh cartilage; 2) mechanically damaged cartilage. NPs distribution was studied using transition electron microscopy, dynamic light scattering and analytical ultracentrifugation techniques. Laser radiation and magnetic field have been applied to accelerate NPs impregnation. It was shown that NPs penetrate by diffusion into the mechanically damaged cartilage, but do not infiltrate healthy cartilage. Temperature dynamics in cartilage impregnated with NPs have been theoretically calculated and measurements using an IR thermo vision system have been performed. Laser-induced alterations of cartilage structure and cellular surviving have been studied for cartilage impregnated with NPs using histological and histochemical techniques. Results of our study suggest that magnetite NPs might be used to provide spatial specificity of laser regeneration. When damaged, the regions of cartilage impreganted with NPs have higher absorption of laser radiation than that for healthy areas. Regions containing NPs form target sites that can be used to generate laser-induced thermo mechanical stress leading to regeneration of cartilage of hyaline type.

  12. Articular cartilage: from formation to tissue engineering.

    Science.gov (United States)

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

    2016-05-26

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

  13. Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance

    Science.gov (United States)

    Boehme, Karen A.; Schleicher, Sabine B.; Rolauffs, Bernd

    2018-01-01

    Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC) in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA) at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC). PMID:29361725

  14. Ingestion of BioCell Collagen®, a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs

    Directory of Open Access Journals (Sweden)

    Schwartz SR

    2012-07-01

    Full Text Available Stephen R Schwartz,1 Joosang Park21International Research Services Inc, Port Chester, NY, USA; 2BioCell Technology, LLC, Newport Beach, CA, USAAbstract: Skin aging and its clinical manifestation is associated with altered molecular metabolism in the extracellular matrix of the dermis. In a pilot open-label study, we investigated the effect of a dietary supplement, BioCell Collagen® (BCC, which contains a naturally occurring matrix of hydrolyzed collagen type II and low-molecular-weight hyaluronic acid and chondroitin sulfate, in 26 healthy females who displayed visible signs of natural and photoaging in the face. Daily supplementation with 1 g of BCC for 12 weeks led to a significant reduction of skin dryness/scaling (76%, P = 0.002 and global lines/wrinkles (13.2%, P = 0.028 as measured by visual/tactile score. Additionally, a significant increase in the content of hemoglobin (17.7%, P = 0.018 and collagen (6.3%, P = 0.002 in the skin dermis was observed after 6 weeks of supplementation. At the end of the study, the increase in hemoglobin remained significant (15%, P = 0.008, while the increase in collagen content was maintained, but the difference from baseline was not significant (3.5%, P = 0.134. This study provides preliminary data suggesting that dietary supplementation with BCC elicits several physiological events which can be harnessed to counteract natural photoaging processes to reduce visible aging signs in the human face. A controlled study is necessary to verify these observations.Keywords: BioCell Collagen, chicken sternal cartilage extract, hydrolyzed collagen type II, low-molecular-weight hyaluronic acid, skin aging

  15. Cartilage tissue engineering: Role of mesenchymal stem cells along with growth factors & scaffolds

    Directory of Open Access Journals (Sweden)

    M B Gugjoo

    2016-01-01

    Full Text Available Articular cartilage injury poses a major challenge for both the patient and orthopaedician. Articular cartilage defects once formed do not regenerate spontaneously, rather replaced by fibrocartilage which is weaker in mechanical competence than the normal hyaline cartilage. Mesenchymal stem cells (MSCs along with different growth factors and scaffolds are currently incorporated in tissue engineering to overcome the deficiencies associated with currently available surgical methods and to facilitate cartilage healing. MSCs, being readily available with a potential to differentiate into chondrocytes which are enhanced by the application of different growth factors, are considered for effective repair of articular cartilage after injury. However, therapeutic application of MSCs and growth factors for cartilage repair remains in its infancy, with no comparative clinical study to that of the other surgical techniques. The present review covers the role of MSCs, growth factors and scaffolds for the repair of articular cartilage injury.

  16. Stem Cells and Gene Therapy for Cartilage Repair

    Directory of Open Access Journals (Sweden)

    Umile Giuseppe Longo

    2012-01-01

    Full Text Available Cartilage defects represent a common problem in orthopaedic practice. Predisposing factors include traumas, inflammatory conditions, and biomechanics alterations. Conservative management of cartilage defects often fails, and patients with this lesions may need surgical intervention. Several treatment strategies have been proposed, although only surgery has been proved to be predictably effective. Usually, in focal cartilage defects without a stable fibrocartilaginous repair tissue formed, surgeons try to promote a natural fibrocartilaginous response by using marrow stimulating techniques, such as microfracture, abrasion arthroplasty, and Pridie drilling, with the aim of reducing swelling and pain and improving joint function of the patients. These procedures have demonstrated to be clinically useful and are usually considered as first-line treatment for focal cartilage defects. However, fibrocartilage presents inferior mechanical and biochemical properties compared to normal hyaline articular cartilage, characterized by poor organization, significant amounts of collagen type I, and an increased susceptibility to injury, which ultimately leads to premature osteoarthritis (OA. Therefore, the aim of future therapeutic strategies for articular cartilage regeneration is to obtain a hyaline-like cartilage repair tissue by transplantation of tissues or cells. Further studies are required to clarify the role of gene therapy and mesenchimal stem cells for management of cartilage lesions.

  17. 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.

  18. Scaffold-assisted cartilage tissue engineering using infant chondrocytes from human hip cartilage.

    Science.gov (United States)

    Kreuz, P C; Gentili, C; Samans, B; Martinelli, D; Krüger, J P; Mittelmeier, W; Endres, M; Cancedda, R; Kaps, C

    2013-12-01

    Studies about cartilage repair in the hip and infant chondrocytes are rare. The aim of our study was to evaluate the use of infant articular hip chondrocytes for tissue engineering of scaffold-assisted cartilage grafts. Hip cartilage was obtained from five human donors (age 1-10 years). Expanded chondrocytes were cultured in polyglycolic acid (PGA)-fibrin scaffolds. De- and re-differentiation of chondrocytes were assessed by histological staining and gene expression analysis of typical chondrocytic marker genes. In vivo, cartilage matrix formation was assessed by histology after subcutaneous transplantation of chondrocyte-seeded PGA-fibrin scaffolds in immunocompromised mice. The donor tissue was heterogenous showing differentiated articular cartilage and non-differentiated tissue and considerable expression of type I and II collagens. Gene expression analysis showed repression of typical chondrocyte and/or mesenchymal marker genes during cell expansion, while markers were re-induced when expanded cells were cultured in PGA-fibrin scaffolds. Cartilage formation after subcutaneous transplantation of chondrocyte loaded PGA-fibrin scaffolds in nude mice was variable, with grafts showing resorption and host cell infiltration or formation of hyaline cartilage rich in type II collagen. Addition of human platelet rich plasma (PRP) to cartilage grafts resulted robustly in formation of hyaline-like cartilage that showed type II collagen and regions with type X collagen. These results suggest that culture of expanded and/or de-differentiated infant hip cartilage cells in PGA-fibrin scaffolds initiates chondrocyte re-differentiation. The heterogenous donor tissue containing immature chondrocytes bears the risk of cartilage repair failure in vivo, which may be possibly overcome by the addition of PRP. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  19. The role of laminins in cartilaginous tissues: from development to regeneration.

    Science.gov (United States)

    Sun, Y; Wang, T L; Toh, W S; Pei, M

    2017-07-21

    As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells) could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus) throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells' proliferation and chondrogenic differentiation. With this information, we hope to facilitate the understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.

  20. The role of laminins in cartilaginous tissues: from development to regeneration

    Directory of Open Access Journals (Sweden)

    Y Sun

    2017-07-01

    Full Text Available As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells’ proliferation and chondrogenic differentiation. With this information, we hope to facilitate the understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.

  1. Degeneration of osteoarthritis cartilage

    DEFF Research Database (Denmark)

    Jørgensen, Dan Richter

    of sensitive biomarkers for monitoring disease progression. This thesis investigates how subregional measures of cartilage thickness can be used to improve upon current imaging biomarkers. The first part of this investigation aims to discover discriminative areas in the cartilage using machine......-learning techniques specifically developed to take advantage of the spatial nature of the problem. The methods were evaluated on data from a longitudinal study where detailed cartilage thickness maps were quantified from magnetic resonance images. The results showed that focal differences in cartilage thickness may...... be relevant for both OA diagnosis and for prediction of future cartilage loss. The second part of the thesis investigates spatial patterns of longitudinal cartilage thickness changes in healthy and OA knees. Based on our findings, we propose a new, conceptually simple biomarker that embraces the heterogeneous...

  2. Thermosensitive hydrogels for 3D bioprinting of cartilage constructs

    NARCIS (Netherlands)

    Abbadessa, A.

    2017-01-01

    Tissue engineering (TE) aims to regenerate damaged tissues by the combined use of biomaterials and cells, often in presence of bioactive molecules, such as growth factors. Particularly for tissues with poor regenerative capacity, such as articular cartilage, TE approaches may lead to promising

  3. Effect of histone deacetylase inhibitor, trichostatin A, on cartilage ...

    African Journals Online (AJOL)

    Purpose: To evaluate the effect of histone deacetylase (HDAC) inhibitor, trichostatin A (TCA), on cartilage regeneration in a rabbit perichondrial graft model. Methods: Perichondrial grafts (20 × 20 mm2) were derived from the ears of New Zealand rabbits and transplanted onto the paravertebral muscle of the face of each ...

  4. Tissue engineering of functional articular cartilage : the current status

    NARCIS (Netherlands)

    Kock, L.M.; Donkelaar, van C.C.; Ito, K.

    2012-01-01

    Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The

  5. Cartilage T2 assessment: differentiation of normal hyaline cartilage and reparative tissue after arthroscopic cartilage repair in equine subjects.

    Science.gov (United States)

    White, Lawrence M; Sussman, Marshall S; Hurtig, Mark; Probyn, Linda; Tomlinson, George; Kandel, Rita

    2006-11-01

    To prospectively assess T2 mapping characteristics of normal articular cartilage and of cartilage at sites of arthroscopic repair, including comparison with histologic results and collagen organization assessed at polarized light microscopy (PLM). Study protocol was compliant with the Canadian Council on Animal Care Guidelines and approved by the institutional animal care committee. Arthroscopic osteochondral autograft transplantation (OAT) and microfracture arthroplasty (MFx) were performed in knees of 10 equine subjects (seven female, three male; age range, 3-5 years). A site of arthroscopically normal cartilage was documented in each joint as a control site. Joints were harvested at 12 (n = 5) and 24 (n = 5) weeks postoperatively and were imaged at 1.5-T magnetic resonance (MR) with a 10-echo sagittal fast spin-echo acquisition. T2 maps of each site (21 OAT harvest, 10 MFx, 12 OAT plug, and 10 control sites) were calculated with linear least-squares curve fitting. Cartilage T2 maps were qualitatively graded as "organized" (normal transition of low-to-high T2 signal from deep to superficial cartilage zones) or "disorganized." Quantitative mean T2 values were calculated for deep, middle, and superficial cartilage at each location. Results were compared with histologic and PLM assessments by using kappa analysis. T2 maps were qualitatively graded as organized at 20 of 53 sites and as disorganized at 33 sites. Perfect agreement was seen between organized T2 and histologic findings of hyaline cartilage and between disorganized T2 and histologic findings of fibrous reparative tissue (kappa = 1.0). Strong agreement was seen between organized T2 and normal PLM findings and between disorganized T2 and abnormal PLM findings (kappa = .92). Quantitative assessment of the deep, middle, and superficial cartilage, respectively, showed mean T2 values of 53.3, 58.6, and 54.9 msec at reparative fibrous tissue sites and 40.7, 53.6, and 61.6 msec at hyaline cartilage sites. A

  6. Hyperinnervation improves Xenopus laevis limb regeneration.

    Science.gov (United States)

    Mitogawa, Kazumasa; Makanae, Aki; Satoh, Akira

    2018-01-15

    Xenopus laevis (an anuran amphibian) shows limb regeneration ability between that of urodele amphibians and that of amniotes. Xenopus frogs can initiate limb regeneration but fail to form patterned limbs. Regenerated limbs mainly consist of cone-shaped cartilage without any joints or branches. These pattern defects are thought to be caused by loss of proper expressions of patterning-related genes. This study shows that hyperinnervation surgery resulted in the induction of a branching regenerate. The hyperinnervated blastema allows the identification and functional analysis of the molecules controlling this patterning of limb regeneration. This paper focuses on the nerve affects to improve Xenopus limb patterning ability during regeneration. The nerve molecules, which regulate limb patterning, were also investigated. Blastemas grown in a hyperinnervated forelimb upregulate limb patterning-related genes (shh, lmx1b, and hoxa13). Nerves projecting their axons to limbs express some growth factors (bmp7, fgf2, fgf8, and shh). Inputs of these factors to a blastema upregulated some limb patterning-related genes and resulted in changes in the cartilage patterns in the regenerates. These results indicate that additional nerve factors enhance Xenopus limb patterning-related gene expressions and limb regeneration ability, and that bmp, fgf, and shh are candidate nerve substitute factors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine.

    Science.gov (United States)

    Bukovsky, Antonin; Caudle, Michael R; Carson, Ray J; Gaytán, Francisco; Huleihel, Mahmoud; Kruse, Andrea; Schatten, Heide; Telleria, Carlos M

    2009-02-13

    The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders.

  8. One-Step Cartilage Repair Technique as a Next Generation of Cell Therapy for Cartilage Defects: Biological Characteristics, Preclinical Application, Surgical Techniques, and Clinical Developments.

    Science.gov (United States)

    Zhang, Chi; Cai, You-Zhi; Lin, Xiang-Jin

    2016-07-01

    To provide a comprehensive overview of the basic science rationale, surgical technique, and clinical outcomes of 1-step cartilage repair technique used as a treatment strategy for cartilage defects. A systematic review was performed in the main medical databases to evaluate the several studies concerning 1-step procedures for cartilage repair. The characteristics of cell-seed scaffolds, behavior of cells seeded into scaffolds, and surgical techniques were also discussed. Clinical outcomes and quality of repaired tissue were assessed using several standardized outcome assessment tools, magnetic resonance imaging scans, and biopsy histology. One-step cartilage repair could be divided into 2 types: chondrocyte-matrix complex (CMC) and autologous matrix-induced chondrogenesis (AMIC), both of which allow a simplified surgical approach. Studies with Level IV evidence have shown that 1-step cartilage repair techniques could significantly relieve symptoms and improve functional assessment (P studies clearly showed hyaline-like cartilage tissue in biopsy tissues by second-look arthroscopy. The 1-step cartilage repair technique, with its potential for effective, homogeneous distribution of chondrocytes and multipotent stem cells on the surface of the cartilage defect, is able to regenerate hyaline-like cartilage tissue, and it could be applied to cartilage repair by arthroscopy. Level IV, systematic review of Level II and IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  9. 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 < 0.01). Our results show that each type of cartilage has different structural features, which may significantly contribute to pathology when damaged. Our findings demonstrate that SHG microscopy holds potential as a clinically relevant diagnostic tool for imaging degenerative tissues or assessing wound repair following cartilage injury.

  10. Repair of full-thickness articular cartilage defect using stem cell-encapsulated thermogel.

    Science.gov (United States)

    Zhang, Yanbo; Zhang, Jin; Chang, Fei; Xu, Weiguo; Ding, Jianxun

    2018-07-01

    Cartilage defect repair by hydrogel-based tissue engineering is becoming one of the most potential treatment strategies. In this work, a thermogel of triblock copolymer poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) was prepared as scaffold of bone marrow mesenchymal stem cells (BMMSCs) for repair of full-thickness articular cartilage defect. At first, the copolymer solution showed a reversible sol-gel transition at physiological temperature range, and the mechanical properties of such thermogel were high enough to support the repair of cartilage. Additionally, excellent biodegradability and biocompatibility of the thermogel were demonstrated. By implanting the BMMSC-encapsulated thermogel into the full-thickness articular cartilage defect (5.0 mm in diameter and 4.0 mm in depth) in the rabbit, it was found that the regenerated cartilage integrated well with the surrounding normal cartilage and subchondral bone at 12 weeks post-surgery. The upregulated expression of glycosaminoglycan and type II collagen in the repaired cartilage, and the comparable biomechanical properties with normal cartilage suggested that the cell-encapsulated PLGA-PEG-PLGA thermogel had great potential in serving as the promising scaffold for cartilage regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Cryogenic regenerators

    International Nuclear Information System (INIS)

    Kush, P.; Joshi, S.C.; Thirumaleshwar, M.

    1986-01-01

    Importance of regenerators in cryogenic refrigerators is highlighted. Design aspects of regenerator are reviewed and the factors involved in the selection of regenerator material are enumerated. Various methods used to calculate the heat transfer coefficient and regenerator effectiveness are mentioned. Variation of effectiveness with various parameters is calculated by a computer programme using the ideal, Ackermann and Tipler formulae. Results are presented in graphical form. Listing of the computer programme is given in the Appendix. (author)

  12. Biomechanical signals guiding stem cell cartilage engineering: from molecular adaption to tissue functionality

    Directory of Open Access Journals (Sweden)

    Y Zhang

    2016-01-01

    Full Text Available In vivo cartilage is in a state of constant mechanical stimulation. It is therefore reasonable to deduce that mechanical forces play an important role in cartilage formation. Mechanical forces, such as compression, tension, and shear force, have been widely applied for cartilage engineering; however, relatively few review papers have summarized the influence of biomechanical signals on stem cell-based neo-cartilage formation and cartilage engineering in both molecular adaption and tissue functionality. In this review, we will discuss recent progress related to the influences of substrate elasticity on stem cell chondrogenic differentiation and elucidate the potential underlying mechanisms. Aside from active sensing and responding to the extracellular environment, stem cells also could respond to various external mechanical forces, which also influence their chondrogenic capacity; this topic will be updated along with associated signaling pathways. We expect that these different regimens of biomechanical signals can be utilized to boost stem cell-based cartilage engineering and regeneration.

  13. Distal regeneration involves the age dependent activity of branchial sac stem cells in the ascidian Ciona intestinalis

    Science.gov (United States)

    2014-01-01

    Abstract Tunicates have high capacities for regeneration but the underlying mechanisms and their relationship to life cycle progression are not well understood. Here we investigate the regeneration of distal structures in the ascidian tunicate Ciona intestinalis. Analysis of regenerative potential along the proximal−distal body axis indicated that distal organs, such as the siphons, their pigmented sensory organs, and the neural complex, could only be replaced from body fragments containing the branchial sac. Distal regeneration involves the formation of a blastema composed of cells that undergo cell proliferation prior to differentiation and cells that differentiate without cell proliferation. Both cell types originate in the branchial sac and appear in the blastema at different times after distal injury. Whereas the branchial sac stem cells are present in young animals, they are depleted in old animals that have lost their regeneration capacity. Thus Ciona adults contain a population of age‐related stem cells located in the branchial sac that are a source of precursors for distal body regeneration. PMID:25893097

  14. A cytochemical study of histones in the muscular cells of Triturus cristatus limbs in normal regeneration of limbs irradiated by X-rays, of irradiated limbs in which the regenerative power is restored by cartilage implants

    International Nuclear Information System (INIS)

    Desselle, J.-C.

    1976-01-01

    The muscular cells of regenerating limbs and of limbs in which regenerative power is restored, show an important decrease in the amount of cytophotometrically detected histones. This decrease is owing to the arginine rich fraction and to the lysine rich fraction. The muscular cells of irradiated limbs show a decrease in the amount of histones. This decrease is owing only to the arginine rich fraction and continues after the thirtieth day of irradiation and amputation [fr

  15. Influence of Structure and Composition on Dynamic Viscoelastic Property of Cartilaginous Tissue: Criteria for Classification between Hyaline Cartilage and Fibrocartilage Based on Mechanical Function

    Science.gov (United States)

    Miyata, Shogo; Tateishi, Tetsuya; Furukawa, Katsuko; Ushida, Takashi

    Recently, many types of methodologies have been developed to regenerate articular cartilage. It is important to assess whether the reconstructed cartilaginous tissue has the appropriate mechanical functions to qualify as hyaline (articular) cartilage. In some cases, the reconstructed tissue may become fibrocartilage and not hyaline cartilage. In this study, we determined the dynamic viscoelastic properties of these two types of cartilage by using compression and shear tests, respectively. Hyaline cartilage specimens were harvested from the articular surface of bovine knee joints and fibrocartilage specimens were harvested from the meniscus tissue of the same. The results of this study revealed that the compressive energy dissipation of hyaline cartilage showed a strong dependence on testing frequency at low frequencies, while that of fibrocartilage did not. Therefore, the compressive energy dissipation that is indicated by the loss tangent could become the criterion for the in vitro assessment of the mechanical function of regenerated cartilage.

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

    Science.gov (United States)

    Nakagawa, Yusuke; Muneta, Takeshi; Otabe, Koji; Ozeki, Nobutake; Mizuno, Mitsuru; Udo, Mio; Saito, Ryusuke; Yanagisawa, Katsuaki; Ichinose, Shizuko; Koga, Hideyuki; Tsuji, Kunikazu; Sekiya, Ichiro

    2016-01-01

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

  17. Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

    Science.gov (United States)

    Fellows, Christopher R.; Matta, Csaba; Zakany, Roza; Khan, Ilyas M.; Mobasheri, Ali

    2016-01-01

    Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue. PMID:28066501

  18. Adipose, Bone Marrow and Synovial Joint-derived Mesenchymal Stem Cells for Cartilage Repair

    Directory of Open Access Journals (Sweden)

    Christopher Fellows

    2016-12-01

    Full Text Available Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple ‘one size fits all’, but more likely an array of solutions that need to applied systematically to achieve regeneration of a biomechanically competent repair tissue.

  19. MRI of the cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Imhof, H.; Noebauer-Huhmann, I.-M.; Krestan, C.; Gahleitner, A.; Marlovits, S.; Trattnig, S. [Department of Osteology, Universitaetklinik fuer Radiodiagnostik, AKH-Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Sulzbacher, I. [Universitaetsklinik fuer Pathologie Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

    2002-11-01

    With the introduction of fat-suppressed gradient-echo and fast spin-echo (FSE) sequences in clinical routine MR visualization of the hyaline articular cartilage is routinely possible in the larger joints. While 3D gradient-echo with fat suppression allows exact depiction of the thickness and surface of cartilage, FSE outlines the normal and abnormal internal structures of the hyaline cartilage; therefore, both sequences seem to be necessary in a standard MRI protocol for cartilage visualization. In diagnostically ambiguous cases, in which important therapeutic decisions are required, direct MR arthrography is the established imaging standard as an add-on procedure. Despite the social impact and prevalence, until recent years there was a paucity of knowledge about the pathogenesis of cartilage damage. With the introduction of high-resolution MRI with powerful surface coils and fat-suppression techniques, visualization of the articular cartilage is now routinely possible in many joints. After a short summary of the anatomy and physiology of the hyaline cartilage, the different MR imaging methods are discussed and recommended standards are suggested. (orig.)

  20. 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.

  1. In Vivo Evaluation of a Novel Oriented Scaffold-BMSC Construct for Enhancing Full-Thickness Articular Cartilage Repair in a Rabbit Model.

    Directory of Open Access Journals (Sweden)

    Shuaijun Jia

    Full Text Available Tissue engineering (TE has been proven usefulness in cartilage defect repair. For effective cartilage repair, the structural orientation of the cartilage scaffold should mimic that of native articular cartilage, as this orientation is closely linked to cartilage mechanical functions. Using thermal-induced phase separation (TIPS technology, we have fabricated an oriented cartilage extracellular matrix (ECM-derived scaffold with a Young's modulus value 3 times higher than that of a random scaffold. In this study, we test the effectiveness of bone mesenchymal stem cell (BMSC-scaffold constructs (cell-oriented and random in repairing full-thickness articular cartilage defects in rabbits. While histological and immunohistochemical analyses revealed efficient cartilage regeneration and cartilaginous matrix secretion at 6 and 12 weeks after transplantation in both groups, the biochemical properties (levels of DNA, GAG, and collagen and biomechanical values in the oriented scaffold group were higher than that in random group at early time points after implantation. While these differences were not evident at 24 weeks, the biochemical and biomechanical properties of the regenerated cartilage in the oriented scaffold-BMSC construct group were similar to that of native cartilage. These results demonstrate that an oriented scaffold, in combination with differentiated BMSCs can successfully repair full-thickness articular cartilage defects in rabbits, and produce cartilage enhanced biomechanical properties.

  2. The identification of CD163 expressing phagocytic chondrocytes in joint cartilage and its novel scavenger role in cartilage degradation.

    Directory of Open Access Journals (Sweden)

    Kai Jiao

    Full Text Available BACKGROUND: Cartilage degradation is a typical characteristic of arthritis. This study examined whether there was a subset of phagocytic chondrocytes that expressed the specific macrophage marker, CD163, and investigated their role in cartilage degradation. METHODS: Cartilage from the knee and temporomandibular joints of Sprague-Dawley rats was harvested. Cartilage degradation was experimentally-induced in rat temporomandibular joints, using published biomechanical dental methods. The expression levels of CD163 and inflammatory factors within cartilage, and the ability of CD163(+ chondrocytes to conduct phagocytosis were investigated. Cartilage from the knees of patients with osteoarthritis and normal cartilage from knee amputations was also investigated. RESULTS: In the experimentally-induced degrading cartilage from temporomandibular joints, phagocytes were capable of engulfing neighboring apoptotic and necrotic cells, and the levels of CD163, TNF-α and MMPs were all increased (P0.05. CD163(+ chondrocytes were found in the cartilage mid-zone of temporomandibular joints and knee from healthy, three-week old rats. Furthermore, an increased number of CD163(+ chondrocytes with enhanced phagocytic activity were present in Col-II(+ chondrocytes isolated from the degraded cartilage of temporomandibular joints in the eight-week experimental group compared with their age-matched controls. Increased number with enhanced phagocytic activity of CD163(+ chondrocytes were also found in isolated Col-II(+ chondrocytes stimulated with TNF-α (P<0.05. Mid-zone distribution of CD163(+ cells accompanied with increased expression of CD163 and TNF-α were further confirmed in the isolated Col-II(+ chondrocytes from the knee cartilage of human patients with osteoarthritis, in contrast to the controls (both P<0.05. CONCLUSIONS: An increased number of CD163(+ chondrocytes with enhanced phagocytic activity were discovered within degraded joint cartilage, indicating a

  3. Quasi-static elastography comparison of hyaline cartilage structures

    Science.gov (United States)

    McCredie, A. J.; Stride, E.; Saffari, N.

    2009-11-01

    Joint cartilage, a load bearing structure in mammals, has only limited ability for regeneration after damage. For tissue engineers to design functional constructs, better understanding of the properties of healthy tissue is required. Joint cartilage is a specialised structure of hyaline cartilage; a poroviscoelastic solid containing fibril matrix reinforcements. Healthy joint cartilage is layered, which is thought to be important for correct tissue function. However, the behaviour of each layer during loading is poorly understood. Ultrasound elastography provides access to depth-dependent information in real-time for a sample during loading. A 15 MHz focussed transducer provided details from scatterers within a small fixed region in each sample. Quasi-static loading was applied to cartilage samples while ultrasonic signals before and during compressions were recorded. Ultrasonic signals were processed to provide time-shift profiles using a sum-squared difference method and cross-correlation. Two structures of hyaline cartilage have been tested ultrasonically and mechanically to determine method suitability for monitoring internal deformation differences under load and the effect of the layers on the global mechanical material behaviour. Results show differences in both the global mechanical properties and the ultrasonically tested strain distributions between the two structures tested. It was concluded that these differences are caused primarily by the fibril orientations.

  4. 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

  5. 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.

  6. Cartilage Health in Knees Treated with Metal Resurfacing Implants or Untreated Focal Cartilage Lesions: A Preclinical Study in Sheep.

    Science.gov (United States)

    Martinez-Carranza, Nicolas; Hultenby, Kjell; Lagerstedt, Anne Sofie; Schupbach, Peter; Berg, Hans E

    2017-07-01

    Background Full-depth cartilage lesions do not heal and the long-term clinical outcome is uncertain. In the symptomatic middle-aged (35-60 years) patient, treatment with metal implants has been proposed. However, the cartilage health surrounding these implants has not been thoroughly studied. Our objective was to evaluate the health of cartilage opposing and adjacent to metal resurfacing implants. Methods The medial femoral condyle was operated in 9 sheep bilaterally. A metallic resurfacing metallic implant was immediately inserted into an artificially created 7.5 mm defect while on the contralateral knee the defect was left untreated. Euthanasia was performed at 6 months. Six animals, of similar age and study duration, from a previous study were used for comparison in the evaluation of cartilage health adjacent to the implant. Cartilage damage to joint surfaces within the knee, cartilage repair of the defect, and cartilage adjacent to the implant was evaluated macroscopically and microscopically. Results Six animals available for evaluation of cartilage health within the knee showed a varying degree of cartilage damage with no statistical difference between defects treated with implants or left untreated ( P = 0.51; 95% CI -3.7 to 6.5). The cartilage adjacent to the implant (score 0-14; where 14 indicates no damage) remained healthy in these 6 animals showing promising results (averaged 10.5; range 9-11.5, SD 0.95). Cartilage defects did not heal in any case. Conclusion Treatment of a critical size focal lesion with a metal implant is a viable alternative treatment.

  7. Vegetative regeneration

    Science.gov (United States)

    George A. Schier; John R. Jones; Robert P. Winokur

    1985-01-01

    Aspen is noted for its ability to regenerate vegetatively by adventitious shoots or suckers that arise on its long lateral roots. It also produces sprouts from stumps and root collars; but they are not common. In a survey of regeneration after clearcutting mature aspen in Utah. Baker (1918b) found that 92% of the shoots originated from roots, 7% from root collars, and...

  8. Liver regeneration

    NARCIS (Netherlands)

    Chamuleau, R. A.; Bosman, D. K.

    1988-01-01

    Despite great advances in analysing hemodynamic, morphological and biochemical changes during the process of liver regeneration, the exact (patho)physiological mechanism is still unknown. A short survey of literature is given of the kinetics of liver regeneration and the significance of different

  9. Integrating three-dimensional printing and nanotechnology for musculoskeletal regeneration

    Science.gov (United States)

    Nowicki, Margaret; Castro, Nathan J.; Rao, Raj; Plesniak, Michael; Zhang, Lijie Grace

    2017-09-01

    The field of tissue engineering is advancing steadily, partly due to advancements in rapid prototyping technology. Even with increasing focus, successful complex tissue regeneration of vascularized bone, cartilage and the osteochondral interface remains largely illusive. This review examines current three-dimensional printing techniques and their application towards bone, cartilage and osteochondral regeneration. The importance of, and benefit to, nanomaterial integration is also highlighted with recent published examples. Early-stage successes and challenges of recent studies are discussed, with an outlook to future research in the related areas.

  10. A Comparison of Outcomes of Particulated Juvenile Articular Cartilage and Bone Marrow Aspirate Concentrate for Articular Cartilage Lesions of the Talus.

    Science.gov (United States)

    Lanham, Nathan S; Carroll, John J; Cooper, Minton T; Perumal, Venkat; Park, Joseph S

    2017-08-01

    Articular cartilage lesions of the talus remain a challenging clinical problem because of the lack of natural regeneration and limited treatment options. Microfracture is often the first-line therapy, however lesions larger than 1.5 cm 2 have been shown to not do as well with this treatment method. The objective of this retrospective study was to evaluate the outcomes of iliac crest bone marrow aspirate concentrate/collagen scaffold (ICBMA) and particulated juvenile articular cartilage (PJAC) for larger articular cartilage lesions of the talus. Fifteen patients undergoing ICBMA or PJAC for articular cartilage lesions of the talus from 2010 to 2013 were reviewed. Twelve patients, 6 from each treatment option, were included in the study. American Orthopaedic Foot and Ankle Surgeons (AOFAS), Foot and Ankle Ability Measure (FAAM), and Short Form-12 (SF-12) outcome scores were collected for each patient. The mean age was 34.7 ± 14.8 years for ICBMA and 31.5 ± 7.4 years for PJAC. Lesion size was 2.0 ± 1.1 cm 2 for ICBMA and 1.9 ± 0.9 cm 2 for PJAC. At a mean follow-up of 25.7 months (range, 12-42 months), the mean AOFAS score was 71.33 for ICBMA and 95.83 for PJAC (  P = .019). The FAAM activities of daily living subscale mean was 77.77 for ICBMA and 97.02 for PJAC (   P = .027). The mean FAAM sports subscale was 45.14 for ICBMA and 86.31 for PJAC (  P = .054). The SF-12 physical health mean was 47.58 for ICBMA and 53.98 for PJAC (  P = .315). The SF-12 mental health mean was 53.25 for ICBMA and 57.8 for PJAC (  P = .315). One patient in treated initially with ICBMA underwent revision fixation for nonunion of their medial malleolar osteotomy, which ultimately resulted in removal of hardware and tibiotalar arthrodesis at 2 years from the index procedure. In the present analysis, PJAC yields better clinical outcomes at 2 years when compared with ICBMA for articular cartilage lesions of the talus that were on average greater than 1.5cm 2 . Therapeutic, Level

  11. 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

  12. Isolation of a stable subpopulation of mobilized dental pulp stem cells (MDPSCs) with high proliferation, migration, and regeneration potential is independent of age.

    Science.gov (United States)

    Horibe, Hiroshi; Murakami, Masashi; Iohara, Koichiro; Hayashi, Yuki; Takeuchi, Norio; Takei, Yoshifumi; Kurita, Kenichi; Nakashima, Misako

    2014-01-01

    Insights into the understanding of the influence of the age of MSCs on their cellular responses and regenerative potential are critical for stem cell therapy in the clinic. We have isolated dental pulp stem cells (DPSCs) subsets based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs) from young and aged donors. The aged MDPSCs were efficiently enriched in stem cells, expressing high levels of trophic factors with high proliferation, migration and anti-apoptotic effects compared to young MDPSCs. In contrast, significant differences in those properties were detected between aged and young colony-derived DPSCs. Unlike DPSCs, MDPSCs showed a small age-dependent increase in senescence-associated β-galactosidase (SA-β-gal) production and senescence markers including p16, p21, Interleukin (IL)-1β, -6, -8, and Groα in long-term culture. There was no difference between aged and young MDPSCs in telomerase activity. The regenerative potential of aged MDPSCs was similar to that of young MDPSCs in an ischemic hindlimb model and an ectopic tooth root model. These results demonstrated that the stem cell properties and the high regenerative potential of MDPSCs are independent of age, demonstrating an immense utility for clinical applications by autologous cell transplantation in dental pulp regeneration and ischemic diseases.

  13. Platelet-Rich Fibrin Improves the Viability of Diced Cartilage Grafts in a Rabbit Model.

    Science.gov (United States)

    Göral, Ali; Aslan, Cem; Bolat Küçükzeybek, Betül; Işık, Dağhan; Hoşnuter, Mübin; Durgun, Mustafa

    2016-04-01

    Diced cartilage may be wrapped with synthetic or biological materials before grafting to a recipient site. These materials have unique advantages and disadvantages, and a gold standard is not available. The authors investigated the effects of platelet-rich fibrin (PRF) on the survival of cartilage grafts in a rabbit model. In this experimental study, diced cartilage pieces from the ears of 9 male rabbits were left unwrapped or were wrapped with PRF, oxidized regenerated cellulose, or fascia. Specimens then were placed into subcutaneous pockets prepared on the backs of the rabbits. The animals were sacrificed 2 months after the procedure, and the grafts were excised for macroscopic and histopathologic examination. The cartilage graft wrapped with PRF showed superior viability compared with the cartilage graft wrapped with oxidized regenerated cellulose. No significant differences were found among the other groups. The groups were not significantly different in terms of rates of inflammation, fibrosis, or vascularization. PRF enhances the viability of diced cartilage grafts and should be considered an appropriate biological wrapping material for cartilage grafting. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  14. Repair and tissue engineering techniques for articular cartilage

    OpenAIRE

    Makris, Eleftherios A.; Gomoll, Andreas H.; Malizos, Konstantinos N.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2014-01-01

    © 2015 Macmillan Publishers Limited. All rights reserved. Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable s...

  15. Degenerated human articular cartilage at autopsy represents preclinical osteoarthritic cartilage: comparison with clinically defined osteoarthritic cartilage

    NARCIS (Netherlands)

    van Valburg, A. A.; Wenting, M. J.; Beekman, B.; te Koppele, J. M.; Lafeber, F. P.; Bijlsma, J. W.

    1997-01-01

    To investigate whether macroscopically fibrillated human articular knee cartilage observed at autopsy can be considered an early, preclinical phase of osteoarthritis (OA). Histological and biochemical characteristics of 3 types of articular knee cartilage were compared: macroscopically degenerated

  16. Manipulations to regenerate aspen ecosystems

    Science.gov (United States)

    Wayne D. Shepperd

    2001-01-01

    Vegetative regeneration of aspen can be initiated through manipulations that provide hormonal stimulation, proper growth environment, and sucker protection - the three elements of the aspen regeneration triangle. The correct course of action depends upon a careful evaluation of the size, vigor, age, and successional status of the existing clone. Soils and site...

  17. The junction between hyaline cartilage and engineered cartilage in rabbits.

    Science.gov (United States)

    Komura, Makoto; Komura, Hiroko; Otani, Yushi; Kanamori, Yutaka; Iwanaka, Tadashi; Hoshi, Kazuto; Tsuyoshi, Takato; Tabata, Yasuhiko

    2013-06-01

    Tracheoplasty using costal cartilage grafts to enlarge the tracheal lumen was performed to treat congenital tracheal stenosis. Fibrotic granulomatous tissue was observed at the edge of grafted costal cartilage. We investigated the junction between the native hyaline cartilage and the engineered cartilage plates that were generated by auricular chondrocytes for fabricating the airway. Controlled, prospecive study. In group 1, costal cartilage from New Zealand white rabbits was collected and implanted into a space created in the cervical trachea. In group 2, chondrocytes from auricular cartilages were seeded on absorbable scaffolds. These constructs were implanted in the subcutaneous space. Engineered cartilage plates were then implanted into the trachea after 3 weeks of implantation of the constructs. The grafts in group 1 and 2 were retrieved after 4 weeks. In group 1, histological studies of the junction between the native hyaline cartilage and the implanted costal cartilage demonstrated chondrogenic tissue in four anastomoses sides out of the 10 examined. In group 2, the junction between the native trachea and the engineered cartilage showed neocartilage tissue in nine anastomoses sides out of 10. Engineered cartilage may be beneficial for engineered airways, based on the findings of the junction between the native and engineered grafts. Copyright © 2012 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep

    Science.gov (United States)

    Mohan, Neethu; Gupta, Vineet; Sridharan, Banu Priya; Mellott, Adam J; Easley, Jeremiah T; Palmer, Ross H; Galbraith, Richard A; Key, Vincent H; Berkland, Cory J; Detamore, Michael S

    2015-01-01

    Background: The microfracture technique for cartilage repair has limited ability to regenerate hyaline cartilage. Aim: The current study made a direct comparison between microfracture and an osteochondral approach with microsphere-based gradient plugs. Materials & methods: The PLGA-based scaffolds had opposing gradients of chondroitin sulfate and β-tricalcium phosphate. A 1-year repair study in sheep was conducted. Results: The repair tissues in the microfracture were mostly fibrous and had scattered fissures with degenerative changes. Cartilage regenerated with the gradient plugs had equal or superior mechanical properties; had lacunated cells and stable matrix as in hyaline cartilage. Conclusion: This first report of gradient scaffolds in a long-term, large animal, osteochondral defect demonstrated potential for equal or better cartilage repair than microfracture. PMID:26418471

  19. Evaluation of focal cartilage lesions of the knee using MRI T2 mapping and delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC).

    Science.gov (United States)

    Årøen, Asbjørn; Brøgger, Helga; Røtterud, Jan Harald; Sivertsen, Einar Andreas; Engebretsen, Lars; Risberg, May Arna

    2016-02-11

    Assessment of degenerative changes of the cartilage is important in knee cartilage repair surgery. Magnetic Resonance Imaging (MRI) T2 mapping and delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) are able to detect early degenerative changes. The hypothesis of the study was that cartilage surrounding a focal cartilage lesion in the knee does not possess degenerative changes. Twenty-eight consecutive patients included in a randomized controlled trial on cartilage repair were evaluated using MRI T2 mapping and dGEMRIC before cartilage treatment was initiated. Inclusion was based on disabling knee problems (Lysholm score of ≤ 75) due to an arthroscopically verified focal femoral condyle cartilage lesion. Furthermore, no major malalignments or knee ligament injuries were accepted. Mean patient age was 33 ± 9.6 years, and the mean duration of knee symptoms was 49 ± 60 months. The MRI T2 mapping and the dGEMRIC measurements were performed at three standardized regions of interest (ROIs) at the medial and lateral femoral condyle, avoiding the cartilage lesion The MRI T2 mapping of the cartilage did not demonstrate significant differences between condyles with or without cartilage lesions. The dGEMRIC results did not show significantly lower values of the affected condyle compared with the opposite condyle and the contra-lateral knee in any of the ROIs. The intraclass correlation coefficient (ICC) of the dGEMRIC readings was 0.882. The MRI T2 mapping and the dGEMRIC confirmed the arthroscopic findings that normal articular cartilage surrounded the cartilage lesion, reflecting normal variation in articular cartilage quality. NCT00885729 , registered April 17 2009.

  20. When is cartilage repair successful?

    International Nuclear Information System (INIS)

    Raudner, M.; Roehrich, S.; Zalaudek, M.; Trattnig, S.; Schreiner, M.M.

    2017-01-01

    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.) [de

  1. MR imaging of articular cartilage

    International Nuclear Information System (INIS)

    Schaefer, F.K.W.; Muhle, C.; Heller, M.; Brossmann, J.

    2001-01-01

    MR imaging has evolved to the best non-invasive method for the evaluation of articular cartilage. MR imaging helps to understand the structure and physiology of cartilage, and to diagnose cartilage lesions. Numerous studies have shown high accuracy and reliability concerning detection of cartilage lesions and early changes in both structure and biochemistry. High contrast-to-noise ratio and high spatial resolution are essential for analysis of articular cartilage. Fat-suppressed 3D-T 1 weighted gradient echo and T 2 -weighted fast spin echo sequences with or without fat suppression are recommended for clinical routine. In this article the anatomy and pathology of hyaline articular cartilage and the complex imaging characteristics of hyaline cartilage will be discussed. (orig.) [de

  2. Lubrication and cartilage.

    Science.gov (United States)

    Wright, V; Dowson, D

    1976-02-01

    Mechanisms of lubrication of human synovial joints have been analysed in terms of the operating conditions of the joint, the synovial fluid and articular cartilage. In the hip and knee during a walking cycle the load may rise up to four times body weight. In the knee on dropping one metre the load may go up to 25 time body weight. The elastic modulus of cartilage is similar to that of the synthetic rubber of a car tyre. The cartilage surface is rough and in elderly specimens the centre line average is 2-75 mum. The friction force generated in reciprocating tests shows that both cartilage and synovial fluid are important in lubrication. The viscosity-shear rate relationships of normal synovial fluid show that it is non-Newtonian. Osteoarthrosic fluid is less so and rheumatoid fluid is more nearly Newtonian. Experiments with hip joints in a pendulum machine show that fluid film lubrication obtains at some phases of joint action. Boundary lubrication prevails under certain conditions and has been examined with a reciprocating friction machine. Digestion of hyaluronate does not alter the boundary lubrication, but trypsin digestion does. Surface active substances (lauryl sulphate and cetyl 3-ammonium bromide) give a lubricating ability similar to that of synovial fluid. The effectiveness of the two substances varies with pH.

  3. Chondroptosis in Alkaptonuric Cartilage

    Science.gov (United States)

    Millucci, Lia; Giorgetti, Giovanna; Viti, Cecilia; Ghezzi, Lorenzo; Gambassi, Silvia; Braconi, Daniela; Marzocchi, Barbara; Paffetti, Alessandro; Lupetti, Pietro; Bernardini, Giulia; Orlandini, Maurizio

    2015-01-01

    Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of treatment is palliative and little is known about AKU physiopathology. Chondroptosis, a peculiar type of cell death in cartilage, has been so far reported to occur in osteoarthritis, a rheumatic disease that shares some features with AKU. In the present work, we wanted to assess if chondroptosis might also occur in AKU. Electron microscopy was used to detect the morphological changes of chondrocytes in damaged cartilage distinguishing apoptosis from its variant termed chondroptosis. We adopted histological observation together with Scanning Electron Microscopy and Transmission Electron Microscopy to evaluate morphological cell changes in AKU chondrocytes. Lipid peroxidation in AKU cartilage was detected by fluorescence microscopy. Using the above‐mentioned techniques, we performed a morphological analysis and assessed that AKU chondrocytes undergo phenotypic changes and lipid oxidation, resulting in a progressive loss of articular cartilage structure and function, showing typical features of chondroptosis. To the best of our knowledge, AKU is the second chronic pathology, following osteoarthritis, where chondroptosis has been documented. Our results indicate that Golgi complex plays an important role in the apoptotic process of AKU chondrocytes and suggest a contribution of chondroptosis in AKU pathogenesis. These findings also confirm a similarity between osteoarthritis and AKU. J. Cell. Physiol. 230: 1148–1157, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:25336110

  4. Similar hyaline-like cartilage repair of osteochondral defects in rabbits using isotropic and anisotropic collagen scaffolds.

    Science.gov (United States)

    de Mulder, Eric L W; Hannink, Gerjon; van Kuppevelt, Toin H; Daamen, Willeke F; Buma, Pieter

    2014-02-01

    Lesions in knee joint articular cartilage (AC) have limited repair capacity. Many clinically available treatments induce a fibrous-like cartilage repair instead of hyaline cartilage. To induce hyaline cartilage repair, we hypothesized that type I collagen scaffolds with fibers aligned perpendicular to the AC surface would result in qualitatively better tissue repair due to a guided cellular influx from the subchondral bone. By specific freezing protocols, type I collagen scaffolds with isotropic and anisotropic fiber architectures were produced. Rabbits were operated on bilaterally and two full thickness defects were created in each knee joint. The defects were filled with (1) an isotropic scaffold, (2) an anisotropic scaffold with pores parallel to the cartilage surface, and (3) an anisotropic scaffold with pores perpendicular to the cartilage surface. Empty defects served as controls. After 4 (n=13) and 12 (n=13) weeks, regeneration was scored qualitatively and quantitatively using histological analysis and a modified O'Driscoll score. After 4 weeks, all defects were completely filled with partially differentiated hyaline cartilage tissue. No differences in O'Driscoll scores were measured between empty defects and scaffold types. After 12 weeks, all treatments led to hyaline cartilage repair visualized by increased glycosaminoglycan staining. Total scores were significantly increased for parallel anisotropic and empty defects over time (phyaline-like cartilage repair. Fiber architecture had no effect on cartilage repair.

  5. Mesenchymal stem cells can survive on the extracellular matrix-derived decellularized bovine articular cartilage scaffold

    Directory of Open Access Journals (Sweden)

    Amin Tavassoli

    2015-12-01

    Full Text Available Objective (s: The scarcity of articular cartilage defect to repair due to absence of blood vessels and tissue engineering is one of the promising approaches for cartilage regeneration. The objective of this study was to prepare an extracellular matrix derived decellularized bovine articular cartilage scaffold and investigate its interactions with seeded rat bone marrow mesenchymal stem cells (BM-MSCs. Materials and Methods: Bovine articular cartilage that was cut into pieces with 2 mm thickness, were decellularized by combination of physical and chemical methods including snap freeze-thaw and treatment with sodium dodecyl sulfate (SDS. The scaffolds were then seeded with 1, 1’-dioctadecyl-3, 3, 3’, 3’-tetramethylindocarbocyanine perchlorate (DiI labeled BM-MSCs and cultured for up to two weeks. Results: Histological studies of decellularized bovine articular cartilage showed that using 5 cycles of snap freeze-thaw in liquid nitrogen and treatment with 2.5% SDS for 4 hr led to the best decellularization, while preserving the articular cartilage structure. Adherence and penetration of seeded BM-MSCs on to the scaffold were displayed by histological and florescence examinations and also confirmed by electron microscopy. Conclusion: ECM-derived decellularized articular cartilage scaffold provides a suitable environment to support adhesion and maintenance of cultured BM-MSCs and could be applied to investigate cellular behaviors in this system and may also be useful for studies of cartilage tissue engineering.

  6. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    Directory of Open Access Journals (Sweden)

    Melissa Lo Monaco

    2018-01-01

    Full Text Available Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs or induced pluripotent stem cells (iPSCs have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  7. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.

    Science.gov (United States)

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  8. Engineering cartilage substitute with a specific size and shape using porous high-density polyethylene (HDPE) as internal support.

    Science.gov (United States)

    Wu, Yujia; Zhu, Lie; Jiang, Hua; Liu, Wei; Liu, Yu; Cao, Yilin; Zhou, Guangdong

    2010-04-01

    Despite the great advances in cartilage engineering, constructing cartilage of large sizes and appropriate shapes remains a great challenge, owing to limits in thickness of regenerated cartilage and to inferior mechanical properties of scaffolds. This study introduces a pre-shaped polyglycolic acid (PGA)-coated porous high-density polyethylene (HDPE) scaffold to overcome these challenges. HDPE was carved into cylindrical rods and wrapped around by PGA fibres to form PGA-HDPE scaffolds. Porcine chondrocytes were seeded into the scaffolds and the constructs were cultured in vitro for 2 weeks before subcutaneous implantation into nude mice. Scaffolds made purely of PGA with the same size and shape were used as a control. After 8 weeks of implantation, the construct formed cartilage-like tissue and retained its pre-designed shape and size. In addition, the regenerated cartilage grew and completely surrounded the HDPE core, which made the entire cartilage substitute biocompatible to its implanted environment as native cartilage similarly does. By contrast, the shape and size of the constructs in the control group seriously deformed and obvious hollow cavity and necrotic tissue were observed in the inner region. These results demonstrate that the use of HDPE as the internal support of a biodegradable scaffold has the potential to circumvent the problems of limitations in size and shape, with promising implications for the development of engineered cartilage appropriate for clinical applications. Copyright 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  9. 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.

  10. Cartilage damage involving extrusion of mineralisable matrix from the articular calcified cartilage and subchondral bone

    Directory of Open Access Journals (Sweden)

    A Boyde

    2011-05-01

    Full Text Available Arthropathy of the distal articular surfaces of the third metacarpal (Mc3 and metatarsal (Mt3 bones in the Thoroughbred racehorse (Tb is a natural model of repetitive overload arthrosis. We describe a novel pathology that affects the articular calcified cartilage (ACC and subchondral bone (SCB and which is associated with hyaline articular cartilage degeneration. Parasagittal slices cut from the palmar quadrant of the distal condyles of the left Mc3/Mt3 of 39 trained Tbs euthanased for welfare reasons were imaged by point projection microradiography, and backscattered electron (BSE scanning electron microscopy (SEM, light microscopy, and confocal scanning light microscopy. Mechanical properties were studied by nanoindentation. Data on the horses' training and racing career were also collected. Highly mineralised projections were observed extending from cracks in the ACC mineralising front into the hyaline articular cartilage (HAC up to two-thirds the thickness of the HAC, and were associated with focal HAC surface fibrillation directly overlying their site. Nanoindentation identified this extruded matrix to be stiffer than any other mineralised phase in the specimen by a factor of two. The presence of projections was associated with a higher cartilage Mankin histology score (P < 0.02 and increased amounts of gross cartilage loss pathologically on the condyle (P < 0.02. Presence of projections was not significantly associated with: total number of racing seasons, age of horse, amount of earnings, number of days in training, total distance galloped in career, or presence of wear lines.

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

    Directory of Open Access Journals (Sweden)

    Amanda J Sutherland

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

  12. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-01-15

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

  14. Modelling merchantable volumes for uneven aged maritime pine (Pinus pinaster Aiton stands establi-shed by natural regeneration in the central Portugal

    Directory of Open Access Journals (Sweden)

    Cristina Alegria

    2013-12-01

    Full Text Available Uneven aged maritime pine stands established by natural regeneration have a great expression in Portugal. These stands being overstocked, as opposed to those established from plantations, provide straight and cylindrical tree boles and logs with less knots that makes them very suitable for certain industrial purposes. Therefore, the aim of this study was to fit a set of equations to predict total volume and merchantable volumes to any merchantable limit for uneven aged maritime pine stands established by natural regeneration in the central inland region of Portugal. Data were collected in 30 circular sampling plots of 500 m2 of area, on 1426 trees and 314 sample trees for volume assessment, corresponding to 2353 diameter/height mea-surements. A total height equation, a total volume equation, a volume ratio equation to any top height limit and a taper equation, over bark, were fitted. To select among the best models, several statistics were computed during model fitting and the independent validation procedure to evaluate model fitting, collinearity and prediction performances. A ranking index was used to support the final decision. The models selected were then fitted again using robust regression and weighted regression techniques, because studentized residuals distribution normality and homogeneity assumptions were not observed. This research showed that the models selected for these stands were not the same as those selected in previous studies for the species in this region, suggesting that these results may be due to the influence of stand density conditions on diameter and total height growth, and consequently, on stem form and volume. This set of equations will also be included as components in a single tree growth and yield model developed for these stands. 

  15. Cartilage Degeneration and Alignment in Severe Varus Knee Osteoarthritis.

    Science.gov (United States)

    Nakagawa, Yasuaki; Mukai, Shogo; Yabumoto, Hiromitsu; Tarumi, Eri; Nakamura, Takashi

    2015-10-01

    The aim of this study was to examine the relationship between cartilage, ligament, and meniscus degeneration and radiographic alignment in severe varus knee osteoarthritis in order to understand the development of varus knee osteoarthritis. Fifty-three patients (71 knees) with primary varus knee osteoarthritis and who underwent total knee arthroplasty were selected for this study. There were 6 men and 47 women, with 40 right knees and 31 left knees studied; their mean age at operation was 73.5 years. The ligament, meniscus, degeneration of joint cartilage, and radiographic alignments were examined visually. The tibial plateau-tibial shaft angle was larger if the condition of the cartilage in the lateral femoral condyle was worse. The femorotibial angle and tibial plateau-tibial shaft angle were larger if the conditions of the lateral meniscus or the cartilage in the lateral tibial plateau were worse. Based on the results of this study, progression of varus knee osteoarthritis may occur in the following manner: medial knee osteoarthritis starts in the central portion of the medial tibial plateau, and accompanied by medial meniscal extrusion and anterior cruciate ligament rupture, cartilage degeneration expands from the anterior to the posterior in the medial tibial plateau. Bone attrition occurs in the medial tibial plateau, and the femoro-tibial angle and tibial plateau-tibial shaft angle increase. Therefore, the lateral intercondylar eminence injures the cartilage of the lateral femoral condyle in the longitudinal fissure type. Thereafter, the cartilage degeneration expands in the whole of the knee joints.

  16. Regeneration of limb joints in the axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Lee, Jangwoo; Gardiner, David M

    2012-01-01

    In spite of numerous investigations of regenerating salamander limbs, little attention has been paid to the details of how joints are reformed. An understanding of the process and mechanisms of joint regeneration in this model system for tetrapod limb regeneration would provide insights into developing novel therapies for inducing joint regeneration in humans. To this end, we have used the axolotl (Mexican Salamander) model of limb regeneration to describe the morphology and the expression patterns of marker genes during joint regeneration in response to limb amputation. These data are consistent with the hypothesis that the mechanisms of joint formation whether it be development or regeneration are conserved. We also have determined that defects in the epiphyseal region of both forelimbs and hind limbs in the axolotl are regenerated only when the defect is small. As is the case with defects in the diaphysis, there is a critical size above which the endogenous regenerative response is not sufficient to regenerate the joint. This non-regenerative response in an animal that has the ability to regenerate perfectly provides the opportunity to screen for the signaling pathways to induce regeneration of articular cartilage and joints.

  17. Regeneration of limb joints in the axolotl (Ambystoma mexicanum.

    Directory of Open Access Journals (Sweden)

    Jangwoo Lee

    Full Text Available In spite of numerous investigations of regenerating salamander limbs, little attention has been paid to the details of how joints are reformed. An understanding of the process and mechanisms of joint regeneration in this model system for tetrapod limb regeneration would provide insights into developing novel therapies for inducing joint regeneration in humans. To this end, we have used the axolotl (Mexican Salamander model of limb regeneration to describe the morphology and the expression patterns of marker genes during joint regeneration in response to limb amputation. These data are consistent with the hypothesis that the mechanisms of joint formation whether it be development or regeneration are conserved. We also have determined that defects in the epiphyseal region of both forelimbs and hind limbs in the axolotl are regenerated only when the defect is small. As is the case with defects in the diaphysis, there is a critical size above which the endogenous regenerative response is not sufficient to regenerate the joint. This non-regenerative response in an animal that has the ability to regenerate perfectly provides the opportunity to screen for the signaling pathways to induce regeneration of articular cartilage and joints.

  18. Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women.

    Science.gov (United States)

    Lou, Chao; Xiang, Guangheng; Weng, Qiaoyou; Chen, Zhaojie; Chen, Deheng; Wang, Qingqing; Zhang, Di; Zhou, Bin; He, Dengwei; Chen, Hongliang

    2016-11-01

    The purpose of this study was to investigate the association between menopause and severity of knee joint cartilage degeneration using a magnetic resonance imaging-based six-level grading system, with six cartilage surfaces, the medial and lateral femoral condyle, the femoral trochlea, the medial and lateral tibia plateau, and the patella. The study cohort comprised 860 healthy women (age 36-83 y), and 5,160 cartilage surfaces were analyzed. Age, weight, height, age at natural menopause, and years since menopause (YSM) were obtained. Cartilage degeneration was assessed using a magnetic resonance imaging-based six-level grading system. After removing the age, height, and weight effects, postmenopausal women had more severe cartilage degeneration than pre- and perimenopausal women (P  0.05). No significant difference was observed in lateral tibia plateau and lateral femoral condyle in postmenopausal women. Menopause is associated with cartilage degeneration of knee joint. After menopause, cartilage showed progressive severe degeneration that occurred in the first 25 YSM, suggesting estrogen deficiency might be a risk factor of cartilage degeneration of the knee joint. Further studies are needed to investigate whether age or menopause plays a more important role in the progression of cartilage degeneration in the knee joint.

  19. Tissue-engineered trachea regeneration using decellularized trachea matrix treated with laser micropore technique.

    Science.gov (United States)

    Xu, Yong; Li, Dan; Yin, Zongqi; He, Aijuan; Lin, Miaomiao; Jiang, Gening; Song, Xiao; Hu, Xuefei; Liu, Yi; Wang, Jinpeng; Wang, Xiaoyun; Duan, Liang; Zhou, Guangdong

    2017-08-01

    Tissue-engineered trachea provides a promising approach for reconstruction of long segmental tracheal defects. However, a lack of ideal biodegradable scaffolds greatly restricts its clinical translation. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration owing to natural tubular structure, cartilage matrix components, and biodegradability. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. To address these problems, a laser micropore technique (LMT) was applied in the current study to modify trachea sample porosity to facilitate decellular treatment and cell ingrowth. Decellularization processing demonstrated that cells in LMT treated samples were more easily removed compared with untreated native trachea. Furthermore, after optimizing the protocols of LMT and decellular treatments, the LMT-treated DTM (LDTM) could retain their original tubular shape with only mild extracellular matrix damage. After seeding with chondrocytes and culture in vitro for 8 weeks, the cell-LDTM constructs formed tubular cartilage with relatively homogenous cell distribution in both micropores and bilateral surfaces. In vivo results further confirmed that the constructs could form mature tubular cartilage with increased DNA and cartilage matrix contents, as well as enhanced mechanical strength, compared with native trachea. Collectively, these results indicate that LDTM is an ideal scaffold for tubular cartilage regeneration and, thus, provides a promising strategy for functional reconstruction of trachea cartilage. Lacking ideal biodegradable scaffolds greatly restricts development of tissue-engineered trachea. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. By laser micropore technique (LMT), the

  20. 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.

  1. 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.

  2. Three-Dimensional Printing Articular Cartilage: Recapitulating the Complexity of Native Tissue.

    Science.gov (United States)

    Guo, Ting; Lembong, Josephine; Zhang, Lijie Grace; Fisher, John P

    2017-06-01

    In the past few decades, the field of tissue engineering combined with rapid prototyping (RP) techniques has been successful in creating biological substitutes that mimic tissues. Its applications in regenerative medicine have drawn efforts in research from various scientific fields, diagnostics, and clinical translation to therapies. While some areas of therapeutics are well developed, such as skin replacement, many others such as cartilage repair can still greatly benefit from tissue engineering and RP due to the low success and/or inefficiency of current existing, often surgical treatments. Through fabrication of complex scaffolds and development of advanced materials, RP provides a new avenue for cartilage repair. Computer-aided design and three-dimensional (3D) printing allow the fabrication of modeled cartilage scaffolds for repair and regeneration of damaged cartilage tissues. Specifically, the various processes of 3D printing will be discussed in details, both cellular and acellular techniques, covering the different materials, geometries, and operational printing conditions for the development of tissue-engineered articular cartilage. Finally, we conclude with some insights on future applications and challenges related to this technology, especially using 3D printing techniques to recapitulate the complexity of native structure for advanced cartilage regeneration.

  3. Three-dimensional evaluation of cartilage thickness and cartilage volume in the knee joint with MR imaging: reproducibility in volunteers

    International Nuclear Information System (INIS)

    Westhoff, J.; Eckstein, F.; Sittek, H.; Faber, S.; Reiser, M.; Loesch, A.; Englmeier, K.H.; Kolem, H.

    1997-01-01

    Objective: To determine the reproductibility of three-dimensional volume and thickness measurements of the knee joint cartilage with MRI in volunteers. Methods: The knees of 7 healthy individuals (ages 23 to 58 yrs.) were sagitally imaged with a resolution of 2x0.31x0.31 mm 3 , using a fat-suppressed FLASH-3 D sequence. The knee was repositioned in between replicate acquisitions, 6 data sets being obtained in each case. After semiautomatic segmentation and three-dimensional reconstruction of the cartilage, the thickness was determined independent of the original section orientation. The coefficient of variation for repeated volume measurements and the deviations of the maximal cartilage thickness values were calculated subsequently. Results: The mean variation of the cartilage volumes of the replicate measurements was 1.4% (±0.8%) in the patella, 1.7% (±1.5%) in the femur, 3.0% (±1.2%) in the medial tibial plateau and 3.5% (±2.0%) in the lateral tibial plateau. The comparison of the distribution patterns of cartilage thickness yielded a high degree of agreement. Only in rare cases deviations of more than 0.5 mm were observed. Conclusions: The results show that the presented method for determining the quantitative distribution of articular cartilage yields a high degree of precision. It offers new possibilities in screening risk groups, monitoring the course of degenerative joint disease and the investigation of functional adaptation of the cartilage to mechanical loading. (orig.) [de

  4. My Regeneration:

    DEFF Research Database (Denmark)

    Carter, Dale

    2017-01-01

    and cultural referents shows that it offers an index to the album. Using its frontier setting and a variety of sacred and secular myths, symbols and icons, ‘Heroes and Villains,’ like Smile as a whole, offers historically-informed visions of national decline, crisis and regeneration that are at once critical...

  5. Patellofemoral instability in children: T2 relaxation times of the patellar cartilage in patients with and without patellofemoral instability and correlation with morphological grading of cartilage damage.

    Science.gov (United States)

    Kang, Chang Ho; Kim, Hee Kyung; Shiraj, Sahar; Anton, Christopher; Kim, Dong Hoon; Horn, Paul S

    2016-07-01

    Patellofemoral instability is one of the most common causes of cartilage damage in teenagers. To quantitatively evaluate the patellar cartilage in patients with patellofemoral instability using T2 relaxation time maps (T2 maps), compare the values to those in patients without patellofemoral instability and correlate them with morphological grades in patients with patellofemoral instability. Fifty-three patients with patellofemoral instability (mean age: 15.9 ± 2.4 years) and 53 age- and gender-matched patients without patellofemoral instability were included. Knee MR with axial T2 map was performed. Mean T2 relaxation times were obtained at the medial, central and lateral zones of the patellar cartilage and compared between the two groups. In the patellofemoral instability group, morphological grading of the patellar cartilage (0-4) was performed and correlated with T2 relaxation times. Mean T2 relaxation times were significantly longer in the group with patellofemoral instability as compared to those of the control group across the patellar cartilage (Student's t-test, Ppatellofemoral instability, patellar cartilage damage occurs across the entire cartilage with the highest T2 values at the apex. T2 relaxation times directly reflect the severity in low-grade cartilage damage, which implies an important role for T2 maps in differentiating between normal and low-grade cartilage damage.

  6. Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence

    Directory of Open Access Journals (Sweden)

    Francesco Perdisa

    2015-01-01

    Full Text Available Among the current therapeutic approaches for the regeneration of damaged articular cartilage, none has yet proven to offer results comparable to those of native hyaline cartilage. Recently, it has been claimed that the use of mesenchymal stem cells (MSCs provides greater regenerative potential than differentiated cells, such as chondrocytes. Among the different kinds of MSCs available, adipose-derived mesenchymal stem cells (ADSCs are emerging due to their abundancy and easiness to harvest. However, their mechanism of action and potential for cartilage regeneration are still under investigation, and many other aspects still need to be clarified. The aim of this systematic review is to give an overview of in vivo studies dealing with ADSCs, by summarizing the main evidence for the treatment of cartilage disease of the knee.

  7. Whole meniscus regeneration using polymer scaffolds loaded with fibrochondrocytes

    Directory of Open Access Journals (Sweden)

    LU Hua-ding

    2012-02-01

    Full Text Available 【Abstract】Objective: To study the feasibility of regenerating a whole menisci using poly- (3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV scaffolds loaded with meniscal cells in rabbits undergoing total meniscectomy, and to explore its protective effect on cartilage degeneration. Methods: A solvent casting and particulate leaching technique was employed to fabricate biodegradable PHBV scaffolds into a meniscal shape. The proliferated meniscal cells were seeded onto the polymer scaffolds, transplanted into rabbit knee joints whose lateral menisci had been removed. Eight to 18 weeks after transplantation, the regenerated neomenisci were evaluated by gross and histological observations. Cartilage degeneration was assessed by Mankin score. Results: Eighteen weeks after transplantation, the implants formed neomenisci. Hematoxylin and eosin (HE staining of the neomenisci sections revealed regeneration of fibrocartilage. Type I collagen in the neomenisci was also proved similar to normal meniscal tissue by immunohistochemical analysis and Sirius scarlet trinitrophenol staining. Articular cartilage degeneration was observed 8 weeks after implantation. It was less severe as compared with that in total meniscectomy controls and no further degeneration was observed at 18 weeks. At that time, the regenerated neomenisci strongly resembled normal meniscal fibrocartilage in gross and histological appearance, and its mechani- cal property was also close to that of normal meniscus. Conclusions: The present study demonstrates the feasibility of tissue-engineering a whole meniscal structure in total meniscectomy rabbit models using biodegradable PHBV scaffolds together with cultured allogeneic meniscal cells. Cartilage degeneration is decreased. But long-term in vivo investigations on the histological structure and cartilage degeneration of the neomenisci regenerated by this method are still necessary to determine the clinical potential of this tissue

  8. Cartilage Repair Using Composites of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel in a Minipig Model.

    Science.gov (United States)

    Ha, Chul-Won; Park, Yong-Beom; Chung, Jun-Young; Park, Yong-Geun

    2015-09-01

    The cartilage regeneration potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with a hyaluronic acid (HA) hydrogel composite has shown remarkable results in rat and rabbit models. The purpose of the present study was to confirm the consistent regenerative potential in a pig model using three different cell lines. A full-thickness chondral injury was intentionally created in the trochlear groove of each knee in 6 minipigs. Three weeks later, an osteochondral defect, 5 mm wide by 10 mm deep, was created, followed by an 8-mm-wide and 5-mm-deep reaming. A mixture (1.5 ml) of hUCB-MSCs (0.5×10(7) cells per milliliter) and 4% HA hydrogel composite was then transplanted into the defect on the right knee. Each cell line was used in two minipigs. The osteochondral defect created in the same manner on the left knee was untreated to act as the control. At 12 weeks postoperatively, the pigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. The cellular characteristics (e.g., cellular proliferation and chondrogenic differentiation capacity) of the hUCB-MSCs influenced the degree of cartilage regeneration potential. This evidence of consistent cartilage regeneration using composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future. To date, several studies have investigated the chondrogenic potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs); however, the preclinical studies are still limited in numbers with various results. In parallel, in the past several years, the cartilage regeneration potential of hUCB-MSCs with a hyaluronic acid (HA) hydrogel composite have been investigated and remarkable results in rat and rabbit models have been attained. (These

  9. Laser-induced modification of structure and shape of cartilage in otolaryngology and orthopaedics

    Science.gov (United States)

    Sobol', E. N.; Baum, O. I.; Omel'chenko, A. I.; Soshnikova, Yu. M.; Yuzhakov, A. V.; Kas'yanenko, E. M.; Tokareva, A. V.; Baskov, A. V.; Svistushkin, V. M.; Selezneva, L. V.; Shekhter, A. B.

    2017-11-01

    We present the results of basic research in laser modification of tissues in otolaryngology (correcting the shape of nasal septum and larynx cartilages), cosmetology (correcting ear and nose shape), orthopaedics and spinal surgery (treatment of diseases of spine disc and joints). The physical processes and mechanisms of laser-induced relaxation of stresses and regeneration of tissues are considered. New results of studies in this fast-developing field of laser surgery are presented, in particular, the results of laser correction of costal cartilage shape in the process of making implants for the treatment of larynx stenosis and controlled regeneration of the hyaline articular cartilage. Presented at the Fundamentals of Laser Assisted Micro- and Nanotechnologies (FLAMN-2016) International Symposium (Pushkin, Leningrad oblast, 27 June to 1 July 2016).

  10. Peculiarities in Ankle Cartilage.

    Science.gov (United States)

    Kraeutler, Matthew J; Kaenkumchorn, Tanyaporn; Pascual-Garrido, Cecilia; Wimmer, Markus A; Chubinskaya, Susanna

    2017-01-01

    Posttraumatic osteoarthritis (PTOA) is the most common form of osteoarthritis (OA) of the ankle joint. PTOA occurs as a result of several factors, including the poor regenerative capacity of hyaline articular cartilage as well as increased contact stresses following trauma. The purpose of this article is to review the epidemiology, pathogenesis, and potential targets for treatment of PTOA in the ankle joint. Previous reviews primarily addressed clinical approaches to ankle PTOA, while the focus of the current article will be specifically on the newly acquired knowledge of the cellular mechanisms that drive PTOA in the ankle joint and means for potential targeted therapeutics that might halt the progression of cartilage degeneration and/or improve the outcome of surgical interventions. Three experimental treatment strategies are discussed in this review: (1) increasing the anabolic potential of chondrocytes through treatment with growth factors such as bone morphogenetic protein-7; (2) limiting chondrocyte cell death either through the protection of cell membrane with poloxamer 188 or inhibiting activity of intracellular proteases, caspases, which are responsible for cell death by apoptosis; and (3) inhibiting catabolic/inflammatory responses of chondrocytes by treating them with anti-inflammatory agents such as tumor necrosis factor-α antagonists. Future studies should focus on identifying the appropriate timing for treatment and an appropriate combination of anti-inflammatory, chondro- and matrix-protective biologics to limit the progression of trauma-induced cartilage degeneration and prevent the development of PTOA in the ankle joint.

  11. Cartilage grafting in nasal reconstruction.

    Science.gov (United States)

    Immerman, Sara; White, W Matthew; Constantinides, Minas

    2011-02-01

    Nasal reconstruction after resection for cutaneous malignancies poses a unique challenge to facial plastic surgeons. The nose, a unique 3-D structure, not only must remain functional but also be aesthetically pleasing to patients. A complete understanding of all the layers of the nose and knowledge of available cartilage grafting material is necessary. Autogenous material, namely septal, auricular, and costal cartilage, is the most favored material in a free cartilage graft or a composite cartilage graft. All types of material have advantages and disadvantages that should guide the most appropriate selection to maximize the functional and cosmetic outcomes for patients. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Shintarou Yamane

    2010-12-01

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

  13. Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Saito, Taku; Yano, Fumiko; Mori, Daisuke; Kawata, Manabu; Hoshi, Kazuto; Takato, Tsuyoshi; Masaki, Hideki; Otsu, Makoto; Eto, Koji; Nakauchi, Hiromitsu; Chung, Ung-il; Tanaka, Sakae

    2015-01-01

    Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints. Three hiPSC clones showed efficient chondrogenic differentiation using an established protocol for human embryonic stem cells. The differentiated hiPSCs formed hyaline cartilage tissues at 8 weeks after transplantation into the articular cartilage of NOD/SCID mouse knee joints. Although tumors were not observed during the 8 weeks after transplantation, an immature teratoma had developed in one mouse at 16 weeks. In conclusion, hiPSCs are a potent cell source for regeneration of hyaline articular cartilage. However, the risk of tumorigenesis should be managed for clinical application in the future.

  14. Physical activity is associated with changes in knee cartilage microstructure.

    Science.gov (United States)

    Halilaj, E; Hastie, T J; Gold, G E; Delp, S L

    2018-06-01

    The purpose of this study was to determine if there is an association between objectively measured physical activity and longitudinal changes in knee cartilage microstructure. We used accelerometry and T 2 -weighted magnetic resonance imaging (MRI) data from the Osteoarthritis Initiative, restricting the analysis to men aged 45-60 years, with a body mass index (BMI) of 25-27 kg/m 2 and no radiographic evidence of knee osteoarthritis. After computing 4-year changes in mean T 2 relaxation time for six femoral cartilage regions and mean daily times spent in the sedentary, light, moderate, and vigorous activity ranges, we performed canonical correlation analysis (CCA) to find a linear combination of times spent in different activity intensity ranges (Activity Index) that was maximally correlated with a linear combination of regional changes in cartilage microstructure (Cartilage Microstructure Index). We used leave-one-out pre-validation to test the robustness of the model on new data. Nineteen subjects satisfied the inclusion criteria. CCA identified an Activity Index and a Cartilage Microstructure Index that were significantly correlated (r = .82, P microstructural changes in different cartilage regions than it is with univariate or cumulative changes, likely because this index separates the effect of activity, which is greater in the medial loadbearing region, from that of patient-specific natural aging. Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  15. 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.

  16. Multiparametric MRI of Epiphyseal Cartilage Necrosis (Osteochondrosis with Histological Validation in a Goat Model.

    Directory of Open Access Journals (Sweden)

    Luning Wang

    Full Text Available To evaluate multiple MRI parameters in a surgical model of osteochondrosis (OC in goats.Focal ischemic lesions of two different sizes were induced in the epiphyseal cartilage of the medial femoral condyles of goats at 4 days of age by surgical transection of cartilage canal blood vessels. Goats were euthanized and specimens harvested 3, 4, 5, 6, 9 and 10 weeks post-op. Ex vivo MRI scans were conducted at 9.4 Tesla for mapping the T1, T2, T1ρ, adiabatic T1ρ and TRAFF relaxation times of articular cartilage, unaffected epiphyseal cartilage, and epiphyseal cartilage within the area of the induced lesion. After MRI scans, safranin O staining was conducted to validate areas of ischemic necrosis induced in the medial femoral condyles of six goats, and to allow comparison of MRI findings with the semi-quantitative proteoglycan assessment in corresponding safranin O-stained histological sections.All relaxation time constants differentiated normal epiphyseal cartilage from lesions of ischemic cartilage necrosis, and the histological staining results confirmed the proteoglycan (PG loss in the areas of ischemia. In the scanned specimens, all of the measured relaxation time constants were higher in the articular than in the normal epiphyseal cartilage, consistently allowing differentiation between these two tissues.Multiparametric MRI provided a sensitive approach to discriminate between necrotic and viable epiphyseal cartilage and between articular and epiphyseal cartilage, which may be useful for diagnosing and monitoring OC lesions and, potentially, for assessing effectiveness of treatment interventions.

  17. A preliminary study of the T1rho values of normal knee cartilage using 3 T-MRI

    International Nuclear Information System (INIS)

    Goto, Hajimu; Iwama, Yuki; Fujii, Masahiko; Aoyama, Nobukazu; Kubo, Seiji; Kuroda, Ryosuke; Ohno, Yoshiharu; Sugimura, Kazuro

    2012-01-01

    Introduction: To investigate the degree of the effect of aging and weight-bearing on T1rho values in normal cartilage. Materials and methods: Thirty-two asymptomatic patients were examined using 3.0-T magnetic resonance imaging (MRI) to determine knee cartilage T1rho values and T2 values. The femoral and tibial cartilage was divided into weight-bearing (WB-Rs) and less-weight-bearing (LWB-Rs) regions. Single regression analysis was used to assess the relationship between cartilage T1rho values and age and between T2 values and age. Analysis of variance and post hoc-testing were used to evaluate differences in WB-Rs and LWB-Rs cartilage T1rho values and T2 values. Multiple linear regression modeling was performed to predict cartilage T1rho values. Results: Cartilage T1rho values correlated positively with age for all cartilage regions tested (p < 0.001). There were no significant correlations between cartilage T2 values and age. In both the medial femoral and tibial cartilage, T1rho values were significantly higher in WB-Rs than in LWB-Rs (p < 0.05). There were no significant differences in T2 values between WB-Rs and LWB-Rs. Multiple linear regression analysis showed that both age and weight-bearing were significant predictors of increased medial knee cartilage T1rho values (p < 0.001). Conclusions: Aging and the degree of weight-bearing correlate with the change in cartilage T1rho values. Based on multiple regression modeling, aging may be a more important factor than weight-bearing for cartilage T1rho values.

  18. Periodontal regeneration.

    Science.gov (United States)

    Ivanovski, S

    2009-09-01

    The ultimate goal of periodontal therapy is the regeneration of the tissues destroyed as a result of periodontal disease. Currently, two clinical techniques, based on the principles of "guided tissue regeneration" (GTR) or utilization of the biologically active agent "enamel matrix derivative" (EMD), can be used for the regeneration of intrabony and Class II mandibular furcation periodontal defects. In cases where additional support and space-making requirements are necessary, both of these procedures can be combined with a bone replacement graft. There is no evidence that the combined use of GTR and EMD results in superior clinical results compared to the use of each material in isolation. Great variability in clinical outcomes has been reported in relation to the use of both EMD and GTR, and these procedures can be generally considered to be unpredictable. Careful case selection and treatment planning, including consideration of patient, tooth, site and surgical factors, is required in order to optimize the outcomes of treatment. There are limited data available for the clinical effectiveness of other biologically active molecules, such as growth factors and platelet concentrates, and although promising results have been reported, further clinical trials are required in order to confirm their effectiveness. Current active areas of research are centred on tissue engineering and gene therapy strategies which may result in more predictable regenerative outcomes in the future.

  19. Regulators of articular cartilage homeostasis

    NARCIS (Netherlands)

    Leijten, Jeroen Christianus Hermanus

    2012-01-01

    Prevention of hypertrophic differentiation is essential for successful cartilage repair strategies. Although this process is essential for longitudinal growth, it also is part of degenerative cartilage diseases such as osteoarthiritis. Moreover, it limits the use of cell types prone to this process

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

    Energy Technology Data Exchange (ETDEWEB)

    Whu, Shu Wen [Department of Orthopaedic Surgery, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Hung, Kun-Che; Hsieh, Kuo-Huang [Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan (China); Chen, Chih-Hwa [Department of Orthopaedic Surgery, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Tsai, Ching-Lin, E-mail: tsaicl@ntuh.gov.tw [Department of Orthopaedics, National Taiwan University Hospital, Taipei, Taiwan (China); Hsu, Shan-hui, E-mail: shhsu@ntu.edu.tw [Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan (China)

    2013-07-01

    Chitosan–gelatin polyelectrolyte complexes were fabricated and evaluated as tissue engineering scaffolds for cartilage regeneration in vitro and in vivo. The crosslinker for the gelatin component was selected among glutaraldehyde, bisepoxy, and a water-soluble carbodiimide (WSC) based upon the proliferation of chondrocytes on the crosslinked gelatin. WSC was found to be the most suitable crosslinker. Complex scaffolds made from chitosan and gelatin with a component ratio equal to one possessed the proper degradation rate and mechanical stability in vitro. Chondrocytes were able to proliferate well and secrete abundant extracellular matrix in the chitosan–gelatin (1:1) complex scaffolds crosslinked by WSC (C1G1{sub WSC}) compared to the non-crosslinked scaffolds. Implantation of chondrocytes-seeded scaffolds in the defects of rabbit articular cartilage confirmed that C1G1{sub WSC} promoted the cartilage regeneration. The neotissue formed the histological feature of tide line and lacunae in 6.5 months. The amount of glycosaminoglycans in C1G1{sub WSC} constructs (0.187 ± 0.095 μg/mg tissue) harvested from the animals after 6.5 months was 14 wt.% of that in normal cartilage (1.329 ± 0.660 μg/mg tissue). The average compressive modulus of regenerated tissue at 6.5 months was about 0.539 MPa, which approached to that of normal cartilage (0.735 MPa), while that in the blank control (3.881 MPa) was much higher and typical for fibrous tissue. Type II collagen expression in C1G1{sub WSC} constructs was similarly intense as that in the normal hyaline cartilage. According to the above results, the use of C1G1{sub WSC} scaffolds may enhance the cartilage regeneration in vitro and in vivo. - Highlights: • We developed a chitosan–gelatin scaffold crosslinked with carbodiimide. • Neocartilage formation was more evident in crosslinked vs. non-crosslinked scaffolds. • Histological features of tide line and lacunae were observed in vivo at 6.5 months. • Compressive

  1. Covalent binding of bone morphogenetic protein-2 and transforming growth factor-β3 to 3D plotted scaffolds for osteochondral tissue regeneration

    NARCIS (Netherlands)

    Di Luca, Andrea; Klein Gunnewiek, Michel; Vancso, Julius; van Blitterswijk, Clemens; Benetti, Edmondo Maria; Moroni, Lorenzo

    2017-01-01

    Engineering the osteochondral tissue presents some challenges mainly relying in its function of transition from the subchondral bone to articular cartilage and the gradual variation in several biological, mechanical, and structural features. A possible solution for osteochondral regeneration might

  2. The architecture of cartilage: Elemental maps and scanning transmission ion microscopy/tomography

    International Nuclear Information System (INIS)

    Reinert, Tilo; Reibetanz, Uta; Schwertner, Michael; Vogt, Juergen; Butz, Tilman; Sakellariou, Arthur

    2002-01-01

    Articular cartilage is not just a jelly-like cover of the bone within the joints but a highly sophisticated architecture of hydrated macromolecules, collagen fibrils and cartilage cells. Influences on the physiological balance due to age-related or pathological changes can lead to malfunction and subsequently to degradation of the cartilage. Many activities in cartilage research are dealing with the architecture of joint cartilage but have limited access to elemental distributions. Nuclear microscopy is able to yield spatially resolved elemental concentrations, provides density information and can visualise the arrangement of the collagen fibres. The distribution of the cartilage matrix can be deduced from the elemental and density maps. The findings showed a varying content of collagen and proteoglycan between zones of different cell maturation. Zones of higher collagen content are characterised by aligned collagen fibres that can form tubular structures. Recently we focused on STIM tomography to investigate the three dimensional arrangement of the collagen structures

  3. 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.

  4. Bioprinting Cartilage Tissue from Mesenchymal Stem Cells and PEG Hydrogel.

    Science.gov (United States)

    Gao, Guifang; Hubbell, Karen; Schilling, Arndt F; Dai, Guohao; Cui, Xiaofeng

    2017-01-01

    Bioprinting based on thermal inkjet printing is one of the most attractive enabling technologies for tissue engineering and regeneration. During the printing process, cells, scaffolds , and growth factors are rapidly deposited to the desired two-dimensional (2D) and three-dimensional (3D) locations. Ideally, the bioprinted tissues are able to mimic the native anatomic structures in order to restore the biological functions. In this study, a bioprinting platform for 3D cartilage tissue engineering was developed using a commercially available thermal inkjet printer with simultaneous photopolymerization . The engineered cartilage demonstrated native zonal organization, ideal extracellular matrix (ECM ) composition, and proper mechanical properties. Compared to the conventional tissue fabrication approach, which requires extended UV exposure, the viability of the printed cells with simultaneous photopolymerization was significantly higher. Printed neocartilage demonstrated excellent glycosaminoglycan (GAG) and collagen type II production, which was consistent with gene expression profile. Therefore, this platform is ideal for anatomic tissue engineering with accurate cell distribution and arrangement.

  5. Radiological, computertomographic, pathoanatomical and histological examination of the rib cartilage of the dog

    International Nuclear Information System (INIS)

    Lorber, B.

    2000-06-01

    This study was concerned with the representation and description of the rib cartilage of the dog and the abnormalities of such by means of radiological, computer tomographic, pathoanatomical and histological examinations and the comparison of the results of the various examination methods. The study material consisted of 100 ventral thorax walls of dogs of different ages and breeds. In 39 of the subjects, no abnormalities of rib cartilage other than unremarkable calcification were observed. Among the subjects, there were 11 puppies (0-3 months), whose rib cartilage appeared soft tissue dense due to the absence of calcification, 14 juvenile animals (4-18 months), the rib cartilage of which showed a typical finely granulated structure, and 14 adult dogs (over 18 months), whose rib cartilage exhibited a homogeneous to net-like calcified appearance. In the calcified rib cartilage, the histological section showed a centrally located spongiosa rod surrounded by a hyaline cartilage shell. The calcification tendency of the first pair of rib cartilage was remarkable: in 70 dogs, the first pair of rib cartilage remained uncalcified despite calcification of the other rib cartilage. Sixty-one dogs exhibited rib cartilage abnormalities. According to the radiological appearance of the abnormalities, they were divided into groups and their incidence was calculated. Abnormalities seen included interruption in the continuity of the calcified rib cartilage with and without callus formation, enlargement of rib cartilage, cuff formation, and abnormalities on the Articulationes sternocostales (projections in or around articulations, calcified and fractured joint surfaces). In addition, remarkable calcification patterns were observed. By means of CT examination the densities of the tissue forming the various abnormalities was determined. In the course of the pathoanatomical examination, it was shown that the interruptions in continuity with callus and the various enlarged areas of the

  6. A new solution in cartilage repair surgery of joint lesions

    Directory of Open Access Journals (Sweden)

    Patrascu JM¹,

    2016-12-01

    Full Text Available OBJECTIVES AND BACKGROUND The purpose of this study is to provide a simple, cost-effective, reproducible technology that is able to regenerate durable hyaline cartilage. Traumas and sports along with different diseases such as obesity or gradual degeneration over time of the joint surface determine cartilage defects resulting in pain and dysfunctionality. MATERIALS AND METHODS Since 2011 a number of 183 pacients were treated using Agili-C, out of which 40 pacients were operated in the IInd Clinic of Orthopaedics of the Timișoara Emergency County Hospital. The implant is a biphasic, porous, resorbable tissue regeneration scaffold used in the treatment of osteochondral defects. The surgical procedure is performed through minimal arthrotomy, with a good exposure of the cartilage defect. The implant is inserted so that the articular surface of the implant is parallel with the surrounding healthy cartilage. When in place, it facilitates vascularization thus allowing tissue formation to commence from the periphery towards the center of the defect. RESULTS Until now, results are promising, showing obvious improvements in pain and function in both degenerative and post-traumatic joint lesions in the knee, ankle and first MP joint. CONCLUSIONS Agili-C is a cell free, single stage, off the shelf implant that will hopefully meet market demands and become a reliable procedure in joint repair surgery in the future. Figure 1: Intra-operative aspect after the implant is in place. REFERENCES 1. Mehdi Kazemzadeh-Narbat et al. Biomaterials.2010. p.31. 2. Scaglione et al. Tissue engineering: Part A. 2009;15:1. FOOTNOTE Agili-C is a product of CartiHeal Company

  7. Scale-dependent variation in nitrogen cycling and soil fungal communities along gradients of forest composition and age in regenerating tropical dry forests.

    Science.gov (United States)

    Waring, Bonnie G; Adams, Rachel; Branco, Sara; Powers, Jennifer S

    2016-01-01

    Rates of ecosystem nitrogen (N) cycling may be mediated by the presence of ectomycorrhizal fungi, which compete directly with free-living microbes for N. In the regenerating tropical dry forests of Central America, the distribution of ectomycorrhizal trees is affected by succession and soil parent material, both of which may exert independent influence over soil N fluxes. In order to quantify these interacting controls, we used a scale-explicit sampling strategy to examine soil N cycling at scales ranging from the microsite to ecosystem level. We measured fungal community composition, total and inorganic N pools, gross proteolytic rate, net N mineralization and microbial extracellular enzyme activity at multiple locations within 18 permanent plots that span dramatic gradients of soil N concentration, stand age and forest composition. The ratio of inorganic to organic N cycling was correlated with variation in fungal community structure, consistent with a strong influence of ectomycorrhiza on ecosystem-scale N cycling. However, on average, > 61% of the variation in soil biogeochemistry occurred within plots, and the effects of forest composition were mediated by this local-scale heterogeneity in total soil N concentrations. These cross-scale interactions demonstrate the importance of a spatially explicit approach towards an understanding of controls on element cycling. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  8. 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.

  9. Natural Type II Collagen Hydrogel, Fibrin Sealant, and Adipose-Derived Stem Cells as a Promising Combination for Articular Cartilage Repair.

    Science.gov (United States)

    Lazarini, Mariana; Bordeaux-Rego, Pedro; Giardini-Rosa, Renata; Duarte, Adriana S S; Baratti, Mariana Ozello; Zorzi, Alessandro Rozim; de Miranda, João Batista; Lenz Cesar, Carlos; Luzo, Ângela; Olalla Saad, Sara Teresinha

    2017-10-01

    Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.

  10. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Moussa, Mayssam, E-mail: Moussa-mayssam@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Lajeunesse, Daniel, E-mail: daniel.lajeunesse@umontreal.ca [Research Centre in Osteoarthritis, Research Centre in Monteral University (Canada); Hilal, George, E-mail: George2266@gmail.com [Cancer and metabolism Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); El Atat, Oula, E-mail: oulaatat@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Haykal, Gaby, E-mail: Gaby.haykal@hdf.usj.edu.lb [Hotel Dieu de France, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Serhal, Rim, E-mail: rim.basbous@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Chalhoub, Antonio, E-mail: Mava.o@hotmail.com [Carantina Hospital, Beirut (Lebanon); Khalil, Charbel, E-mail: charbelk3@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Alaaeddine, Nada, E-mail: Nada.aladdin@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon)

    2017-03-01

    Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1–2–3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. Conclusion: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. - Highlights: • Platelet Rich Plasma is suggested as a new treatment for osteoarthritis. • The proposed therapeutic effect is

  11. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

    International Nuclear Information System (INIS)

    Moussa, Mayssam; Lajeunesse, Daniel; Hilal, George; El Atat, Oula; Haykal, Gaby; Serhal, Rim; Chalhoub, Antonio; Khalil, Charbel; Alaaeddine, Nada

    2017-01-01

    Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1–2–3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. Conclusion: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. - Highlights: • Platelet Rich Plasma is suggested as a new treatment for osteoarthritis. • The proposed therapeutic effect is

  12. Magnetically targeted delivery through cartilage

    Science.gov (United States)

    Jafari, Sahar; Mair, Lamar O.; Chowdhury, Sagar; Nacev, Alek; Hilaman, Ryan; Stepanov, Pavel; Baker-McKee, James; Ijanaten, Said; Koudelka, Christian; English, Bradley; Malik, Pulkit; Weinberg, Irving N.

    2018-05-01

    In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T) generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis.

  13. Magnetically targeted delivery through cartilage

    Directory of Open Access Journals (Sweden)

    Sahar Jafari

    2018-05-01

    Full Text Available In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis.

  14. T2 Relaxation Time Mapping of Proximal Tibiofibular Cartilage by 3-Tesla Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Kwack, Kyu-Sung; Cho, Jae Hyun; Kim, Jun Man; Kim, Sun Yong; Min, Byoung-Hyun; Yoon, Seung-Hyun

    2009-01-01

    Background: The proximal tibiofibular joint (PTFJ) can be considered the fourth compartment of the knee joint. However, there have been no studies of the T2 values (T2 relaxation time) of PTFJ cartilage. Purpose: To assess the T2 values of PTFJ cartilage at 3T magnetic resonance imaging (MRI), and to show the clinical utility of T2 values of PTFJ cartilage for the diagnosis of osteoarthritis (OA). Material and Methods: 118 patients who had knee MR imaging and knee radiography were enrolled. MRI was performed using a 3T MRI scanner, and T2 maps were calculated from a sagittal multi-echo acquisition. Two regions of interest (ROIs) were positioned within PTFJ cartilage and medial femoral condyle (MFC) cartilage. The average T2 value and standard deviation (SD) of each ROI were recorded. Using PTFJ cartilage as a standard reference, the T2 index ((MFC/PTFJ)x100) and T2SD index ((MFCSD/PTFJSD)x100) were calculated. A paired t test was performed to compare the mean and SD of ROIs within PTFJ and MFC cartilage. Correlation analyses were performed among the parameters age, Kellgren-Lawrence (KL) score, means and SDs of ROIs within PTFJ and MFC cartilage, T2 index, and T2SD index. Results: PTFJ cartilage had a significantly shorter T2 value than did MFC cartilage (P<0.0001). ROIs within PTFJ cartilage showed significantly smaller SDs than did those within MFC cartilage (P<0.0001). The average T2 value and SD of MFC and the T2SD index showed a positive correlation to the KL score (P<0.05). The correlation coefficients for the average T2 value, SD, and T2SD index of MFC were R=0.203, 0.254, and 0.268, respectively. However, there was no significant correlation between T2 values of PTFJ cartilage and KL score (P=0.643). Conclusion: PTFJ cartilage showed shorter and more homogeneous T2 values with a small SD than did MFC cartilage, regardless of the degree of OA at femorotibial compartments. PTFJ cartilage may be a useful internal standard reference to diagnose OA and would be

  15. T2 Relaxation Time Mapping of Proximal Tibiofibular Cartilage by 3-Tesla Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kwack, Kyu-Sung; Cho, Jae Hyun; Kim, Jun Man; Kim, Sun Yong (Dept. of Radiology, Ajou Univ. Medical Center, Suwon (Korea)); Min, Byoung-Hyun; Yoon, Seung-Hyun (Cartilage Regeneration Center, Ajou Univ. Medical Center, Suwon (Korea))

    2009-11-15

    Background: The proximal tibiofibular joint (PTFJ) can be considered the fourth compartment of the knee joint. However, there have been no studies of the T2 values (T2 relaxation time) of PTFJ cartilage. Purpose: To assess the T2 values of PTFJ cartilage at 3T magnetic resonance imaging (MRI), and to show the clinical utility of T2 values of PTFJ cartilage for the diagnosis of osteoarthritis (OA). Material and Methods: 118 patients who had knee MR imaging and knee radiography were enrolled. MRI was performed using a 3T MRI scanner, and T2 maps were calculated from a sagittal multi-echo acquisition. Two regions of interest (ROIs) were positioned within PTFJ cartilage and medial femoral condyle (MFC) cartilage. The average T2 value and standard deviation (SD) of each ROI were recorded. Using PTFJ cartilage as a standard reference, the T2 index ((MFC/PTFJ)x100) and T2SD index ((MFCSD/PTFJSD)x100) were calculated. A paired t test was performed to compare the mean and SD of ROIs within PTFJ and MFC cartilage. Correlation analyses were performed among the parameters age, Kellgren-Lawrence (KL) score, means and SDs of ROIs within PTFJ and MFC cartilage, T2 index, and T2SD index. Results: PTFJ cartilage had a significantly shorter T2 value than did MFC cartilage (P<0.0001). ROIs within PTFJ cartilage showed significantly smaller SDs than did those within MFC cartilage (P<0.0001). The average T2 value and SD of MFC and the T2SD index showed a positive correlation to the KL score (P<0.05). The correlation coefficients for the average T2 value, SD, and T2SD index of MFC were R=0.203, 0.254, and 0.268, respectively. However, there was no significant correlation between T2 values of PTFJ cartilage and KL score (P=0.643). Conclusion: PTFJ cartilage showed shorter and more homogeneous T2 values with a small SD than did MFC cartilage, regardless of the degree of OA at femorotibial compartments. PTFJ cartilage may be a useful internal standard reference to diagnose OA and would be

  16. Bionanomaterials for skin regeneration

    CERN Document Server

    Leonida, Mihaela D

    2016-01-01

    This book gives a concise overview of bionanomaterials with applications for skin regeneration. The advantages and challenges of nanoscale materials are covered in detail, giving a basic view of the skin structure and conditions that require transdermal or topical applications. Medical applications, such as wound healing, care for burns, skin disease, and cosmetic care, such as aging of the skin and photodamage, and how they benefit from bionanomaterials, are described in detail. A final chapter is devoted to the ethical and social issues related to the use of bionanomaterials for skin regeneration. This is an ideal book for researchers in materials science, medical scientists specialized in dermatology, and cosmetic chemists working in formulations. It can also serve as a reference for nanotechnologists, dermatologists, microbiologists, engineers, and polymer chemists, as well as students studying in these fields.

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

    Science.gov (United States)

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

    2016-01-01

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

  18. EVALUATION OF INHOMOGENEITIES IN HISTOLOGICAL STRUCTURES (CARTILAGE, RETINA

    Directory of Open Access Journals (Sweden)

    Lutz Muche

    2011-05-01

    Full Text Available This paper investigates histological tissues by means of image analysis and spatial statistics. For the quantification of cell frequencies and accumulations two statistical characteristics, intensity function and cluster density, are suggested. The samples are histological sections of human articular cartilage and human retina considered in view of changes during the ageing process. The articular cartilage is characterized by continuous changes of both functions, the cell intensity as well as the clusterization. In contrast, the retina is a trilaminar structure formed in the early embryonic stage without changes by ageing.

  19. Amphibian tail regeneration in space: effect on the pigmentation of the blastema

    Science.gov (United States)

    Grinfeld, S.; Foulquier, F.; Mitashov, V.; Bruchlinskaia, N.; Duprat, A. M.

    In Urodele amphibians, the tail regenerates after section. This regeneration, including tissues as different as bone (vertebrae), muscle, epidermis and central nervous system (spinal cord), was studied in adult Pleurodeles sent aboard the russian satellite Bion 10 and compared with tail regeneration in synchronous controls. Spinal cord, muscle and cartilage regeneration occurred in space animals as in synchronous controls. One of the most important differences between the two groups was the pigmentation of the blastemas: it was shown in laboratory, to be not due to a difference in light intensity.

  20. Enhanced hyaline cartilage matrix synthesis in collagen sponge scaffolds by using siRNA to stabilize chondrocytes phenotype cultured with bone morphogenetic protein-2 under hypoxia.

    Science.gov (United States)

    Legendre, Florence; Ollitrault, David; Hervieu, Magalie; Baugé, Catherine; Maneix, Laure; Goux, Didier; Chajra, Hanane; Mallein-Gerin, Frédéric; Boumediene, Karim; Galera, Philippe; Demoor, Magali

    2013-07-01

    Cartilage healing by tissue engineering is an alternative strategy to reconstitute functional tissue after trauma or age-related degeneration. However, chondrocytes, the major player in cartilage homeostasis, do not self-regenerate efficiently and lose their phenotype during osteoarthritis. This process is called dedifferentiation and also occurs during the first expansion step of autologous chondrocyte implantation (ACI). To ensure successful ACI therapy, chondrocytes must be differentiated and capable of synthesizing hyaline cartilage matrix molecules. We therefore developed a safe procedure for redifferentiating human chondrocytes by combining appropriate physicochemical factors: hypoxic conditions, collagen scaffolds, chondrogenic factors (bone morphogenetic protein-2 [BMP-2], and insulin-like growth factor I [IGF-I]) and RNA interference targeting the COL1A1 gene. Redifferentiation of dedifferentiated chondrocytes was evaluated using gene/protein analyses to identify the chondrocyte phenotypic profile. In our conditions, under BMP-2 treatment, redifferentiated and metabolically active chondrocytes synthesized a hyaline-like cartilage matrix characterized by type IIB collagen and aggrecan molecules without any sign of hypertrophy or osteogenesis. In contrast, IGF-I increased both specific and noncharacteristic markers (collagens I and X) of chondrocytes. The specific increase in COL2A1 gene expression observed in the BMP-2 treatment was shown to involve the specific enhancer region of COL2A1 that binds the trans-activators Sox9/L-Sox5/Sox6 and Sp1, which are associated with a decrease in the trans-inhibitors of COL2A1, c-Krox, and p65 subunit of NF-kappaB. Our procedure in which BMP-2 treatment under hypoxia is associated with a COL1A1 siRNA, significantly increased the differentiation index of chondrocytes, and should offer the opportunity to develop new ACI-based therapies in humans.

  1. Ingestion of BioCell Collagen®, a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs

    OpenAIRE

    Park, Joosang; Schwartz,

    2012-01-01

    Stephen R Schwartz,1 Joosang Park21International Research Services Inc, Port Chester, NY, USA; 2BioCell Technology, LLC, Newport Beach, CA, USAAbstract: Skin aging and its clinical manifestation is associated with altered molecular metabolism in the extracellular matrix of the dermis. In a pilot open-label study, we investigated the effect of a dietary supplement, BioCell Collagen® (BCC), which contains a naturally occurring matrix of hydrolyzed collagen type II and low-molecular-weig...

  2. Ingestion of BioCell Collagen®, a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs

    OpenAIRE

    Schwartz SR; Park J

    2012-01-01

    Stephen R Schwartz,1 Joosang Park21International Research Services Inc, Port Chester, NY, USA; 2BioCell Technology, LLC, Newport Beach, CA, USAAbstract: Skin aging and its clinical manifestation is associated with altered molecular metabolism in the extracellular matrix of the dermis. In a pilot open-label study, we investigated the effect of a dietary supplement, BioCell Collagen® (BCC), which contains a naturally occurring matrix of hydrolyzed collagen type II and low-molecular-weight h...

  3. Part I: A Comparative Thermal Aging Study on the Regenerability of Rh/Al2O3 and Rh/CexOy-ZrO2 as Model Catalysts for Automotive Three Way Catalysts

    Directory of Open Access Journals (Sweden)

    Qinghe Zheng

    2015-10-01

    Full Text Available The rhodium (Rh component in automotive three way catalysts (TWC experiences severe thermal deactivation during fuel shutoff, an engine mode (e.g., at downhill coasting used for enhancing fuel economy. In a subsequent switch to a slightly fuel rich condition, in situ catalyst regeneration is accomplished by reduction with H2 generated through steam reforming catalyzed by Rh0 sites. The present work reports the effects of the two processes on the activity and properties of 0.5% Rh/Al2O3 and 0.5% Rh/CexOy-ZrO2 (CZO as model catalysts for Rh-TWC. A very brief introduction of three way catalysts and system considerations is also given. During simulated fuel shutoff, catalyst deactivation is accelerated with increasing aging temperature from 800 °C to 1050 °C. Rh on a CZO support experiences less deactivation and faster regeneration than Rh on Al2O3. Catalyst characterization techniques including BET surface area, CO chemisorption, TPR, and XPS measurements were applied to examine the roles of metal-support interactions in each catalyst system. For Rh/Al2O3, strong metal-support interactions with the formation of stable rhodium aluminate (Rh(AlO2y complex dominates in fuel shutoff, leading to more difficult catalyst regeneration. For Rh/CZO, Rh sites were partially oxidized to Rh2O3 and were relatively easy to be reduced to active Rh0 during regeneration.

  4. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage.

    Science.gov (United States)

    Moussa, Mayssam; Lajeunesse, Daniel; Hilal, George; El Atat, Oula; Haykal, Gaby; Serhal, Rim; Chalhoub, Antonio; Khalil, Charbel; Alaaeddine, Nada

    2017-03-01

    Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1-2-3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Cardiomyocyte Regeneration

    Directory of Open Access Journals (Sweden)

    Toshio Nakanishi

    2013-01-01

    Full Text Available The heart was initially believed to be a terminally differentiated organ; once the cardiomyocytes died, no recovery could be made to replace the dead cells. However, around a decade ago, the concept of cardiac stem cells (CSCs in adult hearts was proposed. CSCs differentiate into cardiomyocytes, keeping the heart functioning. Studies have proved the existence of stem cells in the heart. These somatic stem cells have been studied for use in cardiac regeneration. Moreover, recently, induced pluripotent stem cells (iPSCs were invented, and methodologies have now been developed to induce stable cardiomyocyte differentiation and purification of mature cardiomyocytes. A reprogramming method has also been applied to direct reprogramming using cardiac fibroblasts into cardiomyocytes. Here, we address cardiomyocyte differentiation of CSCs and iPSCs. Furthermore, we describe the potential of CSCs in regenerative biology and regenerative medicine.

  6. Heart regeneration.

    Science.gov (United States)

    Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

    2016-07-01

    Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-05-01

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

  8. A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage

    Directory of Open Access Journals (Sweden)

    Nevzat Selim Gokay

    2016-01-01

    Full Text Available The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg, inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg, or nitric oxide precursor L-arginine (200 mg/kg. After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P=0.044 positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

  9. Ingestion of BioCell Collagen(®), a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs.

    Science.gov (United States)

    Schwartz, Stephen R; Park, Joosang

    2012-01-01

    Skin aging and its clinical manifestation is associated with altered molecular metabolism in the extracellular matrix of the dermis. In a pilot open-label study, we investigated the effect of a dietary supplement, BioCell Collagen(®) (BCC), which contains a naturally occurring matrix of hydrolyzed collagen type II and low-molecular-weight hyaluronic acid and chondroitin sulfate, in 26 healthy females who displayed visible signs of natural and photoaging in the face. Daily supplementation with 1 g of BCC for 12 weeks led to a significant reduction of skin dryness/scaling (76%, P = 0.002) and global lines/wrinkles (13.2%, P = 0.028) as measured by visual/tactile score. Additionally, a significant increase in the content of hemoglobin (17.7%, P = 0.018) and collagen (6.3%, P = 0.002) in the skin dermis was observed after 6 weeks of supplementation. At the end of the study, the increase in hemoglobin remained significant (15%, P = 0.008), while the increase in collagen content was maintained, but the difference from baseline was not significant (3.5%, P = 0.134). This study provides preliminary data suggesting that dietary supplementation with BCC elicits several physiological events which can be harnessed to counteract natural photoaging processes to reduce visible aging signs in the human face. A controlled study is necessary to verify these observations.

  10. Ingestion of BioCell Collagen®, a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs

    Science.gov (United States)

    Schwartz, Stephen R; Park, Joosang

    2012-01-01

    Skin aging and its clinical manifestation is associated with altered molecular metabolism in the extracellular matrix of the dermis. In a pilot open-label study, we investigated the effect of a dietary supplement, BioCell Collagen® (BCC), which contains a naturally occurring matrix of hydrolyzed collagen type II and low-molecular-weight hyaluronic acid and chondroitin sulfate, in 26 healthy females who displayed visible signs of natural and photoaging in the face. Daily supplementation with 1 g of BCC for 12 weeks led to a significant reduction of skin dryness/scaling (76%, P = 0.002) and global lines/wrinkles (13.2%, P = 0.028) as measured by visual/tactile score. Additionally, a significant increase in the content of hemoglobin (17.7%, P = 0.018) and collagen (6.3%, P = 0.002) in the skin dermis was observed after 6 weeks of supplementation. At the end of the study, the increase in hemoglobin remained significant (15%, P = 0.008), while the increase in collagen content was maintained, but the difference from baseline was not significant (3.5%, P = 0.134). This study provides preliminary data suggesting that dietary supplementation with BCC elicits several physiological events which can be harnessed to counteract natural photoaging processes to reduce visible aging signs in the human face. A controlled study is necessary to verify these observations. PMID:22956862

  11. Effect of gamma radiation and accelerated aging on the mechanical and thermal behavior of HDPE/HA nano-composites for bone tissue regeneration.

    Science.gov (United States)

    Alothman, Othman Y; Almajhdi, Fahad N; Fouad, H

    2013-09-24

    The replacement of hard tissues demands biocompatible and sometimes bioactive materials with properties similar to those of bone. Nano-composites made of biocompatible polymers and bioactive inorganic nano particles such as HDPE/HA have attracted attention as permanent bone substitutes due to their excellent mechanical properties and biocompatibility. The HDPE/HA nano-composite is prepared using melt blending at different HA loading ratios. For evaluation of the degradation by radiation, gamma rays of 35 kGy, and 70 kGy were used to irradiate the samples at room temperature in vacuum. The effects of accelerated ageing after gamma irradiation on morphological, mechanical and thermal properties of HDPE/HA nano-composites were measured. In Vitro test results showed that the HDPE and all HDPE/HA nano-composites do not exhibit any cytotoxicity to WISH cell line. The results also indicated that the tensile properties of HDPE/HA nano-composite increased with increasing the HA content except fracture strain decreased. The dynamic mechanical analysis (DMA) results showed that the storage and loss moduli increased with increasing the HA ratio and the testing frequency. Finally, it is remarked that all properties of HDPE/HA is dependent on the irradiation dose and accelerated aging. Based on the experimental results, it is found that the addition of 10%, 20% and 30% HA increases the HDPE stiffness by 23%, 44 and 59% respectively. At the same time, the G' increased from 2.25E11 MPa for neat HDPE to 4.7E11 MPa when 30% HA was added to the polymer matrix. Also, significant improvements in these properties have been observed due to irradiation. Finally, the overall properties of HDPE and its nano-composite properties significantly decreased due to aging and should be taken into consideration in the design of bone substitutes. It is attributed that the developed HDPE/HA nano-composites could be a good alternative material for bone tissue regeneration due to their acceptable

  12. Differences in Cartilage-Forming Capacity of Expanded Human Chondrocytes From Ear and Nose and Their Gene Expression Profiles

    NARCIS (Netherlands)

    Hellingman, C.A.; Verwiel, E.T.P.; Slagt, I.; Koevoet, W.; Poublon, R.M.L.; Nolst-Trenite, G.J.; de Jong, R.J.B.; Jahr, H.; van Osch, G.J.V.M.

    2011-01-01

    The aim of this study was to evaluate the potential of culture-expanded human auricular and nasoseptal chondrocytes as cell source for regeneration of stable cartilage and to analyze the differences in gene expression profile of expanded chondrocytes from these specific locations. Auricular

  13. Differences in cartilage-forming capacity of expanded human chondrocytes from ear and nose and their gene expression profiles

    NARCIS (Netherlands)

    Hellingman, Catharine A.; Verwiel, Eugène T. P.; Slagt, Inez; Koevoet, Wendy; Poublon, René M. L.; Nolst-Trenité, Gilbert J.; Baatenburg de Jong, Robert J.; Jahr, Holger; van Osch, Gerjo J. V. M.

    2011-01-01

    The aim of this study was to evaluate the potential of culture-expanded human auricular and nasoseptal chondrocytes as cell source for regeneration of stable cartilage and to analyze the differences in gene expression profile of expanded chondrocytes from these specific locations. Auricular

  14. Premature Calcifications of Costal Cartilages: A New Perspective Premature Calcifications of Costal Cartilages: A New Perspective

    International Nuclear Information System (INIS)

    Rhomberg, W.; Schuster, A.

    2014-01-01

    Calcifications of the costal cartilages occur, as a rule, not until the age of 30 years. The knowledge of the clinical significance of early and extensive calcifications is still incomplete. Materials and Methods. A search was made to find patients below the age of 30 years who showed distinct calcifications of their lower costal cartilages by viewing 360 random samples of intravenous pyelograms and abdominal plain films. The histories, and clinical and laboratory findings of these patients were analyzed. Results. Nineteen patients fulfilled the criteria of premature calcifications of costal cartilages (CCCs). The patients had in common that they were frequently referred to a hospital and were treated by several medical disciplines. Nevertheless many complaints of the patients remained unsolved. Premature CCCs were often associated with rare endocrine disorders, inborn errors of metabolism, and abnormal hematologic findings. Among the metabolic disorders there were 2 proven porphyrias and 7 patients with a suspected porphyria but with inconclusive laboratory findings. Conclusion. Premature CCCs are unlikely to be a normal variant in skeletal radiology. The findings in this small group of patients call for more intensive studies, especially in regard to the putative role of a porphyria

  15. Subchondral drilling for articular cartilage repair: a systematic review of translational research.

    Science.gov (United States)

    Gao, Liang; Goebel, Lars K H; Orth, Patrick; Cucchiarini, Magali; Madry, Henning

    2018-05-03

    Articular cartilage defects may initiate osteoarthritis. Subchondral drilling, a widely applied clinical technique to treat small cartilage defects, does not yield cartilage regeneration. Various translational studies aiming to improve the outcome of drilling have been performed, however, a robust systematic analysis of its translational evidence has been still lacking. Here, we performed a systematic review of the outcome of subchondral drilling for knee cartilage repair in translational animal models. A total of 12 relevant publications studying 198 animals were identified, detailed study characteristics were extracted, and methodological quality and risk of bias were analyzed. Subchondral drilling was superior to defects untreated or treated with abrasion arthroplasty for cartilage repair in multiple translational models. Considerable subchondral bone changes were observed, including subchondral bone cysts and intralesional osteophytes. Furthermore, extensive alterations of the subchondral bone microarchitecture appeared in a temporal pattern in small and large animal models, together with specific topographic aspects of repair. Moreover, variable technical aspects directly affected the outcomes of osteochondral repair. The data from this systematic review indicate that subchondral drilling yields improved short-term structural articular cartilage repair compared with spontaneous repair in multiple small and large animal models. These results have important implications for future investigations aimed at an enhanced translation into clinical settings for the treatment of cartilage defects, highlighting the importance of considering specific aspects of modifiable variables such as improvements in the design and reporting of preclinical studies, together with the need to better understand the underlying mechanisms of cartilage repair following subchondral drilling. © 2018. Published by The Company of Biologists Ltd.

  16. Effects of Chondroitinase ABC-Mediated Proteoglycan Digestion on Decellularization and Recellularization of Articular Cartilage.

    Directory of Open Access Journals (Sweden)

    Catherine A Bautista

    Full Text Available Articular cartilage has a limited capacity to heal itself and thus focal defects often result in the development of osteoarthritis. Current cartilage tissue engineering strategies seek to regenerate injured tissue by creating scaffolds that aim to mimic the unique structure and composition of native articular cartilage. Decellularization is a novel strategy that aims to preserve the bioactive factors and 3D biophysical environment of the native extracellular matrix while removing potentially immunogenic factors. The purpose of this study was to develop a procedure that can enable decellularization and recellularization of intact articular cartilage matrix. Full-thickness porcine articular cartilage plugs were decellularized with a series of freeze-thaw cycles and 0.1% (w/v sodium dodecyl sulfate detergent cycles. Chondroitinase ABC (ChABC was applied before the detergent cycles to digest glycosaminoglycans in order to enhance donor chondrocyte removal and seeded cell migration. Porcine synovium-derived mesenchymal stem cells were seeded onto the decellularized cartilage scaffolds and cultured for up to 28 days. The optimized decellularization protocol removed 94% of native DNA per sample wet weight, while collagen content and alignment were preserved. Glycosaminoglycan depletion prior to the detergent cycles increased removal of nuclear material. Seeded cells infiltrated up to 100 μm into the cartilage deep zone after 28 days in culture. ChABC treatment enhances decellularization of the relatively dense, impermeable articular cartilage by reducing glycosaminoglycan content. ChABC treatment did not appear to affect cell migration during recellularization under static, in vitro culture, highlighting the need for more dynamic seeding methods.

  17. Laser biostimulation of articular cartilage: in vitro evaluation

    Science.gov (United States)

    Jia, Yali; Guo, Zhouyi; Yang, Xiaohong; Zeng, Chang-Chun

    2004-07-01

    In the orthopaedic field, the repair of ariticular cartilage is still a difficult problem, because of the physiological characters of cartilaginous tissues and chondrocytes. To find an effective method of stimulating their regeneration, this in vitro study focuses on the biostimulation of rabbit articular chondrocytes by low-power He-Ne laser. The articular chondrocytes isolated from the cartilage of the medial condyle of the femur of the rabbit were incubated in HamF12 medium. The second passage culture were spread on 24 petri dishes and were irradiated with laser at power density of 2 - 12 mW/cm2 for 6.5 minutes, corresponding to the energy density of 1-6 J/cm2. Laser treatment was performed three times at a 24-hour interval. After lasering, incubation was continued for 24 hours. Non-irradiated cells were kept under the same conditions as the irradiated ones. The cell proliferation activity was evaluated with a XTT colorimetric method. Irradiation of 4 - 6 J/cm2 revealed a considerably higher cell proliferation activity comparing to control cultures. Thereinto, the energy density of 4 and 5 J/cm2 remarkably increased cell growth (P<0.01). The present study showed that a particular laser irradiation stimulates articular chondrocytes proliferation. These findings might be clinically relevant, indicating that low-power laser irradiation treatment is likely to achieve the repair of articular cartilage in clinic.

  18. Repair and tissue engineering techniques for articular cartilage.

    Science.gov (United States)

    Makris, Eleftherios A; Gomoll, Andreas H; Malizos, Konstantinos N; Hu, Jerry C; Athanasiou, Kyriacos A

    2015-01-01

    Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

  19. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and morphologic MRI of cartilage in the long-term follow-up after Legg–Calvé–Perthes disease (LCPD)

    International Nuclear Information System (INIS)

    Holstein, Arne; Zilkens, Christoph; Bittersohl, Bernd

    2011-01-01

    The purpose of the present study was to evaluate the feasibility of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the detection of cartilage changes versus morphologic imaging in the long-term course of Legg–Calvé–Perthes disease (LCPD). A total of 31 hips in 26 patients (mean age, 30.0 years; range, 18–54 years) who were diagnosed with LCPD in childhood were included. Twenty-one radiographically normal contralateral hips served as controls. dGEMRIC indices of femoral and acetabular cartilage in the weight-bearing zone. Cartilage morphology was classified on radial PD-weighted images according to the modified Outerbridge classification. Mean dGEMRIC values of cartilage were significantly lower in hips after LCPD than in the radiographically normal contralateral hips (513 ± 100 ms vs. 579 ± 103 ms; P = 0.026). In 24 out of 31 LCPD hips and in 4 out of 21 radiographically normal contralateral hips, morphological cartilage changes were noted. Analysis of variance analysis revealed a significant influence of Outerbridge grading on decreased T1-values (P = 0.031). Our results suggest that dGEMRIC at 1.5 T is suitable to assess cartilage quality changes in the long-term follow-up after LCPD. The evaluation of biochemical cartilage quality with dGEMRIC may provide additional information about early cartilage changes occurring without visible alterations of cartilage morphology.

  20. 3D Bioprinting of Cartilage for Orthopedic Surgeons: Reading between the Lines.

    Science.gov (United States)

    Di Bella, Claudia; Fosang, Amanda; Donati, Davide M; Wallace, Gordon G; Choong, Peter F M

    2015-01-01

    Chondral and osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopedic surgeon and for the patient. The lack of therapeutic strategies capable to reconstitute the function and structure of hyaline cartilage and to halt the progression toward osteoarthritis has brought clinicians and scientists together, to investigate the potential role of tissue engineering as a viable alternative to current treatment modalities. In particular, the role of bioprinting is emerging as an innovative technology that allows for the creation of organized 3D tissue constructs via a "layer-by-layer" deposition process. This process also has the capability to combine cells and biomaterials in an ordered and predetermined way. Here, we review the recent advances in cartilage bioprinting and we identify the current challenges and the directions for future developments in cartilage regeneration.

  1. 3D-BIOPRINTING OF CARTILAGE FOR ORTHOPAEDIC SURGEONS.READING BETWEEN THE LINES

    Directory of Open Access Journals (Sweden)

    Claudia eDi Bella

    2015-08-01

    Full Text Available Chondral and Osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopaedic surgeon and for the patient. The lack of therapeutic strategies capable to reconstitute the function and structure of hyaline cartilage and to halt the progression towards osteoarthritis has brought clinicians and scientists together, to investigate the potential role of tissue engineering as a viable alternative to current treatment modalities. In particular, the role of bioprinting is emerging as an innovative technology that allows for the creation of organized 3D tissue constructs via a layer-by-layer deposition process. This process also has the capability to combine cells and biomaterials in an ordered and predetermined way. Here we review the recent advances in cartilage bioprinting and we identify the current challenges and the directions for future developments in cartilage regeneration.

  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. 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.

  4. Relationship between the trochlear groove angle and patellar cartilage morphology defined by 3D spoiled gradient-echo imaging

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Yuko; Tokuda, Osamu; Matsunaga, Naofumi [Yamaguchi University Graduate School of Medicine, Department of Radiology, Yamaguchi (Japan); Fukuda, Kouji [Shunan Memorial Hospital, Division of Radiological Technology, Yamaguchi (Japan); Shiraishi, Gen; Motomura, Tetsuhisa [Shunan Memorial Hospital, Department of Orthopedics Surgery, Yamaguchi (Japan); Kimura, Motoichi [Customer Application Gr., GE Healthcare MR Sales and Marketing Department, Osaka (Japan)

    2012-05-15

    To examine whether the femoral trochlear groove angle (TGA) is a determinant of the patellar cartilage volume and patellar cartilage damage. Patellar cartilage was evaluated by MR imaging in 66 patients (22 males and 44 females) with knee pain. Fat-suppressed 3D spoiled gradient-echo images were used to calculate the cartilage volume and to grade the cartilage damage. The proximal and distal TGAs were measured from axial PD-weighted FSE MR images with fat suppression. For every increase in the TGA at the distal femur, the patellar cartilage volume was significantly increased by 6.07 x 10{sup -3} cm{sup 3} (95% CI: 1.27 x 10{sup -3}, 10.9 x 10{sup -3}) after adjustment for age, gender, and patellar bone volume (P < 0.05). The MR grade of medial patellar cartilage damage progressed as the distal TGA became narrower, although there was no significant correlation between the distal TGA and the MR grading of patellar cartilage damage. A more flattened distal TGA was associated with increased patellar cartilage volume. However, there was no association between TGA and patellar cartilage defects. (orig.)

  5. Effect of platelet-rich plasma on fibrocartilage, cartilage, and bone repair in temporomandibular joint.

    Science.gov (United States)

    Kütük, Nükhet; Baş, Burcu; Soylu, Emrah; Gönen, Zeynep Burçin; Yilmaz, Canay; Balcioğlu, Esra; Özdamar, Saim; Alkan, Alper

    2014-02-01

    The purpose of the present study was to explore the potential use of platelet-rich-plasma (PRP) in the treatment of temporomandibular joint osteoarthritis (TMJ-OA). Surgical defects were created bilaterally on the condylar fibrocartilage, hyaline cartilage, and bone to induce an osteoarthritic TMJ in rabbits. PRP was applied to the right joints of the rabbits (PRP group), and the left joints received physiologic saline (control group). After 4 weeks, the rabbits were sacrificed for histologic and scanning electron microscopy (SEM) examinations. The data were analyzed statistically. The new bone regeneration was significantly greater in the PRP group (P fibrocartilage and hyaline cartilage was greater in the PRP group, no statistically significant difference was found between the 2 groups. SEM showed better ultrastructural architecture of the collagen fibrils in the PRP group. PRP might enhance the regeneration of bone in TMJ-OA. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Patellofemoral instability in children: T2 relaxation times of the patellar cartilage in patients with and without patellofemoral instability and correlation with morphological grading of cartilage damage

    International Nuclear Information System (INIS)

    Kang, Chang Ho; Kim, Hee Kyung; Shiraj, Sahar; Anton, Christopher; Kim, Dong Hoon; Horn, Paul S.

    2016-01-01

    Patellofemoral instability is one of the most common causes of cartilage damage in teenagers. To quantitatively evaluate the patellar cartilage in patients with patellofemoral instability using T2 relaxation time maps (T2 maps), compare the values to those in patients without patellofemoral instability and correlate them with morphological grades in patients with patellofemoral instability. Fifty-three patients with patellofemoral instability (mean age: 15.9 ± 2.4 years) and 53 age- and gender-matched patients without patellofemoral instability were included. Knee MR with axial T2 map was performed. Mean T2 relaxation times were obtained at the medial, central and lateral zones of the patellar cartilage and compared between the two groups. In the patellofemoral instability group, morphological grading of the patellar cartilage (0-4) was performed and correlated with T2 relaxation times. Mean T2 relaxation times were significantly longer in the group with patellofemoral instability as compared to those of the control group across the patellar cartilage (Student's t-test, P<0.05) with the longest time at the central area. Positive correlation was seen between mean T2 relaxation time and morphological grading (Pearson correlation coefficiency, P<0.001). T2 increased with severity of morphological grading from 0 to 3 (mixed model, P<0.001), but no statistical difference was seen between grades 3 and 4. In patellofemoral instability, patellar cartilage damage occurs across the entire cartilage with the highest T2 values at the apex. T2 relaxation times directly reflect the severity in low-grade cartilage damage, which implies an important role for T2 maps in differentiating between normal and low-grade cartilage damage. (orig.)

  7. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Peter Succar

    2016-01-01

    Full Text Available Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC therapy are gaining acceptance for knee-osteoarthritis (OA treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL. At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.

  8. Evaluation of degenerative changes in articular cartilage of osteoarthritis by Raman spectroscopy

    Science.gov (United States)

    Oshima, Yusuke; Ishimaru, Yasumitsu; Kiyomatsu, Hiroshi; Hino, Kazunori; Miura, Hiromasa

    2018-02-01

    Osteoarthritis (OA) is a very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this proposal, we aim to develop Raman spectroscopic system for the quality assessment of articular cartilage during arthroscopic surgery. Toward this goal, we are focusing on the proteoglycan content and collagen fiber alignment in cartilage matrix which may be associated with degenerative changes in OA, and we designed an original Raman device for remote sensing during arthroscopic surgery. In this project, we define the grading system for cartilage defect based on Raman spectroscopy, and we complete the evaluation of the Raman probing system which makes it possible to detect early stage of degenerative cartilage as a novel tool for OA diagnosis using human subject.

  9. 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.

  10. 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.

  11. Preserved irradiated homologous cartilage for orbital reconstruction

    International Nuclear Information System (INIS)

    Linberg, J.V.; Anderson, R.L.; Edwards, J.J.; Panje, W.R.; Bardach, J.

    1980-01-01

    Human costal cartilage is an excellent implant material for orbital and periorbital reconstruction because of its light weight, strength, homogeneous consistency and the ease with which it can be carved. Its use has been limited by the necessity of a separate surgical procedure to obtain the material. Preserved irradiated homologous cartilage has been shown to have almost all the autogenous cartilage and is convenient to use. Preserved irradiated homologous cartilage transplants do not elicit rejection reactions, resist infection and rarely undergo absorption

  12. MR Imaging of Articular Hyaline Cartilage

    OpenAIRE

    Uetani, Masataka

    2005-01-01

    MR imaging is still an evolving technique for the diagnosis of joint cartilage lesions. Early morphologic changes in the degenerative cartilage are not reliably diagnosed even with use of tailored MR imaging techniques. The detection of the biochemical changes of cartilage or high-resolution MRI will serve as an important tool for the early diagnosis of cartilage degeneration in near future. Further prospective studies are needed to establish the role of MR imaging in clinical use.

  13. The effect of 3D nanofibrous scaffolds on the chondrogenesis of induced pluripotent stem cells and their application in restoration of cartilage defects.

    Science.gov (United States)

    Liu, Ji; Nie, Huarong; Xu, Zhengliang; Niu, Xin; Guo, Shangchun; Yin, Junhui; Guo, Fei; Li, Gang; Wang, Yang; Zhang, Changqing

    2014-01-01

    The discovery of induced pluripotent stem cells (iPSCs) rendered the reprogramming of terminally differentiated cells to primary stem cells with pluripotency possible and provided potential for the regeneration and restoration of cartilage defect. Chondrogenic differentiation of iPSCs is crucial for their application in cartilage tissue engineering. In this study we investigated the effect of 3D nanofibrous scaffolds on the chondrogenesis of iPSCs and articular cartilage defect restoration. Super-hydrophilic and durable mechanic polycaprolactone (PCL)/gelatin scaffolds were fabricated using two separate electrospinning processes. The morphological structure and mechanical properties of the scaffolds were characterized. The chondrogenesis of the iPSCs in vitro and the restoration of the cartilage defect was investigated using scanning electron microscopy (SEM), the Cell Counting Kit-8 (CCK-8), histological observation, RT-qPCR, and western blot analysis. iPSCs on the scaffolds expressed higher levels of chondrogenic markers than the control group. In an animal model, cartilage defects implanted with the scaffold-cell complex exhibited an enhanced gross appearance and histological improvements, higher cartilage-specific gene expression and protein levels, as well as subchondral bone regeneration. Therefore, we showed scaffolds with a 3D nanofibrous structure enhanced the chondrogenesis of iPSCs and that iPSC-containing scaffolds improved the restoration of cartilage defects to a greater degree than did scaffolds alone in vivo.

  14. The effect of 3D nanofibrous scaffolds on the chondrogenesis of induced pluripotent stem cells and their application in restoration of cartilage defects.

    Directory of Open Access Journals (Sweden)

    Ji Liu

    Full Text Available The discovery of induced pluripotent stem cells (iPSCs rendered the reprogramming of terminally differentiated cells to primary stem cells with pluripotency possible and provided potential for the regeneration and restoration of cartilage defect. Chondrogenic differentiation of iPSCs is crucial for their application in cartilage tissue engineering. In this study we investigated the effect of 3D nanofibrous scaffolds on the chondrogenesis of iPSCs and articular cartilage defect restoration. Super-hydrophilic and durable mechanic polycaprolactone (PCL/gelatin scaffolds were fabricated using two separate electrospinning processes. The morphological structure and mechanical properties of the scaffolds were characterized. The chondrogenesis of the iPSCs in vitro and the restoration of the cartilage defect was investigated using scanning electron microscopy (SEM, the Cell Counting Kit-8 (CCK-8, histological observation, RT-qPCR, and western blot analysis. iPSCs on the scaffolds expressed higher levels of chondrogenic markers than the control group. In an animal model, cartilage defects implanted with the scaffold-cell complex exhibited an enhanced gross appearance and histological improvements, higher cartilage-specific gene expression and protein levels, as well as subchondral bone regeneration. Therefore, we showed scaffolds with a 3D nanofibrous structure enhanced the chondrogenesis of iPSCs and that iPSC-containing scaffolds improved the restoration of cartilage defects to a greater degree than did scaffolds alone in vivo.

  15. T2 Relaxation Time Mapping of the Cartilage Cap of Osteochondromas

    OpenAIRE

    Kim, Hee Kyung; Horn, Paul; Dardzinski, Bernard J.; Kim, Dong Hoon; Laor, Tal

    2016-01-01

    Objective Our aim was to evaluate the cartilage cap of osteochondromas using T2 maps and to compare these values to those of normal patellar cartilage, from age and gender matched controls. Materials and Methods This study was approved by the Institutional Review Board and request for informed consent was waived. Eleven children (ages 5-17 years) with osteochondromas underwent MR imaging, which included T2-weighted fat suppressed and T2 relaxation time mapping (echo time = 9-99/repetition tim...

  16. Modeling the development of tissue engineered cartilage

    NARCIS (Netherlands)

    Sengers, B.G.

    2005-01-01

    The limited healing capacity of articular cartilage forms a major clinical problem. In general, current treatments of cartilage damage temporarily reliefs symptoms, but fail in the long term. Tissue engineering (TE) has been proposed as a more permanent repair strategy. Cartilage TE aims at

  17. Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing.

    Science.gov (United States)

    Cunniffe, Gráinne M; Vinardell, Tatiana; Murphy, J Mary; Thompson, Emmet M; Matsiko, Amos; O'Brien, Fergal J; Kelly, Daniel J

    2015-09-01

    Clinical translation of tissue engineered therapeutics is hampered by the significant logistical and regulatory challenges associated with such products, prompting increased interest in the use of decellularized extracellular matrix (ECM) to enhance endogenous regeneration. Most bones develop and heal by endochondral ossification, the replacement of a hypertrophic cartilaginous intermediary with bone. The hypothesis of this study is that a porous scaffold derived from decellularized tissue engineered hypertrophic cartilage will retain the necessary signals to instruct host cells to accelerate endogenous bone regeneration. Cartilage tissue (CT) and hypertrophic cartilage tissue (HT) were engineered using human bone marrow derived mesenchymal stem cells, decellularized and the remaining ECM was freeze-dried to generate porous scaffolds. When implanted subcutaneously in nude mice, only the decellularized HT-derived scaffolds were found to induce vascularization and de novo mineral accumulation. Furthermore, when implanted into critically-sized femoral defects, full bridging was observed in half of the defects treated with HT scaffolds, while no evidence of such bridging was found in empty controls. Host cells which had migrated throughout the scaffold were capable of producing new bone tissue, in contrast to fibrous tissue formation within empty controls. These results demonstrate the capacity of decellularized engineered tissues as 'off-the-shelf' implants to promote tissue regeneration. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  18. Gender differences in knee joint cartilage thickness, volume and articular surface areas: assessment with quantitative three-dimensional MR imaging

    International Nuclear Information System (INIS)

    Faber, S.C.; Reiser, M.; Englmeier, K.H.

    2001-01-01

    Objective: To compare the cartilage thickness, volume, and articular surface areas of the knee joint between young healthy, non-athletic female and male individuals. Subjects and design. MR imaging was performed in 18 healthy subjects without local or systemic joints disease (9 female, age 22.3±2.4 years, and 9 male, age 22.2.±1.9 years), using a fat-suppressed FLASH 3D pulse sequence (TR=41 ms, TE=11 ms, FA=30 ) with sagittal orientation and a spatial resolution of 2x0.31x0.31 mm 3 . After three-dimensional reconstruction and triangulation of the knee joint cartilage plates, the cartilage thickness (mean and maximal), volume, and size of the articular surface area were quantified, independent of the original section orientation. Results and conclusions: Women displayed smaller cartilage volumes than men, the percentage difference ranging from 19.9% in the patella, to 46.6% in the medial tibia. The gender differences of the cartilage thickness were smaller, ranging from 2.0% in the femoral trochlea to 13.3% in the medial tibia for the mean thickness, and from 4.3% in the medial femoral condyle to 18.3% in the medial tibia for the maximal cartilage thickness. The differences between the cartilage surface areas were similar to those of the volumes, with values ranging from 21.0% in the femur to 33.4% in the lateral tibia. Gender differences could be reduced for cartilage volume and surface area when normalized to body weight and body weight x body height. The study demonstrates significant gender differences in cartilage volume and surface area of men and women, which need to be taken into account when retrospectively estimating articular cartilage loss in patients with symptoms of degenerative joint disease. Differences in cartilage volume are primarily due to differences in joint surface areas (epiphyseal bone size), not to differences in cartilage thickness. (orig.)

  19. Delayed Gadolinium-Enhanced Magnetic Resonance Imaging (dGEMRIC) of Hip Joint Cartilage: Better Cartilage Delineation after Intra-Articular than Intravenous Gadolinium Injection

    International Nuclear Information System (INIS)

    Boesen, M.; Jensen, K. E.; Qvistgaard, E.; Danneskiold-Samsoe, B.; Thomsen, C.; Oestergaard, M.; Bliddal, H.

    2006-01-01

    Purpose: To investigate and compare delayed gadolinium (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in the hip joint using intravenous (i.v.) or ultrasound-guided intra-articular (i.a.) Gd-DTPA injection. Material and Methods: In 10 patients (50% males, mean age 58 years) with clinical and radiographic hip osteoarthritis (OA; Kellgren score II-III), MRI of the hip was performed twice on a clinical 1.5T MR scanner: On day 1, before and 90-180 min after 0.3 mmol/kg body weight i.v. Gd-DTPA and, on day 8, 90-180 min after ultrasound-guided i.a. injection of a 4 mmol/l Gd-DTPA solution. Coronal STIR, coronal T1 fat-saturated spin-echo, and a cartilage-sensitive gradient-echo sequence (3D T1 SPGR) in the sagittal plane were applied. Results: Both the post-i.v. and post-i.a. Gd-DTPA images showed significantly higher signal-to-noise (SNR) and contrast-to-noise (CNR) in the joint cartilage compared to the non-enhanced images ( P <0.002). I.a. Gd-DTPA provided significantly higher SNR and CNR compared to i.v. Gd-DTPA ( P <0.01). Furthermore, a better delineation of the cartilage in the synovial/cartilage zone and of the chondral/subchondral border was observed. Conclusion: The dGEMRIC MRI method markedly improved delineation of hip joint cartilage compared to non-enhanced MRI. The i.a. Gd-DTPA provided the best cartilage delineation. dGEMRIC is a clinically applicable MRI method that may improve identification of early subtle cartilage damage and the accuracy of volume measurements of hip joint cartilage

  20. Current status of imaging of articular cartilage

    International Nuclear Information System (INIS)

    Hodler, J.; Resnick, D.

    1996-01-01

    Various imaging methods have been applied to assessment of articular cartilage. These include standard radiography, arthrography, CT, CT arthrography, ultrasonography, and MR imaging. Radiography remains the initial musculoskeletal imaging method. However, it is insensitive to early stages of cartilage abnormalities. MR imaging has great potential in the assessment of articular cartilage, although high-quality scans are required because imaging signs of cartilage abnormalities may be subtle. The potential and limitations of various sequences and techniques are discussed, including MR arthrography. The role of the other imaging methods in assessment of articular cartilage appears to be limited. (orig.). With 8 figs., 6 tabs

  1. 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.

  2. 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

  3. T2 relaxation time mapping of the cartilage cap of osteochondromas

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Kyung; Horn, Paul; Laor, Tal [Cincinnati Children' s Hospital Medical Center, Cincinnati (United States); Daedzinski, Bernard J. [Dept. of Radiology, Children' s Hospital of Philadelphia, University of Pennsylvania, Philadelphia (United States); Kim, Dong Hoon [Dept. of Radiology, Pharmacology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2016-02-15

    Our aim was to evaluate the cartilage cap of osteochondromas using T2 maps and to compare these values to those of normal patellar cartilage, from age and gender matched controls. This study was approved by the Institutional Review Board and request for informed consent was waived. Eleven children (ages 5-17 years) with osteochondromas underwent MR imaging, which included T2-weighted fat suppressed and T2 relaxation time mapping (echo time = 9-99/repetition time = 1500 msec) sequences. Lesion origins were femur (n = 5), tibia (n = 3), fibula (n = 2), and scapula (n = 1). Signal intensity of the cartilage cap, thickness, mean T2 relaxation times, and T2 spatial variation (mean T2 relaxation times as a function of distance) were evaluated. Findings were compared to those of patellar cartilage from a group of age and gender matched subjects. The cartilage caps showed a fluid-like high T2 signal, with mean thickness of 4.8 mm. The mean value of mean T2 relaxation times of the osteochondromas was 264.0 ± 80.4 msec (range, 151.0-366.0 msec). Mean T2 relaxation times were significantly longer than the values from patellar cartilage (39.0 msec) (p < 0.0001). These findings were observed with T2 spatial variation plots across the entire distance of the cartilage cap, with the most pronounced difference in the middle section of the cartilage. Longer T2 relaxation times of the cartilage caps of osteochondromas should be considered as normal, and likely to reflect an increased water content, different microstructure and component.

  4. T2 relaxation time mapping of the cartilage cap of osteochondromas

    International Nuclear Information System (INIS)

    Kim, Hee Kyung; Horn, Paul; Laor, Tal; Daedzinski, Bernard J.; Kim, Dong Hoon

    2016-01-01

    Our aim was to evaluate the cartilage cap of osteochondromas using T2 maps and to compare these values to those of normal patellar cartilage, from age and gender matched controls. This study was approved by the Institutional Review Board and request for informed consent was waived. Eleven children (ages 5-17 years) with osteochondromas underwent MR imaging, which included T2-weighted fat suppressed and T2 relaxation time mapping (echo time = 9-99/repetition time = 1500 msec) sequences. Lesion origins were femur (n = 5), tibia (n = 3), fibula (n = 2), and scapula (n = 1). Signal intensity of the cartilage cap, thickness, mean T2 relaxation times, and T2 spatial variation (mean T2 relaxation times as a function of distance) were evaluated. Findings were compared to those of patellar cartilage from a group of age and gender matched subjects. The cartilage caps showed a fluid-like high T2 signal, with mean thickness of 4.8 mm. The mean value of mean T2 relaxation times of the osteochondromas was 264.0 ± 80.4 msec (range, 151.0-366.0 msec). Mean T2 relaxation times were significantly longer than the values from patellar cartilage (39.0 msec) (p < 0.0001). These findings were observed with T2 spatial variation plots across the entire distance of the cartilage cap, with the most pronounced difference in the middle section of the cartilage. Longer T2 relaxation times of the cartilage caps of osteochondromas should be considered as normal, and likely to reflect an increased water content, different microstructure and component

  5. Hyaline cartilage thickness in radiographically normal cadaveric hips: comparison of spiral CT arthrographic and macroscopic measurements.

    Science.gov (United States)

    Wyler, Annabelle; Bousson, Valérie; Bergot, Catherine; Polivka, Marc; Leveque, Eric; Vicaut, Eric; Laredo, Jean-Denis

    2007-02-01

    To assess spiral multidetector computed tomographic (CT) arthrography for the depiction of cartilage thickness in hips without cartilage loss, with evaluation of anatomic slices as the reference standard. Permission to perform imaging studies in cadaveric specimens of individuals who had willed their bodies to science was obtained from the institutional review board. Two independent observers measured the femoral and acetabular hyaline cartilage thickness of 12 radiographically normal cadaveric hips (from six women and five men; age range at death, 52-98 years; mean, 76.5 years) on spiral multidetector CT arthrographic reformations and on coronal anatomic slices. Regions of cartilage loss at gross or histologic examination were excluded. CT arthrographic and anatomic measurements in the coronal plane were compared by using Bland-Altman representation and a paired t test. Differences between mean cartilage thicknesses at the points of measurement were tested by means of analysis of variance. Interobserver and intraobserver reproducibilities were determined. At CT arthrography, mean cartilage thickness ranged from 0.32 to 2.53 mm on the femoral head and from 0.95 to 3.13 mm on the acetabulum. Observers underestimated cartilage thickness in the coronal plane by 0.30 mm +/- 0.52 (mean +/- standard error) at CT arthrography (P cartilage thicknesses at the different measurement points was significant for coronal spiral multidetector CT arthrography and anatomic measurement of the femoral head and acetabulum and for sagittal and transverse CT arthrography of the femoral head (P cartilage thickness from the periphery to the center of the joint ("gradients") were found by means of spiral multidetector CT arthrography and anatomic measurement. Spiral multidetector CT arthrography depicts cartilage thickness gradients in radiographically normal cadaveric hips. (c) RSNA, 2007.

  6. Development of artificial articular cartilage

    Indian Academy of Sciences (India)

    Mechanical strength of Poly(vinyl alcohol), PVA is improved up to 35 MPa. Manufacturing method is adopted considering colloidal stability of nano silica particle in PVA sol at specific pH = 1. An adhesive is also prepared from PVA/Si nanocomposite containing 40% TEOS for firm attachment of artificial articular cartilage on ...

  7. Postnatal development of articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.

    2010-01-01

    Articular cartilage (AC) is the thin layer of tissue that covers the ends of the bones in the synovial joints in mammals. Functional adult AC has depth-dependent mechanical properties that are not yet present at birth. These depth-dependent mechanical properties in adult life are the result of a

  8. Strategies for Stratified Cartilage Bioprinting

    NARCIS (Netherlands)

    Schuurman, W.|info:eu-repo/dai/nl/313939322

    2012-01-01

    Multiple materials, cells and growth factors can be combined into one construct by the use of a state–of-the-art bioprinter. This technique may in the future make the fabrication of complete tissues or organs possible. In this thesis the feasibility of the bioprinting of cartilage and the

  9. Chondroma of the cricoid cartilage

    Directory of Open Access Journals (Sweden)

    Melo, Giulianno Molina de

    2008-12-01

    Full Text Available Introduction: The larynx cartilaginous tumors are uncommon and comprise 1% of all cartilaginous tumors. The chondroma is the most common benign tumor affecting the larynx cricoid cartilage (75%, and manifests normally in the male gender with dysphonia, progressive dyspnea and dysphagy in some cases. Objective: The objective of this study is to report a case of cricoid cartilage chondroma, in a patient with the symptom of a nodular lesion in the frontal cervical region of slow and progressive growth. Case Report: The treatment was the modified partial laryngectomy with resection of the lower hemisegment of the thyroid cartilage, cricoid hemicartilage and the first tracheal ring with free margins and reconstruction with a pericondrium and muscular prethyroidean piece. The anatomopathological exam showed a chondroma of 1.1 cm, of atypical low cellularity and low figures of mitosis in the frontal region of the cricoid cartilage. Conclusion: In this report we agreed with the literature for the primarily extensive surgical treatment depending on the location and the size of the cricoid chondroma; however, other modalities of treatment may be adopted in cases where the tumor extension appoints a total laryngectomy or when this is not possible to carry out, aiming at the preservation of the larynx. For the suitable treatment of cricoid chondromas, the understanding of the disease natural evolution and more case reports are still necessary.

  10. 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.

  11. 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.

  12. In Vivo Tibial Cartilage Strains in Regions of Cartilage-to-Cartilage Contact and Cartilage-to-Meniscus Contact in Response to Walking.

    Science.gov (United States)

    Liu, Betty; Lad, Nimit K; Collins, Amber T; Ganapathy, Pramodh K; Utturkar, Gangadhar M; McNulty, Amy L; Spritzer, Charles E; Moorman, Claude T; Sutter, E Grant; Garrett, William E; DeFrate, Louis E

    2017-10-01

    There are currently limited human in vivo data characterizing the role of the meniscus in load distribution within the tibiofemoral joint. Purpose/Hypothesis: The purpose was to compare the strains experienced in regions of articular cartilage covered by the meniscus to regions of cartilage not covered by the meniscus. It was hypothesized that in response to walking, tibial cartilage covered by the meniscus would experience lower strains than uncovered tibial cartilage. Descriptive laboratory study. Magnetic resonance imaging (MRI) of the knees of 8 healthy volunteers was performed before and after walking on a treadmill. Using MRI-generated 3-dimensional models of the tibia, cartilage, and menisci, cartilage thickness was measured in 4 different regions based on meniscal coverage and compartment: covered medial, uncovered medial, covered lateral, and uncovered lateral. Strain was defined as the normalized change in cartilage thickness before and after activity. Within each compartment, covered cartilage before activity was significantly thinner than uncovered cartilage before activity ( P meniscus experiences lower strains than uncovered cartilage in the medial compartment. These findings provide important baseline information on the relationship between in vivo tibial compressive strain responses and meniscal coverage, which is critical to understanding normal meniscal function.

  13. Noninvasive assessment of articular cartilage surface damage using reflected polarized light microscopy

    Science.gov (United States)

    Huynh, Ruby N.; Nehmetallah, George; Raub, Christopher B.

    2017-06-01

    Articular surface damage occurs to cartilage during normal aging, osteoarthritis, and in trauma. A noninvasive assessment of cartilage microstructural alterations is useful for studies involving cartilage explants. This study evaluates polarized reflectance microscopy as a tool to assess surface damage to cartilage explants caused by mechanical scraping and enzymatic degradation. Adult bovine articular cartilage explants were scraped, incubated in collagenase, or underwent scrape and collagenase treatments. In an additional experiment, cartilage explants were subject to scrapes at graduated levels of severity. Polarized reflectance parameters were compared with India ink surface staining, features of histological sections, changes in explant wet weight and thickness, and chondrocyte viability. The polarized reflectance signal was sensitive to surface scrape damage and revealed individual scrape features consistent with India ink marks. Following surface treatments, the reflectance contrast parameter was elevated and correlated with image area fraction of India ink. After extensive scraping, polarized reflectance contrast and chondrocyte viability were lower than that from untreated explants. As part of this work, a mathematical model was developed and confirmed the trend in the reflectance signal due to changes in surface scattering and subsurface birefringence. These results demonstrate the effectiveness of polarized reflectance microscopy to sensitively assess surface microstructural alterations in articular cartilage explants.

  14. Is there crosstalk between subchondral bone, cartilage, and meniscus in the pathogenesis of osteoarthritis?

    Science.gov (United States)

    Atik, O Şahap; Erdoğan, Deniz; Seymen, Cemile Merve; Bozkurt, Hasan Hüseyin; Kaplanoğlu, Gülnur Take

    2016-08-01

    This study aims to investigate if there is any crosstalk between subchondral bone, cartilage, and meniscus in the pathogenesis of osteoarthritis. Twelve female patients (mean age 64 years; range 59 to 71 years) with osteoarthritis in medial compartment were included in the study. The samples of subchondral bone, cartilage and meniscus were obtained during total knee arthroplasty. Degenerated tissue samples obtained from medial compartment were used as the experimental group (12 samples of subchondral bone and cartilage, 1x1 cm each; and 12 samples of meniscus, 1x1 cm each). Healthy tissue samples obtained from lateral compartment were used as the control group (12 samples of subchondral bone and cartilage; 1x1 cm each; and 12 samples of meniscus, 1x1 cm each). After decalcification, tissue samples were evaluated with light and transmission electron microscopy. In the experimental group, light microscopic evaluation of subchondral bone samples demonstrated that the cartilage-to-bone transition region had an irregular structure. Degenerated cartilage cells were observed in the transition region and bone cells were significantly corrupted. In the experimental group, light microscopic evaluation of the meniscus samples demonstrated that the intercellular tissue was partly corrupted. Separation and concentration of the collagen fibers were evident. All findings were supported with ultra structural evaluations. Our findings indicate that degeneration of subchondral bone, cartilage, and meniscus probably plays a role in the pathogenesis of osteoarthritis with crosstalk.

  15. Germline Transgenic Methods for Tracking Cells and Testing Gene Function during Regeneration in the Axolotl

    Science.gov (United States)

    Khattak, Shahryar; Schuez, Maritta; Richter, Tobias; Knapp, Dunja; Haigo, Saori L.; Sandoval-Guzmán, Tatiana; Hradlikova, Kristyna; Duemmler, Annett; Kerney, Ryan; Tanaka, Elly M.

    2013-01-01

    The salamander is the only tetrapod that regenerates complex body structures throughout life. Deciphering the underlying molecular processes of regeneration is fundamental for regenerative medicine and developmental biology, but the model organism had limited tools for molecular analysis. We describe a comprehensive set of germline transgenic strains in the laboratory-bred salamander Ambystoma mexicanum (axolotl) that open up the cellular and molecular genetic dissection of regeneration. We demonstrate tissue-dependent control of gene expression in nerve, Schwann cells, oligodendrocytes, muscle, epidermis, and cartilage. Furthermore, we demonstrate the use of tamoxifen-induced Cre/loxP-mediated recombination to indelibly mark different cell types. Finally, we inducibly overexpress the cell-cycle inhibitor p16INK4a, which negatively regulates spinal cord regeneration. These tissue-specific germline axolotl lines and tightly inducible Cre drivers and LoxP reporter lines render this classical regeneration model molecularly accessible. PMID:24052945

  16. Sagittal-Plane Knee Moment During Gait and Knee Cartilage Thickness.

    Science.gov (United States)

    Schmitz, Randy J; Harrison, David; Wang, Hsin-Min; Shultz, Sandra J

    2017-06-02

      Understanding the factors associated with thicker cartilage in a healthy population is important when developing strategies aimed at minimizing the cartilage thinning associated with knee osteoarthritis progression. Thicker articular cartilage is commonly thought to be healthier cartilage, but whether the sagittal-plane biomechanics important to gait are related to cartilage thickness is unknown.   To determine the relationship of a weight-bearing region of the medial femoral condyle's cartilage thickness to sagittal gait biomechanics in healthy individuals.   Descriptive laboratory study.   Laboratory.   Twenty-eight healthy participants (15 women: age = 21.1 ± 2.1 years, height = 1.63 ± 0.07 m, weight = 64.6 ± 9.9 kg; 13 men: age = 22.1 ± 2.9 years, height = 1.79 ± 0.05 m, weight = 75.2 ± 9.6 kg).   Tibiofemoral angle (°) was obtained via goniometric assessment, thickness of the medial femoral condyle cartilage (mm) was obtained via ultrasound imaging, and peak internal knee-extensor moment (% body weight · height) was measured during 10 trials of over-ground walking at a self-selected pace. We used linear regression to examine the extent to which peak internal knee-extensor moment predicted cartilage thickness after accounting for tibiofemoral angle and sex.   Sex and tibiofemoral angle (12.3° ± 3.2°) were entered in the initial step as control factors (R 2 = 0.01, P = .872). In the final step, internal knee-extensor moment (1.5% ± 1.3% body weight · height) was entered, which resulted in greater knee-extensor moment being related to greater cartilage thickness (2.0 ± 0.3 mm; R 2 Δ = 0.31, PΔ = .003).   Individuals who walked with a greater peak internal knee-extensor moment during gait had a cartilage structure that is generally considered beneficial in a healthy population. Our study offers promising findings that a potentially modifiable biomechanical factor is associated with cartilage status in a healthy population

  17. Association between patellar cartilage defects and patellofemoral geometry: a matched-pair MRI comparison of patients with and without isolated patellar cartilage defects.

    Science.gov (United States)

    Mehl, Julian; Feucht, Matthias J; Bode, Gerrit; Dovi-Akue, David; Südkamp, Norbert P; Niemeyer, Philipp

    2016-03-01

    To compare the geometry of the patellofemoral joint on magnetic resonance images (MRI) between patients with isolated cartilage defects of the patella and a gender- and age-matched control group of patients without patellar cartilage defects. A total of 43 patients (17 female, 26 male) with arthroscopically verified grade III and IV patellar cartilage defects (defect group) were compared with a matched-pair control group of patients with isolated traumatic rupture of the anterior cruciate ligament without cartilage defects of the patellofemoral joint. Preoperative MRI images were analysed retrospectively with regard to patellar geometry (width, thickness, facet angle), trochlear geometry (dysplasia according to Dejour, sulcus angle, sulcus depth, lateral condyle index, trochlea facet asymmetry, lateral trochlea inclination) and patellofemoral alignment (tibial tuberosity-trochlear groove distance, patella height, lateral patella displacement, lateral patellofemoral angle, patella tilt, congruence angle). In addition to the comparison of group values, the measured values were compared to normal values reported in the literature, and the frequency of patients with pathologic findings was compared between both groups. The defect group demonstrated a significantly higher proximal chondral sulcus angle (p patellofemoral joint. In particular, a flat and shallow trochlea, trochlea dysplasia and patella alta seem to contribute to the development of patellar cartilage defects, which must be taken into consideration when planning to do surgical cartilage repair at the patella. III.

  18. Diode laser (980nm) cartilage reshaping

    Science.gov (United States)

    El Kharbotly, A.; El Tayeb, T.; Mostafa, Y.; Hesham, I.

    2011-03-01

    Loss of facial or ear cartilage due to trauma or surgery is a major challenge to the otolaryngologists and plastic surgeons as the complicated geometric contours are difficult to be animated. Diode laser (980 nm) has been proven effective in reshaping and maintaining the new geometric shape achieved by laser. This study focused on determining the optimum laser parameters needed for cartilage reshaping with a controlled water cooling system. Harvested animal cartilages were angulated with different degrees and irradiated with different diode laser powers (980nm, 4x8mm spot size). The cartilage specimens were maintained in a deformation angle for two hours after irradiation then released for another two hours. They were serially measured and photographed. High-power Diode laser irradiation with water cooling is a cheep and effective method for reshaping the cartilage needed for reconstruction of difficult situations in otorhinolaryngologic surgery. Key words: cartilage,diode laser (980nm), reshaping.

  19. Preclinical Studies for Cartilage Repair

    Science.gov (United States)

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

    2011-01-01

    Investigational devices for articular cartilage repair or replacement are considered to be significant risk devices by regulatory bodies. Therefore animal models are needed to provide proof of efficacy and safety prior to clinical testing. The financial commitment and regulatory steps needed to bring a new technology to clinical use can be major obstacles, so the implementation of highly predictive animal models is a pressing issue. Until recently, a reductionist approach using acute chondral defects in immature laboratory species, particularly the rabbit, was considered adequate; however, if successful and timely translation from animal models to regulatory approval and clinical use is the goal, a step-wise development using laboratory animals for screening and early development work followed by larger species such as the goat, sheep and horse for late development and pivotal studies is recommended. Such animals must have fully organized and mature cartilage. Both acute and chronic chondral defects can be used but the later are more like the lesions found in patients and may be more predictive. Quantitative and qualitative outcome measures such as macroscopic appearance, histology, biochemistry, functional imaging, and biomechanical testing of cartilage, provide reliable data to support investment decisions and subsequent applications to regulatory bodies for clinical trials. No one model or species can be considered ideal for pivotal studies, but the larger animal species are recommended for pivotal studies. Larger species such as the horse, goat and pig also allow arthroscopic delivery, and press-fit or sutured implant fixation in thick cartilage as well as second look arthroscopies and biopsy procedures. PMID:26069576

  20. Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease.

    Science.gov (United States)

    Hirose, Jun; Ryan, Lawrence M; Masuda, Ikuko

    2002-12-01

    Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi-generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate-layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC-1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals. Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor beta1 (TGFbeta1), which stimulates ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC-1, and ANK were determined by dot-immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage. Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC-1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC-1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes

  1. Human osteoarthritic cartilage is synthetically more active but in culture less vital than normal cartilage

    NARCIS (Netherlands)

    Lafeber, F. P.; van Roy, H.; Wilbrink, B.; Huber-Bruning, O.; Bijlsma, J. W.

    1992-01-01

    The proteoglycan turnover of human osteoarthritic (OA) cartilage was compared to that of normal (N) cartilage. The cartilage was obtained postmortem from human femoral knee condyles. Short term cultures were compared to longterm cultures, and proteoglycan synthesis rate, content and release

  2. Desulfurization sorbent regeneration

    Science.gov (United States)

    Jalan, V.M.; Frost, D.G.

    1982-07-07

    A spent solid sorbent resulting from the removal of hydrogen sulfide from a fuel gas flow is regenerated with a steam-air mixture. The mixture of steam and air may also include additional nitrogen or carbon dioxide. The gas mixture contacts the spent sorbent containing metal sulfide at a temperature above 500/sup 0/C to regenerate the sulfide to metal oxide or carbonate. Various metal species including the period four transition metals and the lanthanides are suitable sorbents that may be regenerated by this method. In addition, the introduction of carbon dioxide gas permits carbonates such as those of strontium, barium and calcium to be regenerated. The steam permits regeneration of spent sorbent without formation of metal sulfate. Moreover, the regeneration will proceed with low oxygen concentrations and will occur without the increase in temperature to minimize the risk of sintering and densification of the sorbent. This method may be used for high-temperature fuel cells.

  3. Optical properties of nasal septum cartilage

    Science.gov (United States)

    Bagratashvili, Nodar V.; Sviridov, Alexander P.; Sobol, Emil N.; Kitai, Moishe S.

    1998-05-01

    Optical parameters (scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g) of hyaline cartilage were studied for the first time. Optical properties of human and pig nasal septum cartilage, and of bovine ear cartilage were examined using a spectrophotometer with an integrating sphere, and an Optical Multi-Channel Analyser. We measured total transmission Tt, total reflection Rt, and on-axis transmission Ta for light propagating through cartilage sample, over the visible spectral range (14000 - 28000 cm-1). It is shown that transmission and reflection spectra of human, pig and bovine cartilage are rather similar. It allows us to conclude that the pig cartilage can be used for in-vivo studies instead of human cartilage. The data obtained were treated by means of the one-dimensional diffusion approximation solution of the optical transport equation. We have found scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g by the iterative comparison of measured and calculated Tt, Rt and Ta values for human and pig cartilage. We found, in particular, that for 500 nm irradiation s equals 37,6 plus or minus 3.5 cm-1, g equals 0,56 plus or minus 0.05, k approximately equals 0,5 plus or minus 0.3 cm-1. The above data were used in Monte Carlo simulation for spatial intensity profile of light scattered by a cartilage sample. The computed profile was very similar to the profile measured using an Optical Multi-Channel Analyzer (OMA).

  4. Tissue-engineered cartilaginous constructs for the treatment of caprine cartilage defects, including distribution of laminin and type IV collagen.

    Science.gov (United States)

    Jeng, Lily; Hsu, Hu-Ping; Spector, Myron

    2013-10-01

    The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration.

  5. Characterization of Articular Cartilage Recovery and Its Correlation with Optical Response in the Near-Infrared Spectral Range.

    Science.gov (United States)

    Afara, Isaac Oluwaseun; Singh, Sanjleena; Moody, Hayley; Zhang, Lihai; Oloyede, Adekunle

    2017-07-01

    In this study, we examine the capacity of a new parameter, based on the recovery response of articular cartilage, to distinguish between healthy and damaged tissues. We also investigate whether or not this new parameter correlates with the near-infrared (NIR) optical response of articular cartilage. Normal and artificially degenerated (proteoglycan-depleted) bovine cartilage samples were nondestructively probed using NIR spectroscopy. Subsequently they were subjected to a load and unloading protocol, and the recovery response was logged during unloading. The recovery parameter, elastic rebound ( E R ), is based on the strain energy released as the samples underwent instantaneous elastic recovery. Our results reveal positive relationship between the rebound parameter and cartilage proteoglycan content (normal samples: 2.20 ± 0.10 N mm; proteoglycan-depleted samples: 0.50 ± 0.04 N mm for 1 hour of enzymatic treatment and 0.13 ± 0.02 N mm for 4 hours of enzymatic treatment). In addition, multivariate analysis using partial least squares regression was employed to investigate the relationship between E R and NIR spectral data. The results reveal significantly high correlation ( R 2 cal = 98.35% and R 2 val = 79.87%; P cartilage in the combined NIR regions 5,450 to 6,100 cm -1 and 7,500 to 12,500 cm -1 . We conclude that E R can indicate the mechanical condition and state of health of articular cartilage. The correlation of E R with cartilage optical response in the NIR range could facilitate real-time evaluation of the tissue's integrity during arthroscopic surgery and could also provide an important tool for cartilage assessment in tissue engineering and regeneration research.

  6. Rabbit articular cartilage defects treated by allogenic chondrocyte transplantation

    OpenAIRE

    Boopalan, P. R. J. V. C.; Sathishkumar, Solomon; Kumar, Senthil; Chittaranjan, Samuel

    2006-01-01

    Articular cartilage defects have a poor capacity for repair. Most of the current treatment options result in the formation of fibro-cartilage, which is functionally inferior to normal hyaline articular cartilage. We studied the effectiveness of allogenic chondrocyte transplantation for focal articular cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was created in the articular cartilag...

  7. T2 mapping of articular cartilage of the glenohumeral joint at 3.0 T in healthy volunteers: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yusuhn [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Choi, Jung-Ah [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Hallym University Dongtan Sacred Heart Hospital, Department of Radiology, Hwaseong, Gyeonggi-do (Korea, Republic of)

    2016-07-15

    The purpose of this study was to assess the T2 values of the glenohumeral joint cartilage in healthy asymptomatic individuals at 3.0 T and to analyze the T2 profile of the humeral cartilage. This prospective study was approved by our institutional review board and written informed consent was obtained. Thirteen subjects (mean age, 28.6 years; age range, 24-33 years) were included and underwent multiecho spin-echo T2-weighted MR imaging and T2 mapping was acquired. Regions of interest were placed on the humeral cartilage and glenoid cartilage on oblique coronal images. T2 profiles of humeral cartilage were measured from the bone-cartilage interface to the articular surface. Intra-observer agreement was analyzed using intraclass correlation coefficient (ICC). All 13 joints showed normal appearance on conventional T2-weighted images. The mean T2 values of humeral and glenoid cartilage were 50.5 ± 12.1 and 49.0 ± 9.9 ms, respectively. Intra-observer agreement was good, as determined by ICC (0.736). Longer T2 values were observed at the articular surface with a tendency to decrease toward the bone-cartilage interface. The mean cartilage T2 value was 69.03 ± 21.2 ms at the articular surface and 46.99 ± 19.6 ms at the bone-cartilage interface. T2 values of the glenohumeral joint cartilage were similar to reported values of cartilage in the knee. The T2 profile of normal humeral cartilage showed a spatial variation with an increase in T2 values from the subchondral bone to the articular surface. (orig.)

  8. 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

  9. The Urodele Limb Regeneration Blastema: The Cell Potential

    Directory of Open Access Journals (Sweden)

    Kenyon S. Tweedell

    2010-01-01

    Full Text Available The developmental potential of the limb regeneration blastema, a mass of mesenchymal cells of mixed origins, was once considered as being pluripotent, capable of forming all cell types. Now evidence asserts that the blastema is a heterogeneous mixture of progenitor cells derived from tissues of the amputation site, with limited developmental potential, plus various stem cells with multipotent abilities. Many specialized cells, bone, cartilage, muscle, and Schwann cells, at the injury site undergo dedifferentiation to a progenitor state and maintain their cell lineage as they redifferentiate in the regenerate. Muscle satellite reserve stem cells that are active in repair of injured muscle may also dedifferentiate and contribute new muscle cells to the limb blastema. Other cells from the dermis act as multipotent stem cells that replenish dermal fibroblasts and differentiate into cartilage. The blastema primordium is a self-organized, equipotential system, but at the cellular level can compensate for specific cell loss. It is able to induce dedifferentiation of introduced exogenous cells and such cells may be transformed into new cell types. Indigenous cells of the blastema associated with amputated tissues may also transform or possibly transdifferentiate into new cell types. The blastema is a microenvironment that enables dedifferentiation, redifferentiation, transdifferentiation, and stem cell activation, leading to progenitor cells of the limb regenerate.

  10. HISTOMORPHOMETRIC ANALYSIS OF THE KNEE ARTICULAR CARTILAGE AND SYNOVIUM FOR METADIAPHYSEAL LEG LENGTHENING (EXPERIMENTAL-AND-MORPHOLOGICAL STUDY

    Directory of Open Access Journals (Sweden)

    T. A. Stupina

    2013-01-01

    Full Text Available The knee articular cartilage and synovial membrane have been studied for metadiaphyseal leg lengthening using the methods of light miscroscopy, computer morpho- and stereometry. The manner of bone integrity breaking, the rate and rhythm of distraction conformed to the lengthening technique most often used in the clinic. The results of the histomorphometric analysis have demonstrated that when osteotomy at the level of metadiaphysis and manual distraction by 1 mm a day for 4 times is performed, synovitis of mild and moderate degree develops through subsynovial layer hypervascularization, as well as reactive-destructive changes in nerve fibers with the tendency to regeneration. The structural-functional changes of reactive and/or destructive-reparative character have been revealed in the articular cartilage, and the manifestation degree of these changes correlates with synovial membrane changes. The intensity of the destructive-reparative processes in the articular cartilage and synovial membrane depends on fixation stability.

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

    Directory of Open Access Journals (Sweden)

    Jan-Philipp Stromps

    2014-01-01

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

  12. Predicting knee cartilage loss using adaptive partitioning of cartilage thickness maps

    DEFF Research Database (Denmark)

    Jørgensen, Dan Richter; Dam, Erik Bjørnager; Lillholm, Martin

    2013-01-01

    This study investigates whether measures of knee cartilage thickness can predict future loss of knee cartilage. A slow and a rapid progressor group was determined using longitudinal data, and anatomically aligned cartilage thickness maps were extracted from MRI at baseline. A novel machine learning...... framework was then trained using these maps. Compared to measures of mean cartilage plate thickness, group separation was increased by focusing on local cartilage differences. This result is central for clinical trials where inclusion of rapid progressors may help reduce the period needed to study effects...

  13. Bone Marrow Mesenchymal Stem Cell-Based Engineered Cartilage Ameliorates Polyglycolic Acid/Polylactic Acid Scaffold-Induced Inflammation Through M2 Polarization of Macrophages in a Pig Model.

    Science.gov (United States)

    Ding, Jinping; Chen, Bo; Lv, Tao; Liu, Xia; Fu, Xin; Wang, Qian; Yan, Li; Kang, Ning; Cao, Yilin; Xiao, Ran

    2016-08-01

    : The regeneration of tissue-engineered cartilage in an immunocompetent environment usually fails due to severe inflammation induced by the scaffold and their degradation products. In the present study, we compared the tissue remodeling and the inflammatory responses of engineered cartilage constructed with bone marrow mesenchymal stem cells (BMSCs), chondrocytes, or both and scaffold group in pigs. The cartilage-forming capacity of the constructs in vitro and in vivo was evaluated by histological, biochemical, and biomechanical analyses, and the inflammatory response was investigated by quantitative analysis of foreign body giant cells and macrophages. Our data revealed that BMSC-based engineered cartilage suppressed in vivo inflammation through the alteration of macrophage phenotype, resulting in better tissue survival compared with those regenerated with chondrocytes alone or in combination with BMSCs. To further confirm the macrophage phenotype, an in vitro coculture system established by engineered cartilage and macrophages was studied using immunofluorescence, enzyme-linked immunosorbent assay, and gene expression analysis. The results demonstrated that BMSC-based engineered cartilage promoted M2 polarization of macrophages with anti-inflammatory phenotypes including the upregulation of CD206, increased IL-10 synthesis, decreased IL-1β secretion, and alterations in gene expression indicative of M1 to M2 transition. It was suggested that BMSC-seeded constructs have the potential to ameliorate scaffold-induced inflammation and improve cartilaginous tissue regeneration through M2 polarization of macrophages. Finding a strategy that can prevent scaffold-induced inflammation is of utmost importance for the regeneration of tissue-engineered cartilage in an immunocompetent environment. This study demonstrated that bone marrow mesenchymal stem cell (BMSC)-based engineered cartilage could suppress inflammation by increasing M2 polarization of macrophages, resulting

  14. Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression

    Science.gov (United States)

    Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei

    2013-01-01

    Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models. PMID:22788986

  15. Macrophage phagocytosis alters the MRI signal of ferumoxytol-labeled mesenchymal stromal cells in cartilage defects

    Science.gov (United States)

    Nejadnik, Hossein; Lenkov, Olga; Gassert, Florian; Fretwell, Deborah; Lam, Isaac; Daldrup-Link, Heike E.

    2016-05-01

    Human mesenchymal stem cells (hMSCs) are a promising tool for cartilage regeneration in arthritic joints. hMSC labeling with iron oxide nanoparticles enables non-invasive in vivo monitoring of transplanted cells in cartilage defects with MR imaging. Since graft failure leads to macrophage phagocytosis of apoptotic cells, we evaluated in vitro and in vivo whether nanoparticle-labeled hMSCs show distinct MR signal characteristics before and after phagocytosis by macrophages. We found that apoptotic nanoparticle-labeled hMSCs were phagocytosed by macrophages while viable nanoparticle-labeled hMSCs were not. Serial MRI scans of hMSC transplants in arthritic joints of recipient rats showed that the iron signal of apoptotic, nanoparticle-labeled hMSCs engulfed by macrophages disappeared faster compared to viable hMSCs. This corresponded to poor cartilage repair outcomes of the apoptotic hMSC transplants. Therefore, rapid decline of iron MRI signal at the transplant site can indicate cell death and predict incomplete defect repair weeks later. Currently, hMSC graft failure can be only diagnosed by lack of cartilage defect repair several months after cell transplantation. The described imaging signs can diagnose hMSC transplant failure more readily, which could enable timely re-interventions and avoid unnecessary follow up studies of lost transplants.

  16. 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.

  17. MR appearance of cartilage defects of the knee: preliminary results of a spiral CT arthrography-guided analysis

    International Nuclear Information System (INIS)

    Berg, B.C. vande; Lecouvet, F.E.; Maldague, B.; Malghem, J.

    2004-01-01

    The aim of this study was to determine signal intensity patterns of cartilage defects at MR imaging. The MR imaging (3-mm-thick fat-suppressed intermediate-weighted fast spin-echo images) was obtained in 31 knees (21 male and 10 female patients; mean age 45.5 years) blindly selected from a series of 252 consecutive knees investigated by dual-detector spiral CT arthrography. Two radiologists determined in consensus the MR signal intensity of the cartilage areas where cartilage defects had been demonstrated on the corresponding reformatted CT arthrographic images. There were 83 cartilage defects at spiral CT arthrography. In 52 (63%) lesion areas, the MR signal intensity was higher than that of adjacent normal cartilage with signal intensity equivalent to (n=31) or lower than (n=21) that of articular fluid. The MR signal intensity was equivalent to that of adjacent normal cartilage in 17 (20%) lesion areas and lower than that of adjacent cartilage in 8 (10%) lesion areas. In 6 (7%) lesion areas, mixed low and high signal intensity was observed. The MR signal intensity of cartilage defects demonstrated on spiral CT arthrographic images varies from low to high on fat-suppressed intermediate-weighted fast spin-echo MR images obtained with our equipment and MR parameters. (orig.)

  18. No Difference on Quantitative Magnetic Resonance Imaging in Patellofemoral Cartilage Composition Between Patients With Patellofemoral Pain and Healthy Controls.

    Science.gov (United States)

    van der Heijden, Rianne A; Oei, Edwin H G; Bron, Esther E; van Tiel, Jasper; van Veldhoven, Peter L J; Klein, Stefan; Verhaar, Jan A N; Krestin, Gabriel P; Bierma-Zeinstra, Sita M A; van Middelkoop, Marienke

    2016-05-01

    Retropatellar cartilage damage has been suggested as an etiological factor for patellofemoral pain (PFP), a common knee condition among young and physically active individuals. To date, there is no conclusive evidence for an association between cartilage defects and PFP. Nowadays, advanced quantitative magnetic resonance imaging (MRI) techniques enable estimation of cartilage composition. To investigate differences in patellofemoral cartilage composition between patients with PFP and healthy control subjects using quantitative MRI. Cross-sectional study; Level of evidence, 3. Patients with PFP and healthy control subjects underwent 3.0-T MRI including delayed gadolinium-enhanced MRI of cartilage and T1ρ and T2 mapping. Differences in relaxation times of patellofemoral cartilage were compared between groups by linear regression analyses, adjusted for age, body mass index, sex, sports participation, and time of image acquisition. This case-control study included 64 patients and 70 controls. The mean (±SD) age was 23.2 ± 6.4 years and the mean body mass index was 22.9 ± 3.4 kg/m(2); 56.7% were female. For delayed gadolinium-enhanced MRI of cartilage, the mean T1GD relaxation times of patellar (657.8 vs 669.4 ms) and femoral cartilage (661.6 vs 659.8 ms) did not significantly differ between patients and controls. In addition, no significant difference was found in mean T1ρ relaxation times of patellar (46.9 vs 46.0 ms) and femoral cartilage (50.8 vs 50.2 ms) and mean T2 relaxation times of patellar (33.2 vs 32.9 ms) and femoral cartilage (36.7 vs 36.6 ms) between patients and controls. Analysis of prespecified medial and lateral subregions within the patellofemoral cartilage also revealed no significant differences. There was no difference in composition of the patellofemoral cartilage, estimated with multiple quantitative MRI techniques, between patients with PFP and healthy control subjects. However, clinically relevant differences could not be ruled out for T1

  19. On marginal regeneration

    NARCIS (Netherlands)

    Stein, H.N.

    1991-01-01

    On applying the marginal regeneration concept to the drainage of free liquid films, problems are encountered: the films do not show a "neck" of minimum thickness at the film/border transition; and the causes of the direction dependence of the marginal regeneration are unclear. Both problems can be

  20. Cell compaction influences the regenerative potential of passaged bovine articular chondrocytes in an ex vivo cartilage defect model.

    Science.gov (United States)

    Schmutzer, Michael; Aszodi, Attila

    2017-04-01

    The loss and degradation of articular cartilage tissue matrix play central roles in the process of osteoarthritis (OA). New models for evaluating cartilage repair/regeneration are thus of great value for transferring various culture systems into clinically relevant situations. The repair process can be better monitored in ex vivo systems than in in vitro cell cultures. I have therefore established an ex vivo defect model prepared from bovine femoral condyles for evaluating cartilage repair by the implantation of cells cultured in various ways, e.g., monolayer-cultured cells or suspension or pellet cultures of articular bovine chondrocytes representing different cell compactions with variable densities of chondrocytes. I report that the integrin subunit α10 was significantly upregulated in suspension-cultured bovine chondrocytes at passage P2 compared with monolayer-cultured cells at P1 (p = 0.0083) and P2 (p innovation of this system over in vitro differentiation (e.g., micromass, pellet) assays is the possibility of examining and evaluating cartilage regeneration in an environment in which implanted cells are embedded within native surrounding tissue at the defect site. Such ex vivo explants might serve as a better model system to mimic clinical situations. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Magnetic Resonance Imaging of Cartilage Repair

    Science.gov (United States)

    Trattnig, Siegfried; Winalski, Carl S.; Marlovits, Stephan; Jurvelin, Jukka S.; Welsch, Goetz H.; Potter, Hollis G.

    2011-01-01

    Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565

  2. Hyaline cartilage degenerates after autologous osteochondral transplantation.

    Science.gov (United States)

    Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

    2004-11-01

    Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

  3. Cartilage collagen damage in hip osteoarthritis similar to that seen in knee osteoarthritis; a case-control study of relationship between collagen, glycosaminoglycan and cartilage swelling.

    Science.gov (United States)

    Hosseininia, Shahrzad; Lindberg, Lisbeth R; Dahlberg, Leif E

    2013-01-09

    It remains to be shown whether OA shares molecular similarities between different joints in humans. This study provides evidence for similarities in cartilage molecular damage in osteoarthritic (OA) joints. Articular cartilage from osteoarthritic hip joints were analysed and compared to non-OA controls regarding collagen, glycosaminoglycan and water content. Femoral heads from 16 osteoarthritic (OA) and 20 reference patients were obtained from hip replacement surgery due to OA and femoral neck fracture, respectively. Cartilage histological changes were assessed by Mankin grading and denatured collagen type II immunostaining and cartilage was extracted by α-chymotrypsin. Hydroxyproline and Alcian blue binding assays were used to measure collagen and glycosaminoglycan (GAG) content, respectively. Mankin and immunohistology scores were significantly higher in hip OA samples than in reference samples. Cartilage water content was 6% higher in OA samples than in references. 2.5 times more collagen was extracted from OA than from reference samples. There was a positive association between water content and percentage of extractable collagen pool (ECP) in both groups. The amounts of collagen per wet and dry weights did not differ statistically between OA and reference cartilage. % Extractable collagen was not related to collagen per dry weight in either group. However when collagen was expressed by wet weight there was a negative correlation between % extractable and collagen in OA cartilage. The amount of GAG per wet weight was similar in both groups but the amount of GAG per dry weight was higher in OA samples compared to reference samples, which suggests a capacity for GAG biosynthesis in hip OA cartilage. Neither of the studied parameters was related to age in either group. Increased collagen extractability and water content in human hip cartilage is associated with OA pathology and can be observed at early stages of the degenerative hip OA process. Our results

  4. Cartilage collagen damage in hip osteoarthritis similar to that seen in knee osteoarthritis; a case–control study of relationship between collagen, glycosaminoglycan and cartilage swelling

    Directory of Open Access Journals (Sweden)

    Hosseininia Shahrzad

    2013-01-01

    Full Text Available Abstract Background It remains to be shown whether OA shares molecular similarities between different joints in humans. This study provides evidence for similarities in cartilage molecular damage in osteoarthritic (OA joints. Methods Articular cartilage from osteoarthritic hip joints were analysed and compared to non-OA controls regarding collagen, glycosaminoglycan and water content. Femoral heads from 16 osteoarthritic (OA and 20 reference patients were obtained from hip replacement surgery due to OA and femoral neck fracture, respectively. Cartilage histological changes were assessed by Mankin grading and denatured collagen type II immunostaining and cartilage was extracted by α-chymotrypsin. Hydroxyproline and Alcian blue binding assays were used to measure collagen and glycosaminoglycan (GAG content, respectively. Results Mankin and immunohistology scores were significantly higher in hip OA samples than in reference samples. Cartilage water content was 6% higher in OA samples than in references. 2.5 times more collagen was extracted from OA than from reference samples. There was a positive association between water content and percentage of extractable collagen pool (ECP in both groups. The amounts of collagen per wet and dry weights did not differ statistically between OA and reference cartilage. % Extractable collagen was not related to collagen per dry weight in either group. However when collagen was expressed by wet weight there was a negative correlation between % extractable and collagen in OA cartilage. The amount of GAG per wet weight was similar in both groups but the amount of GAG per dry weight was higher in OA samples compared to reference samples, which suggests a capacity for GAG biosynthesis in hip OA cartilage. Neither of the studied parameters was related to age in either group. Conclusions Increased collagen extractability and water content in human hip cartilage is associated with OA pathology and can be observed at

  5. Photoactivated methods for enabling cartilage-to-cartilage tissue fixation

    Science.gov (United States)

    Sitterle, Valerie B.; Roberts, David W.

    2003-06-01

    The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.

  6. Regional dGEMRIC analysis in patients at risk of osteoarthritis provides additional information about activity related changes in cartilage structure

    DEFF Research Database (Denmark)

    Hawezi, Z K; Lammentausta, E; Svensson, J

    2016-01-01

    . PURPOSE: To improve the knowledge about exercise effects on cartilage structure by re-analyzing previous images with regional dGEMRIC analysis. MATERIAL AND METHODS: Thirty patients (age range, 38-50 years) with a previous medial meniscus resection were divided into three groups according to self...... the joint, the largest improvement being observed in lateral posterior cartilage, i.e. the load-bearing cartilage in the compartment without a meniscus lesion. The effects of exercise do not seem to vary with cartilage depth....

  7. Analysis of conifer forest regeneration using Landsat Thematic Mapper data

    Science.gov (United States)

    Fiorella, Maria; Ripple, William J.

    1995-01-01

    Landsat Thematic Mapper (TM) data were used to evaluate young conifer stands in the western Cascade Mountains of Oregon. Regression and correlation analyses were used to describe the relationships between TM band values and age of young Douglas-fir stands (2 to 35 years old). Spectral data from well regenerated Douglas-fir stands were compared to those of poorly regenerated conifer stands. TM bands 1, 2, 3, 5, 6, and 7 were inversely correlated with the age (r greater than or equal to -0.80) of well regenerated Douglas-fir stands. Overall, the 'structural index' (TM 4/5 ratio) had the highest correlation to age of Douglas-fir stands (r = 0.96). Poorly regenerated stands were spectrally distinct from well regenerated Douglas-fir stands after the stands reached an age of approximately 15 years.

  8. Unilateral cleft nasal deformity correction using conchal cartilage lily flower graft.

    Science.gov (United States)

    Hwang, Kun; Kim, Han Joon; Paik, Moo Hyun

    2012-11-01

    We present a conchal cartilage lily flower graft for correcting depressed and laterally displaced alar cartilage for correction of unilateral cleft nasal deformity.After making a V incision at the base of the columellar and then marginal incisions, the alar cartilages were exposed. A fusiform-shaped cartilage larger than 2.5 cm in length and 1 cm in width was obtained. The midline long axis was scored with a No. 15 knife, and the lateral one third was split. Two-thirds length portions were folded in half, and they became straightened in the shape of a stalk of a lily flower. Two symmetrical one-third length portions were fanned out bilaterally in the shape of the leaf of a lily flower. The stalk portion was positioned in a pocket between the medial crura, and the 2 leaf portions were placed on the dome of the alar cartilages. The marked points of the cleft side and contralateral side were secured with sutures. The V incision at the base of the columellar and the marginal incisions were closed with a V-Y shape. In this technique, the 2 leaf portions were placed on the dome of the alar cartilages and sutured; therefore, the suture holds the dome of the cleft side to the contralateral side without peaking.Thirteen patients (6 male and 7 female subjects; age range, 13-30 years) were operated. Among them, 6 patients were very satisfied, and 5 patients were satisfied with the results. Two patients felt they were improved.We think the conchal cartilage lily flower graft might be a good method for correction of depressed and laterally displaced alar cartilage in unilateral cleft nasal deformity.

  9. T1rho MRI of menisci and cartilage in patients with osteoarthritis at 3T

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ligong, E-mail: ligong.wang@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Chang, Gregory, E-mail: gregory.chang@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Xu, Jian, E-mail: jian.xu.sz@siemens.com [Siemens HealthCare, New York, NY (United States); Vieira, Renata L.R., E-mail: Renata.Vieira@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Krasnokutsky, Svetlana, E-mail: Svetlana.Krasnokutsky@nyumc.org [Division of Rheumatology, New York University Langone Medical Center, New York, NY (United States); Abramson, Steven, E-mail: StevenB.Abramson@nyumc.org [Division of Rheumatology, New York University Langone Medical Center, New York, NY (United States); Regatte, Ravinder R., E-mail: Ravinder.Regatte@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States)

    2012-09-15

    Objective: To assess and compare subregional and whole T1rho values (median ± interquartile range) of femorotibial cartilage and menisci in patients with doubtful (Kellgren–Lawrence (KL) grade 1) to severe (KL4) osteoarthritis (OA) at 3T. Materials and methods: 30 subjects with varying degrees of OA (KL1–4, 13 females, 17 males, mean age ± SD = 63.9 ± 13.1 years) were evaluated on a 3T MR scanner using a spin-lock-based 3D GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echo (FSE) images in sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage and meniscus Whole-organ MR imaging score (WORMS) grading. Wilcoxon rank sum test was performed to determine whether there were any statistically significant differences between subregional and whole T1rho values of femorotibial cartilage and menisci in subjects with doubtful to severe OA. Results: Lateral (72 ± 10 ms, median ± interquartile range) and medial (65 ± 10 ms) femoral anterior cartilage subregions in moderate–severe OA subjects had significantly higher T1rho values (P < 0.05) than cartilage subregions and whole femorotibial cartilage in doubtful–minimal OA subjects. There were statistically significant differences in meniscus T1rho values of the medial posterior subregion of subjects with moderate–severe OA and T1rho values of all subregions and the whole meniscus in subjects with doubtful–minimal OA. When evaluated based on WORMS, statistically significant differences were identified in T1rho values between the lateral femoral anterior cartilage subregion in patients with WORMS5–6 (advanced degeneration) and whole femorotibial cartilage and all cartilage subregions in patients with WORMS0–1 (normal). Conclusion: T1rho values are higher in specific meniscus and femorotibial cartilage subregions. These findings suggest that regional damage of both femorotibial hyaline cartilage and menisci may be associated with

  10. T1rho MRI of menisci and cartilage in patients with osteoarthritis at 3T

    International Nuclear Information System (INIS)

    Wang, Ligong; Chang, Gregory; Xu, Jian; Vieira, Renata L.R.; Krasnokutsky, Svetlana; Abramson, Steven; Regatte, Ravinder R.

    2012-01-01

    Objective: To assess and compare subregional and whole T1rho values (median ± interquartile range) of femorotibial cartilage and menisci in patients with doubtful (Kellgren–Lawrence (KL) grade 1) to severe (KL4) osteoarthritis (OA) at 3T. Materials and methods: 30 subjects with varying degrees of OA (KL1–4, 13 females, 17 males, mean age ± SD = 63.9 ± 13.1 years) were evaluated on a 3T MR scanner using a spin-lock-based 3D GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echo (FSE) images in sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage and meniscus Whole-organ MR imaging score (WORMS) grading. Wilcoxon rank sum test was performed to determine whether there were any statistically significant differences between subregional and whole T1rho values of femorotibial cartilage and menisci in subjects with doubtful to severe OA. Results: Lateral (72 ± 10 ms, median ± interquartile range) and medial (65 ± 10 ms) femoral anterior cartilage subregions in moderate–severe OA subjects had significantly higher T1rho values (P < 0.05) than cartilage subregions and whole femorotibial cartilage in doubtful–minimal OA subjects. There were statistically significant differences in meniscus T1rho values of the medial posterior subregion of subjects with moderate–severe OA and T1rho values of all subregions and the whole meniscus in subjects with doubtful–minimal OA. When evaluated based on WORMS, statistically significant differences were identified in T1rho values between the lateral femoral anterior cartilage subregion in patients with WORMS5–6 (advanced degeneration) and whole femorotibial cartilage and all cartilage subregions in patients with WORMS0–1 (normal). Conclusion: T1rho values are higher in specific meniscus and femorotibial cartilage subregions. These findings suggest that regional damage of both femorotibial hyaline cartilage and menisci may be associated with

  11. Elastic cartilage reconstruction by transplantation of cultured hyaline cartilage-derived chondrocytes.

    Science.gov (United States)

    Mizuno, M; Takebe, T; Kobayashi, S; Kimura, S; Masutani, M; Lee, S; Jo, Y H; Lee, J I; Taniguchi, H

    2014-05-01

    Current surgical intervention of craniofacial defects caused by injuries or abnormalities uses reconstructive materials, such as autologous cartilage grafts. Transplantation of autologous tissues, however, places a significant invasiveness on patients, and many efforts have been made for establishing an alternative graft. Recently, we and others have shown the potential use of reconstructed elastic cartilage from ear-derived chondrocytes or progenitors with the unique elastic properties. Here, we examined the differentiation potential of canine joint cartilage-derived chondrocytes into elastic cartilage for expanding the cell sources, such as hyaline cartilage. Articular chondrocytes are isolated from canine joint, cultivated, and compared regarding characteristic differences with auricular chondrocytes, including proliferation rates, gene expression, extracellular matrix production, and cartilage reconstruction capability after transplantation. Canine articular chondrocytes proliferated less robustly than auricular chondrocytes, but there was no significant difference in the amount of sulfated glycosaminoglycan produced from redifferentiated chondrocytes. Furthermore, in vitro expanded and redifferentiated articular chondrocytes have been shown to reconstruct elastic cartilage on transplantation that has histologic characteristics distinct from hyaline cartilage. Taken together, cultured hyaline cartilage-derived chondrocytes are a possible cell source for elastic cartilage reconstruction. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  12. Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application.

    Science.gov (United States)

    Wang, L; Lazebnik, M; Detamore, M S

    2009-03-01

    To compare temporomandibular joint (TMJ) condylar cartilage cells in vitro to hyaline cartilage cells cultured in a three-dimensional (3D) environment for tissue engineering of mandibular condylar cartilage. Mandibular condylar cartilage and hyaline cartilage cells were harvested from pigs and cultured for 6 weeks in polyglycolic acid (PGA) scaffolds. Both types of cells were treated with glucosamine sulfate (0.4 mM), insulin-like growth factor-I (IGF-I) (100 ng/ml) and their combination. At weeks 0 and 6, cell number, glycosaminoglycan (GAG) and collagen content were determined, types I and II collagen were visualized by immunohistochemistry and GAGs were visualized by histology. Hyaline cartilage cells produced from half an order to a full order of magnitude more GAGs and collagen than mandibular condylar cartilage cells in 3D culture. IGF-I was a highly effective signal for biosynthesis with hyaline cartilage cells, while glucosamine sulfate decreased cell proliferation and biosynthesis with both types of cells. In vitro culture of TMJ condylar cartilage cells produced a fibrous tissue with predominantly type I collagen, while hyaline cartilage cells formed a fibrocartilage-like tissue with types I and II collagen. The combination of IGF and glucosamine had a synergistic effect on maintaining the phenotype of TMJ condylar cells to generate both types I and II collagen. Given the superior biosynthetic activity by hyaline cartilage cells and the practical surgical limitations of harvesting cells from the TMJ of a patient requiring TMJ reconstruction, cartilage cells from elsewhere in the body may be a potentially better alternative to cells harvested from the TMJ for TMJ tissue engineering. This finding may also apply to other fibrocartilages such as the intervertebral disc and knee meniscus in applications where a mature cartilage cell source is desired.

  13. Cysts of the semilunar cartilage

    International Nuclear Information System (INIS)

    Bruessermann, M.

    1981-01-01

    On the basis of the studies listed in the bibliography, this dissertation reports on the pathology, clinical symptoms and radiology of cysts of the semilunar cartilage. The author analyses 118 cases of his own, with special regard to the results of pneumo-arthrographic investigations carried through according to a special technique by Schaefer. In the course of this work, measurements of the meniscal base are for the first time used as radiological criteria indicating the presence of a cyst of the semilunar cartilage. Furthermore the well-known radiological signs of cysts, such as bone defects according to Albert and Keller, light central spot in the meniscal body, as well as Rauber's sign and horizontal rupture, are investigated as to the frequency of their incidence. For that purpose all the X-ray pictures were subjected to a further dose scrutiny. A list of all the 118 cases with their clinical and radiological data is found in the annex, together with the results of the operations and patho-anatomical investigations. (orig.) [de

  14. Imaging diagnosis of the articular cartilage disorders

    International Nuclear Information System (INIS)

    Liu Sirun; Zhu Tianyuan; Huang Li; Leng Xiaoming

    2003-01-01

    Objective: To evaluate the diagnosis and differential diagnosis among the chronic osteoarthritis, rheumatoid arthritis and other chronic cartilage lesions on the plain films and MR images. Methods: Eighty-nine cases, including 115 joints, underwent plain film and MRI examination, and enhanced MRI scan was performed on 32 of them, including 44 joints. MRI scan sequences consisted of T 1 WI, T 2 WI + PDWI, STIR, and 3D FS SPGR. There were 90 knee joints in this group and each of the articular cartilage was divided into four parts: patella, femoral medial condyle, femoral lateral condyle, and tibia facet on MR images. The cartilage disorders were classified according to the outerbridge method. In addition, 61 cases including 75 joints were observed as a control group on the plain films and MR images. Results: 115 cartilage lesions were found on MR images, in which thinness of the cartilage (58 cases, 50.4%), bone changes under the cartilage (22 cases, 19.7%), medullar edema (22 cases, 19.7%), and synovial hyperplasia (52 cases, 45.2%) were seen. The patella cartilage was the most likely affected part (81/90, 90%). So the patellar cartilage lesions were divided as group 1 (grade I-II) and group 2 (grade III-IV) on MR images, which were compared with the plain film signs. The narrowing of the joint space and saccules under the articular surface were statistically significant with each other, and χ 2 values were 9.349 and 9.885, respectively (P=0.002). Conclusion: No constant signs could be seen on the plain films with grade I-II cartilage disorders. While the narrowing joint space and saccules under the joint surface could be seen on them with grade III-IV cartilage disorders, which were mainly correlated with the cartilage disorders and bone change