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Sample records for articular cartilage repair

  1. Supporting Biomaterials for Articular Cartilage Repair

    PubMed Central

    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

  2. The Functions of BMP3 in Rabbit Articular Cartilage Repair

    PubMed Central

    Zhang, Zhe; Yang, Wenyu; Cao, Yiting; Shi, Yanping; Lei, Chen; Du, Bo; Li, Xuemin; Zhang, Qiqing

    2015-01-01

    Bone morphogenetic proteins (BMPs) play important roles in skeletal development and repair. Previously, we found fibroblast growth factor 2 (FGF2) induced up-regulation of BMP2, 3, 4 in the process of rabbit articular cartilage repair, which resulted in satisfactory repair effects. As BMP2/4 show a clearly positive effect for cartilage repair, we investigated the functions of BMP3 in rabbit articular cartilage repair. In this paper, we find that BMP3 inhibits the repair of partial-thickness defect of articular cartilage in rabbit by inducing the degradation of extracellular matrix, interfering with the survival of chondrocytes surrounding the defect, and directly inhibiting the expression of BMP2 and BMP4. Meanwhile BMP3 suppress the repair of full-thickness cartilage defect by destroying the subchondral bone through modulating the proliferation and differentiation of bone marrow stem cells (BMSCs), and directly increasing the expression of BMP4. Although BMP3 has different functions in the repair of partial and full-thickness defects of articular cartilage in rabbit, the regulation of BMP expression is involved in both of them. Together with our previous findings, we suggest the regulation of the BMP signaling pathway by BMP3 is essential in articular cartilage repair. PMID:26528966

  3. The Functions of BMP3 in Rabbit Articular Cartilage Repair.

    PubMed

    Zhang, Zhe; Yang, Wenyu; Cao, Yiting; Shi, Yanping; Lei, Chen; Du, Bo; Li, Xuemin; Zhang, Qiqing

    2015-01-01

    Bone morphogenetic proteins (BMPs) play important roles in skeletal development and repair. Previously, we found fibroblast growth factor 2 (FGF2) induced up-regulation of BMP2, 3, 4 in the process of rabbit articular cartilage repair, which resulted in satisfactory repair effects. As BMP2/4 show a clearly positive effect for cartilage repair, we investigated the functions of BMP3 in rabbit articular cartilage repair. In this paper, we find that BMP3 inhibits the repair of partial-thickness defect of articular cartilage in rabbit by inducing the degradation of extracellular matrix, interfering with the survival of chondrocytes surrounding the defect, and directly inhibiting the expression of BMP2 and BMP4. Meanwhile BMP3 suppress the repair of full-thickness cartilage defect by destroying the subchondral bone through modulating the proliferation and differentiation of bone marrow stem cells (BMSCs), and directly increasing the expression of BMP4. Although BMP3 has different functions in the repair of partial and full-thickness defects of articular cartilage in rabbit, the regulation of BMP expression is involved in both of them. Together with our previous findings, we suggest the regulation of the BMP signaling pathway by BMP3 is essential in articular cartilage repair. PMID:26528966

  4. Hydrogels for the Repair of Articular Cartilage Defects

    PubMed Central

    Maher, Suzanne A.; Lowman, Anthony M.

    2011-01-01

    The repair of articular cartilage defects remains a significant challenge in orthopedic medicine. Hydrogels, three-dimensional polymer networks swollen in water, offer a unique opportunity to generate a functional cartilage substitute. Hydrogels can exhibit similar mechanical, swelling, and lubricating behavior to articular cartilage, and promote the chondrogenic phenotype by encapsulated cells. Hydrogels have been prepared from naturally derived and synthetic polymers, as cell-free implants and as tissue engineering scaffolds, and with controlled degradation profiles and release of stimulatory growth factors. Using hydrogels, cartilage tissue has been engineered in vitro that has similar mechanical properties to native cartilage. This review summarizes the advancements that have been made in determining the potential of hydrogels to replace damaged cartilage or support new tissue formation as a function of specific design parameters, such as the type of polymer, degradation profile, mechanical properties and loading regimen, source of cells, cell-seeding density, controlled release of growth factors, and strategies to cause integration with surrounding tissue. Some key challenges for clinical translation remain, including limited information on the mechanical properties of hydrogel implants or engineered tissue that are necessary to restore joint function, and the lack of emphasis on the ability of an implant to integrate in a stable way with the surrounding tissue. Future studies should address the factors that affect these issues, while using clinically relevant cell sources and rigorous models of repair. PMID:21510824

  5. The Role of Tissue Engineering in Articular Cartilage Repair and Regeneration

    PubMed Central

    Zhang, Lijie; Hu, Jerry; Athanasiou, Kyriacos A.

    2011-01-01

    Articular cartilage repair and regeneration continue to be largely intractable due to the poor regenerative properties of this tissue. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased articular cartilage functionality, has evoked intense interest and holds great potential for improving articular cartilage therapy. This review provides an overall description of the current state and progress in articular cartilage repair and regeneration. Traditional therapies and related problems are introduced. More importantly, a variety of promising cell sources, biocompatible tissue engineered scaffolds, scaffoldless techniques, growth factors, and mechanical stimuli used in current articular cartilage tissue engineering are reviewed. Finally, the technical and regulatory challenges of articular cartilage tissue engineering and possible future directions are discussed. PMID:20201770

  6. Repair and tissue engineering techniques for articular cartilage

    PubMed Central

    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 regenerative biological products that over the next decade could revolutionize joint care by functionally healing articular cartilage. These products include cell-based and cell-free materials such as autologous and allogeneic cell-based approaches and multipotent and pluripotent stem-cell-based techniques. 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. PMID:25247412

  7. Biomaterial scaffolds in cartilage-subchondral bone defects influencing the repair of autologous articular cartilage transplants.

    PubMed

    Fan, Wei; Wu, Chengtie; Miao, Xigeng; Liu, Gang; Saifzadeh, Siamak; Sugiyama, Sadahiro; Afara, Isaac; Crawford, Ross; Xiao, Yin

    2013-05-01

    The repair of articular cartilage typically involves the repair of cartilage-subchondral bone tissue defects. Although various bioactive materials have been used to repair bone defects, how these bioactive materials in subchondral bone defects influence the repair of autologous cartilage transplant remains unclear. The aim of this study was to investigate the effects of different subchondral biomaterial scaffolds on the repair of autologous cartilage transplant in a sheep model. Cylindrical cartilage-subchondral bone defects were created in the right femoral knee joint of each sheep. The subchondral bone defects were implanted with hydroxyapatite-β-tricalcium phosphate (HA-TCP), poly lactic-glycolic acid (PLGA)-HA-TCP dual-layered composite scaffolds (PLGA/HA-TCP scaffolds), or autologous bone chips. The autologous cartilage layer was placed on top of the subchondral materials. After 3 months, the effect of different subchondral scaffolds on the repair of autologous cartilage transplant was systematically studied by investigating the mechanical strength, structural integration, and histological responses. The results showed that the transplanted cartilage layer supported by HA-TCP scaffolds had better structural integration and higher mechanical strength than that supported by PLGA/HA-TCP scaffolds. Furthermore, HA-TCP-supported cartilage showed higher expression of acid mucosubstances and glycol-amino-glycan contents than that supported by PLGA/HA-TCP scaffolds. Our results suggested that the physicochemical properties, including the inherent mechanical strength and material chemistry of the scaffolds, play important roles in influencing the repair of autologous cartilage transplants. The study may provide useful information for the design and selection of proper subchondral biomaterials to support the repair of both subchondral bone and cartilage defects. PMID:22684516

  8. Repair of articular cartilage defects in rabbits through tissue-engineered cartilage constructed with chitosan hydrogel and chondrocytes*

    PubMed Central

    ZHAO, Ming; CHEN, Zhu; LIU, Kang; WAN, Yu-qing; LI, Xu-dong; Luo, Xu-wei; Bai, Yi-guang; Yang, Ze-long; Feng, Gang

    2015-01-01

    Objective: In our previous work, we prepared a type of chitosan hydrogel with excellent biocompatibility. In this study, tissue-engineered cartilage constructed with this chitosan hydrogel and costal chondrocytes was used to repair the articular cartilage defects. Methods: Chitosan hydrogels were prepared with a crosslinker formed by combining 1,6-diisocyanatohexane and polyethylene glycol. Chitosan hydrogel scaffold was seeded with rabbit chondrocytes that had been cultured for one week in vitro to form the preliminary tissue-engineered cartilage. This preliminary tissue-engineered cartilage was then transplanted into the defective rabbit articular cartilage. There were three treatment groups: the experimental group received preliminary tissue-engineered cartilage; the blank group received pure chitosan hydrogels; and, the control group had received no implantation. The knee joints were harvested at predetermined time. The repaired cartilage was analyzed through gross morphology, histologically and immunohistochemically. The repairs were scored according to the international cartilage repair society (ICRS) standard. Results: The gross morphology results suggested that the defects were repaired completely in the experimental group after twelve weeks. The regenerated tissue connected closely with subchondral bone and the boundary with normal tissue was fuzzy. The cartilage lacuna in the regenerated tissue was similar to normal cartilage lacuna. The results of ICRS gross and histological grading showed that there were significant differences among the three groups (P<0.05). Conclusions: Chondrocytes implanted in the scaffold can adhere, proliferate, and secrete extracellular matrix. The novel tissue-engineered cartilage constructed in our research can completely repair the structure of damaged articular cartilage. PMID:26537209

  9. An Articular Cartilage Repair Model in Common C57Bl/6 Mice

    PubMed Central

    Matsuoka, Masatake; Sasazawa, Fumio; Momma, Daisuke; Baba, Rikiya; Hontani, Kazutoshi; Iwasaki, Norimasa

    2015-01-01

    To analyze the genetic and biomolecular mechanisms underlying cartilage repair, an optimized mouse model of osteochondral repair is required. Although several models of articular cartilage injury in mice have recently been established, the articular surface in adult C57Bl/6 mice heals poorly. Since C57Bl/6 mice are the most popular strain of genetically manipulated mice, an articular cartilage repair model using C57Bl/6 mice would be helpful for analysis of the mechanisms of cartilage repair. The purpose of this study was to establish a cartilage repair model in C57Bl/6 mice using immature animals. To achieve this goal, full-thickness injuries were generated in 3-week-old (young), 4-week-old (juvenile), and 8-week-old (adult) C57Bl/6 mice. To investigate the reproducibility and consistency of full-thickness injuries, mice were sacrificed immediately after operation, and cartilage thickness at the patellar groove, depth of the cartilage injury, cross-sectional width, and cross-sectional area were compared among the three age groups. The depth of cartilage injury/cartilage thickness ratio (%depth) and the coefficient of variation (CV) for each parameter were also calculated. At 8 weeks postoperatively, articular cartilage repair was assessed using a histological scoring system. With respect to the reproducibility and consistency of full-thickness injuries, cartilage thickness, depth of cartilage injury, and cross-sectional area were significantly larger in young and juvenile mice than in adult mice, whereas cross-sectional width and %depth were almost equal among the three age groups. CVs of %depths were less than 10% in all groups. With respect to articular cartilage repair, young and juvenile mice showed superior results. In conclusion, we established a novel cartilage repair model in C57Bl/6 mice. This model will be valuable in achieving mechanistic insights into the healing process of the joint surface, as it will facilitate the use of genetically modified mice

  10. Strategic Design and Fabrication of Engineered Scaffolds for Articular Cartilage Repair

    PubMed Central

    Izadifar, Zohreh; Chen, Xiongbiao; Kulyk, William

    2012-01-01

    Damage to articular cartilage can eventually lead to osteoarthritis (OA), a debilitating, degenerative joint disease that affects millions of people around the world. The limited natural healing ability of cartilage and the limitations of currently available therapies make treatment of cartilage defects a challenging clinical issue. Hopes have been raised for the repair of articular cartilage with the help of supportive structures, called scaffolds, created through tissue engineering (TE). Over the past two decades, different designs and fabrication techniques have been investigated for developing TE scaffolds suitable for the construction of transplantable artificial cartilage tissue substitutes. Advances in fabrication technologies now enable the strategic design of scaffolds with complex, biomimetic structures and properties. In particular, scaffolds with hybrid and/or biomimetic zonal designs have recently been developed for cartilage tissue engineering applications. This paper reviews critical aspects of the design of engineered scaffolds for articular cartilage repair as well as the available advanced fabrication techniques. In addition, recent studies on the design of hybrid and zonal scaffolds for use in cartilage tissue repair are highlighted. PMID:24955748

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

    PubMed Central

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

    2011-01-01

    Objective: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. Design: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field. Results: Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved. Conclusions: High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project

  12. [Articular cartilage regeneration using scaffold].

    PubMed

    Ishimoto, Yoshiyuki; Hattori, Koji; Ohgushi, Hajime

    2008-12-01

    The self-healing capacity of articular cartilage for repair is limited. For articular cartilage injury, several surgical techniques are used in clinical practice, namely drilling, abrasion arthroplasty, microfracture, or autologous osteochondral grafting, while various methods of autologous chondrocyte transplantation to cartilage defect sites have been reported since 1990s. In a case of chondrocyte transplantation to cartilage defect site, the use of proper scaffold is important. Currently, collagen gel or PLGA is used widely as a scaffold. PMID:19043192

  13. Adult human neural crest-derived cells for articular cartilage repair.

    PubMed

    Pelttari, Karoliina; Pippenger, Benjamin; Mumme, Marcus; Feliciano, Sandra; Scotti, Celeste; Mainil-Varlet, Pierre; Procino, Alfredo; von Rechenberg, Brigitte; Schwamborn, Thomas; Jakob, Marcel; Cillo, Clemente; Barbero, Andrea; Martin, Ivan

    2014-08-27

    In embryonic models and stem cell systems, mesenchymal cells derived from the neuroectoderm can be distinguished from mesoderm-derived cells by their Hox-negative profile--a phenotype associated with enhanced capacity of tissue regeneration. We investigated whether developmental origin and Hox negativity correlated with self-renewal and environmental plasticity also in differentiated cells from adults. Using hyaline cartilage as a model, we showed that adult human neuroectoderm-derived nasal chondrocytes (NCs) can be constitutively distinguished from mesoderm-derived articular chondrocytes (ACs) by lack of expression of specific HOX genes, including HOXC4 and HOXD8. In contrast to ACs, serially cloned NCs could be continuously reverted from differentiated to dedifferentiated states, conserving the ability to form cartilage tissue in vitro and in vivo. NCs could also be reprogrammed to stably express Hox genes typical of ACs upon implantation into goat articular cartilage defects, directly contributing to cartilage repair. Our findings identify previously unrecognized regenerative properties of HOX-negative differentiated neuroectoderm cells in adults, implying a role for NCs in the unmet clinical challenge of articular cartilage repair. An ongoing phase 1 clinical trial preliminarily indicated the safety and feasibility of autologous NC-based engineered tissues for the treatment of traumatic articular cartilage lesions. PMID:25163479

  14. Characterization of Chondrocyte Scaffold Carriers for Cell-based Gene Therapy in Articular Cartilage Repair

    PubMed Central

    Shui, Wei; Yin, Liangjun; Luo, Jeffrey; Li, Ruidong; Zhang, Wenwen; Zhang, Jiye; Huang, Wei; Hu, Ning; Liang, Xi; Deng, Zhong-Liang; Hu, Zhenming; Shi, Lewis; Luu, Hue H.; Haydon, Rex C.; He, Tong-Chuan; Ho, Sherwin

    2014-01-01

    Articular cartilage lesions in the knee are common injuries. Chondrocyte transplant represents a promising therapeutic modality for articular cartilage injuries. Here, we characterize the viability and transgene expression of articular chondrocytes cultured in 3-D scaffolds provided by four types of carriers. Articular chondrocytes are isolated from rabbit knees and cultured in four types of scaffolds: type I collagen sponge, fibrin glue, hyaluronan, and Open-cell PolyLactic Acid (OPLA). The cultured cells are transduced with adenovirus expressing green fluorescence protein (AdGFP) and luciferase (AdGL3-Luc). The viability and gene expression in the chondrocytes are determined with fluorescence microscopy and luciferase assay. Cartilage matrix production is assessed by Alcian blue staining. Rabbit articular chondrocytes are effectively infected by AdGFP and exhibited sustained GFP expression. All tested scaffolds support the survival and gene expression of the infected chondrocytes. However, the highest transgene expression is observed in the OPLA carrier. At four weeks, Alcian blue-positive matrix materials are readily detected in OPLA cultures. Thus, our results indicate that, while all tested carriers can support the survival of chondrocytes, OPLA supports the highest transgene expression and is the most conductive scaffold for matrix production, suggesting that OPLA may be a suitable scaffold for cell-based gene therapy of articular cartilage repairs. PMID:23629940

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

    PubMed Central

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

    2014-01-01

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

  16. Does Low-intensity pulsed ultrasound treatment repair articular cartilage injury? A rabbit model study

    PubMed Central

    2014-01-01

    Background Low-intensity pulsed ultrasound (LIPUS) regiment has been used to treat fractures with non-union and to promote bone union in general. The effect of LIPUS on articular cartilage metabolism has been characterized. Yet, the effect of LIPUS to repair articular cartilage injury remains unclear in vivo. Methods We designed a study to investigate the effect of LIPUS on articular cartilage repairing in a rabbit severe cartilage injury model. Eighteen rabbits were divided into three groups: Sham-operated group, operated group without-LIPUS-treatment, operated group with-LIPUS-treatment (a daily 20-minute treatment for 3 months). Full-thickness cartilage defects were surgically created on the right side distal femoral condyle without intending to penetrate into the subchondral bone, which mimicked severe chondral injury. MR images for experimental joints, morphology grading scale, and histopathological Mankin score were evaluated. Results The preliminary results showed that the operated groups with-LIPUS-treatment and without-LIPUS-treatment had significantly higher Mankin score and morphological grading scale compared with the sham-operated group. However, there was no significant difference between the with-LIPUS-treatment and without-LIPUS-treatment groups. Cartilage defects filled with proliferative tissue were observed in the with-LIPUS-treatment group grossly and under MR images, however which presented less up-take under Alcian blue stain. Furthermore, no new deposition of type II collagen or proliferation of chondrocyte was observed over the cartilage defect after LIPUS treatment. Conclusion LIPUS has no significant therapeutic potential in treating severe articular cartilage injury in our animal study. PMID:24507771

  17. Microstructural Remodeling of Articular Cartilage Following Defect Repair by Osteochondral Autograft Transfer

    PubMed Central

    Raub, CB; Hsu, SC; Chan, EF; Shirazi, R; Chen, AC; Chnari, E; Semler, EJ; Sah, RL

    2013-01-01

    Objective To assess collagen network alterations occurring with flow and other abnormalities of articular cartilage at medial femoral condyle (MFC) sites repaired with osteochondral autograft (OATS) after 6 and 12 months, using quantitative polarized light microscopy (qPLM) and other histopathological methods Design The collagen network structure of articular cartilage of OATS-repaired defects and non-operated contralateral control sites were compared by qPLM analysis of parallelism index (PI), orientation angle (α) relative to the local tissue axes, and retardance (Γ) as a function of depth. qPLM parameter maps were also compared to ICRS and Modified O’Driscoll grades, and cell and matrix sub-scores, for sections stained with H&E and Safranin-O, and for Collagen-I and II Results Relative to non-operated normal cartilage, OATS-repaired regions exhibited structural deterioration, with low PI and more horizontal α, and unique structural alteration in adjacent host cartilage: more aligned superficial zone, and reoriented deep zone lateral to the graft, and matrix disorganization in cartilage overhanging the graft. Shifts in α and PI from normal site-specific values were correlated with histochemical abnormalities and co-localized with changes in cell organization/orientation, cloning, or loss, indicative of cartilage flow, remodeling, and deterioration, respectively Conclusions qPLM reveals a number of unique localized alterations of the collagen network in both adjacent host and implanted cartilage in OATS-repaired defects, associated with abnormal chondrocyte organization. These alterations are consistent with mechanobiological processes and the direction and magnitude of cartilage strain. PMID:23528954

  18. Repair of articular cartilage and meniscal tears by photoactive dyes: in-vivo study

    NASA Astrophysics Data System (ADS)

    Judy, Millard M.; Jackson, Robert W.; Nosir, Hany R.; Matthews, James Lester; Lewis, David E.; Utecht, Ronald E.; Yuan, Dongwu

    1996-12-01

    We describe healing results of our 6 month study of a repair procedure which evokes the healing response in meniscal tears and partial thickness defects in articular cartilage by a non-thermal tissue sparing photochemical weld using 1,8-naphthalimide dyes. Welds of incisional flaps in adult sheep meniscus and femoral articular cartilage were made using the dye MBM Gold 012011012 at 12 mM in PBS, 457.9nm Argon ion laser radiation at 800 mW/cm2, 7.5 minutes with approximately 1 kg/cm2 externally applied pressure. Gross appearance of tissues in all welded knees appeared normal. Hematoxylin and eosin stained sections disclosed close bonding of welded areas and continuing healing response as cellular recruitment.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. Repair of articular cartilage in rabbit osteochondral defects promoted by extracorporeal shock wave therapy

    NASA Astrophysics Data System (ADS)

    Chu, C.-H.; Yen, Y.-S.; Chen, P.-L.; Wen, C.-Y.

    2015-03-01

    This study investigated the stimulative effect of extracorporeal shock wave therapy (ESWT) on the articular cartilage regeneration in the rabbit osteochondral defect model for the first time. An osteochondral defect, 3 mm in diameter and 3 mm in depth, was drilled in the patellar groove at the distal end of each femur in 24 mature New Zealand rabbits. The right patellar defects received 500 impulses of shock waves of (at 14 kV) at 1 week after surgery and were designated as the experimental samples; the left patellar defects served as control. At 4, 8, and 12 weeks after ESWT, cartilage repair was evaluated macroscopically and histologically using a semiquantitative grading scale. The total scores of the macroscopic evaluation at 4, 8, and 12 weeks in the experimental group were superior to those in the control group (statistical significance level ). As to the total scores of the histologic evaluation, the experimental group showed a tendency toward a better recovery than the control group at 4 weeks (). At 8 and 12 weeks the differences between the experimental and control groups became mild and had no significance on statistical analysis. These findings suggested that regeneration of articular cartilage defects might be promoted by ESWT, especially at the early stage. The easy and safe ESWT is potentially viable for clinical application.

  2. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model.

    PubMed

    Mak, J; Jablonski, C L; Leonard, C A; Dunn, J F; Raharjo, E; Matyas, J R; Biernaskie, J; Krawetz, R J

    2016-01-01

    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such as osteoarthritis. In the joint environment there are mesenchymal stem/progenitor cells (MSCs) in the synovial membrane and synovial fluid that can differentiate into cartilage, but it is still under debate if these cells contribute to cartilage repair in vivo. In this study, we isolated a Sca-1 positive, chondrogenesis capable population of mouse synovial MSCs from C57BL6 and MRL/MpJ "super-healer" strains. Intra-articular injection of Sca-1 + GFP + synovial cells from C57BL6 or MRL/MpJ into C57BL6 mice following cartilage injury led to increased cartilage repair by 4 weeks after injury. GFP expression was detected in the injury site at 2 weeks, but not 4 weeks after injury. These results suggest that synovial stem/progenitor cells, regardless of strain background, have beneficial effects when injected into an injured joint. MSCs derived from MRL/MpJ mice did not promote an increased repair capacity compared to MSCs derived from non-healing C57BL6 controls; however, MRL/MpJ MSCs were observed within the defect area at the time points examined, while C57BL6 MSCs were not. PMID:26983696

  3. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model

    PubMed Central

    Mak, J.; Jablonski, C. L.; Leonard, C. A.; Dunn, J. F.; Raharjo, E.; Matyas, J. R.; Biernaskie, J.; Krawetz, R. J.

    2016-01-01

    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such as osteoarthritis. In the joint environment there are mesenchymal stem/progenitor cells (MSCs) in the synovial membrane and synovial fluid that can differentiate into cartilage, but it is still under debate if these cells contribute to cartilage repair in vivo. In this study, we isolated a Sca-1 positive, chondrogenesis capable population of mouse synovial MSCs from C57BL6 and MRL/MpJ “super-healer” strains. Intra-articular injection of Sca-1 + GFP + synovial cells from C57BL6 or MRL/MpJ into C57BL6 mice following cartilage injury led to increased cartilage repair by 4 weeks after injury. GFP expression was detected in the injury site at 2 weeks, but not 4 weeks after injury. These results suggest that synovial stem/progenitor cells, regardless of strain background, have beneficial effects when injected into an injured joint. MSCs derived from MRL/MpJ mice did not promote an increased repair capacity compared to MSCs derived from non-healing C57BL6 controls; however, MRL/MpJ MSCs were observed within the defect area at the time points examined, while C57BL6 MSCs were not. PMID:26983696

  4. A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study

    PubMed Central

    Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V. N.; Poh, Chueh Loo; Wang, Dong-An

    2015-01-01

    In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair. PMID:26549401

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

    PubMed Central

    Pan, Weimin; Liu, Jian; Sun, Wei

    2015-01-01

    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. PMID:26695629

  6. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

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

  7. Effect of tenascin-C on the repair of full-thickness osteochondral defects of articular cartilage in rabbits.

    PubMed

    Ikemura, Shigeto; Hasegawa, Masahiro; Iino, Takahiro; Miyamoto, Keiichi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Sudo, Akihiro

    2015-04-01

    The purpose of this study was to examine the effect of tenascin-C (TNC) on the repair of full-thickness osteochondral defects of articular cartilage in vivo. We used a gellan-gellan-sulfate sponge (Gellan-GS) to maintain a TNC-rich environment in the cartilage defects. We implanted Gellan-GS soaked in PBS only (Group 1), Gellan-GS soaked in 10 µg/ml of TNC (Group 2), and Gellan-GS soaked in 100 µg/ml of TNC (Group 3) into a full-thickness osteochondral defect of the patellar groove of rabbits. The defect area was examined grossly and histologically 4-12 weeks after surgery. Sections of synovium were also immunohistochemically investigated. Histologically as well as macroscopically, the defects in Group 2 showed better repair than the other groups at 8 and 12 weeks after surgery. Inflammation of the synovium tended to diminish over time in all groups, and the degree of synovitis was the same for all three groups at each time point. In conclusion, Gellan-GS soaked in TNC can be used as a novel scaffold for the repair of articular cartilage defects. This study also indicates that TNC promotes the repair of full-thickness osteochondral defects in vivo. PMID:25428773

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

    PubMed

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

    2014-08-01

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

  9. Mechanical properties and structure-function relationships in articular cartilage repaired using IGF-I gene-enhanced chondrocytes.

    PubMed

    Griffin, Darvin J; Ortved, Kyla F; Nixon, Alan J; Bonassar, Lawrence J

    2016-01-01

    Several studies have demonstrated the benefits of IGF-I gene therapy in enhancing the histologic and biochemical content of cartilage repaired by chondrocyte transplantation. However, there is little to no data on the mechanical performance of IGF-I augmented cartilage grafts. This study evaluated the compressive properties of full-thickness chondral defects in the equine femur repaired with and without IGF-I gene therapy. Animals were randomly assigned to one of three study cohorts based on chondrocyte treatment provided in each defect: (i) IGF-I gene delivered by recombinant adeno-associated virus (rAAV)-5; (ii) AAV-5 delivering GFP as a reporter; (iii) naïve cells without virus. In each case, the opposite limb was implanted with a fibrin carrier without cells. Samples were prepared for confined compression testing to measure the aggregate modulus and hydraulic permeability. All treatment groups, regardless of cell content or transduction, had mechanical properties inferior to native cartilage. Overexpression of IGF-I increased modulus and lowered permeability relative to other treatments. Investigation of structure-property relationships revealed that Ha and k were linearly correlated with GAG content but logarithmically correlated with collagen content. This provides evidence that IGF-I gene therapy can improve healing of articular cartilage and can greatly increase the mechanical properties of repaired grafts. PMID:26308948

  10. Repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation

    SciTech Connect

    Grande, D.A.; Pitman, M.I.; Peterson, L.; Menche, D.; Klein, M.

    1989-01-01

    Using the knee joints of New Zealand White rabbits, a baseline study was made to determine the intrinsic capability of cartilage for healing defects that do not fracture the subchondral plate. A second experiment examined the effect of autologous chondrocytes grown in vitro on the healing rate of these defects. To determine whether any of the reconstituted cartilage resulted from the chondrocyte graft, a third experiment was conducted involving grafts with chondrocytes that had been labeled prior to grafting with a nuclear tracer. Results were evaluated using both qualitative and quantitative light microscopy. Macroscopic results from grafted specimens displayed a marked decrease in synovitis and other degenerative changes. In defects that had received transplants, a significant amount of cartilage was reconstituted (82%) compared to ungrafted controls (18%). Autoradiography on reconstituted cartilage showed that there were labeled cells incorporated into the repair matrix.

  11. Towards Regeneration of Articular Cartilage

    PubMed Central

    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

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

    PubMed

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

    2016-05-01

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

  13. Fracture of articular cartilage.

    PubMed

    Chin-Purcell, M V; Lewis, J L

    1996-11-01

    Crack formation and propagation is a significant element of the degeneration process in articular cartilage. In order to understand this process, and separate the relative importance of structural overload and material failure, methods for measuring the fracture toughness of cartilage are needed. In this paper, two such methods are described and used to measure fracture properties of cartilage from the canine patella. A modified single edge notch (MSEN) specimen was used to measure J, and a trouser tear test was used to measure T, both measures of fracture toughness with units of kN/m. A pseudo-elastic modulus was also obtained from the MSEN test. Several potential error sources were examined, and results for the MSEN test compared with another method for measuring the fracture parameter for urethane rubber. Good agreement was found. The two test methods were used to measure properties of cartilage from the patellae of 12 canines: 4-9 specimens from each of 12 patellae, with 5 right-left pairs were tested. Values of J ranged from 0.14-1.2 kN/m. J values correlated with T and were an average of 1.7 times larger than T. A variety of failure responses was seen in the MSEN tests, consequently a grade of 0 to 3 was assigned to each test, where 0 represented a brittle-like crack with minimal opening and 3 represented plastic flow with no crack formation. The initial cracks in 12/82 specimens did not propagate and were assigned to grade 3. The method for reducing data in the MSEN test assumed pseudo-elastic response and could not be used for the grade 3 specimens. Stiffness did not correlate with J. Neither J nor T was statistically different between right-left pairs, but varied between animals. The test methods appear useful for providing a quantitative measure of fracture toughness for cartilage and other soft materials. PMID:8950659

  14. Articular cartilage: structure and regeneration.

    PubMed

    Becerra, José; Andrades, José A; Guerado, Enrique; Zamora-Navas, Plácido; López-Puertas, José M; Reddi, A Hari

    2010-12-01

    Articular cartilage (AC) has no or very low ability of self-repair, and untreated lesions may lead to the development of osteoarthritis. One method that has been proven to result in long-term repair or isolated lesions is autologous chondrocyte transplantation. However, first generation of these cells' implantation has limitations, and introducing new effective cell sources can improve cartilage repair. AC provides a resilient and compliant articulating surface to the bones in diarthrodial joints. It protects the joint by distributing loads applied to it, so preventing potentially damaging stress concentrations on the bone. At the same time it provides a low-friction-bearing surface to enable free movement of the joint. AC may be considered as a visco- or poro-elastic fiber-composite material. Fibrils of predominantly type II collagen provide tensile reinforcing to a highly hydrated proteoglycan gel. The tissue typically comprises 70% water and it is the structuring and retention of this water by the proteoglycans and collagen that is largely responsible for the remarkable ability of the tissue to support compressive loads. PMID:20836752

  15. Engineering lubrication in articular cartilage.

    PubMed

    McNary, Sean M; Athanasiou, Kyriacos A; Reddi, A Hari

    2012-04-01

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

  16. Engineering Lubrication in Articular Cartilage

    PubMed Central

    McNary, Sean M.; Athanasiou, Kyriacos A.

    2012-01-01

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

  17. Proteoglycans and cartilage repair.

    PubMed

    Ouzzine, Mohamed; Venkatesan, Narayanan; Fournel-Gigleux, Sylvie

    2012-01-01

    Repair of damaged articular cartilage in osteoarthritis (OA) is a clinical challenge. Because cartilage is an avascular and aneural tissue, normal mechanisms of tissue repair through recruitment of cells to the site of tissue destruction are not feasible. Proteoglycan (PG) depletion induced by the proinflammatory cytokine interleukin-1β, a principal mediator in OA, is a major factor in the onset and progression of joint destruction. Current symptomatic treatments of OA by anti-inflammatory drugs do not alter the progression of the disease. Various therapeutic strategies have been developed to antagonize the effect of proinflammatory cytokines. However, relatively few studies were conducted to stimulate anabolic activity, in an attempt to enhance cartilage repair. To this aim, a nonviral gene transfer strategy of glycosyltransferases responsible for PG synthesis has been developed and tested for its capacity to promote cartilage PG synthesis and deposition. Transfection of chondrocytes or cartilage explants by the expression vector for the glycosyltransferase β-1,3-glucuronosyltransferase-I (GlcAT-I) enhanced PG synthesis and deposition in the ECM by promoting the synthesis of chondroitin sulfate GAG chains of the cartilage matrix. This indicates that therapy mediated through GT gene delivery may constitute a new strategy for the treatment of OA. PMID:22252645

  18. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage.

    PubMed

    Huang, Brian J; Hu, Jerry C; Athanasiou, Kyriacos A

    2016-08-01

    One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of current research in the field, it is known that 90% of new drugs that advance past animal studies fail clinical trials. The objective of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. PMID:27177218

  19. Imaging of articular cartilage: current concepts

    PubMed Central

    RONGA, MARIO; ANGERETTI, GLORIA; FERRARO, SERGIO; DE FALCO, GIOVANNI; GENOVESE, EUGENIO A.; CHERUBINO, PAOLO

    2014-01-01

    Magnetic resonance imaging (MRI) is the gold standard method for non-invasive assessment of joint cartilage, providing information on the structure, morphology and molecular composition of this tissue. There are certain minimum requirements for a MRI study of cartilage tissue: machines with a high magnetic field (> 1.5 Tesla); the use of surface coils; and the use of T2-weighted, proton density-weighted fast-spin echo (T2 FSE-DP) and 3D fat-suppressed T1-weighted gradient echo (3D-FS T1W GRE) sequences. For better contrast between the different joint structures, MR arthography is a method that can highlight minimal fibrillation or fractures of the articular surface and allow evaluation of the integrity of the native cartilage-repair tissue interface. To assess the biochemical composition of cartilage and cartilage repair tissue, various techniques have been proposed for studying proteoglycans [dGEMRIC, T1rho mapping, sodium (23Na) imaging MRI, etc.], collagen, and water distribution [T2 mapping, “magnetisation transfer contrast”, diffusion-weighted imaging (DWI), and so on]. Several MRI classifications have been proposed for evaluating the processes of joint degeneration (WORMS, BLOKS, ICRS) and post-surgical maturation of repair tissue (MOCART, 3D MOCART). In the future, isotropic 3D sequences set to improve image quality and facilitate the diagnosis of disorders of articular structures adjacent to cartilage. PMID:25606557

  20. [Imaging of articular cartilage].

    PubMed

    Arkun, Remide

    2007-01-01

    There have been many improvements in joint cartilage imaging in recent years with the development of new imaging methods. The purpose of cartilage imaging is to assess the integrity of the cartilage surface, the thickness and volume of the cartilage matrix and its relationship with the subchondral bone. Direct radiography, the conventional imaging method for the skeletal system, is not sufficient for assessing the joint cartilage, nor are arthrography, computed tomography, and arthrography together with computed tomography. Moreover, biomechanical changes in the joint cartilage cannot be assessed with these methods. Magnetic resonance imaging (MRI), with its superior contrast resolution and multiplanar imaging capability across tissues, has become the primary diagnostic method for assessment of joint pathologies. The morphological features of the joint cartilage can be assessed adequately with the use of MRI sequences specific to the cartilage. Appropriate use of MRI sequences to determine the type of cartilage damage, the presence and degree of accompanying pathologies in the subchondral bone will help minimize diagnostic errors. This article reviews cartilage imaging in the following aspects: the technique used in MRI for cartilage imaging, findings of cartilage pathology, and anticipation of future cartilage imaging. PMID:18180582

  1. Repair of an articular cartilage defect using adipose-derived stem cells loaded on a polyelectrolyte complex scaffold based on poly(l-glutamic acid) and chitosan.

    PubMed

    Zhang, Kunxi; Zhang, Yun; Yan, Shifeng; Gong, Lunli; Wang, Jia; Chen, Xuesi; Cui, Lei; Yin, Jingbo

    2013-07-01

    As a synthetic polypeptide water-soluble poly(l-glutamic acid) (PLGA) was designed to fabricate scaffolds for cartilage tissue engineering. Chitosan (CHI) has been employed as a physical cross-linking component in the construction of scaffolds. PLGA/CHI scaffolds act as sponges with a swelling ratio of 760±45% (mass%), showing promising biocompatibility and biodegradation. Autologous adipose-derived stem cells (ASCs) were expanded and seeded on PLGA/CHI scaffolds, ASC/scaffold constructs were then subjected to chondrogenic induction in vitro for 2weeks. The results showed that PLGA/CHI scaffolds could effectively support ASC adherence, proliferation and chondrogenic differentiation. The ASCs/scaffold constructs were then transplanted to repair full thickness articular cartilage defects (4mm in diameter, to the depth of subchondral bone) created in rabbit femur trochlea. Histological observations found that articular defects were covered with newly formed cartilage 6weeks post-implantation. After 12weeks the regenerated cartilage had integrated well with the surrounding native cartilage and subchondral bone. Toluidine blue and immunohistochemical staining confirmed similar accumulation of glycosaminoglycans and type II collagen in engineered cartilage as in native cartilage 12weeks post-implantation. The result was further supported by quantitative analysis of extracellular matrix deposition. The compressive modulus of the engineered cartilage increased significantly from 30% of that of normal cartilage at 6weeks to 83% at 12weeks. Cyto-nanoindentation also showed analogous biomechanical behavior of the engineered cartilage to that of native cartilage. The results of the present study thus demonstrate the potentiality of PLGA/CHI scaffolds in cartilage tissue engineering. PMID:23535234

  2. Surgical Treatment of Articular Cartilage Defects in the Knee: Are We Winning?

    PubMed Central

    Memon, A. R.; Quinlan, J. F.

    2012-01-01

    Articular cartilage (AC) injury is a common disorder. Numerous techniques have been employed to repair or regenerate the cartilage defects with varying degrees of success. Three commonly performed techniques include bone marrow stimulation, cartilage repair, and cartilage regeneration. This paper focuses on current level of evidence paying particular attention to cartilage regeneration techniques. PMID:22655202

  3. Development of artificial articular cartilage.

    PubMed

    Oka, M; Ushio, K; Kumar, P; Ikeuchi, K; Hyon, S H; Nakamura, T; Fujita, H

    2000-01-01

    Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of

  4. Use of a biological reactor and platelet-rich plasma for the construction of tissue-engineered bone to repair articular cartilage defects

    PubMed Central

    Li, Huibo; Sun, Shui; Liu, Haili; Chen, Hua; Rong, Xin; Lou, Jigang; Yang, Yunbei; Yang, Yi; Liu, Hao

    2016-01-01

    Articular cartilage defects are a major clinical burden worldwide. Current methods to repair bone defects include bone autografts, allografts and external fixation. In recent years, the repair of bone defects by tissue engineering has emerged as a promising approach. The present study aimed to assess a novel method using a biological reactor with platelet-rich plasma to construct tissue-engineered bone. Beagle bone marrow mesenchymal stem cells (BMSCs) were isolated and differentiated into osteoblasts and chondroblasts using platelet-rich plasma and tricalcium phosphate scaffolds cultured in a bioreactor for 3 weeks. The cell scaffold composites were examined by scanning electron microscopy (SEM) and implanted into beagles with articular cartilage defects. The expression of osteogenic markers, alkaline phosphatase and bone γ-carboxyglutamate protein (BGLAP) were assessed using polymerase chain reaction after 3 months. Articular cartilage specimens were observed histologically. Adhesion and distribution of BMSCs on the β-tricalcium phosphate (β-TCP) scaffold were confirmed by SEM. Histological examination revealed that in vivo bone defects were largely repaired 12 weeks following implantation. The expression levels of alkaline phosphatase (ALP) and BGLAP in the experimental groups were significantly elevated compared with the negative controls. BMSCs may be optimum seed cells for tissue engineering in bone repair. Platelet-rich plasma (PRP) provides a rich source of cytokines to promote BMSC function. The β-TCP scaffold is advantageous for tissue engineering due to its biocompatibility and 3D structure that promotes cell adhesion, growth and differentiation. The tissue-engineered bone was constructed in a bioreactor using BMSCs, β-TCP scaffolds and PRP and displayed appropriate morphology and biological function. The present study provides an efficient method for the generation of tissue-engineered bone for cartilage repair, compared with previously used

  5. Tissue Engineering of Articular Cartilage with Biomimetic Zones

    PubMed Central

    Klein, Travis J.; Malda, Jos; Sah, Robert L.

    2009-01-01

    Articular cartilage damage is a persistent and increasing problem with the aging population, and treatments to achieve biological repair or restoration remain a challenge. Cartilage tissue engineering approaches have been investigated for over 20 years, but have yet to achieve the consistency and effectiveness for widespread clinical use. One of the potential reasons for this is that the engineered tissues do not have or establish the normal zonal organization of cells and extracellular matrix that appears critical for normal tissue function. A number of approaches are being taken currently to engineer tissue that more closely mimics the organization of native articular cartilage. This review focuses on the zonal organization of native articular cartilage, strategies being used to develop such organization, the reorganization that occurs after culture or implantation, and future prospects for the tissue engineering of articular cartilage with biomimetic zones. PMID:19203206

  6. Autophagy modulates articular cartilage vesicle formation in primary articular chondrocytes.

    PubMed

    Rosenthal, Ann K; Gohr, Claudia M; Mitton-Fitzgerald, Elizabeth; Grewal, Rupinder; Ninomiya, James; Coyne, Carolyn B; Jackson, William T

    2015-05-22

    Chondrocyte-derived extracellular organelles known as articular cartilage vesicles (ACVs) participate in non-classical protein secretion, intercellular communication, and pathologic calcification. Factors affecting ACV formation and release remain poorly characterized; although in some cell types, the generation of extracellular vesicles is associated with up-regulation of autophagy. We sought to determine the role of autophagy in ACV production by primary articular chondrocytes. Using an innovative dynamic model with a light scatter nanoparticle counting apparatus, we determined the effects of autophagy modulators on ACV number and content in conditioned medium from normal adult porcine and human osteoarthritic chondrocytes. Healthy articular chondrocytes release ACVs into conditioned medium and show significant levels of ongoing autophagy. Rapamycin, which promotes autophagy, increased ACV numbers in a dose- and time-dependent manner associated with increased levels of autophagy markers and autophagosome formation. These effects were suppressed by pharmacologic autophagy inhibitors and short interfering RNA for ATG5. Caspase-3 inhibition and a Rho/ROCK inhibitor prevented rapamycin-induced increases in ACV number. Osteoarthritic chondrocytes, which are deficient in autophagy, did not increase ACV number in response to rapamycin. SMER28, which induces autophagy via an mTOR-independent mechanism, also increased ACV number. ACVs induced under all conditions had similar ecto-enzyme specific activities and types of RNA, and all ACVs contained LC3, an autophagosome-resident protein. These findings identify autophagy as a critical participant in ACV formation, and augment our understanding of ACVs in cartilage disease and repair. PMID:25869133

  7. Proteomic Analysis Profile of Engineered Articular Cartilage with Chondrogenic Differentiated Adipose Tissue-Derived Stem Cells Loaded Polyglycolic Acid Mesh for Weight-Bearing Area Defect Repair

    PubMed Central

    Gong, Lunli; Zhou, Xiao; Wu, Yaohao; Zhang, Yun; Wang, Chen; Zhou, Heng; Guo, Fangfang

    2014-01-01

    The present study was designed to investigate the possibility of full-thickness defects repair in porcine articular cartilage (AC) weight-bearing area using chondrogenic differentiated autologous adipose-derived stem cells (ASCs) with a follow-up of 3 and 6 months, which is successive to our previous study on nonweight-bearing area. The isolated ASCs were seeded onto the phosphoglycerate/polylactic acid (PGA/PLA) with chondrogenic induction in vitro for 2 weeks as the experimental group prior to implantation in porcine AC defects (8 mm in diameter, deep to subchondral bone), with PGA/PLA only as control. With follow-up time being 3 and 6 months, both neo-cartilages of postimplantation integrated well with the neighboring normal cartilage and subchondral bone histologically in experimental group, whereas only fibrous tissue in control group. Immunohistochemical and toluidine blue staining confirmed similar distribution of COL II and glycosaminoglycan in the regenerated cartilage to the native one. A vivid remolding process with repair time was also witnessed in the neo-cartilage as the compressive modulus significantly increased from 70% of the normal cartilage at 3 months to nearly 90% at 6 months, which is similar to our former research. Nevertheless, differences of the regenerated cartilages still could be detected from the native one. Meanwhile, the exact mechanism involved in chondrogenic differentiation from ASCs seeded on PGA/PLA is still unknown. Therefore, proteome is resorted leading to 43 proteins differentially identified from 20 chosen two-dimensional spots, which do help us further our research on some committed factors. In conclusion, the comparison via proteome provided a thorough understanding of mechanisms implicating ASC differentiation toward chondrocytes, which is further substantiated by the present study as a perfect supplement to the former one in nonweight-bearing area. PMID:24044689

  8. Concepts in Gene Therapy for Cartilage Repair

    PubMed Central

    Steinert, Andre F.; Nöth, Ulrich; Tuan, Rocky S.

    2009-01-01

    Summary Once articular cartilage is injured, it has a very limited capacity for self-repair. Although current surgical therapeutic procedures to cartilage repair are clinically useful, they cannot restore a normal articular surface. Current research offers a growing number of bioactive reagents, including proteins and nucleic acids, that may be used to augment different aspects of the repair process. As these agents are difficult to administer effectively, gene transfer approaches are being developed to provide their sustained synthesis at sites of repair. To augment regeneration of articular cartilage, therapeutic genes can be delivered to the synovium, or directly to the cartilage lesion. Gene delivery to the cells of the synovial lining is generally considered more suitable for chondroprotective approaches, based on the expression of anti-inflammatory mediators. Gene transfer targeted to cartilage defects can be achieved by either direct vector administration to cells located at or surrounding the defects, or by transplantation of genetically modified chondrogenic cells into the defect. Several studies have shown that exogenous cDNAs encoding growth factors can be delivered locally to sites of cartilage damage, where they are expressed at therapeutically relevant levels. Furthermore, data is beginning to emerge indicating, that efficient delivery and expression of these genes is capable of influencing a repair response toward the synthesis of a more hyaline cartilage repair tissue in vivo. This review presents the current status of gene therapy for cartilage healing and highlights some of the remaining challenges. PMID:18313477

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

    PubMed Central

    Hoffman, James K.; Geraghty, Sandra; Protzman, Nicole M.

    2015-01-01

    Marrow stimulation is frequently employed to treat focal chondral defects of the knee. However, marrow stimulation typically results in fibrocartilage repair tissue rather than healthy hyaline cartilage, which, over time, predisposes the repair to failure. Recently, a cryopreserved viable chondral allograft was developed to augment marrow stimulation. The chondral allograft is comprised of native viable chondrocytes, chondrogenic growth factors, and extracellular matrix proteins within the superficial, transitional, and radial zones of hyaline cartilage. Therefore, host mesenchymal stem cells that infiltrate the graft from the underlying bone marrow following marrow stimulation are provided with the optimal microenvironment to undergo chondrogenesis. The present report describes treatment of a trochlear defect with marrow stimulation augmented with this novel chondral allograft, along with nine month postoperative histological results. At nine months, the patient demonstrated complete resolution of pain and improvement in function, and the repair tissue consisted of 85% hyaline cartilage. For comparison, a biopsy obtained from a patient 8.2 months after treatment with marrow stimulation alone contained only 5% hyaline cartilage. These outcomes suggest that augmenting marrow stimulation with the viable chondral allograft can eliminate pain and improve outcomes, compared with marrow stimulation alone. PMID:25628907

  10. Articular cartilage repair using marrow stimulation augmented with a viable chondral allograft: 9-month postoperative histological evaluation.

    PubMed

    Hoffman, James K; Geraghty, Sandra; Protzman, Nicole M

    2015-01-01

    Marrow stimulation is frequently employed to treat focal chondral defects of the knee. However, marrow stimulation typically results in fibrocartilage repair tissue rather than healthy hyaline cartilage, which, over time, predisposes the repair to failure. Recently, a cryopreserved viable chondral allograft was developed to augment marrow stimulation. The chondral allograft is comprised of native viable chondrocytes, chondrogenic growth factors, and extracellular matrix proteins within the superficial, transitional, and radial zones of hyaline cartilage. Therefore, host mesenchymal stem cells that infiltrate the graft from the underlying bone marrow following marrow stimulation are provided with the optimal microenvironment to undergo chondrogenesis. The present report describes treatment of a trochlear defect with marrow stimulation augmented with this novel chondral allograft, along with nine month postoperative histological results. At nine months, the patient demonstrated complete resolution of pain and improvement in function, and the repair tissue consisted of 85% hyaline cartilage. For comparison, a biopsy obtained from a patient 8.2 months after treatment with marrow stimulation alone contained only 5% hyaline cartilage. These outcomes suggest that augmenting marrow stimulation with the viable chondral allograft can eliminate pain and improve outcomes, compared with marrow stimulation alone. PMID:25628907

  11. Three-dimensional collagen architecture in bovine articular cartilage.

    PubMed

    Jeffery, A K; Blunn, G W; Archer, C W; Bentley, G

    1991-09-01

    The three-dimensional architecture of bovine articular cartilage collagen and its relationship to split lines has been studied with scanning electron microscopy. In the middle and superficial zones, collagen was organised in a layered or leaf-like manner. The orientation was vertical in the intermediate zone, curving to become horizontal and parallel to the articular surface in the superficial zone. Each leaf consisted of a fine network of collagen fibrils. Adjacent leaves merged or were closely linked by bridging fibrils and were arranged according to the split-line pattern. The surface layer (lamina splendens) was morphologically distinct. Although ordered, the overall collagen structure was different in each plane (anisotropic) a property described in previous morphological and biophysical studies. As all components of the articular cartilage matrix interact closely, the three-dimensional organisation of collagen is important when considering cartilage function and the processes of cartilage growth, injury and repair. PMID:1894669

  12. Induced pluripotent stem cells in cartilage repair.

    PubMed

    Lietman, Steven A

    2016-03-18

    Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from iPSCs have usually been formed in condensed cell bodies (resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from iPSCs are problematic but solutions to these problems are on the horizon. These solutions will make iPSCs a viable alternative for articular cartilage repair in the near future. PMID:27004161

  13. Induced pluripotent stem cells in cartilage repair

    PubMed Central

    Lietman, Steven A

    2016-01-01

    Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from iPSCs have usually been formed in condensed cell bodies (resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from iPSCs are problematic but solutions to these problems are on the horizon. These solutions will make iPSCs a viable alternative for articular cartilage repair in the near future. PMID:27004161

  14. Animal models of cartilage repair

    PubMed Central

    Cook, J. L.; Hung, C. T.; Kuroki, K.; Stoker, A. M.; Cook, C. R.; Pfeiffer, F. M.; Sherman, S. L.; Stannard, J. P.

    2014-01-01

    Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair. Cite this article: Bone Joint Res 2014;4:89–94. PMID:24695750

  15. Surface of articular cartilage: immunohistological studies.

    PubMed

    Duance, V C

    1983-10-01

    Using several physical techniques the surface of articular cartilage has been reported to be structurally different from the deeper layers. In this paper using immunohistochemical methods, the surface has been shown to contain a characteristically different collagen, Type I in contrast to Type II which is the major collagen of cartilage. These results support previous proposals for a surface layer, or lamina splendens, the presence of which would be of considerable importance in understanding the degradation of cartilage in arthritides. PMID:6678620

  16. Magnetic Resonance Imaging of Cartilage Repair

    PubMed Central

    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

  17. Combinatorial scaffold morphologies for zonal articular cartilage engineering.

    PubMed

    Steele, J A M; McCullen, S D; Callanan, A; Autefage, H; Accardi, M A; Dini, D; Stevens, M M

    2014-05-01

    Articular cartilage lesions are a particular challenge for regenerative medicine strategies as cartilage function stems from a complex depth-dependent organization. Tissue engineering scaffolds that vary in morphology and function offer a template for zone-specific cartilage extracellular matrix (ECM) production and mechanical properties. We fabricated multi-zone cartilage scaffolds by the electrostatic deposition of polymer microfibres onto particulate-templated scaffolds produced with 0.03 or 1.0mm(3) porogens. The scaffolds allowed ample space for chondrocyte ECM production within the bulk while also mimicking the structural organization and functional interface of cartilage's superficial zone. Addition of aligned fibre membranes enhanced the mechanical and surface properties of particulate-templated scaffolds. Zonal analysis of scaffolds demonstrated region-specific variations in chondrocyte number, sulfated GAG-rich ECM, and chondrocytic gene expression. Specifically, smaller porogens (0.03mm(3)) yielded significantly higher sGAG accumulation and aggrecan gene expression. Our results demonstrate that bilayered scaffolds mimic some key structural characteristics of native cartilage, support in vitro cartilage formation, and have superior features to homogeneous particulate-templated scaffolds. We propose that these scaffolds offer promise for regenerative medicine strategies to repair articular cartilage lesions. PMID:24370641

  18. New techniques in articular cartilage imaging.

    PubMed

    Potter, Hollis G; Black, Brandon R; Chong, Le Roy

    2009-01-01

    Standardized magnetic resonance imaging (MRI) pulse sequences provide an accurate, reproducible assessment of cartilage morphology. Three-dimensional (3D) modeling techniques enable semiautomated models of the joint surface and thickness measurements, which may eventually prove essential in templating before partial or total joint resurfacing as well as focal cartilage repair. Quantitative MRI techniques, such as T2 mapping, T1 rho, and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), provide noninvasive information about cartilage and repair tissue biochemistry. Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) demonstrate information regarding the regional anisotropic variation of cartilage ultrastructure. Further research strengthening the association between quantitative MRI and cartilage material properties may predict the functional capacity of native and repaired tissue. MRI provides an essential objective assessment of cartilage regenerative procedures. PMID:19064167

  19. Regeneration of Articular Cartilage Surface: Morphogens, Cells, and Extracellular Matrix Scaffolds.

    PubMed

    Sakata, Ryosuke; Iwakura, Takashi; Reddi, A Hari

    2015-10-01

    The articular cartilage is a well-organized tissue for smooth and friction-free joint movement for locomotion in animals and humans. Adult articular cartilage has a very low self-regeneration capacity due to its avascular nature. The regeneration of articular cartilage surface is critical to prevent the progression to osteoarthritis (OA). Although various joint resurfacing procedures in experimental articular cartilage defects have been developed, no standardized clinical protocol has yet been established. The three critical ingredients for tissue regeneration are morphogens and growth factors, cells, and scaffolds. The concepts based on the regeneration triad have been extensively investigated in animal models. However, these studies in animal models have demonstrated variable results and outcomes. An optimal animal model must precisely mimic and model the sequence of events in articular cartilage regeneration in human. In this article, the progress and remaining challenges in articular cartilage regeneration in animal models are reviewed. The role of individual morphogens and growth factors in cartilage regeneration has been investigated. In normal articular cartilage homeostasis, morphogens and growth factors function sequentially in tissue regeneration. Mesenchymal stem cell-based repair of articular cartilage defects, performed with or without various growth factors and scaffolds, has been widely attempted in animal models. Stem cells, including embryonic and adult stem cells and induced pluripotent stem cells, have also been reported as attractive cell sources for articular cartilage surface regeneration. Several studies with regard to scaffolds have been advanced, including recent investigations based on nanomaterials, functional mechanocompatible scaffolds, multilayered scaffolds, and extracellular matrix scaffolds for articular cartilage surface regeneration. Continuous refinement of animal models in chondral and osteochondral defects provide opportunities

  20. Treatment of articular cartilage lesions of the knee

    PubMed Central

    Falah, Mazen; Nierenberg, Gabreil; Soudry, Michael; Hayden, Morris

    2010-01-01

    Treatment of articular cartilage lesions in the knee remains a challenge for the practising orthopaedic surgeon. A wide range of options are currently practised, ranging from conservative measures through various types of operations and, recently, use of growth factors and emerging gene therapy techniques. The end result of these methods is usually a fibrous repair tissue (fibrocartilage), which lacks the biomechanical characteristics of hyaline cartilage that are necessary to withstand the compressive forces distributed across the knee. The fibrocartilage generally deteriorates over time, resulting in a return of the original symptoms and occasionally reported progression to osteoarthritis. Our purpose in this study was to review the aetiology, pathogenesis and treatment options for articular cartilage lesions of the knee. At present, autologous cell therapies, growth factor techniques and biomaterials offer more promising avenues of research to find clinical answers. PMID:20162416

  1. Effect of passive motion on articular cartilage in rat osteoarthritis

    PubMed Central

    QIAN, JIE; LIANG, JUN; WANG, YUBIN; WANG, HUIFANG

    2014-01-01

    fibers when compared with the control group, but not when compared with the three-week experimental group. Therefore, proper passive motion can repair and improve the metabolism of chondrocytes and delay the degenerative progress of articular cartilage in OA caused by knee fracture. However, for middle-stage OA, passive motion exhibits no significant repairing effect on the articular cartilage. This therapy increases the levels of proteoglycans and collagen fibers by reducing their decomposition, thereby improving the strength of the articular ligament and the stability of articulation. PMID:25009586

  2. Effect of passive motion on articular cartilage in rat osteoarthritis.

    PubMed

    Qian, Jie; Liang, Jun; Wang, Yubin; Wang, Huifang

    2014-08-01

    fibers when compared with the control group, but not when compared with the three-week experimental group. Therefore, proper passive motion can repair and improve the metabolism of chondrocytes and delay the degenerative progress of articular cartilage in OA caused by knee fracture. However, for middle-stage OA, passive motion exhibits no significant repairing effect on the articular cartilage. This therapy increases the levels of proteoglycans and collagen fibers by reducing their decomposition, thereby improving the strength of the articular ligament and the stability of articulation. PMID:25009586

  3. Vitrification of intact human articular cartilage.

    PubMed

    Jomha, Nadr M; Elliott, Janet A W; Law, Garson K; Maghdoori, Babak; Forbes, J Fraser; Abazari, Alireza; Adesida, Adetola B; Laouar, Leila; Zhou, Xianpei; McGann, Locksley E

    2012-09-01

    Articular cartilage injuries do not heal and large defects result in osteoarthritis with major personal and socioeconomic costs. Osteochondral transplantation is an effective treatment for large joint defects but its use is limited by the inability to store cartilage for long periods of time. Cryopreservation/vitrification is one method to enable banking of this tissue but decades of research have been unable to successfully preserve the tissue while maintaining cartilage on its bone base - a requirement for transplantation. To address this limitation, human knee articular cartilage from total knee arthroplasty patients and deceased donors was exposed to specified concentrations of 4 different cryoprotective agents for mathematically determined periods of time at lowering temperatures. After complete exposure, the cartilage was immersed in liquid nitrogen for up to 3 months. Cell viability was 75.4 ± 12.1% determined by membrane integrity stains and confirmed with a mitochondrial assay and pellet culture documented production of sulfated glycosaminoglycans and collagen II similar to controls. This report documents successful vitrification of intact human articular cartilage on its bone base making it possible to bank this tissue indefinitely. PMID:22698720

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

    PubMed

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

    2008-12-01

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

  5. Body Weight Independently Affects Articular Cartilage Catabolism

    PubMed Central

    Denning, W. Matt; Winward, Jason G.; Pardo, Michael Becker; Hopkins, J. Ty; Seeley, Matthew K.

    2015-01-01

    Although obesity is associated with osteoarthritis, it is unclear whether body weight (BW) independently affects articular cartilage catabolism (i.e., independent from physiological factors that also accompany obesity). The primary purpose of this study was to evaluate the independent effect of BW on articular cartilage catabolism associated with walking. A secondary purpose was to determine how decreased BW influenced cardiovascular response due to walking. Twelve able-bodied subjects walked for 30 minutes on a lower-body positive pressure treadmill during three sessions: control (unadjusted BW), +40%BW, and -40%BW. Serum cartilage oligomeric matrix protein (COMP) was measured immediately before (baseline) and after, and 15 and 30 minutes after the walk. Heart rate (HR) and rate of perceived exertion (RPE) were measured every three minutes during the walk. Relative to baseline, average serum COMP concentration was 13% and 5% greater immediately after and 15 minutes after the walk. Immediately after the walk, serum COMP concentration was 14% greater for the +40%BW session than for the -40%BW session. HR and RPE were greater for the +40%BW session than for the other two sessions, but did not differ between the control and -40%BW sessions. BW independently influences acute articular cartilage catabolism and cardiovascular response due to walking: as BW increases, so does acute articular cartilage catabolism and cardiovascular response. These results indicate that lower-body positive pressure walking may benefit certain individuals by reducing acute articular cartilage catabolism, due to walking, while maintaining cardiovascular response. Key points Walking for 30 minutes with adjustments in body weight (normal body weight, +40% and -40% body weight) significantly influences articular cartilage catabolism, measured via serum COMP concentration. Compared to baseline levels, walking with +40% body weight and normal body weight both elicited significant increases in

  6. Distinguishing ankle and knee articular cartilage.

    PubMed

    Cole, Ada A; Margulis, Arkady; Kuettner, Klaus E

    2003-06-01

    Degenerative changes in the tall and femoral distal cartilages of more than 2,000 tissue donors were graded based on the appearance of articular cartilage and osteophytes. In the ankle and the knee the degenerative changes increased with age; however, the rate of degeneration in the ankle was slower than in the knee. The degenerative changes in the ankle were more severe in men than in women, were predominantly bilateral, and seemed to be correlated with weight. The slower rate of change in the ankle may be caused, in part, by the biochemical and biomechanical tissue properties that distinguish ankle cartilage from that of the knee. PMID:12911243

  7. Resurfacing Damaged Articular Cartilage to Restore Compressive Properties

    PubMed Central

    Grenier, Stephanie; Donnelly, Patrick E.; Gittens, Jamila; Torzilli, Peter A.

    2014-01-01

    Surface damage to articular cartilage is recognized as the initial underlying process causing the loss of mechanical function in early-stage osteoarthritis. In this study, we developed structure-modifying treatments to potentially prevent, stabilize or reverse the loss in mechanical function. Various polymers (chondroitin sulfate, carboxymethylcellulose, sodium hyaluronate) and photoinitiators (riboflavin, irgacure 2959) were applied to the surface of collagenase-degraded cartilage and crosslinked in situ using UV light irradiation. While matrix permeability and deformation significantly increased following collagenase-induced degradation of the superficial zone, resurfacing using tyramine-substituted sodium hyaluronate and riboflavin decreased both values to a level comparable to that of intact cartilage. Repetitive loading of resurfaced cartilage showed minimal variation in the mechanical response over a 7 day period. Cartilage resurfaced using a low concentration of riboflavin had viable cells in all zones while a higher concentration resulted in a thin layer of cell death in the uppermost superficial zone. Our approach to repair surface damage initiates a new therapeutic advance in the treatment of injured articular cartilage with potential benefits that include enhanced mechanical properties, reduced susceptibility to enzymatic degradation and reduced adhesion of macrophages. PMID:25468298

  8. In vitro growth factor-induced bio engineering of mature articular cartilage

    PubMed Central

    Khan, Ilyas M.; Francis, Lewis; Theobald, Peter S.; Perni, Stefano; Young, Robert D.; Prokopovich, Polina; Conlan, R. Steven; Archer, Charles W.

    2013-01-01

    Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Maturation involves gross morphological changes that occur through a process of synchronised growth and resorption of cartilage and generally ends at sexual maturity. The inability to induce maturation in biomaterial constructs designed for cartilage repair has been cited as a major cause for their failure in producing persistent cell-based repair of joint lesions. The combination of growth factors FGF2 and TGFβ1 induces accelerated articular cartilage maturation in vitro such that many molecular and morphological characteristics of tissue maturation are observable. We hypothesised that experimental growth factor-induced maturation of immature cartilage would result in a biophysical and biochemical composition consistent with a mature phenotype. Using native immature and mature cartilage as reference, we observed that growth factor-treated immature cartilages displayed increased nano-compressive stiffness, decreased surface adhesion, decreased water content, increased collagen content and smoother surfaces, correlating with a convergence to the mature cartilage phenotype. Furthermore, increased gene expression of surface structural protein collagen type I in growth factor-treated explants compared to reference cartilages demonstrates that they are still in the dynamic phase of the postnatal developmental transition. These data provide a basis for understanding the regulation of postnatal maturation of articular cartilage and the application of growth factor-induced maturation in vitro and in vivo in order to repair and regenerate cartilage defects. PMID:23182922

  9. The repair of full-thickness articular cartilage defects. Immune responses to reparative tissue formed by allogeneic growth plate chondrocyte implants

    SciTech Connect

    Kawabe, N.; Yoshinao, M. )

    1991-07-01

    Growth plate cartilage cultivated in vitro was attached with a fibrin clot to a full-thickness articular cartilage defect on knee joints in allogeneic New Zealand rabbits. The healing of the defects was assessed by gross examination, light microscopy, and immunologic analysis for 24 weeks. Immunologic assessment of cell-mediated immunity, cytotoxicity of a humoral antibody by a 51 chromium release assay, and immunofluorescence studies were carried out. During the first two weeks following grafting, healing was excellent in 11 of the 17 defects. From three to 24 weeks, 11 of 42 defects examined had good results. Host lymphocytes had accumulated around the allograft at two to 12 weeks. Most of the implanted cartilage grown in vitro died and was replaced by fibrous tissue. The immunologic studies suggested that the implanted cartilage began to degenerate two to three weeks after implantation partially because of a humoral immune response but more importantly because of cell-mediated cytotoxicity.

  10. Analysis of friction between articular cartilage and polyvinyl alcohol hydrogel artificial cartilage.

    PubMed

    Li, Feng; Wang, Anmin; Wang, Chengtao

    2016-05-01

    Many biomaterials are being used to repair damaged articular cartilage. In particular, poly vinyl alcohol hydrogel has similar mechanical properties to natural cartilage under compressive and shearing loading. Here, three-factor and two-level friction experiments and long-term tests were conducted to better evaluate its tribological properties. The friction coefficient between articular cartilage and the poly vinyl alcohol hydrogel depended primarily on the three factors of load, speed, and lubrication. When the speed increased from 10 to 20 mm/s under a load of 10 N, the friction coefficient increased from 0.12 to 0.147. When the lubricant was changed from Ringer's solution to a hyaluronic acid solution, the friction coefficient decreased to 0.084 with loads as high as 22 N. The poly vinyl alcohol hydrogel was severely damaged and lost its top surface layers, which were transferred to the articular cartilage surface. Wear was observed in the surface morphologies, which indicated the occurrence of surface adhesion of bovine cartilage. Surface fatigue and adhesive wear was the dominant wear mechanism. PMID:26970769

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

    PubMed Central

    Tavassoli, Amin; Matin, Maryam Moghaddam; Niaki, Malihe Akbarzade; Mahdavi-Shahri, Nasser; Shahabipour, Fahimeh

    2015-01-01

    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. PMID:26877852

  12. PRP and Articular Cartilage: A Clinical Update

    PubMed Central

    Rossi, Roberto; Castoldi, Filippo; Michielon, Gianni

    2015-01-01

    The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory. PMID:26075244

  13. Stem cells for tissue engineering of articular cartilage.

    PubMed

    Gao, J; Yao, J Q; Caplan, A I

    2007-07-01

    Articular cartilage injuries are one of the most common disorders in the musculo-skeletal system. Injured cartilage tissue cannot spontaneously heal and, if not treated, can lead to osteoarthritis of the affected joints. Although a variety of procedures are being employed to repair cartilage damage, methods that result in consistent durable repair tissue are not yet available. Tissue engineering is a recently developed science that merges the fields of cell biology, engineering, material science, and surgery to regenerate new functional tissue. Three critical components in tissue engineering of cartilage are as follows: first, sufficient cell numbers within the defect, such as chondrocytes or multipotent stem cells capable of differentiating into chondrocytes; second, access to growth and differentiation factors that modulate these cells to differentiate through the chondrogenic lineage; third, a cell carrier or matrix that fills the defect, delivers the appropriate cells, and supports cell proliferation and differentiation. Stem cells that exist in the embyro or in adult somatic tissues are able to renew themselves through cell division without changing their phenotype and are able to differentiate into multiple lineages including the chondrogenic lineage under certain physiological or experimental conditions. Here the application of stem cells as a cell source for cartilage tissue engineering is reviewed. PMID:17822146

  14. Human Adipose-Derived Mesenchymal Progenitor Cells Engraft into Rabbit Articular Cartilage

    PubMed Central

    Wang, Wen; He, Na; Feng, Chenchen; Liu, Victor; Zhang, Luyi; Wang, Fei; He, Jiaping; Zhu, Tengfang; Wang, Shuyang; Qiao, Weiwei; Li, Suke; Zhou, Guangdong; Zhang, Li; Dai, Chengxiang; Cao, Wei

    2015-01-01

    Mesenchymal stem cells (MSCs) are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA). Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated. OA was induced surgically by anterior cruciate ligament transection (ACLT) and medical meniscectomy of knee joints. At six weeks following surgery, hyaluronic acid (HA) or haMPCs was injected into the knee joints, the contralateral knee served as normal control. All animals were sacrificed at the 16th week post-surgery. Assessments were carried out by macroscopic examination, hematoxylin/eosin (HE) and Safranin-O/Fast green stainings and immunohistochemistry. The data showed that haMPC treatment promoted cartilage repair. Signals of human mitochondrial can be directly detected in haMPC treated cartilage. The haMPCs expressed human leukocyte antigen I (HLA-I) but not HLA-II-DR in vivo. These results suggest that intra-articular injection of haMPCs promotes regeneration of articular cartilage in rabbit OA model, and support the notion that MPCs are transplantable between HLA-incompatible individuals. PMID:26023716

  15. Articular cartilage: from formation to tissue engineering.

    PubMed

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

    2016-05-26

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

  16. Damage Control Mechanisms in Articular Cartilage

    PubMed Central

    Martin, James A; Scherb, MB; Lembke, Lois A; Buckwalter, Joseph

    2000-01-01

    Articular chondrocytes maintain cartilage throughout life by replacing lost or damaged matrix with freshly synthesized material. Synthesis activity is regulated, rapidly increasing to well above basal levels in response to cartilage injury. Such responses suggest that synthesis activity is linked to the rate of matrix loss by endogenous "damage control" mechanisms. As a major stimulator of matrix synthesis in cartilage, insulin-like growth factor I (IGF-I) is likely to play a role in such mechanisms. Although IGF-I is nearly ubiquitous, its bioavailability in cartilage is controlled by IGF-I binding proteins (IGFBPs) secreted by chondrocytes. IGFBPs are part of a complex system, termed the IGF-I axis, that tightly regulates IGF-I activities. For the most part, IGFBPs block IGF-I activity by sequestering IGF-I from its cell surface receptor. We recently found that the expression of one binding protein, IGFBP-3, increases with chondrocyte age, paralleling an age-related decline in synthesis activity. In addition, IGFBP-3 is overexpressed in osteoarthritic cartilage, leading to metabolic disturbances that contribute to cartilage degeneration. These observations indicate that IGFBP-3 plays a crucial role in regulating matrix synthesis in cartilage, and suggest that cartilage damage control mechanisms may fail due to age-related changes in IGFBP-3 expression or distribution. Our investigation of this hypothesis began with immunolocalization studies to determine the tissue distribution of IGFBP-3 in human cartilage. We found that IGFBP-3 accumulated around chondrocytes in the pericellular/territorial matrix, where it co-localized with fibronectin, but not with the other matrix proteins tenascin-C and type VI collagen. This result suggested that the IGFBP-3 distribution is determined by binding to fibronectin. Binding studies using purified proteins demonstrated that IGFBP-3 does in fact bind to fibronectin, but not to tenascin-C or type VI collagen. Finally, we

  17. Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair

    PubMed Central

    Park, Sang-Hyug; Kim, Moon Suk; Kim, Young Jick; Choi, Byung Hyune; Lee, Chun Tek; Park, So Ra; Min, Byoung-Hyun

    2016-01-01

    Recombinant human transforming growth factor beta-3 (rhTGF-β3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS) are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+) rhTGF-β3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair. PMID:27258120

  18. Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair.

    PubMed

    Yang, Soon Sim; Jin, Long Hao; Park, Sang-Hyug; Kim, Moon Suk; Kim, Young Jick; Choi, Byung Hyune; Lee, Chun Tek; Park, So Ra; Min, Byoung-Hyun

    2016-01-01

    Recombinant human transforming growth factor beta-3 (rhTGF-β3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS) are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+) rhTGF-β3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair. PMID:27258120

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

    PubMed

    Goldring, Steven R

    2012-08-01

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

  20. Radiography of rabbit articular cartilage with diffraction-enhanced imaging.

    PubMed

    Muehleman, Carol; Chapman, L Dean; Kuettner, Klaus E; Rieff, Joel; Mollenhauer, Juergen A; Massuda, Koichi; Zhong, Zhong

    2003-05-01

    Articular cartilage of synovial joints is not visible with conventional X-ray imaging. Hence, the gradual degeneration and destruction of articular cartilage, which is characteristic of degenerative joint diseases, is only detected at a late stage when the cartilage is lost and the joint space that it once occupied narrows. The development of an X-ray imaging technique that could detect both the degenerative cartilage and bone features of joint diseases is of special interest. Here we show, for the first time, that a high-contrast imaging technique, diffraction-enhanced X-ray imaging (DEI), allows the visualization of articular cartilage of both disarticulated and articulated rabbit knee joints. Furthermore, a single cartilage lesion can be visualized within an intact joint. The results suggest that DEI has the potential to be of use in the study of cartilage degeneration. PMID:12704696

  1. 3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation

    PubMed Central

    Yang, Fan; Bhutani, Nidhi

    2015-01-01

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

  2. 3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Kazemi, Davoud; Fakhrjou, Ashraf

    2015-01-01

    Background: Articular cartilage injuries of the knee are among the most debilitating injuries leading to osteoarthritis due to limited regenerative capability of cartilaginous tissue. The use of platelet concentrates containing necessary growth factors for cartilage healing has recently emerged as a new treatment method. Objectives: The efficacy of two types of different platelet concentrates were compared in the treatment of acute articular cartilage injuries of the knee in an animal model. Materials and Methods: Eighteen adult Iranian mixed breed male dogs were used to conduct this experimental study. Full thickness articular cartilage defects (diameter 6 mm, depth 5 mm) were created in the weight bearing area of femoral condyles of both hind limbs in all dogs (n = 72). Twelve dogs were randomly selected to receive treatment and their right and left hind limb defects were treated by L-PRP and L-PRF implantation respectively, while no treatment was undertaken in six other dogs as controls. The animals were euthanized at 4, 16 and 24 weeks following surgery and the resultant repair tissue was investigated macroscopically and microscopically. At each sampling time, 4 treated dogs and 2 control dogs were euthanized, therefore 8 defects per group were evaluated. Results: Mean macroscopic scores of the treated defects were higher than the controls at all sampling times with significant differences (P < 0.05) observed between L-PRF treated and control defects (10.13 vs. 8.37) and L-PRP treated and control defects (10 vs. 8.5) at 4 and 16 weeks, respectively. A similar trend in mean total microscopic scores was observed with a significant difference (P < 0.05) between L-PRP treated and control defects at 4 (9.87 vs. 7.62) and 16 (13.38 vs. 11) weeks. No significant difference was observed between the platelet concentrate treated defects in either mean macroscopic scores or mean total microscopic scores. Conclusions: Both L-PRP and L-PRF could be used to effectively

  4. Polymer Formulations for Cartilage Repair

    SciTech Connect

    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.

  5. Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

    PubMed Central

    Yamada, Jun; Abula, Kahaer; Inoue, Makiko; Sekiya, Ichiro; Muneta, Takeshi

    2014-01-01

    Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration. PMID:25574420

  6. Simultaneous magnetic resonance imaging and consolidation measurement of articular cartilage.

    PubMed

    Wellard, Robert Mark; Ravasio, Jean-Philippe; Guesne, Samuel; Bell, Christopher; Oloyede, Adekunle; Tevelen, Greg; Pope, James M; Momot, Konstantin I

    2014-01-01

    Magnetic resonance imaging (MRI) offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation) of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP). MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer. PMID:24803188

  7. Simultaneous Magnetic Resonance Imaging and Consolidation Measurement of Articular Cartilage

    PubMed Central

    Wellard, Robert Mark; Ravasio, Jean-Philippe; Guesne, Samuel; Bell, Christopher; Oloyede, Adekunle; Tevelen, Greg; Pope, James M.; Momot, Konstantin I.

    2014-01-01

    Magnetic resonance imaging (MRI) offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation) of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP). MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer. PMID:24803188

  8. Signaling Pathways in Cartilage Repair

    PubMed Central

    Mariani, Erminia; Pulsatelli, Lia; Facchini, Andrea

    2014-01-01

    In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules and biophysical factors, shedding light on these mechanisms appears to be extremely relevant for both the identification of pathogenic key factors, as specific therapeutic targets, and the development of biological approaches for cartilage regeneration. This review will focus on the main signaling pathways that can activate cellular and molecular processes, regulating the functional behavior of cartilage in both physiological and pathological conditions. These networks may be relevant in the crosstalk among joint compartments and increased knowledge in this field may lead to the development of more effective strategies for inducing cartilage repair. PMID:24837833

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

    PubMed Central

    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

  10. Magnetic Resonance Imaging of Cartilage Repair: A Review.

    PubMed

    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

  11. A microanalytical study of the surfaces of normal, delipidized, and artificially "resurfaced" articular cartilage.

    PubMed

    Yusuf, Kehinde Quasim; Motta, Nunzio; Pawlak, Zenon; Oloyede, Adekunle

    2012-01-01

    The surface amorphous layer of articular cartilage is of primary importance to its load-bearing and lubrication function. This lipid-filled layer is degraded/disrupted or eliminated when cartilage degenerates due to diseases. This article examines further the characteristic of this surface overlay using a combination of microscopy and imaging methods to evaluate the hypothesis that the surface of articular cartilage can be repaired by exposing degraded cartilage to aqueous synthetic lipid mixtures. The preliminary results demonstrate that it is possible to create a new surface layer of phospholipids on the surface of cartilage following artificial lipid removal, but such a layer does not possess enough mechanical strength for physiological function when created with either unsaturated palmitoyl-oleoyl-phosphatidylcholine or saturated dipalmitoyl-phosphatidylcholine component of joint lipid composition alone. We conclude that this may be due to low structural cohesivity, inadequate time of exposure, and the mix/content of lipid in the incubation environment. PMID:22141914

  12. Quantitative ultrasound imaging detects degenerative changes in articular cartilage surface and subchondral bone

    NASA Astrophysics Data System (ADS)

    Saarakkala, Simo; Laasanen, Mikko S.; Jurvelin, Jukka S.; Töyräs, Juha

    2006-10-01

    Previous studies have suggested that quantitative ultrasound imaging could sensitively diagnose degeneration of the articular surface and changes in the subchondral bone during the development of osteoarthrosis (OA). We have recently introduced a new parameter, ultrasound roughness index (URI), for the quantification of cartilage surface roughness, and successfully tested it with normal and experimentally degraded articular surfaces. In this in vitro study, the applicability of URI was tested in bovine cartilage samples with spontaneously developed tissue degeneration. Simultaneously, we studied the sensitivity of quantitative ultrasound imaging to detect degenerative changes in the cartilage-bone interface. For reference, histological degenerative grade of the cartilage samples was determined. Mechanical reference measurements were also conducted. Cartilage surface roughness (URI) was significantly (p < 0.05) higher in histologically degenerated samples with inferior mechanical properties. Ultrasound reflection at the cartilage-bone interface was also significantly (p < 0.05) increased in degenerated samples. Furthermore, it was quantitatively confirmed that ultrasound attenuation in the overlying cartilage significantly affects the measured ultrasound reflection values from the cartilage-bone interface. To conclude, the combined ultrasound measurement of the cartilage surface roughness and ultrasound reflection at the cartilage-bone interface complement each other, and may together enable more sensitive and quantitative diagnosis of early OA or follow up after surgical cartilage repair.

  13. Quantitative ultrasound imaging detects degenerative changes in articular cartilage surface and subchondral bone.

    PubMed

    Saarakkala, Simo; Laasanen, Mikko S; Jurvelin, Jukka S; Töyräs, Juha

    2006-10-21

    Previous studies have suggested that quantitative ultrasound imaging could sensitively diagnose degeneration of the articular surface and changes in the subchondral bone during the development of osteoarthrosis (OA). We have recently introduced a new parameter, ultrasound roughness index (URI), for the quantification of cartilage surface roughness, and successfully tested it with normal and experimentally degraded articular surfaces. In this in vitro study, the applicability of URI was tested in bovine cartilage samples with spontaneously developed tissue degeneration. Simultaneously, we studied the sensitivity of quantitative ultrasound imaging to detect degenerative changes in the cartilage-bone interface. For reference, histological degenerative grade of the cartilage samples was determined. Mechanical reference measurements were also conducted. Cartilage surface roughness (URI) was significantly (p<0.05) higher in histologically degenerated samples with inferior mechanical properties. Ultrasound reflection at the cartilage-bone interface was also significantly (p<0.05) increased in degenerated samples. Furthermore, it was quantitatively confirmed that ultrasound attenuation in the overlying cartilage significantly affects the measured ultrasound reflection values from the cartilage-bone interface. To conclude, the combined ultrasound measurement of the cartilage surface roughness and ultrasound reflection at the cartilage-bone interface complement each other, and may together enable more sensitive and quantitative diagnosis of early OA or follow up after surgical cartilage repair. PMID:17019042

  14. Use magnetic resonance imaging to assess articular cartilage

    PubMed Central

    Wang, Yuanyuan; Wluka, Anita E.; Jones, Graeme; Ding, Changhai

    2012-01-01

    Magnetic resonance imaging (MRI) enables a noninvasive, three-dimensional assessment of the entire joint, simultaneously allowing the direct visualization of articular cartilage. Thus, MRI has become the imaging modality of choice in both clinical and research settings of musculoskeletal diseases, particular for osteoarthritis (OA). Although radiography, the current gold standard for the assessment of OA, has had recent significant technical advances, radiographic methods have significant limitations when used to measure disease progression. MRI allows accurate and reliable assessment of articular cartilage which is sensitive to change, providing the opportunity to better examine and understand preclinical and very subtle early abnormalities in articular cartilage, prior to the onset of radiographic disease. MRI enables quantitative (cartilage volume and thickness) and semiquantitative assessment of articular cartilage morphology, and quantitative assessment of cartilage matrix composition. Cartilage volume and defects have demonstrated adequate validity, accuracy, reliability and sensitivity to change. They are correlated to radiographic changes and clinical outcomes such as pain and joint replacement. Measures of cartilage matrix composition show promise as they seem to relate to cartilage morphology and symptoms. MRI-derived cartilage measurements provide a useful tool for exploring the effect of modifiable factors on articular cartilage prior to clinical disease and identifying the potential preventive strategies. MRI represents a useful approach to monitoring the natural history of OA and evaluating the effect of therapeutic agents. MRI assessment of articular cartilage has tremendous potential for large-scale epidemiological studies of OA progression, and for clinical trials of treatment response to disease-modifying OA drugs. PMID:22870497

  15. Remobilization does not fully restore immobilization induced articular cartilage atrophy.

    PubMed

    Haapala, J; Arokoski, J P; Hyttinen, M M; Lammi, M; Tammi, M; Kovanen, V; Helminen, H J; Kiviranta, I

    1999-05-01

    The recovery of articular cartilage from immobilization induced atrophy was studied. The right hind limbs of 29-week-old beagle dogs were immobilized for 11 weeks and then remobilized for 50 weeks. Cartilage from the immobilized knee was compared with tissue from age matched control animals. After the immobilization period, uncalcified articular cartilage glycosaminoglycan concentration was reduced by 20% to 23%, the reduction being largest (44%) in the superficial zone. The collagen fibril network showed no significant changes, but the amount of collagen crosslinks was reduced (13.5%) during immobilization. After remobilization, glycosaminoglycan concentration was restored at most sites, except for in the upper parts of uncalcified cartilage in the medial femoral and tibial condyles (9% to 17% less glycosaminoglycans than in controls). The incorporation of 35SO4 was not changed, and remobilization also did not alter the birefringence of collagen fibrils. Remobilization restored the proportion of collagen crosslinks to the control level. The changes induced by joint unloading were reversible at most sites investigated, but full restoration of articular cartilage glycosaminoglycan concentration was not obtained in all sites, even after remobilization for 50 weeks. This suggests that lengthy immobilization of a joint can cause long lasting articular cartilage proteoglycan alterations at the same time as collagen organization remains largely unchanged. Because proteoglycans exert strong influence on the biomechanical properties of cartilage, lengthy immobilization may jeopardize the well being of articular cartilage. PMID:10335301

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

    PubMed Central

    Jungmann, Pia M.; Baum, Thomas; Bauer, Jan S.; Karampinos, Dimitrios C.; Link, Thomas M.; Li, Xiaojuan; Trattnig, Siegfried; Rummeny, Ernst J.; Woertler, Klaus; Welsch, Goetz H.

    2014-01-01

    Background. New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair. PMID:24877139

  17. Imaging of cartilage repair procedures

    PubMed Central

    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. PMID:25114387

  18. Cartilage repair in transplanted scaffold-free chondrocyte sheets using a minipig model.

    PubMed

    Ebihara, Goro; Sato, Masato; Yamato, Masayuki; Mitani, Genya; Kutsuna, Toshiharu; Nagai, Toshihiro; Ito, Satoshi; Ukai, Taku; Kobayashi, Miyuki; Kokubo, Mami; Okano, Teruo; Mochida, Joji

    2012-05-01

    Lacking a blood supply and having a low cellular density, articular cartilage has a minimal ability for self-repair. Therefore, wide-ranging cartilage damage rarely resolves spontaneously. Cartilage damage is typically treated by chondrocyte transplantation, mosaicplasty or microfracture. Recent advances in tissue engineering have prompted research on techniques to repair articular cartilage damage using a variety of transplanted cells. We studied the repair and regeneration of cartilage damage using layered chondrocyte sheets prepared on a temperature-responsive culture dish. We previously reported achieving robust tissue repair when covering only the surface layer with layered chondrocyte sheets when researching partial-thickness defects in the articular cartilage of domestic rabbits. The present study was an experiment on the repair and regeneration of articular cartilage in a minipig model of full-thickness defects. Good safranin-O staining and integration with surrounding tissues was achieved in animals transplanted with layered chondrocyte sheets. However, tissue having poor safranin-O staining-not noted in the domestic rabbit experiments-was identified in some of the animals, and the subchondral bone was poorly repaired in these. Thus, although layered chondrocyte sheets facilitate articular cartilage repair, further investigations into appropriate animal models and culture and transplant conditions are required. PMID:22369960

  19. A literature review of lasers and articular cartilage.

    PubMed

    Vangsness, C T; Ghaderi, B

    1993-05-01

    Articles from the English literature concerning lasers and articular cartilage were reviewed. Different experimental methods and laser systems were analyzed. Many studies lacked scientific validity. Future investigations with sound biologic foundations are recommended. PMID:8327386

  20. The effects of exercise on human articular cartilage

    PubMed Central

    Eckstein, F; Hudelmaier, M; Putz, R

    2006-01-01

    The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass. PMID:16637874

  1. Leptin plays a catabolic role on articular cartilage.

    PubMed

    Bao, Jia-peng; Chen, Wei-ping; Feng, Jie; Hu, Peng-fei; Shi, Zhong-li; Wu, Li-dong

    2010-10-01

    Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA. PMID:19876764

  2. Stem Cells and Gene Therapy for Cartilage Repair

    PubMed Central

    Longo, Umile Giuseppe; Petrillo, Stefano; Franceschetti, Edoardo; Berton, Alessandra; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    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. PMID:22481959

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

    PubMed

    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. PMID:27324118

  4. Multiscale Biofabrication of Articular Cartilage: Bioinspired and Biomimetic Approaches.

    PubMed

    Tatman, Philip David; Gerull, William; Sweeney-Easter, Sean; Davis, Jeffrey Isaac; Gee, Albert O; Kim, Deok-Ho

    2015-12-01

    Articular cartilage is the load-bearing tissue found inside all articulating joints of the body. It vastly reduces friction and allows for smooth gliding between contacting surfaces. The structure of articular cartilage matrix and cellular composition is zonal and is important for its mechanical properties. When cartilage becomes injured through trauma or disease, it has poor intrinsic healing capabilities. The spectrum of cartilage injury ranges from isolated areas of the joint to diffuse breakdown and the clinical appearance of osteoarthritis. Current clinical treatment options remain limited in their ability to restore cartilage to its normal functional state. This review focuses on the evolution of biomaterial scaffolds that have been used for functional cartilage tissue engineering. In particular, we highlight recent developments in multiscale biofabrication approaches attempting to recapitulate the complex 3D matrix of native articular cartilage tissue. Additionally, we focus on the application of these methods to engineering each zone of cartilage and engineering full-thickness osteochondral tissues for improved clinical implantation. These methods have shown the potential to control individual cell-to-scaffold interactions and drive progenitor cell differentiation into a chondrocyte lineage. The use of these bioinspired nanoengineered scaffolds hold promise for recreation of structure and function on the whole tissue level and may represent exciting new developments for future clinical applications for cartilage injury and restoration. PMID:26200439

  5. Anti-Inflammatory Strategies in Cartilage Repair

    PubMed Central

    Zhang, Ying; Pizzute, Tyler

    2014-01-01

    Cartilage defects are normally concomitant with posttraumatic inflammation and pose a major challenge in cartilage repair. Due to the avascular nature of cartilage and its inability to surmount an inflammatory response, the cartilage is easily attacked by proinflammatory factors and oxidative stress; if left untreated, osteoarthritis may develop. Suppression of inflammation has always been a crux for cartilage repair. Pharmacological drugs have been successfully applied in cartilage repair; however, they cannot optimally work alone. This review article will summarize current pharmacological drugs and their application in cartilage repair. The development of extracellular matrix-based scaffolds and preconditioned tissue-specific stem cells will be emphasized because both of these tissue engineering components could contribute to an enhanced ability not only for cartilage regeneration but also for anti-inflammation. These strategies could be combined to boost cartilage repair under inflammatory conditions. PMID:24846478

  6. Cryoprotectant kinetic analysis of a human articular cartilage vitrification protocol.

    PubMed

    Shardt, Nadia; Al-Abbasi, Khaled K; Yu, Hana; Jomha, Nadr M; McGann, Locksley E; Elliott, Janet A W

    2016-08-01

    We recently published a protocol to vitrify human articular cartilage and a method of cryoprotectant removal in preparation for transplantation. The current study's goal was to perform a cryoprotectant kinetic analysis and theoretically shorten the procedure used to vitrify human articular cartilage. First, the loading of the cryoprotectants was modeled using Fick's law of diffusion, and this information was used to predict the kinetics of cryoprotectant efflux after the cartilage sample had been warmed. We hypothesized that diffusion coefficients obtained from the permeation of individual cryoprotectants into porcine articular cartilage could be used to provide a reasonable prediction of the cryoprotectant loading and of the combined cryoprotectant efflux from vitrified human articular cartilage. We tested this hypothesis with experimental efflux measurements. Osteochondral dowels from three patients were vitrified, and after warming, the articular cartilage was immersed in 3 mL X-VIVO at 4 °C in two consecutive solutions, each for 24 h, with the solution osmolality recorded at various times. Measured equilibrium values agreed with theoretical values within a maximum of 15% for all three samples. The results showed that diffusion coefficients for individual cryoprotectants determined from experiments with 2-mm thick porcine cartilage can be used to approximate the rate of efflux of the combined cryoprotectants from vitrified human articular cartilage of similar thickness. Finally, Fick's law of diffusion was used in a computational optimization to shorten the protocol with the constraint of maintaining the theoretical minimum cryoprotectant concentration needed to achieve vitrification. The learning provided by this study will enable future improvements in tissue vitrification. PMID:27221520

  7. Single cell sorting identifies progenitor cell population from full thickness bovine articular cartilage

    PubMed Central

    Yu, Yin; Zheng, Hongjun; Buckwalter, Joseph A.; Martin, James A.

    2014-01-01

    Objective To date, no approved clinical intervention successfully prevents the progressive degradation of injured articular cartilage that leads to osteoarthritis (OA). Stem/progenitor cell populations within tissues of diarthrodial joint have shown their therapeutic potential in treating OA. However, this potential has not been fully realized due in part to the heterogeneity of these subpopulations. Characterization of clonal populations derived from a single cell may help identify more homogenous stem/progenitor populations within articular cartilage. Moreover, chondrogenic potential of clonal populations from different zones could be further examined to elucidate their differential roles in maintaining articular cartilage homeostasis. Method We combined FACS (Fluorescence-activated cell sorting) and clonogenicity screening to identify stem/progenitor cells cloned from single cells. High-efficiency colony-forming cells (HCCs) were isolated, and evaluated for stem/progenitor cell characteristics. HCCs were also isolated from different zones of articular cartilage. Their function was compared by lineage-specific gene expression, and differentiation potential. Results A difference in colony-forming efficiency was observed in terms of colony sizes. HCCs were highly clonogenic and multipotent, and overexpressed stem/progenitor cell markers. Also, proliferation and migration associated genes were over-expressed in HCCs. HCCs showed zonal differences with deep HCCs more chondrogenic and osteogenic than superficial HCCs. Conclusion Our approach is a simple yet practical way to identify homogeneous stem/progenitor cell populations with clonal origin. The discovery of progenitor cells demonstrates the intrinsic self-repairing potential of articular cartilage. Differences in differentiation potential may represent the distinct roles of superficial and deep zone stem/progenitor cells in the maintenance of articular cartilage homeostasis. PMID:25038490

  8. Targeting TGFβ Signaling in Subchondral Bone and Articular Cartilage Homeostasis

    PubMed Central

    Zhen, Gehau; Cao, Xu

    2014-01-01

    Osteoarthritis (OA) is the most common degenerative joint disease, and there is no disease-modifying therapy for OA currently available. Targeting of articular cartilage alone may not be sufficient to halt this disease progression. Articular cartilage and subchondral bone act as a functional unit. Increasing evidence indicates that transforming growth factor β (TGFβ) plays a crucial role in maintaining homeostasis of both articular cartilage and subchondral bone. Activation of extracellular matrix latent TGFβ at the appropriate time and location is the prerequisite for its function. Aberrant activation of TGFβ in the subchondral bone in response to abnormal mechanical loading environment induces formation of osteroid islets at onset of osteoarthritis. As a result, alteration of subchondral bone structure changes the stress distribution on the articular cartilage and leads to its degeneration. Thus, inhibition of TGFβ activity in the subchondral bone may provide a new avenue of treatment for OA. In this review, we will respectively discuss the role of TGFβ in homeostasis of articular cartilage and subchondral bone as a novel target for OA therapy. PMID:24745631

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

    PubMed Central

    Stromps, Jan-Philipp; Paul, Nora Emilie; Rath, Björn; Nourbakhsh, Mahtab; Bernhagen, Jürgen; Pallua, Norbert

    2014-01-01

    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. PMID:25019085

  10. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    PubMed

    Im, Gun-Il

    2016-04-01

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

  11. Cartilage repair: 2013 Asian update.

    PubMed

    Hui, James H P; Goyal, Deepak; Nakamura, Norimasa; Ochi, Mitsuo

    2013-12-01

    Despite financial and regulatory hurdles, Asian scientists and clinicians have made important contributions in the area of cartilage repair. Because it is impossible to include observations on all the published articles in one review, our attempt is to highlight Asian progress in this area during recent years (2005 to the present), reviewing research development and clinical studies. In the former, our discussion of in vitro studies focuses on (1) potential sources of stem cells--such as mesenchymal stem cells (MSCs) from marrow, cord blood, synovium, and mobilized peripheral blood--which are capable of enhancing cartilage repair and (2) the use of growth factors and scaffolds with and without cells. Our discussion of animal studies attempts to summarize activities in evaluating surgical procedures and determining the route of cell administration, as well as studies on matrices and scaffolds. It ranges from the use of small animals such as rats and rabbits to larger animals like pigs and dogs. The local adherent technique, enhancement of microfracture with poly(l-lactic-co-glycolic acid) scaffold, adenovirus-mediated bone morphogenic protein (BMP) genes, and MSCs--whether they are magnetically labeled, suspended in hyaluronic acid, or immobilized with transforming growth factor-β (TGF-β)--have all been able to engineer a repair of the osteochondral defect. Although published Asian reports of clinical studies on cartilage repair are few, the findings of relevant trials are summarized in our discussion of these investigations. There has been a long history of use of laboratory-derived MSCs for cartilage repair. Recent progress has suggested the potential utility of cord blood and mobilized peripheral blood in this area, as well as more injectable bone marrow (BM)-derived stem cells. Finally, we make a few suggestions on the direction of research and development activities and the need for collaborative approaches by regulatory agencies. PMID:24286798

  12. Optical clearing of articular cartilage: a comparison of clearing agents

    NASA Astrophysics Data System (ADS)

    Bykov, Alexander; Hautala, Tapio; Kinnunen, Matti; Popov, Alexey; Karhula, Sakari; Saarakkala, Simo; Nieminen, Miika T.; Tuchin, Valery

    2015-07-01

    Optical clearing technique was applied to the problem of OCT imaging of articular cartilage and subchondral bone. We show that optical clearing significantly enhances visualization of articular cartilage and cartilage-bone interface. The effect of different clearing agents was analyzed. For the clearing, iohexol solution and propylene glycol (PG) were used. Clearing was performed in vitro at room temperature by immersion method. Cylindrical osteochondral samples (d=4.8mm) were drilled from bovine lateral femur and stored in phosphate-buffered saline at -20°C until clearing. Monitoring of clearing process was performed using high-speed spectral-domain OCT system providing axial resolution of 5.8μm at 930nm. Total duration of experiment was 90-100min to ensure saturation of clearing. We have shown that iohexol solution and PG are capable to optically clear articular cartilage enabling reliable characterization of cartilagebone interface with OCT. Being a low osmolarity agent, iohexol provides minimal changes to the thickness of cartilage sample. Clearing saturation time for the cartilage sample with the thickness of 0.9 mm measured with OCT is of 50 min. However, less than 15 min is enough to reliably detect the rear cartilage boundary. Alternatively, PG significantly (60%) reduces the cartilage thickness enabling better visualization of subchondral bone. It was observed that PG has higher clearing rate. The clearing saturation time is of 30 min, however less than 5 min is enough to detect cartilage-bone interface. We conclude that iohexol solution is superior for OCT imaging of cartilage and cartilage-bone interface, while PG suits better for subhondral bone visualization.

  13. Microscale surface friction of articular cartilage in early osteoarthritis.

    PubMed

    Desrochers, Jane; Amrein, Matthias W; Matyas, John R

    2013-09-01

    Articular cartilage forms the articulating surface of long bones and facilitates energy dissipation upon loading as well as joint lubrication and wear resistance. In normal cartilage, boundary lubrication between thin films at the cartilage surface reduces friction in the absence of interstitial fluid pressurization and fluid film lubrication by synovial fluid. Inadequate boundary lubrication is associated with degenerative joint conditions such as osteoarthritis (OA), but relations between OA and surface friction, lubrication and wear in boundary lubrication are not well defined. The purpose of the present study was to measure microscale boundary mode friction of the articular cartilage surface in an in vivo experimental model to better understand changes in cartilage surface friction in early OA. Cartilage friction was measured on the articular surface by atomic force microscopy (AFM) under applied loads ranging from 0.5 to 5 μN. Microscale AFM friction analyses revealed depth dependent changes within the top-most few microns of the cartilage surface in this model of early OA. A significant increase of nearly 50% was observed in the mean engineering friction coefficient for OA cartilage at the 0.5 μN load level; no significant differences in friction coefficients were found under higher applied loads. Changes in cartilage surface morphology observed by scanning electron microscopy included cracking and roughening of the surface indicative of disruption and wear accompanied by an apparent disintegration of the thin surface lamina from the underlying matrix. Immunohistochemical staining of lubricin - an important cartilage surface boundary lubricant - did not reveal differences in spatial distribution near the cartilage surface in OA compared to controls. The increase in friction at the 0.5 μN force level is interpreted to reflect changes in the interfacial mechanics of the thin surface lamina of articular cartilage: increased friction implies reduced

  14. Inhibition of β-Catenin Signaling in Articular Chondrocytes Results in Articular Cartilage Destruction

    PubMed Central

    Zhu, Mei; Chen, Mo; Zuscik, Michael; Wu, Qiuqian; Wang, Yong-Jun; Rosier, Randy N.; O’Keefe, Regis J.; Chen, Di

    2009-01-01

    Objective Osteoarthritis is a degenerative joint disease whose molecular mechanism is currently unknown. Wnt/β-catenin signaling has been demonstrated to play a critical role in the development and function of articular chondrocytes. To determine the role of β-catenin signaling in articular chondrocyte function, we generated Col2a1-ICAT–transgenic mice to inhibit β-catenin signaling in chondrocytes. Methods The expression of the ICAT transgene was determined by immunostaining and Western blot analysis. Histologic analyses were performed to determine changes in articular cartilage structure and morphology. Cell apoptosis was determined by TUNEL staining and the immunostaining of cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) proteins. Expression of Bcl-2, Bcl-xL, and Bax proteins and caspase 9 and caspase 3/7 activities were examined in primary sternal chondrocytes isolated from 3-day-old neonatal Col2a1-ICAT–transgenic mice and their wild-type littermates and in primary chicken and porcine articular chondrocytes. Results Expression of the ICAT transgene was detected in articular chondrocytes of the transgenic mice. Associated with this, age-dependent articular cartilage destruction was observed in Col2a1-ICAT– transgenic mice. A significant increase in cell apoptosis in articular chondrocytes was identified by TUNEL staining and the immunostaining of cleaved caspase 3 and PARP proteins in these transgenic mice. Consistent with this, Bcl-2 and Bcl-xL expression were decreased and caspase 9 and caspase 3/7 activity were increased, suggesting that increased cell apoptosis may contribute significantly to the articular cartilage destruction observed in Col2a1-ICAT–transgenic mice. Conclusion Inhibition of β-catenin signaling in articular chondrocytes causes increased cell apoptosis and articular cartilage destruction in Col2a1-ICAT–transgenic mice. PMID:18576323

  15. Human cartilage repair with a photoreactive adhesive-hydrogel composite.

    PubMed

    Sharma, Blanka; Fermanian, Sara; Gibson, Matthew; Unterman, Shimon; Herzka, Daniel A; Cascio, Brett; Coburn, Jeannine; Hui, Alexander Y; Marcus, Norman; Gold, Garry E; Elisseeff, Jennifer H

    2013-01-01

    Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel biomaterial and stimulation of adjacent cartilage tissue development by mesenchymal stem cells. For translation to the joint environment, a chondroitin sulfate adhesive was applied to covalently bond and adhere the hydrogel to cartilage and bone tissue in articular defects. After preclinical testing in a caprine model, a pilot clinical study was initiated where the biomaterials system was combined with standard microfracture surgery in 15 patients with focal cartilage defects on the medial femoral condyle. Control patients were treated with microfracture alone. Magnetic resonance imaging showed that treated patients achieved significantly higher levels of tissue fill compared to controls. Magnetic resonance spin-spin relaxation times (T(2)) showed decreasing water content and increased tissue organization over time. Treated patients had less pain compared with controls, whereas knee function [International Knee Documentation Committee (IKDC)] scores increased to similar levels between the groups over the 6 months evaluated. No major adverse events were observed over the study period. With further clinical testing, this practical biomaterials strategy has the potential to improve the treatment of articular cartilage defects. PMID:23303605

  16. Colonies in engineered articular cartilage express superior differentiation.

    PubMed

    Selvaratnam, L; Abd Rahim, S; Kamarul, T; Chan, K Y; Sureshan, S; Penafort, R; Ng, C L L

    2005-07-01

    In view of poor regeneration potential of the articular cartilage, in-vitro engineering of cartilage tissue offers a promising option for progressive joint disease. This study aims to develop a biologically engineered articular cartilage for autologous transplantation. The initial work involved determination of chondrocyte yield and viability, and morphological analysis. Cartilage was harvested from the knee, hip and shoulder joints of adult New Zealand white rabbits and chondrocytes were isolated by enzymatic digestion of the extra-cellular matrix before serial cultivation in DMEM/Ham's F12 media as monolayer cultures. No differences were noted in cell yield. Although chondrocytes viability was optimal (>93%) following harvest from native cartilage, their viability tended to be lowered on passaging. Chondrocytes aggregated in isogenous colonies comprising ovoid cells with intimate intracellular contacts and readily exhibited Safranin-O positive matrix; features typically associated with articular cartilage in-vivo. However, chondrocytes also existed concurrently in scattered bipolar/multipolar forms lacking Safranin-O expression. Therefore, early data demonstrated successful serial culture of adult chondrocytes with differentiated morphology seen in established chondrocyte colonies synthesizing matrix proteoglycans. PMID:16381284

  17. The Challenge and the Promise of Bone Marrow Cells for Human Cartilage Repair

    PubMed Central

    2015-01-01

    The cartilage repair potential of bone marrow–derived stem cells has been well described. Harnessing this potential for human articular cartilage repair remains challenging. Accessing bone marrow repair cells through marrow stimulation techniques such as microfracture is readily achieved with generally good but inconsistent results. Animal and human studies show feasibility for ex vivo processing of bone marrow to isolate, concentrate, and culture mesenchymal stem cells. Nevertheless, it has been difficult to show consistent and clinically meaningful improvement using bone marrow cell preparations above what has been achieved with microfracture. Consequently, microfracture continues to be the simplest and most commonly used method to enhance repair of focal articular cartilage defects. Emerging preclinical work in the equine model suggests a role for enhancing marrow-stimulation techniques through the use of natural scaffolds such as autologous platelet enriched fibrin as well as optimization of joint biology through localized gene therapy to support cartilage repair. In contrast to joint replacement where inert materials of known mechanical properties are used, host biology determines the relative success, failure, and durability of cartilage repair. As such, development of personalized strategies to improve the quality and durability of bone marrow cell–based articular cartilage repair represent exciting new areas of inquiry. Continued advances in stem cell biology, scaffold technologies, and methods to delineate and enhance host biology, both systemically and within the joint, hold promise for harnessing the full power of bone marrow cells to facilitate cartilage repair and regeneration.

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

    PubMed Central

    Wu, Jian P; Kirk, Thomas B; Zheng, Ming H

    2008-01-01

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

  19. Mechanical properties of normal and osteoarthritic human articular cartilage.

    PubMed

    Robinson, Dale L; Kersh, Mariana E; Walsh, Nicole C; Ackland, David C; de Steiger, Richard N; Pandy, Marcus G

    2016-08-01

    Isotropic hyperelastic models have been used to determine the material properties of normal human cartilage, but there remains an incomplete understanding of how these properties may be altered by osteoarthritis. The aims of this study were to (1) measure the material constants of normal and osteoarthritic human knee cartilage using isotropic hyperelastic models; (2) determine whether the material constants correlate with histological measures of structure and/or cartilage tissue damage; and (3) quantify the abilities of two common isotropic hyperelastic material models, the neo-Hookean and Yeoh models, to describe articular cartilage contact force, area, and pressure. Small osteochondral specimens of normal and osteoarthritic condition were retrieved from human cadaveric knees and from the knees of patients undergoing total knee arthroplasty and tested in unconfined compression at loading rates and large strains representative of weight-bearing activity. Articular surface contact area and lateral deformation were measured concurrently and specimen-specific finite element models then were used to determine the hyperelastic material constants. Structural parameters were measured using histological techniques while the severity of cartilage damage was quantified using the OARSI grading scale. The hyperelastic material constants correlated significantly with OARSI grade, indicating that the mechanical properties of cartilage for large strains change with tissue damage. The measurements of contact area described anisotropy of the tissue constituting the superficial zone. The Yeoh model described contact force and pressure more accurately than the neo-Hookean model, whereas both models under-predicted contact area and poorly described the anisotropy of cartilage within the superficial zone. These results identify the limits by which isotropic hyperelastic material models may be used to describe cartilage contact variables. This study provides novel data for the

  20. Studies on cathepsin B in human articular cartilage.

    PubMed Central

    Bayliss, M T; Ali, S Y

    1978-01-01

    The thiol proteinase cathepsin B (EC 3.4.22.1), previously called cathepsin B1, was assayed in human articular cartilage by its hydrolysis of the synthetic substrate alpha-N-benzoyl-DL-arginine 2-naphthylamide. The enzyme was activated by cysteine and EDTA and completely inhibited by iodoacetamide and HgCl2. It was also partially inhibited by whole human serum. Human osteoarthrotic cartilage had increased activity when compared with normal cartilage. Cathepsin B activity of normal cartilage was age-related, being high in juveniles and declining to low values in adult and elderly individuals. Cathepsin D and cathepsin B both exhibited a zonal variation through the cartilage depth; the surface cells appeared to contain more activity than those close to the subchondral bone. PMID:417724

  1. Major biological obstacles for persistent cell-based regeneration of articular cartilage

    PubMed Central

    Steinert, Andre F; Ghivizzani, Steven C; Rethwilm, Axel; Tuan, Rocky S; Evans, Christopher H; Nöth, Ulrich

    2007-01-01

    Hyaline articular cartilage, the load-bearing tissue of the joint, has very limited repair and regeneration capacities. The lack of efficient treatment modalities for large chondral defects has motivated attempts to engineer cartilage constructs in vitro by combining cells, scaffold materials and environmental factors, including growth factors, signaling molecules, and physical influences. Despite promising experimental approaches, however, none of the current cartilage repair strategies has generated long lasting hyaline cartilage replacement tissue that meets the functional demands placed upon this tissue in vivo. The reasons for this are diverse and can ultimately result in matrix degradation, differentiation or integration insufficiencies, or loss of the transplanted cells and tissues. This article aims to systematically review the different causes that lead to these impairments, including the lack of appropriate differentiation factors, hypertrophy, senescence, apoptosis, necrosis, inflammation, and mechanical stress. The current conceptual basis of the major biological obstacles for persistent cell-based regeneration of articular cartilage is discussed, as well as future trends to overcome these limitations. PMID:17561986

  2. A linearized formulation of triphasic mixture theory for articular cartilage, and its application to indentation analysis.

    PubMed

    Lu, Xin L; Wan, Leo Q; Guo, X Edward; Mow, Van C

    2010-03-01

    The negative charges on proteoglycans significantly affect the mechanical behaviors of articular cartilage. Mixture theories, such as the triphasic theory, can describe quantitatively how this charged nature contributes to the mechano-electrochemical behaviors of such tissue. However, the mathematical complexity of the theory has hindered its application to complicated loading profiles, e.g., indentation or other multi-dimensional configurations. In this study, the governing equations of triphasic mixture theory for soft tissue were linearized and dramatically simplified by using a regular perturbation method and the use of two potential functions. We showed that this new formulation can be used for any axisymmetric problem, such as confined or unconfined compressions, hydraulic perfusion, and indentation. A finite difference numerical program was further developed to calculate the deformational, electrical, and flow behaviors inside the articular cartilage under indentation. The calculated tissue response was highly consistent with the data from indentation experiments (our own and those reported in the literature). It was found that the charged nature of proteoglycans can increase the apparent stiffness of the solid matrix and lessen the viscous effect introduced by fluid flow. The effects of geometric and physical properties of indenter tip, cartilage thickness, and that of the electro-chemical properties of cartilage on the resulting deformation and fluid pressure fields across the tissue were also investigated and presented. These results have implications for studying chondrocyte mechanotransduction in different cartilage zones and for tissue engineering designs or in vivo cartilage repair. PMID:19896670

  3. An in vitro model for the pathological degradation of articular cartilage in osteoarthritis.

    PubMed

    Grenier, Stephanie; Bhargava, Madhu M; Torzilli, Peter A

    2014-02-01

    The objective of this study was to develop an in vitro cartilage degradation model that emulates the damage seen in early-stage osteoarthritis. To this end, cartilage explants were collagenase-treated to induce enzymatic degradation of collagen fibers and proteoglycans at the articular surface. To assess changes in mechanical properties, intact and degraded cartilage explants were subjected to a series of confined compression creep tests. Changes in extracellular matrix structure and composition were determined using biochemical and histological approaches. Our results show that collagenase-induced degradation increased the amount of deformation experienced by the cartilage explants under compression. An increase in apparent permeability as well as a decrease in instantaneous and aggregate moduli was measured following collagenase treatment. Histological analysis of degraded explants revealed the presence of surface fibrillation, proteoglycan depletion in the superficial and intermediate zones and loss of the lamina splendens. Collagen cleavage was confirmed by the Col II-3/4Cshort antibody. Degraded specimens experienced a significant decrease in proteoglycan content but maintained total collagen content. Repetitive testing of degraded samples resulted in the gradual collapse of the articular surface and the compaction of the superficial zone. Taken together, our data demonstrates that enzymatic degradation with collagenase can be used to emulate changes seen in early-stage osteoarthritis. Further, our in vitro model provides information on cartilage mechanics and insights on how matrix changes can affect cartilage's functional properties. More importantly, our model can be applied to develop and test treatment options for tissue repair. PMID:24360770

  4. An arthroscopic device to assess articular cartilage defects and treatment with a hydrogel.

    PubMed

    McCarty, William J; Luan, Anna; Sundaramurthy, Priya; Urbanczyk, Caryn; Patel, Atal; Hahr, Jacob; Sotoudeh, Mohammad; Ratcliffe, Anthony; Sah, Robert L

    2011-04-01

    The hydraulic resistance R across osteochondral tissue, especially articular cartilage, decreases with degeneration and erosion. Clinically useful measures to quantify and diagnose the extent of cartilage degeneration and efficacy of repair strategies, especially with regard to pressure maintenance, are still developing. The hypothesis of this study was that hydraulic resistance provides a quantitative measure of osteochondral tissue that could be used to evaluate the state of cartilage damage and repair. The aims were to (1) develop a device to measure R in an arthroscopic setting, (2) determine whether the device could detect differences in R for cartilage, an osteochondral defect, and cartilage treated using a hydrogel ex vivo, and (3) determine how quickly such differences could be discerned. The apparent hydraulic resistance of defect samples was ~35% less than intact cartilage controls, while the resistance of hydrogel-filled groups was not statistically different than controls, suggesting some restoration of fluid pressurization in the defect region by the hydrogel. Differences in hydraulic resistance between control and defect groups were apparent after 4 s. The results indicate that the measurement of R is feasible for rapid and quantitative functional assessment of the extent of osteochondral defects and repair. The arthroscopic compatibility of the device demonstrates the potential for this measurement to be made in a clinical setting. PMID:21107696

  5. Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics.

    PubMed

    Natarajan, Venkatachalam; Madhan, Balaraman; Tiku, Moti L

    2015-01-01

    Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crosslinking type II collagen and the roles of these agents in managing in vivo articular cartilage degradation. The thermal, enzymatic, and physical stability of bovine articular cartilage explants following polyphenolic treatment were assessed for efficiency. Epigallocatechin gallate and tannic acid-treated explants showed >12 °C increase over native cartilage in thermal stability, thereby confirming cartilage crosslinking. Polyphenol-treated cartilage also showed a significant reduction in the percentage of collagen degradation and the release of glycosaminoglycans against collagenase digestion, indicating the increase physical integrity and resistance of polyphenol crosslinked cartilage to enzymatic digestion. To examine the in vivo cartilage protective effects, polyphenols were injected intra-articularly before (prophylactic) and after (therapeutic) the induction of collagen-induced arthritis in rats. The hind paw volume and histomorphological scoring was done for cartilage damage. The intra-articular injection of epigallocatechin gallate and tannic acid did not significantly influence the time of onset or the intensity of joint inflammation. However, histomorphological scoring of the articular cartilage showed a significant reduction in cartilage degradation in prophylactic- and therapeutic-groups, indicating that intra-articular injections of polyphenols bind to articular cartilage and making it resistant to degradation despite ongoing inflammation. These studies establish

  6. Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics

    PubMed Central

    Natarajan, Venkatachalam; Madhan, Balaraman; Tiku, Moti L.

    2015-01-01

    Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crosslinking type II collagen and the roles of these agents in managing in vivo articular cartilage degradation. The thermal, enzymatic, and physical stability of bovine articular cartilage explants following polyphenolic treatment were assessed for efficiency. Epigallocatechin gallate and tannic acid-treated explants showed >12 °C increase over native cartilage in thermal stability, thereby confirming cartilage crosslinking. Polyphenol-treated cartilage also showed a significant reduction in the percentage of collagen degradation and the release of glycosaminoglycans against collagenase digestion, indicating the increase physical integrity and resistance of polyphenol crosslinked cartilage to enzymatic digestion. To examine the in vivo cartilage protective effects, polyphenols were injected intra-articularly before (prophylactic) and after (therapeutic) the induction of collagen-induced arthritis in rats. The hind paw volume and histomorphological scoring was done for cartilage damage. The intra-articular injection of epigallocatechin gallate and tannic acid did not significantly influence the time of onset or the intensity of joint inflammation. However, histomorphological scoring of the articular cartilage showed a significant reduction in cartilage degradation in prophylactic- and therapeutic-groups, indicating that intra-articular injections of polyphenols bind to articular cartilage and making it resistant to degradation despite ongoing inflammation. These studies establish

  7. Radiation synovectomy stimulates glycosaminoglycan synthesis by normal articular cartilage

    SciTech Connect

    Myers, S.L.; Slowman, S.D.; Brandt, K.D.

    1989-07-01

    Radiation synovectomy has been considered a therapeutic alternative to surgical synovectomy. Whether intraarticular irradiation affects the composition or biochemistry, and therefore the biomechanical properties, of normal articular cartilage has not been established. In the present study, yttrium 90 silicate was injected into one knee of nine normal adult dogs, and three other dogs received nonradioactive yttrium silicate. When the animals were killed 4 to 13 weeks after the injection, synovium from the irradiated knees showed areas of necrosis and fibrosis. Up to 29% less hyaluronate was synthesized in vitro by the synovial intima from irradiated knees than by the intima from the contralateral knees (mean difference 18%). Morphologic abnormalities were not observed in articular cartilage from either the irradiated or control knees, nor did the water content or concentrations of uronic acid or DNA in cartilage from the irradiated knees differ from that in cartilage from the contralateral knees. However, net /sup 35/SO/sub 4/-labeled glycosaminoglycan synthesis in organ cultures of cartilage from irradiated knees was increased (mean difference 21%, p = 0.03) in comparison with that in cultures of contralateral knee cartilage.

  8. Acute and chronic response of articular cartilage to Ho:YAG laser irradiation

    NASA Astrophysics Data System (ADS)

    Trauner, Kenneth B.; Nishioka, Norman S.; Flotte, Thomas J.; Patel, Dinesh K.

    1992-06-01

    A Ho:YAG laser system operating at a wavelength of 2.1 microns has recently been introduced for use in arthroscopic surgery. The acceptability of this new tool will be determined not only by its ability to resect tissue, but also by its long term effects on articular surfaces. In order to investigate these issues further, we performed two studies to evaluate the acute and chronic effects of the laser on cartilaginous tissue. We evaluated the acute, in vitro effects of 2.1 micron laser irradiation on articular and fibrocartilage. This included the measurement of ablation efficiency, ablation threshold and thermal damage in both meniscus and articular cartilage. To document the chronic effects on articular cartilage in vivo, we next performed a ten week healing study. Eight sheep weighing 30 - 40 kg underwent bilateral arthrotomy procedures. Multiple full thickness and partial thickness defects were created. Animals were sacrificed at 0, 2, 4, and 10 weeks. The healing study demonstrated: (1) no healing of full or partial thickness defects at 10 weeks with hyaline cartilage; (2) fibrocartilaginous granulation tissue filling full thickness defects at two and four weeks, but no longer evident at ten weeks; (3) chondrocyte necrosis extending to greater than 900 microns distal to ablation craters at four weeks with no evidence of repair at later dates; and (4) chondrocyte hyperplasia at the borders of the damage zone at two weeks but no longer evident at later sacrifice dates.

  9. Current Concepts of Articular Cartilage Restoration Techniques in the Knee

    PubMed Central

    Camp, Christopher L.; Stuart, Michael J.; Krych, Aaron J.

    2014-01-01

    Context: Articular cartilage injuries are common in patients presenting to surgeons with primary complaints of knee pain or mechanical symptoms. Treatment options include comprehensive nonoperative management, palliative surgery, joint preservation operations, and arthroplasty. Evidence Acquisition: A MEDLINE search on articular cartilage restoration techniques of the knee was conducted to identify outcome studies published from 1993 to 2013. Special emphasis was given to Level 1 and 2 published studies. Study Design: Clinical review. Level of Evidence: Level 3. Results: Current surgical options with documented outcomes in treating chondral injuries in the knee include the following: microfracture, osteochondral autograft transfer, osteochondral allograft transplant, and autologous chondrocyte transplantation. Generally, results are favorable regarding patient satisfaction and return to sport when proper treatment algorithms and surgical techniques are followed, with 52% to 96% of patients demonstrating good to excellent clinical outcomes and 66% to 91% returning to sport at preinjury levels. Conclusion: Clinical, functional, and radiographic outcomes may be improved in the majority of patients with articular cartilage restoration surgery; however, some patients may not fully return to their preinjury activity levels postoperatively. In active and athletic patient populations, biological techniques that restore the articular surface may be options that provide symptom relief and return patients to their prior levels of function. PMID:24790697

  10. Telomere erosion and senescence in human articular cartilage chondrocytes.

    PubMed

    Martin, J A; Buckwalter, J A

    2001-04-01

    Aging and the degeneration of articular cartilage in osteoarthritis are distinct processes, but a strong association exists between age and the incidence and prevalence of osteoarthritis. We hypothesized that this association is due to in vivo replicative senescence, which causes age-related declines in the ability of chondrocytes to maintain articular cartilage. For this hypothesis to be tested, senescence-associated markers were measured in human articular chondrocytes from donors ranging in age from 1 to 87 years. These measures included in situ staining for senescence-associated beta-galactosidase activity, (3)H-thymidine incorporation assays for mitotic activity, and Southern blots for telomere length determinations. We found that senescence-associated beta-galactosidase activity increased with age, whereas both mitotic activity and mean telomere length declined. These findings indicate that chondrocyte replicative senescence occurs in vivo and support the hypothesis that the association between osteoarthritis and aging is due in part to replicative senescence. The data also imply that transplantation procedures performed to restore damaged articular surfaces could be limited by the inability of older chondrocytes to form new cartilage after transplantation. PMID:11283188

  11. Direct human cartilage repair using three-dimensional bioprinting technology.

    PubMed

    Cui, Xiaofeng; Breitenkamp, Kurt; Finn, M G; Lotz, Martin; D'Lima, Darryl D

    2012-06-01

    Current cartilage tissue engineering strategies cannot as yet fabricate new tissue that is indistinguishable from native cartilage with respect to zonal organization, extracellular matrix composition, and mechanical properties. Integration of implants with surrounding native tissues is crucial for long-term stability and enhanced functionality. In this study, we developed a bioprinting system with simultaneous photopolymerization capable for three-dimensional (3D) cartilage tissue engineering. Poly(ethylene glycol) dimethacrylate (PEGDMA) with human chondrocytes were printed to repair defects in osteochondral plugs (3D biopaper) in layer-by-layer assembly. Compressive modulus of printed PEGDMA was 395.73±80.40 kPa, which was close to the range of the properties of native human articular cartilage. Printed human chondrocytes maintained the initially deposited positions due to simultaneous photopolymerization of surrounded biomaterial scaffold, which is ideal in precise cell distribution for anatomic cartilage engineering. Viability of printed human chondrocytes increased 26% in simultaneous polymerization than polymerized after printing. Printed cartilage implant attached firmly with surrounding tissue and greater proteoglycan deposition was observed at the interface of implant and native cartilage in Safranin-O staining. This is consistent with the enhanced interface failure strength during the culture assessed by push-out testing. Printed cartilage in 3D biopaper had elevated glycosaminoglycan (GAG) content comparing to that without biopaper when normalized to DNA. These observations were consistent with gene expression results. This study indicates the importance of direct cartilage repair and promising anatomic cartilage engineering using 3D bioprinting technology. PMID:22394017

  12. Direct Human Cartilage Repair Using Three-Dimensional Bioprinting Technology

    PubMed Central

    Cui, Xiaofeng; Breitenkamp, Kurt; Finn, M.G.; Lotz, Martin

    2012-01-01

    Current cartilage tissue engineering strategies cannot as yet fabricate new tissue that is indistinguishable from native cartilage with respect to zonal organization, extracellular matrix composition, and mechanical properties. Integration of implants with surrounding native tissues is crucial for long-term stability and enhanced functionality. In this study, we developed a bioprinting system with simultaneous photopolymerization capable for three-dimensional (3D) cartilage tissue engineering. Poly(ethylene glycol) dimethacrylate (PEGDMA) with human chondrocytes were printed to repair defects in osteochondral plugs (3D biopaper) in layer-by-layer assembly. Compressive modulus of printed PEGDMA was 395.73±80.40 kPa, which was close to the range of the properties of native human articular cartilage. Printed human chondrocytes maintained the initially deposited positions due to simultaneous photopolymerization of surrounded biomaterial scaffold, which is ideal in precise cell distribution for anatomic cartilage engineering. Viability of printed human chondrocytes increased 26% in simultaneous polymerization than polymerized after printing. Printed cartilage implant attached firmly with surrounding tissue and greater proteoglycan deposition was observed at the interface of implant and native cartilage in Safranin-O staining. This is consistent with the enhanced interface failure strength during the culture assessed by push-out testing. Printed cartilage in 3D biopaper had elevated glycosaminoglycan (GAG) content comparing to that without biopaper when normalized to DNA. These observations were consistent with gene expression results. This study indicates the importance of direct cartilage repair and promising anatomic cartilage engineering using 3D bioprinting technology. PMID:22394017

  13. Arthroscopic laser in intra-articular knee cartilage disorders

    NASA Astrophysics Data System (ADS)

    Nosir, Hany R.; Siebert, Werner E.

    1996-12-01

    Different assemblies have endeavored to develop arthroscopic laser surgery. Various lasers have been tried in the treatment of orthopaedic problems, and the most useful has turned out to be the Hol-YAG laser 2.1 nm which is a near- contact laser. By using the laser as a powerful tool, and cutting back on the power level, one is able to better achieve the desired treatment effect. Clinical studies to evaluating the role of the laser in different arthroscopic knee procedures, comparing to conventional techniques, showed that the overall outcome attains a momentous confidence level which is shifted to the side of the laser versus the conventional for all maneuvers, barring meniscectomy where there is not perceiving disparity between laser versus the conventional. Meniscectomy continues to be one of the most commonly performed orthopaedic procedures. Laser provides a single tool which can ablate and debride meniscal rims with efficiency and safety. Chondroplasty can also be accomplished with ease using defocused laser energy. Both lateral release and soft tissue cermilization benefit from the cutting effect of laser along with its hemostatic effect. Synovial reduction with a defocused laser is also easily accomplished. By one gadget, one can cut, ablate, smooth, coagulate, congeal and with authentic tissue depth control The future of laser arthroscopic surgery lies in its ability to weld or repair tissues. Our research study has shown that laser activated photoactive dyes can produce a molecular bonding of collagen fibers, and therefore a repair 'weld' can be achieved with both meniscal tissues and with articular cartilage lesions.

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

    PubMed

    Boyde, A; Riggs, C M; Bushby, A J; McDermott, B; Pinchbeck, G L; Clegg, P D

    2011-01-01

    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 euthanized 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. PMID:21623571

  15. Effects of surgically induced instability on rat knee articular cartilage.

    PubMed Central

    Williams, J M; Felten, D L; Peterson, R G; O'Connor, B L

    1982-01-01

    Degenerative lesions in the articular cartilage were present following transection of the anterior cruciate ligament in the rat. These lesions included surface disruptions, a reduction in matrix proteoglycans, and cellular changes and therefore were similar to lesions seen in dogs following transection of the anterior cruciate ligament as well as lesions seen in other mechanical derangement models. Lesions were more frequently encountered in animals that had been exercised on a treadmill. This suggests that the rat knee joint may be a useful small animal model in studying the effect of mechanical derangement on articular tissues. Images Figs. 1-2 Figs. 3-4 Figs. 5-6 PMID:7076535

  16. Quantitative proteomic profiling of human articular cartilage degradation in osteoarthritis.

    PubMed

    Lourido, Lucía; Calamia, Valentina; Mateos, Jesús; Fernández-Puente, Patricia; Fernández-Tajes, Juan; Blanco, Francisco J; Ruiz-Romero, Cristina

    2014-12-01

    Osteoarthritis (OA) is the most common rheumatic pathology and is characterized primarily by articular cartilage degradation. Despite its high prevalence, there is no effective therapy to slow disease progression or regenerate the damaged tissue. Therefore, new diagnostic and monitoring tests for OA are urgently needed, which would also promote the development of alternative therapeutic strategies. In the present study, we have performed an iTRAQ-based quantitative proteomic analysis of secretomes from healthy human articular cartilage explants, comparing their protein profile to those from unwounded (early disease) and wounded (advanced disease) zones of osteoarthritic tissue. This strategy allowed us to identify a panel of 76 proteins that are distinctively released by the diseased tissue. Clustering analysis allowed the classification of proteins according to their different profile of release from cartilage. Among these proteins, the altered release of osteoprotegerin (decreased in OA) and periostin (increased in OA), both involved in bone remodelling processes, was verified in further analyses. Moreover, periostin was also increased in the synovial fluid of OA patients. Altogether, the present work provides a novel insight into the mechanisms of human cartilage degradation and a number of new cartilage-characteristic proteins with possible biomarker value for early diagnosis and prognosis of OA. PMID:25383958

  17. An In Vitro Model for the Pathological Degradation of Articular Cartilage in Osteoarthritis

    PubMed Central

    Grenier, Stephanie; Bhargava, Madhu M.; Torzilli, Peter A.

    2014-01-01

    The objective of this study was to develop an in vitro cartilage degradation model that emulates the damage seen in early-stage osteoarthritis. To this end, cartilage explants were collagenase-treated to induce enzymatic degradation of collagen fibers and proteoglycans at the articular surface. To assess changes in mechanical properties, intact and degraded cartilage explants were subjected to a series of confined compression creep tests. Changes in extracellular matrix structure and composition were determined using biochemical and histological approaches. Our results show that collagenase-induced degradation increased the amount of deformation experienced by the cartilage explants under compression. An increase in apparent permeability as well as a decrease in instantaneous and aggregate moduli were measured following collagenase treatment. Histological analysis of degraded explants revealed the presence of surface fibrillation, proteoglycan depletion in the superficial and intermediate zones and loss of the lamina splendens. Collagen cleavage was confirmed by the Col II–¾Cshort antibody. Degraded specimens experienced a significant decrease in proteoglycan content but maintained total collagen content. Repetitive testing of degraded samples resulted in the gradual collapse of the articular surface and the compaction of the superficial zone. Taken together, our data demonstrates that enzymatic degradation with collagenase can be used to emulate changes seen in early-stage osteoarthritis. Further, our in vitro model provides information on cartilage mechanics and insights on how matrix changes can affect cartilage’s functional properties. More importantly, our model can be applied to develop and test treatment options for tissue repair. PMID:24360770

  18. Mesenchymal stromal cells for cartilage repair in osteoarthritis.

    PubMed

    Mamidi, M K; Das, A K; Zakaria, Z; Bhonde, R

    2016-08-01

    Treatment for articular cartilage damage is quite challenging as it shows limited repair and regeneration following injury. Non-operative and classical surgical techniques are inefficient in restoring normal anatomy and function of cartilage in osteoarthritis (OA). Thus, investigating new and effective strategies for OA are necessary to establish feasible therapeutic solutions. The emergence of the new discipline of regenerative medicine, having cell-based therapy as its primary focus, may enable us to achieve repair and restore the damaged articular cartilage. This review describes progress and development of employing mesenchymal stromal cell (MSC)-based therapy as a promising alternative for OA treatment. The objective of this review is to first, discuss how in vitro MSC chondrogenic differentiation mimics in vivo embryonic cartilage development, secondly, to describe various chondrogenic differentiation strategies followed by pre-clinical and clinical studies demonstrating their feasibility and efficacy. However, several challenges need to be tackled before this research can be translated to the clinics. In particular, better understanding of the post-transplanted cell behaviour and learning to enhance their potency in the disease microenvironment is essential. Final objective is to underscore the importance of isolation, storage, cell shipment, route of administration, optimum dosage and control batch to batch variations to realise the full potential of MSCs in OA clinical trials. PMID:26973328

  19. Strategies for Controlled Delivery of Biologics for Cartilage Repair

    PubMed Central

    Lam, Johnny; Lu, Steven; Kasper, F. Kurtis; Mikos, Antonios G.

    2014-01-01

    The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential and can also cause unwanted morphological effects. It is therefore imperative to consider the type of biologic to be delivered, the method of delivery, and the temporal as well as spatial presentation of the biologic to achieve the desired effect in cartilage repair. Additionally, the delivery of a single factor may not be sufficient in guiding neo-tissue formation, motivating recent research towards the delivery of multiple factors. This review will discuss the roles of various biologics involved in cartilage repair and the different methods of delivery for appropriate healing responses. A number of spatiotemporal strategies will then be emphasized for the controlled delivery of single and multiple bioactive factors in both in vitro and in vivo cartilage tissue engineering applications. PMID:24993610

  20. Effect of exercise on the proteoglycan metabolism of articular cartilage in growing foals.

    PubMed

    van den Hoogen, B M; van den Lest, C H; van Weeren, P R; van Golde, L M; Barneveld, A

    1999-11-01

    In this study, the effect of different exercise regimens on proteoglycan metabolism of articular cartilage was examined in 43 newborn foals randomly divided into 3 groups: a) box-rest, b) box-rest with training and c) free pasture exercise. They were subjected to these exercise regimens from ages 1 week to 5 months and at 5 months, 24 foals (8 from each group) were sacrificed to assess short-term exercise effects. The remaining 19 foals were subjected to the same regimen of light exercise for an additional 6 months before being sacrificed to evaluate possible long-term effects. Articular cartilage explants were cultured and proteoglycan synthesis, both ex vivo and after 4 days of serum stimulation, release of endogenous and newly synthesised proteoglycans, and DNA- and GAG contents were measured to determine the metabolic state of the cartilage. Cartilage metabolic parameters in the box-rest group at 5 months indicated a retardation in development of the cartilage but, after an additional 6 months, this retardation had almost completely disappeared. The training regimen induced an increase in proteoglycan synthesis at 5 months in cartilage that was, however, accompanied by an increase in proteoglycan release. In the training group at the long-term, the ability of cartilage to increase proteoglycan synthesis when stimulated was severely reduced. We consider this extra proteoglycan synthesis capacity of great importance to repair small injuries and hence as essential to prevent an early onset of degenerative disorders such as osteoarthritis. Therefore, although extrapolation of in vitro data to the in vivo situation always should be done with the utmost care, it is concluded that pasture exercise is best for the development of healthy cartilage resistant to injury and other exercise protocols may carry harmful long-term effects. PMID:10999662

  1. Cellular and Acellular Approaches for Cartilage Repair

    PubMed Central

    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

  2. Fucose content of keratan sulphates from bovine articular cartilage.

    PubMed Central

    Tai, G H; Brown, G M; Morris, H G; Huckerby, T N; Nieduszynski, I A

    1991-01-01

    Alkaline-borohydride-reduced keratan sulphate chains were isolated from bovine articular cartilage (6-8-year-old animals). Nine keratan sulphate fractions of increasing molecular weight were prepared by gel-permeation chromatography on a calibrated column of TSK 30 XL. The samples were analysed for fucose and galactose contents (% by wt. of keratan sulphate) and fucose/galactose ratio. The fucose content increased with molecular size, but the galactose content remained constant. It was concluded that the alpha(1----3)-linked fucose [Thornton, Morris, Cockin, Huckerby, Nieduszynski, Carlstedt, Hardingham & Ratcliffe (1989) Biochem. J. 260, 277-282] was located within the poly-N-acetyl-lactosamine repeat sequence of articular-cartilage keratan sulphate. PMID:1991030

  3. Structural and metabolic changes in articular cartilage induced by iodoacetate.

    PubMed Central

    Dunham, J.; Hoedt-Schmidt, S.; Kalbhen, D. A.

    1992-01-01

    The chemically induced injury to articular cartilage, caused by two successive intra-articular injections of sodium iodoacetate, has been used in studies on the effects of anti-inflammatory and of potentially chondroprotective agents. It has been assumed that the injurious effects are caused by inhibition of the glycolytic pathway. In the present study this inhibition has been shown to be greater than expected from in vitro studies, and to influence equally other oxidative pathways. However, the response is clearly not a simple one in that some of the surface chondrocytes, and synovial lining cells in close proximity to the cartilage, show virtually no inhibition. Images Fig. 2 Fig. 3 Fig. 4 PMID:1390193

  4. 3D braid scaffolds for regeneration of articular cartilage.

    PubMed

    Ahn, Hyunchul; Kim, Kyoung Ju; Park, Sook Young; Huh, Jeong Eun; Kim, Hyun Jeong; Yu, Woong-Ryeol

    2014-06-01

    Regenerating articular cartilage in vivo from cultured chondrocytes requires that the cells be cultured and implanted within a biocompatible, biodegradable scaffold. Such scaffolds must be mechanically stable; otherwise chondrocytes would not be supported and patients would experience severe pain. Here we report a new 3D braid scaffold that matches the anisotropic (gradient) mechanical properties of natural articular cartilage and is permissive to cell cultivation. To design an optimal structure, the scaffold unit cell was mathematically modeled and imported into finite element analysis. Based on this analysis, a 3D braid structure with gradient axial yarn distribution was designed and manufactured using a custom-built braiding machine. The mechanical properties of the 3D braid scaffold were evaluated and compared with simulated results, demonstrating that a multi-scale approach consisting of unit cell modeling and continuum analysis facilitates design of scaffolds that meet the requirements for mechanical compatibility with tissues. PMID:24556323

  5. Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold

    PubMed Central

    Lv, Y. M.; Yu, Q. S.

    2015-01-01

    Objectives The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. Methods The bone–cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid–hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. Results After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. Conclusion This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56–64 PMID:25837672

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

    PubMed

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

    2013-12-17

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

  7. Finite element formulation of biphasic poroviscoelastic model for articular cartilage.

    PubMed

    Suh, J K; Bai, S

    1998-04-01

    The purpose of the present study was to develop a computationally efficient finite element model that could be useful for parametric analysis of the biphasic poroviscoelastic (BPVE) behavior of articular cartilage under various loading conditions. The articular cartilage was modeled as the BPVE mixture of a porous, linear viscoelastic, and incompressible solid and an inviscid and incompressible fluid. A finite element (FE) formulation of the BPVE model was developed using two different algorithms, the continuous and discrete spectrum relaxation functions for the viscoelasticity of the solid matrix. These algorithms were applied to the creep and stress relaxation responses to the confined compression of articular cartilage, and a comparison of their performances was made. It was found that the discrete spectrum algorithm significantly saved CPU time and memory, as compared to the continuous spectrum algorithm. The consistency analysis for the present FE formulation was performed in comparison with the IMSL, a commercially available numerical software package. It was found that the present FE formulation yielded consistent results in predicting model behavior, whereas the IMSL subroutine produced inconsistent results in the velocity field, and thereby in the strain calculation. PMID:10412380

  8. The collagen fibril organization in human articular cartilage.

    PubMed Central

    Minns, R J; Steven, F S

    1977-01-01

    In this scanning electron microscopic study blocks of collagen fibrils were prepared from human articular cartilage, using two techinques which selectively removed either the proteoglycans alone, or both the proteoglycans and the collagen fibrils, of the non-calcified cartilage layer. Amino acid analysis of the fibrils confirmed the purity of the collagen after proteoglycan extraction. The cartilage was scanned in four different ways: (1) normal to the articular surface, (2) in superficial sections, (3) on surfaces of blocks which had been broken in planes parallel to artificial splits make by the insertion of a pin, and (4) on fracture surfaces which traversed the calcified cartilage and the subchondral bone. Five features of the organization of the collagen fibrils were specially noted: (1) Individual fibrils within the trabeculae joined to form small fibre bundles which became grouped into larger bundles at the calcified/uncalcified interface. (2) Fibrils in the deep and middle zones which, exhibiting the characteristic surface periodicity of collagen, were generally oriented towars the articular surface in large bundles approximately 55 micronm across. (3) In the superficial zone, fibrils ran parallel to the surface. (4) The surface fibrils had random orientation, even at the bases of empty lacunae vacated by chondrocytes during specimen preparation. (5) The collagen fibrils of the lacunar walls appeared to be thinner and more closely packed than thos between the lacunae. The fine collagen fibrils associated with the lacunar walls were frequently observed to pass through a large lacunar space, resulting in the formation of two or more compartments, each of which was presumably filled with a chondrocyte in the living cartilage. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:870478

  9. Postnatal development of collagen structure in ovine articular cartilage

    PubMed Central

    2010-01-01

    Background Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Across species, adult AC shows an arcade-like structure with collagen predominantly perpendicular to the subchondral bone near the bone, and collagen predominantly parallel to the articular surface near the articular surface. Recent studies into collagen fibre orientation in stillborn and juvenile animals showed that this structure is absent at birth. Since the collagen structure is an important factor for AC mechanics, the absence of the adult Benninghoff structure has implications for perinatal AC mechanobiology. The current objective is to quantify the dynamics of collagen network development in a model animal from birth to maturity. We further aim to show the presence or absence of zonal differentiation at birth, and to assess differences in collagen network development between different anatomical sites of a single joint surface. We use quantitative polarised light microscopy to investigate properties of the collagen network and we use the sheep (Ovis aries) as our model animal. Results Predominant collagen orientation is parallel to the articular surface throughout the tissue depth for perinatal cartilage. This remodels to the Benninghoff structure before the sheep reach sexual maturity. Remodelling of predominant collagen orientation starts at a depth just below the future transitional zone. Tissue retardance shows a minimum near the articular surface at all ages, which indicates the presence of zonal differentiation at all ages. The absolute position of this minimum does change between birth and maturity. Between different anatomical sites, we find differences in the dynamics of collagen remodelling, but no differences in adult collagen structure. Conclusions The collagen network in articular cartilage remodels between birth and sexual maturity from a network with predominant orientation parallel to the articular surface to a

  10. Regulatory Challenges for Cartilage Repair Technologies.

    PubMed

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment. PMID:26752228

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

    PubMed

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

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment. PMID:26752228

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  14. Articular cartilage of the knee 3 years after ACL reconstruction

    PubMed Central

    Bae, Ji-Hoon; Hosseini, Ali; Wang, Yang; Torriani, Martin; Gill, Thomas J; Grodzinsky, Alan J

    2015-01-01

    Background and purpose T1ρ or T2 relaxation imaging has been increasingly used to evaluate the cartilage of the knee. We investigated the cartilage of ACL-reconstructed knees 3 years after surgery using T2 relaxation times. Patients and methods 10 patients with a clinically successful unilateral ACL reconstruction were examined 3 years after surgery. Multiple-TE fast-spin echo sagittal images of both knees were acquired using a 3T MRI scanner for T2 mapping of the tibiofemoral cartilage. T2 values of the superficial and deep zones of the tibiofemoral cartilage were analyzed in sub-compartmental areas and compared between the ACL-reconstructed and uninjured contralateral knees. Results Higher T2 values were observed in 1 or more sub-compartmental areas of each ACL-reconstructed knee compared to the uninjured contralateral side. Most of the T2 increases were observed at the superficial zones of the cartilage, especially at the medial compartment. At the medial compartment of the ACL-reconstructed knee, the T2 values of the femoral and tibial cartilage were increased by 3–81% compared to the uninjured contralateral side, at the superficial zones of the weight-bearing areas. T2 values in the superficial zone of the central medial femoral condyle differed between the 2 groups (p = 0.002). Interpretation The articular cartilage of ACL-reconstructed knees, although clinically satisfactory, had higher T2 values in the superficial zone of the central medial femoral condyle than in the uninjured contralateral side 3 years after surgery. Further studies are warranted to determine whether these patients would undergo cartilage degeneration over time. PMID:25854533

  15. Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models

    PubMed Central

    Halloran, J. P.; Sibole, S.; van Donkelaar, C. C.; van Turnhout, M. C.; Oomens, C. W. J.; Weiss, J. A.; Guilak, F.; Erdemir, A.

    2012-01-01

    Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes. PMID:22648577

  16. Importance of reference gene selection for articular cartilage mechanobiology studies

    PubMed Central

    Al-Sabah, A.; Stadnik, P.; Gilbert, S.J.; Duance, V.C.; Blain, E.J.

    2016-01-01

    Summary Objective Identification of genes differentially expressed in mechano-biological pathways in articular cartilage provides insight into the molecular mechanisms behind initiation and/or progression of osteoarthritis (OA). Quantitative PCR (qPCR) is commonly used to measure gene expression, and is reliant on the use of reference genes for normalisation. Appropriate validation of reference gene stability is imperative for accurate data analysis and interpretation. This study determined in vitro reference gene stability in articular cartilage explants and primary chondrocytes subjected to different compressive loads and tensile strain, respectively. Design The expression of eight commonly used reference genes (18s, ACTB, GAPDH, HPRT1, PPIA, RPL4, SDHA and YWHAZ) was determined by qPCR and data compared using four software packages (comparative delta-Ct method, geNorm, NormFinder and BestKeeper). Calculation of geometric means of the ranked weightings was carried out using RefFinder. Results Appropriate reference gene(s) for normalisation of mechanically-regulated transcript levels in articular cartilage tissue or isolated chondrocytes were dependent on experimental set-up. SDHA, YWHAZ and RPL4 were the most stable genes whilst glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and to a lesser extent Hypoxanthine-guanine phosphoribosyltransferase (HPRT), showed variable expression in response to load, demonstrating their unsuitability in such in vitro studies. The effect of using unstable reference genes to normalise the expression of aggrecan (ACAN) and matrix metalloproteinase 3 (MMP3) resulted in inaccurate quantification of these mechano-sensitive genes and erroneous interpretation/conclusions. Conclusion This study demonstrates that commonly used ‘reference genes’ may be unsuitable for in vitro cartilage chondrocyte mechanobiology studies, reinforcing the principle that careful validation of reference genes is essential prior to each experiment to

  17. Ultrasound evaluation of site-specific effect of simulated microgravity on articular cartilage.

    PubMed

    Wang, Qing; Zheng, Yong-Ping; Wang, Xiao-Yun; Huang, Yan-Ping; Liu, Mu-Qing; Wang, Shu-Zhe; Zhang, Zong-Kang; Guo, Xia

    2010-07-01

    Space flight induces acute changes in normal physiology in response to the microgravity environment. Articular cartilage is subjected to high loads under a ground reaction force on Earth. The objectives of this study were to investigate the site dependence of morphological and ultrasonic parameters of articular cartilage and to examine the site-specific responses of articular cartilage to simulated microgravity using ultrasound biomicroscopy (UBM). Six rats underwent tail suspension (simulated microgravity) for four weeks and six other rats were kept under normal Earth gravity as controls. Cartilage thickness, ultrasound roughness index (URI), integrated reflection coefficient (IRC) and integrated backscatter coefficient (IBC) of cartilage tissues, as well as histological degeneration were measured at the femoral head (FH), medial femoral condyle (MFC), lateral femoral condyle (LFC), patello-femoral groove (PFG) and patella (PAT). The results showed site dependence not significant in all UBM parameters except cartilage thickness (p < 0.01) in the control specimens. Only minor changes in articular cartilage were induced by 4-week tail suspension, although there were significant decreases in cartilage thickness at the MFC and PAT (p < 0.05) and a significant increase in URI at the PAT (p < 0.01). This study suggested that the 4-week simulated microgravity had only mild effects on femoral articular cartilage in the rat model. This information is useful for human spaceflight and clinical medicine in improving understanding of the effect of microgravity on articular cartilage. However, the effects of longer duration microgravity experience on articular cartilage need further investigation. PMID:20620696

  18. Zn deposition at the bone cartilage interface in equine articular cartilage

    NASA Astrophysics Data System (ADS)

    Bradley, D. A.; Moger, C. J.; Winlove, C. P.

    2007-09-01

    In articular cartilage metalloproteinases, a family of enzymes whose function relies on the presence of divalent cations such as Zn and Ca plays a central role in the normal processes of growth and remodelling and in the degenerative and inflammatory processes of arthritis. Another important enzyme, alkaline phosphatase, involved in cartilage mineralisation also relies on metallic cofactors. The local concentration of divalent cations is therefore of considerable interest in cartilage pathophysiology and several authors have used synchrotron X-ray fluorescence (XRF) to map metal ion distributions in bone and cartilage. We report use of a bench-top XRF analytical microscope, providing spatial resolution of 10 μm and applicable to histological sections, facilitating correlation of the distribution with structural features. The study seeks to establish the elemental distribution in normal tissue as a precursor to investigation of changes in disease. For six samples prepared from equine metacarpophalangeal joint, we observed increased concentration of Zn and Sr ions around the tidemark between normal and mineralised cartilage. This is believed to be an active site of remodelling but its composition has hitherto lacked detailed characterization. We also report preliminary results on two of the samples using Proton-Induced X-ray Emission (PIXE). This confirms our previous observations using synchrotron-based XRF of enhanced deposition of Sr and Zn at the surface of the subchondral bone and in articular cartilage.

  19. Treatment of Articular Cartilage Defects of the Knee With Microfracture and Enhanced Microfracture Techniques.

    PubMed

    Case, Jordan M; Scopp, Jason M

    2016-06-01

    Chondral injuries in the knee are a common source of pain and morbidity. Treatment of symptomatic chondral defects is challenging due to the limited healing capacity of articular cartilage. Microfracture is the most common surgical technique used to treat chondral defects in the knee and utilizes marrow stimulation to generate a fibrocartilage repair. Microfracture has demonstrated good short-term postoperative outcomes. Long-term outcomes following microfracture are variable, with loss of improvement attributed to the poor mechanical qualities of the fibrous repair tissue. Current research is focusing on ways to optimize the repair environment after microfracture using biological scaffolds (enhanced microfracture) to facilitate chondrogenic differentiation and proliferation to improve the quality of repair tissue. PMID:27135288

  20. MRI rotating frame relaxation measurements for articular cartilage assessment

    PubMed Central

    Ellermann, Jutta; Ling, Wen; Nissi, Mikko J.; Arendt, Elizabeth; Carlson, Cathy S.; Garwood, Michael; Michaeli, Shalom; Mangia, Silvia

    2015-01-01

    In the present work we introduced two MRI rotating frame relaxation methods, namely adiabatic T1ρ and Relaxation Along a Fictitious Field (RAFF), along with an inversion-prepared Magnetization Transfer (MT) protocol for assessment of articular cartilage. Given the inherent sensitivity of rotating frame relaxation methods to slow molecular motions that are relevant in cartilage, we hypothesized that adiabatic T1ρ and RAFF would have higher sensitivity to articular cartilage degradation as compared to laboratory frame T2 and MT. To test this hypothesis, a proteoglycan depletion model was used. Relaxation time measurements were performed at 0 and 48 hours in ten bovine patellar specimens, 5 of which were treated with trypsin and 5 untreated controls were stored under identical conditions in isotonic saline for 48 hours. Relaxation times measured at 48 hours were longer than those measured at 0 hours in both groups. The changes in T2 and MT relaxation times after 48 hours were approximately 3 times larger in the trypsin treated specimens as compared to the untreated group, whereas increases of adiabatic T1ρ and RAFF were 4 to 5 fold larger. Overall, these findings demonstrate a higher sensitivity of adiabatic T1ρ and RAFF to the trypsin-induced changes in bovine patellar cartilage as compared to the commonly used T2 and MT. Since adiabatic T1ρ and RAFF are advantageous for human applications as compared to standard continuous-wave T1ρ methods, adiabatic T1ρ and RAFF are promising tools for assessing cartilage degradation in clinical settings. PMID:23993794

  1. A reappraisal of the structure of normal canine articular cartilage.

    PubMed Central

    Dunham, J; Shackleton, D R; Billingham, M E; Bitensky, L; Chayen, J; Muir, I H

    1988-01-01

    It has been shown that some of the controversy over the structure of articular cartilage may be due to slight differences in the orientation of the sample that has been studied. As our decisive criterion we have used the simple physical fact that elongate proteins, such as collagen micelles, that can exhibit form-birefringence, had to show virtually straight extinction when viewed under crossed polars. The use of a variably adjustable microtome chuck facilitated small adjustments in the orientation of the cartilage to meet this criterion. Under these conditions, the collagen of the matrix has been shown to be aligned mainly perpendicularly to the surface which was bounded by a thin lamina in which the collagen showed birefringence at 90 degrees to that of the matrix. The conventionally described zonation of articular cartilage has been shown to be inadequate for that of the dog tibial plateau. The conventional Zone 2 has been shown to consist of two zones, Zones 2a and 2b, with different cell sizes, cell concentrations, and concentration of matrix components. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:3198487

  2. Healing of articular cartilage defects treated with a novel drug-releasing rod-type implant after microfracture surgery.

    PubMed

    Shim, In Kyong; Yook, Yeo Joo; Lee, Sang Young; Lee, Sang Hoon; Park, Ki Dong; Lee, Myung Chul; Lee, Seung Jin

    2008-08-01

    Microfracture therapy is a widely used technique for the repair of articular cartilage defects because it can be readily performed arthroscopically. However, the regenerated cartilage after microfracture surgery clearly differs from normal articular cartilage. This suggests that the clinical outcome of patients undergoing microfracture therapy could be improved. Dehydroepiandrosterone sulfate (DHEA-S) is known to protect against articular cartilage loss. Therefore, in an effort to achieve cartilage regeneration of high efficacy, we manufactured a DHEA-S-releasing rod-type implant for implantation into the holes produced by microfracture surgery. The polymeric rod-type implant was made of biodegradable poly (D, L-lactide-co-glycolide) (PLGA) and beta-tricalcium phosphate to enable controlled release of DHEA-S. The implant was dip-coated with a dilute PLGA solution to prevent the burst release of DHEA-S. The rod-type implant was sufficiently stiff to permit implantation into the holes made by microfracture. DHEA-S was released from the implant for more than four weeks. Furthermore, eight weeks after implantation into rabbit knees, the implants dramatically enhanced cartilage regeneration compared to control. Moreover, the degradation of the implant over the eight weeks from implantation into the knee did not induce any adverse effects. Therefore, this polymeric rod-type implant does not only provide an improvement in microfracture surgery, but also has great potential as a new formulation for drug delivery. PMID:18547670

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  4. [Joint morphogenesis and development of permanent articular cartilage].

    PubMed

    Ohta, Yoichi; Iwamoto, Masahiro

    2011-06-01

    During limb skeletogenesis progenitor mesenchymal cells aggregate at specific times and sites to form continuous precartilaginous condensations. With time the condensations undergo chondrogenesis and give rise to cartilaginous anlagen that exhibit incipient synovial joints at each end. A multitude of factors regulates subdivision into discrete skeletal elements and the formation, organization, morphogenesis and structure of the joints. This review summarizes recent advance of joint morphogenesis and actions of key players of joint and articular cartilage formation. In addition, we would like to discuss possible direction to translate basic research findings towards treatment of joint diseases. PMID:21628794

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

    PubMed

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

    2016-07-01

    Articular cartilage defects, when repaired ineffectively, often lead to further deterioration of the tissue, secondary osteoarthritis and, ultimately, joint replacement. Unfortunately, current surgical procedures are unable to restore normal cartilage function. Tissue engineering of cartilage provides promising strategies for the regeneration of damaged articular cartilage. As yet, there are still significant challenges that need to be overcome to match the long-term mechanical stability and durability of native cartilage. Using electrospinning of different blends of biodegradable poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate), we produced polymer scaffolds and optimised their structure, stiffness, degradation rates and biocompatibility. Scaffolds with a poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate) ratio of 1:0.25 exhibit randomly oriented fibres that closely mimic the collagen fibrillar meshwork of native cartilage and match the stiffness of native articular cartilage. Degradation of the scaffolds into products that could be easily removed from the body was indicated by changes in fibre structure, loss of molecular weight and a decrease in scaffold stiffness after one and four months. Histological and immunohistochemical analysis after three weeks of culture with human articular chondrocytes revealed a hyaline-like cartilage matrix. The ability to fine tune the ultrastructure and mechanical properties using different blends of poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate) allows to produce a cartilage repair kit for clinical use to reduce the risk of developing secondary osteoarthritis. We further suggest the development of a toolbox with tailor-made scaffolds for the repair of other tissues that require a 'guiding' structure to support the body's self-healing process. PMID:27013217

  6. Black Colouration of the Knee Articular Cartilage after Spontaneously Recurrent Haemarthrosis

    PubMed Central

    Ishimaru, Daichi; Ogawa, Hiroyasu; Akiyama, Haruhiko

    2016-01-01

    Mild discolouration of the articular cartilage is known to gradually occur during aging. However, pathological tissue pigmentation is occasionally induced under several specific conditions. In the present case, we performed total knee replacement in a patient with recurrent haemarthrosis. However, during the operation, we observed severe black colouration of the knee articular cartilage, due to the deposition of hemosiderin and lipofuscin. To our knowledge, this is the first report of severe cartilage pigmentation, due to hemosiderin and lipofuscin deposition in articular cartilage. PMID:27293933

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

    PubMed

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

    2012-05-11

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

  8. Preliminary investigation of intrinsic UV fluorescence spectroscopic changes associated with proteolytic digestion of bovine articular cartilage

    NASA Astrophysics Data System (ADS)

    Lewis, William; Padilla-Martinez, Juan-Pablo; Ortega-Martinez, Antonio; Franco, Walfre

    2016-03-01

    Degradation and destruction of articular cartilage is the etiology of osteoarthritis (OA), an entity second only to cardiovascular disease as a cause of disability in the United States. Joint mechanics and cartilage biochemistry are believed to play a role in OA; an optical tool to detect structural and chemical changes in articular cartilage might offer benefit for its early detection and treatment. The objective of the present study was to identify the spectral changes in intrinsic ultraviolet (UV) fluorescence of cartilage that occur after proteolytic digestion of cartilage. Bovine articular cartilage samples were incubated in varying concentrations of collagenase ranging from 10ug/mL up to 5mg/mL for 18 hours at 37°C, a model of OA. Pre- and post-incubation measurements were taken of the UV excitation-emission spectrum of each cartilage sample. Mechanical tests were performed to determine the pre- and post-digestion force/displacement ratio associated with indentation of each sample. Spectral changes in intrinsic cartilage fluorescence and stiffness of the cartilage were associated with proteolytic digestion. In particular, changes in the relative intensity of fluorescence peaks associated with pentosidine crosslinks (330 nm excitation, 390 nm emission) and tryptophan (290 nm excitation, 340 nm emission) were found to correlate with different degrees of cartilage digestion and cartilage stiffness. In principle, it may be possible to use UV fluorescence spectral data for early detection of damage to articular cartilage, and as a surrogate measure for cartilage stiffness.

  9. Designed composites for mimicking compressive mechanical properties of articular cartilage matrix.

    PubMed

    Zhu, Youjia; Wu, Hua; Sun, Shaofa; Zhou, Ting; Wu, Jingjing; Wan, Ying

    2014-08-01

    Collagen, chitosan-polycaprolactone (CH-PCL) copolymer with PCL content of around 40wt% and chondroitin sulfate (CS) were mixed together at various ratios to prepare collagen/CH-PCL/CS composites and the resulting composites were used to build stratified porous scaffolds that are potentially applicable for articular cartilage repair. The ternary composites were designed in such a way that collagen content in the scaffolds decreased from the top layer to the bottom layer while the content of CH-PCL and CS altered in a reversed trend in order to reach partial similarity to cartilage matrix in the composition of main components. Porous structures inside collagen/CH-PCL/CS scaffolds were constructed using a low-temperature deposition processing technique and graded average pore-size and porosity for the scaffolds were established. Such produced scaffolds were further crosslinked using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide under optimized conditions, and the obtained scaffolds showed well-defined elastic compressive properties. Compressive modulus (E) and stress at 10% strain (σ10) of full scaffolds in wet state reached about 2.8MPa and 0.3MPa, respectively, and meanwhile, E and σ10 of layers inside hydrated scaffolds changed in a gradient-increased manner from the top layer to the bottom layer with significant differences between contiguous layers, which partially mimics compressive mechanical properties of cartilage matrix. In addition, in vitro culture of cell-scaffold constructs exhibited that scaffolds were able to well support the ingrowth and migration of seeded cells, and cells also showed relatively uniform distribution throughout the scaffolds. These results suggest that the presently developed collagen/CH-PCL/CS scaffolds have promising potential for applications in articular cartilage repair. PMID:24793172

  10. A nonlinear biphasic viscohyperelastic model for articular cartilage.

    PubMed

    García, José Jaime; Cortés, Daniel Humberto

    2006-01-01

    Experiments on articular cartilage have shown nonlinear stress-strain curves under finite deformations as well as intrinsic viscous effects of the solid phase. The aim of this study was to propose a nonlinear biphasic viscohyperelastic model that combines the intrinsic viscous effects of the proteoglycan matrix with a nonlinear hyperelastic constitutive equation. The proposed equation satisfies objectivity and reduces for uniaxial loading to a solid type viscous model in which the actions of the springs are represented by the hyperelastic function proposed by Holmes and Mow [1990. J. Biomechanics 23, 1145-1156.]. Results of the model, that were efficiently implemented in an updated Lagrangian algorithm, were compared with experimental infinitesimal data reported by DiSilverstro and Suh [2001. J. Biomechanics 34, 519-525.] and showed acceptable fitting for the axial force (R(2)=0.991) and lateral displacement (R(2)=0.914) curves in unconfined compression as well as a good fitting of the axial indentation force curve (R(2)=0.982). In addition, the model showed an excellent fitting of finite-deformation confined compression stress relaxation data reported by Ateshian et al. [1997. J. Biomechanics 30, 1157-1164.] and Huang et al. [2005. J. Biomechanics 38, 799-809.] (R(2)=0.993 and R(2)=0.995, respectively). The constitutive equation may be used to represent the mechanical behavior of the proteoglycan matrix in a fiber reinforced model of articular cartilage. PMID:16316659

  11. Delivering Agents Locally into Articular Cartilage by Intense MHz Ultrasound

    PubMed Central

    Nieminen, Heikki J.; Ylitalo, Tuomo; Suuronen, Jussi-Petteri; Rahunen, Krista; Salmi, Ari; Saarakkala, Simo; Serimaa, Ritva; Hæggström, Edward

    2015-01-01

    There is no cure for osteoarthritis. Current drug delivery relies on systemic delivery or injections into the joint. Because articular cartilage (AC) degeneration can be local and drug exposure outside the lesion can cause adverse effects, localized drug delivery could permit new drug treatment strategies. We investigated whether intense megahertz ultrasound (frequency: 1.138 MHz, peak positive pressure: 2.7 MPa, Ispta: 5 W/cm2, beam width: 5.7 mm at −6 dB, duty cycle: 5%, pulse repetition frequency: 285 Hz, mechanical index: 1.1) can deliver agents into AC without damaging it. Using ultrasound, we delivered a drug surrogate down to a depth corresponding to 53% depth of the AC thickness without causing histologically detectable damage to the AC. This may be important because early osteoarthritis typically exhibits histopathologic changes in the superficial AC. In conclusion, we identify intense megahertz ultrasound as a technique that potentially enables localized non-destructive delivery of osteoarthritis drugs or drug carriers into articular cartilage. PMID:25922135

  12. [The early development of the articular cartilage. IV. The metamorphosing cartilage].

    PubMed

    Knese, K H

    1980-01-01

    The definite articular cartilage originate from 2 anlagen, the primordial tangential layer and the greater part including the joint bone plate from the metamorphosing cartilage. The tangential layer grow by apposition from the perichondrium. Additional the layer becomes also dilatated as a result of the growing volume of the ossification center. In this way the Lamina splendens with residues of cells may be formed. The chondrocytes resemble partly fibroblasts, in older animals possibly even tendocytes. Moreover the cells exhibit a varying different shape. Today it is impossible to interpret the polymorphism of the cells. In the primordial state, the chondrocyts are embedded in a network from thin cartilage fibrils. Later on collagen fibrils from varied thickness (up to 900 A) are formed. The fibrils run only partly parallel to each other, in general they form a network, in which they cross with a low angle. There are great local differences in the fibrillar structure by the same animal. PMID:7461420

  13. Effects of immobilization on articular cartilage: Autohistoradiographic findings with S35

    NASA Technical Reports Server (NTRS)

    Digiovanni, C.; Desantis, E.

    1980-01-01

    The effect of immobilization on the articular cartilage of rabbits was studied by light microscope. The knee joint of each rabbit was immobilized in a plaster in a position midway between flexion and extension for a 10 to 120 days period. Degenerative changes in the articular cartilage of increasing severity were observed. The fixation of the labeled SO4 by cartilage cells was decreased in advanced immobilization.

  14. Modeling IL-1 induced degradation of articular cartilage.

    PubMed

    Kar, Saptarshi; Smith, David W; Gardiner, Bruce S; Li, Yang; Wang, Yang; Grodzinsky, Alan J

    2016-03-15

    In this study, we develop a computational model to simulate the in vitro biochemical degradation of articular cartilage explants sourced from the femoropatellar grooves of bovine calves. Cartilage explants were incubated in culture medium with and without the inflammatory cytokine IL-1α. The spatio-temporal evolution of the cartilage explant's extracellular matrix components is modelled. Key variables in the model include chondrocytes, aggrecan, collagen, aggrecanase, collagenase and IL-1α. The model is first calibrated for aggrecan homeostasis of cartilage in vivo, then for data on (explant) controls, and finally for data on the IL-1α driven proteolysis of aggrecan and collagen over a 4-week period. The model was found to fit the experimental data best when: (i) chondrocytes continue to synthesize aggrecan during the cytokine challenge, (ii) a one to two day delay is introduced between the addition of IL-1α to the culture medium and subsequent aggrecanolysis, (iii) collagen degradation does not commence until the total concentration of aggrecan (i.e. both intact and degraded aggrecan) at any specific location within the explant becomes ≤ 1.5 mg/ml and (iv) degraded aggrecan formed due to the IL-1α induced proteolysis of intact aggrecan protects the collagen network while collagen degrades in a two-step process which, together, significantly modulate the collagen network degradation. Under simulated in vivo conditions, the model predicts increased aggrecan turnover rates in the presence of synovial IL-1α, consistent with experimental observations. Such models may help to infer the course of events in vivo following traumatic joint injury, and may also prove useful in quantitatively evaluating the efficiency of various therapeutic molecules that could be employed to avoid or modify the course of cartilage disease states. PMID:26874194

  15. Biochemical analysis of normal articular cartilage in horses.

    PubMed

    Vachon, A M; Keeley, F W; McIlwraith, C W; Chapman, P

    1990-12-01

    Articular cartilage specimens from the distal articular surface of 32 radiocarpal bones from 24 2- to 5-year-old horses were analyzed. The total collagen content was determined on the basis of the 4-hydroxyproline content, using a colorimetric method. A method for estimating the proportions of types-I and -II collagen by measuring spectrophotometric densities of specific cyanogen bromide peptide bands from mixtures of types-I and -II collagen on sodium dodecyl sulfate-polyacrylamide gels was used. The cyanogen bromide peptides representative of each collagen types-I and -II were identified. The peptide ratios were then computed for each of several standards of type-I and -II mixtures. A standard curve was derived from the correlation between these ratios and the corresponding proportions of type-II collagen in standard mixtures. Galactosamine and glucosamine content (hexosamines) were measured by ion chromatography. The galactosamine-to-glucosamine ratio, chondroitin sulfate and keratan sulfate values, and total glycosaminoglycan content were derived from the measured hexosamine content. The total collagen content averaged 556 mg/g (55.6 mg/100 mg) of tissue (dry weight, [dw]). Type-II collagen was the major collagen type in normal articular cartilage specimens. The ratio of the area under the alpha 1 (II)CB10 peak to the area under the alpha 1 (I)CB 7,8 + alpha 1 (II)CB11 peak was a second-order polynomial function of the proportion of type-II collagen in the specimens. The mean galactosamine and glucosamine content were 20.6 mg/g and 7.9 mg/g (dw), respectively. The mean galactosamine-to-glucosamine ratio was 3.74 +/- 0.62.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2085215

  16. Techniques and Applications of in vivo Diffusion Imaging of Articular Cartilage

    PubMed Central

    Raya, José G.

    2014-01-01

    Early in the process of osteoarthritis (OA) the composition (water, proteoglycan [PG], and collagen) and structure of articular cartilage is altered leading to changes in its mechanical properties. A technique that can assess the composition and structure of the cartilage in vivo can provide insight in the mechanical integrity of articular cartilage and become a powerful tool for the early diagnosis of OA. Diffusion tensor imaging (DTI) has been proposed as a biomarker for cartilage composition and structure. DTI is sensitive to the PG content through the mean diffusivity (MD) and to the collagen architecture through the fractional anisotropy (FA). However, the acquisition of DTI of articular cartilage in vivo is challenging due to the short T2 of articular cartilage (~40 ms at 3 T) and the high resolution needed (0.5–0.7 mm in plane) to depict the cartilage anatomy. We describe the pulse sequences used for in vivo DTI of articular cartilage and discus general strategies for protocol optimization. We provide a comprehensive review of measurements of DTI of articular cartilage from ex vivo validation experiments to its recent clinical applications. PMID:25865215

  17. Techniques and applications of in vivo diffusion imaging of articular cartilage.

    PubMed

    Raya, José G

    2015-06-01

    Early in the process of osteoarthritis (OA) the composition (water, proteoglycan [PG], and collagen) and structure of articular cartilage is altered leading to changes in its mechanical properties. A technique that can assess the composition and structure of the cartilage in vivo can provide insight in the mechanical integrity of articular cartilage and become a powerful tool for the early diagnosis of OA. Diffusion tensor imaging (DTI) has been proposed as a biomarker for cartilage composition and structure. DTI is sensitive to the PG content through the mean diffusivity and to the collagen architecture through the fractional anisotropy. However, the acquisition of DTI of articular cartilage in vivo is challenging due to the short T2 of articular cartilage (∼40 ms at 3 Tesla) and the high resolution needed (0.5-0.7 mm in plane) to depict the cartilage anatomy. We describe the pulse sequences used for in vivo DTI of articular cartilage and discus general strategies for protocol optimization. We provide a comprehensive review of measurements of DTI of articular cartilage from ex vivo validation experiments to its recent clinical applications. PMID:25865215

  18. Thermal energy effects on articular cartilage: a multidisciplinary evaluation

    NASA Astrophysics Data System (ADS)

    Kaplan, Lee D.; Ernsthausen, John; Ionescu, Dan S.; Studer, Rebecca K.; Bradley, James P.; Chu, Constance R.; Fu, Freddie H.; Farkas, Daniel L.

    2002-05-01

    Partial thickness articular cartilage lesions are commonly encountered in orthopedic surgery. These lesions do not have the ability to heal by themselves, due to lack of vascular supply. Several types of treatment have addressed this problem, including mechanical debridement and thermal chondroplasty. The goal of these treatments is to provide a smooth cartilage surface and prevent propagation of the lesions. Early thermal chondroplasty was performed using lasers, and yielded very mixed results, including severe damage to the cartilage, due to poor control of the induced thermal effects. This led to the development (including commercial) of probes using radiofrequency to generate the thermal effects desired for chondroplasty. Similar concerns over the quantitative aspects and control ability of the induced thermal effects in these treatments led us to test the whole range of complex issues and parameters involved. Our investigations are designed to simultaneously evaluate clinical conditions, instrument variables for existing radiofrequency probes (pressure, speed, distance, dose) as well as the associated basic science issues such as damage temperature and controllability (down to the subcellular level), damage geometry, and effects of surrounding conditions (medium, temperature, flow, pressure). The overall goals of this work are (1) to establish whether thermal chondroplasty can be used in a safe and efficacious manner, and (2) provide a prescription for multi-variable optimization of the way treatments are delivered, based on quantitative analysis. The methods used form an interdisciplinary set, to include precise mechanical actuation, high accuracy temperature and temperature gradient control and measurement, advanced imaging approaches and mathematical modeling.

  19. Regeneration of articular cartilage using adipose stem cells.

    PubMed

    Im, Gun-Il

    2016-07-01

    Articular cartilage (AC) has limited potential for self-regeneration and damage to AC eventually leads to the development and progression of osteoarthritis (OA). Cell implantation strategies have emerged as a new treatment modality to regenerate AC. Adipose stem cells/adipose-derived stromal cells (ASCs) have gained attention due to their abundance, excellent proliferative potential, and minimal morbidity during harvest. These advantages lower the cost of cell therapy by circumventing time-consuming procedure of culture expansion. ASCs have drawn attention as a potential source for cartilage regeneration since the feasibility of chondrogenesis from ASCs was first reported. After several groups reported inferior chondrogenesis from ASCs, numerous methods were devised to overcome the intrinsic properties. Most in vivo animal studies have reported good results using predifferentiated or undifferentiated, autologous or allogeneic ASCs to regenerate cartilage in osteochondral defects or surgically-induced OA. In this review, we summarize literature on the isolation and in vitro differentiation processes of ASCs, in vivo studies to regenerate AC in osteochondral defects and OA using ASCs, and clinical applications of ASCs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1830-1844, 2016. PMID:26990234

  20. Tribology approach to the engineering and study of articular cartilage.

    PubMed

    Wimmer, Markus A; Grad, Sibylle; Kaup, Thomas; Hänni, Markus; Schneider, Erich; Gogolewski, Sylwester; Alini, Mauro

    2004-01-01

    This study has been based on the assumption that articular motion is an important aspect of mechanotransduction in synovial joints. For this reason a new bioreactor concept, able to reproduce joint kinematics more closely, has been designed. The prototype consists of a rotating scaffold and/or cartilage pin, which is pressed onto an orthogonally rotating ball. By oscillating pin and ball in phase difference, elliptical displacement trajectories are generated that are similar to the motion paths occurring in vivo. Simultaneously, dynamic compression may be applied with a linear actuator, while two-step-motors generate the rotation of pin and ball. The whole apparatus is placed in an incubator. The control station is located outside. Preliminary investigations at the gene expression level demonstrated promising results. Compared with free-swelling control and/or simply compression-loaded samples, chondrocyte-seeded scaffolds as well as nasal cartilage explants exposed to interface motion both showed elevated levels of cartilage oligomeric matrix protein mRNA. The final design of the bioreactor will include four individual stations in line, which will facilitate the investigation of motion-initiated effects at the contacting surfaces in more detail. PMID:15588403

  1. Evidence for enhanced collagen type III deposition focally in the territorial matrix of osteoarthritic hip articular cartilage

    PubMed Central

    Hosseininia, S.; Weis, M.A.; Rai, J.; Kim, L.; Funk, S.; Dahlberg, L.E.; Eyre, D.R.

    2016-01-01

    SUMMARY Objective To determine if type III collagen is concentrated in the chymotrypsin-extractable collagen pool from osteoarthritic articular cartilage to assess its potential as a biomarker of Osteoarthritis (OA) pathogenic mechanisms. Methods Full thickness articular cartilage from grossly normal surfaces was analyzed from femoral heads, obtained at hip replacement surgery, from OA (n = 10) and fracture (n = 10) patients. Collagen, extracted by α-chymotrypsin, was characterized by SDS-PAGE/Western blot analysis, ELISA and immunohistochemistry using monoclonal antibodies specific to collagens types II and III. Results α-Chymotrypsin extracted more collagen from OA than control cartilage. The extractable pool included collagen types II and III from both OA and control hips. Importantly, OA cartilage contained 6-fold more collagen type III than control cartilage, based on ELISA. The estimated total tissue ratio of collagen III/II was in the 1–10% range for individual OA cartilage samples, based on pepsin-solubilized collagen using SDS-PAGE densitometry. Collagen type III N-propeptide trimers were the main molecular fragments seen on Western blot analysis of OA and control extracts. The chymotrypsin-extracted type II collagen gave primarily full-length α1(II) chains and chain fragments of α1(II) on Western blot analysis from both OA and control tissues. Immunohistochemistry showed that type III collagen was more concentrated in the upper half of OA cartilage and in the territorial matrix around individual chondrocytes and chondrocyte clusters. Conclusions The findings confirm that collagen type III deposition occurs in adult articular cartilage but significantly more pronounced in osteoarthritic joints, presenting a potential marker of matrix repair or pathobiology. PMID:26790721

  2. Amino acid racemization reveals differential protein turnover in osteoarthritic articular and meniscal cartilages

    PubMed Central

    Stabler, Thomas V; Byers, Samuel S; Zura, Robert D; Kraus, Virginia Byers

    2009-01-01

    Introduction Certain amino acids within proteins have been reported to change from the L form to the D form over time. This process is known as racemization and is most likely to occur in long-lived low-turnover tissues such as normal cartilage. We hypothesized that diseased tissue, as found in an osteoarthritic (OA) joint, would have increased turnover reflected by a decrease in the racemized amino acid content. Methods Using high-performance liquid chromatography methods, we quantified the L and D forms of amino acids reported to racemize in vivo on a biological timescale: alanine, aspartate (Asp), asparagine (Asn), glutamate, glutamine, isoleucine, leucine (Leu), and serine (Ser). Furthermore, using a metabolically inactive control material (tooth dentin) and a control material with normal metabolism (normal articular cartilage), we developed an age adjustment in order to make inferences about the state of protein turnover in cartilage and meniscus. Results In the metabolically inactive control material (n = 25, ages 13 to 80 years) and the normal metabolizing control material (n = 19, ages 17 to 83 years), only Asp + Asn (Asx), Ser, and Leu showed a significant change (increase) in racemization with age (P < 0.01). The age-adjusted proportions of racemized to total amino acid (D/D+L expressed as a percentage of the control material) for Asx, Ser, and Leu when compared with the normal articular cartilage control were 97%, 74%, and 73% in OA meniscal cartilage and 97%, 70%, and 78% in OA articular cartilage. We also observed lower amino acid content in OA articular and meniscal cartilages compared with normal articular cartilage as well as a loss of total amino acids with age in the OA meniscal but not the OA articular cartilage. Conclusions These data demonstrate comparable anabolic responses for non-lesioned OA articular cartilage and OA meniscal cartilage but an excess of catabolism over anabolism for the meniscal cartilage. PMID:19267899

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

    NASA Astrophysics Data System (ADS)

    Yin, Jianhua; Xia, Yang

    2014-12-01

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

  4. Tissue-Engineered Articular Cartilage Exhibits Tension-Compression Nonlinearity Reminiscent of the Native Cartilage

    PubMed Central

    Kelly, Terri-Ann N.; Roach, Brendan L.; Weidner, Zachary D.; Mackenzie-Smith, Charles R.; O'Connell, Grace D.; Lima, Eric G.; Stoker, Aaron M.; Cook, James L.; Ateshian, Gerard A.; Hung, Clark T.

    2013-01-01

    The tensile modulus of articular cartilage is much larger than its compressive modulus. This tension-compression nonlinearity enhances interstitial fluid pressurization and decreases the frictional coefficient. The current set of studies examines the tensile and compressive properties of cylindrical chondrocyte-seeded agarose constructs over different developmental stages through a novel method that combines osmotic loading, video microscopy, and uniaxial unconfined compression testing. This method was previously used to examine tension-compression nonlinearity in native cartilage. Engineered cartilage, cultured under free-swelling (FS) or dynamically loaded (DL) conditions, was tested in unconfined compression in hypertonic and hypotonic salt solutions. The apparent equilibrium modulus decreased with increasing salt concentration, indicating that increasing the bath solution osmolarity shielded the fixed charges within the tissue, shifting the measured moduli along the tension-compression curve and revealing the intrinsic properties of the tissue. With this method, we were able to measure the tensile (401±83 kPa for FS and 678±473 kPa for DL) and compressive (161±33 kPa for FS and 348±203 kPa for DL) moduli of the same engineered cartilage specimens. These moduli are comparable to values obtained from traditional methods, validating this technique for measuring the tensile and compressive properties of hydrogel-based constructs. This study shows that engineered cartilage exhibits tension-compression nonlinearity reminiscent of the native tissue, and that dynamic deformational loading can yield significantly higher tensile properties. PMID:23791084

  5. Cartilage-Repair Innovation at a Standstill: Methodologic and Regulatory Pathways to Breaking Free.

    PubMed

    Lyman, Stephen; Nakamura, Norimasa; Cole, Brian J; Erggelet, Christoph; Gomoll, Andreas H; Farr, Jack

    2016-08-01

    Articular cartilage defects strongly predispose patients to developing early joint degeneration and osteoarthritis, but for more than 15 years, no new cartilage-repair technologies that we know of have been approved by the U.S. Food and Drug Administration. Many studies examining novel approaches to cartilage repair, including cell, tissue, or matrix-based techniques, have shown great promise, but completing randomized controlled trials (RCTs) to establish safety and efficacy has been challenging, providing a major barrier to bringing these innovations into clinical use. In this article, we review reasons that surgical innovations are not well-suited for testing through RCTs. We also discuss how analytical methods for reducing bias, such as propensity scoring, make prospective observational studies a potentially viable alternative for testing the safety and efficacy of cartilage-repair and other novel therapies, offering the real possibility of therapeutic innovation. PMID:27489325

  6. Elastin fibers display a versatile microfibril network in articular cartilage depending on the mechanical microenvironments.

    PubMed

    He, Bo; Wu, Jian Ping; Chen, Hong Hui; Kirk, Thomas Brett; Xu, Jiake

    2013-09-01

    Elastin fibers are major extracellular matrix macromolecules that are critical in maintaining the elasticity and resilience of tissues such as blood vessels, lungs and skins. However, the role of elastin in articular cartilage is poorly defined. The present study investigated the organization of elastin fiber in articular cartilage, its relationship to collagen fibers and the architecture of elastin fibers from different mechanical environments by using a kangaroo model. Five morphologies of elastin fibers were identified: Straight fiber, straight fiber with branches, branching fibers directly associated with chondrocyte, wave fiber and fine elastin. The architecture of the elastin network varied significantly with cartilage depth. In the most superficial layer of tibial plateau articular cartilage, dense elastin fibers formed a distinctive cobweb-like meshwork which was parallel to the cartilage surface. In the superficial zone, elastin fibers were well organized in a preferred orientation which was parallel to collagen fibers. In the deep zone, no detectable elastin fiber was found. Moreover, differences in the organization of elastin fibers were also observed between articular cartilage from the tibial plateau, femoral condyle, and distal humerus. This study unravels the detailed microarchitecture of elastin fibers which display a well-organized three-dimensional versatile network in articular cartilage. Our findings imply that elastin fibers may play a crucial role in maintaining the integrity, elasticity, and the mechanical properties of articular cartilage, and that the local mechanical environment affects the architectural development of elastin fibers. PMID:23649803

  7. Comprehensive Genome-Wide Transcriptomic Analysis of Immature Articular Cartilage following Ischemic Osteonecrosis of the Femoral Head in Piglets

    PubMed Central

    Adapala, Naga Suresh; Kim, Harry K. W.

    2016-01-01

    Objective Ischemic osteonecrosis of the femoral head (ONFH) in piglets results in an ischemic injury to the immature articular cartilage. The molecular changes in the articular cartilage in response to ONFH have not been investigated using a transcriptomic approach. The purpose of this study was to perform a genome-wide transcriptomic analysis to identify genes that are upregulated in the immature articular cartilage following ONFH. Methods ONFH was induced in the right femoral head of 6-week old piglets. The unoperated femoral head was used as the normal control. At 24 hours (acute ischemic-hypoxic injury), 2 weeks (avascular necrosis in the femoral head) and 4 weeks (early repair) after surgery (n = 4 piglets/time point), RNA was isolated from the articular cartilage of the femoral head. A microarray analysis was performed using Affymetrix Porcine GeneChip Array. An enrichment analysis and functional clustering of the genes upregulated due to ONFH were performed using DAVID and STRING software, respectively. The increased expression of selected genes was confirmed by a real-time qRTPCR analysis. Results Induction of ONFH resulted in the upregulation of 383 genes at 24 hours, 122 genes at 2 weeks and 124 genes at 4 weeks compared to the normal controls. At 24 hours, the genes involved in oxidoreductive, cell-survival, and angiogenic responses were significantly enriched among the upregulated genes. These genes were involved in HIF-1, PI3K-Akt, and MAPK signaling pathways. At 2 weeks, secretory and signaling proteins involved in angiogenic and inflammatory responses, PI3K-Akt and matrix-remodeling pathways were significantly enriched. At 4 weeks, genes that represent inflammatory cytokines and chemokine signaling pathways were significantly enriched. Several index genes (genes that are upregulated at more than one time point following ONFH and are known to be important in various biological processes) including HIF-1A, VEGFA, IL-6, IL6R, IL-8, CCL2, FGF2, TGFB2

  8. Chondrocyte survival in articular cartilage: the influence of subchondral bone in a bovine model.

    PubMed

    Amin, A K; Huntley, J S; Simpson, A H R W; Hall, A C

    2009-05-01

    The aim of this study was to determine whether subchondral bone influences in situ chondrocyte survival. Bovine explants were cultured in serum-free media over seven days with subchondral bone excised from articular cartilage (group A), subchondral bone left attached to articular cartilage (group B), and subchondral bone excised but co-cultured with articular cartilage (group C). Using confocal laser scanning microscopy, fluorescent probes and biochemical assays, in situ chondrocyte viability and relevant biophysical parameters (cartilage thickness, cell density, culture medium composition) were quantified over time (2.5 hours vs seven days). There was a significant increase in chondrocyte death over seven days, primarily within the superficial zone, for group A, but not for groups B or C (p < 0.05). There was no significant difference in cartilage thickness or cell density between groups A, B and C (p > 0.05). Increases in the protein content of the culture media for groups B and C, but not for group A, suggested that the release of soluble factors from subchondral bone may have influenced chondrocyte survival. In conclusion, subchondral bone significantly influenced chondrocyte survival in articular cartilage during explant culture. The extrapolation of bone-cartilage interactions in vitro to the clinical situation must be made with caution, but the findings from these experiments suggest that future investigation into in vivo mechanisms of articular cartilage survival and degradation must consider the interactions of cartilage with subchondral bone. PMID:19407309

  9. Gene Expression Profiling Reveals Similarities between the Spatial Architectures of Postnatal Articular and Growth Plate Cartilage

    PubMed Central

    Chau, Michael; Lui, Julian C.; Landman, Ellie B. M.; Späth, Stephan-Stanislaw; Vortkamp, Andrea; Baron, Jeffrey; Nilsson, Ola

    2014-01-01

    Articular and growth plate cartilage are discrete tissues but arise from a common cartilaginous condensation and have comparable spatial architectures consisting of distinct layers of chondrocytes. To investigate similarities and differences between articular and growth plate cartilage and to explore transcriptional changes that occur during the onset of their divergence, we performed manual microdissection of 10-day-old rat proximal tibias, microarray analysis, bioinformatics, and real-time PCR to compare gene expression profiles in individual cartilage layers. We found that many genes that were spatially upregulated in the intermediate/deep zone of articular cartilage were also spatially upregulated in the resting zone of growth plate cartilage (overlap greater than expected by chance, P<0.001). Interestingly, the superficial zone of articular cartilage showed an expression profile with similarities to both the proliferative and hypertrophic zones of growth plate cartilage (P<0.001 each). Additionally, significant numbers of known proliferative zone markers (3 out of 6) and hypertrophic zone markers (27 out of 126) were spatially upregulated in the superficial zone (more than expected by chance, P<0.001 each). In conclusion, we provide evidence that the intermediate/deep zone of articular cartilage has a gene expression profile more similar to that of the resting zone of growth plate cartilage, whereas the superficial zone has a gene expression profile more similar to those of the proliferative and hypertrophic zones. These findings suggest that the superficial zone chondrocytes of articular cartilage differentiate according to a program that is not completely different from but instead has distinct similarities to the hypertrophic differentiation program of growth plate chondrocytes. We also present functional signaling pathways implicated by differential gene expression between articular and growth plate cartilage during their initial separation by the

  10. Radiofrequency (electrosurgical) ablation of articular cartilage: a study in sheep.

    PubMed

    Turner, A S; Tippett, J W; Powers, B E; Dewell, R D; Mallinckrodt, C H

    1998-09-01

    The objective of this study was to examine the effect of a bipolar ablation probe on experimentally roughened articular cartilage and compare it with the traditional mechanical shaving technique using the knee joint of sheep. Twenty-eight skeletally mature ewes were divided randomly into two groups: one group was treated with a rotating shaving device and another group was treated using the bipolar ablation probe (Bipolar Arthroscopic Probe; Electroscope, Inc, Boulder, CO). Animals were killed at 0, 6, 12, and 24 weeks, and histological sections of the experimental limbs were compared with sections of the opposite limb using a modified Mankin scale. The following variables were used to determine scores: surface (0-6), cells (0-4), hypocellularity (0-3), matrix staining (transitional zone [0-4], radiate zone [0-4], and focal empty lacunae or hypereosinophilic cells (0-3). Differences in scores for all response variables were calculated as treated limb minus sham limb. Response variables were formed: score >0 recoded as 1 (favorable response treated better than sham), score of 0 recoded as 2 (neutral response no differences), and score <0 recoded as 3 (unfavorable response treated worse than sham). Bipolar ablative probe-treated limbs had 14.29% favorable responses and 35.71% favorable or neutral responses, whereas shave-treated limbs had 0% favorable and only 7.14% favorable or neutral responses. For all variables, bipolar ablative probe-treated limbs had more favorable responses. The less severe histological change in the bipolar ablative probe-treated joints compared with the shave-treated joints suggests that bipolar ablation of articular cartilage may be a better treatment for chondromalacia than the usual shaving methods of debridement. Further, there were no pathological changes in the subchondral bone. PMID:9754476

  11. Regenerating cartilages by engineered ASCs: prolonged TGF-β3/BMP-6 expression improved articular cartilage formation and restored zonal structure.

    PubMed

    Lu, Chia-Hsin; Yeh, Tsung-Szu; Yeh, Chia-Lin; Fang, Yu-Hua Dean; Sung, Li-Yu; Lin, Shih-Yeh; Yen, Tzu-Chen; Chang, Yu-Han; Hu, Yu-Chen

    2014-01-01

    Adipose-derived stem cells (ASCs) hold promise for cartilage regeneration but their chondrogenesis potential is inferior. Here, we used a baculovirus (BV) system that exploited FLPo/Frt-mediated transgene recombination and episomal minicircle formation to genetically engineer rabbit ASCs (rASCs). The BV system conferred prolonged and robust TGF-β3/BMP-6 expression in rASCs cultured in porous scaffolds, which critically augmented rASCs chondrogenesis and suppressed osteogenesis/hypertrophy, leading to the formation of cartilaginous constructs with improved maturity and mechanical properties in 2-week culture. Twelve weeks after implantation into full-thickness articular cartilage defects in rabbits, these engineered constructs regenerated neocartilages that resembled native hyaline cartilages in cell morphology, matrix composition and mechanical properties. The neocartilages also displayed cartilage-specific zonal structures without signs of hypertrophy and degeneration, and eventually integrated with host cartilages. In contrast, rASCs that transiently expressed TGF-β3/BMP-6 underwent osteogenesis/hypertrophy and resulted in the formation of inferior cartilaginous constructs, which after implantation regenerated fibrocartilages. These data underscored the crucial role of TGF-β3/BMP-6 expression level and duration in rASCs in the cell differentiation, constructs properties and in vivo repair. The BV-engineered rASCs that persistently express TGF-β3/BMP-6 improved the chondrogenesis, in vitro cartilaginous constructs production and in vivo hyaline cartilage regeneration, thus representing a remarkable advance in cartilage engineering. PMID:23851345

  12. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  13. Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine.

    PubMed

    Nazempour, A; Van Wie, B J

    2016-05-01

    Articular cartilage (AC) is a highly organized connective tissue lining, covering the ends of bones within articulating joints. Its highly ordered structure is essential for stable motion and provides a frictionless surface easing load transfer. AC is vulnerable to lesions and, because it is aneural and avascular, it has limited self-repair potential which often leads to osteoarthritis. To date, no fully successful treatment for osteoarthritis has been reported. Thus, the development of innovative therapeutic approaches is desperately needed. Autologous chondrocyte implantation, the only cell-based surgical intervention approved in the United States for treating cartilage defects, has limitations because of de-differentiation of articular chondrocytes (AChs) upon in vitro expansion. De-differentiation can be abated if initial populations of AChs are co-cultured with mesenchymal stem cells (MSCs), which not only undergo chondrogenesis themselves but also support chondrocyte vitality. In this review we summarize studies utilizing AChs, non-AChs, and MSCs and compare associated outcomes. Moreover, a comprehensive set of recent human studies using chondrocytes to direct MSC differentiation, MSCs to support chondrocyte re-differentiation and proliferation in co-culture environments, and exploratory animal intra- and inter-species studies are systematically reviewed and discussed in an innovative manner allowing side-by-side comparisons of protocols and outcomes. Finally, a comprehensive set of recommendations are made for future studies. PMID:26987846

  14. Patterns of radiocarpal joint articular cartilage wear in cadavers.

    PubMed

    Gorniak, Gerard C; Conrad, Will; Conrad, Erin; Decker, Bonnie

    2012-05-01

    The radiocarpal joint transmits about 80% of the compression forces crossing the wrist. However, primary osteoarthritis of this joint is surprisingly uncommon, suggesting that articular cartilage wear is not sufficient to produce arthritic symptoms. By examining the distal radius, scaphoid, and lunate in aged cadavers, wear patterns were charted and measured, allowing assessment of radiocarpal joint wear and mechanics. Bilateral radiocarpal joints of 16 females and 14 males (age 77.7 ± 14.4, N = 30) were exposed and measurements of the wear recorded microscopically. Wear locations were mapped, and X-Y loci and wear areas calculated. Gender right and sides compared. Over 95% of distal radius wear showed distinct radial-scaphoid and radial-lunate wear areas. These bilateral areas were in the palmar half of the distal radius. One main central wear area was seen in 95% of the scaphoid, and 97% of the lunate articular surfaces that were examined. Articular wear showed a circular pattern and was minimal in 95.7% of the surfaces, and the lunate showed the largest wear area. Wear patterns in males and females support the literature that for most ADLs the wrist is in slight extension and ulnar deviation. There are gender differences, but wear areas between sides were similar. Female wear indicates their wrist is positioned more often in a more extended and ulnarly deviated position than males. The wear patterns suggest rotational movements of the scaphoid and lunate during wrist motion and that the wrist is most often used in neutral flexion/extension to slight extension. PMID:22095798

  15. Effects of salicylates and other nonsteroidal anti-inflammatory drugs on articular cartilage.

    PubMed

    Brandt, K D; Palmoski, M J

    1984-07-13

    According to in vivo experimental data, salicylates and several other nonsteroidal anti-inflammatory agents suppress proteoglycan biosynthesis in normal and degenerating articular cartilage. Therapeutic levels of aspirin in vivo had a similar adverse effect on degenerating cartilage, as noted in two canine models of osteoarthritis and cartilage atrophy. Because the effective daily antirheumatic dose of nonsteroidal anti-inflammatory drugs is lower than that of salicylates, these drugs may have less negative effects on degenerating articular cartilage. However, clinical significance cannot be extrapolated from these experimental data. PMID:6465163

  16. Time-dependent processes in stem cell-based tissue engineering of articular cartilage

    PubMed Central

    Gadjanski, Ivana; Spiller, Kara; Vunjak-Novakovic, Gordana

    2012-01-01

    Articular cartilage (AC), situated in diarthrodial joints at the end of the long bones, is composed of a single cell type (chondrocytes) embedded in dense extracellular matrix comprised of collagens and proteoglycans. AC is avascular and alymphatic and is not innervated. At first glance, such a seemingly simple tissue appears to be an easy target for the rapidly developing field of tissue engineering. However, cartilage engineering has proven to be very challenging. We focus on time-dependent processes associated with the development of native cartilage starting from stem cells, and the modalities for utilizing these processes for tissue engineering of articular cartilage. PMID:22016073

  17. Imaging articular cartilage using second harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Mansfield, Jessica C.; Winlove, C. Peter; Knapp, Karen; Matcher, Stephen J.

    2006-02-01

    Sub cellular resolution images of equine articular cartilage have been obtained using both second harmonic generation microscopy (SHGM) and two-photon fluorescence microscopy (TPFM). The SHGM images clearly map the distribution of the collagen II fibers within the extracellular matrix while the TPFM images show the distribution of endogenous two-photon fluorophores in both the cells and the extracellular matrix, highlighting especially the pericellular matrix and bright 2-3μm diameter features within the cells. To investigate the source of TPF in the extracellular matrix experiments have been carried out to see if it may originate from the proteoglycans. Pure solutions of the following proteoglycans hyaluronan, chondroitin sulfate and aggrecan have been imaged, only the aggrecan produced any TPF and here the intensity was not great enough to account for the TPF in the extracellular matrix. Also cartilage samples were subjected to a process to remove proteoglycans and cellular components. After this process the TPF from the samples had decreased by a factor of two, with respect to the SHG intensity.

  18. Epigenetic regulation in chondrocyte phenotype maintenance for cell-based cartilage repair

    PubMed Central

    Duan, Li; Liang, Yujie; Ma, Bin; Zhu, Weimin; Wang, Daping

    2015-01-01

    Loss of hyaline chondrocyte phenotype during the monolayer culture in vitro is a major obstacle for cell-based articular cartilage repair. Increasing evidence implicates an important role of the epigenetic regulation in maintaining the chondrocyte phenotype. DNA methylation, histone modifications and microRNAs have all been shown to contribute to chondrocyte dedifferentiation and hypertrophy. Moreover, the interplay among epigenetic regulators forms a complicated epigenetic network in regulating chondrocyte dedifferentiation. This review provides a detailed overview of the epigenetic regulation in maintaining the chondrocyte phenotype for chondrocyte-based cartilage repair. PMID:26807163

  19. Multi-parametric MRI characterization of enzymatically degraded articular cartilage.

    PubMed

    Nissi, Mikko J; Salo, Elli-Noora; Tiitu, Virpi; Liimatainen, Timo; Michaeli, Shalom; Mangia, Silvia; Ellermann, Jutta; Nieminen, Miika T

    2016-07-01

    Several laboratory and rotating frame quantitative MRI parameters were evaluated and compared for detection of changes in articular cartilage following selective enzymatic digestion. Bovine osteochondral specimens were subjected to 44 h incubation in control medium or in collagenase or chondroitinase ABC to induce superficial collagen or proteoglycan (glycosaminoglycan) alterations. The samples were scanned at 9.4 T for T1 , T1 Gd (dGEMRIC), T2 , adiabatic T1 ρ , adiabatic T2 ρ , continuous-wave T1 ρ , TRAFF2 , and T1 sat relaxation times and for magnetization transfer ratio (MTR). For reference, glycosaminoglycan content, collagen fibril orientation and biomechanical properties were determined. Changes primarily in the superficial cartilage were noted after enzymatic degradation. Most of the studied parameters were sensitive to the destruction of collagen network, whereas glycosaminoglycan depletion was detected only by native T1 and T1 Gd relaxation time constants throughout the tissue and by MTR superficially. T1 , adiabatic T1 ρ , adiabatic T2 ρ , continuous-wave T1 ρ , and T1 sat correlated significantly with the biomechanical properties while T1 Gd correlated with glycosaminoglycan staining. The findings indicated that most of the studied MRI parameters were sensitive to both glycosaminoglycan content and collagen network integrity, with changes due to enzymatic treatment detected primarily in the superficial tissue. Strong correlation of T1 , adiabatic T1ρ , adiabatic T2 ρ , continuous-wave T1 ρ , and T1 sat with the altered biomechanical properties, reflects that these parameters were sensitive to critical functional properties of cartilage. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1111-1120, 2016. PMID:26662555

  20. Winner of the 1996 Cabaud Award. The effect of lifelong exercise on canine articular cartilage.

    PubMed

    Newton, P M; Mow, V C; Gardner, T R; Buckwalter, J A; Albright, J P

    1997-01-01

    The effect of long-term exercise on canine knees was studied to determine whether an increased level of lifelong weightbearing exercise causes degeneration, or changes that may lead to degeneration, of articular cartilage. Eleven dogs were exercised on a treadmill at 3 km/hr for 75 minutes 5 days a week for 527 weeks while carrying jackets weighing 130% of their body weight. Ten control dogs were allowed unrestricted activity in cages for the 550 weeks. At the completion of the study all knee joints were inspected for evidence of joint injury and degeneration. Articular cartilage surfaces from the medial tibial plateau were examined by light microscopy, the cartilage thickness was measured, and the intrinsic material properties were determined by mechanical testing. No joints had ligament or meniscal injuries, cartilage erosions, or osteophytes. Light microscopy did not demonstrate cartilage fibrillation or differences in safranin O staining of the tibial articular cartilages between the two groups. Furthermore, the tibial articular cartilage thickness and mechanical properties did not differ between the two groups. These results show that a lifetime of regular weightbearing exercise in dogs with normal joints did not cause alterations in the structure and mechanical properties of articular cartilage that might lead to joint degeneration. PMID:9167804

  1. Diffusion coefficients of articular cartilage for different CT and MRI contrast agents.

    PubMed

    Kulmala, K A M; Korhonen, R K; Julkunen, P; Jurvelin, J S; Quinn, T M; Kröger, H; Töyräs, J

    2010-10-01

    In contrast enhanced magnetic resonance imaging (MRI) and computed tomography (CT), the equilibrium distribution of anionic contrast agent is expected to reflect the fixed charged density (FCD) of articular cartilage. Diffusion is mainly responsible for the transport of contrast agents into cartilage. In osteoarthritis, cartilage composition changes at early stages of disease, and solute diffusion is most likely affected. Thus, investigation of contrast agent diffusion could enable new methods for imaging of cartilage composition. The aim of this study was to determine the diffusion coefficient of four contrast agents (ioxaglate, gadopentetate, iodide, gadodiamide) in bovine articular cartilage. The contrast agents were different in molecular size and charge. In peripheral quantitative CT experiments, penetration of contrast agent into the tissue was allowed either through the articular surface or through deep cartilage. To determine diffusion coefficients, a finite element model based on Fick's law was fitted to experimental data. Diffusion through articular surface was faster than through deep cartilage with every contrast agent. Iodide, being of atomic size, diffused into the cartilage significantly faster (q<0.05) than the other three contrast agents, for either transport direction. The diffusion coefficients of all clinical contrast agents (ioxaglate, gadopentetate and gadodiamide) were relatively low (142.8-253.7 μm(2)/s). In clinical diagnostics, such slow diffusion may not reach equilibrium and this jeopardizes the determination of FCD by standard methods. However, differences between diffusion through articular surface and deep cartilage, that are characterized by different tissue composition, suggest that diffusion coefficients may correlate with cartilage composition. Present method could therefore enable image-based assessment of cartilage composition by determination of diffusion coefficients within cartilage tissue. PMID:20594900

  2. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model

    PubMed Central

    Cheng, N-T.; Cui, Y-P.

    2016-01-01

    Objectives Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Methods Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Results Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Conclusion Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a

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

    PubMed Central

    Orth, Patrick; Rey-Rico, Ana; Venkatesan, Jagadeesh K; Madry, Henning; Cucchiarini, Magali

    2014-01-01

    Protocols based on the delivery of stem cells are currently applied in patients, showing encouraging results for the treatment of articular cartilage lesions (focal defects, osteoarthritis). Yet, restoration of a fully functional cartilage surface (native structural organization and mechanical functions) especially in the knee joint has not been reported to date, showing the need for improved designs of clinical trials. Various sources of progenitor cells are now available, originating from adult tissues but also from embryonic or reprogrammed tissues, most of which have already been evaluated for their chondrogenic potential in culture and for their reparative properties in vivo upon implantation in relevant animal models of cartilage lesions. Nevertheless, particular attention will be needed regarding their safe clinical use and their potential to form a cartilaginous repair tissue of proper quality and functionality in the patient. Possible improvements may reside in the use of biological supplements in accordance with regulations, while some challenges remain in establishing standardized, effective procedures in the clinics. PMID:24520197

  4. Extraction of mechanical properties of articular cartilage from osmotic swelling behavior monitored using high frequency ultrasound.

    PubMed

    Wang, Q; Zheng, Y P; Niu, H J; Mak, A F T

    2007-06-01

    Articular cartilage is a biological weight-bearing tissue covering the bony ends of articulating joints. Negatively charged proteoglycan (PG) in articular cartilage is one of the main factors that govern its compressive mechanical behavior and swelling phenomenon. PG is nonuniformly distributed throughout the depth direction, and its amount or distribution may change in the degenerated articular cartilage such as osteoarthritis. In this paper, we used a 50 MHz ultrasound system to study the depth-dependent strain of articular cartilage under the osmotic loading induced by the decrease of the bathing saline concentration. The swelling-induced strains under the osmotic loading were used to determine the layered material properties of articular cartilage based on a triphasic model of the free-swelling. Fourteen cylindrical cartilage-bone samples prepared from fresh normal bovine patellae were tested in situ in this study. A layered triphasic model was proposed to describe the depth distribution of the swelling strain for the cartilage and to determine its aggregate modulus H(a) at two different layers, within which H(a) was assumed to be linearly dependent on the depth. The results showed that H(a) was 3.0+/-3.2, 7.0+/-7.4, 24.5+/-11.1 MPa at the cartilage surface, layer interface, and deep region, respectively. They are significantly different (p<0.01). The layer interface located at 70%+/-20% of the overall thickness from the uncalcified-calcified cartilage interface. Parametric analysis demonstrated that the depth-dependent distribution of the water fraction had a significant effect on the modeling results but not the fixed charge density. This study showed that high-frequency ultrasound measurement together with triphasic modeling is practical for quantifying the layered mechanical properties of articular cartilage nondestructively and has the potential for providing useful information for the detection of the early signs of osteoarthritis. PMID:17536909

  5. Chitosan/poly(epsilon-caprolactone) blend scaffolds for cartilage repair.

    PubMed

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

    2011-02-01

    Chitosan (CHT)/poly(ɛ-caprolactone) (PCL) blend 3D fiber-mesh scaffolds were studied as possible support structures for articular cartilage tissue (ACT) repair. Micro-fibers were obtained by wet-spinning of three different polymeric solutions: 100:0 (100CHT), 75:25 (75CHT) and 50:50 (50CHT) wt.% CHT/PCL, using a common solvent solution of 100 vol.% of formic acid. Scanning electron microscopy (SEM) analysis showed a homogeneous surface distribution of PCL. PCL was well dispersed throughout the CHT phase as analyzed by differential scanning calorimetry and Fourier transform infrared spectroscopy. The fibers were folded into cylindrical moulds and underwent a thermal treatment to obtain the scaffolds. μCT analysis revealed an adequate porosity, pore size and interconnectivity for tissue engineering applications. The PCL component led to a higher fiber surface roughness, decreased the scaffolds swelling ratio and increased their compressive mechanical properties. Biological assays were performed after culturing bovine articular chondrocytes up to 21 days. SEM analysis, live-dead and metabolic activity assays showed that cells attached, proliferated, and were metabolically active over all scaffolds formulations. Cartilaginous extracellular matrix (ECM) formation was observed in all formulations. The 75CHT scaffolds supported the most neo-cartilage formation, as demonstrated by an increase in glycosaminoglycan production. In contrast to 100CHT scaffolds, ECM was homogenously deposited on the 75CHT and 50CHT scaffolds. Although mechanical properties of the 50CHT scaffold were better, the 75CHT scaffold facilitated better neo-cartilage formation. PMID:20980050

  6. Determination of the collagen fiber `brushing direction' in articular cartilage by conical-scan polarization-sensitive optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lu, Zenghai; Kasaragod, Deepa; Matcher, Stephen J.

    2014-03-01

    A new imaging technique is presented by introducing the concept of conical scan to the variable-incidenc-angle polarimetry (VIA) previously developed by our group. The technique would facilitate the translating of the VIA technique to the clinic by simplifying the requirements of measurements in two orthogonal planes by using a conical scan protocol. Conical scan PS-OCT images could illustrate directly the azimuthal angle of the collage fibers in birefringent tissue, which was validated by measurements on a bovine tendon. We have showed the unique technique can be used to locate the "brushing direction" of collagen fibers in articular cartilage. Measuring this direction over the cartilage surface could potentially help designing of tissue-engineering scaffolds for cartilage repair.

  7. Genetic Inhibition of Fibroblast Growth Factor Receptor 1 in Knee Cartilage Attenuates the Degeneration of Articular Cartilage in Adult Mice

    PubMed Central

    Weng, Tujun; Yi, Lingxian; Huang, Junlan; Luo, Fengtao; Wen, Xuan; Du, Xiaolan; Chen, Qian; Deng, Chuxia; Chen, Di; Chen, Lin

    2013-01-01

    Objective Fibroblast growth factor (FGF) family members are involved in the regulation of articular cartilage homeostasis. The aim of this study was to investigate the function of FGF receptor 1 (FGFR-1) in the development of osteoarthritis (OA) and its underlying mechanisms. Methods FGFR-1 was deleted from the articular chondrocytes of adult mice in a cartilage-specific and tamoxifen-inducible manner. Two OA models (aging-associated spontaneous OA, and destabilization-induced OA), as well as an antigen-induced arthritis (AIA) model, were established and tested in Fgfr1-deficient and wild-type (WT) mice. Alterations in cartilage structure and the loss of proteoglycan were assessed in the knee joints of mice of either genotype, using these 3 arthritis models. Primary chondrocytes were isolated and the expression of key regulatory molecules was assessed quantitatively. In addition, the effect of an FGFR-1 inhibitor on human articular chondrocytes was examined. Results The gross morphologic features of Fgfr1-deficient mice were comparable with those of WT mice at both the postnatal and adult stages. The articular cartilage of 12-month-old Fgfr1-deficient mice displayed greater aggrecan staining compared to 12-month-old WT mice. Fgfr1 deficiency conferred resistance to the proteoglycan loss induced by AIA and attenuated the development of cartilage destruction after surgically induced destabilization of the knee joint. The chondroprotective effect of FGFR-1 inhibition was largely associated with decreased expression of matrix metalloproteinase 13 (MMP-13) and up-regulation of FGFR-3 in mouse and human articular chondrocytes. Conclusion Disruption of FGFR-1 in adult mouse articular chondrocytes inhibits the progression of cartilage degeneration. Down-regulation of MMP-13 expression and up-regulation of FGFR-3 levels may contribute to the phenotypic changes observed in Fgfr1-deficient mice. PMID:22833219

  8. Comparison of nonlinear mechanical properties of bovine articular cartilage and meniscus.

    PubMed

    Danso, E K; Honkanen, J T J; Saarakkala, S; Korhonen, R K

    2014-01-01

    Nonlinear, linear and failure properties of articular cartilage and meniscus in opposing contact surfaces are poorly known in tension. Relationships between the tensile properties of articular cartilage and meniscus in contact with each other within knee joints are also not known. In the present study, rectangular samples were prepared from the superficial lateral femoral condyle cartilage and lateral meniscus of bovine knee joints. Tensile tests were carried out with a loading rate of 5mm/min until the tissue rupture. Nonlinear properties of the toe region, linear properties in larger strains, and failure properties of both tissues were analysed. The strain-dependent tensile modulus of the toe region, Young's modulus of the linear region, ultimate tensile stress and toughness were on average 98.2, 8.3, 4.0 and 1.9 times greater (p<0.05) for meniscus than for articular cartilage. In contrast, the toe region strain, yield strain and failure strain were on average 9.4, 3.1 and 2.3 times greater (p<0.05) for cartilage than for meniscus. There was a significant negative correlation between the strain-dependent tensile moduli of meniscus and articular cartilage samples within the same joints (r=-0.690, p=0.014). In conclusion, the meniscus possesses higher nonlinear and linear elastic stiffness and energy absorption capability before rupture than contacting articular cartilage, while cartilage has longer nonlinear region and can withstand greater strains before failure. These findings point out different load carrying demands that both articular cartilage and meniscus have to fulfil during normal physiological loading activities of knee joints. PMID:24182695

  9. Comparative potential of juvenile and adult human articular chondrocytes for cartilage tissue formation in three-dimensional biomimetic hydrogels.

    PubMed

    Smeriglio, Piera; Lai, Janice H; Dhulipala, Lakshmi; Behn, Anthony W; Goodman, Stuart B; Smith, Robert L; Maloney, William J; Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Regeneration of human articular cartilage is inherently limited and extensive efforts have focused on engineering the cartilage tissue. Various cellular sources have been studied for cartilage tissue engineering including adult chondrocytes, and embryonic or adult stem cells. Juvenile chondrocytes (from donors below 13 years of age) have recently been reported to be a promising cell source for cartilage regeneration. Previous studies have compared the potential of adult and juvenile chondrocytes or adult and osteoarthritic (OA) chondrocytes. To comprehensively characterize the comparative potential of young, old, and diseased chondrocytes, here we examined cartilage formation by juvenile, adult, and OA chondrocytes in three-dimensional (3D) biomimetic hydrogels composed of poly(ethylene glycol) and chondroitin sulfate. All three human articular chondrocytes were encapsulated in the 3D biomimetic hydrogels and cultured for 3 or 6 weeks to allow maturation and extracellular matrix formation. Outcomes were analyzed using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. After 3 and 6 weeks, juvenile chondrocytes showed a greater upregulation of chondrogenic gene expression than adult chondrocytes, while OA chondrocytes showed a downregulation. Aggrecan and type II collagen deposition and glycosaminoglycan accumulation were high for juvenile and adult chondrocytes but not for OA chondrocytes. Similar trend was observed in the compressive moduli of the cartilage constructs generated by the three different chondrocytes. In conclusion, the juvenile, adult and OA chondrocytes showed differential responses in the 3D biomimetic hydrogels. The 3D culture model described here may also provide a useful tool to further study the molecular differences among chondrocytes from different stages, which can help elucidate the mechanisms for age-related decline in the intrinsic capacity for cartilage repair. PMID:25054343

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

    PubMed

    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. PMID:26294356

  11. Role of uppermost superficial surface layer of articular cartilage in the lubrication mechanism of joints

    PubMed Central

    KUMAR, P.; OKA, M.; TOGUCHIDA, J.; KOBAYASHI, M.; UCHIDA, E.; NAKAMURA, T.; TANAKA, K.

    2001-01-01

    The uppermost superficial surface layer of articular cartilage, the ‘lamina splendens’ which provides a very low friction lubrication surface in articular joints, was investigated using atomic force microscopy (AFM). Complementary specimens were also observed under SEM at −10 °C without dehydration or sputter ion coating. Fresh adult pig osteochondral specimens were prepared from the patellas of pig knee joints and digested with the enzymes, hyaluronidase, chondroitinase ABC and alkaline protease. Friction coefficients between a pyrex glass plate and the osteochondral specimens digested by enzymes as well as natural (undigested) specimens were measured, using a thrust collar apparatus. Normal saline, hyaluronic acid (HA) and a mixture of albumin, globulin, HA (AGH) were used as lubrication media. The surface irregularities usually observed in SEM studies were not apparent under AFM. The articular cartilage surface was resistant to hyaluronidase and also to chondroitinase ABC, but a fibrous structure was exhibited in alkaline protease enzymes-digested specimens. AFM analysis revealed that the thickness of the uppermost superficial surface layer of articular cartilage was between 800 nm and 2 μm in adult pig articular cartilage. The coefficient of friction (c.f.) was significantly higher in chondroitinase ABC and alkaline protease enzymes digested specimens. Generally, in normal saline lubrication medium, c.f. was higher in comparison to HA and AGH lubrication media. The role of the uppermost, superficial surface layer of articular cartilage in the lubrication mechanism of joints is discussed. PMID:11554503

  12. Role of uppermost superficial surface layer of articular cartilage in the lubrication mechanism of joints.

    PubMed

    Kumar, P; Oka, M; Toguchida, J; Kobayashi, M; Uchida, E; Nakamura, T; Tanaka, K

    2001-09-01

    The uppermost superficial surface layer of articular cartilage, the 'lamina splendens' which provides a very low friction lubrication surface in articular joints, was investigated using atomic force microscopy (AFM). Complementary specimens were also observed under SEM at -10 degrees C without dehydration or sputter ion coating. Fresh adult pig osteochondral specimens were prepared from the patellas of pig knee joints and digested with the enzymes, hyaluronidase, chondroitinase ABC and alkaline protease. Friction coefficients between a pyrex glass plate and the osteochondral specimens digested by enzymes as well as natural (undigested) specimens were measured, using a thrust collar apparatus. Normal saline, hyaluronic acid (HA) and a mixture of albumin, globulin, HA (AGH) were used as lubrication media. The surface irregularities usually observed in SEM studies were not apparent under AFM. The articular cartilage surface was resistant to hyaluronidase and also to chondroitinase ABC, but a fibrous structure was exhibited in alkaline protease enzymes-digested specimens. AFM analysis revealed that the thickness of the uppermost superficial surface layer of articular cartilage was between 800 nm and 2 microm in adult pig articular cartilage. The coefficient of friction (c.f.) was significantly higher in chondroitinase ABC and alkaline protease enzymes digested specimens. Generally, in normal saline lubrication medium, c.f. was higher in comparison to HA and AGH lubrication media. The role of the uppermost, superficial surface layer of articular cartilage in the lubrication mechanism of joints is discussed. PMID:11554503

  13. T1 assessment of hip joint cartilage following intra-articular gadolinium injection: a pilot study.

    PubMed

    Bittersohl, Bernd; Hosalkar, Harish S; Kim, Young-Jo; Werlen, Stefan; Trattnig, Siegfried; Siebenrock, Klaus A; Mamisch, Tallal C

    2010-10-01

    This pilot study defines the feasibility of cartilage assessment in symptomatic femoroacetabular impingement patients using intra-articular delayed gadolinium-enhanced MRI of cartilage (ia-dGEMRIC). Nine patients were scanned preliminary to study the contrast infiltration process into hip joint cartilage. Twenty-seven patients with symptomatic femoroacetabular impingement were subsequently scanned with intra-articular delayed gadolinium-enhanced MRI of cartilage. These T(1) findings were correlated to morphological findings. Zonal variations were studied. This pilot study demonstrates a significant difference between the pre- and postcontrast T(1) values (P < 0.001) remaining constant for 45 min. We noted higher mean T(1) values in morphologically normal-appearing cartilage than in damaged cartilage, which was statistically significant for all zones except the anterior-superior zone. Intraobserver (0.972) and interobserver correlation coefficients (0.933) were statistically significant. This study outlines the feasibility of intra-articular delayed gadolinium-enhanced MRI of cartilage for assessment of cartilage changes in patients with femoroacetabular impingement. It can also define the topographic extent and differing severities of cartilage damage. PMID:20872764

  14. Treatment of Focal Articular Cartilage Defects in the Knee

    PubMed Central

    Magnussen, Robert A.; Dunn, Warren R.; Carey, James L.

    2008-01-01

    We asked whether autologous chondrocyte implantation or osteochondral autograft transfer yields better clinical outcomes compared with one another or with traditional abrasive techniques for treatment of isolated articular cartilage defects and whether lesion size influences this clinical outcome. We performed a literature search and identified five randomized, controlled trials and one prospective comparative trial evaluating these treatment techniques in 421 patients. The operative procedures included autologous chondrocyte implantation, osteochondral autograft transfer, matrix-induced autologous chondrocyte implantation, and microfracture. Minimum followup was 1 year (mean, 1.7 years; range, 1–3 years). All studies documented greater than 95% followup for clinical outcome measures. No technique consistently had superior results compared with the others. Outcomes for microfracture tended to be worse in larger lesions. All studies reported improvement in clinical outcome measures in all treatment groups when compared with preoperative assessment; however, no control (nonoperative) groups were used in any of the studies. A large prospective trial investigating these techniques with the addition of a control group would be the best way to definitively address the clinical questions. Level of Evidence: Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18196358

  15. Localization of hyaluronic acid in human articular cartilage.

    PubMed

    Asari, A; Miyauchi, S; Kuriyama, S; Machida, A; Kohno, K; Uchiyama, Y

    1994-04-01

    To demonstrate localization of hyaluronic acid (HA) in articular cartilage of the human femur, biotinylated HA-binding region, which specifically binds HA molecules, was applied to the tissue. In sections fixed by 2% paraformaldehyde-2% glutaraldehyde, HA staining was detected in lamina splendens and chondrocytes in the middle zone. By pretreatment with trypsin, intense HA staining appeared in the extracellular matrix of the deep zone and weak staining in the superficial and middle zones. Moreover, pre-treatment with chondroitinase ABC (CHase ABC) intensely enhanced the stainability for HA in the superficial and middle zones and weakly in the deeper zone. Combined pre-treatment of trypsin with CHase ABC abolished intra- and extracellular staining for HA in all zones. By microbiochemical study, the concentrations of HA and dermatan sulfate were high in the middle zone, whereas those of chondroitin sulfate and keratan sulfate were high in the deep zone. These results suggest that HA is abundantly synthesized in and secreted from the chondrocytes, particularly in the middle zone, whereas it is largely masked by proteoglycan constituents in the extracellular matrix. PMID:8126377

  16. Age related changes and osteochondrosis in swine articular and epiphyseal cartilage: light ane electron microscopy.

    PubMed

    Bhatnagar, R; Christian, R G; Nakano, T; Aherne, F X; Thompson, J R

    1981-04-01

    Age related changes and osteochondrosis in swine were studied using light microscopy and electron microscopy in articular cartilage and light microscopy and epiphyseal cartilage of swine from three days to 30 weeks of age. Thickness, cellularity and vascularity of both the epiphyseal and articular cartilage, decreased as the swine aged. Osteochondrotic changes included formation of "plugs" of cartilage indicating localized failure of ossification and separation and space formation in epiphyseal cartilage. Eosinophilic streaks and space formation in epiphyseal cartilage was observed in relation to epiphyseal separation. Electron microscopy showed a continuous fibrillar layer on the surface of the cartilage corresponding to the lamina splendens of light microscopy. This layer increased in the thickness and showed accumulation of amorphous material between the fibrils with aging. In the matrix, the orientation and distribution of the collagen fibers changed with growth and thicker fibers with clear sub banding were more common in older age groups. Also, necrotic cells, glycogen containing bodies and cellular debris were noticed in the matrix of normal cartilage in old animals. Chondrocytes in the younger cartilage showed accumulation of organelles responsible for protein synthesis; while Golgi bodies, vesicles, lysosomes, well developed foot processes and other inclusions were noticed in older cartilage. Cartilage erosions had a clumped and disrupted lamina splendens on the surface and electron lucent patches in the ground substances of the matrix and chondrocyte cytoplasm. PMID:7260732

  17. Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Ellingsen, Pa˚L. Gunnar; Lilledahl, Magnus Borstad; Aas, Lars Martin Sandvik; Davies, Catharina De Lange; Kildemo, Morten

    2011-11-01

    The collagen meshwork in articular cartilage of chicken knee is characterized using Mueller matrix imaging and multiphoton microscopy. Direction and degree of dispersion of the collagen fibers in the superficial layer are found using a Fourier transform image-analysis technique of the second-harmonic generated image. Mueller matrix images are used to acquire structural data from the intermediate layer of articular cartilage where the collagen fibers are too small to be resolved by optical microscopy, providing a powerful multimodal measurement technique. Furthermore, we show that Mueller matrix imaging provides more information about the tissue compared to standard polarization microscopy. The combination of these techniques can find use in improved diagnosis of diseases in articular cartilage, improved histopathology, and additional information for accurate biomechanical modeling of cartilage.

  18. Directed differentiation of induced pluripotent stem cells into chondrogenic lineages for articular cartilage treatment

    PubMed Central

    Lach, Michał; Richter, Magdalena; Pawlicz, Jarosław; Suchorska, Wiktoria M

    2014-01-01

    In recent years, increases in the number of articular cartilage injuries caused by environmental factors or pathological conditions have led to a notable rise in the incidence of premature osteoarthritis. Osteoarthritis, considered a disease of civilization, is the leading cause of disability. At present, standard methods for treating damaged articular cartilage, including autologous chondrocyte implantation or microfracture, are short-term solutions with important side effects. Emerging treatments include the use of induced pluripotent stem cells, a technique that could provide a new tool for treatment of joint damage. However, research in this area is still early, and no optimal protocol for transforming induced pluripotent stem cells into chondrocytes has yet been established. Developments in our understanding of cartilage developmental biology, together with the use of modern technologies in the field of tissue engineering, provide an opportunity to create a complete functional model of articular cartilage. PMID:25383175

  19. CAN OSTEOCHONDRAL GRAFTING BE AUGMENTED WITH MICROFRACTURE IN AN EXTENDED SIZED LESION OF ARTICULAR CARTILAGE

    PubMed Central

    Lane, JG; Healey, RM; Sah, RL; Chen, AC-S; Amiel, D

    2014-01-01

    BACKGROUND Both microfracture and osteochondral autografting procedures have been useful in treating osteochondral lesions. HYPOTHESIS Combining microfracture and osteochondral autografting procedures can extend the size of lesions which can be treated with either technique. STUDY DESIGN Descriptive laboratory study. METHODS Eight adult goats underwent osteochondral autograft transfer of a 4.5mm femoral trochlea plug into an 8mm full thickness chondral defect in the weight bearing portion of the medial femoral condyle. In the gap region surrounding the autograft, microfracture was performed. The animals were allowed normal activity until the end of the experiment at 6 months, at which time the knees were harvested. At harvest the knees were assessed grossly, and then evaluation was performed by histology and histomorphometry, biochemistry and biomechanics. One animal died at 6 wks from gastroenteritis. RESULTS The osteochondral plugs healed well, with integration of the bone and preservation of the chondral cap. The chondral gap between the host site articular cartilage and the transferred plug had decreased from 3 mm at implant to less than 0.1 mm. Histological analysis demonstrated regions of variable cartilage repair, with integration of the cartilage layer at some sites but incomplete healing at others. Histomorphometry demonstrated filling of the chondral gap to 75–85% of the normal volume. Biochemical analysis revealed greater than 90% type II collagen at most sites with some areas containing 80% type II collagen. Biomechanical indentation testing, indicated that the repaired area had variable thickness and stiffness, with a trend of increased stiffness in the bulk graft and decreased softness at the proximal microfracture interface site. CONCLUSIONS The performance of a combined microfracture and osteochondral autograft transfer (OATS) procedure to resurface a large chondral defect appears promising. Transferred cartilage tissue can successfully be

  20. Cartilage defect repair in horses: Current strategies and recent developments in regenerative medicine of the equine joint with emphasis on the surgical approach.

    PubMed

    Cokelaere, Stefan; Malda, Jos; van Weeren, René

    2016-08-01

    Chondral and osteochondral lesions due to injury or other pathology are highly prevalent conditions in horses (and humans) and commonly result in the development of osteoarthritis and progression of joint deterioration. Regenerative medicine of articular cartilage is an emerging clinical treatment option for patients with articular cartilage injury or disease. Functional articular cartilage restoration, however, remains a major challenge, but the field is progressing rapidly and there is an increasing body of supportive clinical and scientific evidence. This review gives an overview of the established and emerging surgical techniques employed for cartilage repair in horses. Through a growing insight in surgical cartilage repair possibilities, surgeons might be more stimulated to explore novel techniques in a clinical setting. PMID:27387728

  1. Demonstration of fibronectin in human articular cartilage by an indirect immunoperoxidase technique.

    PubMed

    Clemmensen, I; Hølund, B; Johansen, N; Andersen, R B

    1982-01-01

    Fresh frozen tissue sections of human articular cartilage was treated without and with human testicular hyaluronidase (2 x 10(6) units/l) for 60 min at 37 degrees C and stained by the indirect immunoperoxidase technique with rabbit antihuman fibronectin. The rabbit antihuman fibronectin was purified by affinity chromatography on human fibronectin-Sepharose. Fibronectin was only found on the acellular surface of the articular cartilage in tissue sections not treated with hyaluronidase. In this surface layer, probably identical to "lamina splendens", the arrangement of fibronectin was as a membrane. No collagen was seen in this area by van Gieson staining. No staining for fibronectin was found in the cartilage matrix or in the chondrocytes. Treatment of the cartilage tissue with hyaluronidase resulted in visualization of high amount of fibronectin in the cartilage matrix, with the highest intensity around the chondrocytes. The staining of the acellular surface layer of the articular cartilage was identical with the results obtained without hyaluronidase treatment. These results indicate that articular cartilage is rich in fibronectin probably in complex with hyaluronic acid, and that the chondrocytes produce fibronectin in situ. It also demonstrates the steric hindrance of hyaluronic acid aggregates in diffusion of the antibody and the value of hyaluronidase treatment of tissue before demonstration of fibronectin. PMID:6757202

  2. The protective effect of meniscus allograft transplantation on articular cartilage: a systematic review of animal studies.

    PubMed

    Rongen, J J; Hannink, G; van Tienen, T G; van Luijk, J; Hooijmans, C R

    2015-08-01

    Despite widespread reporting on clinical results, the effect of meniscus allograft transplantation on the development of osteoarthritis is still unclear. The aim of this study was to systematically review all studies on the effect of meniscus allograft transplantation on articular cartilage in animals. Pubmed and Embase were searched for original articles concerning the effect of meniscus allograft transplantation on articular cartilage compared with both its positive (meniscectomy) and negative (either sham or non-operated) control in healthy animals. Outcome measures related to assessment of damage to articular cartilage were divided in five principal outcome categories. Standardized mean differences (SMD) were calculated and pooled to obtain an overall SMD and 95% confidence interval. 17 articles were identified, representing 14 original animal cohorts with an average timing of data collection of 24 weeks [range 4 weeks; 30 months]. Compared to a negative control, meniscus allograft transplantation caused gross macroscopic (1.45 [0.95; 1.95]), histological (3.43 [2.25; 4.61]) damage to articular cartilage, and osteoarthritic changes on radiographs (3.12 [1.42; 4.82]). Moreover, results on histomorphometrics and cartilage biomechanics are supportive of this detrimental effect on cartilage. On the other hand, meniscus allograft transplantation caused significantly less gross macroscopic (-1.19 [-1.84; -0.54]) and histological (-1.70 [-2.67; -0.74]) damage to articular cartilage when compared to meniscectomy. However, there was no difference in osteoarthritic changes on plain radiographs (0.04 [-0.48; 0.57]), and results on histomorphometrics and biomechanics did neither show a difference in effect between meniscus allograft transplantation and meniscectomy. In conclusion, although meniscus allograft transplantation does not protect articular cartilage from damage, it reduces the extent of it when compared with meniscectomy. PMID:25960117

  3. Optical Determination of Anisotropic Material Properties of Bovine Articular Cartilage in Compression

    PubMed Central

    Wang, Christopher C-B.; Chahine, Nadeen O.; Hung, Clark T.; Ateshian, Gerard A.

    2010-01-01

    The precise nature of the material symmetry of articular cartilage in compression remains to be elucidated. The primary objective of this study was to determine the equilibrium compressive Young’s moduli and Poisson’s ratios of bovine cartilage along multiple directions (parallel and perpendicular to the split line direction, and normal to the articular surface) by loading small cubic specimens (0.9×0.9×0.8 mm, n=15) in unconfined compression, with the expectation that the material symmetry of cartilage could be determined more accurately with the help of a more complete set of material properties. The second objective was to investigate how the tension-compression nonlinearity of cartilage might alter the interpretation of material symmetry. Optimized digital image correlation was used to accurately determine the resultant strain fields within the specimens under loading. Experimental results demonstrated that neither the Young’s moduli nor the Poisson’s ratios exhibit the same values when measured along the three loading directions. The main findings of this study are that the framework of linear orthotropic elasticity (as well as higher symmetries of linear elasticity) is not suitable to describe the equilibrium response of articular cartilage nor characterize its material symmetry; a framework which accounts for the distinctly different responses of cartilage in tension and compression is more suitable for describing the equilibrium response of cartilage; within this framework, cartilage exhibits no lower than orthotropic symmetry. PMID:12594982

  4. In vivo cartilage repair using adipose-derived stem cell-loaded decellularized cartilage ECM scaffolds.

    PubMed

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

    2014-06-01

    We have previously reported a natural, human cartilage ECM (extracellular matrix)-derived three-dimensional (3D) porous acellular scaffold for in vivo cartilage tissue engineering in nude mice. However, the in vivo repair effects of this scaffold are still unknown. The aim of this study was to further explore the feasibility of application of cell-loaded scaffolds, using autologous adipose-derived stem cells (ADSCs), for cartilage defect repair in rabbits. A defect 4 mm in diameter was created on the patellar groove of the femur in both knees, and was repaired with the chondrogenically induced ADSC-scaffold constructs (group A) or the scaffold alone (group B); defects without treatment were used as controls (group C). The results showed that in group A all defects were fully filled with repair tissue and at 6 months post-surgery most of the repair site was filled with hyaline cartilage. In contrast, in group B all defects were partially filled with repair tissue, but only half of the repair tissue was hyaline cartilage. Defects were only filled with fibrotic tissue in group C. Indeed, histological grading score analysis revealed that an average score in group A was higher than in groups B and C. GAG and type II collagen content and biomechanical property detection showed that the group A levels approached those of normal cartilage. In conclusion, ADSC-loaded cartilage ECM scaffolds induced cartilage repair tissue comparable to native cartilage in terms of mechanical properties and biochemical components. PMID:22674864

  5. The study on the mechanical characteristics of articular cartilage in simulated microgravity

    NASA Astrophysics Data System (ADS)

    Niu, Hai-Jun; Wang, Qing; Wang, Yue-Xiang; Li, Ang; Sun, Lian-Wen; Yan, Yan; Fan, Fan; Li, De-Yu; Fan, Yu-Bo

    2012-10-01

    The microgravity environment of a long-term space flight may induce acute changes in an astronaut's musculo-skeletal systems. This study explores the effects of simulated microgravity on the mechanical characteristics of articular cartilage. Six rats underwent tail suspension for 14 days and six additional rats were kept under normal earth gravity as controls. Swelling strains were measured using high-frequency ultrasound in all cartilage samples subject to osmotic loading. Site-specific swelling strain data were used in a triphasic theoretical model of cartilage swelling to determine the uniaxial modulus of the cartilage solid matrix. No severe surface irregularities were found in the cartilage samples obtained from the control or tail-suspended groups. For the tail-suspended group, the thickness of the cartilage at a specified site, as determined by ultrasound echo, showed a minor decrease. The uniaxial modulus of articular cartilage at the specified site decreased significantly, from (6.31 ± 3.37)MPa to (5.05 ± 2.98)MPa ( p < 0.05). The histology-stained image of a cartilage sample also showed a reduced number of chondrocytes and decreased degree of matrix staining. These results demonstrated that the 14 d simulated microgravity induced significant effects on the mechanical characteristics of articular cartilage. This study is the first attempt to explore the effects of simulated microgravity on the mechanical characteristics of articular cartilage using an osmotic loading method and a triphasic model. The conclusions may provide reference information for manned space flights and a better understanding of the effects of microgravity on the skeletal system.

  6. Role of computer aided detection (CAD) integration: case study with meniscal and articular cartilage CAD applications

    NASA Astrophysics Data System (ADS)

    Safdar, Nabile; Ramakrishna, Bharath; Saiprasad, Ganesh; Siddiqui, Khan; Siegel, Eliot

    2008-03-01

    Knee-related injuries involving the meniscal or articular cartilage are common and require accurate diagnosis and surgical intervention when appropriate. With proper techniques and experience, confidence in detection of meniscal tears and articular cartilage abnormalities can be quite high. However, for radiologists without musculoskeletal training, diagnosis of such abnormalities can be challenging. In this paper, the potential of improving diagnosis through integration of computer-aided detection (CAD) algorithms for automatic detection of meniscal tears and articular cartilage injuries of the knees is studied. An integrated approach in which the results of algorithms evaluating either meniscal tears or articular cartilage injuries provide feedback to each other is believed to improve the diagnostic accuracy of the individual CAD algorithms due to the known association between abnormalities in these distinct anatomic structures. The correlation between meniscal tears and articular cartilage injuries is exploited to improve the final diagnostic results of the individual algorithms. Preliminary results from the integrated application are encouraging and more comprehensive tests are being planned.

  7. Persisting High Levels of Synovial Fluid Markers after Cartilage Repair

    PubMed Central

    Konttinen, Yrjö T.; Peterson, Lars; Lindahl, Anders; Kiviranta, Ilkka

    2008-01-01

    Local attempts to repair a cartilage lesion could cause increased levels of anabolic and catabolic factors in the synovial fluid. After repair with regenerated cartilage, the homeostasis of the cartilage ideally would return to normal. In this pilot study, we first hypothesized levels of synovial fluid markers would be higher in patients with cartilage lesions than in patients with no cartilage lesions, and then we hypothesized the levels of synovial fluid markers would decrease after cartilage repair. We collected synovial fluid samples from 10 patients before autologous chondrocyte transplantation of the knee. One year later, a second set of samples was collected and arthroscopic evaluation of the repair site was performed. Fifteen patients undergoing knee arthroscopy for various symptoms but with no apparent cartilage lesions served as control subjects. We measured synovial fluid matrix metalloproteinase-3 (MMP-3) and insulinlike growth factor-I (IGF-I) concentrations with specific activity and enzyme-linked immunosorbent assays, respectively. The levels of MMP-3 and IGF-I were higher in patients having cartilage lesions than in control subjects with no cartilage lesions. One year after cartilage repair, the lesions were filled with repair tissue, but the levels of MMP-3 and IGF-I remained elevated, indicating either graft remodeling or early degeneration. Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18709427

  8. Biological Effects of the Plant-derived Polyphenol Resveratrol in Human Articular Cartilage and Chondrosarcoma Cells

    PubMed Central

    Im, Hee-Jeong; Li, Xin; Chen, Di; Yan, Dongyao; Kim, Jaesung; Ellman, Michael B; Stein, Gary S.; Cole, Brian; Ranjan, KC; Cs-Szabo, Gabriella; van Wijnen, Andre J

    2012-01-01

    The natural phytoestrogen resveratrol (RSV) may have therapeutic potential for arthritic conditions. RSV is chondroprotective for articular cartilage in rabbit models for arthritis, but its biological effects on human articular cartilage and chondrosarcoma cells are unknown. Effects of RSV on human articular cartilage homeostasis were studied by assessing production of matrix-degrading enzymes (MMP-13, ADAMTS-4, and ADAMTS-5), as well as proteoglycan production and synthesis. The counteractions of RSV against catabolic factors (e.g., FGF-2 or IL-1β) were examined by in vitro and ex vivo using monolayer, three-dimensional alginate beads and cartilage explants cultures, respectively. RSV improves cell viability of articular chondrocytes and effectively antagonizes cartilage-degrading protease production that was initiated by catabolic and/or anti-anabolic cytokines in human articular chondrocytes. RSV significantly also enhances BMP7-promoted proteoglycan synthesis as assessed by 35S-sulfate incorporation. Protein-DNA interaction arrays suggest that RSV inhibits the activation of transcription factors involved in inflammation and cartilage catabolic signaling pathways, including direct downstream regulators of MAPK (e.g., AP-1, PEA3) and NFκB. RSV selectively compromises survival of human chondrosarcoma cells, but not primary articular chondrocytes, revealing cell-specific activity of RSV on non-tumorigenic versus tumor-derived cells. We propose that RSV exerts its chondroprotective functions, in part, by deactivating p53-induced apoptosis in human primary chondrocytes, but not human chondrosarcoma. Our findings suggest that RSV has potential as a unique biologic treatment for both prevention and treatment of cartilage degenerative diseases. PMID:22252971

  9. FRICTIONAL RESPONSE OF BOVINE ARTICULAR CARTILAGE UNDER CREEP LOADING FOLLOWING PROTEOGLYCAN DIGESTION WITH CHONDROITINASE ABC

    PubMed Central

    Basalo, Ines M.; Chen, Faye Hui; Hung, Clark T.; Ateshian, Gerard A.

    2010-01-01

    Summary The specific aim of this study was to investigate the effect of chondroitinase ABC treatment on the frictional response of bovine articular cartilage against glass, under creep loading. The hypothesis is that chondroitinase ABC treatment increases the friction coefficient of bovine articular cartilage under creep. Articular cartilage samples (n=12) harvested from two bovine knee joints (1–3 months-old) were divided into a control group (intact specimens) and a treated group (chondroitinase ABC digestion), and tested in unconfined compression with simultaneous continuous sliding (±4 mm at 1 mm/s) under a constant applied stress of 0.5 MPa, for 2,500 s. The time-dependent response of the friction coefficient was measured. With increasing duration of loading, treated samples exhibited a significantly higher friction coefficient than control samples as assessed by the equilibrium value (treated: μeq = 0.19 ± 0.02; control: μeq = 0.12 ± 0.03; p=0.002), though the coefficient achieved immediately upon loading did not increase significantly (treated: μmin = 0.0053 ± 0.0025; control: μmin = 0.037 ± 0.0013; p=0.19). Our results demonstrate that removal of the cartilage glycosaminoglycans using chondroitinase ABC significantly increases the overall time-dependent friction coefficient of articular cartilage. These findings strengthen the motivation for developing chondroprotective strategies by increasing cartilage chondroitin sulfate content in osteoarthritic joints. PMID:16532626

  10. Noncontact evaluation of articular cartilage degeneration using a novel ultrasound water jet indentation system.

    PubMed

    Lu, M-H; Zheng, Y P; Huang, Q-H; Ling, C; Wang, Q; Bridal, L; Qin, L; Mak, A

    2009-01-01

    We previously reported a noncontact ultrasound water jet indentation system for measuring and mapping tissue mechanical properties. The key idea was to utilize a water jet as an indenter as well as the coupling medium for high-frequency ultrasound. In this paper, the system was employed to assess articular cartilage degeneration, using stiffness ratio as an indicator of the mechanical properties of samples. Both the mechanical and acoustical properties of intact and degenerated bovine patellar articular cartilage (n = 8) were obtained in situ. It was found that the stiffness ratio was reduced by 44 +/- 17% after the articular cartilage was treated by 0.25% trypsin at 37 degrees C for 4 h while no significant difference in thickness was observed between the intact and degenerated samples. A significant decrease of 36 +/- 20% in the peak-to-peak amplitude of ultrasound echoes reflected from the cartilage surface was also found for the cartilage samples treated by trypsin. The results also showed that the stiffness obtained with the new method highly correlated with that measured using a standard mechanical testing protocol. A good reproducibility of the measurements was demonstrated. The present results showed that the ultrasound water jet indentation system may provide a potential tool for the non-destructive evaluation of articular cartilage degeneration by simultaneously obtaining mechanical properties, acoustical properties, and thickness data. PMID:19011965

  11. Immunohistochemical demonstration of fibronectin in the most superficial layer of normal rabbit articular cartilage.

    PubMed Central

    Nishida, K; Inoue, H; Murakami, T

    1995-01-01

    OBJECTIVE--To locate fibronectin ultrastructurally in the most superficial layer of normal articular cartilage of rabbits, in order to clarify its role in joint physiology. METHODS--Articular cartilage was obtained from the femoral condyle of seven normal adult rabbits and prepared by a method that included tannic acid fixation. Polyclonal antibodies against rabbit fibronectin were used in an immunohistochemical electron microscopic study, without any enzymic digestion but with a pre-embedding method for the transmission electron microscopy. RESULTS--The cartilage surface was successfully preserved by tannic acid fixation. The most superficial layer in electron photomicrographs was approximately 200-300 nm thick, cell free, and appeared to have two parallel components: the more superficial lamina and the deeper lamina. Gold labelled fibronectin lined this layer in immunohistochemical electron photomicrographs. CONCLUSIONS--Fibronectin covering the surface of the articular cartilage may have a role in joint lubrication and protection of the cartilage by binding with the collagenous matrix and hyaluronic acid in synovial fluid. Chondroitin sulphates may act as a charge barrier in close relationship with the collagen fibrils in the deeper lamina. Significant alteration in these functions may be one of the first causal steps leading to destruction of the articular cartilage. Images PMID:8546534

  12. Permeation of dimethyl sulfoxide into articular cartilage at subzero temperatures.

    PubMed

    Zhang, Shao-Zhi; Yu, Xiao-Yi; Chen, Guang-Ming

    2012-03-01

    Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization would contribute to the commercialization or industrialization of this technology. Vitrification has been thought to be a promising method for successful preservation of articular cartilage (AC), but high concentration cryoprotectants (CPAs) are used which may cause high cellular toxicity. An effective way to reduce CPA toxicity is to increase CPA concentration gradually while the temperature is lowered. Understanding the mechanism of CPA permeation at subzero temperatures is important for designing the cryopreservation protocol. In this research, the permeation of dimethyl sulfoxide (Me(2)SO) in ovine AC at subzero temperatures was studied experimentally. Pretreated AC discs were exposed in Me(2)SO solutions for different time (0, 5, 15, 30, 50, 80, and 120 min) at three temperature levels (-10, -20, and -30 °C). The Me(2)SO concentration within the tissue was determined by ultraviolet (UV) spectrophotometry. The diffusion coefficients were estimated to be 0.85×10(-6), 0.48×10(-6), and 0.27×10(-6) cm(2)/s at -10, -20, and -30 °C, respectively, and the corresponding activation energy was 29.23 kJ/mol. Numerical simulation was performed to compare two Me(2)SO addition protocols, and the results demonstrated that the total loading duration could be effectively reduced with the knowledge of permeation kinetics. PMID:22374614

  13. Modeling the transport of cryoprotective agents in articular cartilage for cryopreservation

    NASA Astrophysics Data System (ADS)

    Torqabeh, Alireza Abazari

    Loading vitrifiable concentrations of cryoprotective agents is an important step for cryopreservation of biological tissues by vitrification for research and transplantation purposes. This may be done by immersing the tissue in a cryoprotective agent (CPA) solution, and increasing the concentration, continuously or in multiple steps, and simultaneously decreasing the temperature to decrease the toxicity effects of the cryoprotective agent on the tissue cellular system. During cryoprotective agent loading, osmotic water movement from the tissue to the surrounding solution, and the resultant tissue shrinkage and stress-strain in the tissue matrix as well as on the cellular system can significantly alter the outcome of the cryopreservation protocol. In this thesis, a biomechanical model for articular cartilage is developed to account for the transport of the cryoprotective agent, the nonideal-nondilute properties of the vitrifiable solutions, the osmotic water movement and the resultant tissue shrinkage and stress-strain in the tissue matrix, and the osmotic volume change of the chondrocytes, during cryoprotective agent loading in the cartilage matrix. Four essential transport parameters needed for the model were specified, the values of which were obtained uniquely by fitting the model to experimental data from porcine articular cartilage. Then, it was shown that using real nonuniform initial distributions of water and fixed charges in cartilage, measured separately in this thesis using MRI, in the model can significantly affect the model predictions. The model predictions for dimethyl sulfoxide diffusion in porcine articular cartilage were verified by comparing to spatially and temporally resolved measurements of dimethyl sulfoxide concentration in porcine articular cartilage using a spectral MRI technique, developed for this purpose and novel to the field of cryobiology. It was demonstrated in this thesis that the developed mathematical model provides a novel tool

  14. Effects of Chondroitinase ABC-Mediated Proteoglycan Digestion on Decellularization and Recellularization of Articular Cartilage

    PubMed Central

    Bautista, Catherine A.; Park, Hee Jun; Mazur, Courtney M.; Aaron, Roy K.

    2016-01-01

    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. PMID:27391810

  15. Are Articular Cartilage Lesions and Meniscus Tears Predictive of IKDC, KOOS, and Marx Activity Level Outcomes after ACL Reconstruction? A 6-Year Multicenter Cohort Study

    PubMed Central

    Cox, Charles L.; Huston, Laura J.; Dunn, Warren R.; Reinke, Emily K.; Nwosu, Samuel K.; Parker, Richard D.; Wright, Rick W.; Kaeding, Christopher C.; Marx, Robert G.; Amendola, Annunziata; McCarty, Eric C.; Wolf, Brian R.; Harrell, Frank E.; Spindler, Kurt P.

    2014-01-01

    on the MFC. Lateral meniscus repairs did not correlate with inferior results, but medial meniscus repairs predicted worse IKDC and KOOS scores. Lateral meniscus tears left alone significantly improved prognosis. Small partial meniscectomies (<33%) on the medial meniscus fared worse, but conversely, larger excisions (>50%) on either the medial or lateral menisci improved prognosis. Analogous to previous studies, other significant predictors of lower outcome scores were lower baseline scores, higher BMI, lower education level, smoking, and ACL revisions. Conclusions Both articular cartilage injury and meniscal tears/treatment at the time of ACLR were significant predictors of IKDC and KOOS scores 6 years following ACLR. Similarly, having a grade 4 MFC lesion significantly reduced a patient’s Marx activity level score at 6 years. PMID:24647881

  16. Autologous bone marrow concentrate: review and application of a novel intra-articular orthobiologic for cartilage disease.

    PubMed

    Sampson, Steven; Botto-van Bemden, Angie; Aufiero, Danielle

    2013-09-01

    Younger adults, aged < 65 years, increasingly present to their physicians with advanced cartilage disease or post-traumatic osteoarthritis. A number of treatments exist for lessening patient pain and improving patient function. However, many patients are becoming aware of the potential of regenerative therapies and are now seeking solutions to the impaired biology underlying their conditions rather than addressing only their symptoms. Patients do not want to merely lessen their symptoms temporarily with a surgical procedure that replaces damaged tissue, but instead seek correction and repair of the underlying biology to regenerate damaged tissue and alleviate their symptoms altogether. Current therapies for patients with cartilage disease or osteoarthritis range from non-surgical intra-articular injections with biologics, such as hyaluronic acid (HA), to total joint arthroplasty for advanced stages of disease. Total joint arthroplasty is a successful procedure for patients aged > 65 years; however, the limited long-term durability of implanted prostheses decreases the preference of using such methods in more active patients aged < 65 years. The potential of cell-based orthobiologic injection therapies (pertaining to therapeutic injectables that aim to restore the biologic environment and/or structural components of diseased or damaged musculoskeletal tissue) is of tremendous interest for younger, more active patients, and is even more appealing in that such therapy can be delivered at point-of-care in the clinic during an office visit. Notably, the exponential rate of progress in biotechnology has allowed for immediate application of myriad novel therapies prior to clear evidence of benefit from randomized clinical trials. Orthobiologic intra-articular injection therapies include HA and platelet-rich plasma (PRP). We report on current, available findings for a third-generation intra-articular orthobiologic injectable therapy for cartilage disease, bone marrow

  17. What can biophotonics tell us about the 3D microstructure of articular cartilage?

    PubMed

    Matcher, Stephen J

    2015-02-01

    Connective tissues such as articular cartilage have been the subject of study using novel optical techniques almost since the invention of polarized light microscopy (PLM). Early studies of polarized light micrographs were the main evidential basis for the establishment of quantitative models of articular cartilage collagen structure by Benninghoff and others. Even now, state of the art optical techniques including quantitative polarized light microscopy (qPLM), optical coherence tomography (OCT), polarization-sensitive optical coherence tomography (PS-OCT), second harmonic generation (SHG) microscopy, Fourier-transform infrared (FTIR) microscopy, Raman and optical hyperspectral reflectance and fluorescence imaging are providing new insights into articular cartilage structure from the nanoscale through to the mesoscale. New insights are promised by emerging modalities such as optical elastography. This short review highlights some key recent results from modern optical techniques. PMID:25694964

  18. What can biophotonics tell us about the 3D microstructure of articular cartilage?

    PubMed Central

    2015-01-01

    Connective tissues such as articular cartilage have been the subject of study using novel optical techniques almost since the invention of polarized light microscopy (PLM). Early studies of polarized light micrographs were the main evidential basis for the establishment of quantitative models of articular cartilage collagen structure by Benninghoff and others. Even now, state of the art optical techniques including quantitative polarized light microscopy (qPLM), optical coherence tomography (OCT), polarization-sensitive optical coherence tomography (PS-OCT), second harmonic generation (SHG) microscopy, Fourier-transform infrared (FTIR) microscopy, Raman and optical hyperspectral reflectance and fluorescence imaging are providing new insights into articular cartilage structure from the nanoscale through to the mesoscale. New insights are promised by emerging modalities such as optical elastography. This short review highlights some key recent results from modern optical techniques. PMID:25694964

  19. Irrigating solutions used in arthroscopy and their effect on articular cartilage. An in vivo study

    SciTech Connect

    Arciero, R.A.; Little, J.S.; Liebenberg, S.P.; Parr, T.J.

    1986-11-01

    The effect of arthroscopic irrigating solutions on articular cartilage was determined by the use of an animal model. Rabbit knee joints were irrigated continuously for two hours with either normal saline, Ringer's lactate, or sterile water. Subsequently, the rate of incorporation of /sup 35/SO/sub 4/ by articular cartilage was used to measure the effect of the irrigants on chondrocyte metabolism. In addition, the irrigated groups were compared to an unirrigated control group. There was no significant difference in /sup 35/SO/sub 4/ incorporation between the groups. This suggested that none of the irrigating solutions used in this study adversely affected articular cartilage function. On the basis of these findings, it appears that normal saline, Ringer's lactate, and sterile water can be safely used as irrigating solutions during most arthroscopic procedures.

  20. Alterations in endogenous osteogenic protein-1 with degeneration of human articular cartilage.

    PubMed

    Merrihew, Charis; Kumar, Bhavna; Heretis, Katherine; Rueger, David C; Kuettner, Klaus E; Chubinskaya, Susan

    2003-09-01

    A synchronized balance between synthesis and breakdown of extracellular matrix (ECM) molecules in normal articular cartilage is disturbed in osteoarthritis (OA). The focus of our study is the anabolic factor, osteogenic protein-1 (OP-1) that is expressed in articular cartilage and is able to induce the synthesis of ECM components. The major aim was to investigate both qualitatively and quantitatively endogenous OP-1 in normal, degenerative, and OA cartilage. Normal and degenerative cartilage was obtained at autopsies from femoral condyles of human organ donors with no documented history of joint disease; OA cartilage was obtained from patients undergoing joint arthroplasty. Appearance of donor cartilage was evaluated by Collins scale, where normal cartilage is assigned grades 0-1, and degenerated cartilage is assigned grades 2-4. OP-1 mRNA expression was assessed by RT-PCR; OP-1 protein (pro- and active forms) was qualitatively analyzed by Western blotting and quantified by OP-1 ELISA. The highest levels of OP-1 expression (mRNA and protein) were detected in normal cartilage of grade 0. The concentration of OP-1 protein was about 50 ng per gram cartilage dry weight. With the progression of cartilage degeneration (increased Collins grades and OA) OP-1 protein was down-regulated up to 9-fold. These changes affected primarily the active form of OP-1. OP-1 message also declined in cartilages with the increase of degenerative changes. In conclusion, an overall decrease in endogenous OP-1 in degenerated and OA tissue suggests that OP-1 could be one of the factors responsible for normal homeostasis and matrix integrity in cartilage. PMID:12919879

  1. Progression of Gene Expression Changes following a Mechanical Injury to Articular Cartilage as a Model of Early Stage Osteoarthritis

    PubMed Central

    McCulloch, R. S.; Ashwell, M. S.; Maltecca, C.; O'Nan, A. T.; Mente, P. L.

    2014-01-01

    An impact injury model of early stage osteoarthritis (OA) progression was developed using a mechanical insult to an articular cartilage surface to evaluate differential gene expression changes over time and treatment. Porcine patellae with intact cartilage surfaces were randomized to one of three treatments: nonimpacted control, axial impaction (2000 N), or a shear impaction (500 N axial, with tangential displacement to induce shear forces). After impact, the patellae were returned to culture for 0, 3, 7, or 14 days. At the appropriate time point, RNA was extracted from full-thickness cartilage slices at the impact site. Quantitative real-time PCR was used to evaluate differential gene expression for 18 OA related genes from four categories: cartilage matrix, degradative enzymes and inhibitors, inflammatory response and signaling, and cell apoptosis. The shear impacted specimens were compared to the axial impacted specimens and showed that shear specimens more highly expressed type I collagen (Col1a1) at the early time points. In addition, there was generally elevated expression of degradative enzymes, inflammatory response genes, and apoptosis markers at the early time points. These changes suggest that the more physiologically relevant shear loading may initially be more damaging to the cartilage and induces more repair efforts after loading. PMID:25478225

  2. Differences in Cartilage Repair between Loading and Unloading Environments in the Rat Knee

    PubMed Central

    Matsuzaki, Taro; Yoshida, Shinya; Kitade, Ippei; Hoso, Masahiro

    2014-01-01

    We investigated the histopathological and immunohistochemical effects of loading on cartilage repair in rat full-thickness articular cartilage defects. A total of 40 male 9-week-old Wistar rats were studied. Full-thickness articular cartilage defects were created over the capsule at the loading portion in the medial condyle of the femur. Twenty rats were randomly allocated into each of the 2 groups: a loading group and a unloading group. Twenty rats from these 2 groups were later randomly allocated to each of the 2 groups for evaluation at 1 and 2 weeks after surgery. At the end of each period, knee joints were examined histopathologically and immunohistochemically. In both groups at 1 and 2 weeks, the defects were filled with a mixture of granulation tissue and some remnants of hyaline cartilage. The repair tissue was not stained with toluidine blue in both groups. Strong staining of type I collagen was observed in the repair tissue of both groups. The area stained with type I collagen was smaller in the unloading group than in the loading groups, and the stained area was smaller at 2 weeks than at 1 week. In the staining for type II collagen, apparent staining of type II collagen was observed in the repair tissue of both groups at 1 week. At 2 weeks, there was a tendency toward a higher degree of apparent staining in the loading group than in the unloading group. Accordingly, these results indicated that loading and unloading in the early phase of cartilage repair have both merits and demerits. PMID:25792905

  3. [Remodeling of the articular cartilage during the replacement of its defect by a biocomposite material].

    PubMed

    Bogatov, V B; Zeinalov, P V; Liubun', G P; Kozadayev, M N; Matveyeva, O V; Sal'kovskiy, Yu Ye; Radzhabov, A M; Puchinyian, D M

    2015-01-01

    The regenerative capacity of articular cartilage was studied in animals in which its defects were replaced by biocomposite materials based on polycaprolactone in combination with hydroxyapatite. Six specimens of the material were used, which consisted of different proportions of these polymers. In the experiment on sheep (n = 6) it was found that these biocomposite materials were replaced by hyaline-like cartilage during healing of artificially created defects in the articular cartilage of the knee joint, while the ratio of composite components had no effect on the quality of the regenerates formed. These results support the view of a possible application of biocomposite materials in the treatment of degenerative and traumatic lesions of hyaline cartilage. PMID:25958731

  4. [Basophilic line of the articular cartilage in normal and various pathological states].

    PubMed

    Gongadze, L R

    1987-04-01

    Epiphyses of long tubular bones in the man and animals of various age, as well as experimental material of the adjuvant arthritis, with special reference to the basal part of the articular cartilage have been studied by means of histological, histochemical and histometrical methods. The structural-chemical organization of the basophilic line (tidemark) of the articular cartilage ensures its barrier role and participation in regulating selective permeability. Reconstruction of the tidemark in the process of physiological ageing and in cases of the articular pathology is aimed to preserve its integrity and in this way a complete differentiation of the noncalcified and calcified structures is secured. Disturbance of the basophilic line results in changes of the articular selective permeability, in invasion of vessels and structural elements of the bone marrow, and in development of profound distrophic and destructive changes of the cartilage--in deforming artrosis. Deflations in the structural-chemical organization of the tidemark indicate certain disturbances in the state of the system articular cartilage--subchondral bone. These data can be of prognostic importance. PMID:3606408

  5. Degenerative lesions in the articular cartilage after meniscectomy: preliminary experimental study in dogs.

    PubMed

    Berjon, J J; Munuera, L; Calvo, M

    1991-03-01

    Articular cartilage degeneration was studied in an experimental model including 68 knees of adult dogs on which five different types of medial meniscectomy had been performed with a followup period of 10 to 450 days. The results were assessed by macroscopic, radiologic, and histologic methods. The degenerative lesions increased proportionally to the amount of meniscal tissue resected and the duration of observation. These lesions proved to be more intense at the tibial plateau compared to the femoral condyle. For both joint surfaces the predominant location was the central zone. Considering the degenerative process by the articular cartilage after total meniscectomy, maximum preservation of meniscal tissue is recommended. PMID:2002520

  6. The effects of joint immobilization on articular cartilage of the knee in previously exercised rats

    PubMed Central

    Maldonado, Diogo Correa; da Silva, Marcelo Cavenaghi Pereira; Neto, Semaan El-Razi; Souza, Mônica Rodrigues; Souza, Romeu Rodrigues

    2013-01-01

    Studies have determined the effects of joint immobilization on the articular cartilage of sedentary animals, but we are not aware of any studies reporting the effects of joint immobilization in previously trained animals. The objective of the present study was to determine whether exercise could prevent degeneration of the articular cartilage that accompanies joint immobilization. We used light microscopy to study the thickness, cell density, nuclear size, and collagen density of articular cartilage of the femoral condyle of Wistar rats subjected to aerobic physical activity on an adapted treadmill five times per week. Four groups of Wistar rats were used: a control group (C), an immobilized group (I), an exercised group (E), and an exercised and then immobilized group (EI). The right knee joints from rats in groups I and EI were immobilized at 90 °C of flexion using a plastic cast for 8 weeks. Cartilage thickness decreased significantly in group I (mean, 120.14 ± 15.6 μm, P < 0.05), but not in group EI (mean, 174 ± 2.25), and increased significantly in group E (mean, 289.49 ± 9.15) compared with group C (mean, 239.20 ± 6.25). The same results were obtained for cell density, nuclear size, and collagen density (in all cases, P < 0.05). We concluded that exercise can prevent degenerative changes in femoral articular cartilage caused by immobilization of the knee joint. PMID:23480127

  7. Quantitative Assessment of Articular Cartilage Morphology via EPIC-μCT

    PubMed Central

    Xie, Liqin; Lin, Angela S.P.; Levenston, Marc E.; Guldberg, Robert E.

    2009-01-01

    Summary Objective The objective of the present study was to validate the ability of EPIC-μCT to nondestructively assess cartilage morphology in the rat model. Design An appropriate contrast agent (Hexabrix) concentration and incubation time for equilibration were determined for reproducible segmentation of femoral articular cartilage from contrast-enhanced μCT scans. Reproducibility was evaluated by triplicate scans of six femora, and the measured articular cartilage thickness was independently compared to thickness determined from needle probe testing and histology. The validated technique was then applied to quantify age-related differences in articular cartilage morphology between 4, 8, and 16-week old (n=5 each) male Wistar rats. Results A 40% Hexabrix/60% PBS solution with 30 minute incubation was optimal for segmenting cartilage from the underlying bone tissue and other soft tissues in the rat model. High reproducibility was indicated by the low coefficient of variation (1.7-2.5%) in cartilage volume, thickness and surface area. EPIC-μCT evaluation of thickness showed a strong linear relationship and good agreement with both needle probing (r2=0.95, slope=0.81, p<0.01, mean difference 11±22μm, n=43) and histology (r2=0.99, slope=0.97, p<0.01, mean difference 12±10μm, n=30). Cartilage volume and thickness significantly decreased with age while surface area significantly increased. Conclusion EPIC-μCT imaging has the ability to nondestructively evaluate three-dimensional articular cartilage morphology with high precision and accuracy in a small animal model. PMID:18789727

  8. Effect of pulsed electromagnetic fields on proteoglycan biosynthesis of articular cartilage is age dependent

    PubMed Central

    Bobacz, K; Graninger, W B; Amoyo, L; Smolen, J S

    2006-01-01

    Objective To investigate the effects of a pulsed electromagnetic field (EMF) on articular cartilage matrix biosynthesis with regard to age and cartilage damage using a matrix depleted cartilage explant model. Methods Cartilage explants were obtained from metacarpophalangeal joints of calves and adult cows. After depletion of the extracellular matrix by trypsin digestion, samples were maintained in serum‐free basal medium with and without the addition of interleukin 1β (IL1β). Half the samples were subjected to an EMF for 24 minutes daily; the other half were left untreated. Undigested and untreated explants served as negative controls. After 7 days, biosynthesis of matrix macromolecules was assessed by [35S]sulphate incorporation and values were normalised to hydroxyproline content. Results The EMF increased matrix macromolecule synthesis in undigested, untreated explants (p<0.009). In matrix depleted samples the EMF had no stimulatory effect on proteoglycan biosynthesis. IL1β significantly decreased the de novo synthesis of matrix macromolecules (p<0.00004) in young and adult samples, but an EMF partly counteracted this inhibitory effect in cartilage samples from young, but not old animals. Conclusion EMF promoted matrix macromolecule biosynthesis in intact tissue explants but had no stimulatory effect on damaged articular cartilage. The supressive effects of IL1β were partially counteracted by EMF exposure, exclusively in cartilage derived from young animals. An EMF has age dependent chondroprotective but not structure modifying properties when cartilage integrity is compromised. PMID:16769781

  9. Quantitative MRI Evaluation of Articular Cartilage Using T2 Mapping Following Hip Arthroscopy for Femoroacetabular Impingement

    PubMed Central

    Mayer, Stephanie W.; Wagner, Naomi; Fields, Kara G.; Wentzel, Catherine; Burge, Alissa; Potter, Hollis G.; Lyman, Stephen; Kelly, Bryan T.

    2016-01-01

    Objectives: Cam-type femoroacetabular impingement (FAI) causes a shearing and delamination injury to the acetabular articular cartilage due to a mismatch between the size of the femoral head and the acetabulum. This mechanism is thought to lead to early osteoarthritis in this population. Cam decompression has been advocated to eliminate impingement, with the ultimate goal of halting the progression of articular cartilage delamination. Although outcomes following this procedure in the young adult population have been favorable at short and medium term follow up, it is not known whether the articular cartilage itself is protected from further injury by changing the biomechanics of the joint with decompression of the cam morphology. The purpose of this study is to compare the pre- and post-operative integrity of the acetabular articular cartilage using T2 mapping to determine if hip arthroscopy is protective of the articular cartilage at short- to medium term follow up. Methods: Males between 18 and 35 years of age who had pre-operative T2 mapping MRIs, underwent hip arthroscopy for cam or mixed-type FAI with an alpha angle greater than 50°, and had at least 2 year follow-up were identified. Post-operative MRIs were performed and T2 relaxation times in the transition zone and weight bearing articular cartilage in the anterosuperior acetabulum at deep and superficial chondral layers were recorded at nine points on three sagittal sequences on pre and post-operative MRIs. A paired t-test was used to compare T2 relaxation values between pre-operative and post-operative scans. Results: Eleven hips were evaluated. Mean age was 26.3 years (range 21 - 35). Mean follow up time to post-operative T2 mapping MRI was 2.6 years (range 2.4 - 2.7). The change in T2 relaxation time was not significantly different between pre- and post-operative MRI scans for any of the nine regions in the deep zone of the acetabular cartilage (p=0.065 - 0.969) or the superficial zone of the

  10. Biologic Treatments for Sports Injuries II Think Tank-Current Concepts, Future Research, and Barriers to Advancement, Part 3: Articular Cartilage.

    PubMed

    Zlotnicki, Jason P; Geeslin, Andrew G; Murray, Iain R; Petrigliano, Frank A; LaPrade, Robert F; Mann, Barton J; Musahl, Volker

    2016-04-01

    Focal chondral defects of the articular surface are a common occurrence in the field of orthopaedics. These isolated cartilage injuries, if not repaired surgically with restoration of articular congruency, may have a high rate of progression to posttraumatic osteoarthritis, resulting in significant morbidity and loss of function in the young, active patient. Both isolated and global joint disease are a difficult entity to treat in the clinical setting given the high amount of stress on weightbearing joints and the limited healing potential of native articular cartilage. Recently, clinical interest has focused on the use of biologically active compounds and surgical techniques to regenerate native cartilage to the articular surface, with the goal of restoring normal joint health and overall function. This article presents a review of the current biologic therapies, as discussed at the 2015 American Orthopaedic Society for Sports Medicine (AOSSM) Biologics Think Tank, that are used in the treatment of focal cartilage deficiencies. For each of these emerging therapies, the theories for application, the present clinical evidence, and specific areas for future research are explored, with focus on the barriers currently faced by clinicians in advancing the success of these therapies in the clinical setting. PMID:27123466