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  1. Rabbit articular cartilage defects treated by allogenic chondrocyte transplantation

    OpenAIRE

    Boopalan, P. R. J. V. C.; Sathishkumar, Solomon; Kumar, Senthil; Chittaranjan, Samuel

    2006-01-01

    Articular cartilage defects have a poor capacity for repair. Most of the current treatment options result in the formation of fibro-cartilage, which is functionally inferior to normal hyaline articular cartilage. We studied the effectiveness of allogenic chondrocyte transplantation for focal articular cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was created in the articular cartilag...

  2. Processed bovine cartilage: an improved biosynthetic implant for contour defects

    International Nuclear Information System (INIS)

    Ersek, R.A.; Hart, W.G. Jr.; Greer, D.; Beisang, A.A.; Flynn, P.J.; Denton, D.R.

    1984-01-01

    Irradiated human cartilage has been found to be a superior implant material for correction of contour defects; however, availability problems have prevented this material from gaining wide acceptance. Implantation of processed irradiated bovine cartilage in primates and rabbits, as described here, provides strong evidence that this material performs like irradiated allograft cartilage antigenically and has certain cosmetic advantages over allograft cartilage. Our studies in primates have shown that there is no systemically measurable antibody-antigen reaction, either cellular or noncellular, to irradiated processed bovine cartilage. Neither primary nor second-set provocative implantations produced any measurable rejection. In rabbits, composite grafts of two pieces of irradiated bovine cartilage adjacent to each other were also well tolerated, with no measurable absorption and with capsule formation typical of a foreign body reaction to an inert object

  3. Advanced Strategies for Articular Cartilage Defect Repair

    Directory of Open Access Journals (Sweden)

    Fergal J. O'Brien

    2013-02-01

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

  4. [Conservative therapy of cartilage defects of the upper ankle joint].

    Science.gov (United States)

    Smolenski, U C; Best, N; Bocker, B

    2008-03-01

    Cartilage defects of the upper ankle joint reflect the problem that great force is transmitted and balanced out over a relatively small surface area. As a pathophysiological factor, cartilage-bone contusions play a significant role in the development of cartilage defects of the upper ankle joint. Physiotherapeutic procedures belong to the standard procedures of conservative therapy. The use and selection of the type of therapy is based on empirical considerations and experience and investigations on effectiveness of particular therapies are relatively rare. At present a symptom-oriented therapy of cartilage defects of the upper ankle joint seems to be the most sensible approach. It can be assumed that it makes sense that the symptomatic treatment of cartilage defects or initial stages of arthritis also includes the subsequent symptoms of pain, irritated condition and limited function. This leads to starting points for physiotherapy with respect to pain therapy, optimisation of pressure relationships, avoidance of pressure points, improvement of diffusion and pressure release. In addition to the differential physiotherapeutic findings, the determination of a curative, preventive or rehabilitative procedure is especially important. In physical therapy special importance is placed on a scheduled serial application corresponding to the findings, employing the necessary methods, such as physiotherapy, sport therapy, medical mechanics, manual therapy, massage, electrotherapy and warmth therapy. From this the findings-related therapy is proposed as a practical therapy concept: locomotive apparatus pain therapy, optimisation of pressure relationships, improvement of diffusion and decongestion therapy. Therapy options have been selected base on the current literature and are summarised in tabular form. The art of symptomatic therapy of cartilage defects of the upper ankle joint does not lie in the multitude of sometimes speculative procedures, but in the targeted selection

  5. Repair of articular cartilage defects in the knee with autologous iliac crest cartilage in a rabbit model.

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    Jing, Lizhong; Zhang, Jiying; Leng, Huijie; Guo, Qinwei; Hu, Yuelin

    2015-04-01

    To demonstrate that iliac crest cartilage may be used to repair articular cartilage defects in the knees of rabbits. Full-thickness cartilage defects were created in the medial femoral condyle on both knees of 36 New Zealand white rabbits. The 72 defects were randomly assigned to be repaired with ipsilateral iliac crest cartilage (Group I), osteochondral tissues removed at defect creation (Group II), or no treatment (negative control, Group III). Animals were killed at 6, 12, and 24 weeks post-operatively. The repaired tissues were harvested for magnetic resonance imaging (MRI), histological studies (haematoxylin and eosin and immunohistochemical staining), and mechanical testing. At 6 weeks, the iliac crest cartilage graft was not yet well integrated with the surrounding articular cartilage, but at 12 weeks, the graft deep zone had partial ossification. By 24 weeks, the hyaline cartilage-like tissue was completely integrated with the surrounding articular cartilage. Osteochondral autografts showed more rapid healing than Group I at 6 weeks and complete healing at 12 weeks. Untreated defects were concave or partly filled with fibrous tissue throughout the study. MRI showed that Group I had slower integration with surrounding normal cartilage compared with Group II. The mechanical properties of Group I were significantly lower than those of Group II at 12 weeks, but this difference was not significant at 24 weeks. Iliac crest cartilage autografts were able to repair knee cartilage defects with hyaline cartilage and showed comparable results with osteochondral autografts in the rabbit model.

  6. Repair of massively defected hemi-joints using demineralized osteoarticular allografts with protected cartilage.

    Science.gov (United States)

    Li, Siming; Yang, Xiaohong; Tang, Shenghui; Zhang, Xunmeng; Feng, Zhencheng; Cui, Shuliang

    2015-08-01

    Surgical replacement of massively defected joints necessarily relies on osteochondral grafts effective to both of bone and cartilage. Demineralized bone matrix (DBM) retains the osteoconductivity but destroys viable chondrocytes in the cartilage portion essential for successful restoration of defected joints. This study prepared osteochondral grafts of DBM with protected cartilage. Protected cartilage portions was characterized by cellular and molecular biology and the grafts were allogenically used for grafting. Protected cartilage showed similar histomorphological structure and protected proteins estimated by total proteins and cartilage specific proteins as in those of fresh controls when DBMs were generated in bone portions. Such grafts were successfully used for simultaneously repair of bone and cartilage in massively defected osteoarticular joints within 16 weeks post-surgery. These results present an allograft with clinical potential for simultaneous restoration of bone and cartilage in defected joints.

  7. Polymers in cartilage defect repair of the knee : Current status and future prospects

    NARCIS (Netherlands)

    Jeuken, R.M.; Roth, A.K.; Peters, R.; van Donkelaar, C.C.; Thies, J.; van Rhijn, L.; Emans, P.

    2016-01-01

    Cartilage defects in the knee are often seen in young and active patients. There is a need for effective joint preserving treatments in patients suffering from cartilage defects, as untreated defects often lead to osteoarthritis. Within the last two decades, tissue engineering based techniques using

  8. Association between patellar cartilage defects and patellofemoral geometry: a matched-pair MRI comparison of patients with and without isolated patellar cartilage defects.

    Science.gov (United States)

    Mehl, Julian; Feucht, Matthias J; Bode, Gerrit; Dovi-Akue, David; Südkamp, Norbert P; Niemeyer, Philipp

    2016-03-01

    To compare the geometry of the patellofemoral joint on magnetic resonance images (MRI) between patients with isolated cartilage defects of the patella and a gender- and age-matched control group of patients without patellar cartilage defects. A total of 43 patients (17 female, 26 male) with arthroscopically verified grade III and IV patellar cartilage defects (defect group) were compared with a matched-pair control group of patients with isolated traumatic rupture of the anterior cruciate ligament without cartilage defects of the patellofemoral joint. Preoperative MRI images were analysed retrospectively with regard to patellar geometry (width, thickness, facet angle), trochlear geometry (dysplasia according to Dejour, sulcus angle, sulcus depth, lateral condyle index, trochlea facet asymmetry, lateral trochlea inclination) and patellofemoral alignment (tibial tuberosity-trochlear groove distance, patella height, lateral patella displacement, lateral patellofemoral angle, patella tilt, congruence angle). In addition to the comparison of group values, the measured values were compared to normal values reported in the literature, and the frequency of patients with pathologic findings was compared between both groups. The defect group demonstrated a significantly higher proximal chondral sulcus angle (p patellofemoral joint. In particular, a flat and shallow trochlea, trochlea dysplasia and patella alta seem to contribute to the development of patellar cartilage defects, which must be taken into consideration when planning to do surgical cartilage repair at the patella. III.

  9. Study of MR sequence in detecting hyaline cartilage defects of the knee joint

    International Nuclear Information System (INIS)

    Li Songbai; He Cuiju; Sun Wenge; Li Chunkui; Qi Xixun; Li Yanliang; Xu Ke; Bai Xizhuang; Wu Zhenhua

    2003-01-01

    Objective: To evaluate the value of various MR imaging sequences for detecting hyaline cartilage defects. Methods: Ten animal models of cartilage defect were established in 5 pig knees. 5 knees were examined with nine different MR sequences. The signal noise ratio of cartilage and contrast noise ratio were calculated and compared between cartilage and adjacent tissue. Measurement of the defect depth and width on the imaging was correlated with the actual measurement before imaging. 23 patients with hyaline cartilage defects of the knee were evaluated with MR imaging. All these patients underwent subsequent arthroscopy. MR imaging protocol included the selected sequences in the experimental study. Results: The cartilage SNR was better in FSE PD, FS 3D FSPGR, and FS FSE PD sequences. CNR between cartilage and subcartilaginous bone was best in FS 3D FSPGR and FS FSE PD sequences. CNR between cartilage and joint fluid was best in FS 3D FSPGR and FS FSE T 2 WI sequences. CNR between cartilage and meniscus and ligament was best in FS 3D FSPGR, FS FSE PD, SE T 1 WI, and IR TI700 sequences. CNR between cartilage and fat was best in FS 3D FSPGR and SE T 1 WI sequences. The width and depth correlation was best in IR TI700 sequence, which showed the statistical significance (P 2 WI sequence, 68%, 99%, and 0.74, respectively with IR TI700 sequence. Conclusion: The sensitivity of FS 3D FSPGR sequence in detecting hyaline cartilage defect is the highest. T 1 WI of spin echo sequence and T 2 WI/PDWI of fast spin-echo with fat saturation should be the standard sequence in the examination of knee joint. T 1 WI of IR sequence has potential clinical value for cartilage examination

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

    Science.gov (United States)

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2018-07-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  14. The immunomodulatory effects of shark cartilage on the mouse and human immune system

    Directory of Open Access Journals (Sweden)

    ali Sheikhian

    2007-01-01

    Materials and methods: In an experimental study, the effects of different doses of shark cartilage on humoral (antibody titer immune response against sheep red blood cells (SRBC, were measured in mouse. In addition, we evaluated the modulatory effects of the shark cartilage on the natural killer (NK activity of the peritoneal cells of mouse against a tumor cell line called K562, according to the standard methods. The proliferative response of the human peripheral blood mononuclear cells was measured under the influence of shark cartilage. Results: Pure shark cartilage enhanced antibody response against SRBC in vivo. The hemagglutination titer which was 1/147 in the control group (injected with hen cartilage, increased to 1/1355 in the test group. The optimal dose was 100 mg/ml. both type of cartilage had blastogenic effect on peripheral blood mononuclear cells (the blastogenic index was 6.7 and 4.9 for impure shark cartilage and hen cartilage, respectively. NK activity was inhibited completely by pure shark cartilage (the amount of the killing activity of the effector peritoneal cells for the control and test groups against target cells was 25.9% and 5.5% respectively. Conclusion: Shark cartilage has a potent immunomodulatory effect on the specific immune mechanisms and some inhibitory effects on the innate immune mechanisms such as NC activity. Since the specific immunity has a more pivotal role against tumor formation, shark cartilage can be used as a cancer immunotherapeutic.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

    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

  17. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

    Science.gov (United States)

    Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

    2014-06-18

    After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

    Zhang, Hai-Ning; Li, Lei; Leng, Ping; Wang, Ying-Zhen; Lv, Cheng-Yu

    2009-04-01

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

  20. Priority of surgical treatment techniques of full cartilage defects of knee joint

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    Андрій Вікторович Літовченко

    2015-10-01

    Full Text Available Aim. Surgical treatment of chondromalacia of knee joint cartilage is an actual problem of the modern orthopedics because the means of conservative therapy can be realized at an initial stage only and almost exhausted at the further ones. Imperfections of palliative surgical techniques are the short-term clinical effect and pathogenetic baselessness because surgical procedure is not directed on reparation of cartilaginous tissue. For today there are a lot of transplantation techniques that are used for biological renewal of articular surface with formation of hyaline or at least hyaline-like cartilage. The deep forage of cartilage defect bottom to the medullary canal is a perspective and priority technique.Methods. The results of treatment of 61 patients with chondromalacia of knee joint of 3-4 degree according to R. Outerbridge are the base of the work. 20 patients of every group underwent microfracturization of cartilage defect bottom and subchondral forage of defect zone. 21 patients underwent the deep forage of defect zone of knee joint according to an offered technique.Result. The results of treatment with microfracturization, subchondral forage and deep forage of defect zone indicate the more strong clinical effect especially in the last clinical group where good and satisfactory results ratios in the term of observation 18 and 24 month remain stable.Conclusions. Deep forage of cartilage defects zone is the most adequate reparative technique of the surgical treatment of local knee joint cartilage defects. Owing to this procedure the number of cells of reparative chondrogenesis predecessors is realized

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

    OpenAIRE

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  4. The effect of oral consumption of shark cartilage on the cellular immune responses of cancer patients

    Directory of Open Access Journals (Sweden)

    somaye Shahrokhi

    2006-11-01

    Conclusion: It seems that shark cartilage could help strengthen cellular immunity which is important in tumor regression in breast cancer patients. So we suppose that it could be a good candidate for cancer treatment along with conventional medicine.

  5. The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits.

    Science.gov (United States)

    Zhang, Z; Li, L; Yang, W; Cao, Y; Shi, Y; Li, X; Zhang, Q

    2017-02-01

    To investigate the effects of different doses of insulin-like growth factor 1 (IGF-1) on the cartilage layer and subchondral bone (SB) during repair of full-thickness articular cartilage (AC) defects. IGF-1-loaded collagen membrane was implanted into full-thickness AC defects in rabbits. The effects of two different doses of IGF-1 on cartilage layer and SB adjacent to the defect, the cartilage structure, formation and integration, and the new SB formation were evaluated at the 1st, 4th and 8th week postoperation. Meanwhile, after 1 week treatment, the relative mRNA expressions in tissues adjacent to the defect, including cartilage and SB were determined by quantitative real-time RT-PCR (qRT-PCR), respectively. Different doses of IGF-1 induced different gene expression profiles in tissues adjacent to the defect and resulted in different repair outcomes. Particularly, at high dose IGF-1 aided cell survival, regulated the gene expressions in cartilage layer adjacent defect and altered ECM composition more effectively, improved the formation and integrity of neo-cartilage. While, at low dose IGF-1 regulated the gene expressions in SB more efficaciously and subsequently promoted the SB remodeling and reconstruction. Different doses of IGF-1 induced different responses of cartilage or SB during the repair of full-thickness AC defects. Particularly, high dose of IGF-1 was more beneficial to the neo-cartilage formation and integration, while low dose of it was more effective for the SB formation. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ralph M. Jeuken

    2016-06-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  8. Repair of full-thickness articular cartilage defects by cultured mesenchymal stem cells transfected with the transforming growth factor {beta}{sub 1} gene

    Energy Technology Data Exchange (ETDEWEB)

    Guo Xiaodong [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zheng Qixin [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Yang Shuhua [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Shao Zengwu [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Yuan Quan [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Pan Zhengqi [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Tang Shuo [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Liu Kai [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Quan Daping [Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (China)

    2006-12-15

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  10. Meckel's and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible.

    Science.gov (United States)

    Biosse Duplan, Martin; Komla-Ebri, Davide; Heuzé, Yann; Estibals, Valentin; Gaudas, Emilie; Kaci, Nabil; Benoist-Lasselin, Catherine; Zerah, Michel; Kramer, Ina; Kneissel, Michaela; Porta, Diana Grauss; Di Rocco, Federico; Legeai-Mallet, Laurence

    2016-07-15

    Activating FGFR3 mutations in human result in achondroplasia (ACH), the most frequent form of dwarfism, where cartilages are severely disturbed causing long bones, cranial base and vertebrae defects. Because mandibular development and growth rely on cartilages that guide or directly participate to the ossification process, we investigated the impact of FGFR3 mutations on mandibular shape, size and position. By using CT scan imaging of ACH children and by analyzing Fgfr3 Y367C/+ mice, a model of ACH, we show that FGFR3 gain-of-function mutations lead to structural anomalies of primary (Meckel's) and secondary (condylar) cartilages of the mandible, resulting in mandibular hypoplasia and dysmorphogenesis. These defects are likely related to a defective chondrocyte proliferation and differentiation and pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 corrects Meckel's and condylar cartilages defects ex vivo. Moreover, we show that low dose of NVP-BGJ398 improves in vivo condyle growth and corrects dysmorphologies in Fgfr3 Y367C/+ mice, suggesting that postnatal treatment with NVP-BGJ398 mice might offer a new therapeutic strategy to improve mandible anomalies in ACH and others FGFR3-related disorders. © The Author 2016. Published by Oxford University Press.

  11. Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint

    DEFF Research Database (Denmark)

    Niemeyer, Philipp; Pestka, Jan M; Kreuz, Peter C

    2008-01-01

    BACKGROUND: Although autologous chondrocyte implantation (ACI) is a well-established therapy for the treatment of isolated cartilage defects of the knee joint, little is known about typical complications and their treatment after ACI. HYPOTHESIS: Unsatisfactory outcome after ACI is associated...

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

    Science.gov (United States)

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

    2017-08-25

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

  13. Treatment of deep hyalin cartilage defects with autologous perichondrial grafts.

    Science.gov (United States)

    Bruns, J; Steinhagen, J

    2003-07-01

    Perichondrial transplantation was performed in 29 patients suffering from a deep chondral lesion with different etiologies. Only those patients with a cartilage lesion in the knee joint were included. Patients were initially and postoperatively examined using the Lysholm- and HSS-Score. In most of the patients (20/29) trauma and the recurrence of osteochondrosis dissecans (6/29) were the cause of the cartilage lesion. Most often the medial femoral condyle (19/29) and, secondly, the lateral femoral condyle (5/29) were involved. In six patients additional therapeutic measures (ACL-plasty, n = 2; high tibial osteotomy because of varus mal-alignment, n = 4) had to be adopted. Follow-up examination was possible in 26/29 patients after a minimum postoperative period of 12 months. All patients exhibited a distinct and significant increase in both the Lysholm and the HSS-score. A follow-up after a minimum of 24 months was possible in 13/29 patients. Even these patients exhibited a distinct and significant improvement. Multiple follow-up examinations in 9/29 patients demonstrated maintenance of the first postoperative results obtained after one postoperative year for a maximum of 49 months in most of the patients. Only in one female patient, implantation of a semi-constrained total knee replacement was necessary because of osteoarthrosis resulting from crystal arthropathy (chondrocalcinosis). It was possible to obtain biopsies from three patients at the time osteosynthetic material was removed. In all cases hyaline-like cartilage was histologically observed. In the treatment of selected patients suffering from a circumscript cartilaginous lesion resulting from trauma or the recurrence of osteochondritis dissecans with a concomitant cartilage lesion but without major signs of osteoarthritis, perichondrial grafting can achieve acceptable clinical results, after a short follow-up period. In order to achieve satisfying results a good selection of patients and additional

  14. Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects.

    Science.gov (United States)

    Sekiya, Ichiro; Muneta, Takeshi; Horie, Masafumi; Koga, Hideyuki

    2015-07-01

    Transplantation of mesenchymal stem cells (MSCs) is one possible strategy to achieve articular cartilage repair. We previously reported that synovial MSCs were highly proliferative and able to undergo chondrogenesis. We also found that placing a suspension of synovial MSCs on a cartilage defect for 10 minutes promoted cartilage repair in rabbit and pig models. However, the in vivo efficacy of this approach has not been tested clinically. We asked whether transplantation of synovial MSCs improves (1) MRI features, (2) histologic features, and (3) clinical evaluation scores in patients with cartilage defects in the knee? Patients with a symptomatic single cartilage lesion of the femoral condyle were indicated for inclusion in our study, and between April 2008 and April 2011, 10 patients were enrolled in this study. All patients completed followups of 3 years or more. The average followup period was 52 months (range, 37-80 months). Synovial MSCs were expanded with 10% autologous human serum for 14 days after digestion. For transplantation, the patient was positioned so that the cartilage defect was facing upward, and synovial MSC suspension was placed on the cartilage defect with a syringe under arthroscopic control. The defect with the applied suspension then was held in the upward position for 10 minutes. Five patients underwent concomitant ACL reconstructions, among whom two had meniscus suturing performed simultaneously. For MRI quantification, the cartilage defect was scored from 0 to 5. Second-look arthroscopy was performed for four patients and biopsy specimens were evaluated histologically. Clinical outcome was assessed using the Lysholm score and Tegner Activity Level Scale at final followup. Comparisons of MRI and Lysholm scores before and after treatment for each patient were analyzed using the Wilcoxon signed-rank test. MRI score (median ± 95% CI) was 1.0 ± 0.3 before and 5.0 ± 0.7 after, and increased after treatment in each patient (p = 0.005). Second

  15. Growth hormone treatment in cartilage-hair hypoplasia: effects on growth and the immune system.

    NARCIS (Netherlands)

    Bocca, G.; Weemaes, C.M.R.; Burgt, C.J.A.M. van der; Otten, B.J.

    2004-01-01

    Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disorder characterized by metaphyseal chondrodysplasia with severe growth retardation and impaired immunity. We studied the effects of growth hormone treatment on growth parameters and the immune system in four children with CHH. The

  16. Macrophage phagocytosis alters the MRI signal of ferumoxytol-labeled mesenchymal stromal cells in cartilage defects

    Science.gov (United States)

    Nejadnik, Hossein; Lenkov, Olga; Gassert, Florian; Fretwell, Deborah; Lam, Isaac; Daldrup-Link, Heike E.

    2016-05-01

    Human mesenchymal stem cells (hMSCs) are a promising tool for cartilage regeneration in arthritic joints. hMSC labeling with iron oxide nanoparticles enables non-invasive in vivo monitoring of transplanted cells in cartilage defects with MR imaging. Since graft failure leads to macrophage phagocytosis of apoptotic cells, we evaluated in vitro and in vivo whether nanoparticle-labeled hMSCs show distinct MR signal characteristics before and after phagocytosis by macrophages. We found that apoptotic nanoparticle-labeled hMSCs were phagocytosed by macrophages while viable nanoparticle-labeled hMSCs were not. Serial MRI scans of hMSC transplants in arthritic joints of recipient rats showed that the iron signal of apoptotic, nanoparticle-labeled hMSCs engulfed by macrophages disappeared faster compared to viable hMSCs. This corresponded to poor cartilage repair outcomes of the apoptotic hMSC transplants. Therefore, rapid decline of iron MRI signal at the transplant site can indicate cell death and predict incomplete defect repair weeks later. Currently, hMSC graft failure can be only diagnosed by lack of cartilage defect repair several months after cell transplantation. The described imaging signs can diagnose hMSC transplant failure more readily, which could enable timely re-interventions and avoid unnecessary follow up studies of lost transplants.

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

    Science.gov (United States)

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

    2017-05-22

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

  18. Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects.

    Science.gov (United States)

    Hoemann, Caroline D; Hurtig, Mark; Rossomacha, Evgeny; Sun, Jun; Chevrier, Anik; Shive, Matthew S; Buschmann, Michael D

    2005-12-01

    Microfracture is a surgical procedure that is used to treat focal articular cartilage defects. Although joint function improves following microfracture, the procedure elicits incomplete repair. As blood clot formation in the microfracture defect is an essential initiating event in microfracture therapy, we hypothesized that the repair would be improved if the microfracture defect were filled with a blood clot that was stabilized by the incorporation of a thrombogenic and adhesive polymer, specifically, chitosan. The objectives of the present study were to evaluate (1) blood clot adhesion in fresh microfracture defects and (2) the quality of the repair, at six months postoperatively, of microfracture defects that had been treated with or without chitosan-glycerol phosphate/blood clot implants, using a sheep model. In eighteen sheep, two 1-cm2 full-thickness chondral defects were created in the distal part of the femur and treated with microfracture; one defect was made in the medial femoral condyle, and the other defect was made in the trochlea. In four sheep, microfracture defects were created bilaterally; the microfracture defects in one knee received no further treatment, and the microfracture defects in the contralateral knee were filled with chitosan-glycerol phosphate/autologous whole blood and the implants were allowed to solidify. Fresh defects in these four sheep were collected at one hour postoperatively to compare the retention of the chitosan-glycerol phosphate/blood clot with that of the normal clot and to define the histologic characteristics of these fresh defects. In the other fourteen sheep, microfracture defects were made in only one knee and either were left untreated (control group; six sheep) or were treated with chitosan-glycerol phosphate/blood implant (treatment group; eight sheep), and the quality of repair was assessed histologically, histomorphometrically, and biochemically at six months postoperatively. In the defects that were examined

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

    Directory of Open Access Journals (Sweden)

    Amir Sotoudeh

    2013-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Jan-Philipp Stromps

    2014-01-01

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

  1. Restoration of limited defects of the cartilage with the use of cell-engineered constructs

    Directory of Open Access Journals (Sweden)

    S. A. Gerasimov

    2017-01-01

    Full Text Available Aim: to develop a three-dimensional composite cell-engineered constructs (CEC for restoration of limited defects of the cartilage in experiment.Materials and methods. To create a cell-engineered constructs (CEC, were used collagenic carriers: «Chondro Gide» impermeable bilayer membrane and «Osteoplast» permeable matrix. A comparative study of their cytotoxic and adhesion properties was made in vitro. Chondroplastic potential of prepared CECs based on collagenous matrices with allogeneic mesenchymal stem cells (MSC of the rabbit bone marrow grown on their surface was assessed in vivo. A cylindrical defect of the cartilage of the medial femoral condyle 3.3 mm in diameter at a depth of 1.5 mm was formed on both rabbit feet. Laboratory animals were divided into 3 groups: control group; Experiment 1 group with Chondro Gide used as the MSC carrier within CEC; Experiment 2 group using Osteoplast matrix. Upon experiment completion, a morphometric and histomorphologic research of tissue specimens was made. For statistical evaluation of the results a defect region recovery factor (RF was offered and used. Results. After a 6-month observation period the control group showed partial recovery of the defect region with the recovery factor (RF of 0.62 ± 0.06. The RF in Experiment 1 group equalled to 0.79 ± 0.07, Experiment 2 group revealed RF at the level of 0.88 ± 0.02. Statistical analysis of the research results shows that the use of CEC used in Experiment 2 group reduces a relative risk of therapeutic failures by 92.9%, and absolute risk – by 43.3% as compared to Experiment 1 group. Histomorphologic research data are indicative of a hyaline cartilage formation in the central defect zone, which is partially close to the intact cartilage to the maximum with zonality marked.Conclusion. Results of the research of the developed three-dimension cell-engineered constructs consisting of mesenchymal stem cells of the bone marrow grown on the Osteoplast

  2. MR appearance of cartilage defects of the knee: preliminary results of a spiral CT arthrography-guided analysis

    International Nuclear Information System (INIS)

    Berg, B.C. vande; Lecouvet, F.E.; Maldague, B.; Malghem, J.

    2004-01-01

    The aim of this study was to determine signal intensity patterns of cartilage defects at MR imaging. The MR imaging (3-mm-thick fat-suppressed intermediate-weighted fast spin-echo images) was obtained in 31 knees (21 male and 10 female patients; mean age 45.5 years) blindly selected from a series of 252 consecutive knees investigated by dual-detector spiral CT arthrography. Two radiologists determined in consensus the MR signal intensity of the cartilage areas where cartilage defects had been demonstrated on the corresponding reformatted CT arthrographic images. There were 83 cartilage defects at spiral CT arthrography. In 52 (63%) lesion areas, the MR signal intensity was higher than that of adjacent normal cartilage with signal intensity equivalent to (n=31) or lower than (n=21) that of articular fluid. The MR signal intensity was equivalent to that of adjacent normal cartilage in 17 (20%) lesion areas and lower than that of adjacent cartilage in 8 (10%) lesion areas. In 6 (7%) lesion areas, mixed low and high signal intensity was observed. The MR signal intensity of cartilage defects demonstrated on spiral CT arthrographic images varies from low to high on fat-suppressed intermediate-weighted fast spin-echo MR images obtained with our equipment and MR parameters. (orig.)

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

    Science.gov (United States)

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

    2011-06-01

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

  4. Cartilage.

    Science.gov (United States)

    Caplan, Arnold I.

    1984-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  6. Bone Marrow Aspirate Concentrate for Cartilage Defects of the Knee: From Bench to Bedside Evidence.

    Science.gov (United States)

    Cotter, Eric J; Wang, Kevin C; Yanke, Adam B; Chubinskaya, Susan

    2018-04-01

    Objective To critically evaluate the current basic science, translational, and clinical data regarding bone marrow aspirate concentrate (BMAC) in the setting of focal cartilage defects of the knee and describe clinical indications and future research questions surrounding the clinical utility of BMAC for treatment of these lesions. Design A literature search was performed using the PubMed and Ovid MEDLINE databases for studies in English (1980-2017) using keywords, including ["bone marrow aspirate" and "cartilage"], ["mesenchymal stem cells" and "cartilage"], and ["bone marrow aspirate" and "mesenchymal stem cells" and "orthopedics"]. A total of 1832 articles were reviewed by 2 independent authors and additional literature found through scanning references of cited articles. Results BMAC has demonstrated promising results in the clinical application for repair of chondral defects as an adjuvant procedure or as an independent management technique. A subcomponent of BMAC, bone marrow derived-mesenchymal stem cells (MSCs) possess the ability to differentiate into cells important for osteogenesis and chondrogenesis. Modulation of paracrine signaling is perhaps the most important function of BM-MSCs in this setting. In an effort to increase the cellular yield, authors have shown the ability to expand BM-MSCs in culture while maintaining phenotype. Conclusions Translational studies have demonstrated good clinical efficacy of BMAC both concomitant with cartilage restoration procedures, at defined time points after surgery, and as isolated injections. Early clinical data suggests BMAC may help stimulate a more robust hyaline cartilage repair tissue response. Numerous questions remain regarding BMAC usage, including cell source, cell expansion, optimal pathology, and injection timing and quantity.

  7. Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing.

    Science.gov (United States)

    Cunniffe, Gráinne M; Vinardell, Tatiana; Murphy, J Mary; Thompson, Emmet M; Matsiko, Amos; O'Brien, Fergal J; Kelly, Daniel J

    2015-09-01

    Clinical translation of tissue engineered therapeutics is hampered by the significant logistical and regulatory challenges associated with such products, prompting increased interest in the use of decellularized extracellular matrix (ECM) to enhance endogenous regeneration. Most bones develop and heal by endochondral ossification, the replacement of a hypertrophic cartilaginous intermediary with bone. The hypothesis of this study is that a porous scaffold derived from decellularized tissue engineered hypertrophic cartilage will retain the necessary signals to instruct host cells to accelerate endogenous bone regeneration. Cartilage tissue (CT) and hypertrophic cartilage tissue (HT) were engineered using human bone marrow derived mesenchymal stem cells, decellularized and the remaining ECM was freeze-dried to generate porous scaffolds. When implanted subcutaneously in nude mice, only the decellularized HT-derived scaffolds were found to induce vascularization and de novo mineral accumulation. Furthermore, when implanted into critically-sized femoral defects, full bridging was observed in half of the defects treated with HT scaffolds, while no evidence of such bridging was found in empty controls. Host cells which had migrated throughout the scaffold were capable of producing new bone tissue, in contrast to fibrous tissue formation within empty controls. These results demonstrate the capacity of decellularized engineered tissues as 'off-the-shelf' implants to promote tissue regeneration. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

    Science.gov (United States)

    Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

    2016-10-22

    Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of

  9. CARTILAGE CONSTRUCTS ENGINEERED FROM CHONDROCYTES OVEREXPRESSING IGF-I IMPROVE THE REPAIR OF OSTEOCHONDRAL DEFECTS IN A RABBIT MODEL

    Science.gov (United States)

    Madry, Henning; Kaul, Gunter; Zurakowski, David; Vunjak-Novakovic, Gordana; Cucchiarini, Magali

    2015-01-01

    Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes over expressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-over expressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects. PMID:23588785

  10. Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model

    Directory of Open Access Journals (Sweden)

    H Madry

    2013-04-01

    Full Text Available Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes overexpressing a human insulin-like growth factor I (IGF-I gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-overexpressing chondrocytes markedly improved osteochondral repair compared with control (lacZ constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects.

  11. Tissue-engineered cartilaginous constructs for the treatment of caprine cartilage defects, including distribution of laminin and type IV collagen.

    Science.gov (United States)

    Jeng, Lily; Hsu, Hu-Ping; Spector, Myron

    2013-10-01

    The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration.

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

    Science.gov (United States)

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

    2016-12-01

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

  13. Articular cartilage defect detectability in human knees with MR-arthrography

    International Nuclear Information System (INIS)

    Engel, A.; Kramer, J.; Stiglbauer, R.; Hajek, P.C.; Imhof, H.

    1993-01-01

    One hundred and thirteen knee joints were examined, of which 48 showed damage of the hyaline cartilage in one or more locations. For the evaluation of the magnetic resonance (MR) arthrographic images we used the macroscopic staging according to Outerbridge, the defect staging according to Bauer, as well as a new MR-arthrographic staging. The results of the evaluation were compared with the surgical findings in 61 knee joints. This revealed a sensitivity of 86 %, a specificity of 100 % and accuracy of 90 %. All lesions that could not be classified on MR-arthrography were of stage-I chondromalacia. (orig.)

  14. Articular cartilage defect detectability in human knees with MR-arthrography

    Energy Technology Data Exchange (ETDEWEB)

    Engel, A. [Orthopaedic Clinic, Univ. of Vienna (Austria); Kramer, J. [MR-Inst., Univ. of Vienna (Austria); Stiglbauer, R. [MR-Inst., Univ. of Vienna (Austria); Hajek, P.C. [MR-Inst., Univ. of Vienna (Austria); Imhof, H. [MR-Inst., Univ. of Vienna (Austria)

    1993-04-01

    One hundred and thirteen knee joints were examined, of which 48 showed damage of the hyaline cartilage in one or more locations. For the evaluation of the magnetic resonance (MR) arthrographic images we used the macroscopic staging according to Outerbridge, the defect staging according to Bauer, as well as a new MR-arthrographic staging. The results of the evaluation were compared with the surgical findings in 61 knee joints. This revealed a sensitivity of 86 %, a specificity of 100 % and accuracy of 90 %. All lesions that could not be classified on MR-arthrography were of stage-I chondromalacia. (orig.)

  15. The skeletal phenotype of achondrogenesis type 1A is caused exclusively by cartilage defects.

    Science.gov (United States)

    Bird, Ian M; Kim, Susie H; Schweppe, Devin K; Caetano-Lopes, Joana; Robling, Alexander G; Charles, Julia F; Gygi, Steven P; Warman, Matthew L; Smits, Patrick J

    2018-01-08

    Inactivating mutations in the ubiquitously expressed membrane trafficking component GMAP-210 (encoded by Trip11 ) cause achondrogenesis type 1A (ACG1A). ACG1A is surprisingly tissue specific, mainly affecting cartilage development. Bone development is also abnormal, but as chondrogenesis and osteogenesis are closely coupled, this could be a secondary consequence of the cartilage defect. A possible explanation for the tissue specificity of ACG1A is that cartilage and bone are highly secretory tissues with a high use of the membrane trafficking machinery. The perinatal lethality of ACG1A prevents investigating this hypothesis. We therefore generated mice with conditional Trip11 knockout alleles and inactivated Trip11 in chondrocytes, osteoblasts, osteoclasts and pancreas acinar cells, all highly secretory cell types. We discovered that the ACG1A skeletal phenotype is solely due to absence of GMAP-210 in chondrocytes. Mice lacking GMAP-210 in osteoblasts, osteoclasts and acinar cells were normal. When we inactivated Trip11 in primary chondrocyte cultures, GMAP-210 deficiency affected trafficking of a subset of chondrocyte-expressed proteins rather than globally impairing membrane trafficking. Thus, GMAP-210 is essential for trafficking specific cargoes in chondrocytes but is dispensable in other highly secretory cells. © 2018. Published by The Company of Biologists Ltd.

  16. The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Cao, Lei; Yang, Fei; Liu, Guangwang; Yu, Degang; Li, Huiwu; Fan, Qiming; Gan, Yaokai; Tang, Tingting; Dai, Kerong

    2011-06-01

    Although Sox9 is essential for chondrogenic differentiation and matrix production, its application in cartilage tissue engineering has been rarely reported. In this study, the chondrogenic effect of Sox9 on bone marrow mesenchymal stem cells (BMSCs) in vitro and its application in articular cartilage repair in vivo were evaluated. Rabbit BMSCs were transduced with adenoviral vector containing Sox9. Toluidine blue, safranin O staining and real-time PCR were performed to check chondrogenic differentiation. The results showed that Sox9 could induce chondrogenesis of BMSCs both in monolayer and on PGA scaffold effectively. The rabbit model with full-thickness cartilage defects was established and then repaired by PGA scaffold and rabbit BMSCs with or without Sox9 transduction. HE, safranin O staining and immunohistochemistry were used to assess the repair of defects by the complex. Better repair, including more newly-formed cartilage tissue and hyaline cartilage-specific extracellular matrix and greater expression of several chondrogenesis marker genes were observed in PGA scaffold and BMSCs with Sox9 transduction, compared to that without transduction. Our findings defined the important role of Sox9 in the repair of cartilage defects in vivo and provided evidence that Sox9 had the potential and advantage in the application of tissue engineering. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Advances in the Surgical Management of Articular Cartilage Defects: Autologous Chondrocyte Implantation Techniques in the Pipeline.

    Science.gov (United States)

    Stein, Spencer; Strauss, Eric; Bosco, Joseph

    2013-01-01

    The purpose of this review is to gain insight into the latest methods of articular cartilage implantation (ACI) and to detail where they are in the Food and Drug Administration approval and regulatory process. A PubMed search was performed using the phrase "Autologous Chondrocyte Implantation" alone and with the words second generation and third generation. Additionally, clinicaltrials.gov was searched for the names of the seven specific procedures and the parent company websites were referenced. Two-Stage Techniques: BioCart II uses a FGF2v1 culture and a fibrinogen, thrombin matrix, whereas Hyalograft-C uses a Hyaff 11 matrix. MACI uses a collagen I/III matrix. Cartipatch consists of an agarose-alginate hydrogel. Neocart uses a high-pressure bioreactor for culturing with a type I collagen matrix. ChondroCelect makes use of a gene expression analysis to predict chondrocyte proliferation and has demonstrated significant clinical improvement, but failed to show superiority to microfracture in a phase III trial. One Step Technique: CAIS is an ACI procedure where harvested cartilage is minced and implanted into a matrix for defect filling. As full thickness defects in articular cartilage continue to pose a challenge to treat, new methods of repair are being researched. Later generation ACI has been developed to address the prevalence of fibrocartilage with microfracture and the complications associated with the periosteal flap of first generation ACI such as periosteal hypertrophy. The procedures and products reviewed here represent advances in tissue engineering, scaffolds and autologous chondrocyte culturing that may hold promise in our quest to alter the natural history of symptomatic chondral disease.

  18. A comparison between platelet-rich plasma (PRP and hyaluronate acid on the healing of cartilage defects.

    Directory of Open Access Journals (Sweden)

    Ji Liu

    Full Text Available Platelet-rich plasma (PRP has offered great promise for the treatment of cartilage degradation, and has been proved to have positive effects on the restoration of cartilage lesions. But no comparative work has been done between PRP and hyaluronate acid (HA concerning their restoring effect on cartilage defect, especially by means of animal experiments and histologic assessments. The purpose of the study was to compare the therapeutic effects of P-PRP and HA on osteoarthritis in rabbit knees. Thirty rabbits were used to establish the animal models by creating a cartilage defect of 5 mm in diameter on the condyles of the femurs, and were randomly divided into three groups: the P-PRP group, HA group and the control group. Then each group was treated with P-PRP, HA or saline solution, respectively. Six and twelve weeks later the rabbits were sacrificed and the samples were collected. The platelet number, the concentrations of growth factors of P-PRP and whole blood, and the IL-1β concentration in the joint fluid were investigated, and the histological assessment of the cartilage were performed according to Mankin's scoring system. Micro-CT was also used to evaluate the restoration of subchondral bone. The platelet concentration in P-PRP is 6.8 fold of that in the whole blood. The IL-1β level in the P-PRP group was lower than in the HA group (p<0.01 and in the control group (p<0.01. The restoration of the defected cartilage as well as the subchondral bone was better in the P-PRP group than in the HA group or the control group (P<0.05. Our data showed that P-PRP is better than HA in promoting the restoration of the cartilage and alleviating the arthritis caused by cartilage damage.

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

    Directory of Open Access Journals (Sweden)

    Vyacheslav Ogay

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

  1. Meckel’s and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible

    Science.gov (United States)

    Biosse Duplan, Martin; Komla-Ebri, Davide; Heuzé, Yann; Estibals, Valentin; Gaudas, Emilie; Kaci, Nabil; Benoist-Lasselin, Catherine; Zerah, Michel; Kramer, Ina; Kneissel, Michaela; Porta, Diana Grauss; Di Rocco, Federico; Legeai-Mallet, Laurence

    2016-01-01

    Activating FGFR3 mutations in human result in achondroplasia (ACH), the most frequent form of dwarfism, where cartilages are severely disturbed causing long bones, cranial base and vertebrae defects. Because mandibular development and growth rely on cartilages that guide or directly participate to the ossification process, we investigated the impact of FGFR3 mutations on mandibular shape, size and position. By using CT scan imaging of ACH children and by analyzing Fgfr3Y367C/+ mice, a model of ACH, we show that FGFR3 gain-of-function mutations lead to structural anomalies of primary (Meckel’s) and secondary (condylar) cartilages of the mandible, resulting in mandibular hypoplasia and dysmorphogenesis. These defects are likely related to a defective chondrocyte proliferation and differentiation and pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 corrects Meckel’s and condylar cartilages defects ex vivo. Moreover, we show that low dose of NVP-BGJ398 improves in vivo condyle growth and corrects dysmorphologies in Fgfr3Y367C/+ mice, suggesting that postnatal treatment with NVP-BGJ398 mice might offer a new therapeutic strategy to improve mandible anomalies in ACH and others FGFR3-related disorders. PMID:27260401

  2. [Incontinentia pigmenti with defect in cellular immunity].

    Science.gov (United States)

    Zamora-Chávez, Antonio; Escobar-Sánchez, Argelia; Sadowinski-Pine, Stanislaw; Saucedo-Ramírez, Omar Josué; Delgado-Barrera, Palmira; Enríquez-Quiñones, Claudia G

    Incontinentia pigmenti is a rare, X-linked genetic disease and affects all ectoderm-derived tissues such as skin, appendages, eyes, teeth and central nervous system as well as disorders of varying degree of cellular immunity characterized by decreasing melanin in the epidermis and increase in the dermis. When the condition occurs in males, it is lethal. We present the case of a 2-month-old infant with severe incontinentia pigmenti confirmed by histological examination of skin biopsy. The condition evolved with severe neurological disorders and seizures along with severe cellular immune deficiency, which affected the development of severe infections and caused the death of the patient. The importance of early clinical diagnosis is highlighted along with the importance of multidisciplinary management of neurological disorders and infectious complications. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  3. Association of childhood adiposity measures with adulthood knee cartilage defects and bone marrow lesions: a 25-year cohort study.

    Science.gov (United States)

    Meng, Tao; Thayer, Shaun; Venn, Alison; Wu, Feitong; Cicuttini, Flavia; March, Lyn; Dwyer, Terence; Halliday, Andrew; Cross, Marita; Laslett, Laura L; Jones, Graeme; Ding, Changhai; Antony, Benny

    2018-05-15

    To describe the associations between childhood adiposity measures and adulthood knee cartilage defects and bone marrow lesions (BMLs) measured 25 years later. 327 participants from the Australian Schools Health and Fitness Survey of 1985 (aged 7-15 years) were followed up 25 years later (aged 31-41 years). Childhood measures (weight, height and skinfolds) were collected in 1985. Body mass index (BMI), overweight status and fat mass were calculated. Participants underwent 1.5T knee magnetic resonance imaging (MRI) during 2008-2010, and cartilage defects and BMLs were scored from knee MRI scans. Log binomial regressions were used to examine the associations. Among 327 participants (47.1% females), 21 (6.4%) were overweight in childhood. Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects (Weight relative risk (RR) 1.05/kg, 95% confidence interval (CI) 1.01 to 1.09; BMI 1.10/kg/m 2 , 1.01 to 1.19; Overweight 2.22/yes, 1.21 to 4.08; fat mass 1.11/kg, 1.01 to 1.22), but not tibiofemoral cartilage defects. Childhood adiposity measures were not significantly associated with adulthood knee BMLs except for the association between childhood overweight status and adulthood patellar BMLs (RR 2.87/yes, 95% CI 1.10 to 7.53). These significant associations persisted after adjustment for corresponding adulthood adiposity measure. Childhood adiposity measures were associated with the increased risk of adulthood patellar cartilage defects and, to a lesser extent, BMLs, independent of adulthood adiposity measures. These results suggest that adiposity in childhood has long-term effects on patellar structural abnormalities in young adults. Copyright © 2018. Published by Elsevier Ltd.

  4. Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondral bone in microdrilled rabbit defects.

    Science.gov (United States)

    Hoemann, C D; Sun, J; McKee, M D; Chevrier, A; Rossomacha, E; Rivard, G-E; Hurtig, M; Buschmann, M D

    2007-01-01

    We have previously shown that microfractured ovine defects are repaired with more hyaline cartilage when the defect is treated with in situ-solidified implants of chitosan-glycerol phosphate (chitosan-GP) mixed with autologous whole blood. The objectives of this study were (1) to characterize chitosan-GP/blood clots in vitro, and (2) to develop a rabbit marrow stimulation model in order to determine the effects of the chitosan-GP/blood implant and of debridement on the formation of incipient cartilage repair tissue. Blood clots were characterized by histology and in vitro clot retraction tests. Bilateral 3.5 x 4 mm trochlear defects debrided into the calcified layer were pierced with four microdrill holes and filled with a chitosan-GP/blood implant or allowed to bleed freely as a control. At 1 day post-surgery, initial defects were characterized by histomorphometry (n=3). After 8 weeks of repair, osteochondral repair tissues between or through the drill holes were evaluated by histology, histomorphometry, collagen type II expression, and stereology (n=16). Chitosan-GP solutions structurally stabilized the blood clots by inhibiting clot retraction. Treatment of drilled defects with chitosan-GP/blood clots led to the formation of a more integrated and hyaline repair tissue above a more porous and vascularized subchondral bone plate compared to drilling alone. Correlation analysis of repair tissue between the drill holes revealed that the absence of calcified cartilage and the presence of a porous subchondral bone plate were predictors of greater repair tissue integration with subchondral bone (Phyaline and integrated repair tissue associated with a porous subchondral bone replete with blood vessels. Concomitant regeneration of a vascularized bone plate during cartilage repair could provide progenitors, anabolic factors and nutrients that aid in the formation of hyaline cartilage.

  5. Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model.

    Science.gov (United States)

    Shimizu, Manabu; Matsumoto, Taro; Kikuta, Shinsuke; Ohtaki, Munenori; Kano, Koichiro; Taniguchi, Hiroaki; Saito, Shu; Nagaoka, Masahiro; Tokuhashi, Yasuaki

    2018-03-20

    Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses the ability to proliferate effectively and the potential to differentiate into multiple linages of mesenchymal tissue; similar to adipose-derived stem cells (ASCs). The purpose of this study is to examine the effects of DFAT cell transplantation on cartilage repair in a rat model of osteochondral defects. Full-thickness osteochondral defects were created in the knees of Sprague-Dawley rats bilaterally. Cartilage-like micromass pellets were prepared from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently transplanted into the affected right knee of these rats. Defects in the left knee were used as a control. Macroscopic and microscopic changes of treated and control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To observe the transplanted cells, sectioned femurs were immunostained for GFP and type II collagen. DFAT cells formed micromass pellets expressing characteristics of immature cartilage in vitro. In the DFAT cell-transplanted limbs, the defects were completely filled with white micromass pellets as early as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted limbs compared to those of the control limbs. The modified O'Driscol histological scores for the DFAT cell-transplanted limbs were significantly higher than those of the control limbs at corresponding time points. GFP-positive DAFT cells were detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post-operation. Transplantation of DFAT cell-derived micromass pellets contribute to cartilage repair in a rat osteochondral defect model. DFAT cell transplantation may be a viable therapeutic strategy for the repair of osteochondral injuries. Copyright © 2018 The Authors. Published by

  6. Correlation between Focal Nodular Low Signal Changes in Hoffa’s Fat Pad Adjacent to Anterior Femoral Cartilage and Focal Cartilage Defect Underlying This Region and Its Possible Implication

    Directory of Open Access Journals (Sweden)

    Chermaine Deepa Antony

    2016-01-01

    Full Text Available Purpose. This study investigates the association between focal nodular mass with low signal in Hoffa’s fat pad adjacent to anterior femoral cartilage of the knee (FNMHF and focal cartilage abnormality in this region. Method. The magnetic resonance fast imaging employing steady-state acquisition sequence (MR FIESTA sagittal and axial images of the B1 and C1 region (described later of 148 patients were independently evaluated by two reviewers and categorized into four categories: normal, FNMHF with underlying focal cartilage abnormality, FNMHF with normal cartilage, and cartilage abnormality with no FNMHF. Results. There was a significant association (p=0.00 between FNMHF and immediate adjacent focal cartilage abnormality with high interobserver agreement. The absence of focal nodular lesions next to the anterior femoral cartilage has a very high negative predictive value for chondral injury (97.8%. Synovial biopsy of focal nodular lesion done during arthroscopy revealed some fibrocollagenous tissue and no inflammatory cells. Conclusion. We postulate that the FNMHF adjacent to the cartilage defects is a form of normal healing response to the cartilage damage. One patient with FHMHF and underlying cartilage abnormality was rescanned six months later. In this patient, the FNMHF disappeared and normal cartilage was observed in the adjacent region which may support this theory.

  7. Successful conservative management of symptomatic bilateral dorsal patellar defects presenting with cartilage involvement and bone marrow edema: MRI findings

    International Nuclear Information System (INIS)

    Kwee, Thomas C.; Sonneveld, Heleen; Nix, Maarten

    2016-01-01

    The dorsal patellar defect is a relatively rare entity that involves the superolateral quadrant of the patella. It is usually considered to represent a delayed ossification process, although its exact origin remains unclear. Because of its usually innocuous nature and clinical course, invasive interventions are generally deemed unnecessary, although curretage has been successfully performed on symptomatic cases. This case report presents a rather unusual case of symptomatic bilateral dorsal patellar defects with cartilage involvement and widespread surrounding bone marrow edema as demonstrated by magnetic resonance imaging (MRI). Both cartilage involvement and bone marrow edema should be considered part of the spectrum of associated MRI findings that can be encountered in this entity. Furthermore, the presented case shows that symptomatic dorsal patellar defects can be treated conservatively with success and that (decrease of) pain symptoms are likely related to (decrease of) bone marrow edema. (orig.)

  8. Successful conservative management of symptomatic bilateral dorsal patellar defects presenting with cartilage involvement and bone marrow edema: MRI findings.

    Science.gov (United States)

    Kwee, Thomas C; Sonneveld, Heleen; Nix, Maarten

    2016-05-01

    The dorsal patellar defect is a relatively rare entity that involves the superolateral quadrant of the patella. It is usually considered to represent a delayed ossification process, although its exact origin remains unclear. Because of its usually innocuous nature and clinical course, invasive interventions are generally deemed unnecessary, although curretage has been successfully performed on symptomatic cases. This case report presents a rather unusual case of symptomatic bilateral dorsal patellar defects with cartilage involvement and widespread surrounding bone marrow edema as demonstrated by magnetic resonance imaging (MRI). Both cartilage involvement and bone marrow edema should be considered part of the spectrum of associated MRI findings that can be encountered in this entity. Furthermore, the presented case shows that symptomatic dorsal patellar defects can be treated conservatively with success and that (decrease of) pain symptoms are likely related to (decrease of) bone marrow edema.

  9. Successful conservative management of symptomatic bilateral dorsal patellar defects presenting with cartilage involvement and bone marrow edema: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Meander Medical Center, Department of Radiology, Amersfoort (Netherlands); Sonneveld, Heleen [Meander Medical Center, Department of Orthopaedics, Amersfoort (Netherlands); Nix, Maarten [Meander Medical Center, Department of Radiology, Amersfoort (Netherlands)

    2016-05-15

    The dorsal patellar defect is a relatively rare entity that involves the superolateral quadrant of the patella. It is usually considered to represent a delayed ossification process, although its exact origin remains unclear. Because of its usually innocuous nature and clinical course, invasive interventions are generally deemed unnecessary, although curretage has been successfully performed on symptomatic cases. This case report presents a rather unusual case of symptomatic bilateral dorsal patellar defects with cartilage involvement and widespread surrounding bone marrow edema as demonstrated by magnetic resonance imaging (MRI). Both cartilage involvement and bone marrow edema should be considered part of the spectrum of associated MRI findings that can be encountered in this entity. Furthermore, the presented case shows that symptomatic dorsal patellar defects can be treated conservatively with success and that (decrease of) pain symptoms are likely related to (decrease of) bone marrow edema. (orig.)

  10. Small subchondral drill holes improve marrow stimulation of articular cartilage defects.

    Science.gov (United States)

    Eldracher, Mona; Orth, Patrick; Cucchiarini, Magali; Pape, Dietrich; Madry, Henning

    2014-11-01

    Subchondral drilling is an established marrow stimulation technique. Osteochondral repair is improved when the subchondral bone is perforated with small drill holes, reflecting the physiological subchondral trabecular distance. Controlled laboratory study. A rectangular full-thickness chondral defect was created in the trochlea of adult sheep (n = 13) and treated with 6 subchondral drillings of either 1.0 mm (reflective of the trabecular distance) or 1.8 mm in diameter. Osteochondral repair was assessed after 6 months in vivo by macroscopic, histological, and immunohistochemical analyses and by micro-computed tomography. The application of 1.0-mm subchondral drill holes led to significantly improved histological matrix staining, cellular morphological characteristics, subchondral bone reconstitution, and average total histological score as well as significantly higher immunoreactivity to type II collagen and reduced immunoreactivity to type I collagen in the repair tissue compared with 1.8-mm drill holes. Analysis of osteoarthritic changes in the cartilage adjacent to the defects revealed no significant differences between treatment groups. Restoration of the microstructure of the subchondral bone plate below the chondral defects was significantly improved after 1.0-mm compared to 1.8-mm drilling, as shown by higher bone volume and reduced thickening of the subchondral bone plate. Likewise, the microarchitecture of the drilled subarticular spongiosa was better restored after 1.0-mm drilling, indicated by significantly higher bone volume and more and thinner trabeculae. Moreover, the bone mineral density of the subchondral bone in 1.0-mm drill holes was similar to the adjacent subchondral bone, whereas it was significantly reduced in 1.8-mm drill holes. No significant correlations existed between cartilage and subchondral bone repair. Small subchondral drill holes that reflect the physiological trabecular distance improve osteochondral repair in a translational

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

    Science.gov (United States)

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

    2018-03-26

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

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

    Directory of Open Access Journals (Sweden)

    Abraham S

    2007-01-01

    -PCR study of the cells of group I were positive for TGF beta 3 (Proliferation, differentiation, and other functions, GR beta, GR alpha (Development, metabolism and immune Response (glucocorticoid receptor alpha, AGGF (Apoptosis, VDR (Vitamin D3 Receptor, Col II (Type II Collagen. Conclusion: We have established a methodology by which Human chondrocytes could be cultured in vitro without any growth factors for a period of 16 weeks in a polymer-hydrogel scaffold. Upon further confirmation of their characteristics, the TGP grown chondrocytes can be used for autologous implantation to repair damaged cartilage area as the Collagen Type II which grows better without growth factors in the scaffold, eventually will become Hyaline cartilage is expected to give a longer disease free duration than the present method of ACI.

  13. Advances of human bone marrow-derived mesenchymal stem cells in the treatment of cartilage defects: a systematic review.

    Science.gov (United States)

    Gopal, Kaliappan; Amirhamed, Haji Alizadeh; Kamarul, Tunku

    2014-06-01

    Mesenchymal stem cell (MSC)-based therapies represent a new option for treating damaged cartilage. However, the outcomes following its clinical application have seldom been previously compared. The present paper presents the systematic review of current literatures on MSC-based therapy for cartilage repair in clinical applications. Ovid, Scopus, PubMed, ISI Web of Knowledge and Google Scholar online databases were searched using several keywords, which include "cartilage" and "stem cells". Only studies using bone marrow-derived MSC (BM-MSC) to treat cartilage defects clinically were included in this review. The clinical outcomes were compared, and the quality of the tissue repair was analysed where possible. Of the 996 articles, only six (n = 6) clinical studies have described the use of BM-MSC in clinical applications. Two studies were cohort observational trials, three were case series, and one was a case report. In the two comparative trials, BM-MSCs produced superior repair to cartilage treatment without cells and have comparable outcomes to autologous chondrocyte implantation. The case series and case-control studies have demonstrated that use of BM-MSCs resulted in better short- to long-term clinical outcomes with minimal complications. In addition, histological analyses in two studies have resulted in good repair tissue formation at the damaged site, composed mainly of hyaline-like cartilage. Although results of the respective studies are highly indicative that BM-MSC-based therapy is superior, due to the differences in methods and selection criteria used, it was not possible to make direct comparison between the studies. In conclusion, published studies do suggest that BM-MSCs could provide superior cartilage repair. However, due to limited number of reports, more robust studies might be required before a definitive conclusion can be drawn.

  14. Histochemical characterization of human osteochondral tissue: comparison between healthy cartilage, arthrotic tissues, and cartilage defect treated with MACI technique

    Directory of Open Access Journals (Sweden)

    F. Tessarolo

    2011-01-01

    Full Text Available Matrix-induced sutologous chondrocytes implantation (MACI is a promising technique for the treatment of articular cartilage lesions, but long time outcome have to be established. We developed and optimized specific techniques of histochemical staining to characterize healthy and pathologic osteochondral tissue. Seven different staining protocols were applied to assess tissue architecture, cells morphology, proteoglycan content, and collagen fibers distribution. Potentialities of histochemical staining and histomorphology of biopsies from second look arthroscopy will be presented.

  15. Cell compaction influences the regenerative potential of passaged bovine articular chondrocytes in an ex vivo cartilage defect model.

    Science.gov (United States)

    Schmutzer, Michael; Aszodi, Attila

    2017-04-01

    The loss and degradation of articular cartilage tissue matrix play central roles in the process of osteoarthritis (OA). New models for evaluating cartilage repair/regeneration are thus of great value for transferring various culture systems into clinically relevant situations. The repair process can be better monitored in ex vivo systems than in in vitro cell cultures. I have therefore established an ex vivo defect model prepared from bovine femoral condyles for evaluating cartilage repair by the implantation of cells cultured in various ways, e.g., monolayer-cultured cells or suspension or pellet cultures of articular bovine chondrocytes representing different cell compactions with variable densities of chondrocytes. I report that the integrin subunit α10 was significantly upregulated in suspension-cultured bovine chondrocytes at passage P2 compared with monolayer-cultured cells at P1 (p = 0.0083) and P2 (p innovation of this system over in vitro differentiation (e.g., micromass, pellet) assays is the possibility of examining and evaluating cartilage regeneration in an environment in which implanted cells are embedded within native surrounding tissue at the defect site. Such ex vivo explants might serve as a better model system to mimic clinical situations. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  16. The effect of 3D nanofibrous scaffolds on the chondrogenesis of induced pluripotent stem cells and their application in restoration of cartilage defects.

    Science.gov (United States)

    Liu, Ji; Nie, Huarong; Xu, Zhengliang; Niu, Xin; Guo, Shangchun; Yin, Junhui; Guo, Fei; Li, Gang; Wang, Yang; Zhang, Changqing

    2014-01-01

    The discovery of induced pluripotent stem cells (iPSCs) rendered the reprogramming of terminally differentiated cells to primary stem cells with pluripotency possible and provided potential for the regeneration and restoration of cartilage defect. Chondrogenic differentiation of iPSCs is crucial for their application in cartilage tissue engineering. In this study we investigated the effect of 3D nanofibrous scaffolds on the chondrogenesis of iPSCs and articular cartilage defect restoration. Super-hydrophilic and durable mechanic polycaprolactone (PCL)/gelatin scaffolds were fabricated using two separate electrospinning processes. The morphological structure and mechanical properties of the scaffolds were characterized. The chondrogenesis of the iPSCs in vitro and the restoration of the cartilage defect was investigated using scanning electron microscopy (SEM), the Cell Counting Kit-8 (CCK-8), histological observation, RT-qPCR, and western blot analysis. iPSCs on the scaffolds expressed higher levels of chondrogenic markers than the control group. In an animal model, cartilage defects implanted with the scaffold-cell complex exhibited an enhanced gross appearance and histological improvements, higher cartilage-specific gene expression and protein levels, as well as subchondral bone regeneration. Therefore, we showed scaffolds with a 3D nanofibrous structure enhanced the chondrogenesis of iPSCs and that iPSC-containing scaffolds improved the restoration of cartilage defects to a greater degree than did scaffolds alone in vivo.

  17. The effect of 3D nanofibrous scaffolds on the chondrogenesis of induced pluripotent stem cells and their application in restoration of cartilage defects.

    Directory of Open Access Journals (Sweden)

    Ji Liu

    Full Text Available The discovery of induced pluripotent stem cells (iPSCs rendered the reprogramming of terminally differentiated cells to primary stem cells with pluripotency possible and provided potential for the regeneration and restoration of cartilage defect. Chondrogenic differentiation of iPSCs is crucial for their application in cartilage tissue engineering. In this study we investigated the effect of 3D nanofibrous scaffolds on the chondrogenesis of iPSCs and articular cartilage defect restoration. Super-hydrophilic and durable mechanic polycaprolactone (PCL/gelatin scaffolds were fabricated using two separate electrospinning processes. The morphological structure and mechanical properties of the scaffolds were characterized. The chondrogenesis of the iPSCs in vitro and the restoration of the cartilage defect was investigated using scanning electron microscopy (SEM, the Cell Counting Kit-8 (CCK-8, histological observation, RT-qPCR, and western blot analysis. iPSCs on the scaffolds expressed higher levels of chondrogenic markers than the control group. In an animal model, cartilage defects implanted with the scaffold-cell complex exhibited an enhanced gross appearance and histological improvements, higher cartilage-specific gene expression and protein levels, as well as subchondral bone regeneration. Therefore, we showed scaffolds with a 3D nanofibrous structure enhanced the chondrogenesis of iPSCs and that iPSC-containing scaffolds improved the restoration of cartilage defects to a greater degree than did scaffolds alone in vivo.

  18. Stability of Collagen Scaffold Implants for Animals with Iatrogenic Articular Cartilage Defects

    Directory of Open Access Journals (Sweden)

    Josef Jančář

    2009-01-01

    Full Text Available Synthesis and characterization of biodegradable hydrogels based on collagen modified by addition of synthetic biodegradable copolymer intended for preparation of porous scaffolds for mesenchymal stem cells used for possible implantation to animals with articular surface defects was investigated. The synthetic biodegradable tri-block copolymer used was the block copolymer of polyethylene glycol (PEG, polylactic acid (PLA, polyglycolic acid (PGA (PEG-PLGA endcapped with itaconic acid (ITA. The water-soluble carbodiimide and N-hydroxysuccimide system (EDC-NHS was chosen as the cross-linking agent used to control the rate of hydrogel resorption. Dependence of the physical properties of the prepared hydrogels on the concentration of the EDC-NHS cross-linker, reaction time and concentration of PEG-PLGA-ITA copolymer was examined. Swelling behaviour, thermal stability, surface morphology and degradation rate were also characterized. Based on the obtained results, it can be concluded that increase in concentration of the cross-linking agent, as well as prolonged cross-linking time and increased amount of synthetic copolymer lead to enhanced thermal stability of the gels together with a reduced swelling ratio and degradation rate in saline. The resorption rate of these gels used in preparation of cartilage scaffolds can be controlled over a wide time interval by varying the collagen/(PEG-PLGA-ITA blend composition or the conditions of the cross-linking reaction.

  19. Gel-type autologous chondrocyte (Chondron™ implantation for treatment of articular cartilage defects of the knee

    Directory of Open Access Journals (Sweden)

    Chun Chung-Woo

    2010-05-01

    Full Text Available Abstract Background Gel-type autologous chondrocyte (Chondron™ implantations have been used for several years without using periosteum or membrane. This study involves evaluations of the clinical results of Chondron™ at many clinical centers at various time points during the postoperative patient follow-up. Methods Data from 98 patients with articular cartilage injury of the knee joint and who underwent Chondron™ implantation at ten Korean hospitals between January 2005 and November 2008, were included and were divided into two groups based on the patient follow-up period, i.e. 13~24-month follow-up and greater than 25-month follow-up. The telephone Knee Society Score obtained during telephone interviews with patients, was used as the evaluation tool. Results On the tKSS-A (telephone Knee Society Score-A, the score improved from 43.52 ± 20.20 to 89.71 ± 13.69 (P Conclusion Gel-type autologous chondrocyte implantation for chondral knee defects appears to be a safe and effective method for both decreasing pain and improving knee function.

  20. Programmed Application of Transforming Growth Factor β3 and Rac1 Inhibitor NSC23766 Committed Hyaline Cartilage Differentiation of Adipose-Derived Stem Cells for Osteochondral Defect Repair.

    Science.gov (United States)

    Zhu, Shouan; Chen, Pengfei; Wu, Yan; Xiong, Si; Sun, Heng; Xia, Qingqing; Shi, Libing; Liu, Huanhuan; Ouyang, Hong Wei

    2014-10-01

    Hyaline cartilage differentiation is always the challenge with application of stem cells for joint repair. Transforming growth factors (TGFs) and bone morphogenetic proteins can initiate cartilage differentiation but often lead to hypertrophy and calcification, related to abnormal Rac1 activity. In this study, we developed a strategy of programmed application of TGFβ3 and Rac1 inhibitor NSC23766 to commit the hyaline cartilage differentiation of adipose-derived stem cells (ADSCs) for joint cartilage repair. ADSCs were isolated and cultured in a micromass and pellet culture model to evaluate chondrogenic and hypertrophic differentiation. The function of Rac1 was investigated with constitutively active Rac1 mutant and dominant negative Rac1 mutant. The efficacy of ADSCs with programmed application of TGFβ3 and Rac1 inhibitor for cartilage repair was studied in a rat model of osteochondral defects. The results showed that TGFβ3 promoted ADSCs chondro-lineage differentiation and that NSC23766 prevented ADSC-derived chondrocytes from hypertrophy in vitro. The combination of ADSCs, TGFβ3, and NSC23766 promoted quality osteochondral defect repair in rats with much less chondrocytes hypertrophy and significantly higher International Cartilage Repair Society macroscopic and microscopic scores. The findings have illustrated that programmed application of TGFβ3 and Rac1 inhibitor NSC23766 can commit ADSCs to chondro-lineage differentiation and improve the efficacy of ADSCs for cartilage defect repair. These findings suggest a promising stem cell-based strategy for articular cartilage repair. ©AlphaMed Press.

  1. Excessive activity of cathepsin K is associated with cartilage defects in a zebrafish model of mucolipidosis II

    Directory of Open Access Journals (Sweden)

    Aaron C. Petrey

    2012-03-01

    The severe pediatric disorder mucolipidosis II (ML-II; also known as I-cell disease is caused by defects in mannose 6-phosphate (Man-6-P biosynthesis. Patients with ML-II exhibit multiple developmental defects, including skeletal, craniofacial and joint abnormalities. To date, the molecular mechanisms that underlie these clinical manifestations are poorly understood. Taking advantage of a zebrafish model of ML-II, we previously showed that the cartilage morphogenesis defects in this model are associated with altered chondrocyte differentiation and excessive deposition of type II collagen, indicating that aspects of development that rely on proper extracellular matrix homeostasis are sensitive to decreases in Man-6-P biosynthesis. To further investigate the molecular bases for the cartilage phenotypes, we analyzed the transcript abundance of several genes in chondrocyte-enriched cell populations isolated from wild-type and ML-II zebrafish embryos. Increased levels of cathepsin and matrix metalloproteinase (MMP transcripts were noted in ML-II cell populations. This increase in transcript abundance corresponded with elevated and sustained activity of several cathepsins (K, L and S and MMP-13 during early development. Unlike MMP-13, for which higher levels of protein were detected, the sustained activity of cathepsin K at later stages seemed to result from its abnormal processing and activation. Inhibition of cathepsin K activity by pharmacological or genetic means not only reduced the activity of this enzyme but led to a broad reduction in additional protease activity, significant correction of the cartilage morphogenesis phenotype and reduced type II collagen staining in ML-II embryos. Our findings suggest a central role for excessive cathepsin K activity in the developmental aspects of ML-II cartilage pathogenesis and highlight the utility of the zebrafish system to address the biochemical underpinnings of metabolic disease.

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Kuo-Hwa Wang

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

  4. Type II collagen in cartilage evokes peptide-specific tolerance and skews the immune response.

    Science.gov (United States)

    Malmström, V; Kjellén, P; Holmdahl, R

    1998-06-01

    T cell recognition of type II collagen (CII) is a crucial event in the induction of collagen-induced arthritis in the mouse. Several CII peptides have been shown to be of importance, dependent on which MHC haplotype the mouse carries. By sequencing the rat CII and comparing the sequence with mouse, human, bovine and chicken CII, we have found that the immunodominant peptides all differ at critical positions compared with the autologous mouse sequence. Transgenic expression of the immunodominant Aq-restricted heterologous CII 256-270 epitope inserted into type I collagen (TSC mice) or type II collagen (MMC-1 mice) led to epitope-specific tolerance. Immunization of TSC mice with chick CII led to arthritis and immune responses, dependent on the subdominant, Aq-restricted and chick-specific CII 190-200 epitope. Immunization of F1 mice, expressing both H-2q and H-2r as well as transgenic expression of the Aq-restricted CII 256-270 epitope in cartilage, with bovine CII, led to arthritis, dependent on the Ar-restricted, bovine-specific epitope CII 607-621. These data show that the immunodominance of CII recognition is directed towards heterologous determinants, and that T cells directed towards the corresponding autologous epitopes are tolerated without evidence of active suppression.

  5. Allogenic lyophilized cartilage grafts for craniomaxillofacial reconstruction

    International Nuclear Information System (INIS)

    Pill Hoon Choung

    1999-01-01

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

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

    International Nuclear Information System (INIS)

    Tao, Hongyue; Feng, Xiaoyuan; Chen, Shuang; Li, Hong; Hua, Yinghui; Chen, Zhongqing

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-26

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

  8. Treatment of a Focal Articular Cartilage Defect of the Talus with Polymer-Based Autologous Chondrocyte Implantation: A 12-Year Follow-Up Period.

    Science.gov (United States)

    Kreuz, Peter Cornelius; Kalkreuth, Richard Horst; Niemeyer, Philipp; Uhl, Markus; Erggelet, Christoph

    Autologous chondrocyte implantation (ACI) is a first-line treatment option for large articular cartilage defects. Although well-established for cartilage defects in the knee, studies of the long-term outcomes of matrix-assisted ACI to treat cartilage defects in the ankle are rare. In the present report, we describe for the first time the long-term clinical and radiologic results 12 years after polymer-based matrix-assisted ACI treat a full-thickness talar cartilage defect in a 25-year-old male patient. The clinical outcome was assessed using the visual analog scale and Freiburg ankle score, magnetic resonance imaging evaluation using the Henderson-Kreuz scoring system and T2 mapping. Clinical assessment revealed improved visual analog scale and Freiburg ankle scores. The radiologic analysis and T2 relaxation time values indicated the formation of hyaline-like repair tissue. Polymer-based autologous chondrocytes has been shown to be a safe and clinically effective long-term treatment of articular cartilage defects in the talus. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2012-03-01

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

  10. Cartilage immunoprivilege depends on donor source and lesion location.

    Science.gov (United States)

    Arzi, B; DuRaine, G D; Lee, C A; Huey, D J; Borjesson, D L; Murphy, B G; Hu, J C Y; Baumgarth, N; Athanasiou, K A

    2015-09-01

    The ability to repair damaged cartilage is a major goal of musculoskeletal tissue engineering. Allogeneic (same species, different individual) or xenogeneic (different species) sources can provide an attractive source of chondrocytes for cartilage tissue engineering, since autologous (same individual) cells are scarce. Immune rejection of non-autologous hyaline articular cartilage has seldom been considered due to the popular notion of "cartilage immunoprivilege". The objective of this study was to determine the suitability of allogeneic and xenogeneic engineered neocartilage tissue for cartilage repair. To address this, scaffold-free tissue engineered articular cartilage of syngeneic (same genetic background), allogeneic, and xenogeneic origin were implanted into two different locations of the rabbit knee (n=3 per group/location). Xenogeneic engineered cartilage and control xenogeneic chondral explants provoked profound innate inflammatory and adaptive cellular responses, regardless of transplant location. Cytological quantification of immune cells showed that, while allogeneic neocartilage elicited an immune response in the patella, negligible responses were observed when implanted into the trochlea; instead the responses were comparable to microfracture-treated empty defect controls. Allogeneic neocartilage survived within the trochlea implant site and demonstrated graft integration into the underlying bone. In conclusion, the knee joint cartilage does not represent an immune privileged site, strongly rejecting xenogeneic but not allogeneic chondrocytes in a location-dependent fashion. This difference in location-dependent survival of allogeneic tissue may be associated with proximity to the synovium. Through a series of in vivo studies this research demonstrates that articular cartilage is not fully immunoprivileged. In addition, we now show that anatomical location of the defect, even within the same joint compartment, strongly influences the degree of the

  11. Autologous chondrocyte implantation: Is it likely to become a saviour of large-sized and full-thickness cartilage defect in young adult knee?

    Science.gov (United States)

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

    2016-05-01

    A literature review of the first-, second- and third-generation autologous chondrocyte implantation (ACI) technique for the treatment of large-sized (>4 cm(2)) and full-thickness knee cartilage defects in young adults was conducted, examining the current literature on features, clinical scores, complications, magnetic resonance image (MRI) and histological outcomes, rehabilitation and cost-effectiveness. A literature review was carried out in the main medical databases to evaluate the several studies concerning ACI treatment of large-sized and full-thickness knee cartilage defects in young adults. ACI technique has been shown to relieve symptoms and improve functional assessment in large-sized (>4 cm(2)) and full-thickness knee articular cartilage defect of young adults in short- and medium-term follow-up. Besides, low level of evidence demonstrated its efficiency and durability at long-term follow-up after implantation. Furthermore, MRI and histological evaluations provided the evidence that graft can return back to the previous nearly normal cartilage via ACI techniques. Clinical outcomes tend to be similar in different ACI techniques, but with simplified procedure, low complication rate and better graft quality in the third-generation ACI technique. ACI based on the experience of cell-based therapy, with the high potential to regenerate hyaline-like tissue, represents clinical development in treatment of large-sized and full-thickness knee cartilage defects. IV.

  12. Radioprotective effects of shark cartilage mucopolysaccharide preparation on immune nad reproductive organs in male mice

    International Nuclear Information System (INIS)

    Luan Jie; Shen Xianrong; Jiang Dingwen; Chen Wei; Lu Min

    2008-01-01

    Objective: To evaluate the protective effects of shark cartilage mucopolysaccharide preparation (SCMP) on immune and reproductive organs in male mice with irradiation damage induced by γ-rays. Methods: 50 mice were randomly divided into normal control group,model control group, the 0.5g/kg. d SCMP group, the 1.0g/kg. d SCMP group, and the 2.0g/kg. d SCMP group. SCMP was administrated by intragastric infusion with the volume of 0.4ml per 20g. Normal control group and model control group were given the same volume of water. 2 weeks later, all of the mice were irradiated by γ-ray of 60 Co(0.83Gy/h) with the dose of 5 Gy. Peripheral blood WBC, the spleen index(SI), thymus index(TI), the gMNC, testicle index, germ cells were detected. Results: Compared with the modal control group, peripheral blood WBC became significantly higher in the treated groups with 1.0g/kg. d and 2.0g/kg. d SCMP after 3 days by irradiation (P<0.05). TI, BMNC and germ cells were significantly higher in the treated groups with 1.0g/kg. d and 2.0g/kg. d SCMP comparing with the control model group (P<0.05) and SI, and Testicle index was significantly compared with the model group (P<0.05) only in 2.0g/ kg. d SCMP treated group. The germ abnormality rate became lower in SCMP treated groups (P<0.01) in 1.0 and 2.0g/kg. d SCMP group. Conclusion: SCMP has radioprotective effects on immune and reproductive organs in male mice. (authors)

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

    NARCIS (Netherlands)

    Mulder, E.L.W. de; Hannink, G.J.; Kuppevelt, T.H. van; Daamen, W.F.; Buma, P.

    2014-01-01

    Lesions in knee joint articular cartilage (AC) have limited repair capacity. Many clinically available treatments induce a fibrous-like cartilage repair instead of hyaline cartilage. To induce hyaline cartilage repair, we hypothesized that type I collagen scaffolds with fibers aligned perpendicular

  14. An experimental model to mimic the mechanical behavior of a scaffold in a cartilage defect

    OpenAIRE

    VIKINGSSON, LINE KARINA ALVA

    2015-01-01

    [EN] Abstract The main purpose of this thesis is the design and characterization of an experimental articular cartilage model. The in vitro model is composed of a macro and micro- porous Polycaprolactone scaffold with a Poly(Vinyl Alcohol) filling. The scaffold/hydrogel construct has been subjected to repeating number of freezing and thawing cycles in order to crosslink the hydrogel inside the scaffold's pores. The Poly(Vinyl Alcohol) resembles the growing cartilaginous tissue inside the ...

  15. POROUS POLYMER IMPLANTS FOR REPAIR OF FULL-THICKNESS DEFECTS OF ARTICULAR-CARTILAGE - AN EXPERIMENTAL-STUDY IN RABBIT AND DOG

    NARCIS (Netherlands)

    JANSEN, HWB; VETH, RPH; NIELSEN, HKL; DEGROOT, JH; PENNINGS, AJ

    1992-01-01

    Full-thickness defects of articular cartilage were repaired by implantation of porous polymer implants in rabbits and dogs. The quality of the repair tissue was determined by collagen typing with antibodies. Implants with varying pore sizes and chemical composition were used. The effect of loading

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

    Science.gov (United States)

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

    2011-02-22

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

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

    Science.gov (United States)

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

    2014-04-01

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

  18. Repair of articular cartilage and subchondral defects in rabbit knee joints with a polyvinyl alcohol/nano-hydroxyapatite/polyamide 66 biological composite material.

    Science.gov (United States)

    Guo, Tao; Tian, Xiaobin; Li, Bo; Yang, Tianfu; Li, Yubao

    2017-11-15

    This study sought to prepare a new PVA/n-HA/PA66 composite to investigate the repair of articular cartilage and subchondral defects in rabbit knee joints. A 5 × 5 × 5 mm-sized defect was created in the patellofemoral joints of 72 healthy adult New Zealand rabbits. The rabbits were then randomly divided into three groups (n = 24): PVA/n-HA+PA66 group, polyvinyl alcohol (PVA) group, and control (untreated) group. Cylindrical PVA/n-HA+PA66, 5 × 5 mm, comprised an upper PVA layer and a lower n-HA+PA66 layer. Macroscopic and histological evaluations were performed at 4, 8, 12, and 24 weeks, postoperatively. Type II collagen was measured by immunohistochemical staining. The implant/cartilage and bone interfaces were observed by scanning electron microscopy. At 24 weeks postoperatively, the lower PVA/n-HA+PA66 layer became surrounded by cartilage, with no obvious degeneration. In the PVA group, an enlarged space was observed between the implant and the host tissue that had undergone degeneration. In the control group, the articular cartilage had become calcified. In the PVA/n-HA+PA66 group, positive type II collagen staining was observed between the composite and the surrounding cartilage and on the implant surface. In the PVA group, positive staining was slightly increased between the PVA and the surrounding cartilage, but reduced on the PVA surface. In the control group, reduced staining was observed throughout. Scanning electron microscopy showed increased bone tissue in the lower n-HA+PA66 layer that was in close approximation with the upper PVA layer of the composite. In the PVA group, the bone tissue around the material had receded, and in the control group, the defect was filled with bone tissue, while the superior aspect of the defect was filled with disordered, fibrous tissue. The diphase biological composite material PVA/n-HA+PA66 exhibits good histocompatibility and offers a satisfactory substitute for articular cartilage and subchondral bone.

  19. Imaging of cartilage repair procedures

    International Nuclear Information System (INIS)

    Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw

    2014-01-01

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

  20. Histological and biochemical evaluation of perichondrial transplants in human articular cartilage defects

    NARCIS (Netherlands)

    Bouwmeester, P; Kuijer, R; Terwindt-Rouwenhorst, E; van der Linden, Ton; Bulstra, K

    1999-01-01

    From 1986 to 1992, 88 patients with articular defects in the knee were treated with a perichondrial arthroplasty. In this study, we report on the results for 22 biopsies of grafted tissue with a mean follow-up of 21 months. Biopsies were obtained at routine arthroscopy after approximately 1 year or

  1. Differentiation between grade 3 and grade 4 articular cartilage defects of the knee: Fat-suppressed proton density-weighted versus fat-suppressed three-dimensional gradient-echo MRI

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Yeon; Jee, Won-Hee; Kim, Sun Ki (Dept. of Radiology, Seoul St Mary' s Hospital, Catholic Univ. of Korea, Seoul (Korea)), e-mail: whjee@catholic.ac.kr; Koh, In-Jun (Dept. of Joint Reconstruction Center, Seoul National Univ. Bundang Hospital, Seoul (Korea)); Kim, Jung-Man (Dept. of Orthopedic Surgery, Seoul St Mary' s Hospital, Catholic Univ. of Korea, Seoul (Korea))

    2010-05-15

    Background: Fat-suppressed (FS) proton density (PD)-weighted magnetic resonance imaging (MRI) and FS three-dimensional (3D) gradient-echo imaging such as spoiled gradient-recalled (SPGR) sequence have been established as accurate methods for detecting articular cartilage defects. Purpose: To retrospectively compare the diagnostic efficacy between FS PD-weighted and FS 3D gradient-echo MRI for differentiating between grade 3 and grade 4 cartilage defects of the knee with arthroscopy as the standard of reference. Material and Methods: Twenty-one patients who had grade 3 or 4 cartilage defects in medial femoral condyle at arthroscopy and knee MRI were included in this study: grade 3, >50% cartilage defects; grade 4, full thickness cartilage defects exposed to the bone. Sagittal FS PD-weighted MR images and FS 3D gradient-echo images with 1.5 T MR images were independently graded for the cartilage abnormalities of medial femoral condyle by two musculoskeletal radiologists. Statistical analysis was performed by Fisher's exact test. Inter-observer agreement in grading of cartilage was assessed using ? coefficients. Results: Arthroscopy revealed grade 3 defects in 17 patients and grade 4 defects in 4 patients in medial femoral condyles. For FS 3D gradient-echo images grade 3 defects were graded as grade 3 (n=15) and grade 4 (n=2), and all grade 4 defects (n=4) were correctly graded. However, for FS PD-weighted MR images all grade 3 defects were misinterpreted as grade 1 (n=1) and grade 4 (n=16), whereas all grade 4 defects (n=4) were correctly graded. FS 3D gradient-echo MRI could differentiate grade 3 from grade 4 defects (P=0.003), whereas FS PD-weighted imaging could not (P=1.0). Inter-observer agreement was substantial (?=0.70) for grading of cartilage using FS PD-weighted imaging, whereas it was moderate (?=0.46) using FS 3D gradient-echo imaging. Conclusion: FS 3D gradient-echo MRI is more helpful for differentiating between grade 3 and grade 4 cartilage

  2. Effects of phosphorylatable short peptide-conjugated chitosan-mediated IL-1Ra and igf-1 gene transfer on articular cartilage defects in rabbits.

    Directory of Open Access Journals (Sweden)

    Ronglan Zhao

    Full Text Available Previously, we reported an improvement in the transfection efficiency of the plasmid DNA-chitosan (pDNA/CS complex by the utilization of phosphorylatable short peptide-conjugated chitosan (pSP-CS. In this study, we investigated the effects of pSP-CS-mediated gene transfection of interleukin-1 receptor antagonist protein (IL-1Ra combined with insulin-like growth factor-1 (IGF-1 in rabbit chondrocytes and in a rabbit model of cartilage defects. pBudCE4.1-IL-1Ra+igf-1, pBudCE4.1-IL-1Ra and pBudCE4.1-igf-1 were constructed and combined with pSP-CS to form pDNA/pSP-CS complexes. These complexes were transfected into rabbit primary chondrocytes or injected into the joint cavity. Seven weeks after treatment, all rabbits were sacrificed and analyzed. High levels of IL-1Ra and igf-1 expression were detected both in the cell culture supernatant and in the synovial fluid. In vitro, the transgenic complexes caused significant proliferation of chondrocytes, promotion of glycosaminoglycan (GAG and collagen II synthesis, and inhibition of chondrocyte apoptosis and nitric oxide (NO synthesis. In vivo, the exogenous genes resulted in increased collagen II synthesis and reduced NO and GAG concentrations in the synovial fluid; histological studies revealed that pDNA/pSP-CS treatment resulted in varying degrees of hyaline-like cartilage repair and Mankin score decrease. The co-expression of both genes produced greater effects than each single gene alone both in vitro and in vivo. The results suggest that pSP-CS is a good candidate for use in gene therapy for the treatment of cartilage defects and that igf-1 and IL-1Ra co-expression produces promising biologic effects on cartilage defects.

  3. Epigenetic Targets for Reversing Immune Defects Caused by Alcohol Exposure

    Science.gov (United States)

    Curtis, Brenda J.; Zahs, Anita; Kovacs, Elizabeth J.

    2013-01-01

    Alcohol consumption alters factors that modify gene expression without changing the DNA code (i.e., epigenetic modulators) in many organ systems, including the immune system. Alcohol enhances the risk for developing several serious medical conditions related to immune system dysfunction, including acute respiratory distress syndrome (ARDS), liver cancer, and alcoholic liver disease (ALD). Binge and chronic drinking also render patients more susceptible to many infectious pathogens and advance the progression of HIV infection by weakening both innate and adaptive immunity. Epigenetic mechanisms play a pivotal role in these processes. For example, alcohol-induced epigenetic variations alter the developmental pathways of several types of immune cells (e.g., granulocytes, macrophages, and T-lymphocytes) and through these and other mechanisms promote exaggerated inflammatory responses. In addition, epigenetic mechanisms may underlie alcohol’s ability to interfere with the barrier functions of the gut and respiratory systems, which also contribute to the heightened risk of infections. Better understanding of alcohol’s effects on these epigenetic processes may help researchers identify new targets for the development of novel medications to prevent or ameliorate alcohol’s detrimental effects on the immune system. PMID:24313169

  4. Immunization against Genital Herpes with a Vaccine Virus That has Defects in Productive and Latent Infection

    Science.gov (United States)

    da Costa, Xavier J.; Jones, Cheryl A.; Knipe, David M.

    1999-06-01

    An effective vaccine for genital herpes has been difficult to achieve because of the limited efficacy of subunit vaccines and the safety concerns about live viruses. As an alternative approach, mutant herpes simplex virus strains that are replication-defective can induce protective immunity. To increase the level of safety and to prove that replication was not needed for immunization, we constructed a mutant herpes simplex virus 2 strain containing two deletion mutations, each of which eliminated viral replication. The double-mutant virus induces protective immunity that can reduce acute viral shedding and latent infection in a mouse genital model, but importantly, the double-mutant virus shows a phenotypic defect in latent infection. This herpes vaccine strain, which is immunogenic but has defects in both productive and latent infection, provides a paradigm for the design of vaccines and vaccine vectors for other sexually transmitted diseases, such as AIDS.

  5. Quadriceps Strength in Patients With Isolated Cartilage Defects of the Knee: Results of Isokinetic Strength Measurements and Their Correlation With Clinical and Functional Results.

    Science.gov (United States)

    Hirschmüller, Anja; Andres, Tasja; Schoch, Wolfgang; Baur, Heiner; Konstantinidis, Lukas; Südkamp, Norbert P; Niemeyer, Philipp

    2017-05-01

    Recent studies have found a significant deficit of maximum quadriceps strength after autologous chondrocyte implantation (ACI) of the knee. However, it is unclear whether muscular strength deficits in patients with cartilage damage exist prior to operative treatment. To isokinetically test maximum quadriceps muscle strength and quantify the impact of possible strength deficits on functional and clinical test results. Cross-sectional study; Level of evidence, 3. To identify clinically relevant muscular strength deficits, 24 patients (5 females, 19 males; mean age, 34.5 years; body mass index, 25.9 kg/m 2 ) with isolated cartilage defects (mean onset, 5.05 years; SD, 7.8 years) in the knee joint underwent isokinetic strength measurements. Maximal quadriceps strength was recorded in 3 different testing modes: pure concentric contraction (flexors and extensors alternating work; con1), concentric-eccentric (only the extensors work concentrically and eccentrically; con2), and eccentric contraction in the alternating mode (ecc). Results were compared for functional performance (single-leg hop test), pain scales (visual analog scale [VAS], numeric rating scale [NRS]), self-reported questionnaires (International Knee Documentation Committee [IKDC], Knee Injury and Osteoarthritis Outcome Scale [KOOS]), and defect size (cm 2 ). Compared with the uninjured leg, significantly lower quadriceps strength was detected in the injured leg in all isokinetic working modes (con1 difference, 27.76 N·m [SD 17.47; P = .003]; con2 difference, 21.45 N·m [SD, 18.45; P =.025]; ecc difference, 29.48 N·m [SD, 21.51; P = .001]), with the largest deficits found for eccentric muscle performance. Moderate negative correlations were observed for the subjective pain scales NRS and VAS. The results of the IKDC and KOOS questionnaires showed low, nonsignificant correlations with findings in the isokinetic measurement. Moreover, defect sizes (mean, 3.13 cm 2 ) were of no importance regarding the

  6. Repair of large full-thickness articular cartilage defects in the rabbit: the effects of joint distraction and autologous bone-marrow-derived mesenchymal cell transplantation.

    Science.gov (United States)

    Yanai, T; Ishii, T; Chang, F; Ochiai, N

    2005-05-01

    We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel. The histological scores were significantly higher in the groups with ACBMT collagen gel (p distraction, collagen gel and ACBMT.

  7. Long-Term Results of Cartilage Repair after Allogeneic Transplantation of Cartilaginous Aggregates Formed from Bone Marrow–Derived Cells for Large Osteochondral Defects in Rabbit Knees

    Science.gov (United States)

    Mishima, Hajime; Sakai, Shinsuke; Uemura, Toshimasa

    2013-01-01

    Objective: The purpose of this study was to evaluate the long-term results of cartilage repair after allogeneic transplantation of cartilaginous aggregates formed from bone marrow–derived cells. Methods: Bone marrow cells were harvested from 12-day-old rabbits. The cells were subjected to a monolayer culture, and the spindle-shaped cells attached to the flask surface were defined as bone marrow–derived mesenchymal cells. After the monolayer culture, a 3-dimensional cartilaginous aggregate was formed using a bioreactor with chondrogenesis. We created osteochondral defects, measuring 5 mm in diameter and 4 mm in depth, at the femoral trochlea of 10-week-old rabbits. Two groups were established, the transplanted group in which the cartilaginous aggregate was transplanted into the defect, and the control group in which the defect was left untreated. Twenty-six and 52 weeks after surgery, the rabbits were sacrificed and their tissue repair status was evaluated macroscopically (International Cartilage Repair Society [ICRS] score) and histologically (O’Driscoll score). Results: The ICRS scores were as follows: at week 26, 7.2 ± 0.5 and 7.6 ± 0.8; at week 52, 7.6 ± 1.1 and 9.7 ± 0.7, for the transplanted and control groups, respectively. O’Driscoll scores were as follows: at week 26, 12.6 ± 1.9 and 10.1 ± 1.9; at week 52, 9.6 ± 3.0 and 14.0 ± 1.4, each for transplanted and control groups, respectively. No significant differences were observed between the groups. Conclusions: This study demonstrates that allogeneic transplantation of cartilaginous aggregates formed from bone marrow–derived cells produces comparable long-term results based on macroscopic and histological outcome measures when compared with osteochondral defects that are left untreated. PMID:26069678

  8. Long-Term Results of Cartilage Repair after Allogeneic Transplantation of Cartilaginous Aggregates Formed from Bone Marrow-Derived Cells for Large Osteochondral Defects in Rabbit Knees.

    Science.gov (United States)

    Yoshioka, Tomokazu; Mishima, Hajime; Sakai, Shinsuke; Uemura, Toshimasa

    2013-10-01

    The purpose of this study was to evaluate the long-term results of cartilage repair after allogeneic transplantation of cartilaginous aggregates formed from bone marrow-derived cells. Bone marrow cells were harvested from 12-day-old rabbits. The cells were subjected to a monolayer culture, and the spindle-shaped cells attached to the flask surface were defined as bone marrow-derived mesenchymal cells. After the monolayer culture, a 3-dimensional cartilaginous aggregate was formed using a bioreactor with chondrogenesis. We created osteochondral defects, measuring 5 mm in diameter and 4 mm in depth, at the femoral trochlea of 10-week-old rabbits. Two groups were established, the transplanted group in which the cartilaginous aggregate was transplanted into the defect, and the control group in which the defect was left untreated. Twenty-six and 52 weeks after surgery, the rabbits were sacrificed and their tissue repair status was evaluated macroscopically (International Cartilage Repair Society [ICRS] score) and histologically (O'Driscoll score). The ICRS scores were as follows: at week 26, 7.2 ± 0.5 and 7.6 ± 0.8; at week 52, 7.6 ± 1.1 and 9.7 ± 0.7, for the transplanted and control groups, respectively. O'Driscoll scores were as follows: at week 26, 12.6 ± 1.9 and 10.1 ± 1.9; at week 52, 9.6 ± 3.0 and 14.0 ± 1.4, each for transplanted and control groups, respectively. No significant differences were observed between the groups. This study demonstrates that allogeneic transplantation of cartilaginous aggregates formed from bone marrow-derived cells produces comparable long-term results based on macroscopic and histological outcome measures when compared with osteochondral defects that are left untreated.

  9. When is cartilage repair successful?

    International Nuclear Information System (INIS)

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

    2017-01-01

    Focal cartilage lesions are a cause of long-term disability and morbidity. After cartilage repair, it is crucial to evaluate long-term progression or failure in a reproducible, standardized manner. This article provides an overview of the different cartilage repair procedures and important characteristics to look for in cartilage repair imaging. Specifics and pitfalls are pointed out alongside general aspects. After successful cartilage repair, a complete, but not hypertrophic filling of the defect is the primary criterion of treatment success. The repair tissue should also be completely integrated to the surrounding native cartilage. After some months, the transplants signal should be isointense compared to native cartilage. Complications like osteophytes, subchondral defects, cysts, adhesion and chronic bone marrow edema or joint effusion are common and have to be observed via follow-up. Radiological evaluation and interpretation of postoperative changes should always take the repair method into account. (orig.) [de

  10. Defective B cell response to T-dependent immunization in lupus-prone mice

    Science.gov (United States)

    Niu, Haitao; Sobel, Eric S.; Morel, Laurence

    2009-01-01

    Lupus anti-nuclear Abs show the characteristics of Ag-driven T cell-dependent (TD) humoral responses. If autoAgs elicit the same response as exogenous Ags, lupus should enhance humoral responses to immunization. Blunted responses to various immunizations have, however, been reported in a significant portion of lupus patients. In this study, we show that lupus-prone B6.Sle1.Sle2.Sle3 (B6.TC) mice produce significantly less Ab in response to TD immunization than congenic controls, while producing significantly more total Ig. This blunted Ab response to TD Ag could be reconstituted with B6.TC B and CD4+ T cells. Multiple defects were found in the B6.TC response to NP-KLH as compared to total Ig, including a smaller percentage of B cells participating to the NP-response, a reduced entry into germinal centers, and highly defective production of NP-specific long-lived plasma cells in the bone marrow. B6.TC plasma cells expressed reduced levels of FcγRIIb, which suggests that reduced apoptosis in resident plasma cells prevents the establishment of newly-formed NP-specific plasma cells in bone marrow niches. Overall, these results show that lupus-prone mice responded differently to auto- and exogenous antigens and suggest that low FcγRIIb, hypergammaglobulinemia and high autoantibody production would be predictive of a poor response to immunization in lupus patients. PMID:18924209

  11. Autosomal dominant precocious osteoarthropathy due to a mutation of the cartilage oligomeric matrix protein (COMP) gene: further expansion of the phenotypic variations of COMP defects

    Energy Technology Data Exchange (ETDEWEB)

    Kawaji, Hiroyuki [Department of Orthopaedic Surgery, Sanyudo Hospital, 6-1-219 Chuou, Yonezawa, Yamagata 992-0045 (Japan); Nishimura, Gen [Department of Radiology, Nasu Chuou Hospital, Tochigi (Japan); Watanabe, Sobei; Sasaki, Akira; Sano, Tokuhisa [Department of Orthopaedic Surgery, Tohoku Kohsei-Nenkin Hospital, Miyagi (Japan); Mabuchi, Akihiko; Ikeda, Toshiyuki; Ikegawa, Shiro [Laboratory for Bone and Joint Diseases, SNP Research Center, Tokyo (Japan); Ohashi, Hirofumi [Division of Medical Genetics, Saitama Children' s Medical Center, Saitama (Japan)

    2002-12-01

    We report on a Japanese family of four generations with an autosomal dominant precocious osteoarthropathy. The cardinal clinical manifestations of affected individuals were painful weight-bearing large joints, which started in late childhood or adolescence. The radiological hallmarks included coxa plana, mild epiphyseal dysplasia of the knee, and round talar domes with tibiotalar slant in childhood, which evolved into degenerative joint diseases in adulthood. The disease phenotype was cosegregated with a mutation of the cartilage oligomeric matrix protein (COMP) gene in the family members, who underwent molecular evaluation. COMP mutations have been reported in a mild form of multiple epiphyseal dysplasia (MED), Ribbing type, as well as allied disorders with more severe manifestations, such as MED Fairbank type and pseudoachondroplasia. Unlike previously reported cases with the Ribbing type, the present patients did not have short stature or brachydactyly. This report expands further the phenotypic variations of COMP defects. (orig.)

  12. Stem Cells and Gene Therapy for Cartilage Repair

    OpenAIRE

    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, sur...

  13. [Current overview of cartilage regeneration procedures].

    Science.gov (United States)

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

    2017-11-01

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

  14. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs

    Directory of Open Access Journals (Sweden)

    Wen-I Lee

    2011-12-01

    Full Text Available Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG or nontuberculous mycobacteria (NTM, and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM (CD40L mutation, CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations, chronic granulomatous disease (CGD and hyper IgE recurrent infection syndromes (HIES. The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8 for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one, presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ, which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively

  15. Immune defects in families and patients with xeroderma pigmentosum and trichothiodystrophy.

    Science.gov (United States)

    Mariani, E; Facchini, A; Honorati, M C; Lalli, E; Berardesca, E; Ghetti, P; Marinoni, S; Nuzzo, F; Astaldi Ricotti, G C; Stefanini, M

    1992-01-01

    Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity, a high incidence of cancer in sun-exposed portions of the skin and a reduced capacity to repair the u.v.-induced DNA damage. One of the XP mutations (XP-D) has also been identified in patients affected by trichothiodystrophy (TTD), a rare autosomal recessive disease characterized by brittle hair, mental and physical retardation, peculiar face and ichthyosis. However, in these patients there is no evidence of increased skin tumour incidence. Since an impairment of cell-mediated immunity has been proposed as a co-factor in the cancer proneness of XP patients, we investigated the involvement of immune defect(s) in five XP patients, five TTD patients, their parents, and 24 TTD relatives. We evaluated the phenotype of circulating lymphocytes, natural killer (NK) cell lytic activity, target cell binding of NK cells at single cell level and the effect of interferons (IFN) alpha and beta on NK cell activity. The relative proportion of CD3+ and CD4+ circulating lymphocytes was reduced in XP but not in TTD patients. NK cell lytic activity was decreased in XP patients and their mothers, but their fathers showed normal lytic activity. NK activity varied among TTD families: four out of five patients and their relatives presented low NK cell activity, and one family was normal. In TTD family members, NK activity increased after incubation with IFN-alpha or IFN-beta, but never reached normal values. In contrast, in XP patients and their mothers, the defect was almost completely corrected after in vitro incubation with IFN-alpha or IFN-beta. Our study indicates impaired NK lytic activity in the majority of TTD and XP patients and that this defect is present also in members of their families. In addition, XP patients present a low number of circulating T cells. These multiple abnormalities, together with DNA repair defects, could be related to the increased cancer risk in XP patients

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

    Science.gov (United States)

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

    2013-01-31

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

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

    Directory of Open Access Journals (Sweden)

    Matsuda Hidetoshi

    2013-01-01

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

  18. Successful conservative management of symptomatic bilateral dorsal patellar defects presenting with cartilage involvement and bone marrow edema : MRI findings

    NARCIS (Netherlands)

    Kwee, Thomas C.; Sonneveld, Heleen; Nix, Maarten

    2016-01-01

    The dorsal patellar defect is a relatively rare entity that involves the superolateral quadrant of the patella. It is usually considered to represent a delayed ossification process, although its exact origin remains unclear. Because of its usually innocuous nature and clinical course, invasive

  19. Engineering Cartilage

    Science.gov (United States)

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

  20. Shark Cartilage

    Science.gov (United States)

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

  1. Coordinate expression of activating Fc gamma receptors I and III and inhibiting Fc gamma receptor type II in the determination of joint inflammation and cartilage destruction during immune complex-mediated arthritis.

    NARCIS (Netherlands)

    Nabbe, K.C.A.M.; Blom, A.B.; Holthuysen, A.E.M.; Boross, P.; Roth, J.; Verbeek, S.; Lent, P.L.E.M. van; Berg, W.B. van den

    2003-01-01

    OBJECTIVE: To study the role of the activating Fc gamma receptor types I and III (Fc gamma RI and Fc gamma RIII, respectively) and the inhibiting Fc gamma receptor II (Fc gamma RII) in inflammation and in various aspects of cartilage destruction during arthritis that is solely induced by immune

  2. Principles of cartilage repair

    CERN Document Server

    Erggelet, Christoph; Mandelbaum, Bert R

    2008-01-01

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

  3. A Comparison of the Outcomes for Cartilage Defects of the Knee Treated With Biologic Resurfacing Versus Focal Metallic Implants.

    Science.gov (United States)

    Pascual-Garrido, Cecilia; Daley, Erika; Verma, Nikhil N; Cole, Brian J

    2017-02-01

    To compare the results of focal metallic resurfacing with biologic procedures in patients more than 35 years of age with isolated, full thickness defects of the femoral condyle. A total of 61 patients met the selection criteria resulting in 30 patients treated with biological procedures, including debridement, microfracture, osteochondral autograft transplantation, osteochondral allograft, and autologous chondrocyte implantation (BIO group), and 32 patients treated with focal metallic resurfacing (CAP group). The BIO and CAP groups were matched according to treatment location, defect grade and size, and age profile. Outcomes included Western Ontario and McMaster Osteoarthritis Index (WOMAC), Short Form-12, and satisfaction. The primary combination endpoint was determined as a 20% improvement (minimum clinically important difference-20) on WOMAC pain and function at 2 years and no additional index lesion-related surgical intervention. Safety and effectiveness were also reported. Thirty patients in the BIO group (mean age of 44.6, range 35-64) had an average follow-up of 2.6 years and 32 patients in the CAP group (mean age 47.9, range 37-68) were followed for 2.0 years. Fifty-three percent in the BIO group and 75% in the CAP group achieved success per the endpoint definition. The mean total WOMAC score improved significantly for both groups (BIO: 57-78; P metal resurfacing procedures for the treatment of isolated focal chondral lesions of the femoral condyle in the knee. Focal metallic resurfacing results in similar clinical outcomes and provides excellent success rates at short-term follow-up. Level III comparative study. Copyright © 2016. Published by Elsevier Inc.

  4. Polymer Formulations for Cartilage Repair

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-05-15

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

  5. Full-thickness knee articular cartilage defects in national football league combine athletes undergoing magnetic resonance imaging: prevalence, location, and association with previous surgery.

    Science.gov (United States)

    Nepple, Jeffrey J; Wright, Rick W; Matava, Matthew J; Brophy, Robert H

    2012-06-01

    To better define the prevalence and location of full-thickness articular cartilage lesions in elite football players undergoing knee magnetic resonance imaging (MRI) at the National Football League (NFL) Invitational Combine and assess the association of these lesions with previous knee surgery. We performed a retrospective review of all participants in the NFL Combine undergoing a knee MRI scan from 2005 to 2009. Each MRI scan was reviewed for evidence of articular cartilage disease. History of previous knee surgery including anterior cruciate ligament reconstruction, meniscal procedures, and articular cartilage surgery was recorded for each athlete. Knees with a history of previous articular cartilage restoration surgery were excluded from the analysis. A total of 704 knee MRI scans were included in the analysis. Full-thickness articular cartilage lesions were associated with a history of any previous knee surgery (P football players at the NFL Combine undergoing MRI. The lateral compartment appears to be at greater risk for full-thickness cartilage loss. Previous knee surgery, particularly meniscectomy, is associated with these lesions. Level IV, therapeutic case series. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2003-12-01

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

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

    OpenAIRE

    Hellingman, Catharine

    2012-01-01

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

  8. Defective pulmonary innate immune responses post-stem cell transplantation; review and results from one model system

    Directory of Open Access Journals (Sweden)

    Racquel eDomingo-Gonzalez

    2013-05-01

    Full Text Available Infectious pulmonary complications limit the success of hematopoietic stem cell transplantation (HSCT as a therapy for malignant and nonmalignant disorders. Susceptibility to pathogens in both autologous and allogeneic HSCT recipients persists despite successful immune reconstitution. As studying the causal effects of these immune defects in the human population can be limiting, a bone marrow transplant (BMT mouse model can be used to understand the defect in mounting a productive innate immune response post-transplantation. When syngeneic BMT is performed, this system allows the study of BMT-induced alterations in innate immune cell function that are independent of the confounding effects of immunosuppressive therapy and graft-versus-host disease. Studies from several laboratories, including our own show that pulmonary susceptibility to bacterial infections post-BMT are largely due to alterations in the lung alveolar macrophages. Changes in these cells post-BMT include cytokine and eicosanoid dysregulations, scavenger receptor alterations, changes in micro RNA profiles, and alterations in intracellular signaling molecules that limit bacterial phagocytosis and killing. The changes that occur highlight mechanisms that promote susceptibility to infections commonly afflicting HSCT recipients and provide insight into therapeutic targets that may improve patient outcomes post-HSCT.

  9. Effects of Platelet-Rich Plasma & Platelet-Rich Fibrin with and without Stromal Cell-Derived Factor-1 on Repairing Full-Thickness Cartilage Defects in Knees of Rabbits

    Directory of Open Access Journals (Sweden)

    Soghra Bahmanpour

    2016-11-01

    Full Text Available Background: The purpose of this study was to create biomaterial scaffolds like platelet-rich plasma (PRP and platelet-rich fibrin (PRF containing stromal cell-derived factor-1 (SDF1 as a chemokine to induce hyaline cartilage regeneration of rabbit knee in a full thickness defect. Methods: We created a full thickness defect in the trochlear groove of thirty-six bilateral knees of eighteen mature male rabbits. The knees were randomly divided into six groups (group I: untreated control, group II: PRP, group III: PRF, group IV: Gelatin+SDF1, group V: PRP+SDF1, and group VI: PRF+SDF1. After four weeks, the tissue specimens were evaluated by macroscopic examination and histological grading, immunofluorescent staining for collagen type II, and analyzed for cartilage marker genes by real-time PCR. The data were compared using statistical methods (SPSS 20, Kruskal-Wallis test, Bonferroni post hoc test and P<0.05. Results: Macroscopic evaluations revealed that international cartilage repair society (ICRS scores of the PRF+SDF1 group were higher than other groups. Microscopic analysis showed that the ICRS score of the PRP group was significantly lower than other groups. Immunofluorescent staining for collagen II demonstrated a remarkable distribution of type II collagen in the Gel+SDF1, PRP+SDF1 and PRF+SDF1 groups compared with other groups. Real-time PCR analysis revealed that mRNA expression of SOX9 and aggrecan were significantly greater in the PRF+SDF1, PRP+SDF1, Gel+SDF1 and PRF groups than the control group (P<0.05. Conclusion: Our results indicate that implantation of PRF scaffold containing SDF1 led to the greatest evaluation scores of full-thickness lesions in rabbits.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

  12. Peptide-Based Materials for Cartilage Tissue Regeneration.

    Science.gov (United States)

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

    2017-01-01

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

  13. [Research of repairing rabbit knee joint cartilage defect by compound material of fibrin glue and decalcified bone matrix (DBM) and chondrocytes].

    Science.gov (United States)

    He, Jie; Yang, Xiang; Yue, Peng-ju; Wang, Guan-yu; Guo, Ting; Zhao, Jian-ning

    2009-07-01

    To investigate the feasibility and effectivity of using compound material of fibrin glue and DBM as scaffolds for cartilage tissue engineering. Chondrocytes isolated from articular cartilage were seeded into prepared scaffolds, after incubation for 4 weeks in vitro. Chondrocytes and fibrin glue and DBM constructs were implanted in the joint cave of rabbit. The specimens were excised at the 4th, 8th, 12th week, examined grossly analyzed by haematoxylin cosine, toluidine blues staining and type II collagen immunohistochemistry reaction. Wakitani score was counted to evaluate the repairing effect. Grossly analysis showed some ivory tissue filled the caves after 4 weeks and the caves were full filled with smooth surface after 12 weeks. The microscope showed a good deal of chondrocytes appeared after 8 weeks and more type II collagen than 4 weeks. Twelve weeks later, cartilage lacuna could be observed. The cells arrangement and the amount of type II collagen both showed the same as the natural one. Complicated material of fibrin glue and DBM as scaffolds can be used as scaffolds for cartilage tissue engineering.

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

    NARCIS (Netherlands)

    C.A. Hellingman (Catharine)

    2012-01-01

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

  15. Supporting Biomaterials for Articular Cartilage Repair

    Science.gov (United States)

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

    2012-01-01

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

  16. X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect.

    Science.gov (United States)

    Ravell, Juan; Chaigne-Delalande, Benjamin; Lenardo, Michael

    2014-12-01

    To describe the role of the magnesium transporter 1 (MAGT1) in the pathogenesis of 'X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia' (XMEN) disease and its clinical implications. The magnesium transporter protein MAGT1 participates in the intracellular magnesium ion (Mg) homeostasis and facilitates a transient Mg influx induced by the activation of the T-cell receptor. Loss-of-function mutations in MAGT1 cause an immunodeficiency named 'XMEN syndrome', characterized by CD4 lymphopenia, chronic EBV infection, and EBV-related lymphoproliferative disorders. Patients with XMEN disease have impaired T-cell activation and decreased cytolytic function of natural killer (NK) and CD8 T cells because of decreased expression of the NK stimulatory receptor 'natural-killer group 2, member D' (NKG2D). Patients may have defective specific antibody responses secondary to T cell dysfunction, but B cells have not been shown to be directly affected by mutations in MAGT1. XMEN disease has revealed a novel role for free intracellular magnesium in the immune system. Further understanding of the MAGT1 signaling pathway may lead to new diagnostic and therapeutic approaches.

  17. Clinical case-study describing the use of skin-perichondrium-cartilage graft from the auricular concha to cover large defects of the nose

    Directory of Open Access Journals (Sweden)

    Inchingolo Francesco

    2012-03-01

    Full Text Available Abstract Background The composite graft from the conchal cartilage is a graft that is often used, especially in surgery on the nose, due to its capacity to resolve problems of cover and tissue deficit, arising from the removal of neoplasms or as the result of trauma, burns or following over-aggressive rhinoplasty. We have started to use skin-perichondrium-cartilage graft from the ear to cover large areas of the nose with very satisfying results as well as we describe in the reported clinical case. Methods The operation consisted of reconstruction of the cartilaginous nasal septum, which had previously been removed, using two vestibular labial mucosa flaps to reconstruct the mucosa, and cartilage from the ear conch for the cartilaginous septum. After this, the skin edges of the fistula were turned to recreate the inner lining of the nose and form a vascular base of wide area to accept the composite graft. The case concerns a female 74-year old patient who had undergone several oncological surgery for a relapsing basal cell carcinoma on the dorsum of the nose. The operation consisted of reconstruction of the cartilaginous nasal septum using two vestibular labial mucosa flaps to reconstruct the mucosa, and cartilage from the ear conch for the cartilaginous septum. Results The perichondrial cutaneous graft has shown in this surgical case very favorable peculiarities that make it usable even in facial plastic surgery. Conclusions We believe that the positive experience that we achieved in the use of composite grafts for the reconstruction of large areas of the nose could be interesting for others surgeons.

  18. The potential of induced pluripotent stem cells as a tool to study skeletal dysplasias and cartilage-related pathologic conditions.

    Science.gov (United States)

    Liu, H; Yang, L; Yu, F F; Wang, S; Wu, C; Qu, C; Lammi, M J; Guo, X

    2017-05-01

    The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too. The same problems which face the present cell-based treatments of cartilage injuries concern also the iPSC-based ones. However, established iPSC lines, which have no genomic aberrations and which efficiently differentiate into extracellular matrix secreting chondrocytes, could be an invaluable cell source for cell transplantations in the future. The safety issues concerning the recipient risks of teratoma formation and immune response still have to be solved before the potential use of iPSCs in cartilage repair of focal cartilage defects and OA. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  19. Defective prevention of immune precipitation in autoimmune diseases is independent of C4A*Q0

    Science.gov (United States)

    Arason, G J; Kolka, R; Hreidarsson, A B; Gudjonsson, H; Schneider, P M; Fry, L; Arnason, A

    2005-01-01

    Increased prevalence of C4 null alleles is a common feature of autoimmune diseases. We have shown previously that complement-dependent prevention of immune precipitation (PIP) is defective in patients with systemic lupus erythematosus (SLE), and correlated this defect with C4A*Q0 and low levels of the C4A isotype. To further clarify the role of C4A in the aetiology of SLE, we now extend our studies to other diseases which have been associated with C4A*Q0. The frequency of C4A*Q0 was increased in Icelandic patients with coeliac disease (0·50; P Grave's disease (0·30; P = 0·002) and insulin-dependent diabetes mellitus (0·23; P = 0·04) and in British patients with dermatitis herpetiformis (0·42; P = 0·002) and this was reflected in low levels of C4A. In spite of this, PIP was normal in these patients, and in marked contrast to our previous observations on connective tissue diseases, PIP measurements in these patient groups correlated more strongly with levels of C4B (r = 0·51, P = 0·0000004) than C4A. Patients with increased levels of anti-C1q antibodies had significantly lower PIP than patients without such antibodies (P cause of the PIP defect in autoimmune connective tissue disease. PMID:15932521

  20. Cartilage repair in the degenerative ageing knee

    Science.gov (United States)

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

    2016-01-01

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

  1. Review on patents for mechanical stimulation of articular cartilage tissue engineering

    NARCIS (Netherlands)

    Donkelaar, van C.C.; Schulz, R.M.

    2008-01-01

    To repair articular cartilage defects in osteoarthritic patients with three-dimensional tissue engineered chondrocyte grafts, requires the formation of new cartilage with sufficient mechanical properties. The premise is that mechanical stimulation during the culturing process is necessary to reach

  2. Bipolar and panic disorders may be associated with hereditary defects in the innate immune system

    DEFF Research Database (Denmark)

    Foldager, Leslie; Köhler, Karl Ole; Steffensen, Rudi Nora

    2014-01-01

    Background: Mannan-binding lectin (MBL) and mannan-binding lectin-associated serine protease-2 (MASP-2) represent important arms of the innate immune system, and different deficiencies may result in infections or autoimmune diseases. Both bipolar and panic disorders are associated with increased...

  3. Recurrent Vulvovaginal Candidiasis: Could It Be Related to Cell-Mediated Immunity Defect in Response to Candida Antigen?

    Directory of Open Access Journals (Sweden)

    Zahra Talaei

    2017-09-01

    Full Text Available Background Recurrent vulvovaginal candidiasis (RVVC is a common cause of morbidity affecting millions of women worldwide. Patients with RVVC are thought to have an underlying immunologic defect. This study has been established to evaluate cell-mediated immunity defect in response to candida antigen in RVVC cases. Materials and Methods Our cross-sectional study was performed in 3 groups of RVVC patients (cases, healthy individuals (control I and known cases of chronic mucocutaneous candidiasis (CMC (control II. Patients who met the inclusion criteria of RVVC were selected consecutively and were allocated in the case group. Peripheral blood mononuclear cells were isolated and labeled with CFSE and proliferation rate was measured in exposure to candida antigen via flow cytometry. Results T lymphocyte proliferation in response to candida was significantly lower in RVVC cases (n=24 and CMC patients (n=7 compared to healthy individuals (n=20, P0.05. Family history of primary immunodeficiency diseases (PID differed significantly among groups (P=0.01, RVVC patients has family history of PID more than control I (29.2 vs. 0%, P=0.008 but not statistically different from CMC patients (29.2 vs. 42.9%, P>0.05. Prevalence of atopy was greater in RVVC cases compared to healthy individuals (41.3 vs. 15%, P=0.054. Lymphoproliferative activity and vaginal symptoms were significantly different among RVVC cases with and without allergy (P=0.01, P=0.02. Conclusion Our findings revealed that T cells do not actively proliferate in response to Candida antigen in some RVVC cases. So it is concluded that patients with cell-mediated immunity defect are more susceptible to recurrent fungal infections of vulva and vagina. Nonetheless, some other cases of RVVC showed normal function of T cells. Further evaluations showed that these patients suffer from atopy. It is hypothesized that higher frequency of VVC in patients with history of atopy might be due to allergic response

  4. Elastic cartilage reconstruction by transplantation of cultured hyaline cartilage-derived chondrocytes.

    Science.gov (United States)

    Mizuno, M; Takebe, T; Kobayashi, S; Kimura, S; Masutani, M; Lee, S; Jo, Y H; Lee, J I; Taniguchi, H

    2014-05-01

    Current surgical intervention of craniofacial defects caused by injuries or abnormalities uses reconstructive materials, such as autologous cartilage grafts. Transplantation of autologous tissues, however, places a significant invasiveness on patients, and many efforts have been made for establishing an alternative graft. Recently, we and others have shown the potential use of reconstructed elastic cartilage from ear-derived chondrocytes or progenitors with the unique elastic properties. Here, we examined the differentiation potential of canine joint cartilage-derived chondrocytes into elastic cartilage for expanding the cell sources, such as hyaline cartilage. Articular chondrocytes are isolated from canine joint, cultivated, and compared regarding characteristic differences with auricular chondrocytes, including proliferation rates, gene expression, extracellular matrix production, and cartilage reconstruction capability after transplantation. Canine articular chondrocytes proliferated less robustly than auricular chondrocytes, but there was no significant difference in the amount of sulfated glycosaminoglycan produced from redifferentiated chondrocytes. Furthermore, in vitro expanded and redifferentiated articular chondrocytes have been shown to reconstruct elastic cartilage on transplantation that has histologic characteristics distinct from hyaline cartilage. Taken together, cultured hyaline cartilage-derived chondrocytes are a possible cell source for elastic cartilage reconstruction. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  5. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

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

    Science.gov (United States)

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

    2004-09-01

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

  7. Hyaline cartilage degenerates after autologous osteochondral transplantation.

    Science.gov (United States)

    Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

    2004-11-01

    Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

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

    Science.gov (United States)

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

    2016-03-01

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

  9. Evaluation of laryngeal cartilage calcification in computed tomography

    International Nuclear Information System (INIS)

    Laskowska, K.; Serafin, Z.; Lasek, W.; Maciejewski, M.; Wieczor, W.; Wisniewski, S.

    2008-01-01

    Computed tomography (CT) is one of the basic methods used for laryngeal carcinoma diagnostics. Osteosclerotic and osteolytic changes of the cartilages are considered as a common radiologic symptom of laryngeal neoplasms. The aim of this paper was to evaluate the prevalence of both osteosclerotic changes and focal calcification defects, which may be suggestive of osteolysis. Calcification was assessed in the thyroid, the cricoid and the arytenoids cartilages on CT images of the neck. We have retrospectively analyzed neck CT examinations of 50 patients without any laryngeal pathology in anamnesis. The grade and symmetry of calcifications was assessed in the thyroid, the cricoid and the arytenoids cartilages. Calcification of the laryngeal cartilages was present in 83% of the patients. Osteosclerotic lesions of the thyroid cartilage were seen in 70% of the patients (asymmetric in 60% of them), of the cricoid catrilage in 50% (asymmetric in 60%), and of the arytenoid cartilages in 24% (asymmetric in 67%). Focal calcification defects were present in the thyroid cartilage in 56% of the patients (asymmetric in 67% of them), in the cricoid catrilage in 8% (asymmetric in all cases), and in the arytenoid cartilages in 20% (asymmetric in 90%). Osteosclerotic changes and focal calcification defects, which may suggest osteolysis, were found in most of the patients. Therefore, they cannot be used as crucial radiological criteria of neoplastic invasion of laryngeal cartilages. (authors)

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

    Science.gov (United States)

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

    2017-07-01

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

  11. Combined role of type IX collagen and cartilage oligomeric matrix protein in cartilage matrix assembly: Cartilage oligomeric matrix protein counteracts type IX collagen-induced limitation of cartilage collagen fibril growth in mouse chondrocyte cultures

    NARCIS (Netherlands)

    Blumbach, K.; Bastiaansen-Jenniskens, Y.M.; Groot, J. de; Paulsson, M.; Osch, G.J.V.M. van; Zaucke, F.

    2009-01-01

    Objective. Defects in the assembly and composition of cartilage extracellular matrix are likely to result in impaired matrix integrity and increased susceptibility to cartilage degeneration. The aim of this study was to determine the functional interaction of the collagen fibril-associated proteins

  12. Stem Cells and Gene Therapy for Cartilage Repair

    Directory of Open Access Journals (Sweden)

    Umile Giuseppe Longo

    2012-01-01

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

  13. Ready-to-Use Tissue Construct for Military Bone and Cartilage Trauma

    Science.gov (United States)

    2012-10-01

    physiologic hyaline cartilage - osseous transition in massive osteochondral defects in large animals. We will conduct functional outcome analysis, X...10-1-0933 TITLE: Ready-to-Use Tissue Construct for Military Bone and Cartilage Trauma PRINCIPAL INVESTIGATOR: Francis Y. Lee... Cartilage Trauma” addresses the current limitations in treating complex, high-energy musculoskeletal wounds incurred in active combat. High-energy

  14. Cartilage repair: Generations of autologous chondrocyte transplantation

    International Nuclear Information System (INIS)

    Marlovits, Stefan; Zeller, Philip; Singer, Philipp; Resinger, Christoph; Vecsei, Vilmos

    2006-01-01

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

  15. Cartilage repair: Generations of autologous chondrocyte transplantation

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-01-15

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

  16. Imaging of articular cartilage

    Directory of Open Access Journals (Sweden)

    Bhawan K Paunipagar

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-11-15

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

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

    Directory of Open Access Journals (Sweden)

    Christoph Bartz

    2016-11-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  1. A retinaculum-sparing surgical approach preserves porcine stifle joint cartilage in an experimental animal model of cartilage repair.

    Science.gov (United States)

    Bonadio, Marcelo B; Friedman, James M; Sennett, Mackenzie L; Mauck, Robert L; Dodge, George R; Madry, Henning

    2017-12-01

    This study compares a traditional parapatellar retinaculum-sacrificing arthrotomy to a retinaculum-sparing arthrotomy in a porcine stifle joint as a cartilage repair model. Surgical exposure of the femoral trochlea of ten Yucatan pigs stifle joint was performed using either a traditional medial parapatellar approach with retinaculum incision and luxation of the patella (n = 5) or a minimally invasive (MIS) approach which spared the patellar retinaculum (n = 5). Both classical and MIS approaches provided adequate access to the trochlea, enabling the creation of cartilage defects without difficulties. Four full thickness, 4 mm circular full-thickness cartilage defects were created in each trochlea. There were no intraoperative complications observed in either surgical approach. All pigs were allowed full weight-bearing and full range of motion immediately postoperatively and were euthanized between 2 and 3 weeks. The traditional approach was associated with increased cartilage wear compared to the MIS approach. Two blinded raters performed gross evaluation of the trochlea cartilage surrounding the defects according to the modified ICRS cartilage injury classification. The traditional approach cartilage received a significantly worse score than the MIS approach group from both scorers (3.2 vs 0.8, p = 0.01 and 2.8 vs 0, p = 0.005 respectively). The MIS approach results in less damage to the trochlear cartilage and faster return to load bearing activities. As an arthrotomy approach in the porcine model, MIS is superior to the traditional approach.

  2. Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established.

    Directory of Open Access Journals (Sweden)

    Nigel J Dimmock

    Full Text Available Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1. Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2018-05-14

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

  5. Preclinical Studies for Cartilage Repair

    Science.gov (United States)

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

    2011-01-01

    Investigational devices for articular cartilage repair or replacement are considered to be significant risk devices by regulatory bodies. Therefore animal models are needed to provide proof of efficacy and safety prior to clinical testing. The financial commitment and regulatory steps needed to bring a new technology to clinical use can be major obstacles, so the implementation of highly predictive animal models is a pressing issue. Until recently, a reductionist approach using acute chondral defects in immature laboratory species, particularly the rabbit, was considered adequate; however, if successful and timely translation from animal models to regulatory approval and clinical use is the goal, a step-wise development using laboratory animals for screening and early development work followed by larger species such as the goat, sheep and horse for late development and pivotal studies is recommended. Such animals must have fully organized and mature cartilage. Both acute and chronic chondral defects can be used but the later are more like the lesions found in patients and may be more predictive. Quantitative and qualitative outcome measures such as macroscopic appearance, histology, biochemistry, functional imaging, and biomechanical testing of cartilage, provide reliable data to support investment decisions and subsequent applications to regulatory bodies for clinical trials. No one model or species can be considered ideal for pivotal studies, but the larger animal species are recommended for pivotal studies. Larger species such as the horse, goat and pig also allow arthroscopic delivery, and press-fit or sutured implant fixation in thick cartilage as well as second look arthroscopies and biopsy procedures. PMID:26069576

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

    Science.gov (United States)

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

    2007-11-01

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

  7. Cartilage Integration: Evaluation of the reasons for failure of integration during cartilage repair. A review

    Directory of Open Access Journals (Sweden)

    IM Khan

    2008-09-01

    Full Text Available Articular cartilage is a challenging tissue to reconstruct or replace principally because of its avascular nature; large chondral lesions in the tissue do not spontaneously heal. Where lesions do penetrate the bony subchondral plate, formation of hematomas and the migration of mesenchymal stem cells provide an inferior and transient fibrocartilagenous replacement for hyaline cartilage. To circumvent the poor intrinsic reparative response of articular cartilage several surgical techniques based on tissue transplantation have emerged. One characteristic shared by intrinsic reparative processes and the new surgical therapies is an apparent lack of lateral integration of repair or graft tissue with the host cartilage that can lead to poor prognosis. Many factors have been cited as impeding cartilage:cartilage integration including; chondrocyte cell death, chondrocyte dedifferentiation, the nature of the collagenous and proteoglycan networks that constitute the extracellular matrix, the type of biomaterial scaffold employed in repair and the origin of the cells used to repopulate the defect or lesion. This review addresses the principal intrinsic and extrinsic factors that impede integration and describe how manipulation of these factors using a host of strategies can positively influence cartilage integration.

  8. Modern cartilage imaging of the ankle

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  9. Recent advances in hydrogels for cartilage tissue engineering.

    Science.gov (United States)

    Vega, S L; Kwon, M Y; Burdick, J A

    2017-01-30

    Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks), new techniques to process hydrogels (e.g. 3D printing) and better incorporation of biological signals (e.g. controlled release). This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

  10. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    Science.gov (United States)

    Im, Gun-Il

    2016-04-01

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

  11. Recent advances in hydrogels for cartilage tissue engineering

    Directory of Open Access Journals (Sweden)

    SL Vega

    2017-01-01

    Full Text Available Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks, new techniques to process hydrogels (e.g. 3D printing and better incorporation of biological signals (e.g. controlled release. This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  13. Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade.

    Science.gov (United States)

    Huffaker, Thomas B; Lee, Soh-Hyun; Tang, William W; Wallace, Jared A; Alexander, Margaret; Runtsch, Marah C; Larsen, Dane K; Thompson, Jacob; Ramstead, Andrew G; Voth, Warren P; Hu, Ruozhen; Round, June L; Williams, Matthew A; O'Connell, Ryan M

    2017-11-10

    MicroRNA-155 (miR-155) regulates antitumor immune responses. However, its specific functions within distinct immune cell types have not been delineated in conditional KO mouse models. In this study, we investigated the role of miR-155 specifically within T cells during the immune response to syngeneic tumors. We found that miR-155 expression within T cells is required to limit syngeneic tumor growth and promote IFNγ production by T cells within the tumor microenvironment. Consequently, we found that miR-155 expression by T cells is necessary for proper tumor-associated macrophage expression of IFNγ-inducible genes. We also found that immune checkpoint-blocking (ICB) antibodies against programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) restored antitumor immunity in miR-155 T cell-conditional KO mice. We noted that these ICB antibodies rescued the levels of IFNγ-expressing T cells, expression of multiple activation and effector genes expressed by tumor-infiltrating CD8 + and CD4 + T cells, and tumor-associated macrophage activation. Moreover, the ICB approach partially restored expression of several derepressed miR-155 targets in tumor-infiltrating, miR-155-deficient CD8 + T cells, suggesting that miR-155 and ICB regulate overlapping pathways to promote antitumor immunity. Taken together, our findings highlight the multifaceted role of miR-155 in T cells, in which it promotes antitumor immunity. These results suggest that the augmentation of miR-155 expression could be used to improve anticancer immunotherapies. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Degeneration of osteoarthritis cartilage

    DEFF Research Database (Denmark)

    Jørgensen, Dan Richter

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

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

    Science.gov (United States)

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

    2011-02-01

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

  16. High-resolution MR imaging of wrist cartilage

    International Nuclear Information System (INIS)

    Rominger, M.B.; Bernreuter, W.K.; Listinsky, J.J.; Lee, D.H.; Kenney, P.J.; Colgin, S.L.

    1991-01-01

    This paper reports that cartilage is an important prognostic factor in arthritis. MR imaging can demonstrate both articular cartilage and subchondral bone. Our purpose was to compare various sequences, for wrist cartilage imaging and determine how extensive damage must be before it is detectable with MR imaging. Six cadaver wrists were imaged before and after arthroscopic cartilage injury (coronal and axial T1- and T2-weighted SE sequences, 3-mm sections; SPGR 45 degrees flip angle volume images with fat saturation. 1.2-mm sections; plus T1-weighted coronal images with fat saturation after injury; General Electric Signa, 1.5 T, with transmit-receive extremity coil). Twenty-two defects were created arthroscopically. Five normal volunteers were imaged for comparison. The greatest contrast among bone, cartilage, and synovial fluid was achieved with T1-weighted fat-suppressed SE image and SPGR. Gradient-recalled volume sequences generated very thin sections but were susceptible to artifact

  17. High fat diet accelerates cartilage repair in DBA/1 mice.

    Science.gov (United States)

    Wei, Wu; Bastiaansen-Jenniskens, Yvonne M; Suijkerbuijk, Mathijs; Kops, Nicole; Bos, Pieter K; Verhaar, Jan A N; Zuurmond, Anne-Marie; Dell'Accio, Francesco; van Osch, Gerjo J V M

    2017-06-01

    Obesity is a well-known risk factor for osteoarthritis, but it is unknown what it does on cartilage repair. Here we investigated whether a high fat diet (HFD) influences cartilage repair in a mouse model of cartilage repair. We fed DBA/1 mice control or HFD (60% energy from fat). After 2 weeks, a full thickness cartilage defect was made in the trochlear groove. Mice were sacrificed, 1, 8, and 24 weeks after operation. Cartilage repair was evaluated on histology. Serum glucose, insulin and amyloid A were measured 24 h before operation and at endpoints. Immunohistochemical staining was performed on synovium and adipose tissue to evaluate macrophage infiltration and phenotype. One week after operation, mice on HFD had defect filling with fibroblast-like cells and more cartilage repair as indicated by a lower Pineda score. After 8 weeks, mice on a HFD still had a lower Pineda score. After 24 weeks, no mice had complete cartilage repair and we did not detect a significant difference in cartilage repair between diets. Bodyweight was increased by HFD, whereas serum glucose, amyloid A and insulin were not influenced. Macrophage infiltration and phenotype in adipose tissue and synovium were not influenced by HFD. In contrast to common wisdom, HFD accelerated intrinsic cartilage repair in DBA/1 mice on the short term. Resistance to HFD induced inflammatory and metabolic changes could be associated with accelerated cartilage repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1258-1264, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2018-03-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  20. Tissue engineering in the treatment of cartilage lesions

    Directory of Open Access Journals (Sweden)

    Jakob Naranđa

    2013-11-01

    Full Text Available Background: Articular cartilage lesions with the inherent limited healing potential are difficult to treat and thus remain a challenging problem for orthopaedic surgeons. Regenerative treatment techniques, such as autologous chondrocyte implantation (ACI, are promising as a treatment option to restore hyaline-like cartilage tissue in damaged articular surfaces, as opposed to the traditional reparative procedures (e.g. bone marrow stimulation – microfracture, which promote a fibrocartilage formation with lower tissue biomechanical properties and poorer clinical results. ACI technique has undergone several advances and is constantly improving. The new concept of cartilage tissue preservation uses tissue-engineering technologies, combining new biomaterials as a scaffold, application of growth factors, use of stem cells, and mechanical stimulation. The recent development of new generations of ACI uses a cartilage-like tissue in a 3-dimensional culture system that is based on the use of biodegradable material which serves as a temporary scaffold for the in vitro growth and subsequent implantation into the cartilage defect. For clinical practice, single stage procedures appear attractive to reduce cost and patient morbidity. Finally, modern concept of tissue engineering facilitates hyaline-like cartilage formation and a permanent treatment of cartilage lesions.Conclusion: The review focuses on innovations in the treatment of cartilage lesions and covers modern concepts of tissue engineering with the use of biomaterials, growth factors, stem cells and bioreactors, and presents options for clinical use.

  1. Cartilage Injuries in the Adult Knee

    Science.gov (United States)

    Moyad, Thomas F.

    2011-01-01

    Cartilage injuries are frequently recognized as a source of significant morbidity and pain in patients with previous knee injuries. The majority of patients who undergo routine knee arthroscopy have evidence of a chondral defect. These injuries represent a continuum of pathology from small, asymptomatic lesions to large, disabling defects affecting a major portion of one or more compartments within the knee joint. In comparison to patients with osteoarthritis, individuals with isolated chondral surface damage are often younger, significantly more active, and usually less willing to accept limitations in activities that require higher impact. At the present time, a variety of surgical procedures exist, each with their unique indications. This heterogeneity of treatment options frequently leads to uncertainty regarding which techniques, if any, are most appropriate for patients. The purpose of this review is to describe the workup and discuss the management techniques for cartilage injuries within the adult knee. PMID:26069581

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

    Directory of Open Access Journals (Sweden)

    M B Gugjoo

    2016-01-01

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

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

    Science.gov (United States)

    Landgraeber, Stefan; Jäger, Marcus; Fickert, Stefan

    2017-11-01

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

  4. MRI of the cartilage

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-11-01

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

  5. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  7. Cysts of the semilunar cartilage

    International Nuclear Information System (INIS)

    Bruessermann, M.

    1981-01-01

    On the basis of the studies listed in the bibliography, this dissertation reports on the pathology, clinical symptoms and radiology of cysts of the semilunar cartilage. The author analyses 118 cases of his own, with special regard to the results of pneumo-arthrographic investigations carried through according to a special technique by Schaefer. In the course of this work, measurements of the meniscal base are for the first time used as radiological criteria indicating the presence of a cyst of the semilunar cartilage. Furthermore the well-known radiological signs of cysts, such as bone defects according to Albert and Keller, light central spot in the meniscal body, as well as Rauber's sign and horizontal rupture, are investigated as to the frequency of their incidence. For that purpose all the X-ray pictures were subjected to a further dose scrutiny. A list of all the 118 cases with their clinical and radiological data is found in the annex, together with the results of the operations and patho-anatomical investigations. (orig.) [de

  8. A retrospective analysis of two independent prospective cartilage repair studies : autogenous perichondrial grafting versus subchondral drilling 10 years post-surgery

    NARCIS (Netherlands)

    Bouwmeester, PSJM; Homminga, GN; Bulstra, SK; Geesink, RGT; Kuijer, Roelof

    Background: Experimental data indicate that perichondrial grafting to restore articular cartilage defects will result in repair with hyaline-like cartilage, In contrast, debridement and drilling results in repair with fibro-cartilage. In this retrospective study the long-term clinical results of

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

    Science.gov (United States)

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

    2018-01-01

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

  10. Particulated articular cartilage: CAIS and DeNovo NT.

    Science.gov (United States)

    Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

    2012-03-01

    Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

  11. Enhanced cellular immune response against SIV Gag induced by immunization with DNA vaccines expressing assembly and release-defective SIV Gag proteins

    International Nuclear Information System (INIS)

    Bu Zhigao; Ye Ling; Compans, Richard W.; Yang Chinglai

    2003-01-01

    Codon-optimized genes were synthesized for the SIVmac239 Gag, a mutant Gag with mutations in the major homology region, and a chimeric Gag containing a protein destruction signal at the N-terminus of Gag. The mutant and chimeric Gag were expressed at levels comparable to that observed for the wild-type Gag protein but their stability and release into the medium were found to be significantly reduced. Immunization of mice with DNA vectors encoding the mutant or chimeric Gag induced fourfold higher levels of anti-SIV Gag CD4 T cell responses than the DNA vector encoding the wild-type SIV Gag. Moreover, anti-SIV Gag CD8 T cell responses induced by DNA vectors encoding the mutant or chimeric Gag were found to be 5- to 10-fold higher than those induced by the DNA construct for the wild-type Gag. These results indicate that mutations disrupting assembly and/or stability of the SIV Gag protein effectively enhance its immunogenicity when expressed from DNA vaccines

  12. Laser surface modification of decellularized extracellular cartilage matrix for cartilage tissue engineering.

    Science.gov (United States)

    Goldberg-Bockhorn, Eva; Schwarz, Silke; Subedi, Rachana; Elsässer, Alexander; Riepl, Ricarda; Walther, Paul; Körber, Ludwig; Breiter, Roman; Stock, Karl; Rotter, Nicole

    2018-02-01

    The implantation of autologous cartilage as the gold standard operative procedure for the reconstruction of cartilage defects in the head and neck region unfortunately implicates a variety of negative effects at the donor site. Tissue-engineered cartilage appears to be a promising alternative. However, due to the complex requirements, the optimal material is yet to be determined. As demonstrated previously, decellularized porcine cartilage (DECM) might be a good option to engineer vital cartilage. As the dense structure of DECM limits cellular infiltration, we investigated surface modifications of the scaffolds by carbon dioxide (CO 2 ) and Er:YAG laser application to facilitate the migration of chondrocytes inside the scaffold. After laser treatment, the scaffolds were seeded with human nasal septal chondrocytes and analyzed with respect to cell migration and formation of new extracellular matrix proteins. Histology, immunohistochemistry, SEM, and TEM examination revealed an increase of the scaffolds' surface area with proliferation of cell numbers on the scaffolds for both laser types. The lack of cytotoxic effects was demonstrated by standard cytotoxicity testing. However, a thermal denaturation area seemed to hinder the migration of the chondrocytes inside the scaffolds, even more so after CO 2 laser treatment. Therefore, the Er:YAG laser seemed to be better suitable. Further modifications of the laser adjustments or the use of alternative laser systems might be advantageous for surface enlargement and to facilitate migration of chondrocytes into the scaffold in one step.

  13. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage.

    Directory of Open Access Journals (Sweden)

    Rebecca Williams

    Full Text Available BACKGROUND: Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC, are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage. METHODS AND FINDINGS: Human articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect. CONCLUSIONS: In conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell

  14. Magnetic resonance imaging of cartilage and cartilage repair

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  15. Magnetic resonance imaging of cartilage and cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-08-01

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

  16. Chondrocytic Potential of Allogenic Mesenchymal Stem Cells Transplanted without Immunosuppression to Regenerate Physeal Defect in Rabbits

    Directory of Open Access Journals (Sweden)

    P. Gál

    2007-01-01

    Full Text Available Mesenchymal stem cells (MSCs from bone marrow are multipotent cells capable of forming cartilage, bone, and other connective tissues. The objective of this study was to determine whether the use of allogenic mesenchymal stem cells could functionally heal a defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. A iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, weighing 2.25 ± 0.24 kg. Each defect, 3.5 mm in width and 12 mm in length, in the right distal femoral physis was treated with allogenic mesenchymal stem cells in new composite hyaluronate/collagen type I/fibrin scaffold. The healing response was evaluated radiographically, by MRI (three weeks and four months after implantation and also histologically, by Pearl’s reaction and with immunofluorescence (four months after implantation. The results were compared with the data for the control defects (without stem cell implantation in left distal femoral physes. On average, right femurs with a damaged distal physis and transplanted MSCs grew more in length (0.55 ± 0.21 cm compared with left femurs with a physeal defect without stem cell transplantation (0.46 ± 0.23 cm. Valgus deformity of right femurs with a physeal defect and transplanted MSCs was mild (0.2 ± 0.1 °. On the contrary, left femurs with a physeal defect without transplanted MSCs showed a significant valgus deformity (2.7 ± 1.6 °. For defects treated with allogenic mesenchymal stem cell implants, no adverse immune response and implant rejection were detected in this model. Histologically, no lymphocytic infiltration occurred. At four months after transplantation, hyaline cartilage had formed throughout the defects treated with allogenic MSCs. Labelled mesenchymal stem cells/differentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescence. The results of this study

  17. PRP and Articular Cartilage: A Clinical Update

    Science.gov (United States)

    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

  18. PRP and Articular Cartilage: A Clinical Update

    Directory of Open Access Journals (Sweden)

    Antonio Marmotti

    2015-01-01

    Full Text Available 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.

  19. Autologous Cartilage Chip Transplantation Improves Repair Tissue Composition Compared With Marrow Stimulation.

    Science.gov (United States)

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

    2017-06-01

    Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Controlled laboratory study. Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P cartilage repair tissue compared with MST at 6 months postoperatively. Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

  20. Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves

    Directory of Open Access Journals (Sweden)

    Wei-ling Cui

    2016-01-01

    Full Text Available Vascularization of acellular nerves has been shown to contribute to nerve bridging. In this study, we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves. The rat nerve defects were treated with acellular nerve grafting (control group alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein (experimental group. As shown through two-dimensional imaging, the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation, and gradually covered the entire graft at day 21. The vascular density, vascular area, and the velocity of revascularization in the experimental group were all higher than those in the control group. These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.

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

    Directory of Open Access Journals (Sweden)

    Shuaijun Jia

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

  2. Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease

    Science.gov (United States)

    Farid, Marjan; Agrawal, Anshu; Fremgen, Daniel; Tao, Jeremiah; Chuyi, He; Nesburn, Anthony B.; BenMohamed, Lbachir

    2014-01-01

    Dry eye disease (DED) is a prevalent public health concern that affects up to 30% of adults and is particularly chronic and severe in the elderly. Two interconnected mechanisms cause DED: (1) an age-related dysfunction of lacrimal and meibomian glands, which leads to decreased tear production and/or an increase in tear evaporation; and (2) an age-related uncontrolled inflammation of the surface of the eye triggered by yet-to-be-determined internal immunopathological mechanisms, independent of tear deficiency and evaporation. In this review we summarize current knowledge on animal models that mimic both the severity and chronicity of inflammatory DED and that have been reliably used to provide insights into the immunopathological mechanisms of DED, and we provide an overview of the opportunities and limitations of the rabbit model in investigating the role of both ocular and nasal mucosal immune systems in the immunopathology of inflammatory DED and in testing novel immunotherapies aimed at delaying or reversing the uncontrolled age-related inflammatory DED. PMID:25535823

  3. Effect of thiram on chicken growth plate cartilage

    Science.gov (United States)

    Thiram is a general use dithiocarbamate pesticide. It causes tibial dyschondroplasia, a growth plate cartilage defect in poultry characterized by growth plate broadening due to the accumulation of nonviable chondrocytes which lead to lameness. Since proteins play significant roles in all aspects cel...

  4. Surgical correction of joint deformities and hyaline cartilage regeneration

    Directory of Open Access Journals (Sweden)

    Vyacheslav Alexandrovich Vinokurov

    2015-12-01

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

  5. Reviewing subchondral cartilage surgery: considerations for standardised and outcome predictable cartilage remodelling: a technical note.

    Science.gov (United States)

    Benthien, Jan P; Behrens, Peter

    2013-11-01

    The potential of subchondral mesenchymal stem cell stimulation (MSS) for cartilage repair has led to the widespread use of microfracture as a first line treatment for full thickness articular cartilage defects. Recent focus on the effects of subchondral bone during cartilage injury and repair has expanded the understanding of the strengths and limitations in MSS and opened new pathways for potential improvement. Comparative studies have shown that bone marrow access has positive implications for pluripotential cell recruitment, repair quality and quantity, i.e. deeper channels elicited better cartilage fill, more hyaline cartilage character with higher type II collagen content and lower type I collagen content compared to shallow marrow access. A subchondral needling procedure using standardised and thin subchondral perforations deep into the subarticular bone marrow making the MSS more consistent with the latest developments in subchondral cartilage remodelling is proposed. As this is a novel method clinical studies have been initiated to evaluate the procedure especially compared to microfracturing. However, the first case studies and follow-ups indicate that specific drills facilitate reaching the subchondral bone marrow while the needle size makes perforation of the subchondral bone easier and more predictable. Clinical results of the first group of patients seem to compare well to microfracturing. The authors suggest a new method for a standardised procedure using a new perforating device. Advances in MSS by subchondral bone marrow perforation are discussed. It remains to be determined by clinical studies how this method compares to microfracturing. The subchondral needling offers the surgeon and the investigator a method that facilitates comparison studies because of its defined depth of subchondral penetration and needle size.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    1997-01-01

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

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

    Science.gov (United States)

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

    2018-02-01

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

  9. Magnetization transfer contrast (MTC) and MTC-subtraction: enhancement of cartilage lesions and intracartilaginous degeneration in vitro

    International Nuclear Information System (INIS)

    Vahlensieck, M.; Dombrowski, F.; Leutner, C.; Wagner, U.; Reiser, M.

    1994-01-01

    Human articular cartilage from 16 cadaveric or amputated knees was studied using standard magnetic resonance imaging (MRI), on-resonance magnetization transfer contrast (MTC) and MTC-subtraction MRI. Results were compared with subsequent macroscopic and histopathological findings. MTC-subtraction and T2-weighted spin-echo images visualized cartilaginous surface defects with high sensitivity and specificity. MTC and T2-weighted spin-echo images revealed intra-cartilaginous signal loss without surface defects in 80% of the cases, corresponding to an increased collagen concentration. It is concluded that MTC is sensitive to early cartilage degeneration and MTC-subtraction can be helpful in detecting cartilage defects. (orig.)

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

    Science.gov (United States)

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

    2013-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-11-15

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

  12. MR imaging of articular cartilage

    International Nuclear Information System (INIS)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  14. Lubrication and cartilage.

    Science.gov (United States)

    Wright, V; Dowson, D

    1976-02-01

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

  15. Chondroptosis in Alkaptonuric Cartilage

    Science.gov (United States)

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

    2015-01-01

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

  16. INJURED ARTICULAR CARTILAGE REPAIR

    Directory of Open Access Journals (Sweden)

    Ariana Barlič

    2008-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-10-15

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

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

    Science.gov (United States)

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

    2016-11-01

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

  19. Overview of existing cartilage repair technology.

    Science.gov (United States)

    McNickle, Allison G; Provencher, Matthew T; Cole, Brian J

    2008-12-01

    Currently, autologous chondrocyte implantation and osteochondral grafting bridge the gap between palliation of cartilage injury and resurfacing via arthroplasty. Emerging technologies seek to advance first generation techniques and accomplish several goals including predictable outcomes, cost-effective technology, single-stage procedures, and creation of durable repair tissue. The biologic pipeline represents a variety of technologies including synthetics, scaffolds, cell therapy, and cell-infused matrices. Synthetic constructs, an alternative to biologic repair, resurface a focal chondral defect rather than the entire joint surface. Scaffolds are cell-free constructs designed as a biologic "net" to augment marrow stimulation techniques. Minced cartilage technology uses stabilized autologous or allogeneic fragments in 1-stage transplantation. Second and third generation cell-based methods include alternative membranes, chondrocyte seeding, and culturing onto scaffolds. Despite the promising early results of these products, significant technical obstacles remain along with unknown long-term durability. The vast array of developing technologies has exceptional promise and the potential to revolutionize the cartilage treatment algorithm within the next decade.

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

    Science.gov (United States)

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

    2014-03-01

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

  1. Advances in cartilage tissue engineering : in vitro

    NARCIS (Netherlands)

    E.W. Mandl (Erik)

    2004-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  3. Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair

    NARCIS (Netherlands)

    Mouser, Vivian H M; Dautzenberg, Noël M M; Levato, Riccardo; van Rijen, Mattie H P; Dhert, Wouter J A; Malda, Jos; Gawlitta, Debby

    2018-01-01

    The implantation of chondrocyte-laden hydrogels is a promising cartilage repair strategy. Chondrocytes can be spatially positioned in hydrogels and thus in defects, while current clinical cell-therapies introduce chondrocytes in the defect depth. The main aim of this study was to evaluate the effect

  4. Towards Regeneration of Articular Cartilage

    Science.gov (United States)

    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

  5. Peculiarities in Ankle Cartilage.

    Science.gov (United States)

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

    2017-01-01

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

  6. Cartilage grafting in nasal reconstruction.

    Science.gov (United States)

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

    2011-02-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2001-09-20

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

  10. The properties of bioengineered chondrocyte sheets for cartilage regeneration

    Directory of Open Access Journals (Sweden)

    Ota Naoshi

    2009-03-01

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

  11. Subchondral drilling for articular cartilage repair: a systematic review of translational research.

    Science.gov (United States)

    Gao, Liang; Goebel, Lars K H; Orth, Patrick; Cucchiarini, Magali; Madry, Henning

    2018-05-03

    Articular cartilage defects may initiate osteoarthritis. Subchondral drilling, a widely applied clinical technique to treat small cartilage defects, does not yield cartilage regeneration. Various translational studies aiming to improve the outcome of drilling have been performed, however, a robust systematic analysis of its translational evidence has been still lacking. Here, we performed a systematic review of the outcome of subchondral drilling for knee cartilage repair in translational animal models. A total of 12 relevant publications studying 198 animals were identified, detailed study characteristics were extracted, and methodological quality and risk of bias were analyzed. Subchondral drilling was superior to defects untreated or treated with abrasion arthroplasty for cartilage repair in multiple translational models. Considerable subchondral bone changes were observed, including subchondral bone cysts and intralesional osteophytes. Furthermore, extensive alterations of the subchondral bone microarchitecture appeared in a temporal pattern in small and large animal models, together with specific topographic aspects of repair. Moreover, variable technical aspects directly affected the outcomes of osteochondral repair. The data from this systematic review indicate that subchondral drilling yields improved short-term structural articular cartilage repair compared with spontaneous repair in multiple small and large animal models. These results have important implications for future investigations aimed at an enhanced translation into clinical settings for the treatment of cartilage defects, highlighting the importance of considering specific aspects of modifiable variables such as improvements in the design and reporting of preclinical studies, together with the need to better understand the underlying mechanisms of cartilage repair following subchondral drilling. © 2018. Published by The Company of Biologists Ltd.

  12. * Human Amniotic Mesenchymal Stromal Cells as Favorable Source for Cartilage Repair.

    Science.gov (United States)

    Muiños-López, Emma; Hermida-Gómez, Tamara; Fuentes-Boquete, Isaac; de Toro-Santos, Javier; Blanco, Francisco Javier; Díaz-Prado, Silvia María

    2017-09-01

    Localized trauma-derived breakdown of the hyaline articular cartilage may progress toward osteoarthritis, a degenerative condition characterized by total loss of articular cartilage and joint function. Tissue engineering technologies encompass several promising approaches with high therapeutic potential for the treatment of these focal defects. However, most of the research in tissue engineering is focused on potential materials and structural cues, while little attention is directed to the most appropriate source of cells endowing these materials. In this study, using human amniotic membrane (HAM) as scaffold, we defined a novel static in vitro model for cartilage repair. In combination with HAM, four different cell types, human chondrocytes, human bone marrow-derived mesenchymal stromal cells (hBMSCs), human amniotic epithelial cells, and human amniotic mesenchymal stromal cells (hAMSCs) were assessed determining their therapeutic potential. A chondral lesion was drilled in human cartilage biopsies simulating a focal defect. A pellet of different cell types was implanted inside the lesion and covered with HAM. The biopsies were maintained for 8 weeks in culture. Chondrogenic differentiation in the defect was analyzed by histology and immunohistochemistry. HAM scaffold showed good integration and adhesion to the native cartilage in all groups. Although all cell types showed the capacity of filling the focal defect, hBMSCs and hAMSCs demonstrated higher levels of new matrix synthesis. However, only the hAMSCs-containing group presented a significant cytoplasmic content of type II collagen when compared with chondrocytes. More collagen type I was identified in the new synthesized tissue of hBMSCs. In accordance, hBMSCs and hAMSCs showed better International Cartilage Research Society scoring although without statistical significance. HAM is a useful material for articular cartilage repair in vitro when used as scaffold. In combination with hAMSCs, HAM showed better

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

    OpenAIRE

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

    2017-01-01

    BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue ...

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

    OpenAIRE

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

    2017-01-01

    Background The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue e...

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

    Directory of Open Access Journals (Sweden)

    Kurokawa Takayuki

    2011-09-01

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

  16. Laser-assisted cartilage reshaping: in vitro and in vivo animal studies

    Science.gov (United States)

    Wang, Zhi; Pankratov, Michail M.; Perrault, Donald F., Jr.; Shapshay, Stanley M.

    1995-05-01

    Correction of cartilaginous defects in the head and neck area remains a challenge for the surgeon. This study investigated a new technique for laser-assisted cartilage reshaping. The pulsed 1.44 micrometers Nd:YAG laser was used in vitro and in vivo experiments to irradiate cartilage to change it's shape without carbonization or vaporization of tissue. Two watts of average power in non contact manner was used to irradiate and reshape the cartilage. The extracted reshaped cartilage specimens underwent testing of elastic force with a computer assisted measurement system that recorded the changes in elastic force in the specimens from 1 hr to 11 days post-irradiation. An animal model of defective tracheal cartilage (collapsed tracheal wall) was created, allowed to heal for 6 weeks and then corrected endoscopically with the laser-assisted technique. The results of the in vitro and in vivo investigations demonstrated that it was possible to alter the cartilage and that cartilage would retain its new shape. The clinical significance of the technique is evident and warrants further animal studies and clinical trials.

  17. Expression of cartilage developmental genes in Hoxc8- and Hoxd4-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Claudia Kruger

    2010-02-01

    Full Text Available Hox genes encode transcription factors, which regulate skeletal patterning and chondrocyte differentiation during the development of cartilage, the precursor to mature bone. Overexpression of the homeobox transcription factors Hoxc8 and Hoxd4 causes severe cartilage defects due to delay in cartilage maturation. Matrix metalloproteinases (MMPs, bone morphogenetic proteins (BMPs and fibroblastic growth factors (FGFs are known to play important roles in skeletal development and endochondral bone formation and remodeling. In order to investigate whether these molecules are aberrantly expressed in Hoxc8- and/or Hoxd4-transgenic cartilage, we performed quantitative RT-PCR on chondrocytes from Hox-transgenic mice. Gene expression levels of Bmp4, Fgf8, Fgf10, Mmp9, Mmp13, Nos3, Timp3, Wnt3a and Wnt5a were altered in Hoxc8-transgenic chondrocytes, and Fgfr3, Ihh, Mmp8, and Wnt3a expression levels were altered in Hoxd4-transgenic chondrocytes, respectively. Notably, Wnt3a expression was elevated in Hoxc8- and reduced in Hoxd4-transgenic cartilage. These results suggest that both transcription factors affect cartilage maturation through different molecular mechanisms, and provide the basis for future studies into the role of these genes and possible interactions in pathogenesis of cartilage defects in Hoxc8- and Hoxd4-transgenic mice.

  18. Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats.

    Science.gov (United States)

    Zhu, Lei; Zhao, Zhi Jun; Ren, Xiao Bin; Li, Qiang; Ding, Hua; Sun, Zhou; Kao, Qing Jun; Wang, Li Hua

    2018-01-01

    The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin (300 ng/kg chow) for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lysoPE (18:0/0:0), lysoPC(14:0), lysoPC[18:4 (6Z,9Z,12Z,15Z)], lysoPC[(16:1(9Z)], lysoPC(16:0), L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  19. Traumatic humeral articular cartilage shear (THACS) lesion in a professional rugby player: a case report.

    Science.gov (United States)

    Jeon, I-H; Wallace, W A

    2004-08-01

    A 20 year old male professional rugby player was seen at the clinic for evaluation of shoulder pain after rugby play. Magnetic resonance imaging showed extensive subchondral bone bruising of the humeral head with defect of the articular cartilage. Arthroscopy showed that the inferior half of the humeral head had extensive articular cartilage loss with nearly 70% of the inferior head having lost its cartilage. Sports medicine doctors should be aware that the shoulder joint in young competitive athletes playing contact sports may be exposed to greater risk of this kind of injury.

  20. Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair.

    Science.gov (United States)

    Zhou, Feifei; Zhang, Xianzhu; Cai, Dandan; Li, Jun; Mu, Qin; Zhang, Wei; Zhu, Shouan; Jiang, Yangzi; Shen, Weiliang; Zhang, Shufang; Ouyang, Hong Wei

    2017-11-01

    The demand of favorable scaffolds has increased for the emerging cartilage tissue engineering. Chondroitin sulfate (CS) and silk fibroin have been investigated and reported with safety and excellent biocompatibility as tissue engineering scaffolds. However, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate neo-tissue similar to natural articular cartilage. Meanwhile the silk fibroin is well used as a structural constituent material because its remarkable mechanical properties, long-lasting in vivo stability and hypoimmunity. The application of composite silk fibroin and CS scaffolds for joint cartilage repair has not been well studied. Here we report that the combination of silk fibroin and CS could synergistically promote articular cartilage defect repair. The silk fibroin (silk) and silk fibroin/CS (silk-CS) scaffolds were fabricated with salt-leaching, freeze-drying and crosslinking methodologies. The biocompatibility of the scaffolds was investigated in vitro by cell adhesion, proliferation and migration with human articular chondrocytes. We found that silk-CS scaffold maintained better chondrocyte phenotype than silk scaffold; moreover, the silk-CS scaffolds reduced chondrocyte inflammatory response that was induced by interleukin (IL)-1β, which is in consistent with the well-documented anti-inflammatory activities of CS. The in vivo cartilage repair was evaluated with a rabbit osteochondral defect model. Silk-CS scaffold induced more neo-tissue formation and better structural restoration than silk scaffold after 6 and 12weeks of implantation in ICRS histological evaluations. In conclusion, we have developed a silk fibroin/ chondroitin sulfate scaffold for cartilage tissue engineering that exhibits immuno-inhibition property and can improve the self-repair capacity of cartilage. Severe cartilage defect such as osteoarthritis (OA) is difficult to self-repair because of its avascular, aneural and alymphatic nature

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Relationship between the trochlear groove angle and patellar cartilage morphology defined by 3D spoiled gradient-echo imaging

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Yuko; Tokuda, Osamu; Matsunaga, Naofumi [Yamaguchi University Graduate School of Medicine, Department of Radiology, Yamaguchi (Japan); Fukuda, Kouji [Shunan Memorial Hospital, Division of Radiological Technology, Yamaguchi (Japan); Shiraishi, Gen; Motomura, Tetsuhisa [Shunan Memorial Hospital, Department of Orthopedics Surgery, Yamaguchi (Japan); Kimura, Motoichi [Customer Application Gr., GE Healthcare MR Sales and Marketing Department, Osaka (Japan)

    2012-05-15

    To examine whether the femoral trochlear groove angle (TGA) is a determinant of the patellar cartilage volume and patellar cartilage damage. Patellar cartilage was evaluated by MR imaging in 66 patients (22 males and 44 females) with knee pain. Fat-suppressed 3D spoiled gradient-echo images were used to calculate the cartilage volume and to grade the cartilage damage. The proximal and distal TGAs were measured from axial PD-weighted FSE MR images with fat suppression. For every increase in the TGA at the distal femur, the patellar cartilage volume was significantly increased by 6.07 x 10{sup -3} cm{sup 3} (95% CI: 1.27 x 10{sup -3}, 10.9 x 10{sup -3}) after adjustment for age, gender, and patellar bone volume (P < 0.05). The MR grade of medial patellar cartilage damage progressed as the distal TGA became narrower, although there was no significant correlation between the distal TGA and the MR grading of patellar cartilage damage. A more flattened distal TGA was associated with increased patellar cartilage volume. However, there was no association between TGA and patellar cartilage defects. (orig.)

  3. Evaluation of degenerative changes in articular cartilage of osteoarthritis by Raman spectroscopy

    Science.gov (United States)

    Oshima, Yusuke; Ishimaru, Yasumitsu; Kiyomatsu, Hiroshi; Hino, Kazunori; Miura, Hiromasa

    2018-02-01

    Osteoarthritis (OA) is a very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this proposal, we aim to develop Raman spectroscopic system for the quality assessment of articular cartilage during arthroscopic surgery. Toward this goal, we are focusing on the proteoglycan content and collagen fiber alignment in cartilage matrix which may be associated with degenerative changes in OA, and we designed an original Raman device for remote sensing during arthroscopic surgery. In this project, we define the grading system for cartilage defect based on Raman spectroscopy, and we complete the evaluation of the Raman probing system which makes it possible to detect early stage of degenerative cartilage as a novel tool for OA diagnosis using human subject.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Amin Tavassoli

    2015-12-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Catherine Baugé

    2015-01-01

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

  8. Regulators of articular cartilage homeostasis

    NARCIS (Netherlands)

    Leijten, Jeroen Christianus Hermanus

    2012-01-01

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

  9. Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model.

    Science.gov (United States)

    McClanahan, Fabienne; Riches, John C; Miller, Shaun; Day, William P; Kotsiou, Eleni; Neuberg, Donna; Croce, Carlo M; Capasso, Melania; Gribben, John G

    2015-07-09

    T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eμ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1(+) T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8(+) T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity. © 2015 by The American Society of Hematology.

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

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

    2017-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Patrascu JM¹,

    2016-12-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  15. Small-Diameter Awls Improve Articular Cartilage Repair After Microfracture Treatment in a Translational Animal Model.

    Science.gov (United States)

    Orth, Patrick; Duffner, Julia; Zurakowski, David; Cucchiarini, Magali; Madry, Henning

    2016-01-01

    Microfracture is the most commonly applied arthroscopic marrow stimulation procedure. Articular cartilage repair is improved when the subchondral bone is perforated by small-diameter microfracture awls compared with larger awls. Controlled laboratory study. Standardized rectangular (4 × 8 mm) full-thickness chondral defects (N = 24) were created in the medial femoral condyle of 16 adult sheep and debrided down to the subchondral bone plate. Three treatment groups (n = 8 defects each) were tested: 6 microfracture perforations using small-diameter awls (1.0 mm; group 1), large-diameter awls (1.2 mm; group 2), or without perforations (debridement control; group 3). Osteochondral repair was assessed at 6 months in vivo using established macroscopic, histological, immunohistochemical, biochemical, and micro-computed tomography analyses. Compared with control defects, histological cartilage repair was always improved after both microfracture techniques (P Subchondral bone cysts and intralesional osteophytes were frequently observed after either microfracture treatment. Macroscopic grading, DNA, proteoglycan, and type I and type II collagen contents as well as degenerative changes within the adjacent cartilage remained unaffected by the awl diameter. Small-diameter microfracture awls improve articular cartilage repair in the translational sheep model more effectively than do larger awls. These data support the use of small microfracture instruments for the surgical treatment of cartilage defects and warrant prolonged clinical investigations. © 2015 The Author(s).

  16. Magnetically targeted delivery through cartilage

    Science.gov (United States)

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

    2018-05-01

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

  17. Magnetically targeted delivery through cartilage

    Directory of Open Access Journals (Sweden)

    Sahar Jafari

    2018-05-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

  19. Bio-inks for 3D printing of Cartilage Implants : Tailoring gelMA and polyHPMA-lac-PEG hydrogels for the fabrication of spatially organized constructs

    NARCIS (Netherlands)

    Mouser, V.H.M.

    2017-01-01

    A promising approach to treat cartilage defects is the implantation of stratified cell-laden hydrogel implants that mimic native cartilage. To fabricate such constructs, three-dimensional (3D) bioprinting techniques are promising, as they allow accurate deposition of (cell-laden) biomaterials, the

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

    DEFF Research Database (Denmark)

    Schmal, Hagen; Niemeyer, Philipp; Zwingmann, Jörn

    2010-01-01

    patients had no cartilage lesion and served as a control group, the other 42 patients with circumscribed cartilage defects were treated by microfracturing (19) or by an Autologous Chondrocyte Implantation (23). The concentrations of BMP-2 and BMP-7 were determined by ELISA. The clinical status...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-01

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

  2. Ventricular septal defect closure in a patient with achondroplasia.

    Science.gov (United States)

    Nakanishi, Keisuke; Kawasaki, Shiori; Amano, Atsushi

    2017-01-01

    Achondroplasia with co-morbid CHD is rare, as are reports of surgical treatment for such patients. We present the case of a 13-year-old girl with achondroplasia and ventricular septal defect. Her ventricular septal defect was surgically repaired focussing on the cardiopulmonary bypass flow, healing of the sternum, and her frail neck cartilage. The surgery and recovery were without complications.

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

    Science.gov (United States)

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

    2012-06-01

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

  4. A modular approach to creating large engineered cartilage surfaces.

    Science.gov (United States)

    Ford, Audrey C; Chui, Wan Fung; Zeng, Anne Y; Nandy, Aditya; Liebenberg, Ellen; Carraro, Carlo; Kazakia, Galateia; Alliston, Tamara; O'Connell, Grace D

    2018-01-23

    Native articular cartilage has limited capacity to repair itself from focal defects or osteoarthritis. Tissue engineering has provided a promising biological treatment strategy that is currently being evaluated in clinical trials. However, current approaches in translating these techniques to developing large engineered tissues remains a significant challenge. In this study, we present a method for developing large-scale engineered cartilage surfaces through modular fabrication. Modular Engineered Tissue Surfaces (METS) uses the well-known, but largely under-utilized self-adhesion properties of de novo tissue to create large scaffolds with nutrient channels. Compressive mechanical properties were evaluated throughout METS specimens, and the tensile mechanical strength of the bonds between attached constructs was evaluated over time. Raman spectroscopy, biochemical assays, and histology were performed to investigate matrix distribution. Results showed that by Day 14, stable connections had formed between the constructs in the METS samples. By Day 21, bonds were robust enough to form a rigid sheet and continued to increase in size and strength over time. Compressive mechanical properties and glycosaminoglycan (GAG) content of METS and individual constructs increased significantly over time. The METS technique builds on established tissue engineering accomplishments of developing constructs with GAG composition and compressive properties approaching native cartilage. This study demonstrated that modular fabrication is a viable technique for creating large-scale engineered cartilage, which can be broadly applied to many tissue engineering applications and construct geometries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Passaged adult chondrocytes can form engineered cartilage with functional mechanical properties: a canine model.

    Science.gov (United States)

    Ng, Kenneth W; Lima, Eric G; Bian, Liming; O'Conor, Christopher J; Jayabalan, Prakash S; Stoker, Aaron M; Kuroki, Keiichi; Cook, Cristi R; Ateshian, Gerard A; Cook, James L; Hung, Clark T

    2010-03-01

    It was hypothesized that previously optimized serum-free culture conditions for juvenile bovine chondrocytes could be adapted to generate engineered cartilage with physiologic mechanical properties in a preclinical, adult canine model. Primary or passaged (using growth factors) adult chondrocytes from three adult dogs were encapsulated in agarose, and cultured in serum-free media with transforming growth factor-beta3. After 28 days in culture, engineered cartilage formed by primary chondrocytes exhibited only small increases in glycosaminoglycan content. However, all passaged chondrocytes on day 28 elaborated a cartilage matrix with compressive properties and glycosaminoglycan content in the range of native adult canine cartilage values. A preliminary biocompatibility study utilizing chondral and osteochondral constructs showed no gross or histological signs of rejection, with all implanted constructs showing excellent integration with surrounding cartilage and subchondral bone. This study demonstrates that adult canine chondrocytes can form a mechanically functional, biocompatible engineered cartilage tissue under optimized culture conditions. The encouraging findings of this work highlight the potential for tissue engineering strategies using adult chondrocytes in the clinical treatment of cartilage defects.

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

    DEFF Research Database (Denmark)

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

    2018-01-01

    for the treatment of large, isolated, full thickness cartilage defects. Several disadvantages such as the need for two surgical procedures or hypertrophic regenerative cartilage, underline the need for alternative cell sources. OBJECTIVE: Mesenchymal stem cells, particularly synovium-derived mesenchymal stem cells......, represent a promising cell source. Synovium-derived mesenchymal stem cells have attracted considerable attention since they display great chondrogenic potential and less hypertrophic differentiation than mesenchymal stem cells derived from bone marrow. The aim of this review was to summarize the current...... knowledge on the chondrogenic potential for synovial stem cells in regard to cartilage repair purposes. RESULTS: A literature search was carried out identifying 260 articles in the databases up to January 2017. Several in vitro and initial animal in vivo studies of cartilage repair using synovia stem cell...

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

    Directory of Open Access Journals (Sweden)

    Ashvin K. Dewan

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-07-05

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

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

    International Nuclear Information System (INIS)

    Zbyn, S.

    2015-01-01

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

  10. Tissue engineering of cartilages using biomatrices

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  11. Laser solder welding of articular cartilage: tensile strength and chondrocyte viability.

    Science.gov (United States)

    Züger, B J; Ott, B; Mainil-Varlet, P; Schaffner, T; Clémence, J F; Weber, H P; Frenz, M

    2001-01-01

    The surgical treatment of full-thickness cartilage defects in the knee joint remains a therapeutic challenge. Recently, new techniques for articular cartilage transplantation, such as mosaicplasty, have become available for cartilage repair. The long-term success of these techniques, however, depends not only on the chondrocyte viability but also on a lateral integration of the implant. The goal of this study was to evaluate the feasibility of cartilage welding by using albumin solder that was dye-enhanced to allow coagulation with 808-nm laser diode irradiation. Conventional histology of light microscopy was compared with a viability staining to precisely determine the extent of thermal damage after laser welding. Indocyanine green (ICG) enhanced albumin solder (25% albumin, 0.5% HA, 0.1% ICG) was used for articular cartilage welding. For coagulation, the solder was irradiated through the cartilage implant by 808-nm laser light and the tensile strength of the weld was measured. Viability staining revealed a thermal damage of typically 500 m in depth at an irradiance of approximately 10 W/cm(2) for 8 seconds, whereas conventional histologies showed only half of the extent found by the viability test. Heat-bath investigations revealed a threshold temperature of minimum 54 degrees C for thermal damage of chondrocytes. Efficient cartilage bonding was obtained by using bovine albumin solder as adhesive. Maximum tensile strength of more than 10 N/cm(2) was achieved. Viability tests revealed that the thermal damage is much greater (up to twice) than expected after light microscopic characterization. This study shows the feasibility to strongly laser weld cartilage on cartilage by use of a dye-enhanced albumin solder. Possibilities to reduce the range of damage are suggested. Copyright 2001 Wiley-Liss, Inc.

  12. Tribological changes in the articular cartilage of a human femoral head with avascular necrosis.

    Science.gov (United States)

    Seo, Eun-Min; Shrestha, Suman K; Duong, Cong-Truyen; Sharma, Ashish Ranjan; Kim, Tae-Woo; Vijayachandra, Ayyappan; Thompson, Mark S; Cho, Myung Guk; Park, Sungchan; Kim, Kwanghoon; Park, Seonghun; Lee, Sang-Soo

    2015-06-29

    The present study evaluated the tribological properties of the articular cartilage surface of the human femoral head with postcollapse stage avascular necrosis (AVN) using atomic force microscopy. The cartilage surface in the postcollapse stage AVN of the femoral head was reported to resemble those of disuse conditions, which suggests that the damage could be reversible and offers the possibilities of success of head-sparing surgeries. By comparing the tribological properties of articular cartilage in AVN with that of osteoarthritis, the authors intended to understand the cartilage degeneration mechanism and reversibility of AVN. Human femoral heads with AVN were explanted from the hip replacement surgery of four patients (60-83 years old). Nine cylindrical cartilage samples (diameter, 5 mm and height, 0.5 mm) were sectioned from the weight-bearing areas of the femoral head with AVN, and the cartilage surface was classified according to the Outerbridge Classification System (AVN0, normal; AVN1, softening and swelling; and AVN2, partial thickness defect and fissuring). Tribological properties including surface roughness and frictional coefficients and histochemistry including Safranin O and lubricin staining were compared among the three groups. The mean surface roughness Rq values of AVN cartilage increased significantly with increasing Outerbridge stages: Rq = 137 ± 26 nm in AVN0, Rq = 274 ± 49 nm in AVN1, and Rq = 452 ± 77 nm in AVN2. Significant differences in Rq were observed among different Outerbridge stages in all cases (p AVN0, μ = 0.143 ± 0.025 in AVN1, and μ = 0.171 ± 0.039 in AVN2. Similarly to the statistical analysis of surface roughness, significant statistical differences were detected between different Outerbridge stages in all cases (p AVN. The underlying mechanism of these results can be related to proteoglycan loss within the articular cartilage that is also observed in osteoarthritis. With regard to the tribological properties, the

  13. Birth Defects

    Science.gov (United States)

    A birth defect is a problem that happens while a baby is developing in the mother's body. Most birth defects happen during the first 3 months of ... in the United States is born with a birth defect. A birth defect may affect how the ...

  14. Combined nanoindentation testing and scanning electron microscopy of bone and articular calcified cartilage in an equine fracture predilection site

    OpenAIRE

    M Doube; EC Firth; A Boyde; AJ Bushby

    2010-01-01

    Condylar fracture of the third metacarpal bone (Mc3) is the commonest cause of racetrack fatality in Thoroughbred horses. Linear defects involving hyaline articular cartilage, articular calcified cartilage (ACC) and subchondral bone (SCB) have been associated with the fracture initiation site, which lies in the sagittal grooves of the Mc3 condyle. We discovered areas of thickened and abnormally-mineralised ACC in the sagittal grooves of several normal 18-month-old horses, at the same site tha...

  15. Osteoarthritic cartilage is more homogeneous than healthy cartilage

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  16. Tri-layered composite plug for the repair of osteochondral defects: in vivo study in sheep

    Directory of Open Access Journals (Sweden)

    Altug Yucekul

    2017-04-01

    Full Text Available Cartilage defects are a source of pain, immobility, and reduced quality of life for patients who have acquired these defects through injury, wear, or disease. The avascular nature of cartilage tissue adds to the complexity of cartilage tissue repair or regeneration efforts. The known limitations of using autografts, allografts, or xenografts further add to this complexity. Autologous chondrocyte implantation or matrix-assisted chondrocyte implantation techniques attempt to introduce cultured cartilage cells to defect areas in the patient, but clinical success with these are impeded by the avascularity of cartilage tissue. Biodegradable, synthetic scaffolds capable of supporting local cells and overcoming the issue of poor vascularization would bypass the issues of current cartilage treatment options. In this study, we propose a biodegradable, tri-layered (poly(glycolic acid mesh/poly(l-lactic acid-colorant tidemark layer/collagen Type I and ceramic microparticle-coated poly(l-lactic acid-poly(ϵ-caprolactone monolith osteochondral plug indicated for the repair of cartilage defects. The porous plug allows the continual transport of bone marrow constituents from the subchondral layer to the cartilage defect site for a more effective repair of the area. Assessment of the in vivo performance of the implant was conducted in an ovine model (n = 13. In addition to a control group (no implant, one group received the implant alone (Group A, while another group was supplemented with hyaluronic acid (0.8 mL at 10 mg/mL solution; Group B. Analyses performed on specimens from the in vivo study revealed that the implant achieves cartilage formation within 6 months. No adverse tissue reactions or other complications were reported. Our findings indicate that the porous biocompatible implant seems to be a promising treatment option for the cartilage repair.

  17. Transcriptomic signatures in cartilage ageing

    Science.gov (United States)

    2013-01-01

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

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

    NARCIS (Netherlands)

    Klompmaker, Jan

    1992-01-01

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

  19. High throughput generated micro-aggregates of chondrocytes stimulate cartilage formation in vitro and in vivo

    NARCIS (Netherlands)

    Moreira Teixeira, Liliana; Leijten, Jeroen Christianus Hermanus; Sobral, J.; Jin, R.; van Apeldoorn, Aart A.; Feijen, Jan; van Blitterswijk, Clemens; Dijkstra, Pieter J.; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Cell-based cartilage repair strategies such as matrix-induced autologous chondrocyte implantation (MACI) could be improved by enhancing cell performance. We hypothesised that micro-aggregates of chondrocytes generated in high-throughput prior to implantation in a defect could stimulate cartilaginous

  20. Preserved irradiated homologous cartilage for orbital reconstruction

    International Nuclear Information System (INIS)

    Linberg, J.V.; Anderson, R.L.; Edwards, J.J.; Panje, W.R.; Bardach, J.

    1980-01-01

    Human costal cartilage is an excellent implant material for orbital and periorbital reconstruction because of its light weight, strength, homogeneous consistency and the ease with which it can be carved. Its use has been limited by the necessity of a separate surgical procedure to obtain the material. Preserved irradiated homologous cartilage has been shown to have almost all the autogenous cartilage and is convenient to use. Preserved irradiated homologous cartilage transplants do not elicit rejection reactions, resist infection and rarely undergo absorption

  1. MR Imaging of Articular Hyaline Cartilage

    OpenAIRE

    Uetani, Masataka

    2005-01-01

    MR imaging is still an evolving technique for the diagnosis of joint cartilage lesions. Early morphologic changes in the degenerative cartilage are not reliably diagnosed even with use of tailored MR imaging techniques. The detection of the biochemical changes of cartilage or high-resolution MRI will serve as an important tool for the early diagnosis of cartilage degeneration in near future. Further prospective studies are needed to establish the role of MR imaging in clinical use.

  2. Biomaterial and Cell Based Cartilage Repair

    NARCIS (Netherlands)

    Zhao, X

    2015-01-01

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

  3. Modeling the development of tissue engineered cartilage

    NARCIS (Netherlands)

    Sengers, B.G.

    2005-01-01

    The limited healing capacity of articular cartilage forms a major clinical problem. In general, current treatments of cartilage damage temporarily reliefs symptoms, but fail in the long term. Tissue engineering (TE) has been proposed as a more permanent repair strategy. Cartilage TE aims at

  4. Transcriptomic profiling of cartilage ageing

    Directory of Open Access Journals (Sweden)

    Mandy Jayne Peffers

    2014-12-01

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

  5. Fibrous metaphyseal defects

    International Nuclear Information System (INIS)

    Hajek, P.C.; Ritschi, P.; Kramer, J.; Imhof, H.; Karnel, F.

    1988-01-01

    Eighty-two patients (107 fibrous metaphyseal defects [FMDs]) were investigated with standard radiography and MR imaging (N = 15). Twenty-two of these were followed up sequentially up to 10 years (mean, 7.3 years). Histologic studies proved that FMDs originate at the site of insertion of a tendon in the perichondrium of the epiphyseal cartilage. After normal bone growth is regained, all FMDs were found to move diaphysically, following a straight line parallel to the long axis of the FMDs. This line pointed to the insertion of the tendon originally involved, a fact that was proved with MR imaging. Four characteristic stages were found to define a typical radiomorphologic course of an FMD

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

    Science.gov (United States)

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

    2010-10-01

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

  7. Hidrogéis de poliHEMA para reparo de defeitos da cartilagem articular: 1 - síntese e caracterização mecânica PolyHEMA hydrogels for repairs or articular cartilage defects: 1 – systhesis and mechanical characterization

    Directory of Open Access Journals (Sweden)

    Sonia M Malmonge

    1997-06-01

    Full Text Available Este trabalho visa a obtenção de hidrogéis de poli(2 hidróxi etil metacrilato - poliHEMA com propriedades mecânicas adequadas ao uso dos mesmos no reparo de defeitos da cartilagem articular. Para tanto, duas alternativas foram estudadas: a variação da densidade de reticulação e a obtenção de blendas do tipo redes semi interpenetrantes (sIPN de poliHEMA reticulado e diferentes polímeros como reforço. Amostras de hidrogéis foram obtidas por polimerização térmica e caracterizadas quanto à capacidade de absorção de água e de solução aquosa de NaCl 0,15 M e quanto ao comportamento mecânico, através de ensaios de fluência a indentação. Os resultados mostraram que a obtenção de blendas sIPN usando copolímero de MMA-AA como reforço é uma alternativa interessante para melhorar as propriedades mecânicas sem diminuir muito a capacidade de absorção de água dos hidrogéis.The purpose of this work was the study of poly-2-hydroxy-ethyl-metacrylate (polyHEMA as a biomaterial for the repair of articular cartilage defects. Improvement of mechanical properties were studied by two distincts routes: changes in cross-link density of the gels and the synthesis of cellulose acetate and poly-methyl metacrylate-acrylic acid copolymers semi interpenetrating blends. The hydrogels were synthesized by thermal polymerization and characterized by swelling behaviour in 0.15 Mol.L-1 NaCl and by creep indentation tests. The results showed that the blending of PolyHEMA with poly-methyl metacrylate-acrylic acid copolymers significantly improved the mechanical properties of hydrogels without changes in their swelling behavior.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Silvia Lopa

    2018-01-01

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

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

    Science.gov (United States)

    Mondadori, Carlotta; Mainardi, Valerio Luca; Talò, Giuseppe; Candrian, Christian; Święszkowski, Wojciech

    2018-01-01

    Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells. Here, we discuss the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics. In particular, we will focus on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D bioprinting applications, on the screening of biochemical and biophysical factors through microfluidic devices to enhance stem cell chondrogenesis, and on the use of microfluidic technology to generate implantable constructs with a complex geometry. Finally, we will describe some new bioprinting applications that pave the way to the clinical use of stem cell-based therapies, such as scaffold-free bioprinting and the development of a 3D handheld device for the in situ repair of cartilage defects. PMID:29535776

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Christopher Fellows

    2016-12-01

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

  14. Current status of imaging of articular cartilage

    International Nuclear Information System (INIS)

    Hodler, J.; Resnick, D.

    1996-01-01

    Various imaging methods have been applied to assessment of articular cartilage. These include standard radiography, arthrography, CT, CT arthrography, ultrasonography, and MR imaging. Radiography remains the initial musculoskeletal imaging method. However, it is insensitive to early stages of cartilage abnormalities. MR imaging has great potential in the assessment of articular cartilage, although high-quality scans are required because imaging signs of cartilage abnormalities may be subtle. The potential and limitations of various sequences and techniques are discussed, including MR arthrography. The role of the other imaging methods in assessment of articular cartilage appears to be limited. (orig.). With 8 figs., 6 tabs

  15. Live vaccinia-rabies virus recombinants, but not an inactivated rabies virus cell culture vaccine, protect B-lymphocyte-deficient A/WySnJ mice against rabies: considerations of recombinant defective poxviruses for rabies immunization of immunocompromised individuals.

    Science.gov (United States)

    Lodmell, Donald L; Esposito, Joseph J; Ewalt, Larry C

    2004-09-03

    Presently, commercially available cell culture rabies vaccines for humans and animals consist of the five inactivated rabies virus proteins. The vaccines elicit a CD4+ helper T-cell response and a humoral B-cell response against the viral glycoprotein (G) resulting in the production of virus neutralizing antibody. Antibody against the viral nucleoprotein (N) is also present, but the mechanism(s) of its protection is unclear. HIV-infected individuals with low CD4+ T-lymphocyte counts and individuals undergoing treatment with immunosuppressive drugs have an impaired neutralizing antibody response after pre- and post-exposure immunization with rabies cell culture vaccines. Here we show the efficacy of live vaccinia-rabies virus recombinants, but not a cell culture vaccine consisting of inactivated rabies virus, to elicit elevated levels of neutralizing antibody in B-lymphocyte deficient A/WySnJ mice. The cell culture vaccine also failed to protect the mice, whereas a single immunization of a vaccinia recombinant expressing the rabies virus G or co-expressing G and N equally protected the mice up to 18 months after vaccination. The data suggest that recombinant poxviruses expressing the rabies virus G, in particular replication defective poxviruses such as canarypox or MVA vaccinia virus that undergo abortive replication in non-avian cells, or the attenuated vaccinia virus NYVAC, should be evaluated as rabies vaccines in immunocompromised individuals.

  16. Radiological evaluation of cartilage after microfracture treatment: A long-term follow-up study

    International Nuclear Information System (INIS)

    Von Keudell, A.; Atzwanger, J.; Forstner, R.; Resch, H.; Hoffelner, T.; Mayer, M.

    2012-01-01

    Introduction: Recent literature revealed good short-term results after microfracturing (MFX) of isolated focal cartilage defects in the knee joint. Study purpose was a long-term evaluation of patients who received MFX through a multimodal approach, correlating clinical scores and morphological pre- and postoperative MRI-scans. Materials and methods: Between 2000 and 2007 158 patients were treated with MFX for focal femoral or tibial defects at our department. Patients with instabilities, secondary surgical intervention, patellofemoral lesions, a plica mediopatellaris or more than one cartilage defect site and age >55 were excluded. 15 patients were included. Minimum postoperative follow-up (FU) was 18 months (18–78 m). Mean age at surgery was 45 years (27–54), mean FU-interval 48 months (18–78 m). Male to female ratio was 9:6. For clinical assessment the Knee Osteoarthritis Outcome Score (KOOS) and Lysholm Score were used, radiological evaluation was performed with radiographs and 3Tesla-MRI. Results: Clinical knee function was rated good to excellent in 1 patient, fair in 2 and poor in 10 patients. 2/15 patients received full knee replacement due to insufficient cartilage repair through MFX during FU period. Evaluation of pre- and postoperative MRI showed good cartilage repair tissue in 1 (7.7%), moderate repair in 2 (15.4%) and poor fill in 10 patients (76.9%). In these 10 patients the defect size increased. Average defect size preoperatively was 187 mm 2 (range 12–800 mm 2 ) and postoperatively 294 mm 2 (40–800 mm 2 ). The KOOS-Pain averaged 60 (39–94), KOOS-Symptoms 60.6 (21–100), KOOS-ADL 69 (21–91), KOOS-Sports 35.7 (5–60) and KOOS-QUL 37.2 (6–81). The average Lysholm Score was 73.9 (58–94). 10 patients showed a varus leg axis deviation (Ø 5.9°), 3 had a neutral alignment. The alignment correlated positively with KOOS and especially with the Lysholm Score. Conclusion: Our study demonstrated that MFX as a treatment option for cartilage

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

    Science.gov (United States)

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

    2011-07-01

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

  18. Defect modelling

    International Nuclear Information System (INIS)

    Norgett, M.J.

    1980-01-01

    Calculations, drawing principally on developments at AERE Harwell, of the relaxation about lattice defects are reviewed with emphasis on the techniques required for such calculations. The principles of defect modelling are outlined and various programs developed for defect simulations are discussed. Particular calculations for metals, ionic crystals and oxides, are considered. (UK)

  19. Development of artificial articular cartilage

    Indian Academy of Sciences (India)

    Mechanical strength of Poly(vinyl alcohol), PVA is improved up to 35 MPa. Manufacturing method is adopted considering colloidal stability of nano silica particle in PVA sol at specific pH = 1. An adhesive is also prepared from PVA/Si nanocomposite containing 40% TEOS for firm attachment of artificial articular cartilage on ...

  20. Postnatal development of articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.

    2010-01-01

    Articular cartilage (AC) is the thin layer of tissue that covers the ends of the bones in the synovial joints in mammals. Functional adult AC has depth-dependent mechanical properties that are not yet present at birth. These depth-dependent mechanical properties in adult life are the result of a

  1. Strategies for Stratified Cartilage Bioprinting

    NARCIS (Netherlands)

    Schuurman, W.|info:eu-repo/dai/nl/313939322

    2012-01-01

    Multiple materials, cells and growth factors can be combined into one construct by the use of a state–of-the-art bioprinter. This technique may in the future make the fabrication of complete tissues or organs possible. In this thesis the feasibility of the bioprinting of cartilage and the

  2. Chondroma of the cricoid cartilage

    Directory of Open Access Journals (Sweden)

    Melo, Giulianno Molina de

    2008-12-01

    Full Text Available Introduction: The larynx cartilaginous tumors are uncommon and comprise 1% of all cartilaginous tumors. The chondroma is the most common benign tumor affecting the larynx cricoid cartilage (75%, and manifests normally in the male gender with dysphonia, progressive dyspnea and dysphagy in some cases. Objective: The objective of this study is to report a case of cricoid cartilage chondroma, in a patient with the symptom of a nodular lesion in the frontal cervical region of slow and progressive growth. Case Report: The treatment was the modified partial laryngectomy with resection of the lower hemisegment of the thyroid cartilage, cricoid hemicartilage and the first tracheal ring with free margins and reconstruction with a pericondrium and muscular prethyroidean piece. The anatomopathological exam showed a chondroma of 1.1 cm, of atypical low cellularity and low figures of mitosis in the frontal region of the cricoid cartilage. Conclusion: In this report we agreed with the literature for the primarily extensive surgical treatment depending on the location and the size of the cricoid chondroma; however, other modalities of treatment may be adopted in cases where the tumor extension appoints a total laryngectomy or when this is not possible to carry out, aiming at the preservation of the larynx. For the suitable treatment of cricoid chondromas, the understanding of the disease natural evolution and more case reports are still necessary.

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

    Directory of Open Access Journals (Sweden)

    Catherine A Bautista

    Full Text Available Articular cartilage has a limited capacity to heal itself and thus focal defects often result in the development of osteoarthritis. Current cartilage tissue engineering strategies seek to regenerate injured tissue by creating scaffolds that aim to mimic the unique structure and composition of native articular cartilage. Decellularization is a novel strategy that aims to preserve the bioactive factors and 3D biophysical environment of the native extracellular matrix while removing potentially immunogenic factors. The purpose of this study was to develop a procedure that can enable decellularization and recellularization of intact articular cartilage matrix. Full-thickness porcine articular cartilage plugs were decellularized with a series of freeze-thaw cycles and 0.1% (w/v sodium dodecyl sulfate detergent cycles. Chondroitinase ABC (ChABC was applied before the detergent cycles to digest glycosaminoglycans in order to enhance donor chondrocyte removal and seeded cell migration. Porcine synovium-derived mesenchymal stem cells were seeded onto the decellularized cartilage scaffolds and cultured for up to 28 days. The optimized decellularization protocol removed 94% of native DNA per sample wet weight, while collagen content and alignment were preserved. Glycosaminoglycan depletion prior to the detergent cycles increased removal of nuclear material. Seeded cells infiltrated up to 100 μm into the cartilage deep zone after 28 days in culture. ChABC treatment enhances decellularization of the relatively dense, impermeable articular cartilage by reducing glycosaminoglycan content. ChABC treatment did not appear to affect cell migration during recellularization under static, in vitro culture, highlighting the need for more dynamic seeding methods.

  4. On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis

    DEFF Research Database (Denmark)

    Holmborn, Katarina; Habicher, Judith; Kasza, Zsolt

    2012-01-01

    The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis of both HS and CS because of defective formation...... levels of CS than control larvae, whereas morpholino-mediated suppression of csgalnact1/csgalnact2 resulted in increased HS biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins influences the HS/CS ratio. A characterization of the pharyngeal cartilage element morphologies...

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

    Directory of Open Access Journals (Sweden)

    Cohn Zachary A

    2007-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Abdul-Rehman Phull

    2016-01-01

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

  7. Repair and tissue engineering techniques for articular cartilage.

    Science.gov (United States)

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

    2015-01-01

    Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

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

    Science.gov (United States)

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

    2012-08-24

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

  9. Light Absorptive Properties of Articular Cartilage, ECM Molecules, Synovial Fluid, and Photoinitiators as Potential Barriers to Light-Initiated Polymer Scaffolding Procedures.

    Science.gov (United States)

    Finch, Anthony J; Benson, Jamie M; Donnelly, Patrick E; Torzilli, Peter A

    2017-06-01

    Objective Many in vivo procedures to repair chondral defects use ultraviolet (UV)-photoinitiated in situ polymerization within the cartilage matrix. Chemical species that absorb UV light might reduce the effectiveness of these procedures by acting as light absorption barriers. This study evaluated whether any of the individual native biochemical components in cartilage and synovial fluid interfered with the absorption of light by common scaffolding photosensitizers. Materials UV-visible spectroscopy was performed on each major component of cartilage in solution, on bovine synovial fluid, and on four photosensitizers, riboflavin, Irgacure 2959, quinine, and riboflavin-5'-phosphate. Molar extinction and absorption coefficients were calculated at wavelengths of maximum absorbance and 365 nm. Intact articular cartilage was also examined. Results The individual major biochemical components of cartilage, Irgacure 2959, and quinine did not exhibit a significant absorption at 365 nm. Riboflavin and riboflavin-5'-phosphate were more effectual light absorbers at 365 nm, compared with the individual native species. Intact cartilage absorbed a significantly greater amount of UV light in comparison with the native species. Conclusion Our results indicate that none of the individual native species in cartilage will interfere with the absorption of UV light at 365 nm by these commonly used photoinitiators. Intact cartilage slices exhibited significant light absorption at 365 nm, while also having distinct absorbance peaks at wavelengths less than 300 nm. Determining the UV absorptive properties of the biomolecules native to articular cartilage and synovial fluid will aid in optimizing scaffolding procedures to ensure sufficient scaffold polymerization at a minimum UV intensity.

  10. A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue

    Science.gov (United States)

    Nyengaard, Jens Randel; Lind, Martin; Spector, Myron

    2015-01-01

    Objective To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin–eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. Results We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm3 (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. Conclusion We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage. PMID:26069715

  11. No Difference on Quantitative Magnetic Resonance Imaging in Patellofemoral Cartilage Composition Between Patients With Patellofemoral Pain and Healthy Controls.

    Science.gov (United States)

    van der Heijden, Rianne A; Oei, Edwin H G; Bron, Esther E; van Tiel, Jasper; van Veldhoven, Peter L J; Klein, Stefan; Verhaar, Jan A N; Krestin, Gabriel P; Bierma-Zeinstra, Sita M A; van Middelkoop, Marienke

    2016-05-01

    Retropatellar cartilage damage has been suggested as an etiological factor for patellofemoral pain (PFP), a common knee condition among young and physically active individuals. To date, there is no conclusive evidence for an association between cartilage defects and PFP. Nowadays, advanced quantitative magnetic resonance imaging (MRI) techniques enable estimation of cartilage composition. To investigate differences in patellofemoral cartilage composition between patients with PFP and healthy control subjects using quantitative MRI. Cross-sectional study; Level of evidence, 3. Patients with PFP and healthy control subjects underwent 3.0-T MRI including delayed gadolinium-enhanced MRI of cartilage and T1ρ and T2 mapping. Differences in relaxation times of patellofemoral cartilage were compared between groups by linear regression analyses, adjusted for age, body mass index, sex, sports participation, and time of image acquisition. This case-control study included 64 patients and 70 controls. The mean (±SD) age was 23.2 ± 6.4 years and the mean body mass index was 22.9 ± 3.4 kg/m(2); 56.7% were female. For delayed gadolinium-enhanced MRI of cartilage, the mean T1GD relaxation times of patellar (657.8 vs 669.4 ms) and femoral cartilage (661.6 vs 659.8 ms) did not significantly differ between patients and controls. In addition, no significant difference was found in mean T1ρ relaxation times of patellar (46.9 vs 46.0 ms) and femoral cartilage (50.8 vs 50.2 ms) and mean T2 relaxation times of patellar (33.2 vs 32.9 ms) and femoral cartilage (36.7 vs 36.6 ms) between patients and controls. Analysis of prespecified medial and lateral subregions within the patellofemoral cartilage also revealed no significant differences. There was no difference in composition of the patellofemoral cartilage, estimated with multiple quantitative MRI techniques, between patients with PFP and healthy control subjects. However, clinically relevant differences could not be ruled out for T1

  12. In Vivo Tibial Cartilage Strains in Regions of Cartilage-to-Cartilage Contact and Cartilage-to-Meniscus Contact in Response to Walking.

    Science.gov (United States)

    Liu, Betty; Lad, Nimit K; Collins, Amber T; Ganapathy, Pramodh K; Utturkar, Gangadhar M; McNulty, Amy L; Spritzer, Charles E; Moorman, Claude T; Sutter, E Grant; Garrett, William E; DeFrate, Louis E

    2017-10-01

    There are currently limited human in vivo data characterizing the role of the meniscus in load distribution within the tibiofemoral joint. Purpose/Hypothesis: The purpose was to compare the strains experienced in regions of articular cartilage covered by the meniscus to regions of cartilage not covered by the meniscus. It was hypothesized that in response to walking, tibial cartilage covered by the meniscus would experience lower strains than uncovered tibial cartilage. Descriptive laboratory study. Magnetic resonance imaging (MRI) of the knees of 8 healthy volunteers was performed before and after walking on a treadmill. Using MRI-generated 3-dimensional models of the tibia, cartilage, and menisci, cartilage thickness was measured in 4 different regions based on meniscal coverage and compartment: covered medial, uncovered medial, covered lateral, and uncovered lateral. Strain was defined as the normalized change in cartilage thickness before and after activity. Within each compartment, covered cartilage before activity was significantly thinner than uncovered cartilage before activity ( P meniscus experiences lower strains than uncovered cartilage in the medial compartment. These findings provide important baseline information on the relationship between in vivo tibial compressive strain responses and meniscal coverage, which is critical to understanding normal meniscal function.

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

    Science.gov (United States)

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

    2013-05-01

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

  14. Role of magnetic resonance imaging in the evaluation of articular cartilage in painful knee joint

    Directory of Open Access Journals (Sweden)

    Digish Shah

    2014-01-01

    Full Text Available Aim: The aim of this study was to determine the role of the magnetic resonance imaging (MRI in patients with atraumatic knee pain. Background and Objectives: Knee pain is one of the most common problems faced by people from time immemorial. There is a wide range of disease ranging from traumatic to degenerative causing knee pain in which articular cartilage is involved. Over the past 15 years, MRI has become the premier, first-line imaging study that should be performed in the evaluation of the painful knee in particular in tears of menisci, cruciate and collateral ligaments, osteochondral abnormalities (chondromalacia, osteoarthritis and osteochondral defects, synovial cysts and bone bruises. MRI, by virtue of its superior soft-tissue contrast, lack of ionizing radiation and multiplanar capabilities, is superior to more conventional techniques for the evaluation of articular cartilage. Materials and Methods: A prospective study was carried out on 150 patients in the Department of Radio-diagnosis, Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune over a period of 2 years from June 2011 to May 2013. Patients having fracture or dislocations of the knee joint were also excluded from the study. Detailed clinical history, physical and systemic examination findings of all patients were noted in addition to the laboratory investigations. All patients were subjected to radiograph of knee anterior-posterior and lateral view. MRI was performed with Siemens 1.5 Tesla MAGNETOM Avanto machine. Results: In our study of 150 patients with knee pain, articular cartilage defect was found in 90 patients (60%. Out of 90 patients with articular cartilage defect, 30 patients (20% had full thickness cartilage defects. Subchondral marrow edema was seen beneath 30 patients (20% with articular cartilage defects. 32 patients (21.1% had a complex or macerated meniscal tear. Complete anterior cruciate ligament tear was found in seven

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

    Science.gov (United States)

    Lv, Y M; Yu, Q S

    2015-04-01

    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. 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. 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. 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. ©2015 The British Editorial Society of Bone & Joint Surgery.

  16. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Formation of Hyaline Cartilage Tissue by Passaged Human Osteoarthritic Chondrocytes.

    Science.gov (United States)

    Bianchi, Vanessa J; Weber, Joanna F; Waldman, Stephen D; Backstein, David; Kandel, Rita A

    2017-02-01

    When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are to be used successfully. Transforming growth factor beta (TGFβ) family members are known to be crucial for regulating differentiation of fetal limb mesenchymal cells and mesenchymal stromal cells to chondrocytes. As passaged chondrocytes acquire a progenitor-like phenotype, the hypothesis of this study was that TGFβ supplementation will stimulate chondrocyte redifferentiation in vitro in serum-free three-dimensional (3D) culture. Human articular chondrocytes were serially passaged twice (P2) in monolayer culture. P2 cells were then placed in high-density (3D) culture on top of membranes (Millipore) and cultured for up to 6 weeks in chemically defined serum-free redifferentiation media (SFRM) in the presence or absence of TGFβ. The tissues were evaluated histologically, biochemically, by immunohistochemical staining, and biomechanically. Passaged human chondrocytes cultured in SFRM supplemented with 10 ng/mL TGFβ3 consistently formed a continuous layer of articular-like cartilage tissue rich in collagen type 2 and aggrecan and lacking collagen type 1 and X in the absence of a scaffold. The tissue developed a superficial zone characterized by expression of lubricin and clusterin with horizontally aligned collagen fibers. This study suggests that passaged human chondrocytes can be used to bioengineer a continuous layer of articular cartilage-like tissue in vitro scaffold free. Further study is required to evaluate their ability to repair cartilage defects in vivo.

  18. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Peter Succar

    2016-01-01

    Full Text Available Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC therapy are gaining acceptance for knee-osteoarthritis (OA treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL. At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.

  19. Effect of low-dose irradiation on structural and mechanical properties of hyaline cartilage-like fibrocartilage.

    Science.gov (United States)

    Öncan, Tevfik; Demirağ, Burak; Ermutlu, Cenk; Yalçinkaya, Ulviye; Özkan, Lütfü

    2013-01-01

    The aim of this study was to analyze the effect of low-dose irradiation on fibrous cartilage and to obtain a hyaline cartilage-like fibrocartilage (HCLF) with similar structural and mechanical properties to hyaline cartilage. An osteochondral defect was created in 40 knees of 20 rabbits. At the 7th postoperative day, a single knee of each rabbit was irradiated with a total dose of 5.0 Gy in 1.0 Gy fractions for 5 days (radiotherapy group), while the other knee was not irradiated (control group). Rabbits were then divided into four groups of 5 rabbits each. The first three groups were sacrificed at the 4th, 8th and the 12th postoperative weeks and cartilage defects were macroscopically and microscopically evaluated. The remaining group of 5 rabbits was sacrificed at the 12th week and biomechanical compression tests were performed on the cartilage defects. There was no significant biomechanical difference between the radiotherapy and the control group (p=0.686). There was no significant macroscopic and microscopic difference between groups (p=0.300). Chondrocyte clustering was observed in the irradiated group. Low-dose irradiation does not affect the mechanical properties of HCLF in vivo. However, structural changes such as chondrocyte clustering were observed.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

    Gaut, Carrie; Sugaya, Kiminobu

    2015-01-01

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

  2. Diode laser (980nm) cartilage reshaping

    Science.gov (United States)

    El Kharbotly, A.; El Tayeb, T.; Mostafa, Y.; Hesham, I.

    2011-03-01

    Loss of facial or ear cartilage due to trauma or surgery is a major challenge to the otolaryngologists and plastic surgeons as the complicated geometric contours are difficult to be animated. Diode laser (980 nm) has been proven effective in reshaping and maintaining the new geometric shape achieved by laser. This study focused on determining the optimum laser parameters needed for cartilage reshaping with a controlled water cooling system. Harvested animal cartilages were angulated with different degrees and irradiated with different diode laser powers (980nm, 4x8mm spot size). The cartilage specimens were maintained in a deformation angle for two hours after irradiation then released for another two hours. They were serially measured and photographed. High-power Diode laser irradiation with water cooling is a cheep and effective method for reshaping the cartilage needed for reconstruction of difficult situations in otorhinolaryngologic surgery. Key words: cartilage,diode laser (980nm), reshaping.

  3. Human osteoarthritic cartilage is synthetically more active but in culture less vital than normal cartilage

    NARCIS (Netherlands)

    Lafeber, F. P.; van Roy, H.; Wilbrink, B.; Huber-Bruning, O.; Bijlsma, J. W.

    1992-01-01

    The proteoglycan turnover of human osteoarthritic (OA) cartilage was compared to that of normal (N) cartilage. The cartilage was obtained postmortem from human femoral knee condyles. Short term cultures were compared to longterm cultures, and proteoglycan synthesis rate, content and release

  4. Rho GTPase protein Cdc42 is critical for postnatal cartilage development

    International Nuclear Information System (INIS)

    Nagahama, Ryo; Yamada, Atsushi; Tanaka, Junichi; Aizawa, Ryo; Suzuki, Dai; Kassai, Hidetoshi; Yamamoto, Matsuo; Mishima, Kenji; Aiba, Atsu; Maki, Koutaro; Kamijo, Ryutaro

    2016-01-01

    Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 "f"l"/"f"l; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 "f"l"/"f"l) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.

  5. Rho GTPase protein Cdc42 is critical for postnatal cartilage development

    Energy Technology Data Exchange (ETDEWEB)

    Nagahama, Ryo [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Department of Orthodontics, School of Dentistry, Showa University, Tokyo (Japan); Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Tanaka, Junichi [Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo (Japan); Aizawa, Ryo [Department of Periodontology, School of Dentistry, Showa University, Tokyo (Japan); Suzuki, Dai [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Kassai, Hidetoshi [Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo (Japan); Yamamoto, Matsuo [Department of Periodontology, School of Dentistry, Showa University, Tokyo (Japan); Mishima, Kenji [Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo (Japan); Aiba, Atsu [Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo (Japan); Maki, Koutaro [Department of Orthodontics, School of Dentistry, Showa University, Tokyo (Japan); Kamijo, Ryutaro [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan)

    2016-02-19

    Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 {sup fl/fl}; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 {sup fl/fl}) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.

  6. Cellular and Acellular Approaches for Cartilage Repair

    Science.gov (United States)

    2015-01-01

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

  7. Optical properties of nasal septum cartilage

    Science.gov (United States)

    Bagratashvili, Nodar V.; Sviridov, Alexander P.; Sobol, Emil N.; Kitai, Moishe S.

    1998-05-01

    Optical parameters (scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g) of hyaline cartilage were studied for the first time. Optical properties of human and pig nasal septum cartilage, and of bovine ear cartilage were examined using a spectrophotometer with an integrating sphere, and an Optical Multi-Channel Analyser. We measured total transmission Tt, total reflection Rt, and on-axis transmission Ta for light propagating through cartilage sample, over the visible spectral range (14000 - 28000 cm-1). It is shown that transmission and reflection spectra of human, pig and bovine cartilage are rather similar. It allows us to conclude that the pig cartilage can be used for in-vivo studies instead of human cartilage. The data obtained were treated by means of the one-dimensional diffusion approximation solution of the optical transport equation. We have found scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g by the iterative comparison of measured and calculated Tt, Rt and Ta values for human and pig cartilage. We found, in particular, that for 500 nm irradiation s equals 37,6 plus or minus 3.5 cm-1, g equals 0,56 plus or minus 0.05, k approximately equals 0,5 plus or minus 0.3 cm-1. The above data were used in Monte Carlo simulation for spatial intensity profile of light scattered by a cartilage sample. The computed profile was very similar to the profile measured using an Optical Multi-Channel Analyzer (OMA).

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Michiel W. Pot

    2016-09-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

    Confronted with articular cartilage's limited capacity for self-repair, joint resurfacing techniques offer an attractive treatment for damaged or diseased tissue. Although tissue engineered cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for the repair of large defects. As routine cell expansion methods tend to elicit negative effects on chondrocyte function, we have developed an approach to generate phenotypically stable, large-sized engineered constructs (≥3 cm(2) ) directly from a small amount of donor tissue or cells (as little as 20,000 cells to generate a 3 cm(2) tissue construct). Using rabbit donor tissue, the bioreactor-cultivated constructs were hyaline-like in appearance and possessed a biochemical composition similar to native articular cartilage. Longer bioreactor cultivation times resulted in increased matrix deposition and improved mechanical properties determined over a 4 week period. Additionally, as the anatomy of the joint will need to be taken in account to effectively resurface large affected areas, we have also explored the possibility of generating constructs matched to the shape and surface geometry of a defect site through the use of rapid-prototyped defect tissue culture molds. Similar hyaline-like tissue constructs were developed that also possessed a high degree of shape correlation to the original defect mold. Future studies will be aimed at determining the effectiveness of this approach to the repair of cartilage defects in an animal model and the creation of large-sized osteochondral constructs. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

  12. Deletion of IFT80 Impairs Epiphyseal and Articular Cartilage Formation Due to Disruption of Chondrocyte Differentiation

    Science.gov (United States)

    Yuan, Xue; Yang, Shuying

    2015-01-01

    Intraflagellar transport proteins (IFT) play important roles in cilia formation and organ development. Partial loss of IFT80 function leads Jeune asphyxiating thoracic dystrophy (JATD) or short-rib polydactyly (SRP) syndrome type III, displaying narrow thoracic cavity and multiple cartilage anomalies. However, it is unknown how IFT80 regulates cartilage formation. To define the role and mechanism of IFT80 in chondrocyte function and cartilage formation, we generated a Col2α1; IFT80f/f mouse model by crossing IFT80f/f mice with inducible Col2α1-CreER mice, and deleted IFT80 in chondrocyte lineage by injection of tamoxifen into the mice in embryonic or postnatal stage. Loss of IFT80 in the embryonic stage resulted in short limbs at birth. Histological studies showed that IFT80-deficient mice have shortened cartilage with marked changes in cellular morphology and organization in the resting, proliferative, pre-hypertrophic, and hypertrophic zones. Moreover, deletion of IFT80 in the postnatal stage led to mouse stunted growth with shortened growth plate but thickened articular cartilage. Defects of ciliogenesis were found in the cartilage of IFT80-deficient mice and primary IFT80-deficient chondrocytes. Further study showed that chondrogenic differentiation was significantly inhibited in IFT80-deficient mice due to reduced hedgehog (Hh) signaling and increased Wnt signaling activities. These findings demonstrate that loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation. PMID:26098911

  13. Transcriptional profiling differences for articular cartilage and repair tissue in equine joint surface lesions

    Directory of Open Access Journals (Sweden)

    Stromberg Arnold J

    2009-09-01

    Full Text Available Abstract Background Full-thickness articular cartilage lesions that reach to the subchondral bone yet are restricted to the chondral compartment usually fill with a fibrocartilage-like repair tissue which is structurally and biomechanically compromised relative to normal articular cartilage. The objective of this study was to evaluate transcriptional differences between chondrocytes of normal articular cartilage and repair tissue cells four months post-microfracture. Methods Bilateral one-cm2 full-thickness defects were made in the articular surface of both distal femurs of four adult horses followed by subchondral microfracture. Four months postoperatively, repair tissue from the lesion site and grossly normal articular cartilage from within the same femorotibial joint were collected. Total RNA was isolated from the tissue samples, linearly amplified, and applied to a 9,413-probe set equine-specific cDNA microarray. Eight paired comparisons matched by limb and horse were made with a dye-swap experimental design with validation by histological analyses and quantitative real-time polymerase chain reaction (RT-qPCR. Results Statistical analyses revealed 3,327 (35.3% differentially expressed probe sets. Expression of biomarkers typically associated with normal articular cartilage and fibrocartilage repair tissue corroborate earlier studies. Other changes in gene expression previously unassociated with cartilage repair were also revealed and validated by RT-qPCR. Conclusion The magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of gene transcripts which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to

  14. Cell Seeding Densities in Autologous Chondrocyte Implantation Techniques for Cartilage Repair.

    Science.gov (United States)

    Foldager, Casper Bindzus; Gomoll, Andreas H; Lind, Martin; Spector, Myron

    2012-04-01

    Cartilage repair techniques have been among the most intensively investigated treatments in orthopedics for the past decade, and several different treatment modalities are currently available. Despite the extensive research effort within this field, the generation of hyaline cartilage remains a considerable challenge. There are many parameters attendant to each of the cartilage repair techniques that can affect the amount and types of reparative tissue generated in the cartilage defect, and some of the most fundamental of these parameters have yet to be fully investigated. For procedures in which in vitro-cultured autologous chondrocytes are implanted under a periosteal or synthetic membrane cover, or seeded onto a porous membrane or scaffold, little is known about how the number of cells affects the clinical outcome. Few published clinical studies address the cell seeding density that was employed. The principal objective of this review is to provide an overview of the cell seeding densities used in cell-based treatments currently available in the clinic for cartilage repair. Select preclinical studies that have informed the use of specific cell seeding densities in the clinic are also discussed.

  15. An integrin-dependent role of pouch endoderm in hyoid cartilage development.

    Directory of Open Access Journals (Sweden)

    Justin Gage Crump

    2004-09-01

    Full Text Available Pharyngeal endoderm is essential for and can reprogram development of the head skeleton. Here we investigate the roles of specific endodermal structures in regulating craniofacial development. We have isolated an integrinalpha5 mutant in zebrafish that has region-specific losses of facial cartilages derived from hyoid neural crest cells. In addition, the cranial muscles that normally attach to the affected cartilage region and their associated nerve are secondarily reduced in integrinalpha5- animals. Earlier in development, integrinalpha5 mutants also have specific defects in the formation of the first pouch, an outpocketing of the pharyngeal endoderm. By fate mapping, we show that the cartilage regions that are lost in integrinalpha5 mutants develop from neural crest cells directly adjacent to the first pouch in wild-type animals. Furthermore, we demonstrate that Integrinalpha5 functions in the endoderm to control pouch formation and cartilage development. Time-lapse recordings suggest that the first pouch promotes region-specific cartilage development by regulating the local compaction and survival of skeletogenic neural crest cells. Thus, our results reveal a hierarchy of tissue interactions, at the top of which is the first endodermal pouch, which locally coordinates the development of multiple tissues in a specific region of the vertebrate face. Lastly, we discuss the implications of a mosaic assembly of the facial skeleton for the evolution of ray-finned fish.

  16. Evaluation of native hyaline cartilage and repair tissue after two cartilage repair surgery techniques with 23Na MR imaging at 7 T: initial experience.

    Science.gov (United States)

    Zbýň, S; Stelzeneder, D; Welsch, G H; Negrin, L L; Juras, V; Mayerhoefer, M E; Szomolanyi, P; Bogner, W; Domayer, S E; Weber, M; Trattnig, S

    2012-08-01

    To compare the sodium normalized mean signal intensity (NMSI) values between patients after bone marrow stimulation (BMS) and matrix-associated autologous chondrocyte transplantation (MACT) cartilage repair procedures. Nine BMS and nine MACT patients were included. Each BMS patient was matched with one MACT patient according to age [BMS 36.7 ± 10.7 (mean ± standard deviation) years; MACT 36.9 ± 10.0 years], postoperative interval (BMS 33.5 ± 25.3 months; MACT 33.2 ± 25.7 months), and defect location. All magnetic resonance imaging (MRI) measurements were performed on a 7 T system. Proton images served for morphological evaluation of repair tissue using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system. Sodium NMSI values in the repair area and morphologically normal cartilage were calculated. Clinical outcome was assessed right after MRI. Analysis of covariance, t-tests, and Pearson correlation coefficients were evaluated. Sodium NMSI was significantly lower in BMS (P = 0.004) and MACT (P = 0.006) repair tissue, compared to reference cartilage. Sodium NMSI was not different between the reference cartilage in MACT and BMS patients (P = 0.664), however it was significantly higher in MACT than in BMS repair tissue (P = 0.028). Better clinical outcome was observed in BMS than in MACT patients. There was no difference between MOCART scores for MACT and BMS patients (P = 0.915). We did not observe any significant correlation between MOCART score and sodium repair tissue NMSI (r = -0.001; P = 0.996). Our results suggest higher glycosaminoglycan (GAG) content, and therefore, repair tissue of better quality in MACT than in BMS patients. Sodium imaging might be beneficial in non-invasive evaluation of cartilage repair surgery efficacy. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  17. Bioreactors for Tissue Engineering of Cartilage

    Science.gov (United States)

    Concaro, S.; Gustavson, F.; Gatenholm, P.

    The cartilage regenerative medicine field has evolved during the last decades. The first-generation technology, autologous chondrocyte transplantation (ACT) involved the transplantation of in vitro expanded chondrocytes to cartilage defects. The second generation involves the seeding of chondrocytes in a three-dimensional scaffold. The technique has several potential advantages such as the ability of arthroscopic implantation, in vitro pre-differentiation of cells and implant stability among others (Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L, N Engl J Med 331(14):889-895, 1994; Henderson I, Francisco R, Oakes B, Cameron J, Knee 12(3):209-216, 2005; Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A, Clin Orthop (374):212-234, 2000; Nagel-Heyer S, Goepfert C, Feyerabend F, Petersen JP, Adamietz P, Meenen NM, et al. Bioprocess Biosyst Eng 27(4):273-280, 2005; Portner R, Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM, J Biosci Bioeng 100(3):235-245, 2005; Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM, Portner R, J Biotechnol 121(4):486-497, 2006; Heyland J, Wiegandt K, Goepfert C, Nagel-Heyer S, Ilinich E, Schumacher U, et al. Biotechnol Lett 28(20):1641-1648, 2006). The nutritional requirements of cells that are synthesizing extra-cellular matrix increase along the differentiation process. The mass transfer must be increased according to the tissue properties. Bioreactors represent an attractive tool to accelerate the biochemical and mechanical properties of the engineered tissues providing adequate mass transfer and physical stimuli. Different reactor systems have been [5] developed during the last decades based on different physical stimulation concepts. Static and dynamic compression, confined and nonconfined compression-based reactors have been described in this review. Perfusion systems represent an attractive way of culturing constructs under dynamic conditions. Several groups showed increased matrix

  18. Predicting knee cartilage loss using adaptive partitioning of cartilage thickness maps

    DEFF Research Database (Denmark)

    Jørgensen, Dan Richter; Dam, Erik Bjørnager; Lillholm, Martin

    2013-01-01

    This study investigates whether measures of knee cartilage thickness can predict future loss of knee cartilage. A slow and a rapid progressor group was determined using longitudinal data, and anatomically aligned cartilage thickness maps were extracted from MRI at baseline. A novel machine learning...... framework was then trained using these maps. Compared to measures of mean cartilage plate thickness, group separation was increased by focusing on local cartilage differences. This result is central for clinical trials where inclusion of rapid progressors may help reduce the period needed to study effects...

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

    Science.gov (United States)

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

    2017-10-01

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

  20. Ectopic bone formation during tissue-engineered cartilage repair using autologous chondrocytes and novel plasma-derived albumin scaffolds.

    Science.gov (United States)

    Robla Costales, David; Junquera, Luis; García Pérez, Eva; Gómez Llames, Sara; Álvarez-Viejo, María; Meana-Infiesta, Álvaro

    2016-10-01

    The aims of this study were twofold: first, to evaluate the production of cartilaginous tissue in vitro and in vivo using a novel plasma-derived scaffold, and second, to test the repair of experimental defects made on ears of New Zealand rabbits (NZr) using this approach. Scaffolds were seeded with chondrocytes and cultured in vitro for 3 months to check in vitro cartilage production. To evaluate in vivo cartilage production, a chondrocyte-seeded scaffold was transplanted subcutaneously to a nude mouse. To check in vivo repair, experimental defects made in the ears of five New Zealand rabbits (NZr) were filled with chondrocyte-seeded scaffolds. In vitro culture produced mature chondrocytes with no extracellular matrix (ECM). Histological examination of redifferentiated in vitro cultures showed differentiated chondrocytes adhered to scaffold pores. Subcutaneous transplantation of these constructs to a nude mouse produced cartilage, confirmed by histological study. Experimental cartilage repair in five NZr showed cartilaginous tissue repairing the defects, mixed with calcified areas of bone formation. It is possible to produce cartilaginous tissue in vivo and to repair experimental auricular defects by means of chondrocyte cultures and the novel plasma-derived scaffold. Further studies are needed to determine the significance of bone formation in the samples. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  1. Magnetic Resonance Imaging of Cartilage Repair

    Science.gov (United States)

    Trattnig, Siegfried; Winalski, Carl S.; Marlovits, Stephan; Jurvelin, Jukka S.; Welsch, Goetz H.; Potter, Hollis G.

    2011-01-01

    Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565

  2. Autologous chondrocyte implantation for cartilage injury treatment in Chiang Mai University Hospital: a case report.

    Science.gov (United States)

    Wongtriratanachai, Prasit; Pruksakorn, Dumnoensun; Pothacharoen, Peraphan; Nimkingratana, Puwapong; Pattamapaspong, Nuttaya; Phornphutkul, Chanakarn; Setsitthakun, Sasiwariya; Fongsatitkul, Ladda; Phrompaet, Sureeporn

    2013-11-01

    Autologous chondrocyte implantation (ACI) has become one of the standard procedures for articular cartilage defect treatment. This technique provides a promising result. However the procedural process requires an approach of several steps from multidisciplinary teams. Although the success of this procedure has been reported from Srinakharinvirot University since 2007, the application of ACI is still limited in Thailand due to the complexity of processes and stringent quality control. This report is to present the first case of the cartilage defect treatment using the first generation-ACI under Chiang Mai University's (CMU) own facility and Ethics Committee. This paper also reviews the process of biotechnology procedures, patient selection, surgical, and rehabilitation techniques. The success of the first case is an important milestone for the further development of the CMU Human Translational Research Laboratory in near future.

  3. Photoactivated methods for enabling cartilage-to-cartilage tissue fixation

    Science.gov (United States)

    Sitterle, Valerie B.; Roberts, David W.

    2003-06-01

    The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.

  4. Biological aspects of tissue-engineered cartilage.

    Science.gov (United States)

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

    2018-04-01

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

  5. Electric Field Stimulation Enhances Healing of Post-Traumatic Osteoarthritic Cartilage

    Science.gov (United States)

    2016-10-01

    those presentations, we will revise our two manuscripts describing our results. We are excited - and ready – to perform the in vivo experiments...injury or condition, or to improve the quality of life. Examples include:  data or databases;  physical collections;  audio or video products... visualize cell accumulation at the cartilage surface and defect site. Chamber Characterization and Validation: Electrical properties of the specimens

  6. Defects and defect processes in nonmetallic solids

    CERN Document Server

    Hayes, W

    2004-01-01

    This extensive survey covers defects in nonmetals, emphasizing point defects and point-defect processes. It encompasses electronic, vibrational, and optical properties of defective solids, plus dislocations and grain boundaries. 1985 edition.

  7. Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application.

    Science.gov (United States)

    Wang, L; Lazebnik, M; Detamore, M S

    2009-03-01

    To compare temporomandibular joint (TMJ) condylar cartilage cells in vitro to hyaline cartilage cells cultured in a three-dimensional (3D) environment for tissue engineering of mandibular condylar cartilage. Mandibular condylar cartilage and hyaline cartilage cells were harvested from pigs and cultured for 6 weeks in polyglycolic acid (PGA) scaffolds. Both types of cells were treated with glucosamine sulfate (0.4 mM), insulin-like growth factor-I (IGF-I) (100 ng/ml) and their combination. At weeks 0 and 6, cell number, glycosaminoglycan (GAG) and collagen content were determined, types I and II collagen were visualized by immunohistochemistry and GAGs were visualized by histology. Hyaline cartilage cells produced from half an order to a full order of magnitude more GAGs and collagen than mandibular condylar cartilage cells in 3D culture. IGF-I was a highly effective signal for biosynthesis with hyaline cartilage cells, while glucosamine sulfate decreased cell proliferation and biosynthesis with both types of cells. In vitro culture of TMJ condylar cartilage cells produced a fibrous tissue with predominantly type I collagen, while hyaline cartilage cells formed a fibrocartilage-like tissue with types I and II collagen. The combination of IGF and glucosamine had a synergistic effect on maintaining the phenotype of TMJ condylar cells to generate both types I and II collagen. Given the superior biosynthetic activity by hyaline cartilage cells and the practical surgical limitations of harvesting cells from the TMJ of a patient requiring TMJ reconstruction, cartilage cells from elsewhere in the body may be a potentially better alternative to cells harvested from the TMJ for TMJ tissue engineering. This finding may also apply to other fibrocartilages such as the intervertebral disc and knee meniscus in applications where a mature cartilage cell source is desired.

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

    Science.gov (United States)

    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. Imaging diagnosis of the articular cartilage disorders

    International Nuclear Information System (INIS)

    Liu Sirun; Zhu Tianyuan; Huang Li; Leng Xiaoming

    2003-01-01

    Objective: To evaluate the diagnosis and differential diagnosis among the chronic osteoarthritis, rheumatoid arthritis and other chronic cartilage lesions on the plain films and MR images. Methods: Eighty-nine cases, including 115 joints, underwent plain film and MRI examination, and enhanced MRI scan was performed on 32 of them, including 44 joints. MRI scan sequences consisted of T 1 WI, T 2 WI + PDWI, STIR, and 3D FS SPGR. There were 90 knee joints in this group and each of the articular cartilage was divided into four parts: patella, femoral medial condyle, femoral lateral condyle, and tibia facet on MR images. The cartilage disorders were classified according to the outerbridge method. In addition, 61 cases including 75 joints were observed as a control group on the plain films and MR images. Results: 115 cartilage lesions were found on MR images, in which thinness of the cartilage (58 cases, 50.4%), bone changes under the cartilage (22 cases, 19.7%), medullar edema (22 cases, 19.7%), and synovial hyperplasia (52 cases, 45.2%) were seen. The patella cartilage was the most likely affected part (81/90, 90%). So the patellar cartilage lesions were divided as group 1 (grade I-II) and group 2 (grade III-IV) on MR images, which were compared with the plain film signs. The narrowing of the joint space and saccules under the articular surface were statistically significant with each other, and χ 2 values were 9.349 and 9.885, respectively (P=0.002). Conclusion: No constant signs could be seen on the plain films with grade I-II cartilage disorders. While the narrowing joint space and saccules under the joint surface could be seen on them with grade III-IV cartilage disorders, which were mainly correlated with the cartilage disorders and bone changes under the articular cartilages. A combination of the plain films and MR images is the best imaging method for examining the joints and joint cartilages. Enhanced MRI scan is very helpful on the diagnosis and differential

  10. High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue.

    Science.gov (United States)

    Babur, Betul Kul; Futrega, Kathryn; Lott, William B; Klein, Travis Jacob; Cooper-White, Justin; Doran, Michael Robert

    2015-09-01

    Engineered biphasic osteochondral tissues may have utility in cartilage defect repair. As bone-marrow-derived mesenchymal stem/stromal cells (MSC) have the capacity to make both bone-like and cartilage-like tissues, they are an ideal cell population for use in the manufacture of osteochondral tissues. Effective differentiation of MSC to bone-like and cartilage-like tissues requires two unique medium formulations and this presents a challenge both in achieving initial MSC differentiation and in maintaining tissue stability when the unified osteochondral tissue is subsequently cultured in a single medium formulation. In this proof-of-principle study, we used an in-house fabricated microwell platform to manufacture thousands of micropellets formed from 166 MSC each. We then characterized the development of bone-like and cartilage-like tissue formation in the micropellets maintained for 8-14 days in sequential combinations of osteogenic or chondrogenic induction medium. When bone-like or cartilage-like micropellets were induced for only 8 days, they displayed significant phenotypic changes when the osteogenic or chondrogenic induction medium, respectively, was swapped. Based on these data, we developed an extended 14-day protocol for the pre-culture of bone-like and cartilage-like micropellets in their respective induction medium. Unified osteochondral tissues were formed by layering 12,000 osteogenic micropellets and 12,000 chondrogenic micropellets into a biphasic structure and then further culture in chondrogenic induction medium. The assembled tissue was cultured for a further 8 days and characterized via histology. The micropellets had amalgamated into a continuous structure with distinctive bone-like and cartilage-like regions. This proof-of-concept study demonstrates the feasibility of micropellet assembly for the formation of osteochondral-like tissues for possible use in osteochondral defect repair.

  11. [Histologic assessment of tissue healing of hyaline cartilage by use of semiquantitative evaluation scale].

    Science.gov (United States)

    Vukasović, Andreja; Ivković, Alan; Jezek, Davor; Cerovecki, Ivan; Vnuk, Drazen; Kreszinger, Mario; Hudetz, Damir; Pećina, Marko

    2011-01-01

    Articular cartilage is an avascular and aneural tissue lacking lymph drainage, hence its inability of spontaneous repair following injury. Thus, it offers an interesting model for scientific research. A number of methods have been suggested to enhance cartilage repair, but none has yet produced significant success. The possible application of the aforementioned methods has brought about the necessity to evaluate their results. The objective of this study was to analyze results of a study of the effects of the use of TGF-beta gene transduced bone marrow clot on articular cartilage defects using ICRS visual histological assessment scale. The research was conducted on 28 skeletally mature sheep that were randomly assigned to four groups and surgically inflicted femoral chondral defects. The articular surfaces were then treated with TGF-beta1 gene transduced bone marrow clot (TGF group), GFP transduced bone marrow clot (GFP group), untransduced bone marrow clot (BM group) or left untreated (NC group). The analysis was performed by visual examination of cartilage samples and results were obtained using ICRS visual histological assessment scale. The results were subsequently subjected to statistical assessment using Kruskal-Wallis and Mann-Whitney tests. Kruskal-Wallis test yielded statistically significant difference with respect to cell distribution. Mann-Whitney test showed statistically significant difference between TGF and NC groups (P = 0.002), as well as between BM and NC groups (P = 0.002 with Bonferroni correction). Twenty-six of the twenty-eight samples were subjected to histologic and subsequent statistical analysis; two were discarded due to faulty histology technique. Our results indicated a level of certainty as to the positive effect of TGF-beta1 gene transduced bone marrow clot in restoration of articular cartilage defects. However, additional research is necessary in the field. One of the significant drawbacks on histologic assessment of cartilage

  12. Congenital tracheal defects: embryonic development and animal models

    Directory of Open Access Journals (Sweden)

    Zenab Arooj Sher

    2016-03-01

    Full Text Available Tracheal anomalies are potentially catastrophic congenital defects. As a newborn begins to breathe, the trachea needs to maintain an appropriate balance of elasticity and rigidity. If the tracheal cartilages are disorganized or structurally weak, the airways can collapse, obstructing breathing. Cartilage rings that are too small or too rigid can also obstruct breathing. These anomalies are frequently associated with craniofacial syndromes, and, despite the importance, are poorly understood. In this review, we summarize the spectrum of pathological phenotypes of the trachea and correlate them with the molecular events uncovered in mouse models.

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

    Science.gov (United States)

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

    2006-11-01

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

  14. Mesenchymal stem cells in cartilage regeneration.

    Science.gov (United States)

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

    2014-01-01

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

  15. Regulatory Challenges for Cartilage Repair Technologies.

    Science.gov (United States)

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

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

  16. Clinical Features and Management of Cartilage-Hair Hypoplasia: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Kobra Shiasi Arani

    2015-01-01

    Full Text Available Context: Cartilage-hair hypoplasia is a rare hereditary cause of short stature. The aim of this study was to familiarize physicians with this rare but important disease. Evidence Acquisition: This article is a narrative review of the scientific literature to inform about clinical features and management of Cartilage-hair hypoplasia. A systematic search identified 127 papers include original and review articles and case reports. Results: Cartilage-Hair Hypoplasia characterized by short-limb dwarfism associated with metaphyseal chondrodysplasia. The inheritance is autosomal recessive. Other findings include hair hypoplasia, anemia, immunodeficiency, propensity to infections, gastrointestinal disorders (Hirschsprung disease, anal stenosis, esophageal atresia and malabsorption, defective spermatogenesis, increased risk of malignancies and higher rate of mortality. Immunodeficiency in cartilage-hair hypoplasia may be an isolated B-cell or isolated T-cell immunodeficiency or combined B and T-cell immunodeficiency; however, severe combined immunodeficiency is rare. There is no known treatment for hair hypoplasia. Growth hormone was used with conflicting results for short stature in children with Cartilage-hair hypoplasia. Skeletal problems must be managed with physiotherapy and appropriate orthopedic interventions. Hirschsprung disease, anal stenosis and esophageal atresia should be surgically corrected. Patients with severe hypoplastic anemia require repeated transfusions. Bone marrow transplantation may be required for patients with severe combined immunodeficiency or severe persistent hypoplastic anemia. Treatment with G-CSF is useful for neutropenia. Patients should be monitored closely for developing malignancy such as skin neoplasms, lymphomas and leukemias. Conclusions: Cartilage-hair hypoplasia is an important hereditary disease with different medical aspects. The high rate of consanguineous marriages in Iran necessitates considering CHH in any

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

    Science.gov (United States)

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

    2009-02-01

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

  18. Diverse roles of integrin receptors in articular cartilage.

    Science.gov (United States)

    Shakibaei, M; Csaki, C; Mobasheri, A

    2008-01-01

    Integrins are heterodimeric integral membrane proteins made up of alpha and beta subunits. At least eighteen alpha and eight beta subunit genes have been described in mammals. Integrin family members are plasma membrane receptors involved in cell adhesion and active as intra- and extracellular signalling molecules in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic spread of tumour cells. Integrin beta 1 (beta1-integrin), the protein encoded by the ITGB1 gene (also known as CD29 and VLAB), is a multi-functional protein involved in cell-matrix adhesion, cell signalling, cellular defense, cell adhesion, protein binding, protein heterodimerisation and receptor-mediated activity. It is highly expressed in the human body (17.4 times higher than the average gene in the last updated revision of the human genome). The extracellular matrix (ECM) of articular cartilage is a unique environment. Interactions between chondrocytes and the ECM regulate many biological processes important to homeostasis and repair of articular cartilage, including cell attachment, growth, differentiation and survival. The beta1-integrin family of cell surface receptors appears to play a major role in mediating cell-matrix interactions that are important in regulating these fundamental processes. Chondrocyte mechanoreceptors have been proposed to incorporate beta1-integrins and mechanosensitive ion channels which link with key ECM, cytoskeletal and signalling proteins to maintain the chondrocyte phenotype, prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression. This review focuses on the expression and function of beta1-integrins in articular chondrocytes, its role in the unique biology of these cells and its distribution in cartilage.

  19. Integration of Stem Cell to Chondrocyte-Derived Cartilage Matrix in Healthy and Osteoarthritic States in the Presence of Hydroxyapatite Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Rupak Dua

    Full Text Available We investigated the effectiveness of integrating tissue engineered cartilage derived from human bone marrow derived stem cells (HBMSCs to healthy as well as osteoarthritic cartilage mimics using hydroxyapatite (HA nanoparticles immersed within a hydrogel substrate. Healthy and diseased engineered cartilage from human chondrocytes (cultured in agar gels were integrated with human bone marrow stem cell (HBMSC-derived cartilaginous engineered matrix with and without HA, and evaluated after 28 days of growth. HBMSCs were seeded within photopolymerizable poly (ethylene glycol diacrylate (PEGDA hydrogels. In addition, we also conducted a preliminary in vivo evaluation of cartilage repair in rabbit knee chondral defects treated with subchondral bone microfracture and cell-free PEGDA with and without HA. Under in vitro conditions, the interfacial shear strength between tissue engineered cartilage derived from HBMSCs and osteoarthritic chondrocytes was significantly higher (p < 0.05 when HA nanoparticles were incorporated within the HBMSC culture system. Histological evidence confirmed a distinct spatial transition zone, rich in calcium phosphate deposits. Assessment of explanted rabbit knees by histology demonstrated that cellularity within the repair tissues that had filled the defects were of significantly higher number (p < 0.05 when HA was used. HA nanoparticles play an important role in treating chondral defects when osteoarthritis is a co-morbidity. We speculate that the calcified layer formation at the interface in the osteoarthritic environment in the presence of HA is likely to have attributed to higher interfacial strength found in vitro. From an in vivo standpoint, the presence of HA promoted cellularity in the tissues that subsequently filled the chondral defects. This higher presence of cells can be considered important in the context of accelerating long-term cartilage remodeling. We conclude that HA nanoparticles play an important role in

  20. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials

    Science.gov (United States)

    Hoemann, Caroline; Kandel, Rita; Roberts, Sally; Saris, Daniel B.F.; Creemers, Laura; Mainil-Varlet, Pierre; Méthot, Stephane; Hollander, Anthony P.; Buschmann, Michael D.

    2011-01-01

    Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character. PMID:26069577

  1. A study on MR images of the articular cartilage in medial-type osteoarthritis of the knee

    International Nuclear Information System (INIS)

    Miyazaki, Hiroyuki; Ishii, Yoshiaki; Hayashi, Mitsutoshi; Kotani, Akihiro

    2001-01-01

    Changes in the articular cartilage of 88 knees of 73 cases (age range 40-78) diagnosed clinically and radiologically as OA (osteoarthritis) were studied by obtaining fat-suppressed MR images of the knee. On 27 knees out of the 88, moreover, macroscopic observation was performed to make a comparative study between the directly-observed findings and MR findings. Fat-suppressed MR images were obtained sagittally by 3D-FLASH (fast low angle shot) sequence. The examined regions consisted of the following 4 sites; the medial condyle of the femur, its lateral condyle, the medial condyle of the tibia, and its lateral condyle. The revealed conditions of the cartilage were morphologically classified into 4 Stages. The evidence of cartilage defect on MR images was most frequently found at the medial condyle of the femur, with the medial condyle of the tibia, the lateral condyle of the femur, and the lateral condyle of the tibia following in a less frequent order. Fat-suppressed MRI's sensitivity to cartilage defect against macroscopy was 94.5%, specificity 95.4%, and accuracy 95.2%. MR imaging using fat-suppression can reveal cartilaginous degeneration and defect so well that this technique provides an important indication for selecting a proper method of treatment. (author)

  2. MR imaging of hyaline cartilage in chondromalacia patellae and osteochondrosis dissecans: A comparison with CT-arthrography and arthroscopy

    International Nuclear Information System (INIS)

    Lehner, K.; Heuck, A.; Lukas, P.; Rodammer, G.; Allgayer, B.; Pasquay, E.

    1987-01-01

    Superior to spin-echo sequences, the articular hyaline cartilage was imaged with fast-field-echo sequences (FFE, Gyroscan 0.5-T, Philips) with an excitation pulse angle of 40 0 to 60 0 . Chondromalaceous lesions could be demonstrated in 30 patients with chondropathia patellae with the same sensitivity compared with CT arthrography. In a further 50 patients with osteochondrosis dissecans, discontinuities of the cartilage could be predicted using the deeply invading articular fluid as an indicator. The sensitivity of MR imaging, as controlled by arthroscopy, was very high in that respect. Separate from the nonhemorrhagic articular fluid, the cartilaginous defects could be imaged directly by variation of the FFE parameters

  3. Diffuse large B-cell lymphoma chemotherapy reveals a combined immunodeficiency syndrome in cartilage hair hypoplasia.

    Science.gov (United States)

    Nguyen, Alexandre; Martin Silva, Nicolas; de Boysson, Hubert; Damaj, Gandhi; Aouba, Achille

    2018-04-24

    Cartilage hair hypoplasia (CHH) is a rare autosomal recessive ribosomopathy characterised by skeletal and integumentary system manifestations. It may also present with varied forms and intensities of haematopoietic and/or immune disorders. We report a 27-year-old female who presented a picture of combined immunodeficiency after receiving an adriamycin-based chemotherapy regimen followed by autologous stem cell transplantation. Her medical history indicated neonatal dwarfism, recurrent ear, nose and throat and respiratory infections, and hypogammaglobulinaemia, which were suggestive of a primary minor B-cell immune deficiency. Taken together, the diagnosis of cartilage hair hypoplasia was suspected and confirmed by means of molecular biological analysis. Here, we discuss the causal relationship and molecular mechanisms existing between both primary immunodeficiency and lymphoma conditions and between chemotherapy cytotoxicity and aggravation of the immune system and associated hematopoietic dysfunction, considering the role of all these components in light of the initially undiagnosed cartilage hair hypoplasia. Finally, this case highlights the importance of screening for primary immunodeficiencies in the setting of a diagnosis of lymphoma and/or dwarfism; moreover, CHH must be distinguished from other causes of small size; its diagnosis and complete check-up must include the molecular characterisation, and its management must be global in collaboration with haematologists, immunologists and internists.

  4. Satisfactory surgical option for cartilage graft absorption in microtia reconstruction.

    Science.gov (United States)

    Han, So-Eun; Oh, Kap Sung

    2016-04-01

    We routinely perform auricular elevation at least 6 months after implantation of framework in microtia reconstruction using costal cartilage. However, in a few cases, cartilage graft absorption has occurred, which has led to contour irregularity with unfavorable long-term results. In the present study, we recount the details of using additional rib cartilage augmentation to achieve an accentuated contour in cartilage graft absorption cases. The cartilage graft absorption was defined as contour irregularity or cartilage graft deformation as evaluated by the surgeon and patient. Depending on the extent of cartilage graft absorption, another rib cartilage framework was added to the previously implanted framework, targeting the absorption area. We used banked cartilage or harvested new cartilage based on three-dimensional rib computed tomography. Additional recontouring of framework was conducted in eight patients who were examined for cartilage graft absorption from 1.5 to 5 years after implantation of the framework. Four patients received additional rib cartilage augmentation and tissue expander insertion simultaneously prior to auricular elevation. Two patients underwent auricular elevation simultaneously. In another two patients, additional rib cartilage augmentation was performed before auricular elevation. The mean follow-up period was 18 months, and in all cases reconstructive results were acceptable. Although further follow-up evaluation is required, additional rib cartilage augmentation is an attractive surgical option for cartilage graft absorption cases. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Michiel W. Pot

    2017-10-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  7. Quantitative Assessment of Degenerative Cartilage and Subchondral Bony Lesions in a Preserved Cadaveric Knee: Propagation-Based Phase-Contrast CT Versus Conventional MRI and CT.

    Science.gov (United States)

    Geith, Tobias; Brun, Emmanuel; Mittone, Alberto; Gasilov, Sergei; Weber, Loriane; Adam-Neumair, Silvia; Bravin, Alberto; Reiser, Maximilian; Coan, Paola; Horng, Annie

    2018-04-09

    The aim of this study was to quantitatively assess hyaline cartilage and subchondral bone conditions in a fully preserved cadaveric human knee joint using high-resolution x-ray propagation-based phase-contrast imaging (PBI) CT and to compare the performance of the new technique with conventional CT and MRI. A cadaveric human knee was examined using an x-ray beam of 60 keV, a detector with a 90-mm 2 FOV, and a pixel size of 46 × 46 μm 2 . PBI CT images were reconstructed with both the filtered back projection algorithm and the equally sloped tomography method. Conventional 3-T MRI and CT were also performed. Measurements of cartilage thickness, cartilage lesions, International Cartilage Repair Society scoring, and detection of subchondral bone changes were evaluated. Visual inspection of the specimen akin to arthroscopy was conducted and served as a standard of reference for lesion detection. Loss of cartilage height was visible on PBI CT and MRI. Quantification of cartilage thickness showed a strong correlation between the two modalities. Cartilage lesions appeared darker than the adjacent cartilage on PBI CT. PBI CT showed similar agreement to MRI for depicting cartilage substance defects or lesions compared with the visual inspection. The assessment of subchondral bone cysts showed moderate to strong agreement between PBI CT and CT. In contrast to the standard clinical methods of MRI and CT, PBI CT is able to simultaneously depict cartilage and bony changes at high resolution. Though still an experimental technique, PBI CT is a promising high-resolution imaging method to evaluate comprehensive changes of osteoarthritic disease in a clinical setting.

  8. Characterization of the cartilage DNA methylome in knee and hip osteoarthritis.

    Science.gov (United States)

    Rushton, Michael D; Reynard, Louise N; Barter, Matt J; Refaie, Ramsay; Rankin, Kenneth S; Young, David A; Loughlin, John

    2014-09-01

    The aim of this study was to characterize the genome-wide DNA methylation profile of chondrocytes from knee and hip cartilage obtained from patients with osteoarthritis (OA) and hip cartilage obtained from patients with femoral neck fracture, providing the first comparison of DNA methylation between OA and non-OA hip cartilage, and between OA hip and OA knee cartilage. The study was performed using the Illumina Infinium HumanMethylation450 BeadChip array, which allows the annotation of ∼480,000 CpG sites. Genome-wide methylation was assessed in chondrocyte DNA extracted from 23 hip OA patients, 73 knee OA patients, and 21 healthy hip control patients with femoral neck fracture. Analysis revealed that chondrocytes from the hip cartilage of OA patients and healthy controls have unique methylation profiles, with 5,322 differentially methylated loci (DMLs) identified between the 2 groups. In addition, a comparison between hip and knee OA chondrocytes revealed 5,547 DMLs between the 2 groups, including DMLs in several genes known to be involved in the pathogenesis of OA. Hip OA samples were found to cluster into 2 groups. A total of 15,239 DMLs were identified between the 2 clusters, with an enrichment of genes involved in inflammation and immunity. Similarly, we confirmed a previous report of knee OA samples that also clustered into 2 groups. We demonstrated that global DNA methylation using a high-density array can be a powerful tool in the characterization of OA at the molecular level. Identification of pathways enriched in DMLs between OA and OA-free cartilage highlight potential etiologic mechanisms that are involved in the initiation and/or progression of the disease and that could be therapeutically targeted. © 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

  9. First and second order stereology of hyaline cartilage: Application on mice femoral cartilage.

    Science.gov (United States)

    Noorafshan, Ali; Niazi, Behnam; Mohamadpour, Masoomeh; Hoseini, Leila; Hoseini, Najmeh; Owji, Ali Akbar; Rafati, Ali; Sadeghi, Yasaman; Karbalay-Doust, Saied

    2016-11-01

    Stereological techniques could be considered in research on cartilage to obtain quantitative data. The present study aimed to explain application of the first- and second-order stereological methods on articular cartilage of mice and the methods applied on the mice exposed to cadmium (Cd). The distal femoral articular cartilage of BALB/c mice (control and Cd-treated) was removed. Then, volume and surface area of the cartilage and number of chondrocytes were estimated using Cavalieri and optical dissector techniques on isotropic uniform random sections. Pair-correlation function [g(r)] and cross-correlation function were calculated to express the spatial arrangement of chondrocytes-chondrocytes and chondrocytes-matrix (chondrocyte clustering/dispersing), respectively. The mean±standard deviation of the cartilage volume, surface area, and thickness were 1.4±0.1mm 3 , 26.2±5.4mm 2 , and 52.8±6.7μm, respectively. Besides, the mean number of chondrocytes was 680±200 (×10 3 ). The cartilage volume, cartilage surface area, and number of chondrocytes were respectively reduced by 25%, 27%, and 27% in the Cd-treated mice in comparison to the control animals (pcartilage components carried potential advantages for investigating the cartilage in different joint conditions. Chondrocyte clustering/dispersing and cellularity can be evaluated in cartilage assessment in normal or abnormal situations. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation: Review of Preclinical and Clinical Studies.

    Science.gov (United States)

    Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke; Wakitani, Shigeyuki

    2014-10-01

    Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored.

  11. Decrease in local volumetric bone mineral density (vBMD) in osteoarthritic joints is associated with the increase in cartilage damage: a pQCT study

    Science.gov (United States)

    Tamaddon, Maryam; Chen, Shen Mao; Vanaclocha, Leyre; Hart, Alister; El-Husseiny, Moataz; Henckel, Johann; Liu, Chaozong

    2017-11-01

    Osteoarthritis (OA) is the most common type of arthritis and a major cause of disability in the adult population. It affects both cartilage and subchondral bone in the joints. There has been some progress in understanding the changes in subchondral bone with progression of osteoarthritis. However, local changes in subchondral bone such as microstructure or volumetric bone mineral density in connection with the defect in cartilage are relatively unexplored. To develop an effective treatment for progression of OA, it is important to understand how the physical environment provided by the subchondral bone affects the overlying cartilage. In this study we examined the volumetric bone mineral density (vBMD) distribution in the osteoarthritic joint tissues obtained from total hip replacement surgeries due to osteoarthritis, using peripheral quantitative CT (pQCT). It was found that there is a significant decrease in volumetric bone mineral density, which co-localises with the damage in the overlying cartilage. This was not limited to the subchondral bone immediately adjacent to the cartilage defect but continued in the layers below. Bone resorption and cyst formation in the OA tissues were also detected. We observed that the bone surrounding subchondral bone cysts exhibited much higher volumetric bone mineral density than that of the surrounding bones. PQCT was able to detect significant changes in vBMD between OA and non-OA samples, as well as between areas of different cartilage degeneration, which points to its potential as a technique for detection of early OA.

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

    Science.gov (United States)

    Erickson, Isaac E.

    2011-12-01

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

  13. Articular cartilage changes in chondromalacia patellae.

    Science.gov (United States)

    Bentley, G

    1985-11-01

    Full thickness samples of articular cartilage were removed from areas of chondromalacia on the medial and "odd" facets of the patellae of 21 adults and examined by histology, autoradiography and electron microscopy. Surface fibrillation, loss of superficial matrix staining and reduced 35SO4 labelling was seen, with little change in the deep zone. Ten cases showed "fibrous metaplasia" of the superficial cartilage with definite evidence of cell division and apparent smoothing of the surface. Scattered chondrocyte replication appeared to occur in the surrounding intact cartilage. The findings suggest that early lesions in chondromalacia patellae may heal either by cartilage or fibrous metaplasia and that this may account for the resolution of clinical symptoms.

  14. PAPAIN-INDUCED CHANGES IN RABBIT CARTILAGE

    Science.gov (United States)

    Tsaltas, Theodore T.

    1958-01-01

    Some biochemical aspects of the collapse of the rabbit ears produced by the intravenous injection of papain have been studied. A marked depletion of chondromucoprotein (M.C.S.) and a reduction of the S35 content of cartilage matrix were found to coincide with the gross and histologic changes in the cartilage. At the same time there was a marked increase in the amount of S35 in the serum and an increase of S35 and glucuronic acid excreted in the urine. Alteration in the composition of the M.C.S. remaining in the cartilage of the papain-injected animals was detected. The findings indicate that the collapse of the rabbit ears is due to loss of chondromucoprotein from cartilage and reduction of chondroitin sulfate in the chondromucoprotein that remains. All these changes were reversed in recovery. PMID:13575681

  15. The minor collagens in articular cartilage

    DEFF Research Database (Denmark)

    Luo, Yunyun; Sinkeviciute, Dovile; He, Yi

    2017-01-01

    Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components......, especially minor collagens, including type IV, VI, IX, X, XI, XII, XIII, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also...... fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including...

  16. Cartilage Repair in Football (Soccer) Athletes

    Science.gov (United States)

    Bekkers, J.E.J.; de Windt, Th.S.; Brittberg, M.

    2012-01-01

    The prevalence of focal articular cartilage lesions among athletes is higher than in the general population. Treatment goals differ considerably between the professional and recreational athlete. High financial stakes and the short duration of a professional career influence the treatment selection for the professional athlete, while such parameters weigh differently in recreational sports. This article describes our investigation of the relation between sports and a high prevalence of focal cartilage lesions. In addition, we provide a critical review of the best available evidence for cartilage surgery and treatment selection, evaluate specific patient profiles for professional and recreational athletes, and propose a treatment algorithm for the treatment of focal cartilage lesions in football (soccer) players. PMID:26069606

  17. Harnessing biomechanics to develop cartilage regeneration strategies.

    Science.gov (United States)

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

    2015-02-01

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

  18. Materials science: Like cartilage, but simpler

    DEFF Research Database (Denmark)

    Skov, Anne Ladegaard

    2015-01-01

    The properties of articular cartilage, which lines bones in joints, depend partlyon repulsion between components of the material. A new synthetic gel that mimics this feature has rare, direction-dependent properties.......The properties of articular cartilage, which lines bones in joints, depend partlyon repulsion between components of the material. A new synthetic gel that mimics this feature has rare, direction-dependent properties....

  19. New Frontiers for Cartilage Repair and Protection

    OpenAIRE

    Zaslav, Kenneth; McAdams, Timothy; Scopp, Jason; Theosadakis, Jason; Mahajan, Vivek; Gobbi, Alberto

    2012-01-01

    Objective: Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and ...

  20. Cartilage proteoglycans inhibit fibronectin-mediated adhesion

    Science.gov (United States)

    Rich, A. M.; Pearlstein, E.; Weissmann, G.; Hoffstein, S. T.

    1981-09-01

    Normal tissues and organs show, on histological examination, a pattern of cellular and acellular zones that is characteristic and unique for each organ or tissue. This pattern is maintained in health but is sometimes destroyed by disease. For example, in mobile joints, the articular surfaces consist of relatively acellular hyaline cartilage, and the joint space is enclosed by a capsule of loose connective tissue with a lining of fibroblasts and macrophages. In the normal joint these cells are confined to the synovial lining and the articular surface remains acellular. In in vitro culture, macrophages and their precursor monocytes are very adhesive, and fibroblasts can migrate and overgrow surfaces such as collagen or plastic used for tissue culture. The fibroblasts adhere to collagen by means of fibronectin, which they synthesize and secrete1. Because the collagen of cartilage is capable of binding serum fibronectin2 and fibronectin is present in cartilage during its development3, these cells should, in theory, slowly migrate from the synovial lining to the articular surface. It is their absence from the articular cartilage in normal circumstances, and then presence in such pathological states as rheumatoid arthritis, that is striking. We therefore set out to determine whether a component of cartilage could prevent fibroblast adherence in a defined adhesion assay. As normal cartilage is composed of 50% proteoglycans and 50% collagen by dry weight4, we tested the possibility that the proteoglycans in cartilage inhibit fibroblast adhesion to collagen. We present here evidence that fibroblast spreading and adhesion to collagenous substrates is inhibited by cartilage proteoglycans.

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

    Science.gov (United States)

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

    2015-11-09

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

  2. Basic science and surgical treatment options for articular cartilage injuries of the knee.

    Science.gov (United States)

    Tetteh, Elizabeth S; Bajaj, Sarvottam; Ghodadra, Neil S

    2012-03-01

    The complex structure of articular cartilage allows for diverse knee function throughout range of motion and weight bearing. However, disruption to the structural integrity of the articular surface can cause significant morbidity. Due to an inherently poor regenerative capacity, articular cartilage defects present a treatment challenge for physicians and therapists. For many patients, a trial of nonsurgical treatment options is paramount prior to surgical intervention. In instances of failed conservative treatment, patients can undergo an array of palliative, restorative, or reparative surgical procedures to treat these lesions. Palliative methods include debridement and lavage, while restorative techniques include marrow stimulation. For larger lesions involving subchondral bone, reparative procedures such as osteochondral grafting or autologous chondrocyte implantation are considered. Clinical success not only depends on the surgical techniques but also requires strict adherence to rehabilitation guidelines. The purpose of this article is to review the basic science of articular cartilage and to provide an overview of the procedures currently performed at our institution for patients presenting with symptomatic cartilage lesions.

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

    Science.gov (United States)

    Monibi, Farrah A; Cook, James L

    2017-08-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  5. Body Weight Independently Affects Articular Cartilage Catabolism

    Directory of Open Access Journals (Sweden)

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

    2015-06-01

    Full Text Available 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.

  6. Precision of hyaline cartilage thickness measurements

    Energy Technology Data Exchange (ETDEWEB)

    Jonsson, K.; Buckwalter, K.; Helvie, M.; Niklason, L.; Martel, W. (Univ. of Michigan Hospitals, Ann Arbor, MI (United States). Dept. of Radiology)

    1992-05-01

    Measurement of cartilage thickness in vivo is an important indicator of the status of a joint as the various degenerative and inflammatory arthritides directly affect the condition of the cartilage. In order to assess the precision of thickness measurements of hyaline articular cartilage, we undertook a pilot study using MR imaging, plain radiography, and ultrasonography (US). We measured the cartilage of the hip and knee joints in 10 persons (4 healthy volunteers and 6 patients). The joints in each patient were examined on two separate occasions using each modality. In the hips a swell as the knee joints, the most precise measuring method was plain film radiography. For radiographs of the knees obtained in the standing position, the coefficient of variation was 6.5%; in the hips this figure was 6.34%. US of the knees and MR imaging of the hips were the second best modalities in the measurement of cartilage thickness. In addition, MR imaging enabled the most complete visualization of the joint cartilage. (orig.).

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Arumugam S

    2011-01-01

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

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

    Science.gov (United States)

    Nagel, Thomas; Kelly, Daniel J

    2013-04-01

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

  10. Clinical and MRI outcome of an osteochondral scaffold plug for the treatment of cartilage lesions in the knee.

    Science.gov (United States)

    Dhollander, Aad; Verdonk, Peter; Almqvist, Karl Fredrik; Verdonk, Rene; Victor, Jan

    2015-12-01

    Conflicting clinical outcomes have been reported recently with the use of an osteochondral scaffold plugs for cartilage repair in the knee. In this study, twenty patients were consecutively treated for their cartilage lesions with the synthetic plug technique. These patients were prospectively clinically evaluated with a mean follow-up of 34.15 months. Magnetic resonance imaging (MRI) was used for morphologic analysis of the cartilage repair. The patients included in this study showed a significant gradual clinical improvement after the osteochondral scaffold plug. However, this clinical improvement was not confirmed by the MRI findings of this cohort study. Subchondral bone changes were seen in all patients on MRI and deficient filling of the defect was noticed in in 30.7% of the cases at 24 months of follow-up. There was no evidence found to support osteoconductive bone ingrowth. Therefore, the use of this type of osteochondral scaffold plug in osteochondral repair is questionable. Level of evidence: IV.

  11. THE USE OF SHARK CARTILAGE EXTRACTS IN POSSIBLE THERAPIES AGAINST CANCER: AREVIEW

    Directory of Open Access Journals (Sweden)

    Gláuber Fernando Ratzkob

    2015-06-01

    Full Text Available The study aims to discuss the use of extracts derived from shark cartilage in potential cancer therapies. This is a literature review based on literature by consulting the scientific articles selected in the Medline, Scopus and DOAJ database. Twenty-seven articles were included after applying the inclusion and not inclusion criteria established by the authors. The selected studies revealed that ther are some extracts derived from shark cartilage with anticancer properties. These properties are mostly related to the blockade of angiogenesis and some extracts also have action on the immune system and inhibition of metastases. The best known shark cartilage extract is the formulation of Neovastat® (AE-941, which was successful in studies conducted in the laboratory, but failed in clinical trials in humans, and therefore ceased to be developed in 2007. Nevertheless, yetmany extracts are under review, and these studies will be important to confirm or not the feasibility and applicability of the use of shark cartilage extracts in the treatment of cancer.

  12. Embedded defects

    International Nuclear Information System (INIS)

    Barriola, M.; Vachaspati, T.; Bucher, M.

    1994-01-01

    We give a prescription for embedding classical solutions and, in particular, topological defects in field theories which are invariant under symmetry groups that are not necessarily simple. After providing examples of embedded defects in field theories based on simple groups, we consider the electroweak model and show that it contains the Z string and a one-parameter family of strings called the W(α) string. It is argued that although the members of this family are gauge equivalent when considered in isolation, each member becomes physically distinct when multistring configurations are considered. We then turn to the issue of stability of embedded defects and demonstrate the instability of a large class of such solutions in the absence of bound states or condensates. The Z string is shown to be unstable for all values of the Higgs boson mass when θ W =π/4. W strings are also shown to be unstable for a large range of parameters. Embedded monopoles suffer from the Brandt-Neri-Coleman instability. Finally, we connect the electroweak string solutions to the sphaleron

  13. Pathways of load-induced cartilage damage causing cartilage degeneration in the knee after meniscectomy

    NARCIS (Netherlands)

    Wilson, W.; Rietbergen, van B.; Donkelaar, van C.C.; Huiskes, R.

    2003-01-01

    Results of both clinical and animal studies show that meniscectomy often leads to osteoarthritic degenerative changes in articular cartilage. It is generally assumed that this process of cartilage degeneration is due to changes in mechanical loading after meniscectomy. It is, however, not known why

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

    NARCIS (Netherlands)

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

    1993-01-01

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

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

    Science.gov (United States)

    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

  16. Free Diced Cartilage: A New Application of Diced Cartilage Grafts in Primary and Secondary Rhinoplasty.

    Science.gov (United States)

    Kreutzer, Christian; Hoehne, Julius; Gubisch, Wolfgang; Rezaeian, Farid; Haack, Sebastian

    2017-09-01

    Irregularities or deformities of the nasal dorsum after hump reduction account for a significant number of revision rhinoplasties. The authors therefore developed a technique of meticulously dicing and exactly placing free diced cartilage grafts, harvested from septum, rib, or ear cartilage. The cartilage paste is used for smoothening, augmentation, or camouflaging of the nasal dorsum in primary or revision rhinoplasties. A retrospective analysis of multisurgeon consecutive open approach rhinoplasties from January to December of 2014 was conducted at a single center. The authors compared the outcome of three different techniques to augment or cover the nasal dorsum after an observation period of 7 months. In group I, 325 patients with free diced cartilage grafts as the only onlay were included. In group II, consisting of 73 patients, the dorsal onlay was either fascia alone or in combination with free diced cartilage grafts. Forty-eight patients in group III received a dorsal augmentation with the classic diced cartilage in fascia technique. Four hundred forty-six patients undergoing primary and secondary rhinoplasties in which one of the above-mentioned diced cartilage techniques was used were included in the study. The authors found revision rates for dorsal irregularities within the 7-month postoperative observation period of 5.2, 8.2, and 25 percent for groups I, II, and III, respectively. The authors' findings strongly support their clinical experience that the free diced cartilage graft technique presents an effective and easily reproducible method for camouflage and augmentation in aesthetic and reconstructive rhinoplasty.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  18. Osteoarthritic human cartilage is more sensitive to transforming growth factor beta than is normal cartilage

    NARCIS (Netherlands)

    Lafeber, F. P.; Vander Kraan, P. M.; Huber-Bruning, O.; Vanden Berg, W. B.; Bijlsma, J. W.

    1993-01-01

    Osteoarthritis is a degenerative joint disease, characterized by the destruction of the articular cartilage. One of the first changes in the osteoarthritic articular cartilage is a reduction in proteoglycan content. In this study we demonstrate that transforming growth factor beta (TGF beta), a

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

    Directory of Open Access Journals (Sweden)

    Pia M. Jungmann

    2014-01-01

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

  20. Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model.

    Science.gov (United States)

    Goodrich, L R; Hidaka, C; Robbins, P D; Evans, C H; Nixon, A J

    2007-05-01

    Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 x 10(7) AdIGF-1 modified chondrocytes and the contralateral joint received 2 x 10(7) naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated. Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and

  1. The cranial cartilages of teleosts and their classification.

    OpenAIRE

    Benjamin, M

    1990-01-01

    The structure and distribution of cartilages has been studied in 45 species from 24 families. The resulting data have been used as a basis for establishing a new classification. A cartilage is regarded as 'cell-rich' if its cells or their lacunae occupy more than half of the tissue volume. Five classes of cell-rich cartilage are recognised (a) hyaline-cell cartilage (common in the lips of bottom-dwelling cyprinids) and its subtypes fibro/hyaline-cell cartilage, elastic/hyaline-cell cartilage ...

  2. Longitudinal evaluation of T1ρ and T2 spatial distribution in osteoarthritic and healthy medial knee cartilage.

    Science.gov (United States)

    Schooler, J; Kumar, D; Nardo, L; McCulloch, C; Li, X; Link, T M; Majumdar, S

    2014-01-01

    To investigate longitudinal changes in laminar and spatial distribution of knee articular cartilage magnetic resonance imaging (MRI) T1ρ and T2 relaxation times, in individuals with and without medial compartment cartilage defects. All subjects (at baseline n = 88, >18 years old) underwent 3-Tesla knee MRI at baseline and annually thereafter for 3 years. The MR studies were evaluated for presence of cartilage defects (modified Whole-Organ Magnetic Resonance Imaging Scoring - mWORMS), and quantitative T1ρ and T2 relaxation time maps. Subjects were segregated into those with (mWORMS ≥2) and without (mWORMS ≤1) cartilage lesions at the medial tibia (MT) or medial femur (MF) at each time point. Laminar (bone and articular layer) and spatial (gray level co-occurrence matrix - GLCM) distribution of the T1ρ and T2 relaxation time maps were calculated. Linear regression models (cross-sectional) and Generalized Estimating Equations (GEEs) (longitudinal) were used. Global T1ρ, global T2 and articular layer T2 relaxation times at the MF, and global and articular layer T2 relaxation times at the MT, were higher in subjects with cartilage lesions compared to those without lesions. At the MT global T1ρ relaxation times were higher at each time point in subjects with lesions. MT T1ρ and T2 became progressively more heterogeneous than control compartments over the course of the study. Spatial distribution of T1ρ and T2 relaxation time maps in medial knee OA using GLCM technique may be a sensitive indicator of cartilage deterioration, in addition to whole-compartment relaxation time data. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  3. A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year.

    Science.gov (United States)

    Siclari, Alberto; Mascaro, Gennaro; Gentili, Chiara; Cancedda, Ranieri; Boux, Eugenio

    2012-03-01

    Bone marrow stimulation techniques in cartilage repair such as drilling are limited by the formation of fibrous to hyaline-like repair tissue. It has been suggested such techniques can be enhanced by covering the defect with scaffolds. We present an innovative approach using a polyglycolic acid (PGA)-hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling. We asked whether (1) PRP immersed in a cell-free PGA-hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in combination with bone marrow stimulation leads to the formation of hyaline-like cartilage repair tissue. We reviewed 52 patients who had arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in articular cartilage defects of the knee pretreated with Pridie drilling. Patients were assessed by KOOS. At 9 months followup, histologic staining was performed in specimens obtained from five patients to assess the repair tissue quality. The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88), activities of daily living (69 to 86), sports and recreation (36 to 70), and quality of life (38 to 73). The histologic evaluation showed a homogeneous hyaline-like cartilage repair tissue. The cell-free PGA-hyaluronan scaffold combined with PRP leads to cartilage repair and improved patient-reported outcomes (KOOS) during 12 months of followup. Histologic sections showed morphologic features of hyaline-like repair tissue. Long-term followup is needed to determine if the cartilage repair tissue is durable. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

  4. Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF.

    Science.gov (United States)

    Cugat, Ramón; Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

    2017-01-01

    Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

  5. Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF

    Directory of Open Access Journals (Sweden)

    Ramón Cugat

    2017-01-01

    Full Text Available Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF. Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them. The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

  6. Outerbridge Grade IV Cartilage Lesions in the Hip Identified at Arthroscopy.

    Science.gov (United States)

    Bhatia, Sanjeev; Nowak, Douglas D; Briggs, Karen K; Patterson, Diana C; Philippon, Marc J

    2016-05-01

    To determine factors associated with grade IV cartilage defects in the hip in patients undergoing hip arthroscopy with joint pain. Data from consecutive patients who underwent hip arthroscopy performed by a single surgeon over a period of 4 years were included in this study. The study group included 1,097 patients (491 women and 606 men; mean age, 37 years) who underwent hip arthroscopy for pain, had no prior hip surgery, and were aged 18 years or older. Preoperative radiographs, patient demographic characteristics, and operative details were used to identify risk factors for cartilage defects. Grade IV chondral defects were present in 308 of 1,097 hips (28%). Isolated chondral lesions were more frequently observed on the acetabulum (76%) than on the femoral head (24%). Defects of the acetabulum were more commonly anterosuperior (94.7%) and less commonly posterolateral (5.3%). Patients with less than 2 mm of joint space on preoperative radiographs were 8 times more likely to have a grade IV lesion than those with more than 2 mm. Men were more likely than women to have grade IV lesions (35% v 19%, P = .0001); patients with grade IV lesions were older than those without (42 years v 34 years, P = .0001). Hips with grade IV lesions had significantly higher alpha angles than those without (74° v 70°, P = .0001). Patients with grade IV defects reported a longer duration of symptoms than those without (37 months v 27 months, P = .007). Independent risk factors for the presence of grade IV chondral defects were less than 2 mm of joint space, male gender, increasing age, larger alpha angle, and longer duration of symptoms. Grade IV chondral defects in patients undergoing hip arthroscopy were associated with decreased joint space, increased time from symptom onset to arthroscopy, male gender, and larger alpha angles associated with femoroacetabular impingement. Level IV, prognostic case series. Copyright © 2016 Arthroscopy Association of North America. Published by

  7. Increasing the Dose of Autologous Chondrocytes Improves Articular Cartilage Repair: Histological and Molecular Study in the Sheep Animal Model.

    Science.gov (United States)

    Guillén-García, Pedro; Rodríguez-Iñigo, Elena; Guillén-Vicente, Isabel; Caballero-Santos, Rosa; Guillén-Vicente, Marta; Abelow, Stephen; Giménez-Gallego, Guillermo; López-Alcorocho, Juan Manuel

    2014-04-01

    We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one. We compared the implantation of different doses of chondrocytes: 1 million (n = 5), 5 million (n = 5), or 5 million mesenchymal cells (n = 5) in the femoral condyle of 15 sheep. Tissue generated by microfracture at the trochlea, and normal cartilage from a nearby region, processed as the tissues resulting from the implantation, were used as references. Histological and molecular (expression of type I and II collagens and aggrecan) studies were performed. The features of the cartilage generated by implantation of mesenchymal cells and elicited by microfractures were similar and typical of a poor repair of the articular cartilage (presence of fibrocartilage, high expression of type I collagen and a low mRNA levels of type II collagen and aggrecan). Nevertheless, in the samples obtained from tissues generated by implantation of chondrocytes, hyaline-like cartilage, cell organization, low expression rates of type I collagen and high levels of mRNA corresponding to type II collagen and aggrecan were observed. These histological features, show less variability and are more similar to those of the normal cartilage used as control in the case of 5 million cells implantation than when 1 million cells were used. The implantation of autologous chondrocytes in type I/III collagen membranes at high density could be a promising tool to repair articular cartilage.

  8. Aggrecan structure in amphibian cartilage

    Directory of Open Access Journals (Sweden)

    Covizi D.Z.

    2000-01-01

    Full Text Available The structure of the large proteoglycan present in the bullfrog epiphyseal cartilage was studied by immunochemical and biochemical methods. The isolated monomer showed a polydisperse behavior on Sepharose CL2B, with a peak at Kav = 0.14. Chondroitin sulfate chains were identified by HPLC analysis of the products formed by chondroitinase digestion and mercuric acetate treatment. These chains have approximately 38 disaccharides, a Di45:Di68 ratio of 1.6 and GalNAc4S + GalNAc4,6S are the main non-reducing terminals. Keratan sulfate was identified by the use of two monoclonal antibodies in Western blots after chondroitinase ABC treatment. A keratan sulfate-rich region (~110 kDa was isolated by sequential treatment with chondroitinase ABC and proteases. We also employed antibodies in Western blotting experiments and showed that the full length deglycosylated core protein is about 300 kDa after SDS-PAGE. Domain-specific antibodies revealed the presence of immunoreactive sites corresponding to G1/G2 and G3 globular domains and the characterization of this large proteoglycan as aggrecan. The results indicate the high conservation of the aggrecan domain structure in this lower vertebrate.

  9. Joint distraction and movement for repair of articular cartilage in a rabbit model with subsequent weight-bearing.

    Science.gov (United States)

    Nishino, T; Chang, F; Ishii, T; Yanai, T; Mishima, H; Ochiai, N

    2010-07-01

    We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.

  10. An update on risk factors for cartilage loss in knee osteoarthritis assessed using MRI-based semiquantitative grading methods

    Energy Technology Data Exchange (ETDEWEB)

    Alizai, Hamza [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); Aspetar Orthopaedic and Sports Medicine Hospital, Doha (Qatar); University of Texas Health Science Center at San Antonio, Department of Radiology, San Antonio, TX (United States); Roemer, Frank W. [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); Aspetar Orthopaedic and Sports Medicine Hospital, Doha (Qatar); University of Erlangen-Nuremberg, Department of Radiology, Erlangen (Germany); Hayashi, Daichi [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); Aspetar Orthopaedic and Sports Medicine Hospital, Doha (Qatar); Yale University School of Medicine, Department of Radiology, Bridgeport Hospital, Bridgeport, CT (United States); Crema, Michel D. [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); Aspetar Orthopaedic and Sports Medicine Hospital, Doha (Qatar); Hospital do Coracao and Teleimagem, Department of Radiology, Sao Paulo (Brazil); Felson, David T. [Boston University School of Medicine, Clinical Epidemiology Research and Training Unit, Boston, MA (United States); Guermazi, Ali [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); Aspetar Orthopaedic and Sports Medicine Hospital, Doha (Qatar); Boston Medical Center, Boston, MA (United States)

    2014-11-07

    Arthroscopy-based semiquantitative scoring systems such as Outerbridge and Noyes' scores were the first to be developed for the purpose of grading cartilage defects. As magnetic resonance imaging (MRI) became available faor evaluation of the osteoarthritic knee joint, these systems were adapted for use with MRI. Later on, grading methods such as the Whole Organ Magnetic Resonance Score, the Boston-Leeds Osteoarthritis Knee Score and the MRI Osteoarthritis Knee Score were designed specifically for performing whole-organ assessment of the knee joint structures, including cartilage. Cartilage grades on MRI obtained with these scoring systems represent optimal outcome measures for longitudinal studies, and are designed to enhance understanding of the knee osteoarthritis disease process. The purpose of this narrative review is to describe cartilage assessment in knee osteoarthritis using currently available MRI-based semiquantitative whole-organ scoring systems, and to provide an update on the risk factors for cartilage loss in knee osteoarthritis as assessed with these scoring systems. (orig.)

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

    International Nuclear Information System (INIS)

    Marlovits, Stefan; Striessnig, Gabriele; Resinger, Christoph T.; Aldrian, Silke M.; Vecsei, Vilmos; Imhof, Herwig; Trattnig, Siegfried

    2004-01-01

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

  12. An update on risk factors for cartilage loss in knee osteoarthritis assessed using MRI-based semiquantitative grading methods

    International Nuclear Information System (INIS)

    Alizai, Hamza; Roemer, Frank W.; Hayashi, Daichi; Crema, Michel D.; Felson, David T.; Guermazi, Ali

    2015-01-01

    Arthroscopy-based semiquantitative scoring systems such as Outerbridge and Noyes' scores were the first to be developed for the purpose of grading cartilage defects. As magnetic resonance imaging (MRI) became available faor evaluation of the osteoarthritic knee joint, these systems were adapted for use with MRI. Later on, grading methods such as the Whole Organ Magnetic Resonance Score, the Boston-Leeds Osteoarthritis Knee Score and the MRI Osteoarthritis Knee Score were designed specifically for performing whole-organ assessment of the knee joint structures, including cartilage. Cartilage grades on MRI obtained with these scoring systems represent optimal outcome measures for longitudinal studies, and are designed to enhance understanding of the knee osteoarthritis disease process. The purpose of this narrative review is to describe cartilage assessment in knee osteoarthritis using currently available MRI-based semiquantitative whole-organ scoring systems, and to provide an update on the risk factors for cartilage loss in knee osteoarthritis as assessed with these scoring systems. (orig.)

  13. Magnetic resonance imaging of the femoral trochlea: evaluation of anatomical landmarks and grading articular cartilage in cadaveric knees

    Energy Technology Data Exchange (ETDEWEB)

    Muhle, Claus [Marienhospital Vechta, Department of Radiology, Vechta (Germany); Veterans Affairs Medical Center, Department of Radiology, San Diego, CA (United States); Mo Ahn, Joong [University of Iowa, Department of Radiology, Iowa, IA (United States); Trudell, Debra; Resnick, Donald [Veterans Affairs Medical Center, Department of Radiology, San Diego, CA (United States)

    2008-06-15

    The purpose of the study was to define magnetic resonance imaging (MRI) findings before and after contrast medium opacification of the knee joint in cadaveric specimens to demonstrate anatomical landmarks of the trochlear surface in relation to the neighboring structures, and to evaluate different MRI sequences in the detection of cartilage defects of the trochlear and patellar surface of the knee. The morphology and relationship of the proximal trochlear surface to the prefemoral fat of the distal femur were investigated by use of different MR sequences before and after intra-articular gadolinium administration into the knee joint in ten cadaveric knees. Anatomic sections were subsequently obtained. In addition, evaluation of the articular surface of the trochlea was performed by two independent observers. The cartilage surfaces were graded using a 2-point system, and results were compared with macroscopic findings. Of 40 cartilage surfaces evaluated, histopathologic findings showed 9 normal surfaces, 20 containing partial-thickness defects, and 11 containing full-thickness defects. Compared with macroscopic data, sensitivity of MR sequences for the two reviewers was between 17 and 90%; specificity, 75 and 100%; positive predictive value, 75 and 100%; negative predictive value, 20 and 100%, depending on patellar or trochlea lesions. Interobserver variability for the presence of disease, which was measured using the kappa statistic, was dependent on the MR sequence used between 0.243 and 0.851. Magnetic resonance imaging sequences can be used to evaluate the cartilage of the trochlear surface with less accuracy when compared with the results of grading the articular cartilage of the patella. (orig.)

  14. Development of a Novel Large Animal Model to Evaluate Human Dental Pulp Stem Cells for Articular Cartilage Treatment.

    Science.gov (United States)

    Fernandes, Tiago Lazzaretti; Shimomura, Kazunori; Asperti, Andre; Pinheiro, Carla Cristina Gomes; Caetano, Heloísa Vasconcellos Amaral; Oliveira, Claudia Regina G C M; Nakamura, Norimasa; Hernandez, Arnaldo José; Bueno, Daniela Franco

    2018-05-04

    Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. The ability of human Dental Pulp Stem Cells (DPSCs) to differentiate into chondroblasts in vitro suggests that this stem cell type may be useful for tissue bioengineering. However, we have yet to identify a study of large animal models in which DPSCs were used to repair articular cartilage. Therefore, this study aimed to describe a novel treatment for cartilage lesion with DPSCs on a large animal model. Mesenchymal stem cells (MSC) were obtained from deciduous teeth and characterized by flow cytometry. DPSCs were cultured and added to a collagen type I/III biomaterial composite scaffold. Brazilian miniature pig (BR-1) was used. A 6-mm diameter, full-thickness chondral defect was created in each posterior medial condyle. The defects were covered with scaffold alone or scaffold + DPSCs on the contralateral side. Animals were euthanized 6 weeks post-surgery. Cartilage defects were analyzed macroscopically and histology according to modified O'Driscoll scoring system. Flow cytometry confirmed characterization of DPSCs as MSCs. Macroscopic and histological findings suggested that this time period was reasonable for evaluating cartilage repair. To our knowledge, this study provides the first description of an animal model using DPSCs to study the differentiation of hyaline articular cartilage in vivo. The animals tolerated the procedure well and did not show clinical or histological rejection of the DPSCs, reinforcing the feasibility of this descriptive miniature pig model for pre-clinical studies.

  15. Effect of platelet-rich plasma on fibrocartilage, cartilage, and bone repair in temporomandibular joint.

    Science.gov (United States)

    Kütük, Nükhet; Baş, Burcu; Soylu, Emrah; Gönen, Zeynep Burçin; Yilmaz, Canay; Balcioğlu, Esra; Özdamar, Saim; Alkan, Alper

    2014-02-01

    The purpose of the present study was to explore the potential use of platelet-rich-plasma (PRP) in the treatment of temporomandibular joint osteoarthritis (TMJ-OA). Surgical defects were created bilaterally on the condylar fibrocartilage, hyaline cartilage, and bone to induce an osteoarthritic TMJ in rabbits. PRP was applied to the right joints of the rabbits (PRP group), and the left joints received physiologic saline (control group). After 4 weeks, the rabbits were sacrificed for histologic and scanning electron microscopy (SEM) examinations. The data were analyzed statistically. The new bone regeneration was significantly greater in the PRP group (P fibrocartilage and hyaline cartilage was greater in the PRP group, no statistically significant difference was found between the 2 groups. SEM showed better ultrastructural architecture of the collagen fibrils in the PRP group. PRP might enhance the regeneration of bone in TMJ-OA. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    James K. Hoffman

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

  18. Study on the treatment of cranio-facial bones fractures and defects

    International Nuclear Information System (INIS)

    Ge Zili

    2003-01-01

    Objective: To observe treatment results of 19 patients suffering from frontal sinus, nasal bone and zygomatic complex fractures. Methods: The 3-D imaging technique was obligatory diagnostic tools pre-operatively. The bicoronal incision was used as the standard surgical approach for all cases. After neurosurgical interventions frontal sinus were obliterated by lyophilized cartilage chips. Anatomic restoration was carried out. Transplantation of lyophilized cartilage was used to reconstruct defects of bone. Results: There was good external contour in all cases after average 21 months postoperatively. X-rays revealed a regular structure of bone trabecular and progressive calcification within the cartilage material post-operatively. Conclusions: 3-D imaging technique, bicoronal incision and lyophilized cartilage implantation can offer three advantages: precise diagnosis, improvement of treatment quality and decrease of operative injury

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

    Directory of Open Access Journals (Sweden)

    M Pei

    2011-11-01

    Full Text Available Cell-based therapy is a promising biological approach for the treatment of cartilage defects. Due to the small size of autologous cartilage samples available for cell transplantation in patients, cells need to be expanded to yield a sufficient cell number for cartilage repair. However, chondrocytes and adult stem cells tend to become replicatively senescent once they are expanded on conventional plastic flasks. Many studies demonstrate that the loss of cell properties is concomitant with the decreased cell proliferation capacity. This is a significant challenge for cartilage tissue engineering and regeneration. Despite much progress having been made in cell expansion, there are still concerns over expanded cell size and quality for cell transplantation applications. Recently, in vivo investigations in stem cell niches have suggested the importance of developing an in vitro stem cell microenvironment for cell expansion and tissue-specific differentiation. Our and other investigators’ work indicates that a decellularized stem cell matrix (DSCM may provide such an expansion system to yield large-quantity and high-quality cells for cartilage tissue engineering and regeneration. This review briefly introduces key parameters in an in vivo stem cell niche and focuses on our recent work on DSCM for its rejuvenating or reprograming effect on various adult stem cells and chondrocytes. Since research in DSCM is still in its infancy, we are only able to discuss some potential mechanisms of DSCM on cell proliferation and chondrogenic potential. Further investigations of the underlying mechanism and in vivo regeneration capacity will allow this approach to be used in clinics.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Mycobacterial antigens stimulate rheumatoid mononuclear cells to cartilage proteoglycan depletion

    NARCIS (Netherlands)

    Wilbrink, B.; Bijlsma, J. W.; Huber-Bruning, O.; van Roy, J. L.; den Otter, W.; van Eden, W.

    1990-01-01

    In a coculture with porcine articular cartilage explants unstimulated blood mononuclear cells (BMC) from patients with rheumatoid arthritis (RA), but not from healthy controls, induced proteoglycan depletion of dead cartilage. Specific stimulation of the RA BMC with Mycobacterium tuberculosis (MT),

  2. Can Glucosamine Supplements Protect My Knee Cartilage from Osteoarthritis?

    Science.gov (United States)

    ... cartilage in osteoarthritis? Can glucosamine supplements protect my knee cartilage from osteoarthritis? Answers from Brent A. Bauer, M.D. Study results on this question have been mixed, with some suggesting possible ...

  3. Properties of Cartilage on Micro- and Nanolevel

    Directory of Open Access Journals (Sweden)

    Sergei A. Chizhik

    2010-01-01

    Full Text Available Results of investigation of the elastic modulus for cartilage tissue using a technique of micro- and nanoindentation performed with help of an atomic force microscope are presented. SEM and AFM methods were applied to visualize a topography of surface layers of the entire cartilage and as well as its slices and thus to reveal features of the collagen fibers orientation. The technique used for a quantitative evaluation of the elastic modulus under compression against a ball microindenter (curvature radius - 350 micron and a nanoindenter (30 nm is described. It was shown that the cartilage behavior is highly stabile under the load if the entire composite structure of cartilage tissue is engaged into the deformation process. Tribological characteristics were investigated using the ball indenter oscillated by a tuning fork. Dependence of the friction coefficient from applied loads was obtained that revealed strong influence of an interstitial fluid on friction properties. Friction coefficient of a rat cartilage tissue as 0.08 was obtained using a developed plant prototype for tribological measurements based on the AFM construction.

  4. New Frontiers for Cartilage Repair and Protection.

    Science.gov (United States)

    Zaslav, Kenneth; McAdams, Timothy; Scopp, Jason; Theosadakis, Jason; Mahajan, Vivek; Gobbi, Alberto

    2012-01-01

    Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage.

  5. Articular cartilage: from formation to tissue engineering.

    Science.gov (United States)

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

    2016-05-26

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

  6. Magneto-therapy of human joint cartilage.

    Science.gov (United States)

    Wierzcholski, Krzysztof; Miszczak, Andrzej

    2017-01-01

    The topic of the present paper concerns the human joint cartilage therapy performed by the magnetic induction field. There is proved the thesis that the applied magnetic field for concrete cartilage illness should depend on the proper relative and concrete values of applied magnetic induction, intensity as well the time of treatment duration. Additionally, very important are frequencies and amplitudes of magnetic field as well as magnetic permeability of the synovial fluid. The research methods used in this paper include: magnetic induction field produced by a new Polish and German magneto electronic devices for the therapy of human joint cartilage diseases, stationary and movable magnetic applicators, magnetic bandage, ferrofluid injections, author's experience gained in Germany research institutes and practical results after measurements and information from patients. The results of this paper concern concrete parameters of time dependent electro-magnetic field administration during the joint cartilage therapy duration and additionally concern the corollaries which are implied from reading values gained on the magnetic induction devices. The main conclusions obtained in this paper are as follows: Time dependent magnetic induction field increases the dynamic viscosity of movable synovial fluid and decreases symptoms of cartilage illness for concrete intensity of magnetic field and concrete field line architecture. The ferrofluid therapy and phospholipids bilayer simultaneously with the administrated external electromagnetic field, increases the dynamic viscosity of movable synovial fluid.

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

    Science.gov (United States)

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

    2015-09-01

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

  8. Systemic immune markers characterizing early stages of rheumatoid arthritis

    NARCIS (Netherlands)

    Chalan, Paulina Luiza

    2016-01-01

    Rheumatoid arthritis is a chronic autoimmune disease occurring in ~1% of the world population. The main feature of the disease is ongoing joint inflammation, caused by immune cells and their soluble factors, leading to irreversible bone erosions and cartilage damage. Early treatment can halt

  9. Chemical changes demonstrated in cartilage by synchrotron infrared microspectroscopy in an antibody-induced murine model of rheumatoid arthritis

    Science.gov (United States)

    Croxford, Allyson M.; Selva Nandakumar, Kutty; Holmdahl, Rikard; Tobin, Mark J.; McNaughton, Don; Rowley, Merrill J.

    2011-06-01

    Collagen antibody-induced arthritis develops in mice following passive transfer of monoclonal antibodies (mAbs) to type II collagen (CII) and is attributed to effects of proinflammatory immune complexes, but transferred mAbs may react directly and damagingly with CII. To determine whether such mAbs cause cartilage damage in vivo in the absence of inflammation, mice lacking complement factor 5 that do not develop joint inflammation were injected intravenously with two arthritogenic mAbs to CII, M2139 and CIIC1. Paws were collected at day 3, decalcified, paraffin embedded, and 5-μm sections were examined using standard histology and synchrotron Fourier-transform infrared microspectroscopy (FTIRM). None of the mice injected with mAb showed visual or histological evidence of inflammation but there were histological changes in the articular cartilage including loss of proteoglycan and altered chondrocyte morphology. Findings using FTIRM at high lateral resolution revealed loss of collagen and the appearance of a new peak at 1635 cm-1 at the surface of the cartilage interpreted as cellular activation. Thus, we demonstrate the utility of synchrotron FTIRM for examining chemical changes in diseased cartilage at the microscopic level and establish that arthritogenic mAbs to CII do cause cartilage damage in vivo in the absence of inflammation.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-03-09

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

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

    Science.gov (United States)

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

    2013-01-01

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

  13. Preparation and characterization of a decellularized cartilage scaffold for ear cartilage reconstruction

    International Nuclear Information System (INIS)

    Utomo, Lizette; Pleumeekers, Mieke M; Van Osch, Gerjo J V M; Nimeskern, Luc; Stok, Kathryn S; Nürnberger, Sylvia; Hildner, Florian

    2015-01-01

    Scaffolds are widely used to reconstruct cartilage. Yet, the fabrication of a scaffold with a highly organized microenvironment that closely resembles native cartilage remains a major challenge. Scaffolds derived from acellular extracellular matrices are able to provide such a microenvironment. Currently, no report specifically on decellularization of full thickness ear cartilage has been published. In this study, decellularized ear cartilage scaffolds were prepared and extensively characterized. Cartilage decellularization was optimized to remove cells and cell remnants from elastic cartilage. Following removal of nuclear material, the obtained scaffolds retained their native collagen and elastin contents as well as their architecture and shape. High magnification scanning electron microscopy showed no obvious difference in matrix density after decellularization. However, glycosaminoglycan content was significantly reduced, resulting in a loss of viscoelastic properties. Additionally, in contact with the scaffolds, human bone-marrow-derived mesenchymal stem cells remained viable and are able to differentiate toward the chondrogenic lineage when cultured in vitro. These results, including the ability to decellularize whole human ears, highlight the clinical potential of decellularization as an improved cartilage reconstruction strategy. (paper)

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

    Directory of Open Access Journals (Sweden)

    M. S. Bozhokin

    2016-01-01

    to form a good hyaline cartilage resistant to high physical load in long term period.Thus, development of methods for articular cartilage repair has long ago went beyond the interests of clinical physicians, and only the close interdisciplinary cooperation of clinicians and specialists for cytology, molecular genetics and, probably, virology would enable replacement of a defect with a rigorous hyaline cartilage.

  15. MRI evaluation of acute articular cartilage injury of knee

    International Nuclear Information System (INIS)

    Zhang Jun; Wu Zhenhua; Fan Guoguang; Pan Shinong; Guo Qiyong

    2003-01-01

    Objective: To study the MRI manifestation of acute articular cartilage injury of knee for evaluating the extension and degree of the injury and guiding treatment. Methods: MRI of 34 patients with acute articular cartilage injury of knee within one day to fifteen days confirmed by arthroscopy and arthrotomy was reviewed and analyzed, with emphasis on articular cartilage and subchondral lesion. And every manifestation on MRI and that of arthroscopy and operation was compared. Results: The articular cartilage injury was diagnosed on MRI in 29 of 34 cases. Cartilage signal changes were found only in 4. The changes of cartilage shape were variable. Thinning of focal cartilage was showed in 3, osteochondral impaction in 3, creases of cartilage in 3, disrupted cartilage with fissuring in 13, cracks cartilage in 2, and cracks cartilage with displaced fragment in 1. Bone bruise and occult fracture were found only on MRI. Conclusion: The assessment of MRI and arthroscopy in acute articular cartilage injury are consistent. Combined with arthroscopy, MRI can succeed in assessing the extension and degree of acute articular injury and allowing treatment planning

  16. Spectrocolorimetric evaluation of repaired articular cartilage after a microfracture

    Directory of Open Access Journals (Sweden)

    Dohi Yoshihiro

    2008-09-01

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

  17. Joint homeostasis in tissue engineering for cartilage repair

    NARCIS (Netherlands)

    Saris, D.B.F.

    2002-01-01

    Traumatic joint damage, articular cartilage and the research into methods of restoring the articulation are not new topics of interest. For centuries, clinicians have recognized the importance of cartilage damage and sought ways of learning about the normal form and function of hyaline cartilage as

  18. Additive manufacturing for in situ repair of osteochondral defects

    International Nuclear Information System (INIS)

    Cohen, Daniel L; Lipton, Jeffrey I; Bonassar, Lawrence J; Lipson, Hod

    2010-01-01

    Tissue engineering holds great promise for injury repair and replacement of defective body parts. While a number of techniques exist for creating living biological constructs in vitro, none have been demonstrated for in situ repair. Using novel geometric feedback-based approaches and through development of appropriate printing-material combinations, we demonstrate the in situ repair of both chondral and osteochondral defects that mimic naturally occurring pathologies. A calf femur was mounted in a custom jig and held within a robocasting-based additive manufacturing (AM) system. Two defects were induced: one a cartilage-only representation of a grade IV chondral lesion and the other a two-material bone and cartilage fracture of the femoral condyle. Alginate hydrogel was used for the repair of cartilage; a novel formulation of demineralized bone matrix was used for bone repair. Repair prints for both defects had mean surface errors less than 0.1 mm. For the chondral defect, 42.8 ± 2.6% of the surface points had errors that were within a clinically acceptable error range; however, with 1 mm path planning shift, an estimated ∼75% of surface points could likely fall within the benchmark envelope. For the osteochondral defect, 83.6 ± 2.7% of surface points had errors that were within clinically acceptable limits. In addition to implications for minimally invasive AM-based clinical treatments, these proof-of-concept prints are some of the only in situ demonstrations to-date, wherein the substrate geometry was unknown a priori. The work presented herein demonstrates in situ AM, suggests potential biomedical applications and also explores in situ-specific issues, including geometric feedback, material selection and novel path planning techniques.

  19. Overexpression of hsa-miR-148a promotes cartilage production and inhibits cartilage degradation by osteoarthritic chondrocytes

    NARCIS (Netherlands)

    Vonk, L A; Kragten, A H M; Dhert, W J A; Saris, D B F; Creemers, L B

    OBJECTIVE: Hsa-miR-148a expression is decreased in Osteoarthritis (OA) cartilage, but its functional role in cartilage has never been studied. Therefore, our aim was to investigate the effects of overexpressing hsa-miR-148a on cartilage metabolism of OA chondrocytes. DESIGN: OA chondrocytes were

  20. Overexpression of hsa-miR-148a promotes cartilage production and inhibits cartilage degradation by osteoarthritic chondrocytes

    NARCIS (Netherlands)

    Vonk, Lucienne A.; Kragten, Angela H.M.; Dhert, Wouter J.; Saris, Daniël B.F.; Creemers, Laura B.

    2014-01-01

    Objective Hsa-miR-148a expression is decreased in OA cartilage, but its functional role in cartilage has never been studied. Therefore, our aim was to investigate the effects of overexpressing hsa-miR-148a on cartilage metabolism of OA chondrocytes. Design OA chondrocytes were transfected with a

  1. Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model

    Science.gov (United States)

    Bell, Angela D.; Hurtig, Mark B.; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D.

    2016-01-01

    Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan–NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro–computed tomography after 1 day (n = 1) and 6 months (n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage. PMID:28934884

  2. Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model.

    Science.gov (United States)

    Bell, Angela D; Hurtig, Mark B; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D

    2017-10-01

    Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan-NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro-computed tomography after 1 day ( n = 1) and 6 months ( n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage.

  3. Allogeneic MSCs and Recycled Autologous Chondrons Mixed in a One-Stage Cartilage Cell Transplantion: A First-in-Man Trial in 35 Patients.

    Science.gov (United States)

    de Windt, Tommy S; Vonk, Lucienne A; Slaper-Cortenbach, Ineke C M; Nizak, Razmara; van Rijen, Mattie H P; Saris, Daniel B F

    2017-08-01

    MSCs are known as multipotent mesenchymal stem cells that have been found capable of differentiating into various lineages including cartilage. However, recent studies suggest MSCs are pericytes that stimulate tissue repair through trophic signaling. Aimed at articular cartilage repair in a one-stage cell transplantation, this study provides first clinical evidence that MSCs stimulate autologous cartilage repair in the knee without engrafting in the host tissue. A phase I (first-in-man) clinical trial studied the one-stage application of allogeneic MSCs mixed with 10% or 20% recycled defect derived autologous chondrons for the treatment of cartilage defects in 35 patients. No treatment-related serious adverse events were found and statistically significant improvement in clinical outcome shown. Magnetic resonance imaging and second-look arthroscopies showed consistent newly formed cartilage tissue. A biopsy taken from the center of the repair tissue was found to have hyaline-like features with a high concentration of proteoglycans and type II collagen. DNA short tandem repeat analysis delivered unique proof that the regenerated tissue contained patient-DNA only. These findings support the hypothesis that allogeneic MSCs stimulate a regenerative host response. This first-in-man trial supports a paradigm shift in which MSCs are applied as augmentations or "signaling cells" rather than differentiating stem cells and opens doors for other applications. Stem Cells 2017;35:1984-1993. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  4. The effect of cartilage and bone density of mushroom-shaped, photooxidized, osteochondral transplants: an experimental study on graft performance in sheep using transplants originating from different species

    Directory of Open Access Journals (Sweden)

    Hilbe Monika

    2005-12-01

    Full Text Available Abstract Background Differences in overall performance of osteochondral photooxidized grafts were studied in accordance of their species origin and a new, more rigorous cleansing procedure using alcohol during preparation. Methods Photooxidized mushroom-shaped grafts of bovine, ovine, human and equine origin were implanted in the femoral condyles of 32 sheep (condyles: n = 64. No viable chondrocytes were present at the time of implantation. Grafts were evaluated at 6 months using plastic embedded sections of non-decalcified bone and cartilage specimens. Graft incorporation, the formation of cyst-like lesions at the base of the cartilage junction as well as cartilage morphology was studied qualitatively, semi-quantitatively using a score system and quantitatively by performing histomorphometrical measurements of percentage of bone and fibrous tissue of the original defects. For statistical analysis a factorial analysis of variance (ANOVA- test was applied. Results Differences of graft performance were found according to species origin and cleansing process during graft preparation. According to the score system cartilage surface integrity was best for equine grafts, as well as dislocation or mechanical stability. The equine grafts showed the highest percentage for bone and lowest for fibrous tissue, resp. cystic lesions. The new, more rigorous cleansing process decreased cartilage persistence and overall graft performance. Conclusion Performance of grafts from equine origin was better compared to bovine, ovine and human grafts. The exact reason for this difference was not proven in the current study, but could be related to differences in density of cartilage and subchondral bone between species.

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

    Directory of Open Access Journals (Sweden)

    R.B. Eleotério

    2015-04-01

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

  6. Quantitative magnetic resonance imaging of articular cartilage in osteoarthritis

    Directory of Open Access Journals (Sweden)

    G Blumenkrantz

    2007-05-01

    Full Text Available Magnetic resonance imaging of articular cartilage has recently been recognized as a tool for the characterization of cartilage morphology, biochemistry and function. In this paper advancements in cartilage imaging, computation of cartilage volume and thickness, and measurement of relaxation times (T2 and T1Ρ are presented. In addition, the delayed uptake of Gadolinium DTPA as a marker of proteoglycan depletion is also reviewed. The cross-sectional and longitudinal studies using these imaging techniques show promise for cartilage assessment and for the study of osteoarthritis.

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

    Science.gov (United States)

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

    2016-11-01

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