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Sample records for osteochondritis

  1. Role of Fresh Osteochondral Allografts for Large Talar Osteochondral Lesions.

    PubMed

    Gross, Christopher E; Adams, Samuel B; Easley, Mark E; Nunley, James A

    2016-01-01

    Osteochondral lesions of the talus, large or small, are challenging for the treating orthopaedic surgeon. These cartilage and bony defects can cause substantial pain and functional disability. Surgical treatment of small osteochondral lesions of the talus has been thoroughly explored and includes retrograde drilling, arthroscopic débridement and marrow stimulation, osteochondral autografting from cartilage/bone unit harvested from the ipsilateral knee (mosaicplasty), and autologous chondrocyte implantation. Although each of these reparative, replacement, or regenerative techniques has varying degrees of success, they may be insufficient for the treatment of large osteochondral lesions of the talus. Large-volume osteochondral lesions of the talus (>1.5 cm in diameter or >150 mm(2) in area) often involve a sizable portion of the weight-bearing section of the talar dome, medially or laterally. A fresh structural osteochondral allograft is a viable treatment option for large osteochondral lesions of the talus. PMID:27049198

  2. Osteochondritis Dissecans (OCD)

    MedlinePlus

    ... exercises or swimming instead as a means of physical therapy. Can osteochondritis dissecans be cured? Young people have the best chance of returning to their usual activity levels, although they might not be able to keep playing sports with repetitive motions, such as pitching in baseball. ...

  3. Role of Fresh Osteochondral Allografts for Large Talar Osteochondral Lesions.

    PubMed

    Gross, Christopher E; Adams, Samuel B; Easley, Mark E; Nunley, James A

    2016-01-01

    Osteochondral lesions of the talus, large or small, present a challenge to the treating orthopaedic surgeon. These cartilage and bony defects can cause substantial pain and functional disability. Surgical treatment of small lesions of the talus has been thoroughly explored and includes retrograde drilling, arthroscopic débridement and marrow stimulation, osteochondral autografting from cartilage/bone unit harvested from the ipsilateral knee (mosaicplasty), and autologous chondrocyte implantation. Although each of these reparative, replacement, or regenerative techniques has various degrees of success, they may be insufficient for the treatment of large osteochondral lesions of the talus. Large-volume osteochondral lesions of the talus (>1.5 cm in diameter or area >150 mm) often involve sizable portions of the weight-bearing section of the talar dome, medially or laterally. To properly treat these osteochondral lesions of the talus, a fresh structural osteochondral allograft is a viable treatment option. PMID:26589459

  4. How I Manage Osteochondritis Dissecans.

    ERIC Educational Resources Information Center

    DiStefano, Vincent J.

    1986-01-01

    Osteochondritis dissecans, a lesion found most often on the femur at the knee joint, occurs most frequently in active adolescents. This article describes treatment for preadolescents, adolescents, and adults. Osteochondritus dissecans of the patella is also presented. (MT)

  5. Osteochondral Lesions of Major Joints

    PubMed Central

    Durur-Subasi, Irmak; Durur-Karakaya, Afak; Yildirim, Omer Selim

    2015-01-01

    This paper provides information about osteochondral lesions (OCL) and example cases of OCL occurring in major joints, some of which are rarely seen. This simple tutorial is presented in question and answer format. PMID:26180500

  6. Osteochondritis dissecans of the talus

    PubMed Central

    ZANON, GIACOMO; DI VICO, GIOVANNI; MARULLO, MATTEO

    2014-01-01

    Osteochondritis dissecans (OCD) is an acquired idiopathic lesion of subchondral bone that can produce delamination and sequestration with or without articular cartilage involvement and instability. The cause of OCD is still debated: the most recognized etiology is the occurrence of repetitive micro-traumas associated with vascular impairment, causing progressive ankle pain and dysfunction in skeletally immature and young adult patients. Ankle OCD is classically located in the medial part of the talus, while lateral and posterior involvement is less frequent. Diagnosis of OCD, based on MRI findings, is quite straightforward; MRI examination can also be very useful for dating the defect and obtaining information about the associated bone bruise. Osteochondritis dissecans, if not recognized and treated appropriately, may lead to secondary osteoarthritis with pain and functional limitation. Surgical treatment is mandatory especially in young patients with unstable cartilage fragments. There are various surgical options: fixation, microfracture, or substitution using autologous chondrocyte implantation techniques. PMID:25606554

  7. Biomimetic biphasic scaffolds for osteochondral defect repair

    PubMed Central

    Li, Xuezhou; Ding, Jianxun; Wang, Jincheng; Zhuang, Xiuli; Chen, Xuesi

    2015-01-01

    The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed. Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues. For osteochondral reconstruction, one intact scaffold should be considered to support the regeneration of both cartilage and subchondral bone. Therefore, the biphasic scaffolds with the mimic structures of osteochondral tissues have been developed to close this chasm. A variety of biomimetic bilayer scaffolds fabricated from natural or synthetic polymers, or the ones loading with growth factors, cells, or both of them make great progresses in osteochondral defect repair. In this review, the preparation and in vitro and/or in vivo verification of bioinspired biphasic scaffolds are summarized and discussed, as well as the prospect is predicted. PMID:26816644

  8. Drilling techniques for osteochondritis dissecans.

    PubMed

    Heyworth, Benton E; Edmonds, Eric W; Murnaghan, M Lucas; Kocher, Mininder S

    2014-04-01

    Although the advanced stages of osteochondritis dissecans remain challenging to treat, most early-stage lesions in skeletally immature patients, if managed appropriately, can be stimulated to heal. For stable lesions that do not demonstrate adequate healing with nonoperative measures, such as activity modification, weight-bearing protection, or bracing, drilling of the subchondral bone has emerged as the gold standard of management. Several techniques of drilling exist, including transarticular drilling, retroarticular drilling, and notch drilling. Although each technique has been shown to be effective in small retrospective studies, higher-powered prospective comparative studies are needed to better elucidate their relative advantages and disadvantages. PMID:24698045

  9. Genetics Home Reference: familial osteochondritis dissecans

    MedlinePlus

    ... 23. Gentili C, Cancedda R. Cartilage and bone extracellular matrix. Curr Pharm Des. 2009;15(12):1334-48. ... in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans. Am ...

  10. Osteochondral lesions in pediatric and adolescent patients.

    PubMed

    Ghahremani, Shahnaz; Griggs, Rachel; Hall, Theodore; Motamedi, Kambiz; Boechat, M Ines

    2014-11-01

    Osteochondral lesions are acquired, potentially reversible injuries of the subchondral bone with or without associated articular cartilage involvement. Injury results in delamination and potential sequestration of the affected bone. Although an association with mechanical and traumatic factors has been established, the etiology remains poorly understood. These lesions commonly occur in the knee; articular surfaces of the elbow, ankle, hip, and shoulder are also affected. Osteochondral lesions are relatively common in children and adolescents, and the incidence is increasing. Prognosis of these lesions depends on stability, location, and size of the lesion.Imaging has an essential role in the diagnosis, staging, and management of osteochondral lesions. Many of these lesions are first diagnosed by plain film. MRI adds value by identifying unstable lesions that require surgical intervention. This review focuses on the clinical and imaging features of osteochondral lesions of the knee, elbow, and ankle. Imaging criteria for staging and management are also reviewed. PMID:25350829

  11. Concomitant Osteochondral Autograft Transplantation and Fixation of Osteochondral Fragment for Treatment of a Massive Osteochondritis Dissecans: A Report of 8-Year Follow-up Results

    PubMed Central

    Lee, Byung Ill

    2015-01-01

    Numerous procedures exist to treat osteochondritis dissecans (OCD); however, it remains a topic of debate which procedure is most ideal. When restoring a massive osteochondral defect, the use of only one procedure may not always allow complete filling of the defect. This case report presents a massive OCD with displaced osteochondral fragment and loose body in the knee joint that occupied almost all of the weight bearing area of the medial femoral condyle and was treated with concomitant osteochondral autograft transplantation and fixation of displaced osteochondral fragment. To our knowledge, this is a rare report on OCD treated with concomitant osteochondral autograft transplantation and fixation of displaced osteochondral fragment. At 8 years after surgery, the clinical outcome was excellent, and radiographs revealed congruence of the medial femoral condyle. The patient returned to sports activities. In massive and complex OCD lesions, individual techniques have limitations. Two or more techniques are needed to increase the rate of success. PMID:26672950

  12. Strategies for osteochondral repair: Focus on scaffolds

    PubMed Central

    Seo, Seog-Jin; Mahapatra, Chinmaya; Singh, Rajendra K; Knowles, Jonathan C

    2014-01-01

    Interest in osteochondral repair has been increasing with the growing number of sports-related injuries, accident traumas, and congenital diseases and disorders. Although therapeutic interventions are entering an advanced stage, current surgical procedures are still in their infancy. Unlike other tissues, the osteochondral zone shows a high level of gradient and interfacial tissue organization between bone and cartilage, and thus has unique characteristics related to the ability to resist mechanical compression and restoration. Among the possible therapies, tissue engineering of osteochondral tissues has shown considerable promise where multiple approaches of utilizing cells, scaffolds, and signaling molecules have been pursued. This review focuses particularly on the importance of scaffold design and its role in the success of osteochondral tissue engineering. Biphasic and gradient composition with proper pore configurations are the basic design consideration for scaffolds. Surface modification is an essential technique to improve the scaffold function associated with cell regulation or delivery of signaling molecules. The use of functional scaffolds with a controllable delivery strategy of multiple signaling molecules is also considered a promising therapeutic approach. In this review, we updated the recent advances in scaffolding approaches for osteochondral tissue engineering. PMID:25343021

  13. Hip Arthroscopic Osteochondral Autologous Transplantation for Treating Osteochondritis Dissecans of the Femoral Head

    PubMed Central

    Kubo, Takanori; Utsunomiya, Hajime; Watanuki, Makoto; Hayashi, Hidetoshi; Sakai, Akinori; Uchida, Soshi

    2015-01-01

    Osteochondritis dissecans (OCD) of the femoral head is not a common source of hip pain. Hip arthroscopy is becoming a more frequent indication for intra-articular pathologies of the hip. Osteochondral autologous transplantation is a promising technique that theoretically can reconstruct osteochondral lesions of the femoral head. We describe our technique for arthroscopic antegrade osteochondral autologous transplantation for the treatment of OCD of the femoral head. The advantages of this technique include that it is a less invasive method with the ability to assess and treat intra-articular pathologies associated with OCD of the femoral head at same time. Case series and outcomes after this technique are not currently reported in the literature; however, it could be a less invasive method and provide favorable clinical outcomes for patients with OCD lesions of the femoral head. PMID:26870645

  14. Osteochondral defects in the ankle: why painful?

    PubMed Central

    Reilingh, Mikel L.; Zengerink, Maartje; van Bergen, Christiaan J. A.

    2010-01-01

    Osteochondral defects of the ankle can either heal and remain asymptomatic or progress to deep ankle pain on weight bearing and formation of subchondral bone cysts. The development of a symptomatic OD depends on various factors, including the damage and insufficient repair of the subchondral bone plate. The ankle joint has a high congruency. During loading, compressed cartilage forces its water into the microfractured subchondral bone, leading to a localized high increased flow and pressure of fluid in the subchondral bone. This will result in local osteolysis and can explain the slow development of a subchondral cyst. The pain does not arise from the cartilage lesion, but is most probably caused by repetitive high fluid pressure during walking, which results in stimulation of the highly innervated subchondral bone underneath the cartilage defect. Understanding the natural history of osteochondral defects could lead to the development of strategies for preventing progressive joint damage. PMID:20151110

  15. Osteochondritis dissecans on the medial aspect of the humeral head

    PubMed Central

    Mima, Yuichiro; Matsumura, Noboru; Ogawa, Kiyohisa; Iwamoto, Takuji; Ochi, Kensuke; Sato, Kazuki; Toyama, Yoshiaki

    2016-01-01

    The case of a 29-year-old man who had osteochondritis dissecans on the medial aspect of the humeral head is reported. Repetitive micro-trauma at a low elevated arm position was thought to have induced the osteochondral lesion.

  16. Multiphasic construct studied in an ectopic osteochondral defect model

    PubMed Central

    Jeon, June E.; Vaquette, Cédryck; Theodoropoulos, Christina; Klein, Travis J.; Hutmacher, Dietmar W.

    2014-01-01

    In vivo osteochondral defect models predominantly consist of small animals, such as rabbits. Although they have an advantage of low cost and manageability, their joints are smaller and more easily healed compared with larger animals or humans. We hypothesized that osteochondral cores from large animals can be implanted subcutaneously in rats to create an ectopic osteochondral defect model for routine and high-throughput screening of multiphasic scaffold designs and/or tissue-engineered constructs (TECs). Bovine osteochondral plugs with 4 mm diameter osteochondral defect were fitted with novel multiphasic osteochondral grafts composed of chondrocyte-seeded alginate gels and osteoblast-seeded polycaprolactone scaffolds, prior to being implanted in rats subcutaneously with bone morphogenic protein-7. After 12 weeks of in vivo implantation, histological and micro-computed tomography analyses demonstrated that TECs are susceptible to mineralization. Additionally, there was limited bone formation in the scaffold. These results suggest that the current model requires optimization to facilitate robust bone regeneration and vascular infiltration into the defect site. Taken together, this study provides a proof-of-concept for a high-throughput osteochondral defect model. With further optimization, the presented hybrid in vivo model may address the growing need for a cost-effective way to screen osteochondral repair strategies before moving to large animal preclinical trials. PMID:24694896

  17. Rabbit Trochlear Model of Osteochondral Allograft Transplantation

    PubMed Central

    To, Nhat; Curtiss, Shane; Neu, Corey P; Salgado, Christopher J; Jamali, Amir A

    2011-01-01

    Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft–host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host–graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host–graft bone interface available for analysis. PMID:22330350

  18. Emerging genetic basis of osteochondritis dissecans.

    PubMed

    Bates, J Tyler; Jacobs, John C; Shea, Kevin G; Oxford, Julia Thom

    2014-04-01

    Genome-wide association studies (GWAS) provide an unbiased approach in the identification of genes that increase the risk for osteochondritis dissecans (OCD). Recent GWAS in humans, horses, and pigs are reviewed and genes identified. The identified genes tended to cluster with respect to function and biologic processes. GWAS in humans are a critical next step in the effort to provide a better understanding of the causes of OCD, which will, in turn, allow preventive strategies for treatment of adolescents and young adults who are at risk for the development of degenerative joint disease due to the effects of OCD. PMID:24698039

  19. Osteochondral Autograft Transplantation Surgery for Metacarpal Head Defects.

    PubMed

    Kitay, Alison; Waters, Peter M; Bae, Donald S

    2016-03-01

    Post-traumatic osteonecrosis of the metacarpal head is a challenging problem, particularly in younger patients in whom arthroplasty may not be a durable option. Although several osteochondral reconstructive options have been proposed, some are associated with considerable donor site morbidity and/or require the use of internal fixation. We present an application of osteochondral autograft transplantation surgery as a treatment option for focal metacarpal head lesions. An osteochondral plug from the non-weight-bearing articular surface of the knee is transferred and press-fit to resurface a focal metacarpal head defect. The technical pearls and pitfalls are reviewed, and an illustrative case is presented. PMID:26803571

  20. Osteochondritis dissecans of the capitellum in adolescents.

    PubMed

    van Bergen, Christiaan Ja; van den Ende, Kimberly Im; Ten Brinke, Bart; Eygendaal, Denise

    2016-02-18

    Osteochondritis dissecans (OCD) is a disorder of articular cartilage and subchondral bone. In the elbow, an OCD is localized most commonly at the humeral capitellum. Teenagers engaged in sports that involve repetitive stress on the elbow are at risk. A high index of suspicion is warranted to prevent delay in the diagnosis. Plain radiographs may disclose the lesion but computed tomography and magnetic resonance imaging are more accurate in the detection of OCD. To determine the best treatment option it is important to differentiate between stable and unstable OCD lesions. Stable lesions can be initially treated nonoperatively with elbow rest or activity modification and physical therapy. Unstable lesions and stable lesions not responding to conservative therapy require a surgical approach. Arthroscopic debridement and microfracturing has become the standard initial procedure for treatment of capitellar OCD. Numerous other surgical options have been reported, including internal fixation of large fragments and osteochondral autograft transfer. The aim of this article is to provide a current concepts review of the etiology, clinical presentation, diagnosis, treatment, and outcomes of elbow OCD. PMID:26925381

  1. Osteochondritis dissecans of the capitellum in adolescents

    PubMed Central

    van Bergen, Christiaan JA; van den Ende, Kimberly IM; ten Brinke, Bart; Eygendaal, Denise

    2016-01-01

    Osteochondritis dissecans (OCD) is a disorder of articular cartilage and subchondral bone. In the elbow, an OCD is localized most commonly at the humeral capitellum. Teenagers engaged in sports that involve repetitive stress on the elbow are at risk. A high index of suspicion is warranted to prevent delay in the diagnosis. Plain radiographs may disclose the lesion but computed tomography and magnetic resonance imaging are more accurate in the detection of OCD. To determine the best treatment option it is important to differentiate between stable and unstable OCD lesions. Stable lesions can be initially treated nonoperatively with elbow rest or activity modification and physical therapy. Unstable lesions and stable lesions not responding to conservative therapy require a surgical approach. Arthroscopic debridement and microfracturing has become the standard initial procedure for treatment of capitellar OCD. Numerous other surgical options have been reported, including internal fixation of large fragments and osteochondral autograft transfer. The aim of this article is to provide a current concepts review of the etiology, clinical presentation, diagnosis, treatment, and outcomes of elbow OCD. PMID:26925381

  2. Treatment of unstable osteochondritis dissecans in adults with autogenous osteochondral grafts (Mosaicplasty): long-term results

    PubMed Central

    RONGA, MARIO; STISSI, PLACIDO; LA BARBERA, GIUSEPPE; VALOROSO, MARCO; ANGERETTI, GLORIA; GENOVESE, EUGENIO; CHERUBINO, PAOLO

    2015-01-01

    Purpose the unstable osteochondritis dissecans (OCD-type II and III according to the ICRS classification) of the knee largher than > 2.5 cm2 in adults are uncommon lesions and there is no consensus on how to treat them. Medium-term studies have reported good results using autogenous osteochondral plugs (mosaicplasty). The aim of this study is to analyze the long-term results of this technique for the treatment of unstable OCD in a selected group of adult patients. Methods four patients with OCD at either one of the femoral condyles were included in this prospective study. The average age was 21.2 years (range, 18–24 years). The OCD lesions were classified as type II in three patients and type III in one patient and the average size was 3.8 cm2 (range, 2.55–5.1 cm2). The lesions were treated in situ with a variable number of autogenous osteochondral plugs (Ø 4.5 mm2). The Modified Cincinnati, Lysholm II and Tegner scores were used for clinical and functional evaluation. Magnetic resonance arthrography (MRA) was performed before surgery and at 2, 5 and 10 years after surgery. A modified MOCART score was used to evaluate MRA findings. Results the average follow-up duration was ten years and 6 months (range, 10–11 years). No complications occurred. At the final follow-up, all scores (clinical, functional and MOCART) improved. In all but one of the patients MRA showed complete osteochondral repair. Conclusions the fixation of large and unstable OCD lesions with mosaicplasty may be a good option for treating type II or III OCD lesions in adults. The advantages of this technique include stable fixation, promotion of blood supply to the base of the OCD fragment, and grafting of autologous cancellous bone that stimulates healing with preservation of the articular surface. Level of evidence Level IV, therapeutic case series. PMID:26904522

  3. Novel nanostructured scaffold for osteochondral regeneration: pilot study in horses.

    PubMed

    Kon, E; Mutini, A; Arcangeli, E; Delcogliano, M; Filardo, G; Nicoli Aldini, N; Pressato, D; Quarto, R; Zaffagnini, S; Marcacci, M

    2010-06-01

    The present in vivo preliminary experiment is aimed at testing mechanical and biological behaviour of a new nano-structured composite multilayer biomimetic scaffold for the treatment of chondral and osteochondral defects. The three-dimensional biomimetic scaffold (Fin-Ceramica Faenza S.p.A., Faenza-Italy) was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles, in two configurations, bi- and tri-layered, to reproduce, respectively, chondral and osteochondral anatomy. Chondral defects (lateral condyle) and deep osteochondral defects (medial condyle) were made in the distal epiphysis of the third metacarpal bone of both forelimbs of two adult horses and treated respectively with the chondral and osteochondral grafts. Both animals were euthanised six months follow up. The images obtained at the second look arthroscopy evaluation, performed two months after surgery, demonstrated good filling of the chondral and osteo-chondral defects without any inflammatory reaction around and inside the lesions. At the histological analysis the growth of trabecular bone in the osteochondral lesion was evident. Only in one case, the whole thickness of the osteochondral lesion was filled by fibrocartilaginous tissue. The formation of a tidemark line was evident at the interface with the newly formed bone. Newly formed fibrocartilaginous tissue was present in the area of the chondral defect. Initial alignment of the collagen fibres was recognisable with polarised light in both groups. The results of the present pilot study showed that this novel osteochondral and chondral scaffold may act as a suitable matrix to facilitate orderly regeneration of bone and hyaline-like cartilage. PMID:20049745

  4. Autologous tissue transplantations for osteochondral repair.

    PubMed

    Christensen, Bjørn Borsøe

    2016-04-01

    Articular cartilage forms the articulating surface of synovial joints. Along with the synovial fluid it facilitates near frictionless movement in healthy joints. Injuries to articular cartilage in the knee are frequent and can lead to severe osteoarthritis, which is expected to affect 25% of the adult population by 2030. Hyaline cartilage does not regenerate spontaneously when injured and the current clinical treatment methods suffer from high cost and relatively high failure rates. This calls for new treatment methods to be developed. The backbone of developing new treatment methods for cartilage injuries is a reliable, cost-effective, clinically relevant large animal model. Study 1 aimed at developing such a model. We hypothesized that in the Göttingen minipig, the repair response of a selection of treatment methods would be similar to what is found in a clinical setting, and that two defects per knee, rather than one, could be applied without affecting the repair outcome. We found that the outcomes of the applied treatments were consistent with the outcomes in clinical studies. Furthermore, the use of two defects per knee did not have any significant effect on the repair response. The Göttingen minipig model was easy to handle, cost-effective, and provided a predictable repair response. Based on this study the use of two defects per knee in male Göttingen minipigs is recommended. The model has been implemented as the standard animal model for cartilage research at the Orthopedic Research Laboratory, Aarhus University Hospital. Synthetic osteochondral scaffolds represent an off-the-shelf, one-step treatment method, and preliminary clinical results have been promising. However, MRI investigations have shown issues related to subchondral healing. In study 2 we aimed at evaluating the osteochondral repair in 10 patients treated with the MaioRegen synthetic scaffold. Of the ten patients, two patients were re-operated due to treatment failure. CT imaging revealed that none of the eight remaining patients had complete regeneration of the subchondral bone. At 2.5 years, 6/8 patients had no or very limited (< 10%) bone formation in the defects and 2/8 had 50-75% bone formation in the treated defect. MRI showed no improvement at either one or 2.5 years compared with baseline. Clinical outcome scores were improved at 2.5 years. These results raise serious concerns about the biological repair potential of the MaioRegen scaffold. The use of the MaioRegen scaffold has been discontinued in Denmark as a result of this study. An alternative treatment approach for osteochondral lesions is combined transplantation of autologous bone graft and cartilage fragments, embedded in fibrin glue. In study 3 we investigated the early biological and clinical outcome of autologous dual-tissue transplantation (ADTT). ADTT is a combined autologous bone and cartilage chips transplantation for treatment of osteochondral injuries. It is easily applicable and bypasses the need for costly cell culturing or synthetic materials. After one year, all eight patients had significant improvements on MRI, CT and all clinical outcome scores. This study establishes ADTT as a promising, low-cost, treatment option for osteochondral injuries in the knee. To investigate the role of the implanted cartilage chips, we tested the isolated effect of the chips in the newly developed Göttingen minipig model. In study 4 we compared ADTT with autologous bone graft alone. The hypothesis was that the presence of cartilage chips would improve the quality of the repair tissue. Twelve Göttingen minipigs were included, and follow-up time was six and 12 months. Follow-up consisted of histomorphometry, immunohistochemistry, semi-quantitative scoring and CT. There was significantly more hyaline cartilage in the ADTT group compared with the autologous bone graft group at both six and 12 months. At both six and 12 months there were significantly more fibrocartilage in the ADTT group compared with the ABG group. The presence of cartilage chips in an osteochondral defect facilitated the formation of fibrocartilage as opposed to fibrous tissue at both six and 12 months. This study substantiates the chondrogenic role of cartilage chips in osteochondral defects, but questions the widely accepted repair mechanism involved in cartilage chip treatment methods. Further studies on the repair mechanism(s) involved are needed to improve the clinical application of autologous cartilage chips. PMID:27034191

  5. Emerging genetic basis of osteochondritis dissecans

    PubMed Central

    Bates, J. Tyler; Jacobs, John C.; Shea, Kevin G.; Oxford, Julia Thom

    2014-01-01

    Genome-wide association studies provide an unbiased approach in the identification of genes that increase the risk for osteochondritis dissecans (OCD). OCD is a disorder of the bone and cartilage that affects humans, horses, pigs, dogs, and other mammals. Recent genome-wide association studies in humans, horses, and pigs are reviewed and genes identified. The identified genes tended to cluster with respect to function and biological processes such as the protein secretion pathway, extracellular matrix molecules, and growth plate maturation. Genome-wide association studies in humans are a critical next step in the effort to provide a better understanding of the causes of OCD, which will, in turn, allow preventive strategies for treatment of adolescent and young adults who are at risk for the development of degenerative joint disease due to the effects of OCD. PMID:24698039

  6. Osteochondral diseases and fibrodysplasia ossificans progressiva.

    PubMed

    Morales-Piga, Antonio; Kaplan, Frederick S

    2010-01-01

    Osteochondrodysplasias like thanatophoric dysplasia, osteogenesis imperfecta, achondroplasia, and other genetic skeletal disorders like fibrodysplasia ossificans progressiva are infrequently seen in clinical practice. In cases of sporadic achondroplasia as well as in fibrodysplasia ossificans progressiva, there is a strong association with paternal age, a relationship that is less evident in other genetic osteochondral diseases. No other constitutional or environmental factor has proven to be associated with these disorders. The use of prenatal ultrasonography as a routine component of prenatal care is crucial in the early suspicion of osteochondrodysplasias whereas definitive diagnosis is usually obtained by pre-natal molecular analysis. In the case of fibrodysplasia ossificans progressiva, recognition of congenital great toe malformations associated with rapidly-appearing soft tissue swelling is sufficient to make the proper clinical diagnosis, which can be confirmed by genetic testing. Large regional centres will improve diagnosis performance, provide accurate genetic counselling, and ensure an integral assistance for these often severe and incapacitating conditions. PMID:20824454

  7. Osteochondral Allograft Transplantation in the Knee.

    PubMed

    Zouzias, Ioannis C; Bugbee, William D

    2016-06-01

    The technique of osteochondral allograft (OCA) transplantation has been used to treat a wide spectrum of cartilage deficiencies in the knee. Its use has been supported by basic science and clinical studies that show it is a safe and effective treatment option. What sets fresh OCA transplantation apart from other cartilage procedures in the knee, is the ability to treat large defects with mature hyaline cartilage. Studies looking at transplantation of fresh OCAs in the general population have shown reliable pain relief and return to activities of daily living. Reports of cartilage injuries in athletes have risen over the years and more research is needed in evaluating the successfulness of OCA transplantation in the athletic population. PMID:27135291

  8. Surgical Treatment for Osteochondritis Dissecans of the Capitellum

    PubMed Central

    Smith, Matthew V.; Bedi, Asheesh; Chen, Neal C.

    2012-01-01

    Context: Osteochondritis dissecans (OCD) of the capitellum is most often seen in adolescents who participate in sports that involve repetitive loading of the elbow. Unstable defects typically require surgical intervention that involves fragment fixation, debridement, or reconstruction with an osteochondral autograft transfer. Optimum surgical management of unstable defects remains controversial. Type of Study: Clinical review. Evidence Acquisition: Relevant articles published after 1992 were identified using MEDLINE, the EMBASE database, and the Cochrane Library. Results: Both debridement and osteochondral autograft transfer for treatment of capitellar OCD lesions result in good short- and midterm outcomes with a high rate of return to sports. Larger defects involving more than 50% of the articular surface or involving the lateral margin of the capitellum may have worse outcomes after debridement and may be better treated with fragment fixation or osteochondral autograft transfer. Conclusions: High-level evidence is lacking to determine the superiority of debridement or osteochondral autograft transfer for the treatment of capitellar OCD lesions. A prospective longitudinal multicenter study, using validated outcome measures, that enrolls a large number of patients is needed to establish optimal treatment for unstable capitellar OCD lesions. PMID:23016116

  9. Surgical treatment for osteochondritis dessicans of the knee.

    PubMed

    Winthrop, Zachary; Pinkowsky, Gregory; Hennrikus, William

    2015-12-01

    Osteochondritis dissecans (OCD) of the knee is a disease of the subchondral bone with secondary injury to the overlying articular cartilage. OCD lesions are generally categorized as juvenile-growth plates open-or adult-growth plates closed. This maturity-based classification scheme has a prognostic value in that many juvenile OCD lesions will heal with conservative care while most symptomatic adult OCD lesions need surgical intervention. OCD can result in pain, knee joint effusions, loose body formation, and arthritis. Short-term treatment goals include pain and symptom resolution while the long-term goal is to minimize arthritis. Surgical options include debridement, drilling, microfracture, reduction and fixation, autograft osteochondral transplantation, autologous chondrocyte implantation, and allograft osteochondreal transplantation. PMID:26409885

  10. Osteochondritis Dissecans of the Capitellum: Diagnosis and Treatment.

    PubMed

    Glait, Sergio; Rokito, Andrew; Bosco, Joseph; Jazrawi, Laith

    2016-03-01

    Osteochondritis dissecans (OCD) of the capitellum is an articular cartilage lesion commonly affecting young adolescents. The exact mechanism for the development of these lesions is still uncertain; however, both traumatic and vascular etiologies have been described. Careful physical examination in conjunction with appropriate diagnostic studies helps the surgeon to classify these lesions as stable or unstable and leads to proper management. There is a diverse array of treatments available for OCD lesions of the capitellum, including fragment excision or fixation, bone marrow stimulation, and osteochondral autograft transplantation. This review helps the orthopaedic surgeon understand the diagnosis and management options available for OCD lesions of the capitellum. PMID:26977547

  11. The knee: internal fixation techniques for osteochondritis dissecans.

    PubMed

    Grimm, Nathan L; Ewing, Christopher K; Ganley, Theodore J

    2014-04-01

    For the athlete with a newly diagnosed osteochondritis dissecans of the knee, the first step in formulating a treatment plan is determining the stability of the lesion. When the lesion is found to be unstable but salvageable, several methods for fixation are available. Fixation of osteochondritis dissecans in the athletic population has been described and each has its own advantages and disadvantages. Determining the most appropriate method for fixation depends on several variables and should include the athlete's level of play, sport, and overall goals. PMID:24698046

  12. [Femoral head chondroblastoma and reconstruction with osteochondral allograft. Case report].

    PubMed

    Orlando-Díaz, C; Guzmán-Vargas, R; Rincon-Cardozo, D F; Mantilla-León, N; Camacho-Casas, J A

    2014-01-01

    Femoral head chondroblastoma is an infrequent tumor, accounting for approximately 1-2% of benign bone tumors. It occurs more frequently in young male patients. It's most frequent locations include the proximal humerus, proximal femur, distal femur and proximal tibia. The femoral head is the third most frequent site of this tumor. There is no specific treatment for this entity; reported treatments range from acetabular osteotomies and osteochondral grafts, to vascularized fibular grafts, all of them with good results. However, this tumor is clinically unpredictable if left untreated. We report a case managed with osteochondral graft and followed-up for three years after the surgical procedure. PMID:26016291

  13. Glenoid dysplasia and osteochondritis dissecans in a cat

    PubMed Central

    Schwarze, Rebecca A.; Tano, Cheryl A.; Carroll, Vincent W.

    2015-01-01

    A 2-year-old Maine coon cat was presented for a right forelimb lameness. Computed tomography of the shoulder revealed a shallow glenoid, osteophyte deposition at the caudal humeral head and medial glenoid, and an intra-articular osseous body. This cat had glenoid dysplasia and osteochondritis dissecans of the glenoid. PMID:26130839

  14. Arthroscopic Approach to Osteochondral Defects, Impingement, and Instability.

    PubMed

    Walker, Roger; Kunkle, William Aaron; Carreira, Dominic S

    2015-10-01

    Osteochondral defects, impingement, and instability of the ankle are common injuries in athletes. In this article, we review these diagnoses and their treatment options, with a focus on arthroscopic approaches. The treatment options continue to evolve, supported by innovation and outcome studies. In this article, we describe the advantages and disadvantages of both open and arthroscopic treatments using published evidence. PMID:26409590

  15. Glenoid dysplasia and osteochondritis dissecans in a cat.

    PubMed

    Schwarze, Rebecca A; Tano, Cheryl A; Carroll, Vincent W

    2015-07-01

    A 2-year-old Maine Coon cat was presented for a right forelimb lameness. Computed tomography of the shoulder revealed a shallow glenoid, osteophyte deposition at the caudal humeral head and medial glenoid, and an intra-articular osseous body. This cat had glenoid dysplasia and osteochondritis dissecans of the glenoid. PMID:26130839

  16. OSTEOCHONDRITIS DISSECANS OF THE KNEE: DIAGNOSIS AND TREATMENT

    PubMed Central

    Mestriner, Luiz Aurélio

    2015-01-01

    Osteochondritis dissecans (OCD) is a pathological process affecting the subchondral bone of the knee in children and adolescents with open growth plates (juvenile OCD) and young adults with closed growth plates (adult OCD). It may lead to secondary effects on joint cartilage, such as pain, edema, possible formation of free bodies and mechanical symptoms, including joint locking. OCD may lead to degenerative changes may develop if left untreated. This article presents a review and update on this problem, with special emphasis on diagnosis and treatment. The latter may include either conservative methods, which show more predictable results for juvenile OCD, or various surgical methods, which include reparative techniques like isolated removal of the fragment, bone drilling and fixation of the osteochondral fragments, and restorative techniques like microfractures, autologous osteochondral transplantation (mosaicplasty), autologous chondrocyte implantation and fresh osteochondral allograft, depending on lesion stability, lesion viability, skeletal maturity and OCD process location. Recent assessments on the results from several types of treatment have shown that there is a lack of studies with reliable levels of evidence and have suggested that further multicenter prospective randomized and controlled studies on management of this disease should be conducted.

  17. Arthroscopic Allograft Cartilage Transfer for Osteochondral Defects of the Talus

    PubMed Central

    Min, Kyong S.; Ryan, Paul M.

    2015-01-01

    Arthroscopic treatment of osteochondral defects is well established but has had mixed results in larger lesions and revision operations. Particulated allograft cartilage transfer may provide an arthroscopic option for lesions that would otherwise have been treated through open approaches or osteotomies. The procedure is performed under noninvasive distraction with standard arthroscopic portals. PMID:26052496

  18. Diagnosing, planning and evaluating osteochondral ankle defects with imaging modalities

    PubMed Central

    van Bergen, Christiaan JA; Gerards, Rogier M; Opdam, Kim TM; Terra, Maaike P; Kerkhoffs, Gino MMJ

    2015-01-01

    This current concepts review outlines the role of different imaging modalities in the diagnosis, preoperative planning, and follow-up of osteochondral ankle defects. An osteochondral ankle defect involves the articular cartilage and subchondral bone (usually of the talus) and is mostly caused by an ankle supination trauma. Conventional radiographs are useful as an initial imaging tool in the diagnostic process, but have only moderate sensitivity for the detection of osteochondral defects. Computed tomography (CT) and magnetic resonance imaging (MRI) are more accurate imaging modalities. Recently, ultrasonography and single photon emission CT have been described for the evaluation of osteochondral talar defects. CT is the most valuable modality for assessing the exact location and size of bony lesions. Cartilage and subchondral bone damage can be visualized using MRI, but the defect size tends to be overestimated due to bone edema. CT with the ankle in full plantar flexion has been shown a reliable tool for preoperative planning of the surgical approach. Postoperative imaging is useful for objective assessment of repair tissue or degenerative changes of the ankle joint. Plain radiography, CT and MRI have been used in outcome studies, and different scoring systems are available. PMID:26716090

  19. Functional tissue engineering of chondral and osteochondral constructs.

    PubMed

    Lima, Eric G; Mauck, Robert L; Han, Shelley H; Park, Seonghun; Ng, Kenneth W; Ateshian, Gerard A; Hung, Clark T

    2004-01-01

    Due to the prevalence of osteoarthritis (OA) and damage to articular cartilage, coupled with the poor intrinsic healing capacity of this avascular connective tissue, there is a great demand for an articular cartilage substitute. As the bearing material of diarthrodial joints, articular cartilage has remarkable functional properties that have been difficult to reproduce in tissue-engineered constructs. We have previously demonstrated that by using a functional tissue engineering approach that incorporates mechanical loading into the long-term culture environment, one can enhance the development of mechanical properties in chondrocyte-seeded agarose constructs. As these gel constructs begin to achieve material properties similar to that of the native tissue, however, new challenges arise, including integration of the construct with the underlying native bone. To address this issue, we have developed a technique for producing gel constructs integrated into an underlying bony substrate. These osteochondral constructs develop cartilage-like extracellular matrix and material properties over time in free swelling culture. In this study, as a preliminary to loading such osteochondral constructs, finite element modeling (FEM) was used to predict the spatial and temporal stress, strain, and fluid flow fields within constructs subjected to dynamic deformational loading. The results of these models suggest that while chondral ("gel alone") constructs see a largely homogenous field of mechanical signals, osteochondral ("gel bone") constructs see a largely inhomogeneous distribution of mechanical signals. Such inhomogeneity in the mechanical environment may aid in the development of inhomogeneity in the engineered osteochondral constructs. Together with experimental observations, we anticipate that such modeling efforts will provide direction for our efforts aimed at the optimization of applied physical forces for the functional tissue engineering of an osteochondral articular cartilage substitute. PMID:15299288

  20. Osteochondral repair with synovial membrane-derived mesenchymal stem cells

    PubMed Central

    LI, HONG; QIAN, JUNCHAO; CHEN, JIWU; ZHONG, KAI; CHEN, SHIYI

    2016-01-01

    The aim of the present study was to analyze cartilage repair tissue quality following synovial membrane-derived mesenchymal stem cell (SMSC) transplantation in a rabbit osteochondral defect. A total of 15 New Zealand white rabbits were randomly distributed into three groups (n=5 in each group). In group 1, an osteochondral defect model was established in the right knee trochlea, prior to transplantation with SMSCs (SMSC group). In group 2, an osteochondral defect model was established without further treatment (control group). Group 3 did not undergo osteochondral defect model establishment and served as the sham control (normal group). All animals were sacrificed 12 weeks following the surgical procedures for magnetic resonance imaging and histological examination. No significant differences were observed between the control and SMSC group in the macroscopic score (P>0.05), the 2D magnetic resonance observation of cartilage repair tissue score (P>0.05) or the modified O'Driscoll scale (P>0.05). Compared with the control group, a significant improvement in tissue quality was observed in the SMSCs group postoperatively. The repair tissue of the SMSCs group had a shorter T2, compared with that of the control group, although no significant difference was detected (P>0.05). Furthermore, the apparent diffusion coefficient in the repair tissue of the SMSC group had a significantly lower value, compared with that of the control group (P=0.016). The results of the present study demonstrated that osteochondral repair using SMSCs facilitated the repair of appropriate tissue texture. PMID:26781689

  1. Osteochondral Lesion of the Bilateral Femoral Heads in a Young Athletic Patient

    PubMed Central

    Lee, Jung Eun; Park, Ji Seon; Cho, Yoon Je; Yoon, So Hee; Park, So Young; Jin, Wook; Lee, Kyung Ryeol

    2014-01-01

    Osteochondral lesions of the femoral head are uncommon and few studies have reported their imaging findings. Since joints are at risk of early degeneration after osteochondral damage, timely recognition is important. Osteochondral lesions of femoral head may often be necessary to differentiate from avascular necrosis. Here, we report a case of osteochondral lesions on bilateral femoral heads. This lesion manifested as subchondral cysts in initial radiographs, which led to further evaluation by computed tomography arthrography and magnetic resonance imaging, which revealed overlying cartilage defects. PMID:25469091

  2. In vitro generation of a multilayered osteochondral construct with an osteochondral interface using rabbit bone marrow stromal cells and a silk peptide-based scaffold.

    PubMed

    Chen, Kelei; Shi, Pujiang; Teh, Thomas Kok Hiong; Toh, Siew Lok; Goh, James Ch

    2016-04-01

    Tissue engineering of a biological osteochondral multilayered construct with a cartilage-interface subchondral bone layer is a key challenge. This study presented a rabbit bone marrow stromal cell (BMSC)/silk fibroin scaffold-based co-culture approach to generate tissue-engineered osteochondral grafts with an interface. BMSC-seeded scaffolds were first cultured separately in osteogenic and chondrogenic stimulation media. The two differentiated pieces were then combined using an RADA self-assembling peptide and subsequently co-cultured. Gene expression, histological and biochemical analyses were used to evaluate the multilayered structure of the osteochondral graft. A complete osteochondral construct with a cartilage-subchondral bone interface was regenerated and BMSCs were used as the only cell source for the osteochondral construct and interface regeneration. Furthermore, in the intermediate region of co-cultured samples, hypertrophic chondrogenic gene markers type X collagen and MMP-13 were found on both chondrogenic and osteogenic section edges after co-culture. However, significant differences gene expression profile were found in distinct zones of the construct during co-culture and the section in the intermediate region had significantly higher hypertrophic chondrocyte gene expression. Biochemical analyses and histology results further supported this observation. This study showed that specific stimulation from osteogenic and chondrogenic BMSCs affected each other in this co-culture system and induced the formation of an osteochondral interface. Moreover, this system provided a possible approach for generating multilayered osteochondral constructs. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23413023

  3. Review of the biomechanics and biotribology of osteochondral grafts used for surgical interventions in the knee

    PubMed Central

    Bowland, Philippa; Ingham, E; Jennings, Louise; Fisher, John

    2015-01-01

    A review of research undertaken to evaluate the biomechanical stability and biotribological behaviour of osteochondral grafts in the knee joint and a brief discussion of areas requiring further improvement in future studies are presented. The review takes into consideration osteochondral autografts, allografts, tissue engineered constructs and synthetic and biological scaffolds. PMID:26614801

  4. Knee hemarthros secondary to osteochondritis dissecans (Knig disease).

    PubMed

    Guilln Astete, Carlos; Alva Garca, Patricia; Carpena Zafrilla, Maria; Medina Quiones, Carmen

    2015-01-01

    A case is presented of a hemarthrosis associated with osteochondritis dissecans in a young man who arrived in the Emergency unit due to tender and swelling of his right knee one hour after a slightly rotational gesture of the lower limb. Many years before the patient suffered a sports injury in the same knee, but it was never assessed. Radiography studies showed bone fragments inside the synovial capsule, and the joint aspiration was compatible with hemarthrosis. A review of the available information of this uncommon condition is also presented. PMID:25936604

  5. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis.

    PubMed

    Walsh, David A; McWilliams, Dan F; Turley, Matthew J; Dixon, Madeleine R; Franss, Rebecca E; Mapp, Paul I; Wilson, Deborah

    2010-10-01

    Objectives. The osteochondral junction can be a source of pain in both RA and OA. Growth of blood vessels and nerves from the subchondral bone into articular cartilage may mediate the association between joint pathology and symptoms. We have investigated associations between angiogenesis, inflammation and neurovascular growth factor expression at the osteochondral junction in human arthritis. Methods. Osteochondral junctions from medial tibial plateaux of patients undergoing arthroplasty for RA (n?=?10) or OA (n?=?11), or from non-arthritic post-mortem controls (n?=?11) were characterized by immunohistochemistry for CD34 and smooth muscle ?-actin (blood vessels), CD68 (macrophages), CD3 (lymphocytes), proliferating cell nuclear antigen, vascular endothelial, platelet-derived and nerve growth factor (NGF). Results. Osteochondral angiogenesis was demonstrated as increased endothelial cell proliferation and vascular density in non-calcified articular cartilage, both in RA and OA. Osteochondral angiogenesis was associated with subchondral bone marrow replacement by fibrovascular tissue expressing VEGF, and with increased NGF expression within vascular channels. RA was characterized by greater lymphocyte infiltration and PDGF expression than OA, whereas chondrocyte expression of VEGF was a particular feature of OA. NGF was observed in vascular channels that contained calcitonin gene-related peptide-immunoreactive sensory nerve fibres. Conclusions. Osteochondral angiogenesis in RA and OA is associated with growth factor expression by cells within subchondral spaces, vascular channels and by chondrocytes. NGF expression and sensory nerve growth may link osteochondral angiogenesis to pain in arthritis. PMID:20581375

  6. Bone Marrow Aspiration Concentrate and Platelet Rich Plasma for Osteochondral Repair in a Porcine Osteochondral Defect Model

    PubMed Central

    Betsch, Marcel; Schneppendahl, Johannes; Thuns, Simon; Herten, Monika; Sager, Martin; Jungbluth, Pascal; Hakimi, Mohssen; Wild, Michael

    2013-01-01

    Background Bone marrow aspiration concentrate (BMAC) may possess a high potency for cartilage and osseous defect healing because it contains stem cells and multiple growth factors. Alternatively, platelet rich plasma (PRP), which contains a cocktail of multiple growth factors released from enriched activated thrombocytes may potentially stimulate the mesenchymal stem cells (MSCs) in bone marrow to proliferate and differentiate. Methods A critical size osteochondral defect (10×6 mm) in both medial femoral condyles was created in 14 Goettinger mini-pigs. All animals were randomized into the following four groups: biphasic scaffold alone (TRUFIT BGS, Smith & Nephew, USA), scaffold with PRP, scaffold with BMAC and scaffold in combination with BMAC and PRP. After 26 weeks all animals were euthanized and histological slides were cut, stained and evaluated using a histological score and immunohistochemistry. Results The thrombocyte number was significantly increased (p = 0.049) in PRP compared to whole blood. In addition the concentration of the measured growth factors in PRP such as BMP-2, BMP-7, VEGF, TGF-β1 and PDGF were significantly increased when compared to whole blood (p<0.05). In the defects of the therapy groups areas of chondrogenic tissue were present, which stained blue with toluidine blue and positively for collagen type II. Adding BMAC or PRP in a biphasic scaffold led to a significant improvement of the histological score compared to the control group, but the combination of BMAC and PRP did not further enhance the histological score. Conclusions The clinical application of BMAC or PRP in osteochondral defect healing is attractive because of their autologous origin and cost-effectiveness. Adding either PRP or BMAC to a biphasic scaffold led to a significantly better healing of osteochondral defects compared with the control group. However, the combination of both therapies did not further enhance healing. PMID:23951201

  7. Fabrication of tissue engineered osteochondral grafts for restoring the articular surface of diarthrodial joints.

    PubMed

    Roach, Brendan L; Hung, Clark T; Cook, James L; Ateshian, Gerard A; Tan, Andrea R

    2015-08-01

    Osteochondral allograft implantation is an effective cartilage restoration technique for large defects (>10 cm(2)), though the demand far exceeds the supply of available quality donor tissue. Large bilayered engineered cartilage tissue constructs with accurate anatomical features (i.e. contours, thickness, architecture) could be beneficial in replacing damaged tissue. When creating these osteochondral constructs, however, it is pertinent to maintain biofidelity to restore functionality. Here, we describe a step-by-step framework for the fabrication of a large osteochondral construct with correct anatomical architecture and topology through a combination of high-resolution imaging, rapid prototyping, impression molding, and injection molding. PMID:25794950

  8. Osteochondral tissue engineering: scaffolds, stem cells and applications

    PubMed Central

    Nooeaid, Patcharakamon; Salih, Vehid; Beier, Justus P; Boccaccini, Aldo R

    2012-01-01

    Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral tissue engineering, which are focused on the application of various materials forming bilayered composite scaffolds, including polymers and ceramics, discussing the variety of scaffold designs and fabrication methods being developed. Additionally, cell sources and biological protein incorporation methods are discussed, addressing their interaction with scaffolds and highlighting the potential for creating a new generation of bilayered composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment. PMID:22452848

  9. OSTEOCHONDRAL AUTOLOGOUS TRANSPLANTATION FOR TREATING CHONDRAL LESIONS IN THE PATELLA

    PubMed Central

    Cohen, Moises; Amaro, Joicemar Tarouco; Fernandes, Ricardo de Souza Campos; Arliani, Gustavo Gonçalves; Astur, Diego da Costa; Kaleka, Camila Cohen; Skaf, Abdalla

    2015-01-01

    Objective: The primary aim of this study was to assess the clinical and functional evolution of patients with total-thickness symptomatic cartilaginous injury of the patellar joint surface, treated by means of osteochondral autologous transplantation. Methods: This prospective study was conducted from June 2008 to March 2011 and involved 17 patients. The specific questionnaires of Lysholm, Kujala and Fulkerson were completed preoperatively and one year postoperatively in order to assess the affected knee, and SF-36 was used to assess these patients’ general quality of life. The nonparametric paired Wilcoxon test was used for statistical analysis on the pre and postoperative questionnaires. The data were analyzed using the SPSS for Windows software, version 16.0, and a significance level of 5% was used. Results: The Lysholm preoperative and postoperative average scores were 54.59 and 75.76 points (p < 0.05). The Fulkerson pre and postoperative average scores were 52.53 and 78.41 points (p < 0.05). Conclusions: We believe that autologous osteochondral transplantation is a good treatment method for total-thickness symptomatic chondral lesions of the joint surface of the patella.

  10. Repair Mechanism of Osteochondral Defect Promoted by Bioengineered Chondrocyte Sheet

    PubMed Central

    Kamei, Naosuke; Adachi, Nobuo; Hamanishi, Michio; Kamei, Goki; Mahmoud, Elhussein Elbadry; Nakano, Tomohiro; Iwata, Takanori; Yamato, Masayuki; Okano, Teruo; Ochi, Mitsuo

    2015-01-01

    Cell sheet engineering has developed as a remarkable method for cell transplantation. In the field of cartilage regeneration, several studies previously reported that cartilage defects could be regenerated by transplantation of a chondrocyte sheet using cell sheet engineering. However, it remains unclear how such a thin cell sheet could repair a deep cartilage defect. We, therefore, focused on the mechanism of cartilage repair using cell sheet engineering in this study. Chondrocyte sheets and synovial cell sheets were fabricated using cell sheet engineering, and these allogenic cell sheets were transplanted to cover an osteochondral defect in a rat model. Macroscopic and histological evaluation was performed at 4 and 12 weeks after transplantation. Analysis of the gene expression of each cell sheet and of the regenerated tissue at 1 week after transplantation was performed. In addition, green fluorescent protein (GFP) transgenic rats were used as donors (transplanted chondrocyte sheets) or recipients (osteochondral defect models) to identify the cell origin of regenerated cartilage. Cartilage repair was significantly better in the group implanted with a chondrocyte sheet than in that with a synovial cell sheet. The results of gene expression analysis suggest that the possible factor contributing to cartilage repair might be TGFβ1. Cell tracking experiments using GFP transgenic rats showed that the regenerated cartilage was largely composed of cells derived from the transplanted chondrocyte sheets. PMID:25396711

  11. Diagnosis of Knee Osteochondral Lesions With Ultrasound Imaging

    PubMed Central

    Penttilä, Pekko; Liukkonen, Jukka; Joukainen, Antti; Virén, Tuomas; Jurvelin, Jukka S.; Töyräs, Juha; Kröger, Heikki

    2015-01-01

    Evaluation of articular cartilage and subchondral bone is essential in the diagnosis of joint diseases and injuries. Interobserver and intraobserver reproducibilities of arthroscopic grading are only poor to moderate. Thus, for quantitative and objective evaluation of cartilage and subchondral bone, ultrasound arthroscopy (UA) has been introduced to clarify this dilemma. Assessment of the clinical feasibility of high-frequency ultrasonography (US) during 6 knee arthroscopies was conducted, and the surgical technique is presented. US imaging was conducted with a flexible 9-MHz US catheter inserted into the joint through conventional portals. US and arthroscopy videos were synchronously recorded, and US parameters for cartilage and subchondral bone characteristics were measured. Arthroscopy and US imaging were combined to perform cartilage grading. UA produced quantitative data on lesion size, as well as cartilage quality, and showed subchondral bone changes. Visualization of an osteochondritis dissecans lesion not detected by conventional arthroscopy and US-guided retrograde drilling were possible with UA. To conclude, UA proved to be clinically feasible and aided in the diagnosis when assessing knee osteochondral lesions. PMID:26697300

  12. Integrated Bi-Layered Scaffold for Osteochondral Tissue Engineering

    PubMed Central

    Galperin, Anna; Oldinski, Rachael A.; Florczyk, Stephen J.; Bryers, James D.; Zhang, Miqin

    2013-01-01

    Osteochondral tissue engineering poses the challenge of combining both cartilage and bone tissue engineering fundamentals. In this study, a sphere-templating technique was applied to fabricate an integrated bi-layered scaffold based on degradable poly(hydroxyethyl methacrylate) hydrogel. One layer of the integrated scaffold was designed with a single defined, monodispersed pore size of 38 μm and pore surfaces coated with hydroxyapatite particles to promote regrowth of subchondral bone while the second layer had 200 μm pores with surfaces decorated with hyaluronan for articular cartilage regeneration. Mechanical properties of the construct as well as cyto-compatibility of the scaffold and its degradation products were elucidated. To examine the potential of the biphasic scaffold for regeneration of osteochondral tissue the designated cartilage and bone layers of the integrated bi-layered scaffold were seeded with chondrocytes differentiated from human mesenchymal stem cells and primary human mesenchymal stem cells, respectively. Both types of cells were co-cultured within the scaffold in standard medium without soluble growth/differentiation factors over four weeks. The ability of the integrated bi-layered scaffold to support simultaneous matrix deposition and adequate cell growth of two distinct cell lineages in each layer during four weeks of co-culture in vitro in the absence of soluble growth factors was demonstrated. PMID:23225568

  13. ARTHROSCOPIC TREATMENT OF OSTEOCHONDRAL LESIONS OF THE TALUS

    PubMed Central

    de Araujo, Mariana Korbage; de Cillo, Mario Sergio Paulillo; Bittar, Cinthia Kelly; Zabeu, José Luis Amin; Cezar, Caroliny Nociti Moreira

    2016-01-01

    ABSTRACT Objective: To assess pain and function of the ankle in patients with injuries up to 1.5 cm diameter by the American Orthopaedic Foot and Ankle Society (AOFAS) score after arthroscopic treatment. Methods: The AOFAS scale was applied before and after arthroscopy, as well as the degree of subjective satisfaction of ambulatory patients. Patients with type I osteochondral injuries, acute trauma, using plaster, presenting lesions in other joints of the lower limbs and cognitive impairment that would prevent the application of the satisfaction questionnaire were excluded from the study. Statistical analysis was performed using unpaired t test with Welch correction, Mann Whitney test, and ANOVA, with Kruskal Wallis test and Dun test, considering p value lower than 0.05. Results: There was an increased AOFAS scores after arthroscopic treatment in 52 (94.5%) patients. The mean values of AOFAS score in 55 patients was 77.32 ± 6.67 points preoperative and 93.10± 8.24 points postoperative, with a mean variation of 15.8 points, p<0.001. Patients with stage II, III and IV injuries showed an increased AOFAS scores after arthroscopic treatment, p<0.001. No difference was found between medial and lateral injuries, p >0.05. Conclusion: Patients with stage II, III or IV osteochondral injuries of the talus of up to 1.5 cm diameter, whether medial or lateral, showed a significant improvement after arthroscopic treatment. Level of Evidence III, Retrospective Study.

  14. Diagnosis of Knee Osteochondral Lesions With Ultrasound Imaging.

    PubMed

    Penttilä, Pekko; Liukkonen, Jukka; Joukainen, Antti; Virén, Tuomas; Jurvelin, Jukka S; Töyräs, Juha; Kröger, Heikki

    2015-10-01

    Evaluation of articular cartilage and subchondral bone is essential in the diagnosis of joint diseases and injuries. Interobserver and intraobserver reproducibilities of arthroscopic grading are only poor to moderate. Thus, for quantitative and objective evaluation of cartilage and subchondral bone, ultrasound arthroscopy (UA) has been introduced to clarify this dilemma. Assessment of the clinical feasibility of high-frequency ultrasonography (US) during 6 knee arthroscopies was conducted, and the surgical technique is presented. US imaging was conducted with a flexible 9-MHz US catheter inserted into the joint through conventional portals. US and arthroscopy videos were synchronously recorded, and US parameters for cartilage and subchondral bone characteristics were measured. Arthroscopy and US imaging were combined to perform cartilage grading. UA produced quantitative data on lesion size, as well as cartilage quality, and showed subchondral bone changes. Visualization of an osteochondritis dissecans lesion not detected by conventional arthroscopy and US-guided retrograde drilling were possible with UA. To conclude, UA proved to be clinically feasible and aided in the diagnosis when assessing knee osteochondral lesions. PMID:26697300

  15. MR imaging of osteochondral grafts and autologous chondrocyte implantation

    PubMed Central

    Millington, S. A.; Szomolanyi, P.; Marlovits, S.

    2006-01-01

    Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible. PMID:16802126

  16. Comprehensive analysis of translational osteochondral repair: Focus on the histological assessment.

    PubMed

    Orth, Patrick; Peifer, Carolin; Goebel, Lars; Cucchiarini, Magali; Madry, Henning

    2015-10-01

    Articular cartilage guarantees for an optimal functioning of diarthrodial joints by providing a gliding surface for smooth articulation, weight distribution, and shock absorbing while the subchondral bone plays a crucial role in its biomechanical and nutritive support. Both tissues together form the osteochondral unit. The structural assessment of the osteochondral unit is now considered the key standard procedure for evaluating articular cartilage repair in translational animal models. The aim of this review is to give a detailed overview of the different methods for a comprehensive evaluation of osteochondral repair. The main focus is on the histological assessment as the gold standard, together with immunohistochemistry, and polarized light microscopy. Additionally, standards of macroscopic, non-destructive imaging such as high resolution MRI and micro-CT, biochemical, and molecular biological evaluations are addressed. Potential pitfalls of analysis are outlined. A second focus is to suggest recommendations for osteochondral evaluation. PMID:26515165

  17. Osteochondral Autograft Transplantation: A Review of the Surgical Technique and Outcomes.

    PubMed

    Richter, Dustin L; Tanksley, John A; Miller, Mark D

    2016-06-01

    Isolated chondral and osteochondral defects of the knee are challenging clinical entities, particularly in younger patients. Cartilage treatment strategies have previously been characterized as palliation (ie, chondroplasty and debridement), repair (ie, drilling and microfracture), or restoration (ie, autologous chondrocyte implantation, osteochondral autograft, and osteochondral allograft). The osteochondral autograft transplantation procedure allows defects to be filled immediately with mature, hyaline articular cartilage by utilizing either an arthroscopic or a mini-open procedure. Graft harvest and placement can be technically demanding, but results show trends toward greater longevity, durability, and improved outcomes in high-demand patients when compared with alternative techniques. Improved results are shown in younger patients with isolated lesions between 1 and 4 cm. PMID:27135290

  18. Contaminated osteochondral plugs: effect of different sterilizing solutions: an experimental study in the rabbit

    PubMed Central

    Yazdi, Hamidreza; Shafiee, Gholamreza; Shahcheraghi, Masoumeh

    2012-01-01

    Background To determine the efficacy of different antiseptic solutions (Control group (I), Antibiotic solution (II), Chlorhexidine 0.4% (III), and povidone – iodine 10% (IV)) in sterilizing contaminated osteochondral plugs. Methods Under sterile conditions, the femoral head and condyles of 20 rabbits were removed and cut into equal osteochondral pieces. A total of 200 osteochondral specimens were obtained. All 200 specimens were dropped on the operating room floor for fifteen seconds and assigned to one of four experimental groups. Group I samples were cultured after washing with normal saline solution (Control group). In other three groups, prior to culturing process, samples were placed in an antibiotic solution after washing with normal saline (Neomycin & Polymyxin) (group II), Chlorhexidine 0.4% (group III), and povidone – iodine 10% (group IV), respectively. Results In group I, 25 of 50 specimens had positive cultures. Of 50 specimens of group II, III and IV, no positive cultures were found after 10 days. Conclusion All three agents including antibiotic solution, povidone-iodine 10% and chlorhexidine 0.4% seem effective in sterilizing the contaminated osteochondral samples. According to the literature, povidone-iodine has no negative effect on the cartilage metabolism and seems to be a proper choice of decontaminating solution for osteochondral plugs.To the best of the authors’ knowledge, such a study on the contaminated osteochondral specimen has not been previously reported in the literature. PMID:23482438

  19. Biomarkers Affected by Impact Severity during Osteochondral Injury.

    PubMed

    Waters, Nicole Poythress; Stoker, Aaron M; Pfeiffer, Ferris M; Cook, James L

    2015-06-01

    Osteochondral injury elevates the risk for developing posttraumatic osteoarthritis (PTOA). Therefore, our objective was to evaluate the relationship between impact severity during injury to cell viability and biomarkers possibly involved in PTOA. Osteochondral explants (6 mm, n = 72) were harvested from cadaveric femoral condyles (N = 6). Using a test machine, each explant (except for No Impact) was subjected to mechanical impact at a velocity of 100 mm/s to 0.25, 0.5, 0.75, 1.0, or 1.25 mm maximum compression corresponding to Low, Low-Moderate, Moderate, Moderate-High, or High impact groups. Cartilage cell viability, collagen content, and proteoglycan content were assessed at either day 0 or after 12 days of culture. Culture media were assessed for prostaglandin E2 (PGE2); nitric oxide; granulocyte macrophage colony-stimulating factor (GM-CSF); interferon gamma (IFNγ); interleukin (IL)-2, -4, -6, -7, -8, -10, -15, -18; interferon gamma-induced protein 10 (IP-10); keratinocyte-derived chemoattractant (KC); monocyte chemoattractant protein-1 (MCP-1); tumor necrosis factor alpha (TNFα); and matrix metalloproteinase-2, -3, -8, -9, -13. There was increased impact energy absorbed for the High group compared with the Moderate-High group, Moderate group, and Low-Moderate group (p = 0.011, 0.048, 0.008, respectively). At day 0, there was decreased area cell viability for the High group compared with the Low-Moderate group (p = 0.035). At day 1, PGE2 was increased for the High group compared with the Moderate, Low-Moderate, Low, and No Impact groups (p ≤ 0.01). Cumulative PGE2 was increased for the Moderate-High and High groups compared with the Moderate, Low-Moderate, Low, and No Impact groups (p ≤ 0.036). At day 1, MCP-1 was increased for the Moderate-High and High groups compared with the Low and No Impact groups (p ≤ 0.032). Impact to osteochondral explants resulted in multiple levels of severity. PGE2 was sensitive to impact severity which may justify its use as a clinically measurable biomarker after joint injury for monitoring early PTOA. PMID:24858662

  20. Optical Clearing in Collagen- and Proteoglycan-Rich Osteochondral Tissues

    PubMed Central

    Neu, Corey P.; Novak, Tyler; Gilliland, Kateri Fites; Marshall, Peter; Calve, Sarah

    2014-01-01

    Objective Recent developments in optical clearing and microscopy technology have enabled the imaging of intact tissues at the millimeter scale to characterize cells via fluorescence labeling. While these techniques have facilitated the three-dimensional cellular characterization within brain and heart, study of dense connective tissues of the musculoskeletal system have been largely unexplored. Here, we quantify how optical clearing impacted the cell and tissue morphology of collagen-, proteoglycan-, and mineral-rich cartilage and bone from the articulating knee joint. Methods Water-based fructose solutions were used for optical clearing of bovine osteochondral tissues, followed by imaging with transmission and confocal microscopy. To confirm preservation of tissue structure during the clearing process, samples were mechanically tested in unconfined compression and visualized by cryoSEM. Results Optical clearing enhanced light transmission through cartilage, but not subchondral bone regions. Fluorescent staining and immunolabeling was preserved through sample preparations, enabling imaging to cartilage depths 5 times deeper than previously reported, limited only by the working distance of the microscope objective. Chondrocyte volume remained unchanged in response to, and upon the reversal, of clearing. Equilibrium modulus increased in cleared samples, and was attributed to exchange of interstitial fluid with the more viscous fructose solution, but returned to control levels upon unclearing. In addition, cryoSEM-based analysis of cartilage showed no ultrastructural changes. Conclusion We anticipate large-scale microscopy of diverse connective tissues will enable the study of intact, three-dimensional interfaces (e.g. osteochondral) and cellular connectivity as a function of development, disease, and regeneration, which have been previously hindered by specimen opacity. PMID:25454370

  1. Additive manufacturing for in situ repair of osteochondral defects.

    PubMed

    Cohen, Daniel L; Lipton, Jeffrey I; Bonassar, Lawrence J; Lipson, Hod

    2010-09-01

    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 approximately 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. PMID:20823507

  2. Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds.

    PubMed

    Castro, Nathan J; O'Brien, Joseph; Zhang, Lijie Grace

    2015-09-01

    The osteochondral interface of an arthritic joint is notoriously difficult to regenerate due to its extremely poor regenerative capacity and complex stratified architecture. Native osteochondral tissue extracellular matrix is composed of numerous nanoscale organic and inorganic constituents. Although various tissue engineering strategies exist in addressing osteochondral defects, limitations persist with regards to tissue scaffolding which exhibit biomimetic cues at the nano to micro scale. In an effort to address this, the current work focused on 3D printing biomimetic nanocomposite scaffolds for improved osteochondral tissue regeneration. For this purpose, two biologically-inspired nanomaterials have been synthesized consisting of (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lactic-co-glycolic) acid (PLGA) nanospheres encapsulated with chondrogenic transforming growth-factor β1 (TGF-β1) for sustained delivery. Then, a novel table-top stereolithography 3D printer and the nano-ink (i.e., nHA + nanosphere + hydrogel) were employed to fabricate a porous and highly interconnected osteochondral scaffold with hierarchical nano-to-micro structure and spatiotemporal bioactive factor gradients. Our results showed that human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation were greatly improved in the biomimetic graded 3D printed osteochondral construct in vitro. The current work served to illustrate the efficacy of the nano-ink and current 3D printing technology for efficient fabrication of a novel nanocomposite hydrogel scaffold. In addition, tissue-specific growth factors illustrated a synergistic effect leading to increased cell adhesion and directed stem cell differentiation. PMID:26234364

  3. Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds

    NASA Astrophysics Data System (ADS)

    Castro, Nathan J.; O'Brien, Joseph; Zhang, Lijie Grace

    2015-08-01

    The osteochondral interface of an arthritic joint is notoriously difficult to regenerate due to its extremely poor regenerative capacity and complex stratified architecture. Native osteochondral tissue extracellular matrix is composed of numerous nanoscale organic and inorganic constituents. Although various tissue engineering strategies exist in addressing osteochondral defects, limitations persist with regards to tissue scaffolding which exhibit biomimetic cues at the nano to micro scale. In an effort to address this, the current work focused on 3D printing biomimetic nanocomposite scaffolds for improved osteochondral tissue regeneration. For this purpose, two biologically-inspired nanomaterials have been synthesized consisting of (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lactic-co-glycolic) acid (PLGA) nanospheres encapsulated with chondrogenic transforming growth-factor β1 (TGF-β1) for sustained delivery. Then, a novel table-top stereolithography 3D printer and the nano-ink (i.e., nHA + nanosphere + hydrogel) were employed to fabricate a porous and highly interconnected osteochondral scaffold with hierarchical nano-to-micro structure and spatiotemporal bioactive factor gradients. Our results showed that human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation were greatly improved in the biomimetic graded 3D printed osteochondral construct in vitro. The current work served to illustrate the efficacy of the nano-ink and current 3D printing technology for efficient fabrication of a novel nanocomposite hydrogel scaffold. In addition, tissue-specific growth factors illustrated a synergistic effect leading to increased cell adhesion and directed stem cell differentiation.

  4. Repairing the Osteochondral Defect in Goat with the Tissue-Engineered Osteochondral Graft Preconstructed in a Double-Chamber Stirring Bioreactor

    PubMed Central

    Pei, Yang; Fan, Jun-jun; Zhang, Xiao-qiang; Zhang, Zhi-yong; Yu, Min

    2014-01-01

    To investigate the reparative efficacy of tissue-engineered osteochondral (TEO) graft for repairing the osteochondral defect in goat, we designed a double-chamber stirring bioreactor to construct the bone and cartilage composites simultaneously in one β-TCP scaffold and observed the reparative effect in vivo. The osteochondral defects were created in goats and all the animals were divided into 3 groups randomly. In groups A, the defect was treated with the TEO which was cultured with mechanical stimulation of stir; in group B, the defect was treated with TEO which was cultured without mechanical stimulation of stir; in groups C, the defect was treated without TEO. At 12 weeks and 24 weeks after operation, the reparative effects in different groups were assessed and compared. The results indicated that the reparative effect of the TEO cultured in the bioreactor was better than the control group, and mechanical stimulation of stir could further improve the reparative effect. We provided a feasible and effective method to construct the TEO for treatment of osteochondral defect using autologous BMSCs and the double-chamber bioreactor. PMID:25061604

  5. Mechanical evaluation of a tissue-engineered zone of calcification in a bonehydrogel osteochondral construct

    PubMed Central

    Hollenstein, Jrme; Terrier, Alexandre; Cory, Esther; Chen, Albert C.; Sah, Robert L.; Pioletti, Dominique P.

    2016-01-01

    The objective of this study was to test the hypothesis that mechanical properties of artificial osteochondral constructs can be improved by a tissue-engineered zone of calcification (teZCC) at the bonehydrogel interface. Experimental push-off tests were performed on osteochondral constructs with or without a teZCC. In parallel, a numerical model of the osteochondral defect treatment was developed and validated against experimental results. Experimental results showed that the shear strength at the bonehydrogel interface increased by 100% with the teZCC. Numerical predictions of the osteochondral defect treatment showed that the shear stress at the bonehydrogel interface was reduced with the teZCC. We conclude that a teZCC in osteochondral constructs can provide two improvements. First, it increases the strength of the bonehydrogel interface and second, it reduces the stress at this interface. PMID:23706035

  6. Outcomes of Total Knee Arthroplasty After Osteochondral Allograft Transplantation

    PubMed Central

    Steinhoff, Amy K.; Bugbee, William D.

    2014-01-01

    Background: Fresh osteochondral allograft (OCA) transplantation is an effective treatment for osteochondral defects. Some patients require further surgical intervention, such as total knee arthroplasty (TKA). The effects of prior OCA transplantation on TKA outcomes are unknown. Purpose: This study evaluated TKA failure rates after long-term follow-up and identified factors that may have contributed to an inferior outcome. Its aims were to (1) assess if having a prior OCA transplantation would increase the surgical complications of the subsequent TKA, (2) measure the infection and failure rates following TKA, (3) ascertain subjective outcomes scores from patients with intact TKA at latest follow-up, and (4) identify potential factors that contributed to inferior outcomes. Study Design: Case series; Level of evidence, 4. Methods: A total of 35 patients who underwent TKA after OCA were identified. Pain, symptoms, function, and quality of life were evaluated using the Knee Society Function score and Knee injury and Osteoarthritis Outcome Score (KOOS). Associations between outcomes scores versus total number of surgeries before TKA were assessed using Spearman correlation. Patient characteristics (age, sex, total OCA area, presentation of osteoarthritis, and number of surgeries before TKA) were calculated between failures and nonfailures. Results: For patients with TKA surviving at latest follow-up (n = 24), mean follow-up time was 9.2 ± 4.3 years after TKA and 16.1 ± 5.2 years after OCA. While TKA after OCA did not present a technical challenge in the operating room, there was a high failure rate (31.4%). Activities of daily living, as measured on KOOS, were negatively correlated with total number of surgeries before TKA (ρ2 = –0.5, P = .041). Patient age and number of surgeries before TKA influenced the failure rate, while sex and OCA area did not appear to be factors associated with inferior outcomes. Conclusion: Patients with multiple knee operations before TKA were more likely to experience functional limitations or TKA failure. The patients who experienced TKA failure were part of a challenging subset of young patients treated with numerous orthopaedic procedures, and while these patients had inferior results with TKA after OCA, the OCA transplantation extended the time before a TKA was required without adding surgical complications. PMID:26535363

  7. Acute Osteochondral Fractures in the Lower Extremities - Approach to Identification and Treatment

    PubMed Central

    Pedersen, M.E; DaCambra, M.P; Jibri, Z; Dhillon, S; Jen, H; Jomha, N.M

    2015-01-01

    Chondral and osteochondral fractures of the lower extremities are important injuries because they can cause pain and dysfunction and often lead to osteoarthritis. These injuries can be misdiagnosed initially which may impact on the healing potential and result in poor long-term outcome. This comprehensive review focuses on current pitfalls in diagnosing acute osteochondral lesions, potential investigative techniques to minimize diagnostic errors as well as surgical treatment options. Acute osteochondral fractures are frequently missed and can be identified more accurately with specific imaging techniques. A number of different methods can be used to fix these fractures but attention to early diagnosis is required to limit progression to osteoarthritis. These fractures are common with joint injuries and early diagnosis and treatment should lead to improved long term outcomes. PMID:26587063

  8. Current strategies in multiphasic scaffold design for osteochondral tissue engineering: A review.

    PubMed

    Yousefi, Azizeh-Mitra; Hoque, Md Enamul; Prasad, Rangabhatala G S V; Uth, Nicholas

    2015-07-01

    The repair of osteochondral defects requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using specifically designed scaffold-cell constructs. Biphasic and triphasic approaches utilize two or three different architectures, materials, or composites to produce a multilayered construct. This article gives an overview of some of the current strategies in multiphasic/gradient-based scaffold architectures and compositions for tissue engineering of osteochondral defects. In addition, the application of finite element analysis (FEA) in scaffold design and simulation of in vitro and in vivo cell growth outcomes has been briefly covered. FEA-based approaches can potentially be coupled with computer-assisted fabrication systems for controlled deposition and additive manufacturing of the simulated patterns. Finally, a summary of the existing challenges associated with the repair of osteochondral defects as well as some recommendations for future directions have been brought up in the concluding section of this article. PMID:25345589

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

    NASA Astrophysics Data System (ADS)

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

    2010-09-01

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

  10. TREATMENT OF OSTEOCHONDRAL LESIONS OF THE TALUS BY MEANS OF THEARTHROSCOPY-ASSISTED MICROPERFORATION TECHNIQUE

    PubMed Central

    de Lima, Everton; de Queiroz, Felipe; Lopes, Osmar Valadão; Spinelli, Leandro de Freitas

    2015-01-01

    Objective: To evaluate patients affected by osteochondral fractures of the talus who were treated surgically by means of arthroscopy-assisted microperforation. Methods: A retrospective study was carried out on 24 patients with osteochondral lesions of the talus who underwent microperforation assisted by videoarthroscopy of the ankle. They were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score system before and after the operation. Results: There were 19 men and 5 women, with a mean age of 35.3 years (minimum of 17 years and maximum of 54 years). The minimum follow-up was two years (maximum of 39 months). All the patients showed an improvement in AOFAS score after surgery, with an average improvement of around 22.5 points. Conclusion: Videoarthroscopy-assisted microperforation is a good option for treating osteochondral lesions of the talus and provides good functional results. PMID:27027076

  11. Unusual osteochondral lesions of the talus in a horse.

    PubMed

    Simpson, C M; Lumsden, J M

    2001-11-01

    A 2-year-old Thoroughbred gelding was evaluated for a grade 3 out of 5 unilateral hind limb lameness. Flexion of the right hock and stifle joints (spavin test) exacerbated the lameness. Response to intra-articular and perineural anaesthesia isolated the source of lameness to the tarsocrural area, despite an absence of tarsocrural joint effusion. Routine radiographic examination of the hock did not reveal any significant abnormalities. Skeletal nuclear scintigraphic evaluation revealed a focal region of increased bone activity in the proximal medial trochlear ridge of the talus. Flexed lateromedial radiographic views identified three discrete semicircular lytic lesions at the proximal articular margin of the medial trochlear ridge of the talus. Conservative management of the lesions was associated with a successful return to racing. The location and appearance of the osteochondral lesions of this report have not been previously reported and may be a manifestation of developmental orthopaedic disease and abnormal endochondral ossification. Nuclear scintigraphy and flexed lateromedial radiographic views facilitated identification of the lesions. This radiographic view is recommended when lameness is isolated to the tarsocrural joint and standard radio-graphic projections fail to identify a cause. PMID:11789910

  12. Results of Osteochondral Autologous Transplantation in the Knee

    PubMed Central

    Muller, Sandra; Breederveld, Roelf S.; Tuinebreijer, Wim E.

    2010-01-01

    Repair of full thickness defects of articular cartilage in the knee is difficult but important to prevent progression to osteoarthritis. The purpose of this retrospective study was to evaluate the clinical results of Osteochondral Autograft Transplant System (OATS) treatment for articular defects of the knee. Between 1999 and 2005, 15 knees (14 patients) were treated by the OATS technique. Age ranged from 27 to 52 years. Cartilage defects were up to 3.75 cm2. The mean follow-up was 42 months. Knee function was assessed by the Lysholmscore and International Knee Documentation Committee (IKDC) Subjective Knee Form. Six patients scored good or excellent. No patient had knee instability. Twelve of 13 patients returned to sports at an intermediate or high level. The subjective assessment score (0-10) changed from 4.7 before operation to 7.2 afterward (P=0.007). The OATS-technique resulted in a decrease in symptoms in patients with localized articular cartilage defects. We consider the OATS technique to be an appropriate treatment for cartilage defects to prevent progression of symptoms. PMID:20361003

  13. Viral Inactivation of Human Osteochondral Grafts with Methylene Blue and Light

    PubMed Central

    Zhao, Zhixing; Call, Gazell M.; Gao, Jizong; Yao, Jian Q.

    2014-01-01

    Objective: Cartilage injury is one of the most common disorders of synovial joints. Fresh osteochondral allografts are becoming a standard treatment; however, they are supply constrained with a potential risk of disease transmission. There are no known virucidal processes available for osteochondral allografts and most methods presently available are detrimental to cartilage. Methylene blue light treatment has been shown to be successful in the literature for viral inactivation of fresh frozen plasma. The purpose of this study was to determine the capacity of methylene blue light treatment to inactivate a panel of clinically relevant viruses inoculated onto osteochondral allografts. Design: Osteochondral grafts recovered from human cadaveric knees were inoculated with one of the following viruses: bovine viral diarrhea virus (BVDV), hepatitis A virus (HAV), human immunodeficiency virus type 1 (HIV-1), porcine parvovirus (PPV), and pseudorabies virus (PrV). The samples were processed through a methylene blue light treatment, which consisted of an initial soak in nonilluminated circulating methylene blue at ambient temperature, followed by light exposure with circulating methylene blue at cool temperatures. The final titer was compared with the recovery control for the viral log reduction. Results: HIV-1, BVDV, and PrV were reduced to nondetectable levels while HAV and PPV were reduced by 3.1 and 5.6 logs, respectively. Conclusions: The methylene blue light treatment was effective in reducing (a) enveloped DNA and RNA viruses to nondetectable levels and (b) nonenveloped DNA and RNA viruses of inoculated human osteochondral grafts by 3.1 to 5.6 logs. This study demonstrates the first practical method for significantly reducing viral load in osteochondral implants. PMID:26069682

  14. The Wnt11 Signaling Pathway in Potential Cellular EMT and Osteochondral Differentiation Progression in Nephrolithiasis Formation

    PubMed Central

    He, Deng; Lu, Yuchao; Hu, Henglong; Zhang, Jiaqiao; Qin, Baolong; Wang, Yufeng; Xing, Shuai; Xi, Qilin; Wang, Shaogang

    2015-01-01

    The molecular events leading to nephrolithiasis are extremely complex. Previous studies demonstrated that calcium and transforming growth factor-β1 (TGF-β1) may participate in the pathogenesis of stone formation, but the explicit mechanism has not been defined. Using a self-created genetic hypercalciuric stone-forming (GHS) rat model, we observed that the increased level of serous/uric TGF-β1 and elevated intracellular calcium in primary renal tubular epithelial cells (PRECs) was associated with nephrolithiasis progression in vivo. In the setting of high calcium plus high TGF-β1 in vitro, PRECs showed great potential epithelial to mesenchymal transition (EMT) progression and osteochondral differentiation properties, representing the multifarious increased mesenchymal and osteochondral phenotypes (Zeb1, Snail1, Col2A1, OPN, Sox9, Runx2) and decreased epithelial phenotypes (E-cadherin, CK19) bythe detection of mRNAs and corresponding proteins. Moreover, TGF-β-dependent Wnt11 knockdown and L-type Ca2+ channel blocker could greatly reverse EMT progression and osteochondral differentiation in PRECs. TGF-β1 alone could effectively promote EMT, but it had no effect on osteochondral differentiation in NRK cells (Rat kidney epithelial cell line). Stimulation with Ca2+ alone did not accelerate differentiation of NRK. Co-incubation of extracellular Ca2+ and TGF-β1 synergistically promotes EMT and osteochondral differentiation in NRK control cells. Our data supplied a novel view that the pathogenesis of calcium stone development may be associated with synergic effects of TGF-β1 and Ca2+, which promote EMT and osteochondral differentiation via Wnt11 and the L-type calcium channel. PMID:26193266

  15. Osteochondritis dissecans of the lateral humeral condyle in a table tennis player.

    PubMed

    Pintore, E; Maffulli, N

    1991-08-01

    The case of a table tennis player suffering from intra-articular loose bodies of the elbow is reported. The patient developed the first signs of osteochondritis dissecans of the right lateral humeral condyle at age 16 but underwent surgery only 6 yr later. He has now resumed training and competition, despite some residual stiffness due to early osteoarthritis. This is the first case of osteochondritis dissecans of the elbow ascribed to this sport. It was probably due to repetitive valgus compressive stresses at the radiocapitellar joint during the forced movements imposed by high-level table tennis in a young athlete. PMID:1956260

  16. Chondroblastoma of the Knee Treated with Resection and Osteochondral Allograft Reconstruction

    PubMed Central

    Fitzgerald, Judd; Broehm, Cory; Treme, Gehron

    2014-01-01

    Case. This case report describes the operative management of 16-year-old male with a symptomatic chondroblastoma of the distal femur with breach of the chondral surface. Following appropriate imaging and core needle biopsy, the diagnosis was confirmed histologically. The patient then underwent intralesional curettage and osteochondral allograft reconstruction of the defect. At one-year follow-up the patient was pain-free and has obtained excellent range of motion. There is radiographic evidence of allograft incorporation and no evidence of local recurrence. Conclusion. Osteochondral allograft reconstruction is an effective option following marginal resection and curettage of chondroblastoma involving the chondral surface of the distal femur. PMID:25548701

  17. Chondroblastoma of the knee treated with resection and osteochondral allograft reconstruction.

    PubMed

    Fitzgerald, Judd; Broehm, Cory; Chafey, David; Treme, Gehron

    2014-01-01

    Case. This case report describes the operative management of 16-year-old male with a symptomatic chondroblastoma of the distal femur with breach of the chondral surface. Following appropriate imaging and core needle biopsy, the diagnosis was confirmed histologically. The patient then underwent intralesional curettage and osteochondral allograft reconstruction of the defect. At one-year follow-up the patient was pain-free and has obtained excellent range of motion. There is radiographic evidence of allograft incorporation and no evidence of local recurrence. Conclusion. Osteochondral allograft reconstruction is an effective option following marginal resection and curettage of chondroblastoma involving the chondral surface of the distal femur. PMID:25548701

  18. Stratified scaffolds for osteochondral tissue engineering applications: electrospun PDLLA nanofibre coated Bioglass®-derived foams.

    PubMed

    Yunos, D M; Ahmad, Z; Salih, V; Boccaccini, A R

    2013-01-01

    This work focuses on designing bilayered constructs by combining electrospun poly-DL-Lactide (PDLLA) fibers and Bioglass®-derived scaffolds for development of osteochondral tissue replacement materials. Electrospinning was carried out using a solution of 5 wt/v% PDLLA in dimethyl carbonate. The PDLLA layer thickness increased from 2 to 150 µm with varying electrospinning time. Bioactivity studies in simulated body fluid showed that HA mineralization decreased as the thickness of the PDLLA layer increased. A preliminary in vitro study using chondrocyte cells (ATDC5) showed that cells attached, proliferated and migrated into the fibrous network, confirming the potential applicability of the bilayered scaffolds in osteochondral defect regeneration. PMID:22090433

  19. Qualitative histological evaluation of photooxidized bovine osteochondral grafts in rabbits: a pilot study.

    PubMed

    Hetherington, Vincent J; Kawalec-Carroll, Jill S; Nadler, Daniel

    2007-01-01

    Photooxidation is a treatment that can render tissue less immunogenic and resistant to enzymatic degradation, while maintaining the mechanical properties of the material. The purpose of this study was to histologically examine the biocompatibility of photooxidized bovine osteochondral grafts when implanted into the rabbit. Two holes were drilled into the patellar groove of the rabbit knee. Photooxidized bovine osteochondral grafts were implanted into the holes. As a control, 1 surgically created hole in each rabbit was left to heal naturally. The animals were killed after 12 weeks. Histological analysis of the control sites indicated that fibrocartilage had begun to regenerate in the defect. Analysis of the grafts revealed a chronic, nonspecific inflammatory reaction. Active remodeling was observed in the graft bone, with "bridging" between host and graft bone evident. The articulating surface and majority of the graft cartilage remained undamaged. In a few instances, however, there was an inflammatory response to the base of the graft cartilage, near the subchondral plate. The surface of the graft cartilage was covered by a thin layer of fibrous tissue, and no viable chondrocytes were present. In most cases, there was no fusion between host and graft cartilage. The results from this study suggest that, while a biological reaction to the grafts occurred, the bone portion of the graft appeared to be in the process of remodeling, and the majority of the graft cartilage, most significantly the articulating surface, remained intact. Photooxidized osteochondral grafts show promise for use in the repair of osteochondral defects. PMID:17586433

  20. Biofabrication of osteochondral tissue equivalents by printing topologically defined, cell-laden hydrogel scaffolds.

    PubMed

    Fedorovich, Natalja E; Schuurman, Wouter; Wijnberg, Hans M; Prins, Henk-Jan; van Weeren, P René; Malda, Jos; Alblas, Jacqueline; Dhert, Wouter J A

    2012-01-01

    Osteochondral defects are prone to induce osteoarthritic degenerative changes. Many tissue-engineering approaches that aim to generate osteochondral implants suffer from poor tissue formation and compromised integration. This illustrates the need for further improvement of heterogeneous tissue constructs. Engineering of these structures is expected to profit from strategies addressing the complexity of tissue organization and the simultaneous use of multiple cell types. Moreover, this enables the investigation of the effects of three-dimensional (3D) organization and architecture on tissue function. In the present study, we characterize the use of a 3D fiber deposition (3DF) technique for the fabrication of cell-laden, heterogeneous hydrogel constructs for potential use as osteochondral grafts. Changing fiber spacing or angle of fiber deposition yielded scaffolds of varying porosity and elastic modulus. We encapsulated and printed fluorescently labeled human chondrocytes and osteogenic progenitors in alginate hydrogel yielding scaffolds of 1×2 cm with different parts for both cell types. Cell viability remained high throughout the printing process, and cells remained in their compartment of the printed scaffold for the whole culture period. Moreover, distinctive tissue formation was observed, both in vitro after 3 weeks and in vivo (6 weeks subcutaneously in immunodeficient mice), at different locations within one construct. These results demonstrate the possibility of manufacturing viable centimeter-scaled structured tissues by the 3DF technique, which could potentially be used for the repair of osteochondral defects. PMID:21854293

  1. Midterm results of biologic fixation or mosaicplasty and drilling in osteochondritis dissecans

    PubMed Central

    Emre, Tuluhan Yunus; Cift, Hakan; Seyhan, Bahadir; Ceyhan, Erman; Uzun, Macit

    2011-01-01

    Background: Osteochondritis dissecans (OCD) primarily affects subchondral bone. Multiple drilling, fixation implant or autogenous osteochondral grafts are reported as treatment options. We present the midterm results of cases in which an OCD lesion was treated by osteochondral autograft transfer and drilling. Materials and Methods: Between 2002 and 2006, 14 knees with International Cartilage Repair Society (ICRS-OCD) type II and III lesions were treated in our clinic using osteochondral autograft transfer and drilling by arthroscopic or open surgery. The average age of our patients was 22.14 years (range 17-29 years) and average followup was of 24.3 months (range 11-40 months). Lesion type was ICRS type II in five patients (35.7%) and ICRS type III in nine patients (64.3%). In cases with ICRS-OCD type II lesions, in situ fixation was applied following circumferential multiple drilling, while mosaicplasty was done following debridement and multiple drilling in cases with ICRS-OCD type III lesion. Mosaicplasty was performed in the lesion area by an average of 2.5 (range 1-3) cylindrical osteochondral autografts. Patients were not allowed to perform loading activities for 3 weeks in the postoperative period; movement was initiated by using CPM device in the early phase; full range of motion was achieved in third week, and full weight bearing was permitted in 6 to 8 weeks Results: While 6 and 8 patients were classified preoperatively as fair and poor, respectively, according to Hughston scale, excellent and good results were obtained postoperatively in 10 and 4 patients, respectively. During the followup, no problems were detected in any of the patients in the regions where osteochondral graft was harvested. Conclusion: Biologic fixation or mosaicplasty and drilling as a technique to treatment of the lesion in OCD by osteochondral autograft transfer has resulted in good and excellent clinical outcomes in our patients and it is considered that providing blood flow to subchondral bone by circumferencial drilling leads to an increase in the robustness of biological internal fixation and shortens the duration of recovery. PMID:21886927

  2. Development of novel three-dimensional printed scaffolds for osteochondral regeneration.

    PubMed

    Holmes, Benjamin; Zhu, Wei; Li, Jiaoyan; Lee, James D; Zhang, Lijie Grace

    2015-01-01

    As modern medicine advances, various methodologies are being explored and developed in order to treat severe osteochondral defects in joints. However, it is still very challenging to cure the osteochondral defects due to their poor inherent regenerative capacity, complex stratified architecture, and disparate biomechanical properties. The objective of this study is to create novel three-dimensional (3D) printed osteochondral scaffolds with both excellent interfacial mechanical properties and biocompatibility for facilitating human bone marrow mesenchymal stem cell (MSC) growth and chondrogenic differentiation. For this purpose, we designed and 3D printed a series of innovative bi-phasic 3D models that mimic the osteochondral region of articulate joints. Our mechanical testing results showed that our bi-phasic scaffolds with key structures have enhanced mechanical characteristics in compression (a maximum Young's modulus of 31 MPa) and shear (a maximum fracture strength of 5768 N/mm(2)) when compared with homogenous designs. These results are also correlated with numerical simulation. In order to improve their biocompatibility, the scaffolds' surfaces were further modified with acetylated collagen (one of the main components in osteochondral extracellular matrix). MSC proliferation results demonstrated that incorporation of a collagen, along with biomimetically designed micro-features, can greatly enhance MSC growth after 5 days in vitro. Two weeks' chondrogenic differentiation results showed that our novel scaffolds (dubbed "key" scaffolds), both with and without surface collagen modification, displayed enhanced chondrogenesis (e.g., 130%, 114%, and 236% increases in glycosaminoglycan, type II collagen deposition, and total protein content on collagen-modified key scaffolds when compared with homogeneous controls). PMID:25088966

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

    PubMed

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

    2014-10-01

    The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formulations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair. PMID:25047629

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

    PubMed Central

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

    2014-01-01

    The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair. PMID:25047629

  5. Development of Novel Three-Dimensional Printed Scaffolds for Osteochondral Regeneration

    PubMed Central

    Holmes, Benjamin; Zhu, Wei; Li, Jiaoyan; Lee, James D.

    2015-01-01

    As modern medicine advances, various methodologies are being explored and developed in order to treat severe osteochondral defects in joints. However, it is still very challenging to cure the osteochondral defects due to their poor inherent regenerative capacity, complex stratified architecture, and disparate biomechanical properties. The objective of this study is to create novel three-dimensional (3D) printed osteochondral scaffolds with both excellent interfacial mechanical properties and biocompatibility for facilitating human bone marrow mesenchymal stem cell (MSC) growth and chondrogenic differentiation. For this purpose, we designed and 3D printed a series of innovative bi-phasic 3D models that mimic the osteochondral region of articulate joints. Our mechanical testing results showed that our bi-phasic scaffolds with key structures have enhanced mechanical characteristics in compression (a maximum Young's modulus of 31 MPa) and shear (a maximum fracture strength of 5768 N/mm2) when compared with homogenous designs. These results are also correlated with numerical simulation. In order to improve their biocompatibility, the scaffolds' surfaces were further modified with acetylated collagen (one of the main components in osteochondral extracellular matrix). MSC proliferation results demonstrated that incorporation of a collagen, along with biomimetically designed micro-features, can greatly enhance MSC growth after 5 days in vitro. Two weeks' chondrogenic differentiation results showed that our novel scaffolds (dubbed “key” scaffolds), both with and without surface collagen modification, displayed enhanced chondrogenesis (e.g., 130%, 114%, and 236% increases in glycosaminoglycan, type II collagen deposition, and total protein content on collagen-modified key scaffolds when compared with homogeneous controls). PMID:25088966

  6. Two Patients with Osteochondral Injury of the Weight-Bearing Portion of the Lateral Femoral Condyle Associated with Lateral Dislocation of the Patella

    PubMed Central

    Inoue, Hiroaki; Atsumi, Satoru; Ichimaru, Shohei; Fujiwara, Hiroyoshi; Kubo, Toshikazu

    2014-01-01

    Complications of patellar dislocation include osteochondral injury of the lateral femoral condyle and patella. Most cases of osteochondral injury occur in the anterior region, which is the non-weight-bearing portion of the lateral femoral condyle. We describe two patients with osteochondral injury of the weight-bearing surface of the lateral femoral condyle associated with lateral dislocation of the patella. The patients were 18- and 11-year-old females. Osteochondral injury occurred on the weight-bearing surface distal to the lateral femoral condyle. The presence of a free osteochondral fragment and osteochondral injury of the lateral femoral condyle was confirmed on MRI and reconstruction CT scan. Treatment consisted of osteochondral fragment fixation or microfracture, as well as patellar stabilization. Osteochondral injury was present in the weight-bearing portion of the lateral femoral condyle in both patients, suggesting that the injury was caused by friction between the patella and lateral femoral condyle when the patella was dislocated or reduced at about 90 flexion of the knee joint. These findings indicate that patellar dislocation may occur and osteochondral injury may extend to the weight-bearing portion of the femur even in deep flexion, when the patella is stabilized on the bones of the femoral groove. PMID:25506015

  7. Mosaicplasty for the treatment of a large traumatic osteochondral femoral head lesion: a case report with 2 year follow-up and review of the literature.

    PubMed

    Anthonissen, J; Rommens, P M; Hofmann, A

    2016-01-01

    Different joint-preserving techniques have been described for the treatment of traumatic osteochondral lesions of the femoral head especially in young active patients. Mosaicplasty with autologous transplantation of osteochondral cylinders is an established surgical technique in the knee. Little evidence, however, exists for the treatment of osteochondral lesions in the hip using this technique. Here, we report on the result of treatment of a traumatic 5 cm(2) osteochondral lesion of the femoral head in a young patient treated with mosaicplasty. Grafts were taken from the ipsilateral knee. After 2 years, the outcome was satisfactory with partial return to previous activity level. PMID:26506828

  8. Steroid-induced femoral head osteonecrosis in immune thrombocytopenia treatment with osteochondral autograft transplantation.

    PubMed

    Fotopoulos, Vasileios Ch; Mouzopoulos, George; Floros, Themistoklis; Tzurbakis, Matthaios

    2015-09-01

    Osteonecrosis of the femoral head is a devastating complication of steroid administration and has rarely been observed in the treatment of immune thrombocytopenia. The treatment of osteochondral defects in advanced stages of avascular necrosis (AVN), characterized by collapse of the subchondral bone, remains an unsolved burden in orthopedic surgery. In this report, we present a case of a 19-year-old female that was admitted in the Emergency Department with walking disability and painful hip joint movement due to steroid-induced femoral head osteonecrosis. Two years before she was diagnosed with immune thrombocytopenia, for which she received pulse steroid therapy with high dose of dexamethasone and underwent a splenectomy. This case report is the first to describe the use of osteochondral autograft transplantation as a treatment of steroid-induced AVN of the femoral head due to immune thrombocytopenia at the age of 19 years with very good clinical and radiological results 3 years postoperatively. PMID:25173503

  9. Percutaneous CT-Guided Treatment of Osteochondritis Dissecans of the Sacroiliac Joint

    SciTech Connect

    Becce, Fabio; Mouhsine, Elyazid; Mosimann, Pascal John; Anaye, Anass; Letovanec, Igor; Theumann, Nicolas

    2012-08-15

    Osteochondritis dissecans (OCD) is a joint disorder that affects the articular cartilage and subchondral bone, most commonly at the knee. OCD of the sacroiliac joint is extremely rare. Management of OCD remains controversial, and surgery is often needed, especially when conservative treatment fails. We present a rare case of OCD involving the left sacroiliac joint successfully treated by percutaneous computed tomography-guided retrograde drilling and debridement.

  10. The effect of devitalized trabecular bone on the formation of osteochondral tissue-engineered constructs

    PubMed Central

    Lima, Eric G.; Chao, Pen-hsiu Grace; Ateshian, Gerard A.; Bal, B. Sonny; Cook, James L.; Vunjak-Novakovic, Gordana; Hung, Clark T.

    2008-01-01

    In the current study, evidence is presented demonstrating that devitalized trabecular bone has an inhibitory effect on in vitro chondral tissue development when used as a base material for the tissue-engineering of osteochondral constructs for cartilage repair. Chondrocyte-seeded agarose hydrogel constructs were cultured alone or attached to an underlying bony base in a chemically defined medium formulation that has been shown to yield engineered cartilaginous tissue with native Young's modulus (EY) and glycosaminoglycan (GAG) content. By day 42 in culture the incorporation of a bony base significantly reduced these properties (EY = 87 ± 12 kPa, GAG = 1.9 ± 0.8%ww) compared to the gel-alone group (EY = 642 ± 97 kPa, GAG = 4.6 ± 1.4%ww). Similarly, the mechanical and biochemical properties of chondrocyte-seeded agarose constructs were inhibited when co-cultured adjacent to bone (unattached), suggesting that soluble factors rather than direct cell–bone interactions mediate the chondro-inhibitory bone effects. Altering the method of bone preparation, including demineralization, or the timing of bone introduction in co-culture did not ameliorate the effects. In contrast, osteochondral constructs with native cartilage properties (EY = 730 ± 65 kPa, GAG = 5.2 ± 0.9%ww) were achieved when a porous tantalum metal base material was adopted instead of bone. This work suggests that devitalized bone may not be a suitable substrate for long-term cultivation of osteochondral grafts. PMID:18718655

  11. Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering.

    PubMed

    Steinmetz, Neven J; Aisenbrey, Elizabeth A; Westbrook, Kristofer K; Qi, H Jerry; Bryant, Stephanie J

    2015-07-01

    A bioinspired multi-layer hydrogel was developed for the encapsulation of human mesenchymal stem cells (hMSCs) as a platform for osteochondral tissue engineering. The spatial presentation of biochemical cues, via incorporation of extracellular matrix analogs, and mechanical cues, via both hydrogel crosslink density and externally applied mechanical loads, were characterized in each layer. A simple sequential photopolymerization method was employed to form stable poly(ethylene glycol)-based hydrogels with a soft cartilage-like layer of chondroitin sulfate and low RGD concentrations, a stiff bone-like layer with high RGD concentrations, and an intermediate interfacial layer. Under a compressive load, the variation in hydrogel stiffness within each layer produced high strains in the soft cartilage-like layer, low strains in the stiff bone-like layer, and moderate strains in the interfacial layer. When hMSC-laden hydrogels were cultured statically in osteochondral differentiation media, the local biochemical and matrix stiffness cues were not sufficient to spatially guide hMSC differentiation after 21 days. However dynamic mechanical stimulation led to differentially high expression of collagens with collagen II in the cartilage-like layer, collagen X in the interfacial layer and collagen I in the bone-like layer and mineral deposits localized to the bone layer. Overall, these findings point to external mechanical stimulation as a potent regulator of hMSC differentiation toward osteochondral cellular phenotypes. PMID:25900444

  12. Spatial Engineering of Osteochondral Tissue Constructs Through Microfluidically Directed Differentiation of Mesenchymal Stem Cells

    PubMed Central

    Goldman, Stephen M.; Barabino, Gilda A.

    2016-01-01

    Abstract The development of tissue engineered osteochondral units has been slowed by a number of technical hurdles associated with recapitulating their heterogeneous nature ex vivo. Subsequently, numerous approaches with respect to cell sourcing, scaffolding composition, and culture media formulation have been pursued, which have led to high variability in outcomes and ultimately the lack of a consensus bioprocessing strategy. As such, the objective of this study was to standardize the design process by focusing on differentially supporting formation of cartilaginous and bony matrix by a single cell source in a spatially controlled manner within a single material system. A cell-polymer solution of bovine mesenchymal stem cells and agarose was cast against micromolds of a serpentine network and stacked to produce tissue constructs containing two independent microfluidic networks. Constructs were fluidically connected to two controlled flow loops and supplied with independently tuned differentiation parameters for chondrogenic and osteogenic induction, respectively. Constructs receiving inductive media showed differential gene expression of both chondrogenic and osteogenic markers in opposite directions along the thickness of the construct that was recapitulated at the protein level with respect to collagens I, II, and X. A control group receiving noninductive media showed homogeneous expression of these biomarkers measured in lower concentrations at both the mRNA and protein level. This work represents an important step in the rational design of engineered osteochondral units through establishment of an enabling technology for further optimization of scaffolding formulations and bioprocessing conditions toward the production of commercially viable osteochondral tissue products. PMID:27190700

  13. Changes in dissipated energy and contact pressure after osteochondral graft transplantation.

    PubMed

    Bobrowitsch, Evgenij; Lorenz, Andrea; Jörg, Johanna; Leichtle, Ulf G; Wülker, Nikolaus; Walter, Christian

    2014-09-01

    Osteochondral autologous transplantation is frequently used to repair small cartilage defects. Incongruence between the osteochondral graft surface and the adjacent cartilage leads to changed friction and contact pressure. The present study wanted to analyze the differences between intact and surgically treated cartilage surface in respect to contact pressure and frictional characteristic (dissipated energy). Six ovine carpometacarpal joints were used in the present study. Dissipated energy during instrumentally controlled joint movement as well as static contact pressure were measured in different cartilage states (intact, defect, deep-, flush-, high-implanted osteochondral graft and cartilage failure simulation on a high-implanted graft). The best contact area restoration was observed after the flush implantation. However, the dissipated energy measurements did not reveal an advantage of the flush implantation compared to the defect and deep-implanted graft states. The high-implanted graft was associated with a significant increase of the mean contact pressure and decrease of the contact area but the dissipated energy was on the level of intact cartilage in contrast to other treatments where the dissipated energy was significantly higher as in the intact state. However the cartilage failure simulation on the high-implanted graft showed the highest increase of the dissipated energy. PMID:25066582

  14. Knee salvage procedures: The indications, techniques and outcomes of large osteochondral allografts

    PubMed Central

    Chui, Karen; Jeys, Lee; Snow, Martyn

    2015-01-01

    The overall incidence of osteochondral defect in the general population is estimated to be 15 to 30 per 100000 people. These lesions can become symptomatic causing pain, swelling and decreased function of the knee, and may eventually progress to osteoarthritis. In the young and active population, partial or total knee arthroplasty (TKA) is rarely the treatment of choice due to risk of early failure. Osteochondral allograft transplantation has been demonstrated to be a safe and effective treatment of large osteochondral and chondral defects of the knee in appropriately selected patients. The treatment reduces pain, improves function and is a viable limb salvage procedure for patients, especially young and active patients for whom TKA is not recommended. Either large dowels generated with commercially available equipment or free hand shell allografts can be implanted in more posterior lesions. Current recommendations for fresh allografts stored at 4C advise implantation within 21-28 d of procurement for optimum chondrocyte viability, following screening and testing protocols. Higher rates of successful allograft transplantation are observed in younger patients, unipolar lesions, normal or corrected malalignment, and defects that are treated within 12 mo of symptom onset. Patients with bipolar lesions, uncorrectable malalignment, advanced osteoarthritis, and those over 40 tend to have less favourable outcomes. PMID:25893177

  15. Development and characterisation of a decellularised bovine osteochondral biomaterial for cartilage repair.

    PubMed

    Fermor, Hazel L; Russell, Serena L; Williams, Sophie; Fisher, John; Ingham, Eileen

    2015-05-01

    It is proposed that an acellular natural osteochondral scaffold will provide a successful repair material for the early intervention treatment of cartilage lesions, to prevent or slow the progression of cartilage deterioration to osteoarthritis. Here, we investigated the efficacy of methods for the decellularisation of bovine osteochondral plugs. The plugs were subject to four freeze/thaw cycles followed by two cycles of washes in hypotonic solution and low concentration (0.1% w/v) sodium dodecyl sulphate with protease inhibitors. Plugs were treated with nuclease (DNase and RNase) treatment followed by sterilization in peracetic acid. Full tissue decellularisation was achieved as confirmed by histological analysis and DNA quantification, however the resultant acellular matrix had reduced glycosaminoglycan content which led to an increased percent deformation of cartilage. Furthermore, the acellular scaffold was not reproducibly biocompatible. Additional terminal washes were included in the process to improve biocompatibility, however, this led to visible structural damage to the cartilage. This damage was found to be minimised by reducing the cut edge to cartilage area ratio through decellularisation of larger cuts of osteochondral tissue. PMID:25893393

  16. Fabrication and development of artificial osteochondral constructs based on cancellous bone/hydrogel hybrid scaffold.

    PubMed

    Song, Kedong; Li, Liying; Yan, Xinyu; Zhang, Yu; Li, Ruipeng; Wang, Yiwei; Wang, Ling; Wang, Hong; Liu, Tianqing

    2016-06-01

    Using tissue engineering techniques, an artificial osteochondral construct was successfully fabricated to treat large osteochondral defects. In this study, porcine cancellous bones and chitosan/gelatin hydrogel scaffolds were used as substitutes to mimic bone and cartilage, respectively. The porosity and distribution of pore size in porcine bone was measured and the degradation ratio and swelling ratio for chitosan/gelatin hydrogel scaffolds was also determined in vitro. Surface morphology was analyzed with the scanning electron microscope (SEM). The physicochemical properties and the composition were tested by using an infrared instrument. A double layer composite scaffold was constructed via seeding adipose-derived stem cells (ADSCs) induced to chondrocytes and osteoblasts, followed by inoculation in cancellous bones and hydrogel scaffolds. Cell proliferation was assessed through Dead/Live staining and cellular activity was analyzed with IpWin5 software. Cell growth, adhesion and formation of extracellular matrix in composite scaffolds blank cancellous bones or hydrogel scaffolds were also analyzed. SEM analysis revealed a super porous internal structure of cancellous bone scaffolds and pore size was measured at an average of 410 ± 59 μm while porosity was recorded at 70.6 ± 1.7 %. In the hydrogel scaffold, the average pore size was measured at 117 ± 21 μm and the porosity and swelling rate were recorded at 83.4 ± 0.8 % and 362.0 ± 2.4 %, respectively. Furthermore, the remaining hydrogel weighed 80.76 ± 1.6 % of the original dry weight after hydration in PBS for 6 weeks. In summary, the cancellous bone and hydrogel composite scaffold is a promising biomaterial which shows an essential physical performance and strength with excellent osteochondral tissue interaction in situ. ADSCs are a suitable cell source for osteochondral composite reconstruction. Moreover, the bi-layered scaffold significantly enhanced cell proliferation compared to the cells seeded on either single scaffold. Therefore, a bi-layered composite scaffold is an appropriate candidate for fabrication of osteochondral tissue. PMID:27180235

  17. Rotational osteoplasty and bioabsorbable polylactate pin fixation in Pipkin type 2 fracture with acute osteochondral defect: a case report.

    PubMed

    Maluta, Tommaso; Micheloni, Gian Mario; Sandri, Andrea; Regis, Dario; Costanzo, Alessandro; Magnan, Bruno

    2016-01-01

    Pipkin fractures are relative rare high-energy lesions characterized by an intra-articular fracture of the femoral head after posterior hip dislocation. Early anatomic reduction and stable fixation are the main goals of treatment. This case evaluates the outcome of managing Pipkin type 2 fracture with acute osteochondral defect of the femoral head using "rotational osteoplasty" and bioabsorbable polylactate pin fixation. 24-year-old male patient was involved in a motorcycle accident, suffering from a left hip fracture-dislocation, and pelvic Computed Tomography revealed a Pipkin type 2 lesion. An open urgent treatment was performed. After  anatomic reduction of the femoral head fragment a large osteochondral defect in the anterior-superior weight bearing surface was evident. The pattern of the fracture allowed us to perform a "rotational osteoplasty" including rotation of the femoral head fragment, to obtain an osteochondral cartilage congruence of the anterior-superior surface. Stable fixation was obtained by three bioabsorbable polylactate pins. At four-year follow up the patient had an excellent outcome and Magnetic Resonance Imaging (MRI) showed fracture healing, minimal signs of arthritis, excluding osteonecrosis of the femoral head. The reported case confirms that Pipkin fractures are very insidious surgical urgencies. In selected cases, "rotational osteoplasty" may be an alternative to osteochondral transplant for acute osteochondral defect of the femoral head. Bioabsorbable polylactate pin fixation allowed us to have a stable fixation evaluating the bone healing process and vitality of femoral head by MRI. PMID:27104330

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

    PubMed

    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. PMID:26177155

  19. Retrograde Percutaneous Drilling for Osteochondritis Dissecans of the Head of the Talus: Case Report and Review of the Literature.

    PubMed

    Corominas, Laura; Sanpera, Ignacio; Masrouha, Karim; Sanpera-Iglesias, Julia

    2016-01-01

    Osteochondral lesions of the talus might be a more common cause of pain than previously recognized, especially among those involved in athletic activities. However, the location of an osteochondral lesion on the talar head is much less common than such lesions localized to the dome of the talus and can pose diagnostic difficulties. We present the case of a 14-year-old soccer player who complained of longstanding pain in his left foot. After unsuccessful conservative treatment consisting of rest and bracing, he was ultimately treated with retrograde percutaneous drilling of the talar head performed by a medial approach. This was followed by casting and non-weightbearing for 6 weeks, after which physical therapy was undertaken. He was able to return to full activity and remained asymptomatic during a 5-year observation period. Although rare, osteochondritis dissecans of the talar head should be considered in young athletes with persistent foot pain that is unresponsive to reasonable therapy. PMID:25459089

  20. Osteochondral Tissue Regeneration using a Bilayered Composite Hydrogel with Modulating Dual Growth Factor Release Kinetics in a Rabbit Model

    PubMed Central

    Kim, Kyobum; Lam, Johnny; Lu, Steven; Spicer, Patrick P.; Lueckgen, Aline; Tabata, Yasuhiko; Wong, Mark E.; Jansen, John A.; Mikos, Antonios G.; Kasper, F. Kurtis

    2013-01-01

    Biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) composite hydrogels have been investigated for the delivery of growth factors (GFs) with the aid of gelatin microparticles (GMPs) and stem cell populations for osteochondral tissue regeneration. In this study, a bilayered OPF composite hydrogel that mimics the distinctive hierarchical structure of native osteochondral tissue was utilized to investigate the effect of transforming growth factor-β3 (TGF-β3) with varying release kinetics and/or insulin-like growth factor-1 (IGF-1) on osteochondral tissue regeneration in a rabbit full-thickness osteochondral defect model. The four groups investigated included (i) a blank control (no GFs), (ii) GMP-loaded IGF-1 alone, (iii) GMP-loaded IGF-1 and gel-loaded TGF-β3, and (iv) GMP-loaded IGF-1 and GMP-loaded TGF-β3 in OPF composite hydrogels. The results of an in vitro release study demonstrated that TGF-β3 release kinetics could be modulated by the GF incorporation method. At 12 weeks post-implantation, the quality of tissue repair in both chondral and subchondral layers was analyzed based on quantitative histological scoring. All groups incorporating GFs resulted in a significant improvement in cartilage morphology compared to the control. Single delivery of IGF-1 showed higher scores in subchondral bone morphology as well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue when compared to a dual delivery of IGF-1 and TGF-β3, independent of the TGF-β3 release kinetics. The results suggest that although the dual delivery of TGF-β3 and IGF-1 may not synergistically enhance the quality of engineered tissue, the delivery of IGF-1 alone from bilayered composite hydrogels positively affects osteochondral tissue repair and holds promise for osteochondral tissue engineering applications. PMID:23541928

  1. High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue.

    PubMed

    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. PMID:25924853

  2. Osteochondral lesion of the talus in a recreational athlete: a case report

    PubMed Central

    deGraauw, Chris

    1999-01-01

    A 23-year-old recreational male athlete presented with intermittent pain of three weeks duration, localized to the left ankle. Pain was aggravated by walking, although his symptoms had not affected the patient’s jogging activity which was performed three times per week. Past history revealed an inversion sprain of the left ankle, sustained fifteen months previously. Examination showed mild swelling anterior to the ankle mortise joint while other tests including range of motion, strength and motion palpation of specific joints of the ankle were noted to be unremarkable. Radiographic findings revealed a defect in the medial aspect of the talus. An orthopaedic referral was made for further evaluation. Tomography revealed a Grade III osteochondral lesion of the talus. It was determined that follow-up views be taken in three months to demonstrate if the lesion was progressing or healing. Within the three month period, activity modifications and modalities for pain control were indicated. Surgery was considered a reasonable option should conservative measures fail. The present case illustrates an osteochondral lesion of the talus, a condition which has not previously been reported in the chiropractic literature. A review of the pertinent orthopaedic literature has indicated an average delay of three years in diagnosing the existence of this lesion. Although considered rare, the diagnostic frequency of the condition appears to be on the rise due to increased awareness and the use of bone and CT scans. The osteochondral lesion of the talus deserves particular consideration by practitioners working with athletes due to its higher incidence within this group. This diagnosis should be considered in patients presenting with chronic ankle pain particularly when a history of an inversion sprain exists. The purpose of this report is to increase awareness of this condition, and review diagnosis and management strategies. ImagesFigure 1Figure 2

  3. Design and characterization of a tissue-engineered bilayer scaffold for osteochondral tissue repair.

    PubMed

    Giannoni, Paolo; Lazzarini, Erica; Ceseracciu, Luca; Barone, Alberto C; Quarto, Rodolfo; Scaglione, Silvia

    2015-10-01

    Treatment of full-thickness cartilage defects relies on osteochondral bilayer grafts, which mimic the microenvironment and structure of the two affected tissues: articular cartilage and subchondral bone. However, the integrity and stability of the grafts are hampered by the presence of a weak interphase, generated by the layering processes of scaffold manufacturing. We describe here the design and development of a bilayer monolithic osteochondral graft, avoiding delamination of the two distinct layers but preserving the cues for selective generation of cartilage and bone. A highly porous polycaprolactone-based graft was obtained by combining solvent casting/particulate leaching techniques. Pore structure and interconnections were designed to favour in vivo vascularization only at the bony layer. Hydroxyapatite granules were added as bioactive signals at the site of bone regeneration. Unconfined compressive tests displayed optimal elastic properties and low residual deformation of the graft after unloading (< 3%). The structural integrity of the graft was successfully validated by tension fracture tests, revealing high resistance to delamination, since fractures were never displayed at the interface of the layers (n = 8). Ectopic implantation of grafts in nude mice, after seeding with bovine trabecular bone-derived mesenchymal stem cells and bovine articular chondrocytes, resulted in thick areas of mature bone surrounding ceramic granules within the bony layer, and a cartilaginous alcianophilic matrix in the chondral layer. Vascularization was mostly observed in the bony layer, with a statistically significant higher blood vessel density and mean area. Thus, the easily generated osteochondral scaffolds, since they are mechanically and biologically functional, are suitable for tissue-engineering applications for cartilage repair. PMID:23172816

  4. OSTEOCHONDRAL INTERFACE REGENERATION OF THE RABBIT KNEE WITH MACROSCOPIC GRADIENTS OF BIOACTIVE SIGNALS

    PubMed Central

    Dormer, Nathan H.; Singh, Milind; Zhao, Liang; Mohan, Neethu; Berkland, Cory J.; Detamore, Michael S.

    2011-01-01

    To date, most interfacial tissue engineering approaches have utilized stratified designs, in which there are two or more discrete layers comprising the interface. Continuously-graded interfacial designs, where there is no discrete transition from one tissue type to another, are gaining attention as an alternative to stratified designs. Given that osteochondral regeneration holds the potential to enhance cartilage regeneration by leveraging the healing capacity of the underlying bone, we endeavored to introduce a continuously graded approach to osteochondral regeneration. The purpose of this study was thus to evaluate the performance of a novel gradient-based scaffolding approach to regenerate osteochondral defects in the New Zealand White rabbit femoral condyle. Bioactive plugs were constructed from poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres with a continuous gradient transition between cartilage-promoting and bone-promoting growth factors. At six and 12 weeks of healing, results suggested that the implants provided support for the neo-synthesized tissue, and the gradient in bioactive signaling may have been beneficial for bone and cartilage regeneration compared to the blank control implant, as evidenced by histology. In addition, the effects of pre-seeding gradient scaffolds with umbilical cord mesenchymal stromal cells (UCMSCs) from the Wharton’s jelly of New Zealand White rabbits were evaluated. Results indicated that there may be regenerative benefits to pre-localizing UCMSCs within scaffold interiors. The inclusion of bioactive factors in a gradient-based scaffolding design is a promising new treatment strategy for defect repair in the femoral condyle. PMID:22009693

  5. Evaluation of an injectable thermoresponsive hyaluronan hydrogel in a rabbit osteochondral defect model.

    PubMed

    D'Este, Matteo; Sprecher, Christoph Martin; Milz, Stefan; Nehrbass, Dirk; Dresing, Iska; Zeiter, Stephan; Alini, Mauro; Eglin, David

    2016-06-01

    Articular cartilage displays very little self-healing capabilities, generating a major clinical need. Here, we introduce a thermoresponsive hyaluronan hydrogel for cartilage repair obtained by covalently grafting poly(N-isopropylacrylamide) to hyaluronan, to give a brush co-polymer HpN. The gel is fluid at room temperature and becomes gel at body temperature. In this pilot study HpN safety and repair response were evaluated in an osteochondral defect model in rabbit. Follow-up was of 1 week and 12 weeks and the empty defect served as a control, for a total of four experimental groups. At 12 weeks the defect sites were evaluated macroscopically and histologically. Local lymph nodes, spleen, liver, and kidneys were analyzed for histopathological evaluation. HpN could be easily injected and remained into the defect throughout the study. The macroscopic score was statistically superior for HpN versus empty. Histological score gave opposite trend but not statistically significant. A slight tissue reaction was observed around HpN, however, vascularization and subchondral bone formation were not impeded. An upper proteoglycans rich fibro-cartilaginous tissue with fairly good continuity and lateral integration into the existing articular cartilage was observed in all cases. No signs of local or systemic acute or subacute toxicity were observed. In conclusion, HpN is easily injectable, remains into an osteochondral defect within a moving synovial joint, is biocompatible and does not interfere with the intrinsic healing response of osteochondral defects in a rabbit model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1469-1478, 2016. PMID:26833870

  6. An Unexpected Complication after Headless Compression Screw Fixation of an Osteochondral Fracture of Patella

    PubMed Central

    Aydoğmuş, Suavi; Keçeci, Tolga

    2016-01-01

    This study evaluated complications associated with implant depth in headless compression screw treatment of an osteochondral fracture associated with a traumatic patellar dislocation in a 21-year-old woman. Computed tomography and X-rays showed one lateral fracture fragment measuring 25 × 16 mm. Osteosynthesis was performed with two headless compression screws. Five months later, the screws were removed because of patella-femoral implant friction. We recommend that the screw heads be embedded to a depth of at least 3 mm below the cartilage surface. Further clinical studies need to examine the variation in cartilage thickness in the fracture fragment. PMID:27051547

  7. Wnt/β-catenin signaling of cartilage canal and osteochondral junction chondrocytes and full thickness cartilage in early equine osteochondrosis.

    PubMed

    Kinsley, Marc A; Semevolos, Stacy A; Duesterdieck-Zellmer, Katja F

    2015-10-01

    The objective of this study was to elucidate gene and protein expression of Wnt signaling molecules in chondrocytes of foals having early osteochondrosis (OC) versus normal controls. The hypothesis was that increased expression of components of Wnt signaling pathway in osteochondral junction (OCJ) and cartilage canal (CC) chondrocytes would be found in early OC when compared to controls. Paraffin-embedded osteochondral samples (7 OC, 8 normal) and cDNA from whole cartilage (7 OC, 10 normal) and chondrocytes surrounding cartilage canals and osteochondral junctions captured with laser capture microdissection (4 OC, 6 normal) were obtained from femoropatellar joints of 17 immature horses. Equine-specific Wnt signaling molecule mRNA expression levels were evaluated by two-step real-time qPCR. Spatial tissue protein expression of β-catenin, Wnt-11, Wnt-4, and Dkk-1 was determined by immunohistochemistry. There was significantly decreased Wnt-11 and increased β-catenin, Wnt-5b, Dkk-1, Lrp6, Wif-1, Axin1, and SC-PEP gene expression in early OC cartilage canal chondrocytes compared to controls. There was also significantly increased β-catenin gene expression in early OC osteochondral junction chondrocytes compared to controls. Based on this study, abundant gene expression differences in OC chondrocytes surrounding cartilage canals suggest pathways associated with catabolism and inhibition of chondrocyte maturation are targeted in early OC pathogenesis. PMID:25676127

  8. The Role of Erythropoietin and Bone Marrow Concentrate in the Treatment of Osteochondral Defects in Mini-Pigs

    PubMed Central

    Betsch, Marcel; Thelen, Simon; Santak, Laila; Herten, Monika; Jungbluth, Pascal; Miersch, Daniel; Hakimi, Mohssen; Wild, Michael

    2014-01-01

    Background All available treatment options for osteochondral and chondral defects do not restore hyaline cartilage and are limited to decreasing associated pain, and maintaining or improving joint function. The purpose of this study was to evaluate the potential of erythropoietin (EPO) in combination with bone marrow aspiration concentrate (BMAC) in the treatment of osteochondral defects of mini-pigs. Methods 14 Goettinger mini-pigs, in which a 6×10 mm osteochondral defect in the medial femoral condyle of both knee joints was created, were randomized into four groups: biphasic scaffold alone, scaffold with EPO, scaffold with BMAC and scaffold in combination with EPO and BMAC. After 26 weeks all animals were euthanized and histological slides were evaluated using a modified ÓDriscoll Score. Results In the therapy groups, areas of chondrogenic tissue that contained collagen II were present. Adding EPO (p = 0.245) or BMAC (p = 0.099) alone to the scaffold led to a non-significant increase in the score compared to the control group. However, the combination of EPO and BMAC in the implanted scaffold showed a significant improvement (p = 0.02) in the histological score. Conclusion The results of our study show that in mini-pigs, the combination of EPO and BMAC leads to an enhanced osteochondral healing. However, additional research is necessary to further improve the repair tissue and to define the role of MSCs and EPO in cartilage repair. PMID:24676029

  9. Advancements in Orthopedic Intervention: Retrograde Drilling and Bone Grafting of Osteochondral Lesions of the Knee Using Magnetic Resonance Imaging Guidance

    SciTech Connect

    Seebauer, Christian J.; Bail, Hermann J.; Rump, Jens C. Walter, Thula Teichgraeber, Ulf K. M.

    2010-12-15

    Computer-assisted surgery is currently a novel challenge for surgeons and interventional radiologists. Magnetic resonance imaging (MRI)-guided procedures are still evolving. In this experimental study, we describe and assess an innovative passive-navigation method for MRI-guided treatment of osteochondritis dissecans of the knee. A navigation principle using a passive-navigation device was evaluated in six cadaveric knee joint specimens for potential applicability in retrograde drilling and bone grafting of osteochondral lesions using MRI guidance. Feasibility and accuracy were evaluated in an open MRI scanner (1.0 T Philips Panorama HFO MRI System). Interactive MRI navigation allowed precise drilling and bone grafting of osteochondral lesions of the knee. All lesions were hit with an accuracy of 1.86 mm in the coronal plane and 1.4 mm the sagittal plane. Targeting of all lesions was possible with a single drilling. MRI allowed excellent assessment of correct positioning of the cancellous bone cylinder during bone grafting. The navigation device and anatomic structures could be clearly identified and distinguished throughout the entire drilling procedure. MRI-assisted navigation method using a passive navigation device is feasible for the treatment of osteochondral lesions of the knee under MRI guidance and allows precise and safe drilling without exposure to ionizing radiation. This method may be a viable alternative to other navigation principles, especially for pediatric and adolescent patients. This MRI-navigated method is also potentially applicable in many other MRI-guided interventions.

  10. Specific inductive potential of a novel nanocomposite biomimetic biomaterial for osteochondral tissue regeneration.

    PubMed

    Manferdini, C; Cavallo, C; Grigolo, B; Fiorini, M; Nicoletti, A; Gabusi, E; Zini, N; Pressato, D; Facchini, A; Lisignoli, G

    2016-05-01

    Osteochondral lesions require treatment to restore the biology and functionality of the joint. A novel nanostructured biomimetic gradient scaffold was developed to mimic the biochemical and biophysical properties of the different layers of native osteochondral structure. The present results show that the scaffold presents important physicochemical characteristics and can support the growth and differentiation of mesenchymal stromal cells (h-MSCs), which adhere and penetrate into the cartilaginous and bony layers. H-MSCs grown in chondrogenic or osteogenic medium decreased their proliferation during days 14-52 on both scaffold layers and in medium without inducing factors used as controls. Both chondrogenic and osteogenic differentiation of h-MSCs occurred from day 28 and were increased on day 52, but not in the control medium. Safranin O staining and collagen type II and proteoglycans immunostaining confirmed that chondrogenic differentiation was specifically induced only in the cartilaginous layer. Conversely, von Kossa staining, osteocalcin and osteopontin immunostaining confirmed that osteogenic differentiation occurred on both layers. This study shows the specific potential of each layer of the biomimetic scaffold to induce chondrogenic or osteogenic differentiation of h-MSCs. These processes depended mainly on the media used but not the biomaterial itself, suggesting that the local milieu is fundamental for guiding cell differentiation. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23495253

  11. A Hydrogel-Mineral Composite Scaffold for Osteochondral Interface Tissue Engineering

    PubMed Central

    Khanarian, Nora T.; Jiang, Jie; Wan, Leo Q.; Mow, Van C.

    2012-01-01

    Osteoarthritis is the leading cause of physical disability among Americans, and tissue engineered cartilage grafts have emerged as a promising treatment option for this debilitating condition. Currently, the formation of a stable interface between the cartilage graft and subchondral bone remains a significant challenge. This study evaluates the potential of a hybrid scaffold of hydroxyapatite (HA) and alginate hydrogel for the regeneration of the osteochondral interface. Specifically, the effects of HA on the response of chondrocytes were determined, focusing on changes in matrix production and mineralization, as well as scaffold mechanical properties over time. Additionally, the optimal chondrocyte population for interface tissue engineering was evaluated. It was observed that the HA phase of the composite scaffold promoted the formation of a proteoglycan- and type II collagenrich matrix when seeded with deep zone chondrocytes. More importantly, the elevated biosynthesis translated into significant increases in both compressive and shear moduli relative to the mineral-free control. Presence of HA also promoted chondrocyte hypertrophy and type X collagen deposition. These results demonstrate that the hydrogelcalcium phosphate composite supported the formation of a calcified cartilage-like matrix and is a promising scaffold design for osteochondral interface tissue engineering. PMID:21919797

  12. Effect of porosities of bilayered porous scaffolds on spontaneous osteochondral repair in cartilage tissue engineering

    PubMed Central

    Dong, Jian; Ding, Jiandong

    2015-01-01

    Poly(lactide-co-glycolide)-bilayered scaffolds with the same porosity or different ones on the two layers were fabricated, and the porosity effect on in vivo repairing of the osteochondral defect was examined in a comparative way for the first time. The constructs of scaffolds and bone marrow-derived mesenchymal stem cells were implanted into pre-created osteochondral defects in the femoral condyle of New Zealand white rabbits. After 12 weeks, all experimental groups exhibited good cartilage repairing according to macroscopic appearance, cross-section view, haematoxylin and eosin staining, toluidine blue staining, immunohistochemical staining and real-time polymerase chain reaction of characteristic genes. The group of 92% porosity in the cartilage layer and 77% porosity in the bone layer resulted in the best efficacy, which was understood by more biomechanical mimicking of the natural cartilage and subchondral bone. This study illustrates unambiguously that cartilage tissue engineering allows for a wide range of scaffold porosity, yet some porosity group is optimal. It is also revealed that the biomechanical matching with the natural composite tissue should be taken into consideration in the design of practical biomaterials, which is especially important for porosities of a multi-compartment scaffold concerning connected tissues. PMID:26813511

  13. Osteochondritis Dissecans of the Talar Dome in a Collegiate Swimmer: A Case Report

    PubMed Central

    Smith, Michelle; Chang, Cindy J.

    1998-01-01

    Objective: To present the case of an intercollegiate swimmer with a stage IV lateral talar dome injury and associated bony fragments. Background: Lack of distinct diagnostic symptoms, low index of clinical suspicion, and the difficulty of visualizing the early stages of this injury on standard x-rays cause frequent misdiagnosis of talar dome lesions. Differential Diagnosis: Ganglion cyst, with inflammatory synovitis secondary to rupture of cyst; loose bodies from previous occult fracture; osteochondral fracture. Treatment: Initial treatment with nonsteroidal antiinflammatory drugs and a posterior splint for comfort, followed by arthroscopic excision of loose bodies with abrasion and drilling arthroplasty. Uniqueness: Patient presented to the team physician for care of acute left medial ankle pain after the athletic trainer had attempted to rupture a ganglion cyst on the anterolateral aspect of the patient's ankle. Conclusions: Increased clinical suspicion is necessary to correctly diagnose osteochondral lesions, particularly in the early stages. Aggressive treatment of talar dome lesions has a good success rate and may be an attractive option for competitive athletes. ImagesFigure 2.Figure 3.Figure 4.Figure 5. PMID:16558537

  14. Three-dimensional osteogenic and chondrogenic systems to model osteochondral physiology and degenerative joint diseases.

    PubMed

    Alexander, Peter G; Gottardi, Riccardo; Lin, Hang; Lozito, Thomas P; Tuan, Rocky S

    2014-09-01

    Tissue engineered constructs have the potential to function as in vitro pre-clinical models of normal tissue function and disease pathogenesis for drug screening and toxicity assessment. Effective high throughput assays demand minimal systems with clearly defined performance parameters. These systems must accurately model the structure and function of the human organs and their physiological response to different stimuli. Musculoskeletal tissues present unique challenges in this respect, as they are load-bearing, matrix-rich tissues whose functionality is intimately connected to the extracellular matrix and its organization. Of particular clinical importance is the osteochondral junction, the target tissue affected in degenerative joint diseases, such as osteoarthritis (OA), which consists of hyaline articular cartilage in close interaction with subchondral bone. In this review, we present an overview of currently available in vitro three-dimensional systems for bone and cartilage tissue engineering that mimic native physiology, and the utility and limitations of these systems. Specifically, we address the need to combine bone, cartilage and other tissues to form an interactive microphysiological system (MPS) to fully capture the biological complexity and mechanical functions of the osteochondral junction of the articular joint. The potential applications of three-dimensional MPSs for musculoskeletal biology and medicine are highlighted. PMID:24994814

  15. Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine

    PubMed Central

    Sundelacruz, Sarah; Kaplan, David L.

    2009-01-01

    In osteochondral tissue engineering, cell recruitment, proliferation, differentiation, and patterning are critical for forming biologically and structurally viable constructs for repair of damaged or diseased tissue. However, since constructs prepared ex vivo lack the multitude of cues present in the in vivo microenvironment, cells often need to be supplied with external biological and physical stimuli to coax them towards targeted tissue functions. To determine which stimuli to present to cells, bioengineering strategies can benefit significantly from endogenous examples of skeletogenesis. As an example of developmental skeletogenesis, the developing limb bud serves as an excellent model system in which to study how an osteochondral structures form from undifferentiated precursor cells. Alongside skeletal formation during embryogenesis, bone also possesses innate regenerative capacity, displaying remarkable ability to heal after damage. Bone fracture healing shares many features with bone development, driving the hypothesis that the regenerative process generally recapitulates development. Similarities and differences between the two modes of bone formation may offer insight into the special requirements for healing damaged or diseased bone. Thus, endogenous fracture healing, as an example of regenerative skeletogenesis, may also inform bioengineering strategies. In this review, we summarize the key cellular events involving stem and progenitor cells in developmental and regenerative skeletogenesis, and discuss in parallel the corresponding cell- and scaffold-based strategies that tissue engineers employ to recapitulate these events in vitro. PMID:19508851

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  17. Osteochondral repair in hemophilic ankle arthropathy: from current options to future perspectives

    PubMed Central

    BUDA, ROBERTO; CAVALLO, MARCO; CASTAGNINI, FRANCESCO; FERRANTI, ENRICO; NATALI, SIMONE; GIANNINI, SANDRO

    2015-01-01

    Young hemophilic patients are frequently affected by ankle arthropathy. At the end stage of the disease, the current treatments are arthrodesis and arthroplasty, which have significant drawbacks. Validated procedures capable of slowing down or even arresting the progression towards the end stage are currently lacking. This review aims to discuss the rationale for and feasibility of applying, in mild hemophilic ankle arthropathy, the main techniques currently used to treat osteochondral defects, focusing in particular on ankle distraction, chondrocyte implantation, mesenchymal stem cell transplantation, allograft transplantation and the use of growth factors. To date, ankle distraction is the only procedure that has been successfully used in hemophilic ankle arthropathy. The use of mesenchymal stem cells have recently been evaluated as feasible for osteochondral repair in hemophilic patients. There may be a rationale for the use of growth factors if they are combined with the previous techniques, which could be useful to arrest the progression of the degeneration or delay end-stage procedures. PMID:26904526

  18. TruFit Plug for Repair of Osteochondral Defects—Where Is the Evidence? Systematic Review of Literature

    PubMed Central

    Clockaerts, S.; Van Osch, G.J.V.M.; Somville, J.; Verdonk, P.; Mertens, P.

    2015-01-01

    Objective: Treatment of osteochondral defects remains a challenge in orthopedic surgery. The TruFit plug has been investigated as a potential treatment method for osteochondral defects. This is a biphasic scaffold designed to stimulate cartilage and subchondral bone formation. The aim of this study is to investigate clinical, radiological, and histological efficacy of the TruFit plug in restoring osteochondral defects in the joint. Design: We performed a systematic search in five databases for clinical trials in which patients were treated with a TruFit plug for osteochondral defects. Studies had to report clinical, radiological, or histological outcome data. Quality of the included studies was assessed. Results: Five studies describe clinical results, all indicating improvement at follow-up of 12 months compared to preoperative status. However, two studies reporting longer follow-up show deterioration of early improvement. Radiological evaluation indicates favorable MRI findings regarding filling of the defect and incorporation with adjacent cartilage at 24 months follow-up, but conflicting evidence exists on the properties of the newly formed overlying cartilage surface. None of the included studies showed evidence for bone ingrowth. The few histological data available confirmed these results. Conclusion: There are no data available that support superiority or equality of TruFit compared to conservative treatment or mosaicplasty/microfracture. Further investigation is needed to improve synthetic biphasic implants as therapy for osteochondral lesions. Randomized controlled clinical trials comparing TruFit plugs with an established treatment method are needed before further clinical use can be supported. PMID:26069706

  19. Involvement of mitochondrial dysfunction and ER-stress in the physiopathology of equine osteochondritis dissecans (OCD).

    PubMed

    Desjardin, Clémence; Chat, Sophie; Gilles, Mailys; Legendre, Rachel; Riviere, Julie; Mata, Xavier; Balliau, Thierry; Esquerré, Diane; Cribiu, Edmond P; Betch, Jean-Marc; Schibler, Laurent

    2014-06-01

    Osteochondrosis (OC) is a developmental bone disorder affecting several mammalian species including the horse. Equine OC is described as a focal disruption of endochondral ossification, leading to osteochondral lesions (osteochondritis dissecans, OCD) that may release free bodies within the joint. OCD lesions trigger joint swelling, stiffness and lameness and affects about 30% of the equine population. OCD is considered as multifactorial but its physiopathology is still poorly understood and genes involved in genetic predisposition are still unknown. Our study compared two healthy and two OC-affected 18-month-old French Trotters diagnosed with OCD lesions at the intermediate ridge of the distal tibia. A comparative shot-gun proteomic analysis of non-wounded cartilage and sub-chondral bone from healthy (healthy samples) and OC-affected foals (predisposed samples) identified 83 and 53 modulated proteins, respectively. These proteins are involved in various biological pathways including matrix structure and maintenance, protein biosynthesis, folding and transport, mitochondrial activity, energy and calcium metabolism. Transmission electron microscopy revealed typical features of mitochondrial swelling and ER-stress, such as large, empty mitochondria, and hyper-dilated rough endoplasmic reticulum, in the deep zone of both OC lesions and predisposed cartilage. Abnormal fibril organization surrounding chondrocytes and abnormal features at the ossification front were also observed. Combining these findings with quantitative trait loci and whole genome sequencing results identified about 140 functional candidate genes carrying putative damaging mutations in 30 QTL regions. In summary, our study suggests that OCD lesions may result from defective hypertrophic terminal differentiation associated with mitochondrial dysfunction and ER-stress, leading to impaired cartilage and bone biomechanical properties, making them prone to fractures. In addition, 11 modulated proteins and several candidate mutations located in QTL regions were identified, bringing new insight into the molecular physiopathology and genetic basis of OCD. PMID:24657499

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

    PubMed Central

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

    2015-01-01

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

  1. Non-destructive monitoring of viability in an ex vivo organ culture model of osteochondral tissue.

    PubMed

    Elson, K M; Fox, N; Tipper, J L; Kirkham, J; Hall, R M; Fisher, J; Ingham, E

    2015-01-01

    Organ culture is an increasingly important tool in research, with advantages over monolayer cell culture due to the inherent natural environment of tissues. Successful organ cultures must retain cell viability. The aim of this study was to produce viable and non-viable osteochondral organ cultures, to assess the accumulation of soluble markers in the conditioned medium for predicting tissue viability. Porcine femoral osteochondral plugs were cultured for 20 days, with the addition of Triton X-100 on day 6 (to induce necrosis), camptothecin (to induce apoptosis) or no toxic additives. Tissue viability was assessed by the tissue destructive XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide tetrazolium salt) assay method and LIVE/DEAD® staining of the cartilage at days 0, 6 and 20. Tissue structure was assessed by histological evaluation using haematoxylin & eosin and safranin O. Conditioned medium was assessed every 3-4 days for glucose depletion, and levels of lactate dehydrogenase (LDH), alkaline phosphatase (AP), glycosaminoglycans (GAGs), and matrix metalloproteinase (MMP)-2 and MMP-9. Necrotic cultures immediately showed a reduction in glucose consumption, and an immediate increase in LDH, GAG, MMP-2 and MMP-9 levels. Apoptotic cultures showed a delayed reduction in glucose consumption and delayed increase in LDH, a small rise in MMP-2 and MMP-9, but no significant effect on GAGs released into the conditioned medium. The data showed that tissue viability could be monitored by assessing the conditioned medium for the aforementioned markers, negating the need for tissue destructive assays. Physiologically relevant whole- or part-joint organ culture models, necessary for research and pre-clinical assessment of therapies, could be monitored this way, reducing the need to sacrifice tissues to determine viability, and hence reducing the sample numbers necessary. PMID:26122871

  2. Osteochondral resurfacing with proximal row carpectomy: 8-year follow-up.

    PubMed

    Fowler, John R; Tang, Peter C; Imbriglia, Joseph E

    2014-10-01

    Degenerative arthrosis of the proximal row remains a challenging problem for both patients and surgeons. Proximal row carpectomy is a motion-preserving treatment option, with studies documenting acceptable long-term outcomes. Proximal row carpectomy is an attractive option because there is no need for fusion to occur between the carpal bones, as in 4-corner fusion. As a result, laborers and smokers may be able to return to work more quickly. However, capitate chondrosis traditionally has been considered a contraindication to proximal row carpectomy. The goal of this study was to review the long-term follow-up of patients who underwent osteochondral resurfacing of capitate chondrosis performed in the same setting as proximal row carpectomy. Final follow-up was obtained in 5 of 8 (63%) patients at an average of 101 months (range, 99-102) after surgery. Grip strength improved at each time point, but wrist flexion and extension decreased. The average Mayo Wrist Score was 74 (range, 65-85) and remained stable or improved in all patients between the 18-month visit and the final visit. The Disabilities of the Arm, Shoulder and Hand (DASH) score was unchanged at final follow-up compared with 18-month follow-up (P=.7). This study found that osteochondral resurfacing of the capitate in the setting of proximal row carpectomy for patients with capitate chondrosis offers good outcomes compared with standard proximal row carpectomy in patients without capitate chondrosis on patient-directed outcome tools (DASH, Mayo Wrist Score) at long-term follow-up of 101 months. PMID:25275971

  3. SURGICAL TREATMENT OF OSTEOCHONDRAL LESIONS OF THE KNEE BY MEANS OF MOSAICPLASTY

    PubMed Central

    De Almeida Lira Neto, Ozório; Da Silveira Franciozi, Carlos Eduardo; De Mello Granata Júnior, Geraldo Sérgio; De Queiroz, Antonio Altenor Bessa; Filho, Mario Carneiro; Navarro, Ricardo Dizioli

    2015-01-01

    Objective: To evaluate the functional results from the technique of mosaicplasty, in the knees of patients with osteochondral lesions. Methods: Between August 1999 and March 2005, 27 patients underwent mosaicplasty on their knees. Twenty-one were male and six were female. The patients' ages ranged from 16 to 64 years (mean of 38.1 years). Seventeen lesions were located on the right knee and ten on the left knee. The lesion was located on the lateral femoral condyle in four patients (15%), on the medial femoral condyle in 18 patients (66.5%) and on the patella in five patients (18.5%). The lesion sizes ranged from 1 to 8 cm2 (mean of 2.7 cm2). The patients were evaluated before and after the operation using Lysholm's functional scale, with a mean follow-up of 2.5 years. Results: Before the operation, the mean was 62.7 points, and after the operation, the mean was 95.4 points. The patients who underwent mosaicplasty on the lateral femoral condyle presented a mean of 51.5 points before the operation, and a mean of 100 points after the operation. In relation to the medial femoral condyle, the mean before the operation was 64.1 points, and it was 95.4 points after the operation. In relation to the patella, the mean before the operation was 66.4 points, and it was 92 points after the operation. Conclusion: Mosaicplasty proved to be a good alternative for treating osteochondral lesions of the knee. It presented better evolution in relation to lesions of the femoral condyles than in relation to lesions located on the patella.

  4. Treatment of osteochondritis dissecans of the knee with a biomimetic scaffold. A prospective multicenter study

    PubMed Central

    DELCOGLIANO, MARCO; MENGHI, AMERIGO; PLACELLA, GIACOMO; SPEZIALI, ANDREA; CERULLI, GIULIANO; CARIMATI, GIULIA; PASQUALOTTO, STEFANO; BERRUTO, MASSIMO

    2014-01-01

    Purpose the aim of the present study was to evaluate the clinical outcome of the treatment of osteochondritis dissecans (OCD) of the knee with a type-I collagen-hydroxyapatite nanostructural biomimetic osteochondral scaffold. Methods twenty-three patients affected by symptomatic knee OCD of the femoral condyles, grade 3 or 4 of the International Cartilage Repair Society (ICRS) scale, underwent biomimetic scaffold implantation. The site of the defect was the medial femoral condyle in 14 patients, whereas in 9 patients the lateral femoral condyle was involved. The average size of the defects was 3.5±1.43 cm2. All patients were clinically evaluated using the ICRS subjective score, the IKDC objective score, the EQ-VAS and the Tegner Activity Score. Minimum follow-up was two years. MRI was performed at 12 and 24 months after surgery and then every 12 months thereafter. Results the ICRS subjective score improved from the baseline value of 50.93±20.6 to 76.44±18.03 at the 12 months (p<0.0005) and 82.23± 17.36 at the two-year follow-up (p<0.0005). The IKDC objective score confirmed the results. The EQ-VAS showed a significant improvement from 3.15±1.09 to 8.15±1.04 (p<0.0005) at two years of follow-up. The Tegner Activity Score improvement was statistically significant (p<0.0005). Conclusions biomimetic scaffold implantation was a good procedure for treating grade 3 and 4 OCD, in which other classic techniques are burdened by different limitations. This open one-step surgery gave promising stable results at short-term follow-up. Level of evidence Level IV, therapeutic case series. PMID:25606552

  5. Osteochondral repair using a scaffold-free tissue-engineered construct derived from synovial mesenchymal stem cells and a hydroxyapatite-based artificial bone.

    PubMed

    Shimomura, Kazunori; Moriguchi, Yu; Ando, Wataru; Nansai, Ryosuke; Fujie, Hiromichi; Hart, David A; Gobbi, Alberto; Kita, Keisuke; Horibe, Shuji; Shino, Konsei; Yoshikawa, Hideki; Nakamura, Norimasa

    2014-09-01

    For an ideal osteochondral repair, it is important to facilitate zonal restoration of the subchondral bone and the cartilage, layer by layer. Specifically, restoration of the osteochondral junction and secure integration with adjacent cartilage could be considered key factors. The purpose of the present study was to investigate the feasibility of a combined material comprising a scaffold-free tissue-engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs) and a hydroxyapatite (HA) artificial bone using a rabbit osteochondral defect model. Osteochondral defects were created on the femoral groove of skeletally mature rabbits. The TEC and HA artificial bone were hybridized to develop a combined implant just before use, which was then implanted into defects (N=23). In the control group, HA alone was implanted (N=18). Histological evaluation and micro-indentation testing was performed for the evaluation of repair tissue. Normal knees were used as an additional control group for biomechanical testing (N=5). At hybridization, the TEC rapidly attached onto the surface of HA artificial bone block, which was implantable to osteochondral defects. Osteochondral defects treated with the combined implants exhibited more rapid subchondral bone repair coupled with the development of cartilaginous tissue with good tissue integration to the adjacent host cartilage when assessed at 6 months post implantation. Conversely, the control group exhibited delayed subchondral bone repair. In addition, the repair cartilaginous tissue in this group had poor integration to adjacent cartilage and contained clustered chondrocytes, suggesting an early osteoarthritis (OA)-like degenerative change at 6 months post implantation. Biomechanically, the osteochondral repair tissue treated with the combined implants at 6 months restored tissue stiffness, similar to normal osteochondral tissue. The combined implants significantly accelerated and improved osteochondral repair. Specifically, earlier restoration of subchondral bone, as well as good tissue integration of repair cartilage to adjacent host tissue could be clinically relevant in terms of the acceleration of postoperative rehabilitation and longer-term durability of repaired articular surface in patients with osteochondral lesions, including those with OA. In addition, the combined implant could be considered a promising MSC-based bio-implant with regard to safety and cost-effectiveness, considering that the TEC is a scaffold-free implant and HA artificial bone has been widely used in clinical practice. PMID:24655056

  6. Osteochondral Tissue Engineering In Vivo: A Comparative Study Using Layered Silk Fibroin Scaffolds from Mulberry and Nonmulberry Silkworms

    PubMed Central

    Saha, Sushmita; Kundu, Banani; Kirkham, Jennifer; Wood, David; Kundu, Subhas C.; Yang, Xuebin B.

    2013-01-01

    The ability to treat osteochondral defects is a major clinical need. Existing polymer systems cannot address the simultaneous requirements of regenerating bone and cartilage tissues together. The challenge still lies on how to improve the integration of newly formed tissue with the surrounding tissues and the cartilage-bone interface. This study investigated the potential use of different silk fibroin scaffolds: mulberry (Bombyx mori) and non-mulberry (Antheraea mylitta) for osteochondral regeneration in vitro and in vivo. After 4 to 8 weeks of in vitro culture in chondro- or osteo-inductive media, non-mulberry constructs pre-seeded with human bone marrow stromal cells exhibited prominent areas of the neo tissue containing chondrocyte-like cells, whereas mulberry constructs pre-seeded with human bone marrow stromal cells formed bone-like nodules. In vivo investigation demonstrated neo-osteochondral tissue formed on cell-free multi-layer silk scaffolds absorbed with transforming growth factor beta 3 or recombinant human bone morphogenetic protein-2. Good bio-integration was observed between native and neo-tissue within the osteochondrol defect in patellar grooves of Wistar rats. The in vivo neo-matrix formed comprised of a mixture of collagen and glycosaminoglycans except in mulberry silk without growth factors, where a predominantly collagenous matrix was observed. Immunohistochemical assay showed stronger staining of type I and type II collagen in the constructs of mulberry and non-mulberry scaffolds with growth factors. The study opens up a new avenue of using inter-species silk fibroin blended or multi-layered scaffolds of a combination of mulberry and non-mulberry origin for the regeneration of osteochondral defects. PMID:24260335

  7. Development of a Comprehensive Osteochondral Allograft MRI Scoring System (OCAMRISS) With Histopathologic, Micro–Computed Tomography, and Biomechanical Validation

    PubMed Central

    Pallante-Kichura, Andrea L.; Bae, Won C.; Du, Jiang; Statum, Sheronda; Wolfson, Tanya; Gamst, Anthony C.; Cory, Esther; Amiel, David; Bugbee, William D.; Sah, Robert L.; Chung, Christine B.

    2014-01-01

    Objective: To describe and apply a semiquantitative MRI scoring system for multifeature analysis of cartilage defect repair in the knee by osteochondral allografts and to correlate this scoring system with histopathologic, micro–computed tomography (µCT), and biomechanical reference standards using a goat repair model. Design: Fourteen adult goats had 2 osteochondral allografts implanted into each knee: one in the medial femoral condyle and one in the lateral trochlea. At 12 months, goats were euthanized and MRI was performed. Two blinded radiologists independently rated 9 primary features for each graft, including cartilage signal, fill, edge integration, surface congruity, calcified cartilage integrity, subchondral bone plate congruity, subchondral bone marrow signal, osseous integration, and presence of cystic changes. Four ancillary features of the joint were also evaluated, including opposing cartilage, meniscal tears, synovitis, and fat-pad scarring. Comparison was made with histologic and µCT reference standards as well as biomechanical measures. Interobserver agreement and agreement with reference standards was assessed. Cohen’s κ, Spearman’s correlation, and Kruskal-Wallis tests were used as appropriate. Results: There was substantial agreement (κ > 0.6, P < 0.001) for each MRI feature and with comparison against reference standards, except for cartilage edge integration (κ = 0.6). There was a strong positive correlation between MRI and reference standard scores (ρ = 0.86, P < 0.01). Osteochondral allograft MRI scoring system was sensitive to differences in outcomes between the types of allografts. Conclusions: We have described a comprehensive MRI scoring system for osteochondral allografts and have validated this scoring system with histopathologic and µCT reference standards as well as biomechanical indentation testing. PMID:24489999

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

    PubMed Central

    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

  9. Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model

    PubMed Central

    2010-01-01

    Background Current research aims to develop innovative approaches to improve chondral and osteochondral regeneration. The objective of this study was to investigate the regenerative potential of platelet-rich plasma (PRP) to enhance the repair process of a collagen-hydroxyapatite scaffold in osteochondral defects in a sheep model. Methods PRP was added to a new, multi-layer gradient, nanocomposite scaffold that was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. Twenty-four osteochondral lesions were created in sheep femoral condyles. The animals were randomised to three treatment groups: scaffold, scaffold loaded with autologous PRP, and empty defect (control). The animals were sacrificed and evaluated six months after surgery. Results Gross evaluation and histology of the specimens showed good integration of the chondral surface in both treatment groups. Significantly better bone regeneration and cartilage surface reconstruction were observed in the group treated with the scaffold alone. Incomplete bone regeneration and irregular cartilage surface integration were observed in the group treated with the scaffold where PRP was added. In the control group, no bone and cartilage defect healing occurred; defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. Conclusions The hydroxyapatite-collagen scaffold enhanced osteochondral lesion repair, but the combination with platelet growth factors did not have an additive effect; on the contrary, PRP administration had a negative effect on the results obtained by disturbing the regenerative process. In the scaffold + PRP group, highly amorphous cartilaginous repair tissue and poorly spatially organised underlying bone tissue were found. PMID:20875101

  10. Osteochondritis dissecans of the lateral femoral condyle in a patient affected by osteogenesis imperfecta: a case report.

    PubMed

    Persiani, Pietro; Di Domenica, Marica; Martini, Lorena; Ranaldi, Filippo M; Zambrano, Anna; Celli, Mauro; Villani, Ciro

    2015-11-01

    Osteochondritis dissecans is a very uncommon phenomenon in osteogenesis imperfecta (OI). A 14-year-old boy, affected by OI and followed in our Center for Congenital Osteodystrophies, had a knee trauma and MRI indicated a hollowed area of 2.51.5?cm in the lateral femoral condyle, which was classified as grade III. The patient underwent surgery, performed as a one-step surgical treatment: the osteochondral fragment was removed, curettage of lesion's bottom was performed, and a biphasic scaffold was used to fill the defect, implanted with a press-fit technique. MRI at 12 and 24 months after surgery showed scaffold integration. At the final follow-up, the patient did not feel any pain or articular limitations. It is difficult to provide a guideline on osteochondritis dissecans in patients affected by OI because of the lack of literature reports on this rare disorder in a rare disease. According to our experience, in these patients, osteosynthesis of the bone fragment and the use of autograft are not recommended because of the patient's bone weakness and osteoporosis. Moreover, compared with two-step surgery, one-step surgery is preferred to reduce the risk related to anesthesia, often observed to be higher in these patients. PMID:25919806

  11. In vitro release and In vivo biocompatibility studies of biomimetic multilayered alginate-chitosan/β-TCP scaffold for osteochondral tissue.

    PubMed

    Algul, Derya; Gokce, Alper; Onal, Ayberk; Servet, Erkan; Dogan Ekici, Asiye Isın; Yener, Fatma Gulgun

    2016-04-01

    Biomimetic three-layered monolithic scaffold (TLS) intended for the treatment of osteocondral defects was prepared by using alginate, chitosan and β-tricalcium phosphate (β-TCP) to study drug release behavior of the alternative drug delivery system and to investigate the therapeutic efficacy of the scaffold. Dexamethasone sodium phosphate (Dex) as a model drug was incorporated into the scaffold by solvent sorption method and in vitro release studies were conducted. In addition, the scaffold was implanted into the defects formed in the trochlea of Sprague-Dawley rats to assess the healing potential of the TLS on the osteochondral defect against reference Maioregen® comparatively. The release studies showed that after an initial burst at 3rd h, dexamethasone is released slowly during a 72-h period. In vivo studies indicated that the TLS has good tissue biocompatibility and biodegradation rate and showed better results during osteochondral healing process compared to the reference. All results demonstrated that the alginate-chitosan/β-TCP scaffold could be evaluated as a good candidate for osteochondral tissue applications. PMID:26764607

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

    PubMed

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

    2015-04-01

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

  13. In vitro generation of whole osteochondral constructs using rabbit bone marrow stromal cells, employing a two-chambered co-culture well design.

    PubMed

    Chen, Kelei; Ng, Kian Siang; Ravi, Sujata; Goh, James C H; Toh, Siew Lok

    2016-04-01

    The regeneration of whole osteochondral constructs with a physiological structure has been a significant issue, both clinically and academically. In this study, we present a method using rabbit bone marrow stromal cells (BMSCs) cultured on a silk-RADA peptide scaffold in a specially designed two-chambered co-culture well for the generation of multilayered osteochondral constructs in vitro. This specially designed two-chambered well can simultaneously provide osteogenic and chondrogenic stimulation to cells located in different regions of the scaffold. We demonstrated that this co-culture approach could successfully provide specific chemical stimulation to BMSCs located on different layers within a single scaffold, resulting in the formation of multilayered osteochondral constructs containing cartilage-like and subchondral bone-like tissue, as well as the intermediate osteochondral interface. The cells in the intermediate region were found to be hypertrophic chondrocytes, embedded in a calcified extracellular matrix containing glycosaminoglycans and collagen types I, II and X. In conclusion, this study provides a single-step approach that highlights the feasibility of rabbit BMSCs as a single-cell source for multilayered osteochondral construct generation in vitro. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23495238

  14. Development of a Large Animal Model of Osteochondritis Dissecans of the Knee

    PubMed Central

    Pfeifer, Christian G.; Kinsella, Stuart D.; Milby, Andrew H.; Fisher, Matthew B.; Belkin, Nicole S.; Mauck, Robert L.; Carey, James L.

    2015-01-01

    Background: Treatment of osteochondritis dissecans (OCD) of the knee is challenging, and evidence for stage-dependent treatment options is lacking. Basic science approaches utilizing animal models have provided insight into the etiology of OCD but have yet to produce a reliable and reproducible large animal model of the disease on which to test new surgical strategies. Purpose/Hypotheses: The purpose of this study was to develop an animal model featuring an OCD-like lesion in terms of size, location, and International Cartilage Repair Society (ICRS) grading. The hypothesis was that surgical creation of an osteochondral defect followed by placement of a barrier between parent bone and progeny fragment would generate a reproducible OCD-like lesion. Study Design: Controlled laboratory study. Methods: Bilateral osteochondral lesions were created in the medial femoral condyles of 9 Yucatan minipigs. After lesion creation, a biodegradable membrane was interposed between the progeny and parent bone. Five different treatment groups were evaluated at 2 weeks: a control with no membrane (ctrl group; n = 4), a slowly degrading nanofibrous poly(∊-caprolactone) membrane (PCL group; n = 4), a fenestrated PCL membrane with 1.5-mm holes covering 25% of surface area (fenPCL group; n = 4), a collagen membrane (Bio-Gide) (CM group; n = 3), and a fenestrated CM (fenCM group; n = 3). Five unperturbed lateral condyles (1 from each treatment group) served as sham controls. After euthanasia on day 14, the lesion was evaluated by gross inspection, fluoroscopy, micro–computed tomography (micro-CT), and histology. To quantify changes between groups, a scoring system based on gross appearance (0-2), fluoroscopy (0-2), and micro-CT (0-6) was established. Micro-CT was used to quantify bone volume per total volume (BV/TV) in a defined region surrounding and inclusive of the defect. Results: The no scaffold group showed healing of the subchondral bone at 2 weeks, with continuity of subchondral bone elements. Conversely, condyles treated with PCL or CM showed substantial remodeling, with loss of bone in both the progeny fragment and surrounding parent bone. When these membranes were fenestrated (fenPCL and fenCM groups), bone loss was less severe. Histological analysis showed no integration in the cartilage layer in any treatment group, while fibrous tissue formed between the parent and progeny fragments. Micro-CT showed significant differences in mean BV/TV between the PCL (27.4% ± 2.3%) and the sham (47.7% ± 1.4%) or no scaffold (54.9% ± 15.1%) groups (P < .01 and P < .05, respectively). In addition, a significant difference in bone loss was evident between the PCL and fenPCL groups (mean BV/TV, 46.6% ± 15.2%; P < .05), as well as between the PCL and fenCM (mean BV/TV, 50.9% ± 3.5%) and fenPCL groups (P < .01). Grading by 6 blinded reviewers using an OCD scoring system with 3 subcategories showed a significant difference between control and PCL groups. Conclusion: This study successfully developed a large animal model of OCD-like lesions in the knee joint of Yucatan minipigs. The lesions generated matched characteristics of an ICRS grade 3 OCD lesion in humans. These findings set the stage for ongoing model refinement as well as exploration of novel interventional therapies to restore function and bone and cartilage patency in individuals affected by this rare but significant disease. Clinical Relevance: This developed model will serve as a platform on which to further investigate the natural course as well as emerging treatment options for OCD. PMID:26535380

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

    PubMed Central

    Hopper, Niina; Wardale, John; Brooks, Roger; Power, Jonathan; Rushton, Neil; Henson, Frances

    2015-01-01

    This study characterized peripheral blood mononuclear cells (PBMC) in terms of their potential in cartilage repair and investigated their ability to improve the healing in a pre-clinical large animal model. Human PBMCs were isolated with gradient centrifugation and adherent PBMC’s were evaluated for their ability to differentiate into adipogenic, chondrogenic and osteogenic lineages and also for their expression of musculoskeletal genes. The phenotype of the PBMCs was evaluated using Stro-1, CD34, CD44, CD45, CD90, CD106, CD105, CD146 and CD166 cell surface markers. Osteochondral defects were created in the medial femoral condyle (MFC) of 24 Welsh mountain sheep and evaluated at a six month time point. Four cell treatment groups were evaluated in combination with collagen-GAG-scaffold: (1) MSC alone; (2) MSCs and PBMCs at a ratio of 20:1; (3) MSCs and PBMC at a ratio of 2:1 and (4) PBMCs alone. Samples from the surgical site were evaluated for mechanical properties, ICRS score and histological repair. Fresh PBMC samples were 90% positive for hematopoietic cell surface markers and negative for the MSC antibody panel (<1%, p = 0.006). However, the adherent PBMC population expressed mesenchymal stem cell markers in hypoxic culture and lacked CD34/45 positive cells (<0.2%). This finding demonstrated that the adherent cells had acquired an MSC-like phenotype and transformed in hypoxia from their original hematopoietic lineage. Four key genes in muskuloskeletal biology were significantly upregulated in adherent PBMCs by hypoxia: BMP2 4.2-fold (p = 0.0007), BMP6 10.7-fold (p = 0.0004), GDF5 2.0-fold (p = 0.002) and COL1 5.0-fold (p = 0.046). The monolayer multilineage analysis confirmed the trilineage mesenchymal potential of the adherent PBMCs. PBMC cell therapy was equally good as bone marrow MSC therapy for defects in the ovine large animal model. Our results show that PBMCs support cartilage healing and oxygen tension of the environment was found to have a key effect on the derivation of a novel adherent cell population with an MSC-like phenotype. This study presents a novel and easily attainable point-of-care cell therapy with PBMCs to treat osteochondral defects in the knee avoiding any cell manipulations outside the surgical room. PMID:26252391

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

    PubMed

    Hopper, Niina; Wardale, John; Brooks, Roger; Power, Jonathan; Rushton, Neil; Henson, Frances

    2015-01-01

    This study characterized peripheral blood mononuclear cells (PBMC) in terms of their potential in cartilage repair and investigated their ability to improve the healing in a pre-clinical large animal model. Human PBMCs were isolated with gradient centrifugation and adherent PBMC's were evaluated for their ability to differentiate into adipogenic, chondrogenic and osteogenic lineages and also for their expression of musculoskeletal genes. The phenotype of the PBMCs was evaluated using Stro-1, CD34, CD44, CD45, CD90, CD106, CD105, CD146 and CD166 cell surface markers. Osteochondral defects were created in the medial femoral condyle (MFC) of 24 Welsh mountain sheep and evaluated at a six month time point. Four cell treatment groups were evaluated in combination with collagen-GAG-scaffold: (1) MSC alone; (2) MSCs and PBMCs at a ratio of 20:1; (3) MSCs and PBMC at a ratio of 2:1 and (4) PBMCs alone. Samples from the surgical site were evaluated for mechanical properties, ICRS score and histological repair. Fresh PBMC samples were 90% positive for hematopoietic cell surface markers and negative for the MSC antibody panel (<1%, p = 0.006). However, the adherent PBMC population expressed mesenchymal stem cell markers in hypoxic culture and lacked CD34/45 positive cells (<0.2%). This finding demonstrated that the adherent cells had acquired an MSC-like phenotype and transformed in hypoxia from their original hematopoietic lineage. Four key genes in muskuloskeletal biology were significantly upregulated in adherent PBMCs by hypoxia: BMP2 4.2-fold (p = 0.0007), BMP6 10.7-fold (p = 0.0004), GDF5 2.0-fold (p = 0.002) and COL1 5.0-fold (p = 0.046). The monolayer multilineage analysis confirmed the trilineage mesenchymal potential of the adherent PBMCs. PBMC cell therapy was equally good as bone marrow MSC therapy for defects in the ovine large animal model. Our results show that PBMCs support cartilage healing and oxygen tension of the environment was found to have a key effect on the derivation of a novel adherent cell population with an MSC-like phenotype. This study presents a novel and easily attainable point-of-care cell therapy with PBMCs to treat osteochondral defects in the knee avoiding any cell manipulations outside the surgical room. PMID:26252391

  17. The Incidence of Surgery in Osteochondritis Dissecans in Children and Adolescents

    PubMed Central

    Weiss, Jennifer M.; Nikizad, Hooman; Shea, Kevin G.; Gyurdzhyan, Samvel; Jacobs, John C.; Cannamela, Peter C.; Kessler, Jeffrey I.

    2016-01-01

    Background: The frequency of osteochondritis dissecans (OCD), a disorder of the subchondral bone and articular cartilage, is not well described. Purpose: To assess the frequency of pediatric OCD lesions that progress to surgery based on sex, joint involvement, and age. Study Design: Descriptive epidemiology study. Methods: A retrospective chart review (2007-2011) was performed on OCD. Inclusion criteria included OCD of any joint and patients aged 2 to 19 years. Exclusion criteria included traumatic osteochondral fractures or coexistence of non-OCD intra-articular lesions. Differences in progression toward surgery were compared between age groups, sex, and joint location. Logistical regression analysis was performed by sex, age, and ethnicity. Results: Overall, 317 patients with a total of 334 OCD lesions were found. The majority of lesions (61.7%) were in the knee, with ankle, elbow, shoulder, and foot lesions representing 25.4%, 12.0%, 0.6%, and 0.3% of all lesions, respectively. The majority of joints needing surgery were in the knee (58.5%), with ankle and elbow lesions representing 22.9% and 18.6% of surgeries performed, respectively. The percentage of all OCD lesions progressing to surgery was 35.3%; surgical progression for knee, ankle, and elbow joints was 33.5%, 31.8%, and 55.0%, respectively. Logistic regression analysis found no statistically significant different risk of progressing to surgery for OCD of the knee, elbow, and ankle between sexes. Patients aged 12 to 19 years had a 7.4-times greater risk of progression to surgery for knee OCD lesions than 6- to 11-year-olds. Patients aged 12 to 19 years were 8.2 times more likely to progress to surgery for all OCD lesions than patients aged 6 to 11 years. Progression to surgery of ankle OCD did not significantly differ based on location. Three of 4 trochlear lesions progressed to surgery, along with 1 of 1 tibial, 1 of 3 patellar, 40.3% of lateral femoral condylar, and 28.2% of medial femoral condylar lesions. Conclusion: In this large cohort study of pediatric OCD patients, 35% progressed to surgery. Progression to surgery did not differ significantly between sexes with OCD of any joint. Progression to surgery for OCD of the knee, elbow, and ankle strongly correlated with patient age at the time of diagnosis. Clinical Relevance: The knowledge of likelihood of progression to surgery of OCD by location, sex, and age is useful in counseling patients and in planning treatment. This study confirms a worse prognosis in the nonoperative treatment of older patients with OCD. PMID:27047984

  18. OSTEOCHONDRAL INTERFACE REGENERATION OF THE RABBIT MANDIBULAR CONDYLE WITH BIOACTIVE SIGNAL GRADIENTS

    PubMed Central

    Dormer, Nathan H.; Busaidy, Kamal; Berkland, Cory J.; Detamore, Michael S.

    2011-01-01

    PURPOSE Tissue engineering solutions focused on the temporomandibular joint (TMJ) have expanded in number and variety over the past decade to address the treatment of TMJ disorders. The existing literature on approaches for healing small defects in the TMJ condylar cartilage and subchondral bone, however, is sparse. The purpose of this study was thus to evaluate the performance of a novel gradient-based scaffolding approach to regenerate osteochondral defects in the rabbit mandibular condyle. MATERIALS AND METHODS Miniature bioactive plugs for regeneration of small mandibular condylar defects in New Zealand White rabbits were fabricated. The plugs were constructed from poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres with a gradient transition between cartilage-promoting and bone-promoting growth factors. RESULTS At six weeks of healing, results suggested that the implants provided support for the neo-synthesized tissue as evidenced by histology and 9.4T magnetic resonance imaging. CONCLUSION The inclusion of bioactive factors in a gradient-based scaffolding design is a promising new treatment strategy for focal defect repair in the TMJ. PMID:21470747

  19. Novel metallic implantation technique for osteochondral defects of the medial talar dome

    PubMed Central

    van Bergen, Christiaan J A

    2010-01-01

    Background and purpose A metallic inlay implant (HemiCAP) with 15 offset sizes has been developed for the treatment of localized osteochondral defects of the medial talar dome. The aim of this study was to test the following hypotheses: (1) a matching offset size is available for each talus, (2) the prosthetic device can be reproducibly implanted slightly recessed in relation to the talar cartilage level, and (3) with this implantation level, excessive contact pressures on the opposite tibial cartilage are avoided. Methods The prosthetic device was implanted in 11 intact fresh-frozen human cadaver ankles, aiming its surface 0.5 mm below cartilage level. The implantation level was measured at 4 margins of each implant. Intraarticular contact pressures were measured before and after implantation, with compressive forces of 1,000–2,000 N and the ankle joint in plantigrade position, 10° dorsiflexion, and 14° plantar flexion. Results There was a matching offset size available for each specimen. The mean implantation level was 0.45 (SD 0.18) mm below the cartilage surface. The defect area accounted for a median of 3% (0.02–18) of the total ankle contact pressure before implantation. This was reduced to 0.1% (0.02–13) after prosthetic implantation. Interpretation These results suggest that the implant can be applied clinically in a safe way, with appropriate offset sizes for various talar domes and without excessive pressure on the opposite cartilage. PMID:20515434

  20. Stimulation of Early Osteochondral Differentiation of Human Mesenchymal Stem Cells Using Binary Colloidal Crystals (BCCs).

    PubMed

    Wang, Peng-Yuan; Thissen, Helmut; Kingshott, Peter

    2016-02-24

    A new surface based on self-assembly of two colloids into well-defined nanostructures, so-called binary colloidal crystals (BCCs), was fabricated for stem cell culture. The facile fabrication process are able to cover large surface areas (>3 cm-diameter, i.e. > 7 cm(2)) with ordered surface nanotopographies that is often a challenge particularly in biomaterials science. From our library, four different combinations of BCCs were selected using mixtures of silica, polystyrene and poly(methyl methacrylate) particles with sizes in the range from 100 nm to 5 μm. Cell spreading, proliferation, and surface-induced lineage commitment of human adipose-derived stem cells (hADSCs) was studied using quantitative real time polymerase chain reaction (qRT-PCR) and immunostaining. The results showed that BCCs induced osteo- and chondro- but not adipo-gene expression in the absence of induction medium suggesting that the osteochondral lineage can be stimulated by the BCCs. When applying induction media, higher osteo- and chondro-gene expression on BCCs was found compared with tissue culture polystyrene (TCPS) and flat silica (Si) controls, respectively. Colony forming of chondrogenic hADSCs was found on BCCs and TCPS but not Si controls, suggesting that the differentiation of stem cells is surface-dependent. BCCs provide access to complex nanotopographies and chemistries, which can find applications in cell culture and regenerative medicine. PMID:26812467

  1. Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in a simulated osteochondral environment is hydrogel dependent.

    PubMed

    de Vries-van Melle, M L; Tihaya, M S; Kops, N; Koevoet, W J L M; Murphy, J M; Verhaar, J A N; Alini, M; Eglin, D; van Osch, G J V M

    2014-01-01

    Hydrogels pose interesting features for cartilage regeneration strategies, such as the option for injectability and in situ gelation resulting in optimal filling of defects. We aimed to study different hydrogels for their capability to support chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs). hBMSCs were encapsulated in alginate, alginate with hyaluronic acid (alginate/HA), fibrin or thermoresponsive HA grafted with poly(N-isopropyl acrylamide) side-chains (HA-pNIPAM). Glycosaminoglycan production and cartilage-related gene expression were significantly higher in hBMSC-alginate and hBMSC-fibrin constructs than in the other constructs. Supplementation of alginate with HA was not beneficial. hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs were placed in simulated defects in osteochondral biopsies and cultured in vitro for 28d. Biopsies containing hBMSC-alginate and hBMSC-fibrin were implanted subcutaneously in nude mice for 12 weeks. hBMSC-alginate constructs had significantly higher cartilage-related gene expression after 28d of culture as well as significantly more safranin-O positive repair tissue after 12 weeks in vivo than hBMSC-fibrin constructs. Although initial experiments with hBMSC-hydrogel constructs suggested comparable results of hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs, culture in the osteochondral biopsy model in vitro as well as in vivo revealed differences, suggests that chondrogenesis of hBMSCs in an osteochondral environment is hydrogel-dependent. PMID:24488855

  2. Bone marrow-derived cell concentrates have limited effects on osteochondral reconstructions in the mini pig.

    PubMed

    Jagodzinski, Michael; Liu, Chaoxu; Guenther, Daniel; Burssens, Arne; Petri, Maximilian; Abedian, Reza; Willbold, Elmar; Krettek, Christian; Haasper, Carl; Witte, Frank

    2014-03-01

    This study investigates the effects of seeding a chondrogenic and osteogenic scaffold with a bone marrow-derived cell concentrate (BMCC) and reports the histological and mechanical properties 3 months after implantation in the miniature pig. Twenty defects (7×10 mm) were created in the femoral condyles of 10 miniature pigs. The defects were left empty (E), filled with the grafted cylinder upside down (U) or with a combined scaffold (S) containing a spongious bone cylinder (Tutobone®) covered with a collagen membrane (Chondrogide®). In a fourth group, the same scaffolds were implanted but seeded with a stem cell concentrate (S+ BMCC). The animals were stained with calcein green after 2 weeks and xylenol orange after 4 weeks. After 3 months, the animals were sacrificed, and a mechanical analysis (Young's modulus), macroscopic, and histologic (ICRS Score) examination of the specimens was conducted. Young's modulus in the periphery was significantly lower for group E (67.5±15.3 kPa) compared with untreated controls (171.7±21.6 kPa, p<0.04). Bone defects were smaller in group S (10%±8%) compared with E (27%±7%; p<0.05). There was a trend toward smaller bony defects on comparing groups E and S+ BMCC (11%±8%; p=0.07). More red fluorescence was detected in group S+ BMCC (2.3%±1.1%) compared with groups E (0.4%±0.2%) and U (0.5%±0.2%, p<0.03). ICRS scores were higher for groups S (25.3±3.8) and S+ BMCC (26.2±5.2, p<0.01). In this animal model of osteochondral defects, stem cell concentrates enhance new bone apposition but fail to improve mechanical properties or histological appearance of cartilage regenerates in critical-sized defects. PMID:23815398

  3. A system for engineering an osteochondral construct in the shape of an articular surface: preliminary results.

    PubMed

    Haasper, Carl; Colditz, Michael; Kirsch, Ludger; Tschernig, Thomas; Viering, Jörg; Graubner, Götz; Runtemund, Anette; Zeichen, Johannes; Meller, Rupert; Glasmacher, Birgit; Windhagen, Henning; Krettek, Christian; Hurschler, Christof; Jagodzinski, Michael

    2008-01-01

    A tissue-engineered articular condyle could provide a new alternative approach to joint replacement. This study describes progress made towards engineering an articular condyle in vitro using human bone marrow stromal cells (hBMSCs) in a biphasic matrix. hBMSCs were transferred to a rat collagen-I hydrogel which was then pressed onto a bovine cancellous bone matrix. The gel/cell suspensions, each at a density of approximately 5 x 10(5)cells/ml containing fourth passage cells pressed into an adult human tibial condyle form using CT scan based moulds. The osteochondral constructs fabricated in vitro were stimulated in a bioreactor using cyclic compression and continuous perfusion. Penetration and cell distribution were demonstrated as homogeneous and cells were found to be viable after gel compression. The filamentous structure of the collagen fibres was more dense and homogeneous using compression. Mechanical tests showed a significant enhancement of primary matrix stability after initial compression. Stiffness was not observed to increase significantly over 7 days under loading in a bioreactor. The successful integration of mechanical stimulation in the tissue engineering process leads to an improvement in the structural and biomechanical properties of these tissues and offers new possibilities in the management of joint injuries and degenerative diseases. Remarkably, the stiffness was enhanced in our setting after initial compression of the construct in the glass cylinder without observing a negative influence on cell viability. Further studies need to clarify the influence of compression and various mechanical and hydrostatic stress patterns over different periods of time. PMID:18462930

  4. Association between intraarticular cytokine levels and clinical parameters of osteochondritis dissecans in the ankle

    PubMed Central

    2014-01-01

    Background Reliable data about in vivo regulation of cytokines in osteochondritis dissecans (OCD) of the ankle are still missing. Disease-specific regulation patterns were hypothesized. Methods 28 patients with a mean age of 30.7 ± 14.8 years undergoing an arthroscopy of the ankle because of OCD were prospectively included in a clinical trial. Lavage fluids were analyzed by ELISA for levels of aggrecan, BMP-2, BMP-7, IGF-1, IGF-1R, bFGF, endoglin, MMP-13, and IL-1β. Additionally, clinical parameters and scores (FFI, CFSS, AOFAS) were evaluated and supplemented by the Kellgren Lawrence Score (KLS) for conventional X-rays and the Ankle Osteoarthritis Scoring System (AOSS) for MRI. Results Grading of OCD lesions statistically significant increased with age and was higher in case of previously performed operations (p < 0.03). A worse clinical function reflected by low AOFAS and CFSS scores or high FFI was associated with high grading of cartilage damage or OCD (p < 0.03). Similarly, high radiological scores (KLS and AOSS) indicating progress of OA positively correlated with grading of cartilage damage and OCD. The concordance between the MRI and arthroscopic classification was overall moderate (κ = 0.52). Biochemically, only IGF/IGF-1R levels were consistently negatively associated with OCD grading, ICRS score, FFI and KLS (p < 0.05). Correlation data is supported by post hoc statistics. Conclusions Radiological and clinical parameters in association with synovial IGF-1/IGF-1R levels indicated an increasing joint degeneration with rising OCD stage. Trial registration German Clinical Trials Register DRKS00000365, 11/03/2008. PMID:24885831

  5. Outcomes are favorable after arthroscopic treatment of osteochondritis dissecans of the talus.

    PubMed

    Goh, Graham Seow Hng; Bin Abd Razak, Hamid Rahmatullah; Mitra, Amit Kanta

    2015-01-01

    Arthroscopic treatment of osteochondritis dissecans (OCD) of the talus has resulted in outcomes as good as, or better than, those after arthrotomy. We noted a lack of prospective studies investigating the outcomes of arthroscopic treatment. As such, we conducted a prospective study investigating the functional outcomes, pain scores, patient satisfaction, and expectation scores of patients undergoing arthroscopic treatment of OCD of the talus, hypothesizing that these patients would have good outcomes and satisfaction. A total of 61 patients underwent arthroscopic chondroplasty, removal of loose bodies, and microfracture for OCD of the talus and completed ≥1 year of follow-up. We evaluated patients pre- and postoperatively at 6 and 12 months using the Ankle-Hindfoot score, visual analog scale for pain, and Medical Outcomes Study short-form 36 questionnaires. We also evaluated the patients' expectations and satisfaction. The mean Ankle-Hindfoot score improved significantly from 53.0 ± 14.3 points preoperatively to 77.8 ± 19.1 at 6 months and 83.1 ± 18.3 at 12 months after arthroscopic treatment (p < .001). The overall scores at the final follow-up visit were excellent for 30 (49%), good for 6 (10%), fair for 18 (30%), and poor for 7 (11%). The patients also experienced significant improvement in the visual analog scale score and physical component score of the short-form 36 questionnaire (p < .001). Of the 61 patients, 67% had their expectations fulfilled and 74% were satisfied with their surgery at 12 months of follow-up. Arthroscopic treatment of OCD of the talus continues to be a successful procedure to alleviate pain and loss of function. It is also associated with improvements to quality of life and good patient satisfaction. PMID:25441271

  6. Influence of juvenile osteochondral conditions on racing performance in Thoroughbreds born in Normandy.

    PubMed

    Robert, Céline; Valette, Jean-Paul; Jacquet, Sandrine; Denoix, Jean-Marie

    2013-07-01

    The relationship between osteoarticular status and future athletic capacity is commonly accepted in equine practice, but there is little to support this belief in Thoroughbreds. The objective of this study was to assess the prevalence of juvenile osteochondral conditions (JOCC) in Thoroughbred yearlings and to investigate the significance of these with regard to subsequent racing performance. The radiographic files from 328 Thoroughbred yearlings born in Normandy were assessed in a consistent manner and entered into a database together with racing records. Logistic regression models were used to quantify the association between each radiographic parameter and racing performance (raced/not raced, placed/not placed, performer/not performer) at 2, 3, 4 and 5years of age. The front fetlock (30.2% of horses), the dorsal aspect of the hind fetlock (18%), the carpus (15.9%) and the distal part of the hock (15.5%) were the most commonly affected joints. Most horses (87.5%) raced either in turf flat races or in hurdle races. Starting a race at 2years old was more frequent for yearlings without radiographic findings (RF) on the carpus or with less than one RF of moderate severity. The proportions of horses placed at 3years old decreased with increasing number or severity of RF. In racing horses, there was no association between the presence of RF and earnings. The radiographic score, calculated as the sum of all the severity indices found on the radiographic file of the horse appeared well correlated with performance. Using this synthetic index might help veterinarians to evaluate radiographs of Thoroughbred yearlings for potential buyers. PMID:23639369

  7. Surface energy and stiffness discrete gradients in additive manufactured scaffolds for osteochondral regeneration.

    PubMed

    Di Luca, Andrea; Longoni, Alessia; Criscenti, Giuseppe; Lorenzo-Moldero, Ivan; Klein-Gunnewiek, Michel; Vancso, Julius; van Blitterswijk, Clemens; Mota, Carlos; Moroni, Lorenzo

    2016-03-01

    Swift progress in biofabrication technologies has enabled unprecedented advances in the application of developmental biology design criteria in three-dimensional scaffolds for regenerative medicine. Considering that tissues and organs in the human body develop following specific physico-chemical gradients, in this study, we hypothesized that additive manufacturing (AM) technologies would significantly aid in the construction of 3D scaffolds encompassing such gradients. Specifically, we considered surface energy and stiffness gradients and analyzed their effect on adult bone marrow derived mesenchymal stem cell differentiation into skeletal lineages. Discrete step-wise macroscopic gradients were obtained by sequentially depositing different biodegradable biomaterials in the AM process, namely poly(lactic acid) (PLA), polycaprolactone (PCL), and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) copolymers. At the bulk level, PEOT/PBT homogeneous scaffolds supported a higher alkaline phosphatase (ALP) activity compared to PCL, PLA, and gradient scaffolds, respectively. All homogeneous biomaterial scaffolds supported also a significantly higher amount of glycosaminoglycans (GAGs) production compared to discrete gradient scaffolds. Interestingly, the analysis of the different material compartments revealed a specific contribution of PCL, PLA, and PEOT/PBT to surface energy gradients. Whereas PEOT/PBT regions were associated to significantly higher ALP activity, PLA regions correlated with significantly higher GAG production. These results show that cell activity could be influenced by the specific spatial distribution of different biomaterial chemistries in a 3D scaffold and that engineering surface energy discrete gradients could be considered as an appealing criterion to design scaffolds for osteochondral regeneration. PMID:26924824

  8. Cartilage Repair and Subchondral Bone Migration Using 3D Printing Osteochondral Composites: A One-Year-Period Study in Rabbit Trochlea

    PubMed Central

    Li, Dichen; Wang, Kunzheng; Hao, Dingjun; Bian, Weiguo; He, Jiankang; Jin, Zhongmin

    2014-01-01

    Increasing evidences show that subchondral bone may play a significant role in the repair or progression of cartilage damage in situ. However, the exact change of subchondral bone during osteochondral repair is still poorly understood. In this paper, biphasic osteochondral composite scaffolds were fabricated by 3D printing technology using PEG hydrogel and β-TCP ceramic and then implanted in rabbit trochlea within a critical size defect model. Animals were euthanized at 1, 2, 4, 8, 16, 24, and 52 weeks after implantation. Histological results showed that hyaline-like cartilage formed along with white smooth surface and invisible margin at 24 weeks postoperatively, typical tidemark formation at 52 weeks. The repaired subchondral bone formed from 16 to 52 weeks in a “flow like” manner from surrounding bone to the defect center gradually. Statistical analysis illustrated that both subchondral bone volume and migration area percentage were highly correlated with the gross appearance Wayne score of repaired cartilage. Therefore, subchondral bone migration is related to cartilage repair for critical size osteochondral defects. Furthermore, the subchondral bone remodeling proceeds in a “flow like” manner and repaired cartilage with tidemark implies that the biphasic PEG/β-TCP composites fabricated by 3D printing provides a feasible strategy for osteochondral tissue engineering application. PMID:25177697

  9. Expression of colony-stimulating factor 1 is associated with occurrence of osteochondral change in pigmented villonodular synovitis.

    PubMed

    Ota, Takehiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Tsukushi, Satoshi; Shimoyama, Yoshie; Ishiguro, Naoki; Nishida, Yoshihiro

    2015-07-01

    Pigmented villonodular synovitis (PVNS) is a benign, translocation-derived neoplasm. Because of its high local recurrence rate after surgery and occurrence of osteochondral destruction, a novel therapeutic target is required. The present study aimed to evaluate the significance of protein expression possibly associated with the pathogenesis during the clinical course of PVNS. In 40 cases of PVNS, positivity of colony-stimulated factor 1 (CSF1), its receptor (CSF1R), and receptor activator of nuclear factor kappa-B ligand (RANKL) were immunohistochemically determined. The relationship between the positivity and clinical outcomes was investigated. High positivity of CSF1 staining intensity was associated with an increased incidence of osteochondral lesions (bone erosion and osteoarthritis) (p = 0.009), but not with the rate of local recurrence. Positivity of CSF1R and RANKL staining was not associated with any clinical variables. The number of giant cells was not correlated with positivity of any of the three proteins, or with the clinical outcome. Focusing on knee cases, CSF1 positivity was also associated with the incidence of osteochondal change (p = 0.02). CSF1R positivity was high in cases which had local recurrence, but not significantly so (p = 0.129). Determination of CSF1 and CSF1R expression may be useful as a prognosticator of the clinical course and/or outcomes of PVNS. PMID:25854167

  10. Classification of histologically scored human knee osteochondral plugs by quantitative analysis of magnetic resonance images at 3T.

    PubMed

    Lukas, Vanessa A; Fishbein, Kenneth W; Lin, Ping-Chang; Schär, Michael; Schneider, Erika; Neu, Corey P; Spencer, Richard G; Reiter, David A

    2015-05-01

    This work evaluates the ability of quantitative MRI to discriminate between normal and pathological human osteochondral plugs characterized by the Osteoarthritis Research Society International (OARSI) histological system. Normal and osteoarthritic human osteochondral plugs were scored using the OARSI histological system and imaged at 3 T using MRI sequences producing T1 and T2 contrast and measuring T1, T2, and T2* relaxation times, magnetization transfer, and diffusion. The classification accuracies of quantitative MRI parameters and corresponding weighted image intensities were evaluated. Classification models based on the Mahalanobis distance metric for each MRI measurement were trained and validated using leave-one-out cross-validation with plugs grouped according to OARSI histological grade and score. MRI measurements used for classification were performed using a region-of-interest analysis which included superficial, deep, and full-thickness cartilage. The best classifiers based on OARSI grade and score were T1- and T2-weighted image intensities, which yielded accuracies of 0.68 and 0.75, respectively. Classification accuracies using OARSI score-based group membership were generally higher when compared with grade-based group membership. MRI-based classification--either using quantitative MRI parameters or weighted image intensities--is able to detect early osteoarthritic tissue changes as classified by the OARSI histological system. These findings suggest the benefit of incorporating quantitative MRI acquisitions in a comprehensive clinical evaluation of OA. PMID:25641500

  11. Osteochondral fragments within the dorsal pouch or dorsal joint capsule of the proximal intertarsal joint of the horse.

    PubMed

    Stephens, P R; Richardson, D W; Ross, M W; Ford, T S

    1989-01-01

    The anatomy of the dorsal pouch of the proximal intertarsal joint (PIJ) and its communication with the tarsocrural joint (TCJ) was studied in 15 pairs of hocks from young and mature horses. The mediolateral length of the TCJ-PIJ fenestration was 14 to 29 mm. The potential volume of the dorsal pouch of the PIJ was 3 to 5 ml, and a recess extended 10 to 28 mm medial to the medial commissure of the TCJ-PIJ fenestration. In a correlated clinical study, osteochondral fragments were identified radiographically within the dorsal pouch (category 1) or dorsal joint capsule (category 2) of the PIJ in 17 horses undergoing arthroscopic surgery of the TCJ. In six horses with category 1 lesions, osteochondral fragments were found free within the dorsal pouch and were removed. In five horses, category 1 fragments were not located. All 11 horses were reported by owners to be sound after surgery. In seven horses, a minimally displaced fragment was identified at the distal aspect of the medial trochlear ridge, within the insertion of the synovium separating TCJ and PIJ (one horse had both types of lesions in the same hock). Five of the seven category 2 fragments were removed at surgery. Of the seven horses with category 2 lesions, four were training or racing, two were unsound, and one was still convalescing at the time of follow-up. PMID:2728337

  12. Composite scaffolds for osteochondral repair obtained by combination of additive manufacturing, leaching processes and hMSC-CM functionalization.

    PubMed

    Díaz Lantada, Andrés; Alarcón Iniesta, Hernán; García-Ruíz, Josefa Predestinación

    2016-02-01

    Articular repair is a relevant and challenging area for the emerging fields of tissue engineering and biofabrication. The need of significant gradients of properties, for the promotion of osteochondral repair, has led to the development of several families of composite biomaterials and scaffolds, using different effective approaches, although a perfect solution has not yet been found. In this study we present the design, modeling, rapid manufacturing and in vitro testing of a composite scaffold aimed at osteochondral repair. The presented composite scaffold stands out for having a functional gradient of density and stiffness in the bony phase, obtained in titanium by means of computer-aided design combined with additive manufacture using selective laser sintering. The chondral phase is obtained by sugar leaching, using a PDMS matrix and sugar as porogen, and is joined to the bony phase during the polymerization of PDMS, therefore avoiding the use of supporting adhesives or additional intermediate layers. The mechanical performance of the construct is biomimetic and the stiffness values of the bony and chondral phases can be tuned to the desired applications, by means of controlled modifications of different parameters. A human mesenchymal stem cell (h-MSC) conditioned medium (CM) is used for improving scaffold response. Cell culture results provide relevant information regarding the viability of the composite scaffolds used. PMID:26652367

  13. The effect of osteochondral regeneration using polymer constructs and continuous passive motion therapy in the lower weight-bearing zone of femoral trocheal groove in rabbits.

    PubMed

    Chang, Nai-Jen; Lin, Chih-Chan; Li, Chien-Feng; Su, Kai; Yeh, Ming-Long

    2013-02-01

    Remedying patellofemoral osteochondral defects using clinical therapy remains challenging. Construct-based and cell-based regenerative medicine with in vitro physical stimuli has been progressively implemented. However, the effect of physical stimuli in situ in knee joints with degradable constructs is still not well-documented. Therefore, we studied whether it was practical to achieve articular cartilage repair using a poly(lactic-co-glycolic acid) (PLGA) construct in addition to early short-term continuous passive motion (CPM) for treatment of full-thickness osteochondral defects in the lower-weigh bearing (LWB) zone of the femoral trocheal groove. Twenty-six rabbits were randomly allocated into either intermittent active motion (IAM) or CPM treatment groups with or without PLGA constructs, termed PLGA construct-implanted (PCI) and empty defect knee models, respectively. Gross observation, histology, inflammatory cells, which were identified using H&E staining, total collagen and alignment, studied qualitatively using Masson's trichrome staining, glycosaminoglycan (GAG), identified using Alcian blue staining, and newly formed bone, observed using micro-CT, were evaluated at 4 and 12 weeks after surgery. Repair of osteochondral defects in the PCI-CPM group was more promising than all other groups. The better osteochondral defect repair in the PCI-CPM group corresponded to smooth cartilage surfaces, no inflammatory reaction, hyaline cartilaginous tissues composition, sound collagen alignment with positive collagen type II expression, higher GAG content, mature bone regeneration with osteocyte, clear tidemark formation, and better degradation of PLGA. In summary, the use of a simple PLGA construct coupled with passive motion promotes positive healing and may be a promising clinical intervention for osteochondral regeneration in LWB defects. PMID:22987137

  14. Evaluation of chitosan-GP hydrogel biocompatibility in osteochondral defects: an experimental approach

    PubMed Central

    2014-01-01

    Background Articular cartilage, because of its avascular nature, has little capacity for spontaneous healing, and tissue engineering approaches, employing different biomaterials and cells, are under development. Among the investigated biomaterials are the chitosan-based hydrogels. Although thoroughly studied in other mammalian species, studies are scarce in equines. So, the aim of the present study was to investigate the biocompatibility of chitosan-GP in horse joints submitted to high mechanical loads. Results An osteochondral defect was created by arthroscopy in the medial surface of lateral trochlea of talus of left or right leg, randomly selected, from six healthy geldings. The defect was filled up with chitosan-GP. The contralateral joint received an identical defect with no implant. The chondral fragment removed to produce the defect was collected, processed and used as the “Initial” sample (normal cartilage) for histology, immunohistochemistry, and metabolic labelling of PGs. After 180 days, the repair tissues were collected, and also analyzed. At the end of the experiment (180 days after lesion), the total number of cells per field in repair tissues was equal to control, and macrophages and polymorphonuclear cells were not detected, suggesting that no significant inflammation was present. These cells were able to synthesize type II collagen and proteoglycans (PGs). Nevertheless, the cell population in these tissues, both in presence of chitosan-GP and in untreated controls, were heterogeneous, with a lower proportion of type II collagen-positives cells and some with a fibroblastic aspect. Moreover, the PGs synthesized in repair tissues formed in presence or absence of chitosan-GP were similar to those of normal cartilage. However, the chitosan-GP treated tissue had an disorganized appearance, and blood vessels were present. Conclusions Implanted chitosan-GP did not evoke an important inflammatory reaction, and permitted cell growth. These cells were able to synthesize type II collagen and PGs similar to those synthesized in normal cartilage and in healing tissue without implant, indicating its chondrocyte nature. PMID:25160583

  15. Bilateral osteochondritis dissecans of the lateral femoral condyle following bilateral total removal of lateral discoid meniscus: a case report.

    PubMed

    Hashimoto, Yusuke; Yoshida, Gen; Tomihara, Tomohiro; Matsuura, Takeshi; Satake, Shinji; Kaneda, Kunikazu; Shimada, Nagakazu

    2008-11-01

    Osteochondritis dissecans (OCD) of the lateral femoral condyle sometimes occurs with a discoid lateral meniscus. Recently, it was reported that OCD of the lateral femoral condyle occurred after total removal of the lateral meniscus. We report the case of a 12-year-old boy with bilateral OCD of the lateral femoral condyle following bilateral total removal for discoid lateral meniscus. Valgus deviation of the knee after total removal and increased sporting activity might have concentrated excessive stress on the lateral condyles in the standing position. As a result, bilateral OCD might have occurred. Drilling of the areas of OCD on the bilateral lateral femoral condyles was done and the patient wore inner wedge arch supports postoperatively. After 2 years, neither knee pain nor arthrosis has occurred so far, but long-term follow-up of this patient is considered to be necessary. PMID:17985146

  16. Knee Osteochondritis Dissecans Treated by the AO Hook Fixation System: A Four Year Follow-Up of an Alternative Technique

    PubMed Central

    Pengas, Ioannis P; Assiotis, Angelos; Kokkinakis, Michail; Khan, Wasim S; Meyers, Paul; Arbuthnot, James; Mcnicholas, Michael J

    2014-01-01

    Surgical fixation is recommended for stable osteochondritis dissecans (OCD) lesions that have failed nonoperative management and for all unstable lesions. In this study we set out to describe and evaluate an alternative method of surgical fixation for such lesions. Five knees with unstable OCD lesions in four male adolescent patients with open physes were treated with the AO Hook Fixation System. The outcome was evaluated both clinically and with three separate outcome systems (IKDC 2000, KOOS, Lysholm) at one and a mean four year follow-up. We demonstrated excellent clinical results in all patients. At four years, all scoring systems demonstrated statistically significant improvement when compared to the preoperative status. Our study suggests that the AO Hook Fixation System is an alternative method of surgical intervention with comparable medium term results with other existing modes of fixation and the added biomechanical advantage of the absence of distracting forces during hardware removal. PMID:25067976

  17. Polyvinyl Alcohol Hydrogel Irradiated and Acetalized for Osteochondral Defect Repair: Mechanical, Chemical, and Histological Evaluation after Implantation in Rat Knees

    PubMed Central

    Batista, N. A.; Rodrigues, A. A.; Bavaresco, V. P.; Mariolani, J. R. L.; Belangero, W. D.

    2012-01-01

    Polyvinyl Alcohol (PVA) hydrogel plugs were implanted in artificial osteochondral defects on the trochlear groove of rat knees. After 0, 3, 6, 12, and 24 weeks of followup, samples containing the implants were mechanically evaluated by creep indentation test, chemically, and histologically by optical microscopy. The mechanical test pointed towards an increase of the implant creep modulus and the chemical analysis exhibited an increasing concentration of calcium and phosphorus within the implants over time. Optical microscopy showed no foreign body reaction and revealed formation, differentiation, and maintenance of new tissue at the defect/implant interface. The absence of implant wear indicated that the natural articular lubrication process was not disturbed by the implant. The performance of the irradiated and acetalized PVA was considered satisfactory for the proposed application. PMID:23197982

  18. Evaluation of Cartilage Repair by Mesenchymal Stem Cells Seeded on a PEOT/PBT Scaffold in an Osteochondral Defect.

    PubMed

    Barron, V; Merghani, K; Shaw, G; Coleman, C M; Hayes, J S; Ansboro, S; Manian, A; O'Malley, G; Connolly, E; Nandakumar, A; van Blitterswijk, C A; Habibovic, P; Moroni, L; Shannon, F; Murphy, J M; Barry, F

    2015-09-01

    The main objective of this study was to evaluate the effectiveness of a mesenchymal stem cell (MSC)-seeded polyethylene-oxide-terephthalate/polybutylene-terephthalate (PEOT/PBT) scaffold for cartilage tissue repair in an osteochondral defect using a rabbit model. Material characterisation using scanning electron microscopy indicated that the scaffold had a 3D architecture characteristic of the additive manufacturing fabrication method, with a strut diameter of 296 ± 52 μm and a pore size of 512 ± 22 μm × 476 ± 25 μm × 180 ± 30 μm. In vitro optimisation revealed that the scaffold did not generate an adverse cell response, optimal cell loading conditions were achieved using 50 μg/ml fibronectin and a cell seeding density of 25 × 10(6) cells/ml and glycosaminoglycan (GAG) accumulation after 28 days culture in the presence of TGFβ3 indicated positive chondrogenesis. Cell-seeded scaffolds were implanted in osteochondral defects for 12 weeks, with cell-free scaffolds and empty defects employed as controls. On examination of toluidine blue staining for chondrogenesis and GAG accumulation, both the empty defect and the cell-seeded scaffold appeared to promote repair. However, the empty defect and the cell-free scaffold stained positive for collagen type I or fibrocartilage, while the cell-seeded scaffold stained positive for collagen type II indicative of hyaline cartilage and was statistically better than the cell-free scaffold in the blinded histological evaluation. In summary, MSCs in combination with a 3D PEOT/PBT scaffold created a reparative environment for cartilage repair. PMID:25589372

  19. Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

    PubMed Central

    van Bergen, Christiaan JA; Blankevoort, Leendert; de Haan, Rob J; Sierevelt, Inger N; Meuffels, Duncan E; d'Hooghe, Pieter RN; Krips, Rover; van Damme, Geert; van Dijk, C Niek

    2009-01-01

    Background Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society – Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration Netherlands Trial Register (NTR1636) PMID:19591674

  20. One-Step Surgical Procedure for the Treatment of Osteochondral Defects with Adipose-Derived Stem Cells in a Caprine Knee Defect: A Pilot Study

    PubMed Central

    Jurgens, Wouter J.F.M.; Kroeze, Robert Jan; Zandieh-Doulabi, Behrouz; van Dijk, Annemieke; Renders, Greetje A.P.; Smit, Theo H.; van Milligen, Florine J.; Ritt, Marco J.P.F.

    2013-01-01

    Abstract Regenerative therapies offer attractive alternatives for the treatment of osteochondral defects. Adipose-derived stromal vascular fraction (SVF) cells allow the development of one-step surgical procedures by their abundant availability and high frequency. In this pilot study we evaluated the in vivo safety, feasibility, and efficacy of this concept using scaffolds seeded with freshly isolated (SVF) or cultured adipose stem cells (ASCs), and compared these to their acellular counterparts. Osteochondral defects were created in medial condyles and trochlear grooves in knees of eight goats. Defects were filled with acellular collagen I/III scaffolds or scaffolds seeded with SVF cells or cultured ASCs. Osteochondral regeneration was evaluated after 1 and 4 months by macroscopy, immunohistochemistry, biomechanical analysis, microCT analysis, and biochemistry. After 1 month, no adverse effects were noted. Microscopic, but not macroscopic evaluation showed considerable yet not significant differences, with cell-loaded constructs showing more extensive regeneration. After 4 months, acellular constructs displayed increased regeneration, however, to a lesser degree than cell-treated constructs. The latter exhibited more extensive collagen type II, hyaline-like cartilage, and higher elastic moduli, and their glycosaminoglycan content in the cartilaginous layer better approached native tissue values. Moreover, their defect regions contained higher levels of regenerated, mature subchondral bone with more intense collagen type I staining. SVF cells tended to perform best on all parameters. In summary, this pilot study demonstrated the preclinical safety and feasibility of a one-step surgical procedure for osteochondral defect regeneration. Similar regeneration was found between freshly isolated SVF cells and cultured ASCs. Larger studies with longer follow-up are required to substantiate these findings. PMID:23914338

  1. Osteochondral Defect Repair Using Bilayered Hydrogels Encapsulating Both Chondrogenically and Osteogenically Pre-differentiated Mesenchymal Stem Cells in a Rabbit Model

    PubMed Central

    Lam, Johnny; Lu, Steven; Lee, Esther J.; Trachtenberg, Jordan E.; Meretoja, Ville V.; Dahlin, Rebecca L.; van den Beucken, Jeroen J. J. P.; Tabata, Yasuhiko; Wong, Mark E.; Jansen, John A.; Mikos, Antonios G.; Kasper, F. Kurtis

    2014-01-01

    Objective To investigate the ability of cell-laden bilayered hydrogels encapsulating chondrogenically and osteogenically (OS) pre-differentiated mesenchymal stem cells (MSCs) to effect osteochondral defect repair in a rabbit model. By varying the period of chondrogenic pre- differentiation from 7 (CG7) to 14 days (CG14), the effect of chondrogenic differentiation stage on osteochondral tissue repair was also investigated. Methods Rabbit MSCs were subjected to either chondrogenic or osteogenic pre-differentiation, encapsulated within respective chondral/subchondral layers of a bilayered hydrogel construct, and then implanted into femoral condyle osteochondral defects. Rabbits were randomized into one of four groups (MSC/MSC, MSC/OS, CG7/OS, and CG14/OS; chondral/subchondral) and received two similar constructs bilaterally. Defects were evaluated after 12 weeks. Results All groups exhibited similar overall neo-tissue filling. The delivery of OS cells when compared to undifferentiated MSCs in the subchondral construct layer resulted in improvements in neo-cartilage thickness and regularity. However, the addition of CG cells in the chondral layer, with OS cells in the subchondral layer, did not augment tissue repair as influenced by the latter when compared to the control. Instead, CG7/OS implants resulted in more irregular neo- tissue surfaces when compared to MSC/OS implants. Notably, the delivery of CG7 cells, when compared to CG14 cells, with OS cells stimulated morphologically superior cartilage repair. However, neither osteogenic nor chondrogenic pre-differentiation affected detectable changes in subchondral tissue repair. Conclusions Cartilage regeneration in osteochondral defects can be enhanced by MSCs that are chondrogenically and osteogenically pre-differentiated prior to implantation. Longer chondrogenic pre-differentiation periods, however, lead to diminished cartilage repair. PMID:25008204

  2. Establishing proof of concept: Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus

    PubMed Central

    Smyth, Niall A; Murawski, Christopher D; Haleem, Amgad M; Hannon, Charles P; Savage-Elliott, Ian; Kennedy, John G

    2012-01-01

    Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative (microfracture) or replacement (autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration, with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus. PMID:22816065

  3. Cell-free multi-layered collagen-based scaffolds demonstrate layer specific regeneration of functional osteochondral tissue in caprine joints.

    PubMed

    Levingstone, Tanya J; Ramesh, Ashwanth; Brady, Robert T; Brama, Pieter A J; Kearney, Clodagh; Gleeson, John P; O'Brien, Fergal J

    2016-05-01

    Developing repair strategies for osteochondral tissue presents complex challenges due to its interfacial nature and complex zonal structure, consisting of subchondral bone, intermediate calcified cartilage and the superficial cartilage regions. In this study, the long term ability of a multi-layered biomimetic collagen-based scaffold to repair osteochondral defects is investigated in a large animal model: namely critical sized lateral trochlear ridge (TR) and medial femoral condyle (MC) defects in the caprine stifle joint. The study thus presents the first data in a clinically applicable large animal model. Scaffold fixation and early integration was demonstrated at 2 weeks post implantation. Macroscopic analysis demonstrated improved healing in the multi-layered scaffold group compared to empty defects and a market approved synthetic polymer osteochondral scaffold groups at 6 and 12 months post implantation. Radiological analysis demonstrated superior subchondral bone formation in both defect sites in the multi-layered scaffold group as early as 3 months, with complete regeneration of subchondral bone by 12 months. Histological analysis confirmed the formation of well-structured subchondral trabecular bone and hyaline-like cartilage tissue in the multi-layered scaffold group by 12 months with restoration of the anatomical tidemark. Demonstration of improved healing following treatment with this natural polymer scaffold, through the recruitment of host cells with no requirement for pre-culture, shows the potential of this device for the treatment of patients presenting with osteochondal lesions. PMID:26901430

  4. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    NASA Astrophysics Data System (ADS)

    Shim, Jin-Hyung; Lee, Jung-Seob; Kim, Jong Young; Cho, Dong-Woo

    2012-08-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed.

  5. Hyaluronic Acid (800 kDa) Supplementation of University of Wisconsin Solution Improves Viability of Osteochondral Grafts and Reduces Matrix Metalloproteinase Expression during Cold Preservation

    PubMed Central

    Yamada, Takuya; Uchida, Kentaro; Onuma, Kenji; Inoue, Gen; Aikawa, Jun; Takano, Shotaro; Sekiguchi, Hiroyuki; Fujimaki, Hisako; Miyagi, Masayuki; Takaso, Masashi

    2015-01-01

    Osteochondral allografting is a promising option for the treatment of large cartilage defects. However, because the cell viability of osteochondral tissues (OCTs) gradually reduces during storage at 4°C, methods for maintaining the cell viability of fresh OCTs are needed to improve transplantation outcomes. Here, we evaluated whether the supplementation of preservation solution with one of three different molecular weight forms of hyaluronic acid (HA) improved the viability of rat OCTs during long-term cold storage. The supplementation of University of Wisconsin (UW) solution with 800 kDa significantly improved the cell viability of OCT after 14 days at 4°C compared to nonsupplemented UW solution. In contrast, UW solution supplemented with either 1900 or 6000 kDa HA did not markedly improve the cell viability of the OCT. Real-time PCR analysis revealed that the levels of matrix metalloproteinases 2, 3, and 9 were significantly decreased in OCT stored in UW solution supplemented with 800 kDa HA. Although further studies in human OCT are warranted, these findings demonstrate that the use of 800 kDa HA in place of serum may be a suitable approach for the long-term preservation of osteochondral allografts designated for the repair of large cartilage defects in the clinical setting. PMID:26199955

  6. Generation of Osteochondral Tissue Constructs with Chondrogenically and Osteogenically Pre-differentiated Mesenchymal Stem Cells Encapsulated in Bilayered Hydrogels

    PubMed Central

    Lam, Johnny; Lu, Steven; Meretoja, Ville V.; Tabata, Yasuhiko; Mikos, Antonios G.; Kasper, F. Kurtis

    2014-01-01

    This study investigated the capacity of chondrogenic and osteogenic pre-differentiation of mesenchymal stem cells (MSCs) for the development of osteochondral tissue constructs using injectable bilayered oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel composites. We hypothesized that the combinatorial approach of encapsulating cell populations of both chondrogenic and osteogenic lineages in a spatially controlled manner within bilayered constructs would enable these cells to maintain their respective phenotypes via the exchange of biochemical factors even without the influence of external growth factors. During monolayer expansion prior to hydrogel encapsulation, it was found that 7 (CG7) and 14 (CG14) days of MSC exposure to TGF-β3 allowed for the generation of distinct cell populations with corresponding chondrogenic maturities as indicated by increasing aggrecan and type II collagen/type I collagen expression. Chondrogenic and osteogenic cells were then encapsulated within their respective (chondral/subchondral) layers in bilayered hydrogel composites to include four experimental groups. Encapsulated CG7 cells within the chondral layer exhibited enhanced chondrogenic phenotype when compared to other cell populations based on stronger type II collagen and aggrecan gene expression and higher glycosaminoglycans-to-hydroxyproline ratios. Osteogenic cells that were co-cultured with chondrogenic cells (in the chondral layer) showed higher cellularity over time, suggesting that chondrogenic cells stimulated the proliferation of osteogenic cells. Groups with osteogenic cells displayed mineralization in the subchondral layer, confirming the effect of osteogenic pre-differentiation. In summary, it was found that MSCs that underwent 7 days, but not 14 days, of chondrogenic pre-differentiation most closely resembled the phenotype of native hyaline cartilage when combined with osteogenic cells in a bilayered OPF hydrogel composite, indicating that the duration of chondrogenic preconditioning is an important factor to control. Furthermore, the respective chondrogenic and osteogenic phenotypes were maintained for 28 days in vitro without the need for external growth factors, demonstrating the exciting potential of this novel strategy for the generation of osteochondral tissue constructs for cartilage engineering applications. PMID:24300948

  7. Three-Dimensional Matrix-Induced Autologous Chondrocytes Implantation for Osteochondral Lesions of the Talus: Midterm Results

    PubMed Central

    Magnan, B.; Samaila, E.; Bondi, M.; Vecchini, E.; Micheloni, G. M.; Bartolozzi, P.

    2012-01-01

    Introduction. We evaluate the midterm results of thirty patients who underwent autologous chondrocytes implantation for talus osteochondral lesions treatment. Materials and Methods. From 2002 to 2009, 30 ankles with a mean lesion size of 2,36 cm2 were treated. We evaluated patients using American Orthopaedic Foot and Ankle Surgery and Coughlin score, Van Dijk scale, recovering time, and Musculoskeletal Outcomes Data Evaluation and Management System. Results. The mean AOFAS score varied from 36.9 to 83.9 at follow-up. Average of Van Dijk scale was 141.1. Coughlin score was excellent/good in 24 patients. MOCART score varied from 6.3 to 3.8. Discussion. This matrix is easy to handle conformable to the lesion and apply by arthroscopy. No correlation between MRI imaging and clinical results is found. Conclusions. Our results, compared with those reported in literature with other surgical procedures, show no superiority evidence for our technique compared to the others regarding the size of the lesions. PMID:22570793

  8. Osteochondral autograft transplantation or autologous chondrocyte implantation for large cartilage defects of the knee: a meta-analysis.

    PubMed

    Li, Zeng; Zhu, Tianyi; Fan, Weimin

    2016-03-01

    Autologous chondrocyte implantation (ACI) and osteochondral autograft transplantation (OAT or mosaicplasty) are two effective surgeries for the treatment of large cartilage defects for more than two decades. But there are always some controversies about which one has the better outcomes for the patients. The purpose of this meta-analysis is to compare the outcomes of these two surgeries and give an advice to the clinical practices. The literature search was performed on multiple electronic databases with specific included criteria. After the assessments, five Randomized controlled trials (level II) were included and two of them were in the same cohort. The continuous data of outcomes were categorized into ranked ones (excellent, good, fair and poor) for comparisons. In the six comparisons of excellent or good results and poor results, the outcomes of ACI were significantly better than OAT in only one comparison (RR 2.57, 95 % CI 1.09-6.07, P = 0.03) while others had no significant differences. We may reach a primary conclusion that there is no significant different outcome between ACI and OAT in a short-term follow-up but it may indicate that the patients with OAT may be more likely to have worse condition than that with ACI for a long-term period. PMID:26068598

  9. Is Antegrade Transmalleolar Drilling Method for Osteochondral Lesion of Talus Necessary? Iatrogenic Cystic Formation at the Tibia: A Report of Five Cases

    PubMed Central

    Kim, Jae Young; Reyes, Francis Joseph V.; Yi, Young

    2016-01-01

    Antegrade transmalleolar drilling method is one of the options for the treatment of osteochondral lesion of talus (OLT). We present five patients who underwent tibial drilling for treatment of OLT and later developed distal tibial cystic formation induced by cartilage opening or heat necrosis during drilling. Antegrade transmalleolar drilling can be a possible option for the treatment of OLT if the lesion is not easily reachable; however, other viable treatment should be considered due to its possibility of distal tibial pathologic change. PMID:26929810

  10. Effect of Self-assembling Peptide, Chondrogenic Factors, and Bone Marrow Derived Stromal Cells on Osteochondral Repair

    PubMed Central

    Miller, Rachel E.; Grodzinsky, Alan J.; Vanderploeg, Eric J.; Lee, Christina; Ferris, Dora J.; Barrett, Myra F.; Kisiday, John D.; Frisbie, David D.

    2010-01-01

    Objective The goal of this study was to test the ability of an injectable self-assembling peptide (KLD) hydrogel with or without chondrogenic factors (CF) and allogeneic bone marrow stromal cells (BMSCs) to stimulate cartilage regeneration in a full-thickness, critically-sized, rabbit cartilage defect model in vivo. We used CF treatments to test the hypotheses that CF would stimulate chondrogenesis and matrix production by cells migrating into acellular KLD (KLD+CF) or by BMSCs delivered in KLD (KLD+CF+BMSCs). Design Three groups were tested against contralateral untreated controls: KLD, KLD+CF, and KLD+CF+BMSCs, n=67. TGF-?1, dexamethasone, and IGF-1 were used as chondrogenic factors (CF) pre-mixed with KLD and BMSCs before injection. Evaluations included gross, histological, immunohistochemical and radiographic analyses. Results KLD without CF or BMSCs showed the greatest repair after 12 weeks with significantly higher Safranin-O, collagen II immunostaining, and cumulative histology scores than untreated contralateral controls. KLD+CF resulted in significantly higher aggrecan immunostaining than untreated contralateral controls. Including allogeneic BMSCs+CF markedly reduced the quality of repair and increased osteophyte formation compared to KLD alone. Conclusions These data show that KLD can fill full-thickness osteochondral defects in situ and improve cartilage repair as shown by Safranin-O, collagen II immunostaining, and cumulative histology. In this small animal model, the full-thickness critically-sized defect provided access to the marrow, similar in concept to abrasion arthroplasty or spongialization in large animal models, and suggests that combining KLD with these techniques may improve current practice. PMID:20851201

  11. COMPARATIVE MACROSCOPIC STUDY OF OSTEOCHONDRAL DEFECTS PRODUCED IN FEMURS OF RABBITS REPAIRED WITH BIOPOLYMER GEL CANE SUGAR

    PubMed Central

    de Albuquerque, Paulo Cezar Vidal Carneiro; dos Santos, Saulo Monteiro; de Andrade Aguiar, José Lamartine; Filho, Nicodemus Pontes; de Mello, Roberto José Vieira; Costa, Mariana Lúcia Correia Ramos; de Albuquerque Olbertz, Clarissa Miranda Carneiro; de Souza Almeida, Tarciana Mendonça; da Silva Santos, Alessandro Henrique; da Silva, Joacil Carlos

    2015-01-01

    Objective: To study the surface, coloring, consistency, continuity and healing of osteochondral defects produced in the femoral condyles of rabbits and filled with sugar cane biopolymer gel (SCBG), after 90, 120 and 180 days, and in comparison with a control group. Method: Sixteen adult New Zealand white rabbits aged 6 to 7 months, weighing between 2 and 2.5 kg and without locomotor system abnormalities were studied. In all the animals, a defect was made in the femoral condyles of the right and left knees, measuring 3.2 mm in diameter and 4 mm in depth, using a trephine. The animals were divided into two groups: study group formed by the right knees, in which the medial and lateral condyles received implants of SCBG; and control group formed by the left knees, in which the medial and lateral condyles were allowed to heal naturally. The knees were assessed 90, 120 and 180 days after the operation. After the animals had been sacrificed, the anatomical specimens were resected and placed in Bouin's solution. They were then photographed with a Nikon Coolpix 5400® coupled to a Nikon SM2800® stereoscopic loupe, to analyze the surface, coloring, consistency, continuity and healing. Results: The results were evaluated using the chi-square test. There were no significant differences in the macroscopic assessments of healing between the study and control groups. Conclusion: With regard to the surface, coloring, consistency, continuity and healing of the defects, the macroscopic appearance of the tissue repaired with SCBG was similar to that of the control group. PMID:27027057

  12. Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model.

    PubMed

    Miot, S; Brehm, W; Dickinson, S; Sims, T; Wixmerten, A; Longinotti, C; Hollander, A P; Mainil-Varlet, P; Martin, I

    2012-01-01

    This study was designed to determine if the maturation stage of engineered cartilage implanted in a goat model of cartilage injury influences the repair outcome. Goat engineered cartilage was generated from autologous chondrocytes cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre-culture and implanted above hydroxyapatite/hyaluronic acid sponges into osteochondral defects. Control defects were left untreated or treated with cell-free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months post implantation by histological staining, modified O'Driscoll scoring and biochemical analyses. Increasing pre-culture time resulted in progressive maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the repair was not improved by any treatment. After 8 months, O'Driscoll histology scores indicated poor cartilage architecture for untreated (29.7 ± 1.6) and cell-free treated groups (24.3 ± 5.8). The histology score was improved when cellular grafts were implanted, with best scores observed for grafts pre-cultured for 2 weeks (16.3 ± 5.8). As compared to shorter pre-culture times, grafts cultured for 6 weeks (histology score: 22.3 ± 6.4) displayed highest type II/I collagen ratios but also inferior architecture of the surface and within the defect, as well as lower integration with native cartilage. Thus, pre-culture of engineered cartilage for 2 weeks achieved a suitable compromise between tissue maturity and structural/integrative properties of the repair tissue. The data demonstrate that the stage of development of engineered cartilage is an important parameter to be considered in designing cartilage repair strategies. PMID:22481226

  13. Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

    PubMed Central

    Santo, Vítor E.; Mano, João F.; Reis, Rui L.

    2013-01-01

    The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors. PMID:23249320

  14. The Normandy field study on juvenile osteochondral conditions: conclusions regarding the influence of genetics, environmental conditions and management, and the effect on performance.

    PubMed

    van Weeren, P René; Denoix, Jean-Marie

    2013-07-01

    Juvenile osteochondral conditions (JOCC) have a major impact on the equine industry and include many musculoskeletal disorders of the young horse, of which osteochondrosis (OC) is the most prominent. The Breeding, Osteochondral Status and Athletic Career (BOSAC) project is the first large, comprehensive, longitudinal field study on the subject conducted in three breeds of performance horses (Thoroughbreds, Standardbred Trotters and Warmbloods) that were monitored in their natural environment where they were reared under common field conditions. The BOSAC study used a radiographic protocol designed for field use coupled to an internally validated severity scoring system, providing weighted radiographic findings as the primary outcome measure. The natural courses of various JOCC appear to differ, according to the joint and condition involved. Genetically, there were also large differences with moderate heritabilities in the tarsocrural and metacarpophalangeal/metatarsophalangeal joints and virtually no heritability for femoropatellar OC. There was a strong influence of exercise history (as an environmental condition) on the manifestation and natural course of JOCC. In the younger age class (<6months) lack of exercise or irregular exercise had a negative effect, as had exposure to excessive exercise. In the yearling category, (exercise-associated) intrinsic trauma seemed to be the most important negative factor. In terms of later function, the association of a poor radiographic score with poorer performance in racing Trotters could be demonstrated. PMID:23639367

  15. Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint.

    PubMed

    Shim, Jin-Hyung; Jang, Ki-Mo; Hahn, Sei Kwang; Park, Ju Young; Jung, Hyuntae; Oh, Kyunghoon; Park, Kyeng Min; Yeom, Junseok; Park, Sun Hwa; Kim, Sung Won; Wang, Joon Ho; Kim, Kimoon; Cho, Dong-Woo

    2016-03-01

    The use of cell-rich hydrogels for three-dimensional (3D) cell culture has shown great potential for a variety of biomedical applications. However, the fabrication of appropriate constructs has been challenging. In this study, we describe a 3D printing process for the preparation of a multilayered 3D construct containing human mesenchymal stromal cells with a hydrogel comprised of atelocollagen and supramolecular hyaluronic acid (HA). This construct showed outstanding regenerative ability for the reconstruction of an osteochondral tissue in the knee joints of rabbits. We found that the use of a mechanically stable, host-guest chemistry-based hydrogel was essential and allowed two different types of extracellular matrix (ECM) hydrogels to be easily printed and stacked into one multilayered construct without requiring the use of potentially harmful chemical reagents or physical stimuli for post-crosslinking. To the best of our knowledge, this is the first study to validate the potential of a 3D printed multilayered construct consisting of two different ECM materials (atelocollagen and HA) for heterogeneous tissue regeneration using an in vivo animal model. We believe that this 3D printing-based platform technology can be effectively exploited for regeneration of various heterogeneous tissues as well as osteochondral tissue. PMID:26844597

  16. Treatment of Osteochondral Lesions of the Talus With Bone Marrow Stimulation and Chitosan–Glycerol Phosphate/Blood Implants (BST-CarGel)

    PubMed Central

    Vilá y Rico, Jesús; Dalmau, Antonio; Chaqués, Francisco Javier; Asunción, Jordi

    2015-01-01

    Bone marrow stimulation (BMS) techniques represent the first-line treatment for unstable osteochondral lesions of the talus or after conservative treatment failure. These techniques are intended to penetrate the subchondral bone to elicit bleeding and allow precursor cells and cytokines from bone marrow to populate the lesion. However, the fibrocartilaginous repair tissue arising after marrow stimulation confers inferior mechanical and biological properties compared with the original hyaline cartilage. The limitations of BMS can be overcome by the use of the soluble chitosan-based polymer BST-CarGel (Piramal Life Sciences, Laval, Quebec, Canada). When mixed with freshly drawn autologous whole blood and applied to a lesion surgically prepared by BMS, BST-CarGel acts as a natural bioscaffold that increases the quantity and improves the residency of the blood clot formed in the cartilage lesion, enhancing the local healing response. The use of BST-CarGel has been previously described in the knee and hip joints with successful results. We describe the arthroscopic technique for BST-CarGel application in combination with BMS techniques for the treatment of osteochondral lesions of the talus. PMID:26870643

  17. Bilayered chitosan-based scaffolds for osteochondral tissue engineering: influence of hydroxyapatite on in vitro cytotoxicity and dynamic bioactivity studies in a specific double-chamber bioreactor.

    PubMed

    Malafaya, Patrícia B; Reis, Rui L

    2009-02-01

    Osteochondral tissue engineering presents a current research challenge due to the necessity of combining both bone and cartilage tissue engineering principles. In the present study, bilayered chitosan-based scaffolds are developed based on the optimization of both polymeric and composite scaffolds. A particle aggregation methodology is proposed in order to achieve an improved integrative bone-cartilage interface needed for this application, since any discontinuity is likely to cause long-term device failure. Cytotoxicity was evaluated by the MTS assay with the L929 fibroblast cell line for different conditions. Surprisingly, in composite scaffolds using unsintered hydroxyapatite, cytotoxicity was observed in vitro. This work reports the investigation that was conducted to overcome and explain this behaviour. It is suggest that the uptake of divalent cations may induce the cytotoxic behaviour. Sintered hydroxyapatite was consequently used and showed no cytotoxicity when compared to the controls. Microcomputed tomography (micro-CT) was carried out to accurately quantify porosity, interconnectivity, ceramic content, particle and pore sizes. The results showed that the developed scaffolds are highly interconnected and present the ideal pore size range to be morphometrically suitable for the proposed applications. Dynamical mechanical analysis (DMA) demonstrated that the scaffolds are mechanically stable in the wet state even under dynamic compression. The obtained elastic modulus was, respectively, 4.21+/-1.04, 7.98+/-1.77 and 6.26+/-1.04 MPa at 1 Hz frequency for polymeric, composite and bilayered scaffolds. Bioactivity studies using both a simulated body fluid (SBF) and a simulated synovial fluid (SSF) were conducted in order to assure that the polymeric component for chondrogenic part would not mineralize, as confirmed by scanning electron microscopy (SEM), inductively coupled plasma-optical emission spectroscopy (ICP) and energy-dispersive spectroscopy (EDS) for different immersion periods. The assays were carried out also under dynamic conditions using, for this purpose, a specifically designed double-chamber bioreactor, aiming at a future osteochondral application. It was concluded that chitosan-based bilayered scaffolds produced by particle aggregation overcome any risk of delamination of both polymeric and composite parts designed, respectively, for chondrogenic and osteogenic components that are mechanically stable. Moreover, the proposed bilayered scaffolds could serve as alternative, biocompatible and safe biodegradable scaffolds for osteochondral tissue engineering applications. PMID:18951857

  18. Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part I: Recapitulation of Native Tissue Healing and Variables for the Design of Delivery Systems

    PubMed Central

    Santo, Vítor E.; Mano, João F.; Reis, Rui L.

    2013-01-01

    The potential of growth factors to stimulate tissue healing through the enhancement of cell proliferation, migration, and differentiation is undeniable. However, critical parameters on the design of adequate carriers, such as uncontrolled spatiotemporal presence of bioactive factors, inadequate release profiles, and supraphysiological dosages of growth factors, have impaired the translation of these systems onto clinical practice. This review describes the healing cascades for bone, cartilage, and osteochondral interface, highlighting the role of specific growth factors for triggering the reactions leading to tissue regeneration. Critical criteria on the design of carriers for controlled release of bioactive factors are also reported, focusing on the need to provide a spatiotemporal control over the delivery and presentation of these molecules. PMID:23268651

  19. Treatment of extended osteochondral lesions of the talus with a free vascularised bone graft from the medial condyle of the femur.

    PubMed

    Hintermann, B; Wagener, J; Knupp, M; Schweizer, C; J Schaefer, D

    2015-09-01

    Large osteochondral lesions (OCLs) of the shoulder of the talus cannot always be treated by traditional osteochondral autograft techniques because of their size, articular geometry and loss of an articular buttress. We hypothesised that they could be treated by transplantation of a vascularised corticoperiosteal graft from the ipsilateral medial femoral condyle. Between 2004 and 2011, we carried out a prospective study of a consecutive series of 14 patients (five women, nine men; mean age 34.8 years, 20 to 54) who were treated for an OCL with a vascularised bone graft. Clinical outcome was assessed using a visual analogue scale (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score. Radiological follow-up used plain radiographs and CT scans to assess graft incorporation and joint deterioration. At a mean follow-up of 4.1 years (2 to 7), the mean VAS for pain had decreased from 5.8 (5 to 8) to 1.8 (0 to 4) (p = 0.001) and the mean AOFAS hindfoot score had increased from 65 (41 to 70) to 81 (54 to 92) (p = 0.003). Radiologically, the talar contour had been successfully reconstructed with stable incorporation of the vascularised corticoperiosteal graft in all patients. Joint degeneration was only seen in one ankle. Treatment of a large OCL of the shoulder of the talus with a vascularised corticoperiosteal graft taken from the medial condyle of the femur was found to be a safe, reliable method of restoring the contour of the talus in the early to mid-term. PMID:26330592

  20. 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.

    PubMed

    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. PMID:24394983

  1. Percutaneous osteoplasty for the treatment of a painful osteochondral lesion of the talus: a case report and literature review.

    PubMed

    Seo, Sung-Suk; Park, Joo-Yeon; Kim, Hae-Jin; Yoon, Ji-Wook; Park, Sang-Hyun; Kim, Kyung-Hoon

    2012-01-01

    An osteochondral lesion of the talus (OLT) is a lesion involving the talar articular cartilage and its subchondral bone. OLT is a known cause of chronic ankle pain after ankle sprains in the active population. The lesion causes deep ankle pain associated with weight-bearing, impaired function, limited range of motion, stiffness, catching, locking, and swelling. There are 2 common patterns of OLTs. Anterolateral talar dome lesions result from inversion and dorsiflexion injuries of the ankle at the area impacting against the fibula. Posteromedial lesions result from inversion, plantar flexion, and external rotation injuries of the ankle at the area impacting against the tibial ceiling of the ankle joint. Early diagnosis of an OLT is particularly important because the tibiotalar joint is exposed to more compressive load per unit area than any other joint in the body. Failure of diagnosis can lead to the evolution of a small, stable lesion into a larger lesion or an unstable fragment, which can result in chronic pain, joint instability, and premature osteoarthritis. A 43-year-old man, with a history of ankle sprain one year previously, visited our pain clinic for continuous right ankle pain after walking or standing for more than 30 minutes. There was a focal tenderness on the posteromedial area of the right talus. Imaging studies revealed a posteromedial OLT classified as having a geode form according to the FOG (fractures, osteonecroses, geodes) radiological classification and categorized as a stage 2a lesion on magnetic resonance imaging. The patient was scheduled for aspiration and osteoplasty with hydroxyapatite under arthroscopic and fluoroscopic guidance. A 26-gauge needle was inserted to infiltrate local anesthetics into the skin over the cyst and ankle joint. An arthroscope was placed into the joint to approach the OLT. The arthroscopic view showed that there was no connection between the OLT and the cyst of the talus body. A 13-gauge bone biopsy needle was inserted into the cyst, and aspiration was performed. Aspirated fluid from the cyst was originally white and clear; however, it changed to a blood-tinged, reddish color due to mixing with the incisional blood. After aspiration, contrast medium was injected, and the shape of the spread was observed. Bone cement comprising hydroxyapatite was injected to fill the bone defect of the cyst. A 1.5 mL volume of cement was injected into the talus under vigilant fluoroscopic and arthroscopic monitoring to prevent its dissemination into the joint. There was no cement leakage into the vessels or articular space. Postoperative fluoroscopy and computed tomography images showed bone cement filling of the defect. In the present case, arthroscopic and fluoroscopic guidance was used for aspiration of an OLT and for performing percutaneous osteoplasty with hydroxyapatite for one defect; this treatment decreased pain upon weight bearing and enabled a return to work without any restrictions one week after the procedure. The purpose of this report was to highlight the presence of OLT in chronic ankle pain and to review its management strategies. PMID:22996869

  2. A new arthroscopic-assisted drilling method through the radius in a distal-to-proximal direction for osteochondritis dissecans of the elbow.

    PubMed

    Arai, Yuji; Hara, Kunio; Fujiwara, Hiroyoshi; Minami, Ginjiro; Nakagawa, Shuji; Kubo, Toshikazu

    2008-02-01

    We developed a new arthroscopic-assisted drilling method through the radius in a distal-to-proximal direction for osteochondritis dissecans (OCD) of the elbow. Only 1 drill hole is created in the radius by use of a single 1.8-mm K-wire inserted from the shaft of the radius approximately 3 cm distal to the humeroradial joint into the joint, which allows drilling of the entire OCD lesion. The forearm is supinated so that the tip of the K-wire is at the lateral side of the lesion in the humeral capitellum, and drilling is performed at 30 degrees elbow flexion. The flexion angle is changed from 30 degrees to 60 degrees to 90 degrees to 120 degrees while maintaining supination, to drill in 4 sites (1 site for each angle of flexion) of the lateral side of the OCD lesion. Next, we move the forearm from supination to pronation so that the tip of the K-wire is placed in the medial side of the lesion in the humeral capitellum, and as with the lateral side, drilling is performed in 4 sites. With this technique, the entire OCD lesion can be vertically drilled under arthroscopic guidance. This method is minimally invasive, and an early return to sports could be possible. PMID:18237711

  3. Arthroscopic removal of palmar/plantar osteochondral fragments (POF) in the metacarpo- and metatarso-phalangeal joints of standardbred trotters--outcome and possible genetic background to POF.

    PubMed

    Roneus, B; Arnason, T; Collinder, E; Rasmussen, M

    1998-01-01

    A clinical material of 133 Standardbred horses with palmar/plantar osteochondral fragments (POF) in the metacarpo- and metatarsophalangeal joints were studied. All horses had their fragments removed with arthroscopic surgery. 102 of the horses were 3 years old or younger when surgery was performed. Anatomical localisations of the fragments were in agreement with earlier reports. There was no statistical significant difference in month of birth in the POF--group compared to the total population. Eighty % of the horses that had raced before surgery came back to racing. The racing performance relative to their contemporaries remained the same after the POF operation. 65% of the horses that had not raced before surgery raced after the operation. The breeding index BLUP (Best Linear Unbiased Prediction) was used to evaluate if the POF-horses differed genetically in racing ability from the total population. The average BLUP value of the POF group was 103.4 (+/- 0.65), while the mean BLUP value of the total population was 98.9. This difference was highly significant and indicated that these POF horses belonged to a selected group. A homogeneity test of allele frequencies in blood type systems was performed to evaluate if any genetic difference was persistent between POF horses compared to the total population. The statistical analysis of gene frequencies for alleles in blood type systems indicated a genetic discrimination in blood type systems D and Tf. PMID:9592942

  4. Osteochondritis dissecans of the elbow: excellent mid-term follow-up results in teenage athletes treated by arthroscopic debridement and microfracture

    PubMed Central

    Bojanić, Ivan; Smoljanović, Tomislav; Dokuzović, Stjepan

    2012-01-01

    Aim To extend the microfracture procedure, which has been proven successful on osteochondritis dissecans (OCD) lesions in the knee and ankle, to OCD lesions in the elbow. Methods Nine young patients were treated by arthroscopic debridement and microfracture by a single surgeon. The average age at operation was 15.0 years (median 15; range 12-19). The average length of the follow-up was 5.3 years (median 5; range 2-9). The follow-up included physical examination and patient interview with elbow function scoring. Success of treatment was determined according to pre-operative and follow-up Mayo Elbow Performance Index scores and the patients’ return to sports. Results Eight patients scored excellent results on the follow-up and 1 scored a good result. Four out of 9 patients were able to increase their training intensity, 2 returned to the same level of activity, 2 changed sports (due to reasons unrelated to the health of their elbow), and 1 left professional sports and started training only recreationally. No patients stopped participating in sports altogether. Conclusions We advocate arthroscopic microfracturing, followed by a strict rehabilitation regime, as a highly effective treatment for OCD of the humeral capitellum. PMID:22351577

  5. Assessment of biocompatibility and initial evaluation of genipin cross-linked elastin-like polypeptides in the treatment of an osteochondral knee defect in rabbits.

    PubMed

    Hrabchak, Christopher; Rouleau, Jessica; Moss, Isaac; Woodhouse, Kimberly; Akens, Margarete; Bellingham, Catherine; Keeley, Fred; Dennis, Madison; Yee, Albert

    2010-06-01

    Polypeptides based on the alternating hydrophobic and cross-linking domain structure of human elastin are capable of undergoing self-assembly to produce polymeric matrices with unique biological and mechanical properties. Here, we test the initial feasibility of using a genipin cross-linked elastin-based material as an acellular plug in the treatment of an osteochondral defect in the rabbit knee. Full-thickness defects in the weight-bearing surface of the medial femoral condyle in 18 New Zealand White rabbits were surgically produced and press fitted with cylindrical pads composed of genipin cross-linked elastin-like polypeptides, with identical wounds in the opposite knee left untreated as controls. The biocompatibility of the material, overall wound healing and regeneration of subchondral tissue was assessed at 2, 4 and 6weeks by histological evaluation, synovial fluid analysis and microcomputerized tomography scanning. Histological analysis revealed the regeneration of subchondral bone at the periphery of the material, with evidence of hyaline-like overgrowth across the apical surface in 11/16 cases. Pads developed tight contacts with host tissue and appeared completely biocompatible, with no evidence of localized immune response or increased inflammation compared to controls. The material was stable to 6weeks, with an aggregate elastic modulus calculated at approximately 470kPa when tested under confined compression. Further studies are required to assess material degradation over time and long-term replacement with repair tissue. PMID:20026437

  6. Scanning Small- and Wide-Angle X-ray Scattering Microscopy Selectively Probes HA Content in Gelatin/Hydroxyapatite Scaffolds for Osteochondral Defect Repair.

    PubMed

    Altamura, Davide; Pastore, Stella G; Raucci, Maria G; Siliqi, Dritan; De Pascalis, Fabio; Nacucchi, Michele; Ambrosio, Luigi; Giannini, Cinzia

    2016-04-01

    This study is aimed at investigating the structure of a scaffold made of bovine gelatin and hydroxyapatite for bone tissue engineering purposes. In particular, the detailed characterization of such a material has a great relevance because of its application in the healing process of the osteochondral defect that consists of a damage of cartilage and injury of the adjacent subchondral bone, significantly compromising millions of patient's quality of life. Two different techniques exploiting X-ray radiation, with table-top setups, are used: microtomography (micro-CT) and microdiffraction. Micro-CT characterizes the microstructure in the three dimensions at the micrometer scale spatial resolution, whereas microdiffraction provides combined structural/morphological information at the atomic and nanoscale, in two dimensional microscopy images with a hundred micrometer spatial resolution. The combination of these two techniques allowed an appropriate structural characterization for the purpose of validating the engineering approach used for the realization of the hydroxyapatite gradient across the scaffold, with properties close to the natural model. PMID:27020229

  7. Evaluation of the Early In Vivo Response of a Functionally Graded Macroporous Scaffold in an Osteochondral Defect in a Rabbit Model.

    PubMed

    Barron, Valerie; Neary, Martin; Mohamed, Khalid Merghani Salid; Ansboro, Sharon; Shaw, Georgina; O'Malley, Grace; Rooney, Niall; Barry, Frank; Murphy, Mary

    2016-05-01

    Cartilage tissue engineering is a multifactorial problem requiring a wide range of material property requirements from provision of biological cues to facilitation of mechanical support in load-bearing diarthrodial joints. The study aim was to design, fabricate and characterize a template to promote endogenous cell recruitment for enhanced cartilage repair. A polylactic acid poly-ε-caprolactone (PLCL) support structure was fabricated using laser micromachining technology and thermal crimping to create a functionally-graded open pore network scaffold with a compressive modulus of 9.98 ± 1.41 MPa and a compressive stress at 50% strain of 8.59 ± 1.35 MPa. In parallel, rabbit mesenchymal stem cells were isolated and their growth characteristics, morphology and multipotency confirmed. Sterilization had no effect on construct chemical structure and cellular compatibility was confirmed. After four weeks implantation in an osteochondral defect in a rabbit model to assess biocompatibility, there was no evidence of inflammation or giant cells. Moreover, acellular constructs performed better than cell-seeded constructs with endogenous progenitor cells homing through microtunnels, differentiating to form neo-cartilage and strengthening integration with native tissue. These results suggest, albeit at an early stage of repair, that by modulating the architecture of a macroporous scaffold, pre-seeding with MSCs is not necessary for hyaline cartilage repair. PMID:26438451

  8. Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: In vitro and in vivo assessment of biological performance.

    PubMed

    Yan, Le-Ping; Silva-Correia, Joana; Oliveira, Mariana B; Vilela, Carlos; Pereira, Hélder; Sousa, Rui A; Mano, João F; Oliveira, Ana L; Oliveira, Joaquim M; Reis, Rui L

    2015-01-01

    Novel porous bilayered scaffolds, fully integrating a silk fibroin (SF) layer and a silk-nano calcium phosphate (silk-nanoCaP) layer for osteochondral defect (OCD) regeneration, were developed. Homogeneous porosity distribution was achieved in the scaffolds, with calcium phosphate phase only retained in the silk-nanoCaP layer. The scaffold presented compressive moduli of 0.4MPa in the wet state. Rabbit bone marrow mesenchymal stromal cells (RBMSCs) were cultured on the scaffolds, and good adhesion and proliferation were observed. The silk-nanoCaP layer showed a higher alkaline phosphatase level than the silk layer in osteogenic conditions. Subcutaneous implantation in rabbits demonstrated weak inflammation. In a rabbit knee critical size OCD model, the scaffolds firmly integrated into the host tissue. Histological and immunohistochemical analysis showed that collagen II positive cartilage and glycosaminoglycan regeneration presented in the silk layer, and de novo bone ingrowths and vessel formation were observed in the silk-nanoCaP layer. These bilayered scaffolds can therefore be promising candidates for OCD regeneration. PMID:25449920

  9. Comparative repair capacity of knee osteochondral defects using regenerated silk fiber scaffolds and fibrin glue with/without autologous chondrocytes during 36 weeks in rabbit model.

    PubMed

    Kazemnejad, Somaieh; Khanmohammadi, Manijeh; Mobini, Sahba; Taghizadeh-Jahed, Masoud; Khanjani, Sayeh; Arasteh, Shaghayegh; Golshahi, Hannaneh; Torkaman, Giti; Ravanbod, Roya; Heidari-Vala, Hamed; Moshiri, Ali; Tahmasebi, Mohammad-Naghi; Akhondi, Mohammad-Mehdi

    2016-06-01

    The reconstruction capability of osteochondral (OCD) defects using silk-based scaffolds has been demonstrated in a few studies. However, improvement in the mechanical properties of natural scaffolds is still challengeable. Here, we investigate the in vivo repair capacity of OCD defects using a novel Bombyx mori silk-based composite scaffold with great mechanical properties and porosity during 36 weeks. After evaluation of the in vivo biocompatibility and degradation rate of these scaffolds, we examined the effectiveness of these fabricated scaffolds accompanied with/without autologous chondrocytes in the repair of OCD lesions of rabbit knees after 12 and 36 weeks. Moreover, the efficiency of these scaffolds was compared with fibrin glue (FG) as a natural carrier of chondrocytes using parallel clinical, histopathological and mechanical examinations. The data on subcutaneous implantation in mice showed that the designed scaffolds have a suitable in vivo degradation rate and regenerative capacity. The repair ability of chondrocyte-seeded scaffolds was typically higher than the scaffolds alone. After 36 weeks of implantation, most parts of the defects reconstructed by chondrocytes-seeded silk scaffolds (SFC) were hyaline-like cartilage. However, spontaneous healing and filling with a scaffold alone did not eventuate in typical repair. We could not find significant differences between quantitative histopathological and mechanical data of SFC and FGC. The fabricated constructs consisting of regenerated silk fiber scaffolds and chondrocytes are safe and suitable for in vivo repair of OCD defects and promising for future clinical trial studies. PMID:26822846

  10. Matrix generation within a macroporous non-degradable implant for osteochondral defects is not enhanced with partial enzymatic digestion of the surrounding tissue: evaluation in an in vivo rabbit model.

    PubMed

    Krych, Aaron J; Wanivenhaus, Florian; Ng, Kenneth W; Doty, Stephen; Warren, Russell F; Maher, Suzanne A

    2013-10-01

    Articular cartilage defects are a significant source of pain, have limited ability to heal, and can lead to the development of osteoarthritis. However, a surgical solution is not available. To tackle this clinical problem, non-degradable implants capable of carrying mechanical load immediately after implantation and for the duration of implantation, while integrating with the host tissue, may be viable option. But integration between articular cartilage and non-degradable implants is not well studied. Our objective was to assess the in vivo performance of a novel macroporous, nondegradable, polyvinyl alcohol construct. We hypothesized that matrix generation within the implant would be enhanced with partial digestion of the edges of articular cartilage. Our hypothesis was tested by randomizing an osteochondral defect created in the trochlea of 14 New Zealand white rabbits to treatment with: (i) collagenase or (ii) saline, prior to insertion of the implant. At 1 and 3-month post-operatively, the gross morphology and histologic appearance of the implants and the surrounding tissue were assessed. At 3 months, the mechanical properties of the implant were also quantified. Overall, the hydrogel implants performed favorably; at all time-points and in all groups the implants remained well fixed, did not cause inflammation or synovitis, and did not cause extensive damage to the opposing articular cartilage. Regardless of treatment with saline or collagenase, at 1 month post-operatively implants from both groups had a contiguous interface with adjacent cartilage and were populated with chondrocyte-like cells. At 3 months fibrous encapsulation of all implants was evident, there was no difference between area of aggrecan staining in the collagenase versus saline groups, and implant modulus was similar in both groups; leading us to reject our hypothesis. In summary, a porous PVA osteochondral implant remained well fixed in a short term in vivo osteochondral defect model; however, matrix generation within the implant was not enhanced with partial digestion of adjacent articular cartilage. PMID:23846837

  11. Matrix generation within a macroporous non-degradable implant for osteochondral defects is not enhanced with partial enzymatic digestion of the surrounding tissue: evaluation in an in vivo rabbit model

    PubMed Central

    Krych, Aaron J.; Wanivenhaus, Florian; Ng, Kenneth W.; Doty, Stephen; Warren, Russell F.

    2013-01-01

    Articular cartilage defects are a significant source of pain, have limited ability to heal, and can lead to the development of osteoarthritis. However, a surgical solution is not available. To tackle this clinical problem, non-degradable implants capable of carrying mechanical load immediately after implantation and for the duration of implantation, while integrating with the host tissue, may be viable option. But integration between articular cartilage and non-degradable implants is not well studied. Our objective was to assess the in vivo performance of a novel macroporous, nondegradable, polyvinyl alcohol construct. We hypothesized that matrix generation within the implant would be enhanced with partial digestion of the edges of articular cartilage. Our hypothesis was tested by randomizing an osteochondral defect created in the trochlea of 14 New Zealand white rabbits to treatment with: (i) collagenase or (ii) saline, prior to insertion of the implant. At 1 and 3-month post-operatively, the gross morphology and histologic appearance of the implants and the surrounding tissue were assessed. At 3 months, the mechanical properties of the implant were also quantified. Overall, the hydrogel implants performed favorably; at all time-points and in all groups the implants remained well fixed, did not cause inflammation or synovitis, and did not cause extensive damage to the opposing articular cartilage. Regardless of treatment with saline or collagenase, at 1 month post-operatively implants from both groups had a contiguous interface with adjacent cartilage and were populated with chondrocyte-like cells. At 3 months fibrous encapsulation of all implants was evident, there was no difference between area of aggrecan staining in the collagenase versus saline groups, and implant modulus was similar in both groups; leading us to reject our hypothesis. In summary, a porous PVA osteochondral implant remained well fixed in a short term in vivo osteochondral defect model; however, matrix generation within the implant was not enhanced with partial digestion of adjacent articular cartilage. PMID:23846837

  12. Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model

    PubMed Central

    Boakye, Lorraine A; Ross, Keir A; Pinski, John M; Smyth, Niall A; Haleem, Amgad M; Hannon, Charles P; Fortier, Lisa A; Kennedy, John G

    2015-01-01

    AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1 (TGF-β1) in cartilage following autologous osteochondral transplantation (AOT) in a rabbit knee cartilage defect model. METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma (PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest (ROI) (left, right and center of the autologous grafts interfaces) were evaluated using MetaMorph. Percentage of chondrocytes positive for TGF-β1 was then assessed. RESULTS: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs (left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point (P = 6.6 × 10-4, 3.1 × 10-4 and 7.3 × 10-3 for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees (36% ± 29% vs 15% ± 18%) (P = 1.8 × 10-6) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo. PMID:26716092

  13. Arthroscopic Bioabsorbable Screw Fixation of Unstable Osteochondritis Dissecans in Adolescents: Clinical Results, Magnetic Resonance Imaging, and Second-Look Arthroscopic Findings

    PubMed Central

    Chun, Keun Churl; Kim, Kwang Mee; Jeong, Ki Joon; Lee, Yong Chan; Kim, Jeong Woo

    2016-01-01

    Background This study aimed to evaluate the clinical and radiological outcomes of arthroscopic bioabsorbable screw fixation in osteochondritis dissecans (OCD) in adolescent patients with unstable lesions causing pain. Methods The study included 11 patients (10 males and 1 female) with OCD who underwent arthroscopic bioabsorbable screw fixation between July 2007 and February 2014 and were available for follow-up for more than 12 months. The mean age at diagnosis was 16.3 years (range, 11 to 19 years), and the average follow-up period was 51 months (range, 12 to 91 months). Clinical results were evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm knee score, and International Knee Documentation Committee (IKDC) score measured before surgery and at follow-up. Functional evaluation was made using the Tegner activity scale. Magnetic resonance imaging (MRI) and second-look arthroscopy were performed at the 12-month follow-up. Results Between the preoperative assessment and follow-up, improvements were seen in the KOOS (range, 44.9 to 88.1), Lysholm knee score (range, 32.6 to 82.8), and IKDC score (range, 40.8 to 85.6). The Tegner activity scale also improved from 2.8 to 6.1. Based on postoperative MRI, there were eight Dipaola grade I cases and three grade II cases. No complications due to fixation failure developed in any case. Second-look arthroscopy at 12 months postoperatively revealed that the lesion was covered with cartilage in all cases. Conclusions For unstable OCD lesions causing pain in adolescents, arthroscopic bioabsorbable screw fixation provided favorable outcomes with reduced pain and restoration of movement. Therefore, it should be considered as an effective treatment for OCD. PMID:26929800

  14. Improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model

    PubMed Central

    Araki, Susumu; Imai, Shinji; Ishigaki, Hirohito; Mimura, Tomohiro; Nishizawa, Kazuya; Ueba, Hiroaki; Kumagai, Kousuke; Kubo, Mitsuhiko; Mori, Kanji; Ogasawara, Kazumasa; Matsusue, Yoshitaka

    2015-01-01

    Background and purpose Integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. We investigated whether incorporation of mesenchymal stem cells (MSCs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. Methods Cynomolgus macaque bone marrow-derived MSCs were isolated and incorporated into type-I collagen gel. Full-thickness osteochondral defects (3 mm in diameter, 5 mm in depth) were created in the patellar groove of 36 knees of 18 macaques and were either left untreated (null group, n = 12), had collagen gel alone inserted (gel group, n = 12), or had collagen gel incorporating MSCs inserted (MSC group, n = 12). After 6, 12, and 24 weeks, the cartilage integration and tissue response were evaluated macroscopically and histologically (4 null, 4 gel, and 4 MSC knees at each time point). Results The gel group showed most cartilage-rich reparative tissue covering the defect, owing to formation of excessive cartilage extruding though the insufficient subchondral bone. Despite the fact that a lower amount of new cartilage was produced, the MSC group had better-quality cartilage with regular surface, seamless integration with neighboring naïve cartilage, and reconstruction of trabecular subchondral bone. Interpretation Even with intensive investigation, MSC-based cell therapy has not yet been established in experimental cartilage repair. Our model using cynomolgus macaques had optimized conditions, and the method using MSCs is superior to other experimental settings, allowing the possibility that the procedure might be introduced to future clinical practice. PMID:25175660

  15. The Effect of Exercise on the Early Stages of Mesenchymal Stromal Cell-Induced Cartilage Repair in a Rat Osteochondral Defect Model

    PubMed Central

    Yamaguchi, Shoki; Aoyama, Tomoki; Ito, Akira; Nagai, Momoko; Iijima, Hirotaka; Tajino, Junichi; Zhang, Xiangkai; Kiyan, Wataru; Kuroki, Hiroshi

    2016-01-01

    The repair of articular cartilage is challenging owing to the restriction in the ability of articular cartilage to repair itself. Therefore, cell supplementation therapy is possible cartilage repair method. However, few studies have verified the efficacy and safety of cell supplementation therapy. The current study assessed the effect of exercise on early the phase of cartilage repair following cell supplementation utilizing mesenchymal stromal cell (MSC) intra-articular injection. An osteochondral defect was created on the femoral grooves bilaterally of Wistar rats. Mesenchymal stromal cells that were obtained from male Wistar rats were cultured in monolayer. After 4 weeks, MSCs were injected into the right knee joint and the rats were randomized into an exercise or no-exercise intervention group. The femurs were divided as follows: C group (no exercise without MSC injection); E group (exercise without MSC injection); M group (no exercise with MSC injection); and ME group (exercise with MSC injection). At 2, 4, and 8 weeks after the injection, the femurs were sectioned and histologically graded using the Wakitani cartilage repair scoring system. At 2 weeks after the injection, the total histological scores of the M and ME groups improved significantly compared with those of the C group. Four weeks after the injection, the scores of both the M and ME groups improved significantly. Additionally, the scores in the ME group showed a significant improvement compared to those in the M group. The improvement in the scores of the E, M, and ME groups at 8 weeks were not significantly different. The findings indicate that exercise may enhance cartilage repair after an MSC intra-articular injection. This study highlights the importance of exercise following cell transplantation therapy. PMID:26968036

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

    PubMed

    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 findings suggest that cysts occurring after OCAs may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface. PMID:23958821

  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

    PubMed Central

    2013-01-01

    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 < 0.05), although there were no significant differences between Groups I and IV at a 3.0-mm deep vacant space. The expression levels of type-2 collagen in Groups II and III were significantly higher (p < 0.05) than that in Group IV. 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. PMID:23369101

  18. Continuous multilayered composite hydrogel as osteochondral substitute.

    PubMed

    Leone, G; Volpato, M D; Nelli, N; Lamponi, S; Boanini, E; Bigi, A; Magnani, A

    2015-08-01

    Cartilage is a highly organized avascular soft tissue that assembles from nano-to macro-scale to produce a complex structural network. To mimic cartilage tissue, we developed a stable multilayered composite material, characterized by a tailored gradient of mechanical properties. The optimized procedure implies chemical crosslinking of each layer directly onto the previous one and ensures a drastic reduction of the material discontinuities and brittleness. The multilayered composite was characterized by infrared spectroscopy, differential scanning calorimetry, thermogravimetry, and scanning electron microscopy in order to compare its physico-chemical characteristics with those of cartilage tissue. The rheological behavior of the multilayered composite was similar to that of human cartilage. Finally its cytocompatibility toward chondrocytes and osteoblasts was evaluated. PMID:25504681

  19. Osteochondral grafting of knee joint using mosaicplasty.

    PubMed

    Wajid, Muhammad Abdul; Shah, Muhammad Idrees; Mohsin-e-Azam; Ahmad, Tashfeen

    2011-03-01

    Focal cartilage defects of articular surface-traumatic and degenerative are difficult to treat, thus a variety of surgical techniques have been developed and reported for treatment of such defects. Procedures such as Priddies perforations, microfracture, abrasion chondroplasty have shown long-term results which are often less than adequate. One of the reasons is that all these techniques lead to the formation of fibrocartilage which has inferior mechanical properties as compared to the native hyaline cartilage. Mosaicplasty is a procedure which aims at replacing the lost articular cartilage with hyaline cartilage including underlying bone support, thus providing adequate stability to the cartilage and better cartilage/bone integration. A young man underwent this procedure for recalcitrant knee pain at our institution. At 2 years follow-up, his knee pain has significantly improved. We hereby present medium term results (2 years) of this first case report in local literature. PMID:21419031

  20. Detection of intra-articular osteochondral bodies in the knee using computed arthrotomography

    SciTech Connect

    Sartoris, D.J.; Kursunoglu, S.; Pineda, C.; Kerr, R.; Pate, D.; Resnick, D.

    1985-05-01

    A new technique using air arthrography followed by computed tomography enables identification of free osteocartilaginous fragments in the knee joint. Clinical examples with useful diagnostic information are presented, and potential pitfalls in the interpretation of this information are discussed.

  1. Morphogenetically active scaffold for osteochondral repair (polyphosphate/alginate/N,O-carboxymethyl chitosan).

    PubMed

    Müller, W E; Neufurth, M; Wang, S; Tolba, E; Schröder, H C; Wang, X

    2016-01-01

    Here we describe a novel bioinspired hydrogel material that can be hardened with calcium ions to yield a scaffold material with viscoelastic properties matching those of cartilage. This material consists of a negatively charged biopolymer triplet, composed of morphogenetically active natural inorganic polyphosphate (polyP), along with the likewise biocompatible natural polymers N,O-carboxymethyl chitosan (N,O-CMC) and alginate. The porosity of the hardened scaffold material obtained after calcium exposure can be adjusted by varying the pre-processing conditions. Various compression tests were applied to determine the local (nanoindentation) and bulk mechanical properties (tensile/compression test system for force measurements) of the N,O-CMC-polyP-alginate material. Determinations of the Young's modulus revealed that the stiffness of this comparably water rich (and mouldable) material increases during successive compression cycles to values measured for native cartilage. The material not only comprises viscoelastic properties suitable for a cartilage substitute material, but also displays morphogenetic activity. It upregulates the expression of genes encoding for collagen type II and aggrecan, the major proteoglycan within the articular cartilage, in human chondrocytes, and the expression of alkaline phosphatase in human bone-like SaOS-2 cells, as revealed in RT qPCR experiments. Further, we demonstrate that the new polyP-based material can be applied for manufacturing 3D solid models of cartilage bone such as of the tibial epiphyseal plate and the superior articular cartilage surface. Since the material is resorbable and enhances the activity of cells involved in regeneration of cartilage tissue, this material has the potential to be used for artificial articular cartilage implants. PMID:26898843

  2. Decellularized Cartilage May Be a Chondroinductive Material for Osteochondral Tissue Engineering

    PubMed Central

    Sutherland, Amanda J.; Beck, Emily C.; Dennis, S. Connor; Converse, Gabriel L.; Hopkins, Richard A.; Berkland, Cory J.; Detamore, Michael S.

    2015-01-01

    Extracellular matrix (ECM)-based materials are attractive for regenerative medicine in their ability to potentially aid in stem cell recruitment, infiltration, and differentiation without added biological factors. In musculoskeletal tissue engineering, demineralized bone matrix is widely used, but recently cartilage matrix has been attracting attention as a potentially chondroinductive material. The aim of this study was thus to establish a chemical decellularization method for use with articular cartilage to quantify removal of cells and analyze the cartilage biochemical content at various stages during the decellularization process, which included a physically devitalization step. To study the cellular response to the cartilage matrix, rat bone marrow-derived mesenchymal stem cells (rBMSCs) were cultured in cell pellets containing cells only (control), chondrogenic differentiation medium (TGF-β), chemically decellularized cartilage particles (DCC), or physically devitalized cartilage particles (DVC). The chemical decellularization process removed the vast majority of DNA and about half of the glycosaminoglycans (GAG) within the matrix, but had no significant effect on the amount of hydroxyproline. Most notably, the DCC group significantly outperformed TGF-β in chondroinduction of rBMSCs, with collagen II gene expression an order of magnitude or more higher. While DVC did not exhibit a chondrogenic response to the extent that DCC did, DVC had a greater down regulation of collagen I, collagen X and Runx2. A new protocol has been introduced for cartilage devitalization and decellularization in the current study, with evidence of chondroinductivity. Such bioactivity along with providing the ‘raw material’ building blocks of regenerating cartilage may suggest a promising role for DCC in biomaterials that rely on recruiting endogenous cell recruitment and differentiation for cartilage regeneration. PMID:25965981

  3. An olecranon chondral flap and osteochondral coronoid fracture in a spontaneously reduced elbow dislocation in a child.

    PubMed

    Quick, Tom J; Gibbons, Paul; Smith, Nick

    2013-09-01

    Elbow injuries in children are very common and radiographs are often difficult to interpret because of the radiolucency of the cartilaginous anlage and the progressive appearance of multiple secondary ossification centres. Elbow dislocations are rare injuries in children. Coronoid fractures can occur during dislocation or relocation of the elbow and can be the only hallmark of a severe injury. The understanding of the mechanics of these injuries has undergone considerable evolution over the past decade. Intra-articular chondral flap fractures are a traumatic elevation of the hyaline cartilage from the subchondral bone. They are also rare injuries in children but should be included in the differential when examining an injured joint. The infrequency of these injuries provides little opportunity to become accustomed to the radiographic signs. We present a case report of a 4-year-old boy with both an olecranon chondral flap and coronoid cartilaginous fracture after a joint dislocation. We present his plain radiography and MRI with illustrated photographic records of the operative findings. This injury has been little described in the literature and never with such imaging to aid understanding of both the pathology and the injury mechanism. PMID:23629489

  4. Up-regulation of the chemo-attractive receptor ChemR23 and occurrence of apoptosis in human chondrocytes isolated from fractured calcaneal osteochondral fragments

    PubMed Central

    Sena, Paola; Manfredini, Giuseppe; Benincasa, Marta; Mariani, Francesco; Smargiassi, Alberto; Catani, Fabio; Palumbo, Carla

    2014-01-01

    To study the expression level of a panel of pro/anti-apoptotic factors and inflammation-related receptors in chondral fragments from patients undergoing surgical treatment for intra-articular calcaneal fractures, cartilage fragments were retrieved from calcaneal fractures of 20 patients subjected to surgical treatment. Primary cultures were performed using chondral fragments from fractured and control patients. Chondrocyte cultures from each patient of the fractured and control groups were subjected to immunofluorescence staining and quantitatively analyzed under confocal microscopy. Proteins extracted from the cultured chondrocytes taken from the fractured and control groups were processed for Western blot experiments and densitometric analysis. The percentage of apoptotic cells was determined using the cleaved PARP-1 antibody. The proportion of labelled cells was 35% for fractured specimens, compared with 7% for control samples. Quantification of caspase-3 active and Bcl-2 proteins in chondrocyte cultures showed a significant increase of the apoptotic process in fractured specimens compared with control ones. Fractured chondrocytes were positively stained for ChemR23 with statistically significant differences with respect to control samples. Densitometric evaluation of the immunoreactive bands confirmed these observations. Human articular chondrocytes obtained from patients with intra-articular calcaneal fractures express higher levels of pivotal pro-apoptotic factors, and of the chemo-attractive receptor ChemR23, compared with control cultures. On the basis of these observations, the authors hypothesize that consistent prolonged chondrocyte death, associated with the persistence of high levels of pro-inflammatory factors, could enhance the deterioration of cartilage tissue with consequent development of post-traumatic arthritis following intra-articular bone fracture. PMID:24689495

  5. Synthetic implants for the repair of osteochondral defects of the medial femoral condyle: a biomechanical and histological evaluation in the rabbit knee.

    PubMed

    Messner, K; Gillquist, J

    1993-06-01

    Polyurethane-coated and uncoated polytetrafluoroethylene (PTFE) (Teflon) and polyester (Dacron) felts were used for repair of full-thickness cartilage defects in the rabbit knee. At 3 months the indentation characteristics and the histological appearance of the repairs were compared with those of a sham-operation, natural repair, and periosteal grafting. Joint compressive load-displacement and indentation characteristics of the cartilage adjacent to the defect were normal for all alternatives. All the repair sites had a higher compliance than had normal cartilage-bone, but synthetic grafting had values closer to normal than periosteal grafting. The adjacent cartilage appeared macroscopically normal, except with periosteal grafting and coated PTFE implants where it showed surface irregularities in some cases. With periosteal and uncoated synthetic implants the defects were completely filled, but not in the natural repair sites. Most of the coated implants failed by separation within the implant. On histological examination, ingrowth of trabecular bone from the base of the defect into the synthetic material was seen in all the specimens. The neocartilage 'score' was equally low with all the repairs reaching only one-third of the maximum points. All the repairs were associated with synovitis. Further, some of the knees with the synthetic materials repair had debris particles in the synovium. We conclude that none of the biological resurfacing techniques described achieved normal articular cartilage characteristics at 3 months, although the compliance of the repair site was closer to normal with synthetic than with periosteal grafting. PMID:8329524

  6. Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition

    PubMed Central

    2013-01-01

    Background In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls. Methods Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair. Results All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue. Conclusions Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair. PMID:23324433

  7. Overview of cartilage biology and new trends in cartilage stimulation.

    PubMed

    Triche, Rachel; Mandelbaum, Bert R

    2013-03-01

    This article reviews the basics of articular cartilage biology, which provide a necessary foundation for understanding the evolving field of articular cartilage injury and repair. The currently popular treatment options for osteochondral injury (microfracture, osteochondral autograft transfer system, osteochondral allograft, autologous chondrocyte implantation, and the use of scaffolds with autologous chondrocyte implantation) document the significant advances made in this area in the past 2 decades. Integration of newly available information and technology derived from advances in molecular biology and tissue engineering holds even greater promise for continued advances in optimal management of this challenging problem. PMID:23465945

  8. Cartilage lesions in patellofemoral dislocations: Incidents/locations/when to treat

    PubMed Central

    Covell, D. Jeff; Lattermann, Christian

    2014-01-01

    Patellofemoral dislocations are frequently associated with chondral injury. Chondral and osteochondral lesions are often associated with traumatic (high energy) patellofemoral dislocations whereas atraumatic (low energy) patellofemoral dislocations in patients with significant patellofemoral risk factors have a much lower incidence of osteochondral damage. This article provides a historical overview and delineates the current state of radiographic and clinical outcomes of osteochondral lesions after patellofemoral dislocation. The importance of understanding risk factors of redislocation is emphasized and the current treatment options for these cartilage lesions associated with patellofemoral dislocation are briefly summarized. PMID:22878659

  9. Cartilage lesions of the patella: management after acute patellar dislocation.

    PubMed

    Metzler, Adam V; Lattermann, Christian; Johnson, Darren L

    2015-05-01

    Articular cartilage injuries to the patella are frequent after patellar dislocation. The management of these acute cartilage injuries in the acute setting can be challenging. It is well documented that acute fixation is the optimal choice for treatment of osteochondral injuries. This article discusses the challenges and potential treatment options for acute chondral/osteochondral injuries to the patella after acute patellar dislocation. PMID:25970358

  10. [Arthroscopic treatment of chondral lesions of the ankle joint : Evidence-based therapy].

    PubMed

    Thomas, M; Jordan, M; Hamborg-Petersen, E

    2016-02-01

    Ankle sprains are the most relevant injuries of the lower extremities and can lead to damage to ligaments and osteochondral lesions. Up to 50 % of patients with a sprained ankle later develop a lesion of the cartilage in the ankle joint or an osteochondral lesion of the talus. This can lead to osteoarthritis of the injured ankle joint. Spontaneous healing is possible in all age groups in cases of a bone bruise in the subchondral bone but in isolated chondral injuries is only useful in pediatric patients. In many cases chondral and osteochondral injuries lead to increasing demarcation of the affected area and can result in progressive degeneration of the joint if not recognized in time. There also exist a certain number of osteochondral changes of the articular surface of the talus without any history of relevant trauma, which are collectively grouped under the term osteochondrosis dissecans. Perfusion disorders are discussed as one of many possible causes of these alterations. Nowadays, chondral and osteochondral defects can be treated earlier due to detection using very sensitive magnetic resonance imaging (MRI) and computed tomography (CT) techniques. The use of conservative treatment only has a chance of healing in pediatric patients. Conservative measures for adults should only be considered as adjuvant treatment to surgery.Based on a comprehensive analysis of the current literature, this article gives an overview and critical analysis of the current concepts for treatment of chondral and osteochondral injuries and lesions of the talus. With arthroscopic therapy curettage and microfracture of talar lesions are the predominant approaches or retrograde drilling of the defect is another option when the chondral coating is retained. Implantation of autologous chondral cells or homologous juvenile cartilage tissue is also possible with arthroscopic techniques. Osteochondral fractures (flake fracture) are usually performed as a mini-open procedure supported by arthroscopy. The use of the osteochondral autograft transfer system (OATS), implantation of membranes with or without autologous bone marrow transfer and possibly with growth factors or implantation of stem cells are carried out in combination with arthroscopic mini-open procedures. The results from the literature are discussed and compared with own results after arthroscopic treatment of chondral lesions of the talus. PMID:26810230

  11. Particulated Juvenile Articular Cartilage Implantation in the Knee

    PubMed Central

    Stevens, Hazel Y.; Shockley, Blake E.; Willett, Nick J.; Lin, Angela S.P.; Raji, Yazdan; Labib, Sameh A.

    2014-01-01

    Objective: The goal of this report is to describe the outcome of sequential particulated cartilage allograft and autologous osteochondral transfer treatments for an osteochondral lesion of the medial femoral condyle. Methods: A 44-year-old woman was treated with a particulated juvenile articular cartilage allograft (DeNovo NT) for a chondral lesion of the knee. As a result of continued pain, she had 2 further surgeries, including an autologous osteochondral transfer system procedure and finally a unicondylar knee arthroplasty. At the final procedure, the areas of the allograft and autograft tissue were biopsied for histological evaluation. The quality of the residual cartilage tissue was assessed first by equilibrium partitioning of an ionic contrast agent via micro–computed tomography (EPIC-µCT), and then by hematoxylin and eosin, Safranin O staining, and polarized light microscopy. Results: Despite showing good healing at 7 months postsurgery by MRI, at 28 months post DeNovo NT tissue implantation the excised cartilage tissue was heterogeneous, with some regions of hyaline-like cartilage and some regions of fibrocartilage. The later mosaicplasty may have helped maintain hyaline-like cartilage of the DeNovo NT tissue in its vicinity. Conclusion: This case report describes the cartilage repair tissue produced by DeNovo NT implantation and compares it with autologous osteochondral plug tissue. PMID:26069686

  12. Cartilage repair techniques of the talus: An update

    PubMed Central

    Baums, Mike H; Schultz, Wolfgang; Kostuj, Tanja; Klinger, Hans-Michael

    2014-01-01

    Symptomatic chondral or osteochondral defects of the talus reduce the quality of life of many patients. Although their pathomechanism is well understood, it is well known that different aetiologic factors play a role in their origin. Additionally, it is well recognised that the talar articular cartilage strongly differs from that in the knee. Despite this fact, many recommendations for the management of talar cartilage defects are based on approaches that were developed for the knee. Conservative treatment seems to work best in paediatric and adolescent patients with osteochondritis dissecans. However, depending on the size of the lesions, surgical approaches are necessary to treat many of these defects. Bone marrow stimulation techniques may achieve good results in small lesions. Large lesions may be treated by open procedures such as osteochondral autograft transfer or allograft transplantation. Autologous chondrocyte transplantation, as a restorative procedure, is well investigated in the knee and has been applied in the talus with increasing popularity and promising results but the evidence to date is poor. The goals of the current article are to summarise the different options for treating chondral and osteochondral defects of the talus and review the available literature. PMID:25035819

  13. Synovial osteochrondomatosis of the talonavicular joint: a case report.

    PubMed

    Dawson-Bowling, Sebastian; Hamilton, Paul; Bismil, Quamar; Gaddipati, Mohan; Bendall, Stephen

    2008-02-01

    Synovial osteochondromatosis is a condition of unknown etiology affecting articular synovium, characterised by the formation of osteochondral nodules. Occurrences in the foot and ankle are rare. To our knowledge, this condition has never previously been described in the talonavicular joint. In the following article, we present two cases and review the literature regarding this condition. PMID:18315983

  14. Osteomyelitis of the head and neck: sequential radionuclide scanning in diagnosis and therapy

    SciTech Connect

    Strauss, M.; Kaufman, R.A.; Baum, S.

    1985-01-01

    Sequential technetium and gallium scans of the head and neck were used to confirm the diagnosis of osteomyelitis and as an important therapeutic aid to delineate the transformation of active osteomyelitis to inactive osteomyelitis in 11 cases involving sites in the head and neck. Illustrative cases are presented of frontal sinus and cervical spine osteomyelitis and laryngeal osteochondritis.

  15. Hip Arthroscopic Management for Femoral Head Fractures and Posterior Acetabular Wall Fractures (Pipkin Type IV)

    PubMed Central

    Park, Myung-Sik; Yoon, Sun-Jung; Choi, Seung-Min

    2013-01-01

    Femoral head fractures associated with acetabular fractures are usually treated by an open method. After a closed reduction of a hip dislocation, open reduction and internal fixation of acetabular fractures usually depend on the type of acetabular fracture. Acetabular fractures associated with femoral head fractures, torn labrums, or osteochondral fractures are often managed simultaneously by a posterior approach. The patient in this study was referred to us because of pain and limited motion after open reduction and internal fixation of an acetabular fracture. Postoperative computed tomography showed remnant osteochondral fragments located in the cotyloid fossa. Using hip arthroscopy, we found a torn labrum and multiple osteochondral fragments in the cotyloid fossa. The avulsed torn labrum was reattached with 2 anchors through the midanterior portal. Osteochondral fragments were curetted and removed. This article reviews the treatment of the torn labrum and multiple fragments after acetabular fracture reduction. The patient recovered immediately and had a satisfactory outcome. We conclude that hip arthroscopy is a valuable option for treating femoral head fracture dislocations associated with acetabular fractures. PMID:24265988

  16. Clinics in diagnostic imaging (163). Transient lateral patellar dislocation with trochlear dysplasia

    PubMed Central

    Zhang, Junwei; Lee, Chin Hwee

    2015-01-01

    A 14-year-old girl presented with left knee pain and swelling after an injury. Magnetic resonance (MR) imaging showed a transient lateral patellar dislocation with patellar osteochondral fracture, medial patellofemoral ligament tear and underlying femoral trochlear dysplasia. Open reduction and internal fixation of the osteochondral fracture, plication of the medial patellar retinaculum and lateral release were performed. As lateral patellar dislocation is often clinically unsuspected, an understanding of its characteristic imaging features is important in making the diagnosis. Knowledge of the various predisposing factors for patellar instability may also influence the choice of surgical management. We also discuss signs of acute injury and chronic instability observed on MR imaging, and the imaging features of anatomical variants that predispose an individual to lateral patellar dislocation. Treatment options and postsurgical imaging appearances are also briefly described. PMID:26512145

  17. Outcomes in orthopedics and traumatology: translating research into practice

    PubMed Central

    de Moraes, Vincius Ynoe; Ferrari, Paula Martins de Oliveira; Gracitelli, Guilherme Conforto; Faloppa, Flvio; Belloti, Joo Carlos

    2014-01-01

    Clinical research is focused in generating evidence that is feasible to be applicable to practitioners. However, translating research-focused evidence into practice may be challenging and often misleading. This article aims is to pinpoint these challenges and suggest some methodological safeguards, taking platelet-rich plasma therapies and knee osteochondral injuries as examples. Studies and systematic reviews involving the following concepts will be investigated: clinically relevant outcomes, systematic errors on sample calculation, internal and external validity. Relevant studies on platelet-rich plasma for muscle-tendon lesions and updates on osteochondral lesions treatment were included in this analysis. Authors and clinicians should consider these concepts for the implementation and application of dissemination of the best evidence. Research results should be challenged by a weighted analysis of its methodological soundness and applicability. Level of Evidence V, Therapeutic Studies - Investigating the Results of Treatment. PMID:25538481

  18. Success Rates and Immunologic Responses of Autogenic, Allogenic, and Xenogenic Treatments to Repair Articular Cartilage Defects

    PubMed Central

    Revell, Christopher M.

    2009-01-01

    This review examines current approaches available for articular cartilage repair, not only in terms of their regeneration potential, but also as a function of immunologic response. Autogenic repair techniques, including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most widely accepted clinical treatment options due to the lack of immunogenic reactions, but only moderate graft success rates have been reported. Although suspended allogenic chondrocytes are shown to evoke an immune response upon implantation, allogenic osteochondral plugs and tissue-engineered grafts using allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques produce neotissue with success rates approaching those of currently available autogenic repair techniques, while simultaneously obviating their major hindrance of donor tissue scarcity. To date, limited research has been performed with xenogenic tissue, although several studies demonstrate the potential for its long-term success. This article focuses on the various treatment options for cartilage repair and their associated success rates and immunologic responses. PMID:19063664

  19. Experimentally produced fractures of articular cartilage and bone. The effects of shear forces on the pig knee.

    PubMed

    Tomatsu, T; Imai, N; Takeuchi, N; Takahashi, K; Kimura, N

    1992-05-01

    Experimental injuries of cartilage and bone were produced by applying shear force to the articular surfaces of the lateral femoral condyles of six-month-old pigs under various loading conditions. The lesions were divided into two groups, 'open' or 'closed', depending on the presence of a crack on the articular surface. Each was further divided into four types according to the depth of penetrating injury: (1) splitting of uncalcified cartilage; (2) splitting at the subchondral plate; (3) subchondral fracture; and (4) intra-articular fracture. When shear force was applied at high speed but with low energy, the articular cartilage surface was the first to crack. At low speed and low energy, splits occurred in the deeper layers first. As the energy increased, both loading conditions eventually resulted in similar open lesions. Experimentally produced shear injuries are useful models for clinical osteochondral fracture, osteochondritis dissecans, and chondromalacia patellae. PMID:1587902

  20. Biomaterials for Tissue Engineering

    PubMed Central

    Lee, Esther J.; Kasper, F. Kurtis; Mikos, Antonios G.

    2013-01-01

    Biomaterials serve as an integral component of tissue engineering. They are designed to provide architectural framework reminiscent of native extracellular matrix in order to encourage cell growth and eventual tissue regeneration. Bone and cartilage represent two distinct tissues with varying compositional and mechanical properties. Despite these differences, both meet at the osteochondral interface. This article presents an overview of current biomaterials employed in bone and cartilage applications, discusses some design considerations, and alludes to future prospects within this field of research. PMID:23820768

  1. [A 15-year-old adolescent presenting both Madelung deformity with Vickers' ligament and additional palmaris profundus muscle].

    PubMed

    Spies, C K; Hahn, P; Leclère, F M; Unglaub, F

    2014-06-01

    The palmaris profundus muscle is a rare entity which has been mentioned in association with nerve compressions. Madelung deformity is based both on an osteochondral lesion of the distal radial physis and often on the Vickers' ligament which originates around the lunate and inserts proximally in the radial physis. A 15-year-old right-handed female adolescent suffered from symptomatic left-sided Madelung deformity with Vickers' ligament and additional palmaris profundus muscle. PMID:24573910

  2. Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

    SciTech Connect

    Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

    2011-08-01

    During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered)) . Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research Highlights: > 3-Day imatinib treatment. > Causes growth plate anomalies in young rats. > Causes biomechanical changes and significant bone loss at distal trabecular bone. > Results in loss of osteoclasts at osteochondral junction.

  3. Radial head and neck injuries in children with elbow dislocations: a report of three cases.

    PubMed

    bin Mohd Fadil, Muhammad Farhan; Mahadev, Arjandas; Gera, Sumanth Kumar

    2014-08-01

    In children, traumatic elbow dislocations usually occur after the epiphysis has closed and with associated radial head and neck fractures and osteochondral fragments. The fragments are also usually interposed in the joint restricting complete congruent joint motion. We report on 3 children with traumatic elbow fracture-dislocation with associated radial head and neck injuries treated with open reduction and stabilisation. All patients achieved good outcomes and returned to pre-injury level of activities. PMID:25163968

  4. Autoarthroplasty of knee cartilage defects by osteoperiosteal grafts.

    PubMed

    Korkala, O L; Kuokkanen, H O

    1995-01-01

    Five fresh osteochondral fractures of the knee, which could not be fixed because of extensive fragmentation, were treated by excision of the fragments and reconstruction of the joint surface defect by an autogenous osteoperiosteal graft. The procedure was also used for joint surface reconstruction in sclerotic osteochondritis of the femoral condyle (nine knees) and grave patellofemoral chondromalacia (three knees). Plaster cast immobilization for 3 weeks was used in the two early cases. In all other cases, we employed a passive motion apparatus for 2 days postoperatively, followed by active mobilization in a knee brace with extension-flexion 30 to 90 degrees (femoral condyle reconstruction) or 0 to 45 degrees (patellar reconstruction). Gradual free movements were started 3 weeks postoperatively. The results after 1.5 to 6.5 years were satisfactory in all but one case. One arthroscopic removal of the loose graft was performed, as were two arthroscopic graft margin shavings. Three other reoperations were unrelated to the osteoperiosteal reconstruction. It appears that periosteal reconstruction should be considered in local osteochondral lesions, where excision of the injured cartilage is mandatory. The results were best in fresh trauma cases and younger people. PMID:7577214

  5. Trends in biological joint resurfacing

    PubMed Central

    Myers, K. R.; Sgaglione, N. A.; Grande, D. A.

    2013-01-01

    The treatment of osteochondral lesions and osteoarthritis remains an ongoing clinical challenge in orthopaedics. This review examines the current research in the fields of cartilage regeneration, osteochondral defect treatment, and biological joint resurfacing, and reports on the results of clinical and pre-clinical studies. We also report on novel treatment strategies and discuss their potential promise or pitfalls. Current focus involves the use of a scaffold providing mechanical support with the addition of chondrocytes or mesenchymal stem cells (MSCs), or the use of cell homing to differentiate the organism’s own endogenous cell sources into cartilage. This method is usually performed with scaffolds that have been coated with a chemotactic agent or with structures that support the sustained release of growth factors or other chondroinductive agents. We also discuss unique methods and designs for cell homing and scaffold production, and improvements in biological joint resurfacing. There have been a number of exciting new studies and techniques developed that aim to repair or restore osteochondral lesions and to treat larger defects or the entire articular surface. The concept of a biological total joint replacement appears to have much potential. Cite this article: Bone Joint Res 2013;2:193–9. PMID:24043640

  6. Joint sparing treatments in early ankle osteoarthritis: current procedures and future perspectives.

    PubMed

    Castagnini, Francesco; Pellegrini, Camilla; Perazzo, Luca; Vannini, Francesca; Buda, Roberto

    2016-12-01

    Ankle osteoarthritis (AOA) is a severe pathology, mostly affecting a post-traumatic young population. Arthroscopic debridement, arthrodiastasis, osteotomy are the current joint sparing procedures, but, in the available studies, controversial results were achieved, with better outcomes in case of limited degeneration. Only osteotomy in case of malalignment is universally accepted as a joint sparing procedure in case of partial AOA. Recently, the biological mechanism of osteoarthritis has been intensively studied: it is a whole joint pathology, affecting cartilage, bone and synovial membrane. In particular, the first stage is characterized by a reversible catabolic activity with a state of chondropenia. Thus, biological procedures for early AOA were proposed in order to delay or to avoid end stage procedures. Mesenchymal stem cells (MSCs) may be a good solution to prevent or reverse degeneration, due to their immunomodulatory features (able to control the catabolic joint environment) and their regenerative osteochondral capabilities (able to treat the chondral defects). In fact, MSCs may regulate the cytokine cascade and the metalloproteinases release, restoring the osteochondral tissue as well. After interesting reports of mesenchymal stem cells seeded on scaffold and applied to cartilage defects in non-degenerated joints, bone marrow derived cells transplantation appears to be a promising technique in order to control the degenerative pathway and restore the osteochondral defects. PMID:26915003

  7. Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers.

    PubMed

    Levato, Riccardo; Visser, Jetze; Planell, Josep A; Engel, Elisabeth; Malda, Jos; Mateos-Timoneda, Miguel A

    2014-09-01

    Bioprinting allows the fabrication of living constructs with custom-made architectures by spatially controlled deposition of multiple bioinks. This is important for the generation of tissue, such as osteochondral tissue, which displays a zonal composition in the cartilage domain supported by the underlying subchondral bone. Challenges in fabricating functional grafts of clinically relevant size include the incorporation of cues to guide specific cell differentiation and the generation of sufficient cells, which is hard to obtain with conventional cell culture techniques. A novel strategy to address these demands is to combine bioprinting with microcarrier technology. This technology allows for the extensive expansion of cells, while they form multi-cellular aggregates, and their phenotype can be controlled. In this work, living constructs were fabricated via bioprinting of cell-laden microcarriers. Mesenchymal stromal cell (MSC)-laden polylactic acid microcarriers, obtained via static culture or spinner flask expansion, were encapsulated in gelatin methacrylamide-gellan gum bioinks, and the printability of the composite material was studied. This bioprinting approach allowed for the fabrication of constructs with high cell concentration and viability. Microcarrier encapsulation improved the compressive modulus of the hydrogel constructs, facilitated cell adhesion, and supported osteogenic differentiation and bone matrix deposition by MSCs. Bilayered osteochondral models were fabricated using microcarrier-laden bioink for the bone compartment. These findings underscore the potential of this new microcarrier-based biofabrication approach for bone and osteochondral constructs. PMID:25048797

  8. Clinical relevance of scaffolds for cartilage engineering.

    PubMed

    LaPorta, Thomas F; Richter, Alexander; Sgaglione, Nicholas A; Grande, Daniel A

    2012-04-01

    The repair of articular cartilage defects in patients' knees presents a particular challenge to the orthopedic surgeon because cartilage lacks the ability to repair or regenerate itself. Various cartilage repair techniques have not produced a superior or uniform outcome, which has led to a new generation of cartilage repair based on tissue-engineering strategies and the use of biological scaffolds. Clinical advances have been made regarding the regeneration of articular cartilage, and continue to be made toward the achievement of a suitable treatment method for resurfacing osteochondral defects, through cartilage tissue engineering and the use of pluripotent cells seeded on bio-scaffolds. PMID:22480473

  9. [MR of the knee joint. Imaging of the normal anatomy and pathological findings using surface coils].

    PubMed

    Steinbrich, W; Beyer, D; Friedmann, G; Ermers, J W; Buess, G; Schmidt, K H

    1985-08-01

    A special surface coil was developed with the intention of producing optimal resolution and signal-to-noise ratio for the examination of the knee joint by MRI. Eight volunteers and 25 patients with various abnormalities of the knee have been examined. Normal anatomical structures can be differentiated and there is high diagnostic reliability for lesions of the meniscus, as confirmed by arthroscopy and surgery. Cartilage lesions are less well demonstrated. Total rupture of cruciate ligaments is clearly shown, but partial rupture can often be recognised on the basis of indirect signs only. Good diagnostic results were obtained in cases of osteochondritis dissecans and chondropathia of the patella. PMID:2992030

  10. Extra-articular Synovial Chondromatosis Eroding and Penetrating the Acromion

    PubMed Central

    El Rassi, George; Matta, Jihad; Hijjawi, Ayman; Khair, Ousama Abou; Fahs, Sara

    2015-01-01

    Synovial chondromatosis of the shoulder is an uncommon disorder. It usually affects the glenohumeral joint and is characterized by metaplasia of the synovium leading to the formation of osteochondral loose bodies. Few cases of extra-articular subacromial synovial chondromatosis involving the rotator cuff tendon have been reported in the literature. The treatment of previously reported cases consisted of open bursectomy and removal of loose bodies. We report a case of subacromial synovial chondromatosis without rotator cuff involvement but with severe erosion and fracture of the acromion. Treatment consisted of shoulder arthroscopy to remove all loose bodies, total bursectomy, and debridement of the acromion. Potential benefits of arthroscopy were also evaluated. PMID:26697302

  11. Musculoskeletal Pathology.

    PubMed

    Peat, Frances J; Kawcak, Christopher E

    2015-08-01

    The current understanding of pathology as it relates to common diseases of the equine musculoskeletal system is reviewed. Conditions are organized under the fundamental categories of developmental, exercise-induced, infectious, and miscellaneous pathology. The overview of developmental pathology incorporates the new classification system of juvenile osteochondral conditions. Discussion of exercise-induced pathology emphasizes increased understanding of the contribution of cumulative microdamage caused by repetitive cyclic loading. Miscellaneous musculoskeletal pathology focuses on laminitis, which current knowledge indicates should be regarded as a clinical syndrome with a variety of possible distinct mechanisms of structural failure that are outlined in this overview. PMID:26037607

  12. Synergistic Action of IL-8 and Bone Marrow Concentrate on Cartilage Regeneration Through Upregulation of Chondrogenic Transcription Factors.

    PubMed

    Yoon, Dong Suk; Lee, Kyoung-Mi; Kim, Sung-Hwan; Kim, Su Hee; Jung, Youngmee; Kim, Soo Hyun; Park, Kwang Hwan; Choi, Yoorim; Ryu, Hyun Aae; Choi, Woo Jin; Lee, Jin Woo

    2016-02-01

    The objective of this study was to determine whether a biphasic scaffold loaded with a combination of a chemokine and bone marrow concentrate (BMC) could improve tissue regeneration in knee articular cartilage of beagles with cylindrical osteochondral defects. For this investigation, an osteochondral defect (6 mm in diameter and 8 mm deep) was created in the weight-bearing articular surface of the femoral medial condyle in beagles. Bone marrow was aspirated from the posterior iliac crests of beagles to obtain mesenchymal stem cells (MSCs) for in vitro assay. Hematoxylin and eosin (HE), Masson's trichrome (MT), safranin O/fast green staining, and immunohistochemistry were performed for histological analysis. Quantitative real-time polymerase chain reaction was performed to understand the roles of BMC in chondrogenic differentiation of MSCs. At 12 weeks after transplantation of biphasic scaffolds, we observed that interleukin-8 (IL-8) or the combination of IL-8 and BMC induced massive bone regeneration compared to saline, BMC only, and MSCs. In gross appearance, the osteochondral defect site was nearly completely filled with repair tissue in the group that received the combination of IL-8 and BMC but not in the other groups. Moreover, histological analysis showed obvious differences in cartilage regeneration among groups. HE and MT staining showed that the cartilage defect sites of the group receiving the combination of IL-8 and BMC were regenerated with cartilage-like tissues showing chondrocyte morphology. Safranin O staining showed hyaline cartilage regeneration in the group receiving IL-8 and BMC, whereas fibrous-like tissues were formed in the other groups. Furthermore, immunostaining revealed the presence of type II collagen and aggrecan in regenerated cartilage tissue of the group receiving IL-8 and BMC, whereas regenerated cartilage tissues of the other groups weakly expressed type II collagen and aggrecan. These results indicate that the combination of a chemokine IL-8 and BMC has significant positive effects on osteochondral regeneration in a beagle model through enhancing expression of the chondrogenic transcription factors and markers such as Sox9 and type II collagen. PMID:26871861

  13. High intensity focused ultrasound as a tool for tissue engineering: Application to cartilage.

    PubMed

    Nover, Adam B; Hou, Gary Y; Han, Yang; Wang, Shutao; O'Connell, Grace D; Ateshian, Gerard A; Konofagou, Elisa E; Hung, Clark T

    2016-02-01

    This article promotes the use of High Intensity Focused Ultrasound (HIFU) as a tool for affecting the local properties of tissue engineered constructs in vitro. HIFU is a low cost, non-invasive technique used for eliciting focal thermal elevations at variable depths within tissues. HIFU can be used to denature proteins within constructs, leading to decreased permeability and potentially increased local stiffness. Adverse cell viability effects remain restricted to the affected area. The methods described in this article are explored through the scope of articular cartilage tissue engineering and the fabrication of osteochondral constructs, but may be applied to the engineering of a variety of different tissues. PMID:26724968

  14. IMAGING DIAGNOSIS-RADIOGRAPHIC, ULTRASONOGRAPHIC, COMPUTED TOMOGRAPHIC, AND FLUOROSCOPIC APPEARANCE OF A DISTAL PELVIC LIMB ARTERIOVENOUS MALFORMATION IN A YOUNG GERMAN SHEPHERD DOG.

    PubMed

    Shaikh, Layla S; Holmes, Shannon P; Selberg, Kurt T; Jarrett, Carla; Holladay, Steven D; Thomason, Justin; Coleman, Amanda E

    2016-03-01

    A German shepherd puppy presented for evaluation of a suspected arteriovenous fistula on the distal aspect of the right pelvic limb. Radiographs demonstrated expansion and resorption of the tarsal and metatarsal bones, and ultrasound detected a vascular abnormality. Using computed tomographic angiography, a complex arteriovenous malformation (AVM) involving the distal tibia, tarsus, and the metatarsus and an osteochondritis dissecans (OCD) lesion of the talus were identified. Based on these findings, therapeutic limb amputation was performed. Fluoroscopic angiography, vascular casting, and dissection were then used to further characterize features of this previously unreported AVM with concurrent bony lesions and OCD. PMID:26346616

  15. Cartilage Repair With or Without Meniscal Transplantation and Osteotomy for Lateral Compartment Chondral Defects of the Knee

    PubMed Central

    Harris, Joshua D.; Hussey, Kristen; Saltzman, Bryan M.; McCormick, Frank M.; Wilson, Hillary; Abrams, Geoffrey D.; Cole, Brian J.

    2014-01-01

    Background: Treatment decision making for chondral defects in the knee is multifactorial. Articular cartilage pathology, malalignment, and meniscal deficiency must all be addressed to optimize surgical outcomes. Purpose: To determine whether significant clinical improvements in validated clinical outcome scores are observed at minimum 2-year follow-up after articular cartilage repair of focal articular cartilage defects of the lateral compartment of the knee with or without concurrent distal femoral osteotomy and lateral meniscus transplant. Study Design: Case series; Level of evidence, 4. Methods: Symptomatic adults who underwent surgical treatment (microfracture, autologous chondrocyte implantation [ACI], osteochondral autograft or allograft) of full-thickness lateral compartment chondral defects of the knee with or without a postmeniscectomy compartment or valgus malalignment by a single surgeon with minimum 2-year follow-up were analyzed. Validated patient-reported and surgeon-measured outcomes were collected pre- and postsurgery. Pre- and postoperative outcomes were compared via Student t tests. Results: Thirty-five subjects (mean age, 29.6 ± 10.5 years) were analyzed. Patients had been symptomatic for 2.51 ± 3.52 years prior to surgery and had undergone 2.11 ± 1.18 surgeries prior to study enrollment, with a mean duration of follow-up of 3.65 ± 1.71 years. The mean defect size was 4.42 ± 2.06 cm2. Surgeries included ACI (n = 18), osteochondral allograft (n = 14), osteochondral autograft (n = 2), and microfracture (n = 1). There were 18 subjects who underwent concomitant surgery (14 lateral meniscus transplant, 3 distal femoral osteotomy, and 1 combined). Statistically significant (P < .05) and clinically meaningful improvements were observed at final follow-up in Lysholm, subjective International Knee Documentation Committee (IKDS), Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, Short Form–12 (SF-12) scores, and patient satisfaction. At follow-up, patients undergoing isolated articular cartilage surgery had a significantly higher KOOS quality of life subscore than did those undergoing articular cartilage surgery and lateral meniscus transplant (P = .039). Otherwise, there were no significant postoperative differences between the isolated and combined surgery groups in any outcome score. Five patients underwent 6 reoperations (1 revision osteochondral allograft, 5 chondroplasties). No patient was converted to knee arthroplasty. Conclusion: In patients with lateral compartment focal chondral defects with or without lateral meniscal deficiency and valgus malalignment, surgical cartilage repair and correction of concomitant pathology can significantly improve clinical outcomes at 2-year follow-up with no significant differences between isolated and combined surgery and a low rate of complications and reoperations. PMID:26535271

  16. Acute traumatic patellar dislocation.

    PubMed

    Duthon, V B

    2015-02-01

    Inaugural traumatic patellar dislocation is most often due to trauma sustained during physical or sports activity. Two-thirds of acute patellar dislocations occur in young active patients (less than 20 years old). Non-contact knee sprain in flexion and valgus is the leading mechanism in patellar dislocation, accounting for as many as 93% of all cases. The strong displacement of the patella tears the medial stabilizing structures, and notably the medial patellofemoral ligament (MPFL), which is almost always injured in acute patellar dislocation, most frequently at its femoral attachment. Lateral patellar glide can be assessed with the knee in extension or 20° flexion. Displacement by more than 50% of the patellar width is considered abnormal and may induce apprehension. Plain X-ray and CT are mandatory to diagnose bony risk factors for patellar dislocation, such as trochlear dysplasia or increased tibial tubercle-trochlear groove distance (TT-TG), and plan correction. MRI gives information on cartilage and capsulo-ligamentous status for treatment planning: free bodies or osteochondral fracture have to be treated surgically. If patellar dislocation occurs in an anatomically normal knee and osteochondral fracture is ruled out on MRI, non-operative treatment is usually recommended. PMID:25592052

  17. Attachment, Proliferation, and Chondroinduction of Mesenchymal Stem Cells on Porous Chitosan-Calcium Phosphate Scaffolds

    PubMed Central

    Elder, Steven; Gottipati, Anuhya; Zelenka, Hilary; Bumgardner, Joel

    2013-01-01

    Symptomatic osteochondral lesions occur frequently, but relatively few treatment options are currently available. The purpose of this study was to conduct a preliminary investigation into a new tissue engineering approach to osteochondral regeneration. The concept is a biphasic construct consisting of a porous, osteoconductive chitosan-calcium phosphate scaffold supporting a layer of neocartilage formed by marrow-derived mesenchymal stem cells. Two experiments were conducted to assess the feasibility of this approach. The first experiment characterized the attachment efficiency and proliferation of primary human marrow-derived mesenchymal stem cells seeded relatively sparely onto the scaffolds surface. The second experiment compared two different methods of creating a biphasic construct using a much higher density of primary porcine marrow stromal cells. About 40% of the sparsely seeded human cells attached and proliferated rapidly. Constructs formed by one of the two experimental techniques exhibited a layer of cartilaginous tissue which only partially covered the scaffolds surface due to inadequate adhesion between the cells and the scaffold. This study demonstrates some potential for the approach to yield an implantable biphasic construct, but further development is required to improve cell-scaffold adhesion. PMID:23986794

  18. Enhanced chondrocyte culture and growth on biologically inspired nanofibrous cell culture dishes

    PubMed Central

    Bhardwaj, Garima; Webster, Thomas J

    2016-01-01

    Chondral and osteochondral defects affect a large number of people in which treatment options are currently limited. Due to its ability to mimic the natural nanofibrous structure of cartilage, this current in vitro study aimed at introducing a new scaffold, called XanoMatrix™, for cartilage regeneration. In addition, this same scaffold is introduced here as a new substrate onto which to study chondrocyte functions. Current studies on chondrocyte functions are limited due to nonbiologically inspired cell culture substrates. With its polyethylene terephthalate and cellulose acetate composition, good mechanical properties and nanofibrous structure resembling an extracellular matrix, XanoMatrix offers an ideal surface for chondrocyte growth and proliferation. This current study demonstrated that the XanoMatrix scaffolds promote chondrocyte growth and proliferation as compared with the Corning and Falcon surfaces normally used for chondrocyte cell culture. The XanoMatrix scaffolds also have greater hydrophobicity, three-dimensional surface area, and greater tensile strength, making them ideal candidates for alternative treatment options for chondral and osteochondral defects as well as cell culture substrates to study chondrocyte functions. PMID:26917958

  19. A comparative radiological assessment of polylactide pins over 3 years in vivo.

    PubMed

    Prokop, Axel; Jubel, Axel; Hahn, Ulrich; Dietershagen, Martin; Bleidistel, Mirko; Peters, Christiane; Höfl, Andreas; Rehm, Klaus E

    2005-07-01

    Biodegradable polylactide implants allow secure fixation of osteochondral fractures with minimal adverse effects. The goal of this prospective, randomized animal study was to show whether osteoconductive effects can be achieved through the development of poly-L/DL(70/30)lactide composite implants with 10% beta-tricalcium phosphate, and whether degradation can be positively influenced and adverse effects minimized using such implants. An additional goal was to clarify which radiological procedure is most suitable to observe the course of follow-up. Thirtysix medial femoral condyle osteotomies of sheep were fixed with either 3 poly-L/DL-lactide pins or 3 composite pins, and the pin canal widths were measured with conventional radiographs, with CT, MRI, and histologically after 3, 18, and 36 months. All fractures healed completely without displacement or clinically relevant complications. The pin canals dilated secondary to pin degradation at the 12th month, and then decreased in size later. At 36 months, the pins had microscopically disappeared, and the canals were filled with bone or scar tissue. There were no statistically significant differences between the pin-types. Poly-L/DL-lactide pins and composite C-pins are suitable for secure fixation of small osteochondral fractures. Osteoconductive effects of biocompatibility or osseous integration relating to composite development were not evident. Conventional radiography and computer tomography were suitable techniques for observation of pin canals. Due to frequently observed artifact, MRI was not suitable to observe the course of the implants. PMID:15664640

  20. Biological, biochemical and biomechanical characterisation of articular cartilage from the porcine, bovine and ovine hip and knee.

    PubMed

    Fermor, H L; McLure, S W D; Taylor, S D; Russell, S L; Williams, S; Fisher, J; Ingham, E

    2015-01-01

    This study aimed to determine the optimal starting material for the development of an acellular osteochondral graft. Osteochondral tissues from three different species were characterised; pig (6 months), cow (18 months) and two ages of sheep (8-12 months and >4 year old). Tissues from the acetabulum and femoral head of the hip, and the groove, medial and lateral condyles and tibial plateau of the knee were assessed. Histological analysis of each tissue allowed for qualification of cartilage histoarchitecture, glycosaminoglycan (GAG) distribution, assessment of cellularity and cartilage thickness. Collagen and GAG content were quantified and cartilage water content was defined. Following biomechanical testing, the percentage deformation, permeability and equilibrium elastic modulus was determined. Results showed that porcine cartilage had the highest concentration of sulphated proteoglycans and that the condyles and groove of the knee showed higher GAG content than other joint areas. Cartilage from younger tissues (porcine and young ovine) had higher cell content and was thicker, reflecting the effects of age on cartilage structure. Cartilage from older sheep had a much higher elastic modulus and was less permeable than other species. PMID:26407200

  1. Regeneration of articular cartilage using adipose stem cells.

    PubMed

    Im, Gun-Il

    2016-07-01

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

  2. Racing performance of Swedish Standardbred trotting horses with proximal palmar/plantar first phalangeal (Birkeland) fragments compared to fragment free controls.

    PubMed

    Carmalt, James L; Borg, Hanna; Näslund, Hans; Waldner, Cheryl

    2014-10-01

    The aim of this study was to determine whether horses with a proximal palmar/plantar first phalangeal osteochondral fragment (POF) had comparable racing careers (prior to and following surgery) to horses without this fracture. A retrospective cohort study included 174 Swedish Standardbred trotters with osteochondral fragmentation in the palmar/plantar fetlock joint and 613 radiographically negative control horses presented for prepurchase examinations. Medical records and radiographs were examined for each horse. Racing data were retrieved from online Swedish Standardbred harness racing records. The effect of having a POF on race speed compared to radiographically negative control horses was examined using generalised estimating equations. Multivariable regression was used to examine differences in money earned and career longevity. The horses raced a total of 16,448 races. Horses gained speed as a function of race number. There was no difference in racing speed between horses with POF fractures that raced before surgery and control horses. Horses did not slow before, nor speed up after, surgery. There was no difference in the number of days between the last race prior to, or the first race after, the hospital visit between POF and control horses. Career earnings and lifetime starts were not significantly different between groups. The results of this study suggest the need to reevaluate the previously reported benefits of surgical intervention for POF. PMID:25163613

  3. Midterm Results of a Combined Biological and Mechanical Approach for the Treatment of a Complex Knee Lesion

    PubMed Central

    Filardo, G.; Di Martino, A.; Delcogliano, M.; Marcacci, M.

    2012-01-01

    Objective: Complex fractures of the tibial plateau are difficult to treat and present a high complication rate. The goal of this report is to describe a combined biological and mechanical approach to restore all morphological and functional knee properties. Methods: We treated a 50-year-old woman, who was affected by a posttraumatic osteochondral lesion and depression of the lateral tibial plateau with knee valgus deviation. The mechanical axis was corrected with a lateral tibial plateau elevation osteotomy, the damaged joint surface was replaced by a recently developed biomimetic osteochondral scaffold, and a hinged dynamic external fixator was applied to protect the graft and at the same time to allow postoperative joint mobilization. Results: A marked clinical improvement was documented at 12 months and further improved up to 5 years, with pain-free full range of motion and return to previous activities. The MRI evaluation at 12 and 24 months showed that the implant remained in site with a hyaline-like signal and restoration of the articular surface. Conclusion: This case report describes a combined surgical approach for complex knee lesions that could represent a treatment option to avoid or at least delay posttraumatic osteoarthritis and more invasive procedures. PMID:26069639

  4. Guided differentiation of bone marrow stromal cells on co-cultured cartilage and bone scaffolds.

    PubMed

    Lee, Paul; Tran, Katelyn; Zhou, Gan; Bedi, Asheesh; Shelke, Namdev B; Yu, Xiaojun; Kumbar, Sangamesh G

    2015-10-14

    Focal chondral defects that result from traumatic injuries to the knee remain one of the most common causes of disability in patients. Current solutions for healing focal cartilage defects are mainly limited by the production of inferior cartilage-like tissue and subsequent delamination due to incomplete healing of the subchondral bone. In this experiment a polymeric osteochondral implant for guiding autologous bone marrow stem cells (BMSCs) to populate the scaffold to create distinctive bone and cartilage tissue is used. The cartilage component presents bioactive aligned nanofibers containing chondroitin sulfate and hyaluronic acid while the bone component includes hydroxyapatite to promote chondrogenic and osteogenic differentiation of the rat BMSCs in vitro. The different cartilage and bone components resulted in the elevated expression of osteogenic markers such as bone sialoprotein, runt related transcription factor 2, and bone morphogenetic protein 2 in the deeper bone layer and chondrogenic markers such as collagen type II and aggrecan in the cartilage layer. Through immunofluorescence imaging, the alignment of the secreted collagen type II fibrils and aggrecan was visualized and quantified on the cartilage component of the scaffold. These current studies show that the biodegradable biphasic osteochondral implant may be effective in promoting more hyaline-like tissue to fill in chondral defects of the knee. PMID:26292727

  5. Long-term storage and preservation of tissue engineered articular cartilage.

    PubMed

    Nover, Adam B; Stefani, Robert M; Lee, Stephanie L; Ateshian, Gerard A; Stoker, Aaron M; Cook, James L; Hung, Clark T

    2016-01-01

    With limited availability of osteochondral allografts, tissue engineered cartilage grafts may provide an alternative treatment for large cartilage defects. An effective storage protocol will be critical for translating this technology to clinical use. The purpose of this study was to evaluate the efficacy of the Missouri Osteochondral Allograft Preservation System (MOPS) for room temperature storage of mature tissue engineered grafts, focusing on tissue property maintenance during the current allograft storage window (28 days). Additional research compares MOPS to continued culture, investigates temperature influence, and examines longer-term storage. Articular cartilage constructs were cultured to maturity using adult canine chondrocytes, then preserved with MOPS at room temperature, in refrigeration, or kept in culture for an additional 56 days. MOPS storage maintained desired chondrocyte viability for 28 days of room temperature storage, retaining 75% of the maturity point Young's modulus without significant decline in biochemical content. Properties dropped past this time point. Refrigeration maintained properties similar to room temperature at 28 days, but proved better at 56 days. For engineered grafts, MOPS maintained the majority of tissue properties for the 28-day window without clearly extending that period as it had for native grafts. These results are the first evaluating engineered cartilage storage. PMID:26296185

  6. UPDATING ON DIAGNOSIS AND TREATMENT OF CHONDRAL LESION OF THE KNEE

    PubMed Central

    da Cunha Cavalcanti, Filho Marcantonio Machado; Doca, Daniel; Cohen, Moisés; Ferretti, Mário

    2015-01-01

    ABSTRACTS The treatment of chondral knee injuries remains a challenge for the orthopedic surgeon, mainly owing to the characteristics of the cartilage tissue, which promote low potential for regeneration. Chondral lesions can be caused by metabolic stimulation, or by genetic, vascular and traumatic events, and are classified according to the size and thickness of the affected cartilage. Clinical diagnosis can be difficult, especially due to insidious symptoms. Additional tests, as Magnetic Resonance Imaging (MRI), may be needed. The treatment of these lesions usually starts with non-operative management. Surgery should be reserved for patients with detached chondral fragments, blocked range of motion, or the failure of non-operative treatment. The surgical techniques used for the treatment of partial thickness defects are Debridement and Ablation. These techniques aim to improve symptoms, since they do not restore normal structure and function of the cartilage. For full-thickness defects (osteochondral lesion), available treatments are Abrasion, Drilling, Microfracture, Osteochondral Autologous and Allogeneic Transplantation, and biological techniques such as the use of Autologous Chondrocyte Transplantation, Minced Cartilage and stem cells. PMID:27027078

  7. The use of continuous passive motion following knee cartilage defect surgery: a systematic review.

    PubMed

    Fazalare, Joseph A; Griesser, Michael J; Siston, Robert A; Flanigan, David C

    2010-12-01

    We evaluated the clinical evidence of using continuous passive motion postoperatively after treating articular cartilage lesions of the knee. We hypothesized that postoperatively, the use of continuous passive motion improves the outcomes of cartilage restoration procedures. Multiple medical databases (MEDLINE, EMBASE, CINAHL, PubMed, Sport-Discus, and Cochrane) were searched for Level I through IV evidence with specific study inclusion and exclusion criteria. The following key words were searched: microfracture, mosaicplasty, OATS, ACI, osteochondral autograft, osteochondral allograft, autologous chondrocyte implantation, autologous chondrocyte transplantation, CPM, continuous passive motion, motion therapy, postoperative knee rehabilitation, cartilage, knee. All studies were independently reviewed by the authors and the references were checked for any missed articles. Four Level III studies were identified that met inclusion criteria for our hypothesis. No randomized, controlled studies were identified. A meta-analysis could not be performed as a result of the heterogeneity of the procedures and outcome measures. Definitive conclusions regarding the benefits of continuous passive motion postoperatively in knee cartilage surgery could not be made secondary to this heterogeneity. Continuous passive motion is commonly used postoperatively following cartilage surgery. Unfortunately, the clinical evidence (only 4 studies) to support the use of continuous passive motion is lacking despite an overwhelming abundance of basic science support and the common clinical practice of continuous passive motion implementation postoperatively in knee cartilage restoration procedures. There is a great need for well-conducted, high-level evidence studies to address this void in our literature. PMID:21162503

  8. Isolation, culture, and osteogenic/chondrogenic differentiation of bone marrow-derived mesenchymal stem cells.

    PubMed

    Grssel, Susanne; Stckl, Sabine; Jenei-Lanzl, Zsuzsa

    2012-01-01

    Musculoskeletal disorders, as non-healing fractures and large bone defects, articular cartilage and subchondral bone injuries, often result in lifelong chronic pain and compromised quality of life. Although generally a natural process, failure of large bone defects to heal such as after complex fractures, resection of tumours, infections, or revisions of joint replacements remains a critical challenge that requires more appropriate solutions as those currently available. In addition, regeneration of chondral and osteochondral defects continues to be a challenge until to date. A profound understanding of the underlying mechanisms of endogenous regeneration is a prerequisite for successful bone and cartilage regeneration. Presently, one of the most promising therapeutic approaches is cell-based tissue engineering which provides a healthy population of cells to the injured site. Use of differentiated cells has severe limitations; an excellent alternative would be the application of adult marrow stromal cells/mesenchymal stem cells (MSC) which possess extensive proliferation potential and proven capability to differentiate along the osteochondral pathway. The process of osteo-/chondrogenesis can be mimicked in vitro by inducing osteo-chondroprogenitor stem cells to undergo osteogenesis and chondrogenesis through exposure of osteo-/chondrogenic favourable microenvironmental, mechanical, and nutritional conditions. This chapter provides comprehensive protocols for the isolation, expansion, and osteo-/chondrogenic differentiation of adult bone marrow-derived MSC. PMID:22610563

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    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 expressed lubricin in the superficial cartilage. Conclusion Cartilage derived from MSCs expressed lubricin protein both in vitro and in vivo. Aggregation promoted lubricin expression of MSCs in vitro and transplantation of aggregates of MSCs regenerated cartilage including the superficial zone in a rat osteochondral defect model. Our results indicate that aggregated MSCs could be clinically relevant for therapeutic approaches to articular cartilage regeneration with an appropriate superficial zone in the future. PMID:26867127

  11. Ultrasound Backscattering Is Anisotropic in Bovine Articular Cartilage.

    PubMed

    Inkinen, Satu I; Liukkonen, Jukka; Tiitu, Virpi; Virén, Tuomas; Jurvelin, Jukka S; Töyräs, Juha

    2015-07-01

    Collagen, proteoglycans and chondrocytes can contribute to ultrasound scattering in articular cartilage. However, anisotropy of ultrasound scattering in cartilage is not fully characterized. We investigate this using a clinical intravascular ultrasound device with ultrasound frequencies of 9 and 40 MHz. Osteochondral samples were obtained from intact bovine patellas, and cartilage was imaged in two perpendicular directions: through articular and lateral surfaces. At both frequencies, ultrasound backscattering was higher (p < 0.05) when measured through the lateral surface of cartilage. In addition, the composition and structure of articular cartilage were investigated with multiple reference methods involving light microscopy, digital densitometry, polarized light microscopy and Fourier infrared imaging. Reference methods indicated that acoustic anisotropy of ultrasound scattering arises mainly from non-uniform distribution of chondrocytes and anisotropic orientation of collagen fibers. To conclude, ultrasound backscattering in articular cartilage was found to be anisotropic and dependent on the frequency in use. PMID:25933711

  12. Chordoma of the thoracic vertebrae in a Bengal tiger (Panthera tigris tigris).

    PubMed

    Kuramochi, Mizuki; Izawa, Takeshi; Hori, Mayuka; Kusuda, Kayo; Shimizu, Junichiro; Iseri, Toshie; Akiyoshi, Hideo; Ohashi, Fumihito; Kuwamura, Mitsuru; Yamate, Jyoji

    2015-07-01

    A 19-year-old female Bengal tiger (Panthera tigris tigris) was presented with hind limb weakness, ataxia and respiratory distress. Computed tomography revealed a mass between the left side of the T7 vertebra and the base of the left 7th rib. The tiger then died, and necropsy was performed. Grossly, the vertebral mass was 6 5.7 3 cm, and invaded the adjacent vertebral bone and compressed the T7 spinal cord. Histologically, the mass was composed of large, clear, vacuolated and polygonal cells with osteochondral matrix. Cellular and nuclear atypia were moderate. The vacuolated cells stained positively for cytokeratin and vimentin and negatively for S-100. Based on these findings, the present case was diagnosed as a vertebral chordoma; the first report in a tiger. PMID:25766770

  13. Canine elbow dysplasia and primary lesions in German shepherd dogs in France.

    PubMed

    Remy, D; Neuhart, L; Fau, D; Genevois, J P

    2004-05-01

    Five hundred and twenty German shepherd dogs were screened for elbow dysplasia. The following primary lesions were analysed: joint incongruity (JI), fragmented medial coronoid process (FCP), osteochondrosis or osteochondritis of the medial humeral condyle and ununited anconeal process (UAP). Three radiographic views were used for each joint to achieve a definitive diagnosis. The prevalence of elbow dysplasia was 19.4 per cent. The most frequent lesion was JI (16.3 per cent), followed by FCP (11.3 per cent). UAP was diagnosed rarely (1.1 per cent). Combinations of lesions were very frequent (42.2 per cent of the dysplastic elbows). Although these results may be biased due to prescreening of dogs with UAP, it should be highlighted that JI and FCP occur frequently in German shepherd dogs and are probably the most common primary lesions of elbow dysplasia, although they have been under-reported until now. PMID:15163051

  14. EVALUATION OF DMSO TRANSPORT IN HUMAN ARTICULAR CARTILAGE: VEHICLE SOLUTIONS AND EFFECTS ON CELL FUNCTION.

    PubMed

    Kay, A G; Rooney, P; Kearney, J; Pegg, D E

    2015-01-01

    Osteochondral allografting techniques are limited by the availability of suitable donor tissue; there is an urgent need for effective cryopreservation. A fundamental requirement is the need to establish initial conditions of exposure to cryoprotectant that the chondrocytes will tolerate and that load the tissue with an adequate concentration of cryoprotectant. Three vehicle solutions to transport DMSO into the tissue were studied. Knee joints were obtained from deceased donors with appropriate consent. Whole condyles were treated with 20% w/w DMSO in each of three vehicle solutions and chondrocyte function and tissue CPA content measured. The results showed that exposure to 20% DMSO in each vehicle solution for 2 hours at 0 degrees C was tolerated without loss of GAG synthetic activity. It was observed that penetration of DMSO increased little after 1 hour of CPA exposure at 0 degrees C but the final tissue concentration of CPA was markedly lower than that in the medium. PMID:26510337

  15. ADVANCES IN THE USE OF STEM CELLS IN ORTHOPEDICS

    PubMed Central

    Cristante, Alexandre Fogaça; Narazaki, Douglas Kenji

    2015-01-01

    Primordial cells or stem cells are multipotent undifferentiated cells with the capacity to originate any type of cell in the organism. They may have their origins in the blastocyst and thus are classified as embryonic, or tissues developed in fetuses, newborns or adults and thus are known as somatic stem cells. Bone marrow is one of the main locations for isolating primordial cells, and there are two lineages: hematopoietic and mesenchymal progenitor cells. There are several uses for these undifferentiated cells in orthopedics, going from cartilaginous lesions in osteoarthrosis, osteochondritis dissecans and patellar chondromalacia, to bone lesions like in pseudarthrosis or bone losses, or nerve lesions like in spinal cord trauma. Studying stem cells is probably the most promising field of study of all within medicine, and this is shortly going to revolutionize all medical specialties (both clinical and surgical) and thus provide solutions for diseases that today are difficult to deal with. PMID:27027022

  16. Biomaterial and mesenchymal stem cell for articular cartilage reconstruction.

    PubMed

    Shen, Yun; Fu, Yao; Wang, Jing; Li, Guo; Zhang, Xu; Xu, Yuanzhi; Lin, Yunfeng

    2014-05-01

    Cartilage has poor ability of spontaneous repair. Traditional treatments such as microfracture, bone drilling and autologous osteochondral graft were not fully satisfactory to fulfill the clinical needs. The idea of mesenchymal stem cell (MSCs-based cartilage regeneration has been put forward for decades. Large number of studies have been conducted on the biological properties of MSCs, the factors which might facilitate chondrogenic differentiation of MSCs, as well as the scaffold materials for tissue engineering. Promising results have been reported for cartilage repair in animal models. But before massive clinical application of MSCs, more efforts are needed on: differentiation improvement toward mature cartilage chondrocytes instead of hypertrophic chondrocyes and in vitro/in vivo phenotype maintenance; engineering an ideal biomaterial, which can meet the needs of the cartilage regeneration; and performing more studies on critical defects of large animals. PMID:24524788

  17. Detection of avascular necrosis in adults by single photon emission computed tomography

    SciTech Connect

    Collier, B.D.; Johnston, R.P.; Carrera, G.; Isitman, A.T.; Hellman, R.S.; Zielonka, J.S.

    1984-01-01

    Twenty-one adult patients with the clinical diagnosis of avascular necrosis (AVN) of the femoral head were examined with planar bone scintigraphy (high resolution collimator) and single photon emission computed tomography (SPECT). The duration of hip pain ranged from 1 day to 18 months. Risk factors (including steroids, renal transplantation, alcoholism, and trauma) were present in 17 cases. A final diagnosis of AVN (20 hips), osteochondral facture, or stress fracture, was established for 17 patients. The 4 remaining patients, who were radiographically normal and did not complain of pain 3 months later, were thought to have no significant bone pathology. SPECT and planar bone scintigraphy were reported as positive for AVN only if a photopenic bony defect could be identified. In particular, uniformly increased activity throughout the femoral head was not considered to be diagnostic of AVN. The authors conclude that by identifying a photopenic defect which is not evident on planar bone scintigraphy, SPECT can contribute to accurate diagnosis of AVN.

  18. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

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

  19. Evaluation and Management of Patellar Instability in Pediatric and Adolescent Athletes

    PubMed Central

    Khormaee, Sariah; Kramer, Dennis E.; Yen, Yi-Meng; Heyworth, Benton E.

    2015-01-01

    Context: The rising popularity and intensity of youth sports has increased the incidence of patellar dislocation. These sports-related injuries may be associated with significant morbidity in the pediatric population. Treatment requires understanding and attention to the unique challenges in the skeletally immature patient. Evidence Acquisition: PubMed searches spanning 1970-2013. Study Design: Clinical review. Level of Evidence: Level 5. Results: Although nonoperative approaches are most often suitable for first-time patellar dislocations, surgical treatment is recommended for acute fixation of displaced osteochondral fractures sustained during primary instability and for patellar realignment in the setting of recurrent instability. While a variety of procedures can prevent recurrence, the risk of complications is not minimal. Conclusion: Patellar stabilization and realignment procedures in skeletally immature patients with recurrent patellar dislocation can effectively treat patellar instability without untoward effects on growth if careful surgical planning incorporates protection of growth parameters in the skeletally immature athlete. PMID:25984256

  20. Chordoma of the thoracic vertebrae in a Bengal tiger (Panthera tigris tigris)

    PubMed Central

    KURAMOCHI, Mizuki; IZAWA, Takeshi; HORI, Mayuka; KUSUDA, Kayo; SHIMIZU, Junichiro; ISERI, Toshie; AKIYOSHI, Hideo; OHASHI, Fumihito; KUWAMURA, Mitsuru; YAMATE, Jyoji

    2015-01-01

    A 19-year-old female Bengal tiger (Panthera tigris tigris) was presented with hind limb weakness, ataxia and respiratory distress. Computed tomography revealed a mass between the left side of the T7 vertebra and the base of the left 7th rib. The tiger then died, and necropsy was performed. Grossly, the vertebral mass was 6 × 5.7 × 3 cm, and invaded the adjacent vertebral bone and compressed the T7 spinal cord. Histologically, the mass was composed of large, clear, vacuolated and polygonal cells with osteochondral matrix. Cellular and nuclear atypia were moderate. The vacuolated cells stained positively for cytokeratin and vimentin and negatively for S-100. Based on these findings, the present case was diagnosed as a vertebral chordoma; the first report in a tiger. PMID:25766770

  1. [Elbow problems associated with sports injuries in children].

    PubMed

    Demirhan, Mehmet; Güneşli, Taner

    2004-01-01

    Elbow problems associated with sports injuries may result from overuse, micro- or macrotraumas. Overuse injuries are frequent and are often closely related to mechanical characteristics of sports. Sports-related elbow injuries mainly occur in sports involving throwing such as baseball and javelin throwing, which require forced valgus and extension of the elbow, predisposing it to overuse injuries. Overuse injuries in child athletes are generally defined as Little League elbow, the most common of which are medial epicondyle apophysitis, osteochondritis dissecans of the capitellum, radial head deformation, flexion contractures, and injuries to the olecranon. Most of these injuries can be healed without or with minimal sequelae by early diagnosis and proper treatment. Therefore, mechanisms of, and risk factors for, elbow problems encountered in pediatric athletes should be well-understood in order to avoid the risks for a permanent deformity in the child's anatomy. PMID:15187462

  2. Overuse and throwing injuries in the skeletally immature athlete.

    PubMed

    Hutchinson, Mark R; Ireland, Mary Lloyd

    2003-01-01

    Over 25 million children participate in school-sponsored sports, and an additional 20 million participate in extracurricular organized sports. Over the past decade, increased intensity of training, more pressure for success, new opportunities for structured play, and more organized advanced leagues and traveling teams have led to a corresponding increase in overuse injuries in the skeletally immature athlete. Perhaps the classic sports model for overuse injuries of the upper extremity is baseball. Throwing sports contribute to an increased incidence of elbow and shoulder injuries that might be related to intensity of training, throwing mechanics, and poor conditioning, including core strength. Specific areas of concern regarding overuse injuries in young athletes include such diagnoses as little leaguer's shoulder, little leaguer's elbow, osteochondritis dissecans of the elbow, tennis elbow, and distal radial epiphysitis. Ultimately, overuse injuries, and particularly physeal injuries, should be suspected in any young athlete who has pain in the upper extremity. Comparative bilateral radiographs are the rule in workup. PMID:12690838

  3. Disorders of the first metatarsophalangeal joint: diagnosis of great-toe pain.

    PubMed

    Chou, L B

    2000-07-01

    Disorders of the joint at the base of the hallux are common in active patients. Great-toe sprains (turf toe) can range from mild to severe with associated fractures. Hallux rigidus, a painful flexion deformity, is often seen in athletes who stress the joint repetitively. Heredity may predispose athletes to hallux valgus (bunion) but improper footwear, injury, and hyperpronation can also be implicated. Weight-bearing activities, climbing stairs, or wearing high-heeled shoes will aggravate sesamoiditis. Stress fractures, osteochondral defects, and gout are other causes of toe pain. X-rays are essential for accurate diagnosis. Nonoperative measures can reduce pain, but surgery is an option for recalcitrant cases. PMID:20086649

  4. Allograft Replacement for Absent Native Tissue

    PubMed Central

    Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J.; Warren, Russell F.; Doyle, Maureen; Rodeo, Scott A.

    2013-01-01

    Context: Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. Objective: This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs. PMID:24427387

  5. Feet injuries in rock climbers

    PubMed Central

    Schöffl, Volker; Küpper, Thomas

    2013-01-01

    While injuries of the upper extremity are widely discussed in rock climbers, reports about the lower extremity are rare. Nevertheless almost 50 percent of acute injuries involve the leg and feet. Acute injuries are either caused by ground falls or rock hit trauma during a fall. Most frequently strains, contusions and fractures of the calcaneus and talus. More rare injuries, as e.g., osteochondral lesions of the talus demand a highly specialized care and case presentations with combined iliac crest graft and matrix associated autologous chondrocyte transplantation are given in this review. The chronic use of tight climbing shoes leads to overstrain injuries also. As the tight fit of the shoes changes the biomechanics of the foot an increased stress load is applied to the fore-foot. Thus chronic conditions as subungual hematoma, callosity and pain resolve. Also a high incidence of hallux valgus and hallux rigidus is described. PMID:24147257

  6. Magnetic Resonance Imaging Findings in Small Patella Syndrome.

    PubMed

    Kim, Hyoung-Soo; Yoo, Jeong-Hyun; Park, Noh-Hyuck; Chang, Jun-Hee; Ban, Yun-Seong; Song, Sang-Heon

    2016-03-01

    Small patella syndrome (SPS) is characterized by aplasia or hypoplasia of the patella and pelvic girdle abnormalities, including bilateral absence or delayed ossification of the ischiopubic junction and infra-acetabular axe-cut notches. Here, we report a case of SPS in a 26-year-old female. Magnetic resonance image (MRI) showed a small patella with thick eccentric non-ossified patellar cartilage and femoral trochlear dysplasia with hypoplastic patellar undersurface. To our knowledge, this is the first report of MRI findings in SPS. MRI findings could be clinically relevant because elongation of the medial patellofemoral ligament and trochlear dysplasia with eccentric non-ossified patellar cartilage might lead to patellofemoral maltracking with an osteochondral lesion or acute dislocation or an extensor mechanism injury. Though the patient presented in this case report only had a gastrocnemius injury at the origin site, physicians should carefully examine abnormalities with MRI when an SPS patient has a trauma to the knee. PMID:26955616

  7. Magnetic Resonance Imaging Findings in Small Patella Syndrome

    PubMed Central

    Kim, Hyoung-Soo; Yoo, Jeong-Hyun; Park, Noh-Hyuck; Chang, Jun-Hee; Ban, Yun-Seong

    2016-01-01

    Small patella syndrome (SPS) is characterized by aplasia or hypoplasia of the patella and pelvic girdle abnormalities, including bilateral absence or delayed ossification of the ischiopubic junction and infra-acetabular axe-cut notches. Here, we report a case of SPS in a 26-year-old female. Magnetic resonance image (MRI) showed a small patella with thick eccentric non-ossified patellar cartilage and femoral trochlear dysplasia with hypoplastic patellar undersurface. To our knowledge, this is the first report of MRI findings in SPS. MRI findings could be clinically relevant because elongation of the medial patellofemoral ligament and trochlear dysplasia with eccentric non-ossified patellar cartilage might lead to patellofemoral maltracking with an osteochondral lesion or acute dislocation or an extensor mechanism injury. Though the patient presented in this case report only had a gastrocnemius injury at the origin site, physicians should carefully examine abnormalities with MRI when an SPS patient has a trauma to the knee. PMID:26955616

  8. [Current status of magnetic resonance tomography in diagnosis of the ankle joint--a critical evaluation].

    PubMed

    Murer, J; Mller, F; Vogl, T J; Hosten, N; Langer, R; Felix, R

    1994-05-01

    Anatomical preparations of the ankle were examined by T1-weighted SE-sequences in three planes to identify normal topography. The current status of magnetic resonance imaging (MRI) was assessed and illustrated by image examples. Together with conventional radiography, MRI yields relevant information for therapy planning. This technique allows accurate staging of traumatic and degenerative involving the soft tissues of the joint, including tendons and ligaments. MRI clearly delineates joint fluid, osteochondral abnormalities, and is helpful in the diagnosis of inflammatory changes of the synovia and bone marrow. Furthermore, it is the modality of choice for evaluating tissue neoplasma. Its advantages are not only the detection of the process and definition of its extent, but also the determination of local soft-tissue infiltration. PMID:8049280

  9. Histopathologic findings of spontaneous osteonecrosis of the knee at an early stage: a case report.

    PubMed

    Hatanaka, Hiroyuki; Yamamoto, Takuaki; Motomura, Goro; Sonoda, Kazuhiko; Iwamoto, Yukihide

    2016-05-01

    We histopathologically examined a surgically resected full specimen obtained from an early-stage spontaneous osteonecrosis of the knee (SPONK). On a mid-coronal cut section of the resected medial femoral condyle, a linear fracture line paralleling the subchondral bone endplate was found. Histopathologically, prominent callus formation was seen comprising of reactive woven bone and granulation tissue on both sides of the fracture. Fracture-related bone debris was focally observed at the osteochondral side of the fracture. Definitive features of antecedent bone infarction such as creeping substitution and bone marrow necrosis were not detected. These findings suggested that SPONK was the result of a subchondral fracture rather than primary osteonecrosis. PMID:26768133

  10. Supramolecular GAG-like Self-Assembled Glycopeptide Nanofibers Induce Chondrogenesis and Cartilage Regeneration.

    PubMed

    Ustun Yaylaci, Seher; Sardan Ekiz, Melis; Arslan, Elif; Can, Nuray; Kilic, Erden; Ozkan, Huseyin; Orujalipoor, Ilghar; Ide, Semra; Tekinay, Ayse B; Guler, Mustafa O

    2016-02-01

    Glycosaminoglycans (GAGs) and glycoproteins are vital components of the extracellular matrix, directing cell proliferation, differentiation, and migration and tissue homeostasis. Here, we demonstrate supramolecular GAG-like glycopeptide nanofibers mimicking bioactive functions of natural hyaluronic acid molecules. Self-assembly of the glycopeptide amphiphile molecules enable organization of glucose residues in close proximity on a nanoscale structure forming a supramolecular GAG-like system. Our in vitro culture results indicated that the glycopeptide nanofibers are recognized through CD44 receptors, and promote chondrogenic differentiation of mesenchymal stem cells. We analyzed the bioactivity of GAG-like glycopeptide nanofibers in chondrogenic differentiation and injury models because hyaluronic acid is a major component of articular cartilage. Capacity of glycopeptide nanofibers on in vivo cartilage regeneration was demonstrated in microfracture treated osteochondral defect healing. The glycopeptide nanofibers act as a cell-instructive synthetic counterpart of hyaluronic acid, and they can be used in stem cell-based cartilage regeneration therapies. PMID:26716910

  11. Chondral Injury in Patellofemoral Instability

    PubMed Central

    Lustig, Sébastien; Servien, Elvire; Neyret, Philippe

    2014-01-01

    Objective: Patellofemoral instability is common and affects a predominantly young age group. Chondral injury occurs in up to 95%, and includes osteochondral fractures and loose bodies acutely and secondary degenerative changes in recurrent cases. Biomechanical abnormalities, such as trochlear dysplasia, patella alta, and increased tibial tuberosity-trochlear groove distance, predispose to both recurrent dislocations and patellofemoral arthrosis. Design: In this article, we review the mechanisms of chondral injury in patellofemoral instability, diagnostic modalities, the distribution of lesions seen in acute and episodic dislocation, and treatments for articular cartilage lesions of the patellofemoral joint. Results: Little specific evidence exists for cartilage treatments in patellofemoral instability. In general, the results of reparative and restorative procedures in the patellofemoral joint are inferior to those observed in other compartments of the knee. Conclusion: Given the increased severity of chondral lesions and progression to osteoarthritis seen with recurrent dislocations, careful consideration should be given to early stabilisation in patients with predisposing factors. PMID:26069693

  12. 2013-2014 sterling bunnell traveling fellowship report.

    PubMed

    Higgins, James P

    2015-02-01

    Since 1982, the American Society for Surgery of the Hand has sponsored a young member each year as its Bunnell Traveling Fellow. The Sterling Bunnell Traveling Fellowship enables young hand surgeons to foster national and international relationships that contribute to their pursuit of higher learning and advance the principles of scholarship by improving treatment of hand and upper extremity disorders. As the Sterling Bunnell Traveling Fellow for 2013 to 2014, I studied microvascular osteochondral reconstruction of the upper extremity. The year allowed me to pursue research abroad and participate in novel operations. These experiences have challenged how I approach common osteoarticular problems in hand surgery. Leaders in wrist surgery around the globe helped me reconsider the treatment of osteonecrotic, degenerative, and posttraumatic cartilage loss in radical new ways. PMID:25617958

  13. Common medial elbow injuries in the adolescent athlete.

    PubMed

    Leahy, Ian; Schorpion, Melissa; Ganley, Theodore

    2015-01-01

    Recently there has been increased year-round sports participation among children and adolescents with limited to no rest periods. This has led to increases in pediatric repetitive stress injuries, once considered a rarity. Whether in the throwing athlete or in the athlete that experiences repetitive axial loading; increased medial tension and overload syndromes can lead to stress reactions and fractures. This occurs in the developing athlete due to the bone being weaker than the surrounding tendons and ligaments. The medial elbow is a high stress area and is susceptible to many conditions including apophysitis , avulsion fractures and ulnar collateral ligament disruption. Valgus stress can cause injury to the medial elbow which can lead to increased lateral compression, Panner's disease and osteochondral lesions of the capitellum and olecranon. The purpose of this manuscript is to review common elbow disorders in the adolescent population, outline management and highlight important features of rehabilitation. PMID:25840494

  14. Recent Advances in Cartilage Tissue Engineering: From the Choice of Cell Sources to the Use of Bioreactors

    NASA Astrophysics Data System (ADS)

    Martin, Ivan; Démarteau, Olivier; Braccini, Alessandra

    Grafting engineered cartilage tissues represents a promising approach for the repair of joint injuries. Recent animal experiments have demonstrated that tissues engineered by culturing chondrocytes on 3D scaffolds in bioreactors provide functional templates for orderly repair of large osteochondral lesions. To date, however, a reproducible generation of uniform cartilage tissues of predefined size starting from adult human cells has not been achieved. In this paper we review some of the recent advances and challenges ahead in the identification of appropriate (i) cell sources, (ii) bioactive factors, (iii) 3D scaffolds and (iv) bioreactors for human cartilage tissue engineering. We also present an example of how integrated efforts in these different areas can help addressing fundamental questions and advancing the field of cartilage tissue engineering towards clinical use. The presented experiment demonstrates that human nasal chondrocytes are responsive to dynamic loading and thus could be further investigated as a cell source for implantation in a joint environment.

  15. 3D Bioprinting of Cartilage for Orthopedic Surgeons: Reading between the Lines

    PubMed Central

    Di Bella, Claudia; Fosang, Amanda; Donati, Davide M.; Wallace, Gordon G.; Choong, Peter F. M.

    2015-01-01

    Chondral and osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopedic surgeon and for the patient. The lack of therapeutic strategies capable to reconstitute the function and structure of hyaline cartilage and to halt the progression toward osteoarthritis has brought clinicians and scientists together, to investigate the potential role of tissue engineering as a viable alternative to current treatment modalities. In particular, the role of bioprinting is emerging as an innovative technology that allows for the creation of organized 3D tissue constructs via a “layer-by-layer” deposition process. This process also has the capability to combine cells and biomaterials in an ordered and predetermined way. Here, we review the recent advances in cartilage bioprinting and we identify the current challenges and the directions for future developments in cartilage regeneration. PMID:26322314

  16. [The role of MRI in dislocations of the patella and other knee pathologies].

    PubMed

    Mauch, F; Ammann, B; Kraus, M

    2014-03-01

    In addition to ultrasound and conventional x-ray, magnetic resonance imaging (MRI) plays an important role in the visualization of lesions of the knee. It allows the orthopaedic surgeon to safely detect ruptures of the cruciate ligaments, the meniscus, osteochondral lesions and other ligamentary structures such as the collateral ligaments and the medial patellofemoral ligament (MPFL). In patellar dislocations, risk factors for recurrent dislocations can be determined and the therapy can be adjusted accordingly.This articles aims to give the reader a comprehensive overview on current concepts and techniques in the use of MRI for lesions of the knee. It focuses on patellar dislocations, where MRI plays a dominant role in supporting decision making for the best therapeutic strategy. PMID:24557452

  17. Dermochondrocorneal dystrophy (Francois syndrome) in a Mexican patient and literature review.

    PubMed

    Hidalgo-Bravo, Alberto; Acosta-Nieto, Maria L; Normendez-Martinez, Monica I; Rodriguez-Gonzalez, Nubia F; Paz-Gomez, Francisco; Valdes-Flores, Margarita; Kramis-Hollands, Mirelle

    2016-02-01

    Dermochondrocorneal Dystrophy (OMIM 221800) is a very rare disease first described by Francois in 1949. It is characterized by the appearance of skin nodules, osteochondral deformities, and corneal opacities during childhood. Only a few cases have been reported. There is uncertainty about the inheritance pattern and no gene or genes have been associated to this disease. We report a patient from Mexican mestizo origin with the classic manifestations of Dermochondrocorneal Dystrophy. We perform a multidisciplinary assessment in order to contribute to the knowledge of the clinical presentation of this uncommon condition. Among the few documented patients, this is the third patient of Mexican ancestry reported with this syndrome. © 2015 Wiley Periodicals, Inc. PMID:26440764

  18. Closed Sagittal Band Injury of the Metacarpophalangeal Joint.

    PubMed

    Kleinhenz, Benjamin P; Adams, Brian D

    2015-07-01

    Although it is an uncommon injury, traumatic rupture of the sagittal band often results in subluxation or dislocation of the extensor digitorum communis tendon. The radial sagittal band prevents ulnar subluxation of the extensor tendon at the metacarpophalangeal joint. Injury may result from a direct blow to the hand or from relatively low-energy mechanisms. Symptoms range from metacarpophalangeal joint pain and edema to dislocation of the extensor tendon. Associated injuries include collateral ligament sprains, capsular injury, and osteochondral fractures. Many acute injuries can be managed nonsurgically with extension splints. Optimal management of subacute or chronic injuries remains undefined. Surgical management consists of repair or reconstruction of the radial sagittal band. Numerous adjunctive surgical techniques have been described to prevent subluxation of the extensor tendon. PMID:26111875

  19. The knee: Surface-coil MR imaging at 1. 5 T

    SciTech Connect

    Beltran, J.; Noto, A.M.; Mosure, J.C.; Weiss, K.L.; Zuelzer, W.; Christoforidis, A.J.

    1986-06-01

    Seven normal knees (in five volunteers) and seven injured knees (in seven patients) were examined by high-resolution magnetic resonance (MR) imaging at 1.5 T with a surface coil. Seven medial meniscal tears, three anterior cruciate ligament tears, one posterior cruciate ligament avulsion, an old osteochondral fracture, femoral condylar chondro-malacia, and one case of semimembranous tendon reinsertion were identified. MR images correlated well with recent double-contrast arthrograms or results of surgery. All tears were identified in both the sagittal and coronal planes. Because of its ability to demonstrate small meniscal lesions and ligamentous injuries readily, MR imaging with a surface coil may eventually replace the more invasive arthrography.

  20. Subtalar dislocation secondary to a low energy injury.

    PubMed

    McKeag, Philip; Lyske, Jonathan; Reaney, Jonathan; Thompson, Neville

    2015-01-01

    An 18-year-old young man presented with an ankle injury, after landing on a supinated right foot following jumping while playing football. A plain X-ray revealed a medial subtalar dislocation. Despite obvious ankle deformity, the surrounding skin remained intact. Closed reduction of the subtalar joint was successfully performed under general anaesthesia in theatre. A CT of the ankle, after reduction, demonstrated a non-displaced fracture of the neck of the talus; no osteochondral defect was observed. This was successfully managed conservatively, with immobilisation of the ankle, in a non-weight bearing cast for 6 weeks. This case highlights that subtalar dislocation may follow a low-energy mechanism and that such injuries can be managed without open reduction. PMID:25650063

  1. Evaluation and management of posterior ankle pain in dancers.

    PubMed

    Luk, Pamela; Thordarson, David; Charlton, Timothy

    2013-01-01

    Posterior ankle pain is a common complaint in dancers. There are multiple structures in the posterior ankle that have the potential to be the source of pain. The objective of this article is to review several of the most common causes of posterior ankle pain: peroneal tendon subluxation, posterior impingement syndrome secondary to a painful os trigonum, posterior talus osteochondritis dissecans, flexor hallucis longus tendinopathy, and posterior tibial tendinopathy. For dancers, we offer typical clinical presentations of these disorders to increase awareness and provide guidance regarding when to seek professional medical attention. For medical personnel who are responsible for optimizing dancers' health and training, we include a discussion of pertinent physical exam findings, diagnostic imaging options, non-operative and operative management, as well as surgical suggestions and postoperative rehabilitation guidelines. PMID:23759482

  2. Progressive paralyzing sciatica revealing a pelvic pseudoaneurysm a year after hip surgery in a 12yo boy.

    PubMed

    Boulouis, Grégoire; Shotar, Eimad; Dangouloff-Ros, Volodia; Janklevicz, Pierre-Henri; Boddaert, Nathalie; Naggara, Olivier; Brunelle, Francis

    2016-01-01

    Identifying extra spinal causes of a lumbar radiculopathy or polyneuropathy can be a tricky diagnosis challenge, especially in children. Among them, traumatic or iatrogenic pseudoaneurysms of iliac arteries have been seldom reported, in adults' series. The authors report an unusual case of progressive paralyzing left sciatica and lumbar plexopathy in a 12 years old boy, 12 months after a pelvic osteotomy for bilateral hip luxation secondary to osteochondritis dissecans. Spine MRI and pelvic CT angiography revealed a giant internal iliac artery pseudoaneurysm, enclosed in a chronic hematoma. The patient was successfully treated with endovascular coil embolization, and subsequent surgical hematoma evacuation. However, three months after treatment, neurological recovery was incomplete. This case highlights the importance of a rapid and extensive diagnosis work up of all causes of lower limb radiculopathies in children, including pelvic arteries lesions especially after pelvic surgery to avoid therapeutic delays that may jeopardize the chances of neurological recovery. PMID:26545958

  3. Prenatal diagnosis of hypophosphatasia congenita using ultrasonography

    PubMed Central

    2016-01-01

    Congenital hypophosphatasia is a rare fatal skeletal dysplasia. Antenatal determinants of Epub ahead of print lethality include small thoracic circumference with pulmonary hypoplasia and severe micromelia. These features were present in the fetus of a 25-year-old female who came for an anomaly scan in her second trimester of pregnancy. Additional findings of generalized demineralization and osteochondral spurs led to the diagnosis of hypophosphatasia congenita. The pregnancy was terminated, and the findings were confirmed on autopsy. Common differential diagnoses with clues to diagnose the above mentioned condition have been discussed here. Early and accurate detection of this medical condition is important as no treatment has been established for this condition. Therefore, antenatal ultrasonography helps in diagnosing and decision making with respect to the current pregnancy and lays the foundation for the genetic counseling of the couple. PMID:25971898

  4. [Rupture of the pes anserinus superficialis and partial rupture of the patellar ligament. Rare concomitant injures in complex knee injuries].

    PubMed

    Pointinger, H; Munk, P; Poeschl, G P

    1999-01-01

    We present a rare case of combined knee joint lesions in a 25 year old patient. Besides the commonly reported injuries of the knee joint due to directly applied valgus force, forceful quadriceps muscle contraction, external rotation at flexed knee causing combined lesions such as rupture of the anterior cruciate ligament, rupture of the posterior cruciate ligament and rupture of the medial collateral ligament, a rare combination of the above mentioned lesions and a rupture of the lateral meniscus, an osteochondral fracture of the lateral femur condylus, a rupture of the medial patellofemoral retinacula as well as a complete rupture of the superficial pes anserinus and a partial rupture of the patellar ligament was encountered. PMID:10095409

  5. First-time patellar dislocation: surgery or conservative treatment?

    PubMed

    Sillanpää, Petri J; Mäenpää, Heikki M

    2012-09-01

    Primary patellar dislocation injures the medial patellofemoral ligament (MPFL), the major soft-tissue stabilizer of the patella, which may lead to recurrent patellar instability. Recurrent patellar dislocation are common and may require surgical intervention. The variation in location of injury of the MPFL and the presence of an osteochondral fracture produces challenges in clinical decision making between nonoperative and operative treatment, including the surgical modality, to repair or reconstruct the MPFL. Current evidence suggests that not all primary dislocations should undergo the same treatment. MPFL reconstruction may theoretically be more reliable than repair, but the optimal time to perform additional bony corrections is not known. A normal or minor dysplastic patellofemoral joint may be suitable for nonoperative treatment, whereas a higher grade of trochlear dysplasia or other significant abnormalities may benefit from surgical treatment. In this paper, we present a treatment algorithm for primary patellar dislocation. PMID:22878653

  6. The Long-Term Clinical Outcomes Following Autogenous Bone Grafting for Large-Volume Defects of the Knee

    PubMed Central

    Delano, Mark; Spector, Myron; Pittsley, Andrew; Gottschalk, Alexander

    2014-01-01

    Objective: We report the long-term clinical outcomes of patients who underwent autogenous bone grafting of large-volume osteochondral defects of the knee due to osteochondritis dessicans (OCD) and osteonecrosis (ON). This is the companion report to one previous published on the biological response. We hypothesized that these grafts would integrate with host bone and the articular surface would form fibrocartilage providing an enduring clinical benefit. Design: Three groups (patients/knees) were studied: OCD without a fragment (n = 12/13), OCD with a partial fragment (n = 14/16), and ON (n = 25/26). Twenty-five of 52 patients were available for clinical follow-up between 12 and 21 years. Electronic medical records provided comparison clinical information. In addition, there were plain film radiographs, MRIs, plus repeat arthroscopy and biopsy on 14 patients. Results: Autogenous bone grafts integrated with the host bone. MRI showed soft tissue covering all the grafts at long-term follow-up. Biopsy showed initial surface fibrocartilage that subsequently converted to fibrocartilage and hyaline cartilage at 20 years. OCD patients had better clinical outcomes than ON patients. No OCD patients were asymptomatic at anytime following surgery. Half of the ON patients came to total knee replacement within 10 years. Conclusions: Autogenous bone grafting provides an alternative biological matrix to fill large-volume defects in the knee as a singular solution integrating with host bone and providing an enduring articular cartilage surface. The procedure is best suited for those with OCD. The treatment for large-volume articular defects by this method remains salvage in nature and palliative in outcome. PMID:26069688

  7. Osteoarticular transplantation: recognizing expected postsurgical appearances and complications.

    PubMed

    Favinger, Jennifer L; Ha, Alice S; Brage, Michael E; Chew, Felix S

    2015-01-01

    Despite technologic advances in prosthetic joint replacement, young patients who have lost a large volume of bone or soft tissue because of a tumor or traumatic injury may not be good candidates for prosthetic implants, which have limited longevity relative to that of biologic tissue grafts. In recent years, the use of biologic materials in orthopedic surgery has increased. Such materials, known as allografts, consist of cadaveric bone, cartilage, and other soft tissues that can be transplanted into a living patient. Alternatively, osteochondral autografts, or autologous grafts of the patient's own bone and/or cartilage, can be harvested from one body site and transplanted to another. Surgical procedures range from the local implantation of small osteochondral plugs to the replacement of entire joints with allografts. The size of the allograft used depends on the amount of bone and soft tissue needed. The use of allografts in patients with large-volume bone loss often preserves limb function, obviating amputation, which makes it an attractive option for treatment of young patients. Advantages of using allografts include the similarity of graft materials to native tissues and the decreased patient morbidity in the absence of an autograft donor site; disadvantages include slower biologic remodeling and graft incorporation than are typical with the use of autologous grafts. Potential complications of allograft tissue implantation include graft nonunion, collapse, and failure; infection; and secondary osteoarthritis. The article discusses the indications for and basic steps involved in each type of transplant procedure, normal pre- and postoperative imaging appearances, and imaging features that may be indicative of transplant complications. PMID:25969934

  8. Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation

    PubMed Central

    Khurana, Aman; Chapelin, Fanny; Beck, Graham; Lenkov, Olga D.; Donig, Jessica; Nejadnik, Hossein; Messing, Solomon; Derugin, Nikita; Chan, Ray Chun-Fai; Gaur, Amitabh; Sennino, Barbara; McDonald, Donald M.; Kempen, Paul J.; Tikhomirov, Grigory A.; Rao, Jianghong

    2013-01-01

    Purpose: To determine whether intravenous ferumoxytol can be used to effectively label mesenchymal stem cells (MSCs) in vivo and can be used for tracking of stem cell transplants. Materials and Methods: This study was approved by the institutional animal care and use committee. Sprague-Dawley rats (68 weeks old) were injected with ferumoxytol 48 hours prior to extraction of MSCs from bone marrow. Ferumoxytol uptake by these MSCs was evaluated with fluorescence, confocal, and electron microscopy and compared with results of traditional ex vivolabeling procedures. The in vivolabeled cells were subsequently transplanted in osteochondral defects of 14 knees of seven athymic rats and were evaluated with magnetic resonance (MR) imaging up to 4 weeks after transplantation. T2 relaxation times of in vivolabeled MSC transplants and unlabeled control transplants were compared by using t tests. MR data were correlated with histopathologic results. Results: In vivolabeled MSCs demonstrated significantly higher ferumoxytol uptake compared with ex vivolabeled cells. With electron microscopy, iron oxide nanoparticles were localized in secondary lysosomes. In vivolabeled cells demonstrated significant T2 shortening effects in vitro and in vivo when they were compared with unlabeled control cells (T2 in vivo, 15.4 vs 24.4 msec; P < .05) and could be tracked in osteochondral defects for 4 weeks. Histologic examination confirmed the presence of iron in labeled transplants and defect remodeling. Conclusion: Intravenous ferumoxytol can be used to effectively label MSCs in vivo and can be used for tracking of stem cell transplants with MR imaging. This method eliminates risks of contamination and biologic alteration of MSCs associated with ex vivolabeling procedures. RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130858/-/DC1 PMID:23850832

  9. Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury

    PubMed Central

    Boyce, Mary K.; Trumble, Troy N.; Carlson, Cathy S.; Groschen, Donna M.; Merritt, Kelly A.; Brown, Murray P.

    2013-01-01

    Objective Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). Methods An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. Results Osteochondral fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P=0.0012), while joint circumference (P<0.0001) and effusion scores (P<0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. Conclusion Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery. PMID:23467035

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

    PubMed Central

    2011-01-01

    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. PMID:21955995

  11. Morphological MRI and T2 mapping of cartilage repair tissue after mosaicplasty with tissue-engineered cartilage in a pig model

    PubMed Central

    Chen, Qichun; Zuo, Qiang; Hu, Qianqian; Feng, Yang; Cui, Weiding; Fan, Weimin; Zou, Yuefen

    2014-01-01

    Abstract The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs were used. The right knee underwent mosaicplasty with tissue-engineered cartilage for treatment of focal osteochondral defects, while the left knee was repaired via single mosaicplasty as controls. At 6, 12, 18 and 26 weeks after surgery, repair tissue was evaluated by magnetic resonance imaging (MRI) with the cartilage repair tissue (MOCART) scoring system and T2 mapping. Then, the results of MRI for 26 weeks were compared with findings of macroscopic and histologic studies. The MOCART scores showed that the repaired tissue of the tissue-engineered cartilage group was statistically better than that of controls (P < 0.001). A significant correlation was found between macroscopic and MOCART scores (P < 0.001). Comparable mean T2 values were found between adjacent cartilage and repair tissue in the experimental group (P > 0.05). For zonal T2 value evaluation, there were no significant zonal T2 differences for repair tissue in controls (P > 0.05). For the experimental group, zonal T2 variation was found in repair tissue (P < 0.05). MRI, macroscopy and histology showed better repair results and bony incorporation in mosaicplasty with the tissue-engineered cartilage group than those of the single mosaicplasty group. Mosaicplasty with the tissue-engineered cartilage is a promising approach to repair osteochodndral defects. Morphological MRI and T2 mapping provide a non-invasive method for monitoring the maturation and integration of cartilage repair tissue in vivo. PMID:25050115

  12. Activity-Related Outcomes of Articular Cartilage Surgery

    PubMed Central

    Chalmers, Peter N.; Vigneswaran, Hari; Harris, Joshua D.

    2013-01-01

    Objective: The purpose of this systematic review was to compare activity-based outcomes after microfracture, autologous chondrocyte implantation (ACI), and osteochondral autograft (OAT). Design: Multiple databases were searched with specific inclusion and exclusion criteria for level III and higher studies with activity outcomes after microfracture, OAT, osteochondral allograft, and ACI. Activity-based outcomes included the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Tegner Score, the Cincinnati Knee scores, the International Knee Documentation Committee (IKDC) subjective knee score, the Marx activity score, and/or the rate of return-to-sport. Results: Twenty studies were included (1,375 patients). Although results were heterogeneous, significant advantages were seen for ACI and OAT as compared with microfracture in Tegner scores at 1 year (ACI vs. microfracture, P = 0.0016), IKDC scores at 2 years (ACI vs microfracture, P = 0.046), Lysholm scores at 1 year (OAT vs microfracture, P = 0.032), and Marx scores at 2 years (OAT vs microfracture, P < 0.001). The only score or time point to favor microfracture was Lysholm score at 1 year (ACI vs microfracture, P = 0.037). No other standardized outcome measures or time points were significantly different. Several studies demonstrated significantly earlier return to competition with microfracture. Overall reoperation rates were similar, but of reoperations, a higher proportion of those following ACI were unplanned with the majority of performed for graft delamination or hypertrophy. Conclusions: ACI and OAT may have some benefits over microfracture, although return-to-sport is fastest following microfracture. Heterogeneity in technique, outcome measures, and patient populations hampers systematic comparison within the current literature. PMID:26069665

  13. Stem cell-coated titanium implants for the partial joint resurfacing of the knee.

    PubMed

    Frosch, Karl-Heinz; Drengk, Anja; Krause, Petra; Viereck, Volker; Miosge, Nicolai; Werner, Carola; Schild, Detlev; Strmer, Ewa K; Strmer, Klaus M

    2006-04-01

    The goal of the present study was to evaluate the partial surface replacement of the knee with stem cell-coated titanium implants and to provide a basis for a successful treatment of large osteochondral defects. Mesenchymal stem cells (MSCs) were isolated from bone marrow aspirates of adult sheep. Round titanium implants with a diameter of 2 x 7.3 mm were seeded with autologous MSC and inserted into an osteochondral defect in the medial femoral condyle. As controls, defects received either an uncoated implant or were left untreated. Nine animals with 18 defects were sacrificed after 6 months. Histological evaluation was performed by intravital polychrome fluorescent labelling, intravital perfusion with Indian ink, microradiographs and differential staining with toluidine blue. The quality of regenerated cartilage was assessed by in situ hybridization of collagen type II and immunohistochemistry of collagen types I and II. In 50% of the cases, defects treated with MSC-coated implants showed a complete regeneration of the subchondral bone layer. In these cases collagen type II and only traces of collagen type I were detected. A high level of collagen type II mRNA expression compared to articular cartilage indicates regenerating hyaline-like cartilage. A total of 50% of MSC-coated and uncoated implants failed to osseointegrate and formation of fibrocartilage was observed. Untreated defects as well as defects treated with uncoated implants demonstrated incomplete healing of subchondral bone and formation of fibrous cartilage. A modified histological score according to Wakitani significantly demonstrated better results for cell-coated implants (8.8+/-6.4) than for uncoated implants (5.5+/-3.9) and for untreated defects (2.8+/-2.5). Our results demonstrate that, in a significant number of cases, a partial joint resurfacing of the knee with stem cell-coated titanium implants occur. A slow bone and cartilage regeneration and an incomplete healing in half of the MSC-coated implants are limitations of the presented method. To improve our approach and optimize the experimental parameters, further investigations are needed prior to clinical application. PMID:16368134

  14. Development of artificial articular cartilage.

    PubMed

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

    2000-01-01

    Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of the possible use of this material in articular resurfacing and joint replacement are discussed. PMID:10718051

  15. The effect of insulin-loaded chitosan particle-aggregated scaffolds in chondrogenic differentiation.

    PubMed

    Malafaya, Patrícia B; Oliveira, João T; Reis, Rui L

    2010-02-01

    Osteochondral defect repair requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using a scaffold-cell construct. One ideal approach would be to engineer in vitro a hybrid material using a single-cell source. For that purpose, the scaffold should be able to provide the adequate biochemical cues to promote the selective but simultaneous differentiation of both tissues. In this work, attention was paid primarily to the chondrogenic differentiation by focusing on the development of polymeric systems that provide biomolecules release to induce chondrogenic differentiation. For that, different formulations of insulin-loaded chitosan particle-aggregated scaffolds were developed as a potential model system for cartilage and osteochondral tissue engineering applications using insulin as a potent bioactive substance known to induce chondrogenic differentiation. The insulin encapsulation efficiency was shown to be high with values of 70.37 +/- 0.8%, 84.26 +/- 1.76%, and 87.23 +/- 1.58% for loadings of 0.05%, 0.5%, and 5%, respectively. The in vitro release profiles were assessed in physiological conditions mimicking the cell culture procedures and quantified by Micro-BCA protein assay. Different release profiles were obtained that showed to be dependent on the initial insulin-loading percentage. Further, the effect on prechondrogenic ATDC5 cells was investigated for periods up to 4 weeks by studying the influence of these release systems on cell morphology, DNA and glycosaminoglycan content, histology, and gene expression of collagen types I and II, Sox-9, and aggrecan assessed by real-time polymerase chain reaction. When compared with control conditions (unloaded scaffolds cultured with the standard chondrogenic-inducing medium), insulin-loaded scaffolds upregulated the Sox-9 and aggrecan expression after 4 weeks of culture. From the overall results, it is reasonable to conclude that the developed loaded scaffolds when seeded with ATDC5 can provide biochemical cues for chondrogenic differentiation. Among the tested formulations, the higher insulin-loaded system (5%) was the most effective in promoting chondrogenic differentiation. PMID:19772454

  16. An amphiphilic degradable polymer/hydroxyapatite composite with enhanced handling characteristics promotes osteogenic gene expression in bone marrow stromal cells

    PubMed Central

    Kutikov, Artem B.; Song, Jie

    2013-01-01

    Electrospun polymer/hydroxyapatite (HA) composites combining biodegradability with osteoconductivity are attractive for skeletal tissue engineering applications. However, most biodegradable polymers such as PLA are hydrophobic and do not blend with adequate interfacial adhesion with HA, compromising the structural homogeneity, mechanical integrity, and biological performance of the composite. To overcome this challenge, we incorporated a hydrophilic polyethylene glycol (PEG) block to poly(D,L-lactic acid) to improve the adhesion of the degradable polymer with HA. The amphiphilic triblock copolymer PLA-PEG-PLA (PELA) improved the stability of HA-PELA suspension at 25 wt% HA content, which was readily electrospun into HA-PELA composite scaffolds with uniform fiber dimensions. HA-PELA was highly extensible (failure strain >200% vs. <40% for HA-PLA), superhydrophilic (~0° water contact angle vs. >100° for HA-PLA), and exhibited an 8-fold storage modulus increase (unlike deterioration for HA-PLA) upon hydration, owing to the favorable interaction between HA and PEG. HA-PELA also better promoted osteochondral lineage commitment of bone marrow stromal cells in unstimulated culture and supported far more potent osteogenesis upon induction than HA-PLA. We demonstrate that the chemical incorporation of PEG is an effective strategy to improve the performance of degradable polymer/HA composites for bone tissue engineering applications. PMID:23791675

  17. Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment.

    PubMed

    Hu, Jia-Jie; Yin, Zi; Shen, Wei-Liang; Xie, Yu-Bin; Zhu, Ting; Lu, Ping; Cai, You-Zhi; Kong, Min-Jian; Heng, Boon Chin; Zhou, Yi-Ting; Chen, Wei-Shan; Chen, Xiao; Ouyang, Hong-Wei

    2016-04-01

    Calcification of soft tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1 inclined form) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves. Proinflammatory microenvironment, rather than hypoxia, is correlated with HIF-2alpha activation and promoted osteochondrogenic differentiation of tendon stem/progenitor cells (TSPCs). Abnormal upregulation of HIF-2alpha served as a key switch to direct TSPCs differentiation into osteochondral-lineage rather than teno-lineage. Notably, Scleraxis (Scx), an essential tendon specific transcription factor, was suppressed on constitutive activation of HIF-2alpha and mediated the effect of HIF-2alpha on TSPCs fate decision. Moreover, pharmacological inhibition of HIF-2alpha with digoxin, which is a widely utilized drug, can efficiently inhibit calcification and enhance tenogenesis in vitro and in the Achilles's tendinopathy model. Taken together, these findings reveal the significant role of the tissue stem/progenitor cells fate decision and suggest that pharmacological regulation of HIF-2alpha function is a promising approach for soft tissue calcification treatment. Stem Cells 2016;34:1083-1096. PMID:26851078

  18. Occult posterolateral rotatory dislocation of the elbow with olecranon fracture in a child: a case report

    PubMed Central

    2012-01-01

    Introduction Acute posterolateral rotator elbow dislocation in a child is rare and can be easily misdiagnosed due to immaturity of the epiphysis. This is the first case of occult posterolateral rotator elbow dislocation in combination with an olecranon fracture. We report our experience with this case, which was not diagnosed correctly by plain radiographs. Case presentation An 11-year-old Asian boy suffered severe pain and swelling of his right elbow after his outstretched arm hit a car dashboard in a motor vehicle accident. Plain radiographs showed only a minimally displaced olecranon fracture and a tiny lateral epicondylar avulsion fracture. However, stress radiographs under general anesthesia revealed severe posterolateral rotatory instability. During surgery, we found that the cartilaginous lateral epicondylar apophysis was much larger than the epicondylar fragment on the radiographs. After the lateral epicondylar osteochondral fragment and lateral collateral ligament complex were fixed, the instability disappeared. Conclusion Our experience with this case shows that it is important to check for instability with pediatric elbow fractures, because a tiny avulsion fracture was able to cause severe posterolateral rotatory instability in a child. PMID:22943424

  19. Mosaic arthroplasty of the medial femoral condyle in horses - An experimental study.

    PubMed

    Bodó, Gábor; Vásárhelyi, Gábor; Hangody, László; Módis, László

    2014-06-01

    One Arabian and 5 Hungarian half-bred horses were used to study the macroscopic and microscopic survival of autologous osteochondral grafts in the weight-bearing surface of the medial femoral condyle (MFC). Grafts were harvested from the cranial surface of the medial femoral trochlea (MFT) under arthroscopic control. Three of them were transplanted into the weight-bearing surface of the contralateral MFC using an arthrotomy approach. Three months later this transplantation procedure was repeated on the opposite stifle joints in the same animals, but at that time transplantation was performed arthroscopically. Follow-up arthroscopy was carried out 12 months after the first operations, and biopsies were taken from both the recipient and the donor sites for histological examination. During follow-up arthroscopy, the transplanted areas looked congruent and smooth. Microscopically, the characteristics of hyaline cartilage were present in 5 out of the 10 biopsies examined; however, in the other half of biopsies glycosaminoglycan (GAG) loss and change in the architecture of the transplanted cartilage was observed. In a 16-year-old horse, all grafts broke during harvesting, and thus transplantation was not performed. No radiological signs of osteoarthritic changes were detected 9 to 12 months after the operations in the donor and recipient joints. Clinically, no lameness or effusion was present three months after the transplantations. PMID:24334083

  20. Mechanical evaluation of nHAp scaffold coated with poly-3-hydroxybutyrate for bone tissue engineering.

    PubMed

    Foroughi, Mohammad Reza; Karbasi, Saeed; Ebrahimi-Kahrizsangi, Reza

    2013-02-01

    Regeneration of bone, cartilage and osteochondral tissues by tissue engineering has attracted intense attention due to its potential advantages over the traditional replacement of tissues with synthetic implants. Nevertheless, there is still a dearth of ideal or suitable scaffolds based on porous biomaterials, and the present study was undertaken to develop and evaluate a useful porous composite scaffold system. In this study, nano hydroxyapatite (nHAp) powder made (about 35-45 nm) by heating at temperature of 900 degrees C and porous hydroxyapatite (40, 50 and 60 wt% solution) for making scaffold, by using Polyurethane sponge replication method. In order to increase the scaffolds mechanical properties, they coated with 2, 4 and 6 wt% Poly-3-hydroxybutyrate (P3HB) for 30 sec and 60 sec, respectively; after the scaffold coated by Polymer and survey results, this scaffold is nHAp/P3HB composite. Based on these results, this scaffold is an optimized one among three tested above mentioned composition and can be utilized in bone tissue engineering. In the result, the best of scaffold is with 50 wt% HAp and 6 wt% P3HB and porosity of present is between 80-90% with compressive strength and modulus 1.51 MPa and 22.73 MPa, respectively, that it can be application in bone tissue engineering. PMID:23646681

  1. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes

    PubMed Central

    2013-01-01

    Osteoarthritis (OA) is a major cause of disability in the adult population. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone, osteophyte formation, muscle weakness, and inflammation of the synovium tissue and tendon. Although OA has long been viewed as a primary disorder of articular cartilage, subchondral bone is attracting increasing attention. It is commonly reported to play a vital role in the pathogenesis of OA. Subchondral bone sclerosis, together with progressive cartilage degradation, is widely considered as a hallmark of OA. Despite the increase in bone volume fraction, subchondral bone is hypomineralized, due to abnormal bone remodeling. Some histopathological changes in the subchondral bone have also been detected, including microdamage, bone marrow edema-like lesions and bone cysts. This review summarizes basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage. Importantly, we discuss risk factors influencing subchondral bone integrity. We also focus on the microarchitectural and histopathological changes of subchondral bone in OA, and provide an overview of their potential contribution to the progression of OA. A hypothetical model for the pathogenesis of OA is proposed. PMID:24321104

  2. Steroid atrophy scarring treated with fat grafting in a patient with complex regional pain syndrome: A case report.

    PubMed

    Strickland, Leah R; Collawn, Sherry S

    2016-06-01

    Subcutaneous atrophy is a known complication of steroid injections. Excellent results with fat grafting for the treatment of steroid atrophy have been documented. However, the benefit of treating steroid-induced subcutaneous atrophy in an extremity diagnosed with complex regional pain syndrome (CRPS) has not been described. CRPS, known formerly as reflex sympathetic dystrophy or RSD, causalgia, or reflex neurovascular dystrophy, is a severe, progressive musculoskeletal pain syndrome characterized by pain which is disproportionate to the severity of the inciting event, edema, or skin changes. Common treatment modalities include pharmacotherapy, physical therapy, and nerve blocks-each therapy producing varying results. We present a literature review of CRPS and the case of a 15-year-old female who developed CRPS of the left lower leg after arthroscopic debridement with retrograde drilling of an osteochondral lesion. Steroid atrophy of the involved area following a saphenous nerve block complicated the patient's treatment course. The area of atrophy was treated with autologous fat grafting. Following the adipose injection procedure, the patient experienced almost complete resolution of her CPRS-associated pain symptoms, along with improved cosmetic appearance of the area. PMID:26735938

  3. In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

    NASA Astrophysics Data System (ADS)

    McCanless, Jonathan D.

    Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

  4. The effect of a gelatin β-tricalcium phosphate sponge loaded with mesenchymal stem cells (MSC), bone morphogenic protein-2, and platelet-rich plasma (PRP) on equine articular cartilage defect

    PubMed Central

    Tsuzuki, Nao; Seo, Jong-pil; Yamada, Kazutaka; Haneda, Shingo; Furuoka, Hidefumi; Tabata, Yasuhiko; Sasaki, Naoki

    2013-01-01

    We evaluated the curative efficacy of a gelatin β-tricalcium phosphate (β-TCP) sponge loaded with mesenchymal stem cells (MSC), bone morphogenic protein-2 (BMP-2), and platelet-rich plasma (PRP) by insertion into an experimentally induced osteochondral defect. A hole of 10 mm diameter and depth was drilled in the bilateral medial femoral condyles of 7 thoroughbred horses, and into each either a loaded sponge (treatment) or a saline-infused β-TCP sponge (control) was inserted. After 16 weeks, defects were examined by computed tomography, macroscopic analyses, and histological analyses. The median subchondral bone density and macroscopic subscores for joint healing were significantly higher in the treatment legs (P < 0.05). Although there was no significant difference in total histological scores between groups, hyaline cartilaginous tissue was observed across a wider area in the treatment group. Equine joint healing can be enhanced by inserting a BMP-2-, MSC-, and PRP-impregnated β-TCP sponge at the lesion site. PMID:24155448

  5. Impact of feeding and housing on the development of osteochondrosis in foals-A longitudinal study.

    PubMed

    Mendoza, Luis; Lejeune, Jean-Philippe; Caudron, Isabelle; Detilleux, Johann; Sandersen, Charlotte; Deliège, Brigitte; Serteyn, Didier

    2016-05-01

    Osteochondrosis dissecans (OCD) is a developmental orthopedic disease caused by a failure of the endochondral ossification in epiphyseal plates and joint cartilage. This trouble may induce the presence of osteochondral fragments in the articulation, fissures or subchondral bone cysts in the growth cartilage. Occurrence of osteochondrosis is influenced by a complex interaction of different factors. Among these, the effect of the housing and the feeding of the foals during their first months of life, have been described as risk factors for the development of osteochondrosis. The aim of this study was to investigate the evolution of OCD lesions with a longitudinal study in 204 young foals from 6 to 18 months in comparison to the type of feeding and the type of housing conditions. These factors and OCD status were obtained by a questionnaire and radiological examination, respectively. This allowed dividing the foals into four groups according to the initial OCD status and the evolution of the condition. As a result, we found that foals fed with concentrates show a higher probability to develop OCD lesions (p=0.06), while foals not receiving concentrates, had a higher probability to heal from existing OCD lesions (p=0.001). This study supports the theory that management factors such as feeding or housing may influence the evolution of the osteochondrosis disease. PMID:27094134

  6. Analysis of αSMA-Labeled Progenitor Cell Commitment Identifies Notch Signaling as an Important Pathway in Fracture Healing

    PubMed Central

    Matthews, Brya G; Grcevic, Danka; Wang, Liping; Hagiwara, Yusuke; Roguljic, Hrvoje; Joshi, Pujan; Shin, Dong-Guk; Adams, Douglas J; Kalajzic, Ivo

    2016-01-01

    Fracture healing is a regenerative process that involves coordinated responses of many cell types, but characterization of the roles of specific cell populations in this process has been limited. We have identified alpha smooth muscle actin (αSMA) as a marker of a population of mesenchymal progenitor cells in the periosteum that contributes to osteochondral elements during fracture healing. Using a lineage tracing approach, we labeled αSMA-expressing cells, and characterized changes in the periosteal population during the early stages of fracture healing by histology, flow cytometry, and gene expression profiling. In response to fracture, the αSMA-labeled population expanded and began to differentiate toward the osteogenic and chondrogenic lineages. The frequency of mesenchymal progenitor cell markers such as Sca1 and PDGFRα increased after fracture. By 6 days after fracture, genes involved in matrix production and remodeling were elevated. In contrast, genes associated with muscle contraction and Notch signaling were downregulated after fracture. We confirmed that activating Notch signaling in αSMA-labeled cells inhibited differentiation into osteogenic and adipogenic lineages in vitro and ectopic bone formation in vivo. By characterizing changes in a selected αSMA-labeled progenitor cell population during fracture callus formation, we have shown that modulation of Notch signaling may determine osteogenic potential of αSMA-expressing progenitor cells during bone healing. PMID:24190076

  7. Magnetic Resonance Imaging of Ferumoxide-Labeled Mesenchymal Stem Cells in Cartilage Defects: In Vitro and In Vivo Investigations

    PubMed Central

    Henning, Tobias D.; Gawande, Rakhee; Khurana, Aman; Tavri, Sidhartha; Mandrussow, Lydia; Golovko, Daniel; Horvai, Andrew; Sennino, Barbara; McDonald, Donald; Meier, Reinhard; Wendland, Michael; Derugin, Nikita; Link, Thomas M.; Daldrup-Link, Heike E.

    2013-01-01

    The purpose of this study was to (1) compare three different techniques for ferumoxide labeling of mesenchymal stem cells (MSCs), (2) evaluate if ferumoxide labeling allows in vivo tracking of matrix-associated stem cell implants (MASIs) in an animal model, and (3) compare the magnetic resonance imaging (MRI) characteristics of ferumoxide-labeled viable and apoptotic MSCs. MSCs labeled with ferumoxide by simple incubation, protamine transfection, or Lipofectin transfection were evaluated with MRI and histopathology. Ferumoxide-labeled and unlabeled viable and apoptotic MSCs in osteochondral defects of rat knee joints were evaluated over 12 weeks with MRI. Signal to noise ratios (SNRs) of viable and apoptotic labeled MASIs were tested for significant differences using t-tests. A simple incubation labeling protocol demonstrated the best compromise between significant magnetic resonance signal effects and preserved cell viability and potential for immediate clinical translation. Labeled viable and apoptotic MASIs did not show significant differences in SNR. Labeled viable but not apoptotic MSCs demonstrated an increasing area of T2 signal loss over time, which correlated to stem cell proliferation at the transplantation site. Histopathology confirmed successful engraftment of viable MSCs. The engraftment of iron oxide–labeled MASIs by simple incubation can be monitored over several weeks with MRI. Viable and apoptotic MASIs can be distinguished via imaging signs of cell proliferation at the transplantation site. PMID:22554484

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

    PubMed

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

    2015-12-01

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

  9. Development and evaluation of a device for simultaneous uniaxial compression and optical imaging of cartilage samples in vitro.

    PubMed

    Steinert, Marian; Kratz, Marita; Jaedicke, Volker; Hofmann, Martin R; Jones, David B

    2014-10-01

    In this paper, we present a system that allows imaging of cartilage tissue via optical coherence tomography (OCT) during controlled uniaxial unconfined compression of cylindrical osteochondral cores in vitro. We describe the system design and conduct a static and dynamic performance analysis. While reference measurements yield a full scale maximum deviation of 0.14% in displacement, force can be measured with a full scale standard deviation of 1.4%. The dynamic performance evaluation indicates a high accuracy in force controlled mode up to 25 Hz, but it also reveals a strong effect of variance of sample mechanical properties on the tracking performance under displacement control. In order to counterbalance these disturbances, an adaptive feed forward approach was applied which finally resulted in an improved displacement tracking accuracy up to 3 Hz. A built-in imaging probe allows on-line monitoring of the sample via OCT while being loaded in the cultivation chamber. We show that cartilage topology and defects in the tissue can be observed and demonstrate the visualization of the compression process during static mechanical loading. PMID:25362424

  10. Current Concepts for Patellar Dislocation

    PubMed Central

    Petri, Maximilian; Ettinger, Max; Stuebig, Timo; Brand, Stephan; Krettek, Christian; Jagodzinski, Michael; Omar, Mohamed

    2015-01-01

    Context: Patellar dislocation usually occurs to the lateral side, leading to ruptures of the Medial Patellofemoral Ligament (MPFL) in about 90% of the cases. Even though several prognostic factors are identified for patellofemoral instability after patellar dislocation so far, the appropriate therapy remains a controversial issue. Evidence Acquisition: Authors searched the Medline library for studies on both surgical and conservative treatment for patellar dislocation and patellofemoral instability. Additionally, the reference list of each article was searched for additional studies. Results: A thorough analysis of the anatomical risk factors with a particular focus on patella alta, increased Tibial Tuberosity-Trochlear Groove (TT-TG) distance, trochlear dysplasia as well as torsional abnormalities should be performed early after the first dislocation to allow adequate patient counseling. Summarizing the results of all published randomized clinical trials and comparing surgical and conservative treatment after the first-time patellar dislocation until today indicated no significant evident difference for children, adolescents, and adults. Therefore, nonoperative treatment was indicated after a first-time patellar dislocation in the vast majority of patients. Conclusions: Surgical treatment for patellar dislocation is indicated primarily in case of relevant concomitant injuries such as osteochondral fractures, and secondarily for recurrent dislocations. PMID:26566512

  11. Mechanical Stress and ATP Synthesis are coupled by Mitochondrial Oxidants in Articular Cartilage

    PubMed Central

    Wolff, Katherine J; Ramakrishnan, Prem S; Brouillette, Marc J; Journot, Brice; Mckinley, Todd O; Buckwalter, JA; Martin, James A

    2013-01-01

    Metabolic adaptation of articular cartilage under joint loading is evident and matrix synthesis seems to be critically tied to ATP. Chondrocytes utilize the glycolytic pathway for energy requirements but seem to require mitochondrial reactive oxygen species (ROS) to sustain ATP synthesis. The role of ROS in regulating ATP reserves under a mechanically active environment is not clear. It is believed that physiological strains cause deformation of the mitochondria, potentially releasing ROS for energy production. We hypothesized that mechanical loading stimulates ATP synthesis via mitochondrial release of ROS. Bovine osteochondral explants were dynamically loaded at 0.5Hz with amplitude of 0.25MPa for 1 Hour. Cartilage response to mechanical loading was assessed by imaging with dihydroethidium (ROS indicator) and a Luciferase based ATP assay. Electron transport inhibitor rotenone and mitochondrial ROS scavenger MitoQ significantly suppressed mechanically induced ROS production and ATP synthesis. Our findings indicate that mitochondrial ROS are produced as a result of physiological mechanical strains. Taken together with our previous findings of ROS involvement in blunt impact injuries, mitochondrial ROS are important contributors to cartilage metabolic adaptation and their precise role in the pathogenesis of osteoarthritis warrants further investigation. PMID:22930474

  12. Stem cell origin differently affects bone tissue engineering strategies

    PubMed Central

    Mattioli-Belmonte, Monica; Teti, Gabriella; Salvatore, Viviana; Focaroli, Stefano; Orciani, Monia; Dicarlo, Manuela; Fini, Milena; Orsini, Giovanna; Di Primio, Roberto; Falconi, Mirella

    2015-01-01

    Bone tissue engineering approaches are encouraging for the improvement of conventional bone grafting technique drawbacks. Thanks to their self-renewal and multi-lineage differentiation ability, stem cells are one of the major actors in tissue engineering approaches, and among these adult mesenchymal stem cells (MSCs) hold a great promise for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs) are the first- identified and well-recognized stem cell population used in bone tissue engineering. Nevertheless, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The fruitful selection and combination of tissue engineered scaffold, progenitor cells, and physiologic signaling molecules allowed the surgeon to reconstruct the missing natural tissue. On the basis of these considerations, we analyzed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e., periodontal ligament, maxillary periosteum) as well as adipose-derived stem cells (ASCs), in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, taking into account their specific features, they could be intriguing cell sources in different stem cell-based bone/periodontal tissue regeneration approaches. PMID:26441682

  13. State of the Art: MR Imaging after Knee Cartilage Repair Surgery.

    PubMed

    Guermazi, Ali; Roemer, Frank W; Alizai, Hamza; Winalski, Carl S; Welsch, Goetz; Brittberg, Mats; Trattnig, Siegfried

    2015-10-01

    Cartilage injuries are common, especially in athletes. Because these injuries frequently affect young patients, and they have the potential to progress to osteoarthritis, treatment to alleviate symptoms and delay joint degeneration is warranted. A number of surgical techniques are available to treat focal chondral defects, including marrow stimulation, osteochondral auto- and allografting, and autologous chondrocyte implantation. Although arthroscopy is considered the standard of reference for the evaluation of cartilage before and after repair, it is invasive with associated morbidity and cannot adequately depict the deep cartilage layer and underlying bone. Magnetic resonance (MR) imaging provides unparalleled noninvasive assessment of the repair site and all other joint tissues. MR observation of cartilage repair tissue is a well-established semiquantitative scoring system for repair tissue that has primarily been used in clinical research studies. The cartilage repair osteoarthritis knee score (CROAKS) optimizes comprehensive morphologic assessment of the knee joint after cartilage repair. Furthermore, quantitative, compositional MR imaging measurements (eg, T2, T2*, T1ρ), delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC), and sodium imaging are available for biochemical assessment. These quantitative MR imaging techniques help assess collagen content and orientation, water content, and glycosaminoglycan and/or proteoglycan content both in the repair tissue as it matures and in the "native" cartilage. In this review, the authors discuss the principles of state-of-the-art morphologic and compositional MR imaging techniques for imaging of cartilage repair and their application to longitudinal studies. PMID:26402492

  14. Nondegradable hydrogels for the treatment of focal cartilage defects.

    PubMed

    Maher, S A; Doty, S B; Torzilli, P A; Thornton, S; Lowman, A M; Thomas, J D; Warren, R; Wright, T M; Myers, E

    2007-10-01

    Nondegradable materials have long been suggested for the treatment of articular cartilage defects; however, the mechanics of the implant/tissue system necessary to ensure long-term function are unknown. The objective of this study was to explore the performance of nondegradable hydrogel implants in cartilage defects. Our hypothesis was that the structural integrity of the implant and surrounding tissue would be influenced by the compressive modulus of the material used, and that superior results would be obtained with the implantation of a more compliant material. Poly(vinyl alcohol)-poly(vinyl pyrrolidone) hydrogel implants of two different moduli were implanted into osteochondral defects in a rabbit model. Six-month postoperative histological and mechanical data were used to assess the wear and fixation of the implants. The compliant implants remained well fixed and a thin layer of soft tissue grew over the surface of the implants. However, gross deformation of the compliant implants occurred and debris was evident in surrounding bone. The stiffer implants were dislocated from their implantation site, but with no accompanying evidence of debris or implant deformation. Our hypothesis that superior results would be obtained with implantation of a more compliant material was rejected; a compromise between the wear and fixation properties dependent on modulus was found. PMID:17390320

  15. Gout in a 15-year-old boy with juvenile idiopathic arthritis: a case study

    PubMed Central

    2014-01-01

    Joint pain is a common complaint in pediatrics and is most often attributed to overuse or injury. In the face of persistent, severe, or recurrent symptoms, the differential typically expands to include bony or structural causes versus rheumatologic conditions. Rarely, a child has two distinct causes for joint pain. In this case, an obese 15-year-old male was diagnosed with gout, a disease common in adults but virtually ignored in the field of pediatrics. The presence of juvenile idiopathic arthritis (JIA) complicated and delayed the consideration of this second diagnosis. Indeed, the absence of gout from this patient’s differential diagnosis resulted in a greater than two-year delay in receiving treatment. The patients’ BMI was 47.4, and he was also mis-diagnosed with osteochondritis dissecans and underwent medical treatment for JIA, assorted imaging studies, and multiple surgical procedures before the key history of increased pain with red meat ingestion, noticed by the patient, and a subsequent elevated uric acid confirmed his ultimate diagnosis. With the increased prevalence of obesity in the adolescent population, the diagnosis of gout should be an important consideration in the differential diagnosis for an arthritic joint in an overweight patient, regardless of age. PMID:24393408

  16. Absence of the medial sesamoid bone associated with metatarsophalangeal pain.

    PubMed

    Kanatli, Ulunay; Ozturk, Akif Muhtar; Ercan, Nil Gulizar Tokgoz; Ozalay, Metin; Daglar, Bulent; Yetkin, Haluk

    2006-10-01

    Pain at the first metatarsophalangeal (MTP) joint can result from inflammation, chondromalacia, flexor hallucis brevis tendinitis, osteochondritis dessecans, fracture of a sesamoid bone, avascular necrosis of sesamoids, inflamed bursae, intractable keratoses, infection, sesamoiditis, gout arthropathy, and rheumatoid arthritis. Congenital absence of a sesamoid bone is extremely rare. We present a 17-year-old male patient with pain at the plantar aspect of the right MTP joint associated with congenital absence of the medial sesamoid. There was tenderness and the range of motion was minimally restricted. He described the pain as necessitating changes in his social life. On radiographs, the medial hallucial sesamoid was absent on the right side. The MTP joint was also evaluated using magnetic resonance imaging (MRI). A metatarsal pad was prescribed and the patient was satisfied with the treatment at the 2 months follow-up period. MRI revealed no pathological tissue at the medial sesamoid site. Hallucial sesamoids absorb pressure, reduce friction, protect the tendons, act like a fulcrum to increase the mechanical force of the tendons, and provide a dynamic function to the great toe by elevating first metatarsal head. Congenital absence of these bones is very rare but we must consider it in a patient with MTP joint pain. PMID:16506237

  17. Management and Prognostic Factors for Delayed Reconstruction of Neglected Posterior Shoulder Fracture-Dislocation

    PubMed Central

    Bekmezci, Taner; Altan, Egemen

    2015-01-01

    Introduction: Posterior fracture-dislocations of the shoulder are rare conditions. Misdiagnosis can occur in 50% - 80% of the patients. Due to the size of the lesion, stability of the joint could not be achieved with transfer of subscapular tendon or tuberosity. Case Presentation: A 54-year-old male patient was referred to our hospital with a neglected posterior shoulder fracture-dislocation. Functional results of the patient, and technical informations were explained in this case report. The reverse Hill-Sachs lesion involved 40% of the articular surface. Depressed and malunited fragment was elevated, and fixated to the humeral head. Conclusions: Glenohumeral joint reduction with reconstruction of the humeral head seems to be possible even in a neglected locked posterior shoulder fracture-dislocation. If the depressed osteochondral fragment is still spheric, signs of the avascular necrosis are absent on CT, and malunion of the fragment has occurred, it is quite possible to reconstruct the head. Although results of the case are good, it is worthwhile to follow these patients for long-term complications. PMID:26848474

  18. Stem cell origin differently affects bone tissue engineering strategies.

    PubMed

    Mattioli-Belmonte, Monica; Teti, Gabriella; Salvatore, Viviana; Focaroli, Stefano; Orciani, Monia; Dicarlo, Manuela; Fini, Milena; Orsini, Giovanna; Di Primio, Roberto; Falconi, Mirella

    2015-01-01

    Bone tissue engineering approaches are encouraging for the improvement of conventional bone grafting technique drawbacks. Thanks to their self-renewal and multi-lineage differentiation ability, stem cells are one of the major actors in tissue engineering approaches, and among these adult mesenchymal stem cells (MSCs) hold a great promise for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs) are the first- identified and well-recognized stem cell population used in bone tissue engineering. Nevertheless, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The fruitful selection and combination of tissue engineered scaffold, progenitor cells, and physiologic signaling molecules allowed the surgeon to reconstruct the missing natural tissue. On the basis of these considerations, we analyzed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e., periodontal ligament, maxillary periosteum) as well as adipose-derived stem cells (ASCs), in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, taking into account their specific features, they could be intriguing cell sources in different stem cell-based bone/periodontal tissue regeneration approaches. PMID:26441682

  19. Autologous chondrocyte implantation in a novel alginate-agarose hydrogel: outcome at two years.

    PubMed

    Selmi, T A S; Verdonk, P; Chambat, P; Dubrana, F; Potel, J-F; Barnouin, L; Neyret, P

    2008-05-01

    Autologous chondrocyte implantation is an established method of treatment for symptomatic articular defects of cartilage. CARTIPATCH is a monolayer-expanded cartilage cell product which is combined with a novel hydrogel to improve cell phenotypic stability and ease of surgical handling. Our aim in this prospective, multicentre study on 17 patients was to investigate the clinical, radiological, arthroscopic and histological outcome at a minimum follow-up of two years after the implantation of autologous chondrocytes embedded in a three-dimensional alginate-agarose hydrogel for the treatment of chondral and osteochondral defects. Clinically, all the patients improved significantly. Patients with lesions larger than 3 cm(2) improved significantly more than those with smaller lesions. There was no correlation between the clinical outcome and the body mass index, age, duration of symptoms and location of the defects. The mean arthroscopic International Cartilage Repair Society score was 10 (5 to 12) of a maximum of 12. Predominantly hyaline cartilage was seen in eight of the 13 patients (62%) who had follow-up biopsies. Our findings suggest that autologous chondrocyte implantation in combination with a novel hydrogel results in a significant clinical improvement at follow-up at two years, more so for larger and deeper lesions. The surgical procedure is uncomplicated, and predominantly hyaline cartilage-like repair tissue was observed in eight patients. PMID:18450625

  20. Current concepts in the treatment of cartilage damage. A review.

    PubMed

    Musumeci, Giuseppe; Loreto, Carla; Castorina, Sergio; Imbesi, Rosa; Leonardi, Rosalia; Castrogiovanni, Paola

    2013-01-01

    A literature review of tile treatment of cartilage defects was conducted, examining the current literature on the well-known treatments. In particular, advantages and drawbacks of each of the discussed treatments were evaluated considering outcomes available in literature. The literature search was conducted on PubMed and Scopus using appropriate keywords in relation to cartilage defects. Main research articles were selected for review. Cartilage damage affects thousands of persons each year; they are treated with implants and surgery. A major problem in the treatment of cartilage defects is the inability of cartilage to repair, which reduces the effectiveness of the treatment. In addition, cyclic loading of joints further degrades cartilage even after treatment. In relation to the conditions of cartilage lesions and the features of patients, a specific treatment is required in each case. Current treatments are often unpredictable in results but result in long term improvements for many patients, especially young patients. The well established treatments such as osteochondral implants, bone marrow stimulation techniques, chondrogenic cell implantations have advantages and drawbacks, so that the search has not been interrupted for new strategies, such as scaffold materials. In this review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness. PMID:25338409

  1. Management and prevention of acute and chronic lateral ankle instability in athletic patient populations

    PubMed Central

    McCriskin, Brendan J; Cameron, Kenneth L; Orr, Justin D; Waterman, Brian R

    2015-01-01

    Acute and chronic lateral ankle instability are common in high-demand patient populations. If not managed appropriately, patients may experience recurrent instability, chronic pain, osteochondral lesions of the talus, premature osteoarthritis, and other significant long-term disability. Certain populations, including young athletes, military personnel and those involved in frequent running, jumping, and cutting motions, are at increased risk. Proposed risk factors include prior ankle sprain, elevated body weight or body mass index, female gender, neuromuscular deficits, postural imbalance, foot/ankle malalignment, and exposure to at-risk athletic activity. Prompt, accurate diagnosis is crucial, and evidence-based, functional rehabilitation regimens have a proven track record in returning active patients to work and sport. When patients fail to improve with physical therapy and external bracing, multiple surgical techniques have been described with reliable results, including both anatomic and non-anatomic reconstructive methods. Anatomic repair of the lateral ligamentous complex remains the gold standard for recurrent ankle instability, and it effectively restores native ankle anatomy and joint kinematics while preserving physiologic ankle and subtalar motion. Further preventative measures may minimize the risk of ankle instability in athletic cohorts, including prophylactic bracing and combined neuromuscular and proprioceptive training programs. These interventions have demonstrated benefit in patients at heightened risk for lateral ankle sprain and allow active cohorts to return to full activity without adversely affecting athletic performance. PMID:25793157

  2. The feasibility of using irreversible electroporation to introduce pores in bacterial cellulose scaffolds for tissue engineering.

    PubMed

    Baah-Dwomoh, Adwoa; Rolong, Andrea; Gatenholm, Paul; Davalos, Rafael V

    2015-06-01

    This work investigates the feasibility of the use of irreversible electroporation (IRE) in the biofabrication of 3D cellulose nanofibril networks via the bacterial strain Gluconacetobacter xylinus. IRE uses electrical pulses to increase membrane permeability by altering the transmembrane potential; past a threshold, damage to the cell becomes too great and leads to cell death. We hypothesized that using IRE to kill the bacteria at specific locations and particular times, we could introduce conduits in the overall scaffold by preventing cellulose biosynthesis locally. Through mathematical modeling and experimental techniques, electrical effects were investigated and the parameters for IRE of G. xylinus were determined. We found that for a specific set of parameters, an applied electric field of 8 to 12.5 kV/cm, producing a local field of 3 kV/cm, was sufficient to kill most of the bacteria and create a localized pore. However, an applied electric field of 17.5 kV/cm was required to kill all. Results suggest that IRE may be an effective tool to create scaffolds with appropriate porosity for orthopedic applications. Ideally, these engineered scaffolds could be used to successfully treat osteochondral defects. PMID:25690311

  3. Customized biomimetic scaffolds created by indirect three-dimensional printing for tissue engineering

    PubMed Central

    Lee, Ju-Yeon; Choi, Bogyu; Wu, Benjamin; Lee, Min

    2013-01-01

    Three-dimensional printing (3DP) is a rapid prototyping (RP) technique that can create complex 3D structures by inkjet printing of a liquid binder onto powder biomaterials for tissue engineering scaffolds. Direct fabrication of scaffolds from 3DP, however, imposes a limitation on material choices by manufacturing processes. In this study, we report an indirect 3DP approach wherein a positive replica of desired shapes was printed using gelatin particles, and the final scaffold was directly produced from the printed mold. To create patient-specific scaffolds that match precisely to a patient’s external contours, we integrated our indirect 3DP technique with imaging technologies and successfully created custom scaffolds mimicking human mandibular condyle using polycaprolactone (PCL) and chitosan (CH) for potential osteochondral tissue engineering. To test the ability of the technique to precisely control the internal morphology of the scaffolds, we created orthogonal interconnected channels within the scaffolds using computer-aided-design (CAD) models. Because very few biomaterials are truly osteoinductive, we modified inert 3D printed materials with bioactive apatite coating. The feasibility of these scaffolds to support cell growth was investigated using bone marrow stromal cells (BMSC). The BMSCs showed good viability in the scaffolds, and the apatite-coating further enhanced cellular spreading and proliferation. This technique may be valuable for complex scaffold fabrication. PMID:24060622

  4. Management and prevention of acute and chronic lateral ankle instability in athletic patient populations.

    PubMed

    McCriskin, Brendan J; Cameron, Kenneth L; Orr, Justin D; Waterman, Brian R

    2015-03-18

    Acute and chronic lateral ankle instability are common in high-demand patient populations. If not managed appropriately, patients may experience recurrent instability, chronic pain, osteochondral lesions of the talus, premature osteoarthritis, and other significant long-term disability. Certain populations, including young athletes, military personnel and those involved in frequent running, jumping, and cutting motions, are at increased risk. Proposed risk factors include prior ankle sprain, elevated body weight or body mass index, female gender, neuromuscular deficits, postural imbalance, foot/ankle malalignment, and exposure to at-risk athletic activity. Prompt, accurate diagnosis is crucial, and evidence-based, functional rehabilitation regimens have a proven track record in returning active patients to work and sport. When patients fail to improve with physical therapy and external bracing, multiple surgical techniques have been described with reliable results, including both anatomic and non-anatomic reconstructive methods. Anatomic repair of the lateral ligamentous complex remains the gold standard for recurrent ankle instability, and it effectively restores native ankle anatomy and joint kinematics while preserving physiologic ankle and subtalar motion. Further preventative measures may minimize the risk of ankle instability in athletic cohorts, including prophylactic bracing and combined neuromuscular and proprioceptive training programs. These interventions have demonstrated benefit in patients at heightened risk for lateral ankle sprain and allow active cohorts to return to full activity without adversely affecting athletic performance. PMID:25793157

  5. Ferumoxytol: a new, clinically applicable label for stem-cell tracking in arthritic joints with MRI

    PubMed Central

    Khurana, Aman; Nejadnik, Hossein; Chapelin, Fanny; Lenkov, Olga; Gawande, Rakhee; Lee, Sungmin; Gupta, Sandeep N; Aflakian, Nooshin; Derugin, Nikita; Messing, Solomon; Lin, Guiting; Lue, Tom F; Pisani, Laura; Daldrup-Link, Heike E

    2013-01-01

    Aim To develop a clinically applicable MRI technique for tracking stem cells in matrix-associated stem-cell implants, using the US FDA-approved iron supplement ferumoxytol. Materials & methods Ferumoxytol-labeling of adipose-derived stem cells (ADSCs) was optimized in vitro. A total of 11 rats with osteochondral defects of both femurs were implanted with ferumoxytol- or ferumoxides-labeled or unlabeled ADSCs, and underwent MRI up to 4 weeks post matrix-associated stem-cell implant. The signal-to-noise ratio of different matrix-associated stem-cell implant was compared with t-tests and correlated with histopathology. Results An incubation concentration of 500 µg iron/ml ferumoxytol and 10 µg/ml protamine sulfate led to significant cellular iron uptake, T2 signal effects and unimpaired ADSC viability. In vivo, ferumoxytol-and ferumoxides-labeled ADSCs demonstrated significantly lower signal-to-noise ratio values compared with unlabeled controls (p < 0.01). Histopathology confirmed engraftment of labeled ADSCs, with slow dilution of the iron label over time. Conclusion Ferumoxytol can be used for in vivo tracking of stem cells with MRI. PMID:23534832

  6. Repair and tissue engineering techniques for articular cartilage

    PubMed Central

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

    2015-01-01

    Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of regenerative biological products that over the next decade could revolutionize joint care by functionally healing articular cartilage. These products include cell-based and cell-free materials such as autologous and allogeneic cell-based approaches and multipotent and pluripotent stem-cell-based techniques. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed. PMID:25247412

  7. Development and evaluation of a device for simultaneous uniaxial compression and optical imaging of cartilage samples in vitro

    SciTech Connect

    Steinert, Marian; Kratz, Marita; Jones, David B.; Jaedicke, Volker; Hofmann, Martin R.

    2014-10-15

    In this paper, we present a system that allows imaging of cartilage tissue via optical coherence tomography (OCT) during controlled uniaxial unconfined compression of cylindrical osteochondral cores in vitro. We describe the system design and conduct a static and dynamic performance analysis. While reference measurements yield a full scale maximum deviation of 0.14% in displacement, force can be measured with a full scale standard deviation of 1.4%. The dynamic performance evaluation indicates a high accuracy in force controlled mode up to 25 Hz, but it also reveals a strong effect of variance of sample mechanical properties on the tracking performance under displacement control. In order to counterbalance these disturbances, an adaptive feed forward approach was applied which finally resulted in an improved displacement tracking accuracy up to 3 Hz. A built-in imaging probe allows on-line monitoring of the sample via OCT while being loaded in the cultivation chamber. We show that cartilage topology and defects in the tissue can be observed and demonstrate the visualization of the compression process during static mechanical loading.

  8. Bioinspired nanofibers support chondrogenesis for articular cartilage repair

    PubMed Central

    Coburn, Jeannine M.; Gibson, Matthew; Monagle, Sean; Patterson, Zachary; Elisseeff, Jennifer H.

    2012-01-01

    Articular cartilage repair remains a significant and growing clinical challenge with the aging population. The native extracellular matrix (ECM) of articular cartilage is a 3D structure composed of proteinaceous fibers and a hydrogel ground substance that together provide the physical and biological cues to instruct cell behavior. Here we present fibrous scaffolds composed of poly(vinyl alcohol) and the biological cue chondroitin sulfate with fiber dimensions on the nanoscale for application to articular cartilage repair. The unique, low-density nature of the described nanofiber scaffolds allows for immediate cell infiltration for optimal tissue repair. The capacity for the scaffolds to facilitate cartilage-like tissue formation was evaluated in vitro. Compared with pellet cultures, the nanofiber scaffolds enhance chondrogenic differentiation of mesenchymal stems cells as indicated by increased ECM production and cartilage specific gene expression while also permitting cell proliferation. When implanted into rat osteochondral defects, acellular nanofiber scaffolds supported enhanced chondrogenesis marked by proteoglycan production minimally apparent in defects left empty. Furthermore, inclusion of chondroitin sulfate into the fibers enhanced cartilage-specific type II collagen synthesis in vitro and in vivo. By mimicking physical and biological cues of native ECM, the nanofiber scaffolds enhanced cartilaginous tissue formation, suggesting their potential utility for articular cartilage repair. PMID:22665791

  9. Regulatory Challenges for Cartilage Repair Technologies.

    PubMed

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

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

  10. NFAT restricts osteochondroma formation from entheseal progenitors

    PubMed Central

    Ge, Xianpeng; Tsang, Kelly; He, Lizhi; Garcia, Roberto A.; Ermann, Joerg; Mizoguchi, Fumitaka; Zhang, Minjie; Zhou, Bin; Zhou, Bin; Aliprantis, Antonios O.

    2016-01-01

    Osteochondromas are common benign osteocartilaginous tumors in children and adolescents characterized by cartilage-capped bony projections on the surface of bones. These tumors often cause pain, deformity, fracture, and musculoskeletal dysfunction, and they occasionally undergo malignant transformation. The pathogenesis of osteochondromas remains poorly understood. Here, we demonstrate that nuclear factor of activated T cells c1 and c2 (NFATc1 and NFATc2) suppress osteochondromagenesis through individual and combinatorial mechanisms. In mice, conditional deletion of NFATc1 in mesenchymal limb progenitors, Scleraxis-expressing (Scx-expressing) tendoligamentous cells, or postnatally in Aggrecan-expressing cells resulted in osteochondroma formation at entheses, the insertion sites of ligaments and tendons onto bone. Combinatorial deletion of NFATc1 and NFATc2 gave rise to larger and more numerous osteochondromas in inverse proportion to gene dosage. A population of entheseal NFATc1- and Aggrecan-expressing cells was identified as the osteochondroma precursor, previously believed to be growth plate derived or perichondrium derived. Mechanistically, we show that NFATc1 restricts the proliferation and chondrogenesis of osteochondroma precursors. In contrast, NFATc2 preferentially inhibits chondrocyte hypertrophy and osteogenesis. Together, our findings identify and characterize a mechanism of osteochondroma formation and suggest that regulating NFAT activity is a new therapeutic approach for skeletal diseases characterized by defective or exaggerated osteochondral growth. PMID:27158674

  11. Reinforcement of Mono- and Bi-layer Poly(Ethylene Glycol) Hydrogels with a Fibrous Collagen Scaffold.

    PubMed

    Kinneberg, K R C; Nelson, A; Stender, M E; Aziz, A H; Mozdzen, L C; Harley, B A C; Bryant, S J; Ferguson, V L

    2015-11-01

    Biomaterial-based tissue engineering strategies hold great promise for osteochondral tissue repair. Yet significant challenges remain in joining highly dissimilar materials to achieve a biomimetic, mechanically robust design for repairing interfaces between soft tissue and bone. This study sought to improve interfacial properties and function in a bi-layer hydrogel interpenetrated with a fibrous collagen scaffold. 'Soft' 10% (w/w) and 'stiff' 30% (w/w) PEGDM was formed into mono- or bi-layer hydrogels possessing a sharp diffusional interface. Hydrogels were evaluated as single-(hydrogel only) or multi-phase (hydrogel + fibrous scaffold penetrating throughout the stiff layer and extending >500 μm into the soft layer). Including a fibrous scaffold into both soft and stiff mono-layer hydrogels significantly increased tangent modulus and toughness and decreased lateral expansion under compressive loading. Finite element simulations predicted substantially reduced stress and strain gradients across the soft-stiff hydrogel interface in multi-phase, bilayer hydrogels. When combining two low moduli constituent materials, composites theory poorly predicts the observed, large modulus increases. These results suggest material structure associated with the fibrous scaffold penetrating within the PEG hydrogel as the major contributor to improved properties and function-the hydrogel bore compressive loads and the 3D fibrous scaffold was loaded in tension thus resisting lateral expansion. PMID:26001970

  12. Cell-based cartilage repair strategies in the horse.

    PubMed

    Ortved, Kyla F; Nixon, Alan J

    2016-02-01

    Damage to the articular cartilage surface is common in the equine athlete and, due to the poor intrinsic healing capabilities of cartilage, can lead to osteoarthritis (OA). Joint disease and OA are the leading cause of retirement in equine athletes and currently there are no effective treatments to stop the progression of OA. Several different cell-based strategies have been investigated to bolster the weak regenerative response of chondrocytes. Such techniques aim to restore the articular surface and prevent further joint degradation. Cell-based cartilage repair strategies include enhancement of endogenous repair mechanisms by recruitment of stem cells from the bone marrow following perforation of the subchondral bone plate; osteochondral implantation; implantation of chondrocytes that are maintained in defects by either a membrane cover or scaffold, and transplantation of mesenchymal stem cells into cartilage lesions. More recently, bioengineered cartilage and scaffoldless cartilage have been investigated for enhancing repair. This review article focuses on the multitude of cell-based repair techniques for cartilage repair across several species, with special attention paid to the horse. PMID:26702950

  13. Arthroscopic chondral cyst excision in a stiff Perthes' hip.

    PubMed

    Pardiwala, Dinshaw N; Nagda, Taral V

    2007-08-01

    Persistent hip stiffness in Perthes' disease indicates a poor prognosis and is a therapeutic challenge. We report a case of a 13-year-old boy with a stiff Perthes' hip that was nonresponsive to prolonged nonsurgical treatment. Imaging revealed Catterall group IV Perthes' disease in an advanced reossification stage, with a focal defect in the weight-bearing area of the capital femoral epiphysis. A focal, compressible chondral elevation was detected on hip arthroscopy; on incision, flocculent fluid was released. After the cyst was excised, microfracture revascularization of the chondral defect was undertaken. Postoperatively, the patient had immediate pain relief, correction of deformity, and restoration of painless range of motion; this has continued for 4 years since surgery was performed. Persistence of an unhealed necrotic segment in Perthes' disease has traditionally been associated with osteochondritis dissecans; however, in this case, the unhealed and nonossified segment produced an elevated painful chondral cyst that caused spasm and stiffness of the hip. Although 2 distinct types of chondral lesions have been described in Perthes' disease, stiffness arising because of these lesions has not been reported. Patients with this unusual third type of chondral lesion of the capital femoral epiphysis, which causes persistent stiffness in Perthes' hip, may be identified and successfully treated with the use of arthroscopic techniques. PMID:17681219

  14. Osteochondroses in athletes.

    PubMed Central

    Orava, S.; Virtanen, K.

    1982-01-01

    Osteochondroses are disorders of primary and secondary growth centres, or lesions at the apophyseal or epiphyseal growth areas of bones. Although there are many types of osteochondroses, the history, clinical symptoms and findings as well as radiological findings are typical. Physical exercise is one of the factors that provokes symptoms. In a series of 185 osteochondroses in active young athletes, there were 18 different disorders. The commonest were Osgood-Schlatter's disease, Sever's disease, osteochondritis dissecans of the femoral condyles, various other patellar osteochondroses and Scheuermann's disease. Most of the athletes were from individual events; track and field sports (53.5%), cross-country skiing (8.1%), gymnastics (3.2%) and power events (2.7%). Of the team sports soccer produced the most (20.0%). The treatment was conservative in 84.3% and operative in 15.7%. The duration of symptoms in these athletes persisted in about 43% for less than one year and in 57% for more. The late changes of osteodhondroses do not cause serious risks for a normal life, if the treatment is active and the follow-up efficient. Images p161-a p161-b Fig. 2 Fig. 3 C Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 p168-a PMID:7139227

  15. LIMPING IN CHILDREN

    PubMed Central

    Santili, Cláudio; Júnior, Wilson Lino; Goiano, Ellen de Oliveira; Lins, Romero Antunes Barreto; Waisberg, Gilberto; Braga, Susana dos Reis; Akkari, Miguel

    2015-01-01

    Limping in children is a common complaint at pediatric, pediatric orthopaedic offices and in emergency rooms. There are several causes for this condition, and identifying them is a challenge. The older the patient, the better the anamnesis and more detailed the physical examination will be, enabling an easier medical assessment for searching the source of the disorder. In order to make the approach easier, three age groups can and should be considered. Among infants (1 to 3 years old), diagnosis will most likely be: transitory synovitis, septic arthritis, neurological disorders (mild brain palsy (BP) and muscular dystrophy), congenital hip dislocation (CHD), varus thigh, juvenile rheumatoid arthritis (JRA) and neoplasias (osteoid osteoma, leukemia); in the scholar age group, between 4 and 10 years old, in addition to the diagnoses above, Legg-Calvé-Perthes disease, discoid meniscus, inferior limbs discrepancy and unspecific muscular pain; in adolescents (11 to 15 years old): slipped capital femoral epiphysis, congenital hip dislocation, chondrolysis, overuse syndromes, dissecans osteochondritis, and tarsal coalition. The purpose of this study is to provide an update on how to approach pediatric patients presenting with limping, and to discuss its potential causes. PMID:27022509

  16. The Transient Chondrocyte Phenotype in Human Osteophytic Cartilage

    PubMed Central

    Klinger, Patricia; Beyer, Christian; Ekici, Arif B.; Carl, Hans-Dieter; Schett, Georg; Swoboda, Bernd; Hennig, Friedrich F.

    2013-01-01

    Objective: To identify factors that are responsible for the phenotypic differences between transient chondrocytes within human osteophytes prone to endochondral ossification and permanent chondrocytes within articular cartilage persisting for decades. Methods: Differential gene expression of chondrocytes from human osteophytes or from articular cartilage was detected by cDNA microarray analysis. The expression of pigment epithelium-derived factor (PEDF), one of the most impressively differentially expressed genes, was validated by quantitative reverse transcriptase polymerase chain reaction as well as immunohistochemistry. The mode of action of PEDF was explored by cell viability assays and by detecting target genes. Results: PEDF mRNA expression was upregulated by 118.5-fold (P = 0.01) in human osteophytic cartilage compared with articular cartilage, which was reflected by strong immunostaining for PEDF in the cartilaginous layer of osteophytes but largely negative staining in articular cartilage. Elevated levels of PEDF in osteophytes were associated with enhanced apoptosis. PEDF increased the expression of the proapoptotic factor FasL and induced cell death in cell culture. Osteochondral progenitor cells were more responsive to PEDF than differentiated articular chondrocytes. Conclusions: The induction of the proapoptotic factor PEDF within the osteophyte cartilage suggests a molecular concept for the transient chondrocyte phenotype that arises from progenitor cells and is prone to terminal differentiation and cell death. PMID:26069671

  17. [Catheter- associated bacteremia caused by Ochrobactrum anthropi].

    PubMed

    Soloaga, Rolando; Carrion, Natalia; Pidone, Juan; Guelfand, Liliana; Margari, Alejandra; Altieri, Roxana

    2009-01-01

    Ochrobactrum anthropi is a non-glucose fermentative, aerobic gram-negative bacillus, formerly known as Achromobacter sp or CDC group Vd. It has been isolated from the environment and from infections in usually immunocompromised human beings. The documented infections frequently involved catheter related bacteremia whereas endophthalmitis, urinary infections, meningitis, endocarditis, hepatic abscess, osteochondritis, pelvic abscess and pancreatic abscess were rarely involved. Here it is presented the case of a male patient aged 69 years with sustained hypotension, four day febrile syndrome, chill, lavish perspiration and sensorium deterioration. He had type 2 diabetes and antecedent of cerebrovascular accident. A double-lumen dialysis catheter was present due to chronic renal insufficiency. An episode of catheter-related bloodstream infection was documented by using Bact-Alert Blood Culture System and Differential-Time-to-Positivity Method for central venous catheter versus peripheral blood cultures (>120 min). Once removed, it was confirmed through Maki semi quantitative technique (>15 FCU). The microorganism was identified by API 20NE and Vitek 1 as Ochrobactrum anthropi. PMID:20053608

  18. A Brief Review of Infrequent Spontaneous Findings, Peculiar Anatomical Microscopic Features, and Potential Artifacts in Göttingen Minipigs.

    PubMed

    McInnes, E F; McKeag, S

    2016-04-01

    Minipigs are now used in greater numbers in contract research organizations (CROs) as well as in the pharmaceutical industry. Most CROs or pharmaceutical companies use the Göttingen minipig, which displays a number of important background lesions. This review will discuss some of the more infrequent minipig background changes. Porcine stress syndrome is an autosomal recessive pharmacogenetic disorder in minipigs causing malignant hyperthermia and muscle necrosis. Possible triggers, clinical pathology as well as heart, muscle, liver, lung, and kidney histopathology are discussed. Additional spontaneous changes, background findings, and peculiar anatomical and histological features include thrombocytopenic purpura syndrome, spontaneous glomerulonephritis, osteochondritis, ellipsoids, or Schweigger-Seidel sheaths in the spleen, as well as the presence of a perimesenteric plexus adjacent to mesenteric lymph nodes, squamous epithelial metaplasia of the salivary gland, and cupping of the optic disk in the minipig eye. In order to maximize the data gained from minipig studies, the interpretation of pathology findings requires the input of experienced pathologists who understand the significance of artifacts and spontaneous, background lesions in minipigs and can distinguish these from induced lesions. PMID:26839330

  19. Research Advancements in Porcine Derived Mesenchymal Stem Cells.

    PubMed

    Bharti, Dinesh; Shivakumar, Sharath Belame; Subbarao, Raghavendra Baregundi; Rho, Gyu-Jin

    2016-01-01

    In the present era of stem cell biology, various animals such as Mouse, Bovine, Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem cells (MSCs before their actual use for stem cell based application in humans. Among them pigs have many similarities to humans in the form of organ size, physiology and their functioning, therefore they have been considered as a valuable model system for in vitro studies and preclinical assessments. Easy assessability, few ethical issues, successful MSC isolation from different origins like bone marrow, skin, umbilical cord blood, Wharton's jelly, endometrium, amniotic fluid and peripheral blood make porcine a good model for stem cell therapy. Porcine derived MSCs (pMSCs have shown greater in vitro differentiation and transdifferention potential towards mesenchymal lineages and specialized lineages such as cardiomyocytes, neurons, hepatocytes and pancreatic beta cells. Immunomodulatory and low immunogenic profiles as shown by autologous and heterologous MSCs proves them safe and appropriate models for xenotransplantation purposes. Furthermore, tissue engineered stem cell constructs can be of immense importance in relation to various osteochondral defects which are difficult to treat otherwise. Using pMSCs successful treatment of various disorders like Parkinson's disease, cardiac ischemia, hepatic failure, has been reported by many studies. Here, in this review we highlight current research findings in the area of porcine mesenchymal stem cells dealing with their isolation methods, differentiation ability, transplantation applications and their therapeutic potential towards various diseases. PMID:26201864

  20. Interventional articular and para-articular knee procedures.

    PubMed

    Lalam, Radhesh K; Winn, Naomi; Cassar-Pullicino, Victor N

    2016-03-01

    The knee is a common area of the body to undergo interventional procedures. This article discusses image-guided interventional issues specific to the knee area. The soft tissues in and around the knee are frequently affected by sport-related injuries and often need image-guided intervention. This article details the specific technical issues related to intervention in these soft tissues, including the iliotibial tract, fat pads, patellar tendon and other tendons, bursae and the meniscus. Most often, simple procedures such as injection and aspiration are performed without image guidance. Rarely image-guided diagnostic arthrography and therapeutic joint injections are necessary. The technique, indications and diagnostic considerations for arthrography are discussed in this article. Primary bone and soft-tissue tumours may involve the knee and adjacent soft tissues. Image-guided biopsies are frequently necessary for these lesions; this article details the technical issues related to image-guided biopsy around the knee. A number of newer ablation treatments are now available, including cryoablation, high-frequency ultrasound and microwave ablation. Radiofrequency ablation, however, still remains the most commonly employed ablation technique. The indications, technical and therapeutic considerations related to the application of this technique around the knee are discussed here. Finally, we briefly discuss some newer, but as of yet, unproven image-guided interventions for osteochondral lesions and Brodie's abscess. PMID:26682669

  1. Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases.

    PubMed

    Patzkowski, Michael S

    2016-03-01

    Ehlers-Danlos syndrome is an inherited disorder of collagen production that results in multiorgan dysfunction. Patients with hypermobility type display skin hyperextensibility and joint laxity, which can result in chronic joint instability, dislocation, peripheral neuropathy, and severe musculoskeletal pain. A bleeding diathesis can be found in all subtypes of varying severity despite a normal coagulation profile. There have also been reports of resistance to local anesthetics in these patients. Several sources advise against the use of regional anesthesia in these patients citing the 2 previous features. There have been reports of successful neuraxial anesthesia, but few concerning peripheral nerve blocks, none of which describe nerves of the lower extremity. This report describes 2 cases of successful peripheral regional anesthesia in the lower extremity. In case 1, a 16-year-old adolescent girl with hypermobility type presented for osteochondral grafting of tibiotalar joint lesions. She underwent a popliteal sciatic (with continuous catheter) and femoral nerve block under ultrasound guidance. She proceeded to surgery and tolerated the procedure under regional block and intravenous sedation. She did not require any analgesics for the following 15 hours. In case 2, an 18-year-old woman with hypermobility type presented for medial patellofemoral ligament reconstruction for chronic patella instability. She underwent a saphenous nerve block above the knee with analgesia in the distribution of the saphenous nerve lasting for approximately 18 hours. There were no complications in either case. Prohibitions against peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type, appear unwarranted. PMID:26897449

  2. Current concepts: tissue engineering and regenerative medicine applications in the ankle joint

    PubMed Central

    Correia, S. I.; Pereira, H.; Silva-Correia, J.; Van Dijk, C. N.; Espregueira-Mendes, J.; Oliveira, J. M.; Reis, R. L.

    2014-01-01

    Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving restoration of biological functions and rehabilitation. The mainstream components required to obtain a functional regeneration of tissues may include biodegradable scaffolds, drugs or growth factors and different cell types (either autologous or heterologous) that can be cultured in bioreactor systems (in vitro) prior to implantation into the patient. Particularly in the ankle, which is subject to many different injuries (e.g. acute, chronic, traumatic and degenerative), there is still no definitive and feasible answer to ‘conventional’ methods. This review aims to provide current concepts of TERM applications to ankle injuries under preclinical and/or clinical research applied to skin, tendon, bone and cartilage problems. A particular attention has been given to biomaterial design and scaffold processing with potential use in osteochondral ankle lesions. PMID:24352667

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

    PubMed

    Blum, Michelle M; Ovaert, Timothy C

    2013-10-01

    The mechanical and tribological properties of a novel biomaterial, a boundary lubricant functionalized hydrogel, were investigated and compared to natural cartilage tissue. This low friction hydrogel material was developed for use as a synthetic replacement for focal defects in articular cartilage. The hydrogel was made by functionalizing the biocompatible polymer polyvinyl alcohol with a carboxylic acid derivative boundary lubricant molecule. Two different gel processing techniques were used to create the hydrogels. The first method consisted of initially functionalizing the boundary lubricant to the polyvinyl alcohol and then creating hydrogels by physically crosslinking the reacted polymer. The second method consisted of creating non-functionalized polyvinyl alcohol hydrogels and then performing the functionalization reaction on the fully formed gel. Osteochondral bovine samples were collected and replicate experiments were conducted to compare the mechanical and tribological performance of the boundary lubricant functionalized hydrogels to non-functionalized hydrogels and native cartilage. Friction experiments displayed a maximum decrease in friction coefficient of 70% for the functionalized hydrogels compared to neat polyvinyl alcohol. Indentation investigated the elastic modulus of the hydrogels, demonstrating that stability of the hydrogel was affected by processing method. Hydrogel performance was within the lower ranges of natural cartilage tested under the exact same conditions, showing the potential of the boundary lubricant functionalized hydrogels to perform as a biomimetic synthetic articular cartilage replacement. PMID:23910356

  4. Periosteum derived stem cells for regenerative medicine proposals: Boosting current knowledge

    PubMed Central

    Ferretti, Concetta; Mattioli-Belmonte, Monica

    2014-01-01

    Periosteum is a thin fibrous layer that covers most bones. It resides in a dynamic mechanically loaded environment and provides a niche for pluripotent cells and a source for molecular factors that modulate cell behaviour. Elucidating periosteum regenerative potential has become a hot topic in orthopaedics. This review discusses the state of the art of osteochondral tissue engineering rested on periosteum derived progenitor cells (PDPCs) and suggests upcoming research directions. Periosteal cells isolation, characterization and migration in the site of injury, as well as their differentiation, are analysed. Moreover, the role of cell mechanosensing and its contribution to matrix organization, bone microarchitecture and bone stenght is examined. In this regard the role of periostin and its upregulation under mechanical stress in order to preserve PDPC survival and bone tissue integrity is contemplated. The review also summarized the role of the periosteum in the field of dentistry and maxillofacial reconstruction. The involvement of microRNAs in osteoblast differentiation and in endogenous tissue repair is explored as well. Finally the novel concept of a guided bone regeneration based on the use of periosteum itself as a smart material and the realization of constructs able to mimic the extracellular matrix features is talked out. Additionally, since periosteum can differentiate into insulin producing cells it could be a suitable source in allogenic transplantations. That innovative applications would take advantage from investigations aimed to assess PDPC immune privilege. PMID:25126377

  5. Stem cell regulatory function mediated by expression of a novel mouse Oct4 pseudogene

    SciTech Connect

    Lin, Huey; Shabbir, Arsalan; Molnar, Merced; Lee, Techung . E-mail: chunglee@buffalo.edu

    2007-03-30

    Multiple pseudogenes have been proposed for embryonic stem (ES) cell-specific genes, and their abundance suggests that some of these potential pseudogenes may be functional. ES cell-specific expression of Oct4 regulates stem cell pluripotency and self-renewing state. Although Oct4 expression has been reported in adult tissues during gene reprogramming, the detected Oct4 signal might be contributed by Oct4 pseudogenes. Among the multiple Oct4 transcripts characterized here is a {approx}1 kb clone derived from P19 embryonal carcinoma stem cells, which shares a {approx}87% sequence homology with the parent Oct4 gene, and has the potential of encoding an 80-amino acid product (designated as Oct4P1). Adenoviral expression of Oct4P1 in mesenchymal stem cells promotes their proliferation and inhibits their osteochondral differentiation. These dual effects of Oct4P1 are reminiscent of the stem cell regulatory function of the parent Oct4, and suggest that Oct4P1 may be a functional pseudogene or a novel Oct4-related gene with a unique function in stem cells.

  6. Early Intra-Articular Complement Activation in Ankle Fractures

    PubMed Central

    Salzmann, Gian M.; Niemeyer, Philipp; Guo, Renfeng

    2014-01-01

    Cytokine regulation possibly influences long term outcome following ankle fractures, but little is known about synovial fracture biochemistry. Eight patients with an ankle dislocation fracture were included in a prospective case series and matched with patients suffering from grade 2 osteochondritis dissecans (OCD) of the ankle. All fractures needed external fixation during which joint effusions were collected. Fluid analysis was done by ELISA measuring aggrecan, bFGF, IL-1β, IGF-1, and the complement components C3a, C5a, and C5b-9. The time periods between occurrence of fracture and collection of effusion were only significantly associated with synovial aggrecan and C5b-9 levels (P < 0.001). Furthermore, synovial expressions of both proteins correlated with each other (P < 0.001). Although IL-1β expression was relatively low, intra-articular levels correlated with C5a (P < 0.01) and serological C-reactive protein concentrations 2 days after surgery (P < 0.05). Joint effusions were initially dominated by neutrophils, but the portion of monocytes constantly increased reaching 50% at day 6 after fracture (P < 0.02). Whereas aggrecan and IL-1β concentrations were not different in fracture and OCD patients, bFGF, IGF-1, and all complement components were significantly higher concentrated in ankle joints with fractures (P < 0.01). Complement activation and inflammatory cell infiltration characterize the joint biology following acute ankle fractures. PMID:24967368

  7. High density infill in cracks and protrusions from the articular calcified cartilage in osteoarthritis in standardbred horse carpal bones.

    PubMed

    Laverty, Sheila; Lacourt, Mathieu; Gao, Chan; Henderson, Janet E; Boyde, Alan

    2015-01-01

    We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC mineralizing (tidemark) front (MF) into hyaline articular cartilage (HAC). We hypothesized and we show that 20-µm µCT resolution in 10-mm diameter samples is sufficient to detect HDMI and HDMP: these are lost upon tissue decalcification for routine paraffin wax histology owing to their predominant mineral content. The findings show that µCT is sufficient to discover HDMI and HDMP, which were seen in 2/10 controls, 6/9 early OA and 8/10 advanced OA cases. This is the first report of HDMI and HDMP in the equine carpus and in the Standardbred breed and the first to rely solely on µCT. HDMP are a candidate cause for mechanical tissue destruction in OA. PMID:25927581

  8. Development of an equine groove model to induce metacarpophalangeal osteoarthritis: a pilot study on 6 horses.

    PubMed

    Maninchedda, Ugo; Lepage, Olivier M; Gangl, Monika; Hilairet, Sandrine; Remandet, Bernard; Meot, Francoise; Penarier, Geraldine; Segard, Emilie; Cortez, Pierre; Jorgensen, Christian; Steinberg, Régis

    2015-01-01

    The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or "grooves" were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy. PMID:25680102

  9. GROSS AND HISTOPATHOLOGIC CORRELATION OF LOW-FIELD MAGNETIC RESONANCE IMAGING FINDINGS IN THE STIFLE OF ASYMPTOMATIC HORSES.

    PubMed

    Santos, Marcos P; Gutierrez-Nibeyro, Santiago D; McKnight, Alexia L; Singh, Kuldeep

    2015-01-01

    With the recent introduction of a 0.25T rotating MRI system, clinical evaluation of the equine stifle joint is now possible in the average equine athlete. A recent publication described common abnormalities of horses with stifle lameness detected with a low-field MRI system; however, postmortem corroboration of the lesions detected was not possible. Therefore, our objective was to compare postmortem findings with low-field MRI findings in equine cadaver stifle joints. Ten fresh cadaver stifle joints from horses without clinical signs of stifle disease were evaluated using low-field MRI, gross dissection, and histopathology. In eight stifles, either the lateral or medial cranial meniscotibial ligament had an irregular shape, fiber separation, or moderate abnormal signal intensity (SI) on all sequences. In five stifles, the medial femoral condyle had articular cartilage fibrillation with or without an osteochondral defect over the weight bearing surface of the medial femoral condyle. All stifles had abnormal SI on all sequences within the patellar ligaments that corresponded with adipose tissue infiltrating between the collagen bundles. Other abnormalities identified included articular cartilage fibrillation of the tibial condyles in three stifles, and articular cartilage fibrillation with chondral defects in the patella in three stifles. All abnormalities detected with low-field MRI were corroborated by gross dissection. Findings from the current study supported the use of low-field MRI for detection of stifle joint lesions in horses and demonstrated that some stifle joint pathologies may be subclinical in horses. PMID:25545132

  10. Hip arthroscopy: current indications, treatment options, and management issues.

    PubMed

    Kelly, Bryan T; Williams, Riley J; Philippon, Marc J

    2003-01-01

    The management of hip injuries in athletes has evolved significantly in the past few years with the advancement of arthroscopic techniques. The application of minimally invasive surgical techniques has facilitated relatively rapid returns to sporting activity in both recreational and elite athletes. Recent advancements in both hip arthroscopy and magnetic resonance imaging have elucidated several sources of intraarticular abnormalities that result in chronic and disabling hip symptoms. Many of these conditions were previously unrecognized and, thus, left untreated. Current indications for hip arthroscopy include the presence of symptomatic acetabular labral tears, hip capsule laxity and instability, chondral lesions, osteochondritis dissecans, ligamentum teres injuries, snapping hip syndrome, iliopsoas bursitis, and loose bodies (for example, synovial chondromatosis). Less common indications include management of osteonecrosis of the femoral head, bony impingment, synovial abnormalities, crystalline hip arthropathy (gout and pseudogout), infection, and posttraumatic intraarticular debris. In rare cases, hip arthroscopy can be used to temporize the symptoms of mild-to-moderate hip osteoarthritis with associated mechanical symptoms. This article discusses the current clinical and radiographic methods to detect early hip joint disease and the current indications and surgical techniques of hip arthroscopy. PMID:14623676

  11. Sports-related overuse injuries in children.

    PubMed

    Launay, F

    2015-02-01

    Increased intensity of sports activities combined with a decrease in daily physical activity is making overuse injuries in children more common. These injuries are located mainly in the epiphyseal cartilage. The broad term for these injuries is osteochondrosis, rather than osteochondritis, which more specifically refers to inflammatory conditions of bone and cartilage. The osteochondrosis may be epiphyseal, physeal, or apophyseal, depending on the affected site. The condition can either be in the primary deformans form or the dissecans form. While there is no consensus on the etiology of osteochondrosis, multiple factors seem to be involved: vascular, traumatic, or even microtraumatic factors. Most overuse injuries involve the lower limbs, especially the knees, ankle and feet. The most typical are Osgood-Schlatter disease and Sever's disease; in both conditions, the tendons remain relatively short during the pubescent grown spurt. The main treatment for these injuries is temporary suspension of athletic activities, combined with physical therapy in many cases. Surgery may be performed if conservative treatment fails. It is best, however, to try to prevent these injuries by analyzing and correcting problems with sports equipment, lifestyle habits, training intensity and the child's level of physical activity, and by avoiding premature specialization. Pain in children during sports should not be considered normal. It is a warning sign of overtraining, which may require the activity to be modified, reduced or even discontinued. PMID:25555804

  12. Regenerating Articular Tissue by Converging Technologies

    PubMed Central

    Paoluzzi, Luca; Pieper, Jeroen; de Wijn, Joost R.; van Blitterswijk, Clemens A.

    2008-01-01

    Scaffolds for osteochondral tissue engineering should provide mechanical stability, while offering specific signals for chondral and bone regeneration with a completely interconnected porous network for cell migration, attachment, and proliferation. Composites of polymers and ceramics are often considered to satisfy these requirements. As such methods largely rely on interfacial bonding between the ceramic and polymer phase, they may often compromise the use of the interface as an instrument to direct cell fate. Alternatively, here, we have designed hybrid 3D scaffolds using a novel concept based on biomaterial assembly, thereby omitting the drawbacks of interfacial bonding. Rapid prototyped ceramic particles were integrated into the pores of polymeric 3D fiber-deposited (3DF) matrices and infused with demineralized bone matrix (DBM) to obtain constructs that display the mechanical robustness of ceramics and the flexibility of polymers, mimicking bone tissue properties. Ostechondral scaffolds were then fabricated by directly depositing a 3DF structure optimized for cartilage regeneration adjacent to the bone scaffold. Stem cell seeded scaffolds regenerated both cartilage and bone in vivo. PMID:18716660

  13. Effects of different crosslinking conditions on the chemical-physical properties of a novel bio-inspired composite scaffold stabilised with 1,4-butanediol diglycidyl ether (BDDGE).

    PubMed

    Nicoletti, A; Fiorini, M; Paolillo, J; Dolcini, L; Sandri, M; Pressato, D

    2013-01-01

    Serious cartilage lesions (Outerbridge III, IV) may be successfully treated with a three-layered gradient scaffold made by magnesium-doped hydroxyapatite and type I collagen, manufactured through a bio-inspired process and stabilised by a reactive bis-epoxy (1,4-butanediol diglycidyl ether, BDDGE). Each layer was analysed to elucidate the effects of crosslinking variables (concentration, temperature and pH). The chemical stabilisation led to an homogeneous and aligned collagenous matrix: the fibrous structures switched to a laminar foils-based arrangement and organic phases acquired an highly coordinated 3D-organization. These morphological features were strongly evident when crosslinking occurred in alkaline solution, with BDDGE concentration of at least 1 wt%. The optimised crosslinking conditions did not affect the apatite nano-crystals nucleated into self-assembling collagen fibres. The present work allowed to demonstrate that acting on BDDGE reaction parameters might be an useful tool to control the chemical-physical properties of bio-inspired scaffold suitable to heal wide osteochondral defects, even through arthroscopic procedure. PMID:23053811

  14. In vitro observation of cartilage-degeneration progression by Fourier-domain OCT

    NASA Astrophysics Data System (ADS)

    Marx, Ulrich; Schmitt, Robert; Nebelung, Sven; Tingart, Markus; Lüring, Christian; Rath, Björn

    2012-03-01

    Optical Coherence Tomography (OCT) as emerging clinical diagnostic imaging technology for dermatology and other semitransparent tissues has shown high potential in monitoring and evaluating the inner structure of articular cartilages. Since novel therapies for the limitation of cartilage degeneration in early stages of osteoarthritis are available, the early minimal invasive diagnosis of cartilage degradation is clinically essential for further treatment options. With the advancing performance and thus diagnostic opportunities of 3D-OCT devices, we carried out a systematic study by monitoring arthrotic alterations of porcine osteochondral explants that are mechanically induced under traumatic impaction. As for in-vitro tomographic imaging we utilized two OCT devices, a Thorlabs FD-OCT device with 92KHz A-scan rate and 1310nm as central wavelength and a self-developed FD-OCT device at 840nm central wavelength. This allows the comparison in image contrast and optical penetration of cartilage tissue between these two spectral bandwidths. Further we analyzed human biopsies of articular cartilages with various degrees of osteoarthritis. The 2D and 3D OCT tomograms are characterized qualitatively regarding the inner tissue structure and quantitatively regarding the tissue absorption parameters. Therefore, we are developing image processing algorithms for the automated monitoring of cartilage tissue. A scoring system for 3D-monitoring allows the characterization of the probe volume regarding the morphological structure and tissue compactness by processing the C - scan data.

  15. Flexor Digitorum Accessorius Longus: Importance of Posterior Ankle Endoscopy

    PubMed Central

    Batista, Jorge Pablo; del Vecchio, Jorge Javier; Golanó, Pau; Vega, Jordi

    2015-01-01

    Endoscopy for the posterior region of the ankle through two portals is becoming more widespread for the treatment of a large number of conditions which used to be treated with open surgery years ago. The tendon of the flexor hallucis longus (FHL) travels along an osteofibrous tunnel between the posterolateral and posteromedial tubercles of the talus. Chronic inflammation of this tendon may lead to painful stenosing tenosynovitis. The aim of this report is to describe two cases depicting an accessory tendon which is an anatomical variation of the flexor hallucis longus in patients with posterior friction syndrome due to posterior ankle impingement and associated with a posteromedial osteochondral lesion of the talus. The anatomical variation (FDAL) described was a finding during an endoscopy of the posterior region of the ankle, and we have spared it by sectioning the superior flexor retinaculum only. The accessory flexor digitorum longus is an anatomical variation and should be taken into account when performing an arthroscopy of the posterior region of the ankle. We recommend this treatment on this type of injury although we admit this does not make a definite conclusion. PMID:26060592

  16. Flexor Digitorum Accessorius Longus: Importance of Posterior Ankle Endoscopy.

    PubMed

    Batista, Jorge Pablo; Del Vecchio, Jorge Javier; Golanó, Pau; Vega, Jordi

    2015-01-01

    Endoscopy for the posterior region of the ankle through two portals is becoming more widespread for the treatment of a large number of conditions which used to be treated with open surgery years ago. The tendon of the flexor hallucis longus (FHL) travels along an osteofibrous tunnel between the posterolateral and posteromedial tubercles of the talus. Chronic inflammation of this tendon may lead to painful stenosing tenosynovitis. The aim of this report is to describe two cases depicting an accessory tendon which is an anatomical variation of the flexor hallucis longus in patients with posterior friction syndrome due to posterior ankle impingement and associated with a posteromedial osteochondral lesion of the talus. The anatomical variation (FDAL) described was a finding during an endoscopy of the posterior region of the ankle, and we have spared it by sectioning the superior flexor retinaculum only. The accessory flexor digitorum longus is an anatomical variation and should be taken into account when performing an arthroscopy of the posterior region of the ankle. We recommend this treatment on this type of injury although we admit this does not make a definite conclusion. PMID:26060592

  17. The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification

    PubMed Central

    Laurie, Lindsay E.; Kokubo, Hiroki; Nakamura, Masataka; Saga, Yumiko; Funato, Noriko

    2016-01-01

    The developing long bone is a model of endochondral ossification that displays the morphological layers of chondrocytes toward the ossification center of the diaphysis. Indian hedgehog (Ihh), a member of the hedgehog family of secreted molecules, regulates chondrocyte proliferation and differentiation, as well as osteoblast differentiation, through the process of endochondral ossification. Here, we report that the basic helix-loop-helix transcription factor Hand1, which is expressed in the cartilage primordia, is involved in proper osteogenesis of the bone collar via its control of Ihh production. Genetic overexpression of Hand1 in the osteochondral progenitors resulted in prenatal hypoplastic or aplastic ossification in the diaphyses, mimicking an Ihh loss-of-function phenotype. Ihh expression was downregulated in femur epiphyses of Hand1-overexpressing mice. We also confirmed that Hand1 downregulated Ihh gene expression in vitro by inhibiting Runx2 transactivation of the Ihh proximal promoter. These results demonstrate that Hand1 in chondrocytes regulates endochondral ossification, at least in part through the Runx2-Ihh axis. PMID:26918743

  18. Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair

    NASA Astrophysics Data System (ADS)

    Liu, Xiaohua; Jin, Xiaobing; Ma, Peter X.

    2011-05-01

    To repair complexly shaped tissue defects, an injectable cell carrier is desirable to achieve an accurate fit and to minimize surgical intervention. However, the injectable carriers available at present have limitations, and are not used clinically for cartilage regeneration. Here, we report nanofibrous hollow microspheres self-assembled from star-shaped biodegradable polymers as an injectable cell carrier. The nanofibrous hollow microspheres, integrating the extracellular-matrix-mimicking architecture with a highly porous injectable form, were shown to efficiently accommodate cells and enhance cartilage regeneration, compared with control microspheres. The nanofibrous hollow microspheres also supported a significantly larger amount of, and higher-quality, cartilage regeneration than the chondrocytes-alone group in an ectopic implantation model. In a critical-size rabbit osteochondral defect-repair model, the nanofibrous hollow microspheres/chondrocytes group achieved substantially better cartilage repair than the chondrocytes-alone group that simulates the clinically available autologous chondrocyte implantation procedure. These results indicate that the nanofibrous hollow microspheres are an excellent injectable cell carrier for cartilage regeneration.

  19. Autologous Chondrocyte Implantation: Past, Present, and Future.

    PubMed

    Welch, Tyler; Mandelbaum, Bert; Tom, Minas

    2016-06-01

    Focal cartilage defects of the knee are relatively common and may increase the risk of developing osteoarthritis. Autologous chondrocyte implantation (ACI) aims to restore the integrity of isolated cartilage lesions through the induction of hyaline-like cartilage formation. Although ACI has traditionally been used as a second-line treatment, recent evidence suggests that ACI should be considered as a first-line treatment option in certain patients. Recent controlled trials also suggest that there are improved clinical outcomes among those patients who undergo ACI over the mid-term and long-term compared with those treated with microfracture or osteochondral autograft/mosaicplasty, regardless of lesion size. Recent literature also indicates that arthroscopic, second-generation and third-generation techniques are associated with better outcomes and fewer complications than first-generation ACI. In summary, ACI is an effective tool for cartilage restoration that may be more efficacious and durable than other cartilage restoration techniques for appropriate candidates. PMID:27135292

  20. Material characterization of microsphere-based scaffolds with encapsulated raw materials.

    PubMed

    Sridharan, BanuPriya; Mohan, Neethu; Berkland, Cory J; Detamore, Michael S

    2016-06-01

    "Raw materials," or materials capable of serving both as building blocks and as signals, which are often but not always natural materials, are taking center stage in biomaterials for contemporary regenerative medicine. In osteochondral tissue engineering, a field leveraging the underlying bone to facilitate cartilage regeneration, common raw materials include chondroitin sulfate (CS) for cartilage and β-tricalcium phosphate (TCP) for bone. Building on our previous work with gradient scaffolds based on microspheres, here we delved deeper into the characterization of individual components. In the current study, the release of CS and TCP from poly(d,l-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds was evaluated over a time period of 4weeks. Raw material encapsulated groups were compared to 'blank' groups and evaluated for surface topology, molecular weight, and mechanical performance as a function of time. The CS group may have led to increased surface porosity, and the addition of CS improved the mechanical performance of the scaffold. The finding that CS was completely released into the surrounding media by 4weeks has a significant impact on future in vivo studies, given rapid bioavailability. The addition of TCP seemed to contribute to the rough external appearance of the scaffold. The current study provides an introduction to degradation patterns of homogenous raw material encapsulated scaffolds, providing characterization data to advance the field of microsphere-based scaffolds in tissue engineering. PMID:27040236

  1. Organ-Level Histological and Biomechanical Responses from Localized Osteoarticular Injury in the Rabbit Knee

    PubMed Central

    Vaseenon, Tanawat; Tochigi, Yuki; Heiner, Anneliese D.; Goetz, Jessica E.; Baer, Thomas E.; Fredericks, Douglas; Martin, James A.; Rudert, M. James; Hillis, Stephen L.; Brown, Thomas D.; McKinley, Todd O.

    2013-01-01

    The processes of whole-joint osteoarthritis development following localized joint injuries are not well understood. To demonstrate this local-to-global linkage, it was hypothesized that a localized osteoarticular injury in the rabbit knee would not only cause biomechanical and histological abnormalities in the involved compartment, but also concurrent histological changes in the non-involved compartment. Twenty rabbits had an acute osteoarticular injury that involved localized joint incongruity (a 2 mm osteochondral defect created in the weight-bearing area of the medial femoral condyle), while another twenty received control sham surgery. At the time of sacrifice at eight or sixteen weeks post-surgery, the experimental knees were subjected to sagittal-plane laxity measurement, followed by cartilage histo-morphological evaluation using the Mankin score. The immediate effects of defect creation on joint stability and contact mechanics were explored in concomitant rabbit cadaver experimentation. The injured animals had cartilage histological scores significantly higher than in the sham surgery group (p<0.01) on the medial femoral, medial tibial, and lateral femoral surfaces (predominantly on the medial surfaces), accompanied by slight (mean 20%) increase of sagittal-plane laxity. Immediate injury-associated alterations in the medial compartment contact mechanics were also demonstrated. Localized osteoarticular injury in this survival animal model resulted in global joint histological changes. PMID:20886656

  2. Irreducible dislocation of the thumb interphalangeal joint due to displaced flexor pollicis longus tendon: case report and new reduction technique.

    PubMed

    Naito, Kiyohito; Sugiyama, Yoichi; Igeta, Yuka; Kaneko, Kazuo; Obayashi, Osamu

    2014-08-01

    Dislocation of the thumb interphalangeal (IP) joint is uncommon because of the inherent stability of the joint. Cases in which reduction was blocked by the volar plate, the flexor pollicis longus (FPL) tendon, the sesamoid bone, and an osteochondral fragment have been described in the literature. This article reports a case of closed thumb IP joint dislocation caused by the displacement of the FPL tendon. A new percutaneous reduction technique for this injury will also be presented. A 63-year-old woman presented to the emergency room with an obvious thumb deformity. Radiographs confirmed dorsal dislocation of the thumb IP joint without associated fracture. Closed reduction was not successful. Percutaneous reduction was performed under locoregional anesthesia, because the dislocation was due to an FPL tendon that had displaced dorsally and radially to the proximal phalanx. After reduction, Kirschner wire fixation was not needed, but IP joint immobilization with a splint was required for 3 weeks. Postoperatively, there were no complications in soft tissues and the operative scar was almost unrecognizable. This technique enables a mini-invasive reduction by operating percutaneously on the FPL. In addition, unlike with a volar zigzag approach, it is possible to suppress the occurrence of postoperative adhesion of the flexor tendon. This new minimally invasive reduction technique is useful for irreducible dislocation of the thumb IP joint due to a displaced FPL tendon. PMID:24902518

  3. Intraosseous Infiltration of Platelet-Rich Plasma for Severe Knee Osteoarthritis

    PubMed Central

    Sánchez, Mikel; Fiz, Nicolás; Guadilla, Jorge; Padilla, Sabino; Anitua, Eduardo; Sánchez, Pello; Delgado, Diego

    2014-01-01

    We describe a new technique of platelet-rich plasma (PRP) infiltration for the treatment of severe knee osteoarthritis. PRP intra-articular infiltration is a promising treatment for knee osteoarthritis, but it still has some limitations in high-degree osteoarthritis. Diagnosis of osteoarthritis is based on clinical and radiographic findings, and patients with grade III or IV knee tibiofemoral osteoarthritis based on the Ahlbäck scale are considered candidates for this technique. The technique consists of performing intraosseous infiltration of PRP into the subchondral bone, which acts on this tissue and consequently on cartilage-bone communication. Although the intraosseous injection hinders the conventional knee intra-articular infiltration, it allows an extension of the range of action of the PRP, which acts directly on the subchondral bone, which is involved in the progression of osteoarthritis. Thus this technique involves a new administration of PRP that can delay knee arthroplasty; moreover, it can be applied for not only severe osteoarthritis but also other pathologies in which the subchondral bone is critical in the etiology, such as necrosis and osteochondral lesions. PMID:25685680

  4. The Healing Effect of Adipose-Derived Mesenchymal Stem Cells in Full-thickness Femoral Articular Cartilage Defects of Rabbit

    PubMed Central

    Mehrabani, D.; Babazadeh, M.; Tanideh, N.; Zare, S.; Hoseinzadeh, S.; Torabinejad, S.; Koohi-Hosseinabadi, O.

    2015-01-01

    Background: Articular cartilage defect can lead to degradation of subchondral bone and osteoarthritis (OA). Objective: To determine the healing effect of transplantation of adipose-derived mesenchymal stem cells (Ad-MSCs) in full-thickness femoral articular cartilage defects in rabbit. Methods: 12 rabbits were equally divided into cell-treated and control groups. In cell-treated group, 2×106 cells of third passage suspended in 1 mL of DMEM was injected into articular defect. The control group just received 1 mL of DMEM. Dulbecco’s modified Eagles medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin and streptomycin and 2 mM L-glutamine were used for cell culture. To induce cartilage defect, 4 mm articular cartilage full-thickness defect was created in the knee. For histological evaluation in each group (H&E, safranin-O and toluidine blue), 3 rabbits were sacrificed 4 weeks and 3 animals, 8 weeks after cell transplantation. Results: In cell therapy group post-transplantation, no abnormal gross findings were noticed. Neo-formed tissues in cell-treated groups were translucent with a smooth and intact surface and less irregularity. In cell-treated group after 8 weeks post-transplantation, the overall healing score of experimental knees were superior when compared to other groups. Conclusion: We showed that Ad-MSCs, as an available and non-invasive produced source of cells, could be safely administered in knee osteochondral defects. PMID:26576262

  5. Chondrogenesis of Infrapatellar Fat Pad Derived Adipose Stem Cells in 3D Printed Chitosan Scaffold

    PubMed Central

    Ye, Ken; Felimban, Raed; Traianedes, Kathy; Moulton, Simon E.; Wallace, Gordon G.; Chung, Johnson; Quigley, Anita; Choong, Peter F. M.; Myers, Damian E.

    2014-01-01

    Infrapatellar fat pad adipose stem cells (IPFP-ASCs) have been shown to harbor chondrogenic potential. When combined with 3D polymeric structures, the stem cells provide a source of stem cells to engineer 3D tissues for cartilage repair. In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGF?3 and BMP6. By week 4, a pearlescent, cartilage-like matrix had formed that penetrated the top layers of the chitosan scaffold forming a cap on the scaffold. Chondrocytic morphology showed typical cells encased in extracellular matrix which stained positively with toluidine blue. Immunohistochemistry demonstrated positive staining for collagen type II and cartilage proteoglycans, as well as collagen type I. Real time PCR analysis showed up-regulation of collagen type II, aggrecan and SOX9 genes when IPFP-ASCs were stimulated by TGF?3 and BMP6. Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGF?3 and BMP6 and the cartilage-like tissue that forms on the surface of 3D-printed chitosan scaffold may prove useful as an osteochondral graft. PMID:24918443

  6. Artificial Niche Combining Elastomeric Substrate and Platelets Guides Vascular Differentiation of Bone Marrow Mononuclear Cells

    PubMed Central

    Wu, Wei; Allen, Robert; Gao, Jin

    2011-01-01

    Bone marrow-derived progenitor cells are promising cell sources for vascular tissue engineering. However, conventional bone marrow mesenchymal stem cell expansion and induction strategies require plating on tissue culture plastic, a stiff substrate that may itself influence cell differentiation. Direct scaffold seeding avoids plating on plastic; to the best of our knowledge, there is no report of any scaffold that induces the differentiation of bone marrow mononuclear cells (BMNCs) to vascular cells in vitro. In this study, we hypothesize that an elastomeric scaffold with adsorbed plasma proteins and platelets will induce differentiation of BMNCs to vascular cells and promote vascular tissue formation by combining soft tissue mechanical properties with platelet-mediated tissue repairing signals. To test our hypothesis, we directly seeded rat primary BMNCs in four types of scaffolds: poly(lactide-co-glycolide), elastomeric poly(glycerol sebacate) (PGS), platelet-poor plasma-coated PGS, and PGS coated by plasma supplemented with platelets. After 21 days of culture, osteochondral differentiation of cells in poly(lactide-co-glycolide) was detected, but most of the adhered cells on the surface of all PGS scaffolds expressed calponin-I and α-smooth muscle actin, suggesting smooth muscle differentiation. Cells in PGS scaffolds also produced significant amount of collagen and elastin. Further, plasma coating improves seeding efficiency, and platelet increases proliferation, the number of differentiated cells, and extracellular matrix content. Thus, the artificial niche composed of platelets, plasma, and PGS is promising for artery tissue engineering using BMNCs. PMID:21449713

  7. Current concepts: tissue engineering and regenerative medicine applications in the ankle joint.

    PubMed

    Correia, S I; Pereira, H; Silva-Correia, J; Van Dijk, C N; Espregueira-Mendes, J; Oliveira, J M; Reis, R L

    2014-03-01

    Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving restoration of biological functions and rehabilitation. The mainstream components required to obtain a functional regeneration of tissues may include biodegradable scaffolds, drugs or growth factors and different cell types (either autologous or heterologous) that can be cultured in bioreactor systems (in vitro) prior to implantation into the patient. Particularly in the ankle, which is subject to many different injuries (e.g. acute, chronic, traumatic and degenerative), there is still no definitive and feasible answer to 'conventional' methods. This review aims to provide current concepts of TERM applications to ankle injuries under preclinical and/or clinical research applied to skin, tendon, bone and cartilage problems. A particular attention has been given to biomaterial design and scaffold processing with potential use in osteochondral ankle lesions. PMID:24352667

  8. Thermal chondroplasty of chondromalacic human cartilage. An ex vivo comparison of bipolar and monopolar radiofrequency devices.

    PubMed

    Edwards, Ryland B; Lu, Yan; Nho, Shane; Cole, Brian J; Markel, Mark D

    2002-01-01

    We compared the effects of treatment with bipolar and monopolar radiofrequency energy on 30 osteochondral sections harvested from 22 patients with spontaneously occurring chondromalacia who were undergoing knee arthroplasty. Specimens with chondromalacia grades 2 or 3 were randomly assigned to one of two bipolar or one monopolar treatment groups. All samples were marked and mounted on a jig to allow simulation of an arthroscopic surgical procedure with a flow rate of 100 ml/min of a balanced electrolyte solution at 22 degrees C. Under arthroscopic visualization, the designated area was treated until smooth, and the total treatment time was recorded. There was no difference in patients' ages, chondromalacia grade, or cartilage thickness among groups. Significant chondrocyte death, as determined by cell viability staining with confocal laser microscopy, was observed with each group. The bipolar devices produced significantly greater depths of chondrocyte death (2228 +/- 1003 microm and 2810 +/- 517 microm) than did the monopolar device (737 +/- 391 microm). The bipolar devices caused cell death to subchondral bone significantly more often (13 of 20 specimens) than did the monopolar device (0 of 10 specimens). Caution should be used in treating fibrillated cartilage with radiofrequency energy, particularly with the bipolar devices tested. PMID:11799002

  9. Characterization of mesenchymal stem cells isolated from the rabbit fetal liver.

    PubMed

    Moreno, Rafael; Martínez-González, Itziar; Rosal, Marta; Farwati, Abduljalil; Gratacós, Eduard; Aran, Josep M

    2010-10-01

    Physiological attributes of mesenchymal stem cells (MSCs) including straightforward manipulation, multilineage differentiation, immunoregulation, and tropism for injury settings render them ideal therapeutic agents for tissue repair/regeneration. Nevertheless, further studies in suitable animal models of disease are needed to translate the potential of MSCs into clinical applications. We report here the isolation and preliminary characterization of MSCs from fetal rabbit liver (fl-MSCs). Compared with MSCs isolated from adult rabbit bone marrow, fl-MSCs had superior growth rate, clonogenic capability, and plastic adherence owing to their developmental immaturity. Both cytochemical staining and mRNA expression analysis of fl-MSCs confirmed mesodermal lineage differentiation into adipocytes, osteocytes, and chondrocytes. Moreover, fl-MSCs were capable to prevent lymphocyte proliferation both in a 2-way MLC and upon phytohemagglutinin (PHA) stimulation. In contrast, fl-MSCs co-cultured with allogeneic lymphocytes induced proliferation of the latter. Relatedly, although freshly isolated fl-MSCs did express neither major histocompatibility complex (MHC) class I/II nor CD80/CD86, all these immune synapse components were induced upon in vitro culture. Furthermore, fl-MSCs became efficiently transduced for long-term transgene expression with a retroviral vector. Thus, the special biological qualities of fl-MSCs endow them as model candidate vehicles/agents for gene/cell therapy strategies applied to a variety of rabbit models of injury, such as osteochondral lesions. PMID:20148649

  10. Tailoring chemical and physical properties of fibrous scaffolds from block copolyesters containing ether and thio-ether linkages for skeletal differentiation of human mesenchymal stromal cells.

    PubMed

    Chen, Honglin; Gigli, Matteo; Gualandi, Chiara; Truckenmüller, Roman; van Blitterswijk, Clemens; Lotti, Nadia; Munari, Andrea; Focarete, Maria Letizia; Moroni, Lorenzo

    2016-01-01

    Bioactive scaffolds for tissue engineering call for demands on new materials which can enhance traditional biocompatibility requirements previously considered for clinical implantation. The current commercially available thermoplastic materials, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ε-caprolactone) (PCL) and their copolymers, have been used to fabricate scaffolds for regenerative medicine. However, these polymers have limitations including lacking of broadly tuning mechanical and degradable properties, and activation of specific cell-scaffold interactions, which limit their further application in tissue engineering. In the present study, electrospun scaffolds were successfully fabricated from a new class of block poly(butylene succinate)-based (PBS-based) copolyesters containing either butylene thiodiglycolate (BTDG) or butylene diglycolate (BDG) sequences. The polyesters displayed tunable mechanical properties and hydrolysis rate depending on the molecular architecture and on the kind of heteroatom introduced along the polymer backbone. To investigate their potential for skeletal regeneration, human mesenchymal stromal cells (hMSCs) were cultured on the scaffolds in basic, osteogenic and chondrogenic media. Our results demonstrated that PBS-based copolyesters containing thio-ether linkages (i.e. BTDG segments) were more favorable for chondrogenesis of hMSCs than those containing ether linkages (i.e. BDG sequences). In contrast, PBS-based copolyesters containing ether linkages showed enhanced mineralization. Therefore, these new functional scaffolds might hold potential for osteochondral tissue engineering applications. PMID:26546918

  11. AUTOLOGOUS CHONDROCYTE TRANSPLANTATION-SERIES OF 3 CASES

    PubMed Central

    Gobbi, Riccardo Gomes; Demange, Marco Kawamura; Barreto, Ronald Bispo; Pécora, José Ricardo; Rezende, Múrcia Uchõa de; Filho, Tarcisio E.P Barros; Lombello, Christiane Bertachini

    2015-01-01

    Hyaline cartilage covers joint surfaces and plays an important role in reducing friction and mechanical loading on synovial joints such as the knee. This tissue is not supplied with blood vessels, nerves or lymphatic circulation, which may be one of the reasons why joint cartilage has such poor capacity for healing. Chondral lesions that reach the subchondral bone (osteochondral lesions) do not heal and may progress to arthrosis with the passage of time. In young patients, treatment of chondral defects of the knee is still a challenge, especially in lesions larger than 4 cm. One option for treating these patients is autologous chondrocyte transplantation/implantation. Because this treatment does not violate the subchondral bone and repairs the defect with tissue similar to hyaline cartilage, it has the theoretical advantage of being more biological, and mechanically superior, compared with other techniques. In this paper, we describe our experience with autologous chondrocyte transplantation/implantation at the Institute of Orthopedics and Traumatology, Hospital das Clínicas, University of Sâo Paulo, through a report on three cases. PMID:27022579

  12. Imaging of cartilage repair procedures.

    PubMed

    Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw

    2014-07-01

    The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts. PMID:25114387

  13. A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor

    PubMed Central

    Colombo, Elisa A.; Carra, Silvia; Fontana, Laura; Bresciani, Erica; Cotelli, Franco; Larizza, Lidia

    2015-01-01

    Poikiloderma with Neutropenia (PN) is an autosomal recessive genodermatosis characterized by early-onset poikiloderma, pachyonychia, hyperkeratosis, bone anomalies and neutropenia, predisposing to myelodysplasia. The causative C16orf57/USB1 gene encodes a conserved phosphodiesterase that regulates the stability of spliceosomal U6-RNA. The involvement of USB1 in splicing has not yet allowed to unveil the pathogenesis of PN and how the gene defects impact on skin and bone tissues besides than on the haematological compartment. We established a zebrafish model of PN using a morpholino-knockdown approach with two different splicing morpholinos. Both usb1-depleted embryos displayed developmental abnormalities recapitulating the signs of the human syndrome. Besides the pigmentation and osteochondral defects, usb1-knockdown caused defects in circulation, manifested by a reduced number of circulating cells. The overall morphant phenotype was also obtained by co-injecting sub-phenotypic dosages of the two morpholinos and could be rescued by human USB1 RNA. Integrated in situ and real-time expression analyses of stage-specific markers highlighted defects of primitive haematopoiesis and traced back the dramatic reduction in neutrophil myeloperoxidase to the myeloid progenitors showing down-regulated pu.1 expression. Our vertebrate model of PN demonstrates the intrinsic requirement of usb1 in haematopoiesis and highlights PN as a disorder of myeloid progenitors associated with bone marrow dysfunction. PMID:26522474

  14. Elbow arthroscopy: setup, portal placement, and simple procedures.

    PubMed

    Ahmad, Christopher S; Vitale, Mark A

    2011-01-01

    Elbow arthroscopy has become an accepted treatment for numerous elbow conditions, including loose bodies, lateral epicondylitis, contractures, painful osteophytes, synovitis, osteochondritis dissecans, synovial plica, and osteoarthritis. It is absolutely necessary that the treating surgeon have complete knowledge of elbow anatomy. Three options exist for patient positioning: supine, prone, and lateral decubitus. Standard arthroscopic probes, grasping forceps, punches, and motorized shavers and burrs are used in the procedure. Retractors are essential for visualizing, exposing, and protecting nerves. Specially designed capsular biters can be used to develop a plane between the capsule and the surrounding soft tissues to facilitate capsulotomy and capsulectomy. Among elbow arthroscopists, the sequence of portal placement varies; however, there is little variation in the exact location of portal placement because of neurovascular constraints. Loose body removal and extensor carpi radialis brevis release for lateral epicondylitis are common procedures suitable for the beginning arthroscopist. For beginning and advanced procedures, the surgeon's skill and competence must be at a level consistent with the procedure to avoid complications. PMID:21553771

  15. High Density Infill in Cracks and Protrusions from the Articular Calcified Cartilage in Osteoarthritis in Standardbred Horse Carpal Bones

    PubMed Central

    Laverty, Sheila; Lacourt, Mathieu; Gao, Chan; Henderson, Janet E.; Boyde, Alan

    2015-01-01

    We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC mineralizing (tidemark) front (MF) into hyaline articular cartilage (HAC). We hypothesized and we show that 20-µm µCT resolution in 10-mm diameter samples is sufficient to detect HDMI and HDMP: these are lost upon tissue decalcification for routine paraffin wax histology owing to their predominant mineral content. The findings show that µCT is sufficient to discover HDMI and HDMP, which were seen in 2/10 controls, 6/9 early OA and 8/10 advanced OA cases. This is the first report of HDMI and HDMP in the equine carpus and in the Standardbred breed and the first to rely solely on µCT. HDMP are a candidate cause for mechanical tissue destruction in OA. PMID:25927581

  16. Three-dimensional imaging and analysis of human cartilage degeneration using Optical Coherence Tomography.

    PubMed

    Nebelung, Sven; Brill, Nicolai; Marx, Ulrich; Quack, Valentin; Tingart, Markus; Schmitt, Robert; Rath, Bjrn; Jahr, Holger

    2015-05-01

    Optical Coherence Tomography (OCT) is an evolving imaging technology allowing non-destructive imaging of cartilage tissue at near-histological resolution. This study investigated the diagnostic value of real time 3-D OCT in comparison to conventional 2-D OCT in the comprehensive grading of human cartilage degeneration. Fifty-three human osteochondral samples were obtained from eight total knee arthroplasties. OCT imaging was performed by either obtaining a single two-dimensional cross-sectional image (2-D OCT) or by collecting 100 consecutive parallel 2-D OCT images to generate a volumetric data set of 8??8?mm (3-D OCT). OCT images were assessed qualitatively according to a modified version of the DJD classification and quantitatively by algorithm-based evaluation of surface irregularity, tissue homogeneity, and signal attenuation. Samples were graded according to the Outerbridge classification and statistically analyzed by one-way ANOVA, Kruskal Wallis and Tukey's or Dunn's post-hoc tests. Overall, the generation of 3-D volumetric datasets and their multiple reconstructions such as rendering, surface topography, parametric, and cross-sectional views proved to be of potential diagnostic value. With increasing distance to the mid-sagittal plane and increasing degeneration, score deviations increased, too. In conclusion, 3-D imaging of cartilage with image analysis algorithms adds considerable potential diagnostic value to conventional OCT diagnostics. PMID:25641346

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

    PubMed Central

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

    2014-01-01

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

  18. [Classification, significance and sequelae of posttraumatic "occult" bone and cartilage fractures of the knee. The role of magnetic resonance].

    PubMed

    Macarini, L; Zaccheo, N; Garribba, A P; Angelelli, G; Rotondo, A

    1995-12-01

    Magnetic Resonance Imaging (MRI) shows, in the post-traumatic knee, a fairly high number of bone and cartilage injuries missed by conventional radiography and therefore called occult. Our aim is to classify these injuries, to correlate their site and distribution with associated menisco-ligamentous injuries and with trauma mechanisms. Thirty-eight patients with a history of acute knee trauma and negative X-ray findings were examined with MRI within 15 days of trauma. 1.5- and 0.5-T units and SE T1-weighted GE T2*-weighted and SE T2-weighted sequences were used. The injuries were classified as intraosseous and osteochondral bruises or fractures. Twenty-three patients with menisco-ligamentous injuries were submitted to therapeutic arthroscopy; the sites of bone and cartilage injuries depicted with MRI were studied with arthroscopy. Seven patients were followed-up with MRI at 6-12 months to investigate subchondral injury evolution: 5 of 7 patients were also submitted to arthroscopy. MRI showed a statistically significant correlation between site and distribution of bone and cartilage injuries and between internal derangement and trauma mechanisms, i.e., contusion, distortion, stress. In our experience, MRI could identify and characterize occult subchondral injuries, thus allowing appropriate treatment. PMID:8685452

  19. Treatment of Lateral Knee Pain Using Soft Tissue Mobilization in Four Female Triathletes

    PubMed Central

    Winslow, John

    2014-01-01

    Study Design Prospective case series. Background These case reports present results of the treatment of lateral knee pain in four female amateur triathletes. The athletes were referred to the author’s clinic with either a diagnosis of iliotibial band friction syndrome or patellofemoral pain syndrome, all four having symptoms for longer than seven months. Changes in training routines were identified as the possible cause of the overuse injuries that eventually developed into chronic conditions. Intervention Treatment involved soft tissue mobilization of the musculotendinous structures on the lateral aspect of the knee. Results At four weeks, three of the athletes improved 9 to 19 points on the Lower Extremity Functional Scale, 3 to 5 points on the Global Rating of Change Scale, and demonstrated improvement in hamstring and iliotibial band flexibility. At eight weeks the Global Rating of Change for these three athletes was a 7 (“a very great deal better”) and they had returned to triathlon training with no complaints of lateral knee pain. One athlete did not respond to treatment and eventually underwent arthroscopic surgery for debridement of a lateral meniscus tear. Conclusions After ruling out common causes for lateral knee pain such as lateral meniscus tear, lateral collateral ligament sprain, patellofemoral dysfunction, osteochondral injury, biceps femoris tendonitis, iliotibial band friction syndrome or osteoarthritis, soft tissue restriction should be considered a potential source of dysfunction. In some cases soft tissue restriction is overlooked; athletes go undiagnosed and are limited from sports participation. PMID:25184012

  20. Mesenchymal stem cells as a potent cell source for articular cartilage regeneration

    PubMed Central

    Baghaban Eslaminejad, Mohamadreza; Malakooty Poor, Elham

    2014-01-01

    Since articular cartilage possesses only a weak capacity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is associated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechanical properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical procedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morphological features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells (MSCs) to be an appropriate cellular material for articular cartilage repair. These cells were originally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic differentiation is an inherent property of MSCs noticed at the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative properties. Moreover, these cells possess a considerable immunomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review. PMID:25126383

  1. Basic fibroblast growth factor enhances osteogenic and chondrogenic differentiation of human bone marrow mesenchymal stem cells in coral scaffold constructs.

    PubMed

    Zheng, You-Hua; Su, Kai; Jian, Yu-Tao; Kuang, Shi-Jun; Zhang, Zhi-Guang

    2011-07-01

    Temporomandibular joint (TMJ) disorders are commonly occurring degenerative joint diseases that require surgical replacement of the mandibular condyle in severe cases. Transplantation of tissue-engineered mandibular condyle constructs may solve some of the current surgical limitations to TMJ repair. We evaluated the feasibility of mandibular condyle constructs engineered from human bone marrow-derived mesenchymal cells (BMSCs). Specifically, human BMSCs were transfected with basic FGF (bFGF) gene-encoding plasmids and induced to differentiate into osteoblasts and chondroblasts. The cells were seeded onto mandibular condyle-shaped porous coral scaffolds and evaluated for osteogenic/chondrogenic differentiation, cell proliferation, collagen deposition and tissue vascularization. Transfected human BMSCs expressed bFGF and were highly proliferative. Osteogenesis was irregular, showing neovascularization around new bone tissue. There was no evidence of bilayered osteochondral tissue present in normal articulating surfaces. Collagen deposition, characteristic of bone and cartilage, was observed. Subcutaneous transplantation of seeded coral/hydrogel hyaluran constructs into nude mice resulted in bone formation and collagen type I and type II deposition. Neovascularization was observed around newly formed bone tissue; bFGF expression was detected in implanted constructs seeded with bFGF expressing hBMSCs. This report demonstrates that engineered porous coral constructs using bFGF gene-transfected human BMSCs may be a feasible option for surgical transplantation in TMJ repair. PMID:21695795

  2. Platelet-rich plasma loaded hydrogel scaffold enhances chondrogenic differentiation and maturation with up-regulation of CB1 and CB2.

    PubMed

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

    2012-05-10

    Three-dimensional scaffolds like hydrogels can be used for cell and drug delivery and have become a major research focus in tissue engineering. Presently, we investigated the regenerative potency of platelet-rich plasma (PRP) combined with a chondrocyte/hydrogel composite scaffold in the repair of articular cartilage defects using a rabbit model. Primary isolated joint chondrocytes from the trachlear groove of rabbit were cultured in hydrogels as follows; hydrogel (2900 Pa or 5900 Pa)+chondrocytes and hydrogel+chondrocytes+PRP for in vitro analysis and in vivo implantation. The 5900 Pa hydrogel markedly increased cellular viability and development in a time-dependent manner. Furthermore, the hydrogels attenuated the expression of SOX-9, aggrecan, and type II collagen. PRP-containing hydrogels produced an immediate increase in mRNA levels of cannabinoid receptor (CB)1 and CB2, compared with control and PRP-free hydrogels. Osteochondral defects were enhanced recovery with formation of cartilage and perichondrium in the 5900 Pa hydrogel+chondrocytes+PRP. Hydrogel may provide a suitable environment for proliferation and maturation of joint chondrocytes in relation to the gelation density and bioactive sources like PRP resulting in improvement for cartilage regeneration. PMID:22366523

  3. Early tissue response to citric acid-based micro- and nanocomposites

    PubMed Central

    Chung, Eun Ji; Qiu, Hongjin; Kodali, Pradeep; Yang, Scott; Sprague, Stuart M.; Hwong, James; Koh, Jason; Ameer, Guillermo A.

    2010-01-01

    Composites based on calcium phosphates and biodegradable polymers are desirable for orthopaedic applications due to their potential to mimic bone. Herein, we describe the fabrication, characterization, and in vivo response of novel citric acid-based microcomposites and nanocomposites. Poly(1,8-octanediol-co-citrate) (POC) was mixed with increasing amounts of HA nanoparticles or microparticles (up to 60 wt%), and the morphology and mechanical properties of the resulting composites were assessed. To investigate tissue response, nanocomposites, microcomposites, POC, and poly(L-lactide) (PLL) were implanted in osteochondral defects in rabbits and harvested at 6 weeks for histological evaluation. SEM confirmed increased surface roughness of microcomposites relative to nanocomposites. The mechanical properties of both types of composites increased with increasing amounts of HA (8–328 MPa), although nanocomposites with 60 wt.% HA displayed the highest strength and stiffness. Based on tissue-implant interfacial assessments, all implants integrated well with the surrounding bone and cartilage with no evidence of inflammation. Both nanocomposites and microcomposites supported bone remodeling; however, nanocomposites induced more trabecular bone formation at the tissue-implant interface. The mechanical properties of citric acid-based composites are within the range of human trabecular bone (1–1524 MPa, 211±78 MPa mean modulus) and tissue response was dependent on the size and content of HA, providing new perspectives of design and fabrication criteria for orthopaedic devices such as interference screws and fixation pins. PMID:20949482

  4. Management of Focal Chondral Lesion in the Knee Joint

    PubMed Central

    Kim, Chang-Wan; Jung, Dae-Won

    2011-01-01

    Articular cartilage does not contain vascular, nervous and lymphatic tissue and chondrocytes hardly participate in the healing or repair process of chondral tissue because of being surrounded by plenty of extracellular matrix. Therefore, the injury to articular cartilage frequently requires an operative treatment. The goal of surgical repair of articular cartilage is to regenerate nearly normal chondral tissue and prevent degenerative arthritis caused by the articular cartilage defect. Microfracture is a kind of cartilage repair procedure that makes a fibrin clot containing mesenchymal stem cells in the chondral lesion. Microfracture is a simple procedure but it has a disadvantage that the repaired tissue is fibrocartilage. Autologous chondrocyte implantation has an advantage that it implants fully differentiated chondrocytes to the lesion, which theoretically produces hyaline cartilage. Its disadvantages are that it is a two stage and a costly procedure. Osteochondral autograft transplantation is a one stage procedure and repairs the lesion with hyaline cartilage. But its limitation is the lack of donor site availability. Surgeons who understand the theoretical background, indications, surgical methods, rehabilitation, complications, and clinical course of cartilage repair procedures can achieve the goal of preventing degenerative arthritis. PMID:22570833

  5. In vivo telemetric determination of shear and axial loads on a regenerative cartilage scaffold following ligament disruption.

    PubMed

    Szivek, John A; Heden, Gregory J; Geffre, Christopher P; Wenger, Karl H; Ruth, John T

    2014-10-01

    Recent interest in repair of chondral and osteochondral cartilage defects to prevent osteoarthritis caused by ligament disruption has led to the research and development of biomimetic scaffolds combined with cell-based regeneration techniques. Current clinical focal defect repair strategies have had limited success. New scaffold-based approaches may provide solutions that can repair extensive damage and prevent osteoarthritis. This study utilized a novel scaffold design that accommodated strain gauges for shear and axial load monitoring in the canine stifle joint through implantable telemetry technology. Loading changes induced by ligament disruption are widely implicated in the development of injury-related osteoarthritis. Seeding the scaffold end with progenitor cells resulted in higher shear stress than without cell seeding and histology showed significantly more bone and cartilage formation. Biomechanically, the effect of transecting the anterior cruciate ligament was a significant reduction in braking load in shear, but no change axially, and conversely a significant reduction in push-off load axially, but no change in shear. This is the first study to report shear loads measured directly in knee joint tissue. Further, advances of these measurement techniques are critical to developing improved regeneration strategies and personalizing reliable rehabilitation protocols. PMID:24678004

  6. Development of an Equine Groove Model to Induce Metacarpophalangeal Osteoarthritis: A Pilot Study on 6 Horses

    PubMed Central

    Maninchedda, Ugo; Lepage, Olivier M.; Gangl, Monika; Hilairet, Sandrine; Remandet, Bernard; Meot, Francoise; Penarier, Geraldine; Segard, Emilie; Cortez, Pierre; Jorgensen, Christian; Steinberg, Régis

    2015-01-01

    The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or “grooves” were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy. PMID:25680102

  7. In vivo cell tracking by bioluminescence imaging after transplantation of bioengineered cell sheets to the knee joint.

    PubMed

    Takaku, Yuko; Murai, Kunihiko; Ukai, Taku; Ito, Satoshi; Kokubo, Mami; Satoh, Masaaki; Kobayashi, Eiji; Yamato, Masayuki; Okano, Teruo; Takeuchi, Mamoru; Mochida, Joji; Sato, Masato

    2014-02-01

    In our previous studies, we have demonstrated effective regeneration of cartilage through the creation and application of layered cell sheets that combine both chondrocytes and synovial cells. In this study, we were able to demonstrate that cells derived from cell sheets can survive for long periods after transplantation into rat knee joints having osteochondral defects. We established a method for generating cell sheets from firefly luciferase-expressing chondrocytes obtained from transgenic Lewis rats, and carried out allogenic transplantation of these cell sheets into wild-type Lewis rats. We then administered luciferin and monitored the survival of the transplanted cells by using bioluminescence imaging (BLI). Our data showed that the transplanted cells survived and could be detected for more than 21 months, which was longer than expected. Furthermore, the BLI data showed that the transplanted cells remained in the knee joint and did not migrate to other parts of the body, thus confirming the safety of the cell sheets. In this study, we monitored the duration of survival of cell sheets composed of only chondrocytes, only synovial cells, or both chondrocytes and synovial cells, and found that all three types of cell sheets survived for an extended period of time. PMID:24360579

  8. Evaluation of Gelatin Microparticles as Adherent-Substrates for Mesenchymal Stem Cells in a Hydrogel Composite.

    PubMed

    Lu, Steven; Lee, Esther J; Lam, Johnny; Tabata, Yasuhiko; Mikos, Antonios G

    2016-06-01

    Due to the lack of cell-adhesive moieties in traditional synthetic hydrogels, the present work investigated the use of degradable gelatin microparticles (GMPs) as temporary adherent substrates for anchorage-dependent mesenchymal stem cells (MSCs). MSCs were seeded onto GMPs of varying crosslinking densities and sizes to investigate their role on influencing MSC differentiation and aggregation. The MSC-seeded GMPs were then encapsulated in poly(ethylene glycol)-based hydrogels and cultured in serum-free, growth factor-free osteochondral medium. Non-seeded MSCs co-encapsulated with GMPs in the hydrogels were used as a control for comparison. Over the course of 35 days, MSCs seeded on GMPs exhibited more cell-cell contacts, greater chondrogenic potential, and a down-regulation of osteogenic markers compared to the controls. Although the factors of GMP crosslinking and size had nominal influence on MSC differentiation and aggregation, GMPs demonstrate potential as an adherent-substrate for improving cell delivery from hydrogel scaffolds by facilitating cell-cell contacts and improving MSC differentiation. PMID:26935924

  9. Advances in autologous chondrocyte implantation and related techniques for cartilage repair.

    PubMed

    Foldager, Casper Bindzus

    2013-04-01

    Articular cartilage is a specialized tissue exhibiting low intrinsic capabilities of regeneration or healing after injury. Autologous chondrocyte implantation (ACI) and scaffold-supported ACI are often used for treatment of larger chondral defects (> 2 cm2). These utilize open surgery re-implantation of ex vivo cultured autologous chondrocytes harvested as a biopsy arthroscopically in a prior surgery. This two-step procedure is an advanced and expensive treatment that despite high expectations have failed to regenerate articular cartilage in a consistent and predictable fashion, and as many as 25% the operated of patients have dissatisfactory outcomes. The objective of the present thesis was to address and investigate methods for optimizing the steps involved in the ACI and scaffold-supported ACI treatment including chondrocyte culture environment, chondrocyte labeling and tracking, improved biomaterials, and cell seeding densities. We hypothesized that these areas were eligible for targeted optimization, which has been addressed in the five papers constituting the work performed in the present thesis. The first two studies address the in vitro cell expansion of chondrocytes before re-implantation. After validation of hypoxia-suitable housekeeping genes for quantitative gene expression analysis using previously validated algorithms (study 1) the effect of combined hypoxic- and 3D culture on human chondrocytes gene expression was investigated (study 2). An in vitro experiment was performed to determine the effect on gene expression of an intracellular superparamagnetic labeling agent for 1.5T MRI-tracking of alginate-embedded human chondrocytes (study 3). We further performed a literature study, reviewing the cell seeding densities of the implanted chondrocytes used in clinically available cell transplantation-based treatments for cartilage repair (study 4). Finally, we tested the addition of dermatan sulfate to a clinically approved methoxy-polyethen-glycol (MPEG) substituted polylactide-co-glycolic acid (PLGA) scaffold by implantation of cell-free scaffolds in an osteochondral rabbit model (study 5). We determined a set of hypoxia-stable reference genes in study 1 that were then used in study 2. We observed that there was a positive effect on chondrogenic gene expression in human chondrocytes when culturing in 3D compared to monolayer and in hypoxia compared to normoxia and that there was an additional positive combined effect of 3D and hypoxia. Using a clinical MRI-system we were able to track labeled chondrocytes for up to 4 weeks, but we found that the labeling agent had significant effects on chondrocyte gene expression, which could potentially confound results when used in vivo. In our review of chondrocyte seeding densities we found large variability between commercial products and a very limited preclinical basis for the applied densities. Lastly, we found that there was no positive effect in vivo of adding dermatan sulfate to MPEG-PLGA scaffold in osteochondral repair. We conclude that while the outcome of ACI-related treatments certainly is multifactorial it may be improved by optimizing the in vitro culture by hypoxic and 3D culture and by adjusting the chondrocyte seeding density. Our studies on biomaterials and potential system for cell tracking in vivo did not show results that justified further studies and clinical trials. PMID:23651721

  10. Inorganic-organic hydrogel scaffolds for tissue engineering

    NASA Astrophysics Data System (ADS)

    Bailey, Brennan Margaret

    Analogous to the extracellular matrix (ECM) of natural tissues, properties of a tissue engineering scaffold direct cell behavior and thus regenerated tissue properties. These include both physical properties (e.g. morphology and modulus) and chemical properties (e.g. hydrophobicity, hydration and bioactivity). Notably, recent studies suggest that scaffold properties (e.g. modulus) may be as potent as growth factors in terms of directing stem cell fate. Thus, 3D scaffolds possessing specific properties modified for optimal cell regeneration have the potential to regenerate native-like tissues. Photopolymerizable poly(ethylene glycol) diacrylate (PEG-DA)-based hydrogels are frequently used as scaffolds for tissue engineering. They are ideal for controlled studies of cell-material interactions due to their poor protein adsorption in the absence of adhesive ligands thereby making them "biological blank slates". However, their range of physical and chemical properties is limited. Thus, hydrogel scaffolds which maintain the benefits of PEG-DA but possess a broader set of tunable properties would allow the establishment of predictive relationships between scaffold properties, cell behavior and regenerated tissue properties. Towards this goal, this work describes a series of unique hybrid inorganic-organic hydrogel scaffolds prepared using different solvents and also in the form of continuous gradients. Properties relevant to tissue regeneration were investigated including: swelling, morphology, modulus, degradation rates, bioactivity, cytocompatibility, and protein adhesion. These scaffolds were based on the incorporation of hydrophobic, bioactive and osteoinductive methacrylated star polydimethylsiloxane (PDMSstar-MA) ["inorganic component"] into hydrophilic PEG-DA ["organic component"]. The following parameters were varied: molecular weight (Mn) of PEG-DA (Mn = 3k & 6k g/mol) and PDMSstar-MA (Mn = 1.8k, 7k, 14k), ratio of PDMSstar-MA to PEG-DA (0:100 to 20:80), total macromer concentration (5 to 20 wt%) and utilizing either water or dichloromethane (DCM) fabrication solvent. The use of DCM produced solvent induced phase separation (SIPS) resulting in scaffolds with macroporous morphologies, enhanced modulus and a more homogenous distribution of the PDMSstar-MA component throughout. These hybrid hydrogel scaffolds were prepared in the form of continuous gradients such that a single scaffold contains spatially varied chemical and physical properties. Thus, cell-material interaction studies may be conducted more rapidly at different "zones" defined along the gradient. These gradients are also expected to benefit the regeneration of the osteochondral interface, an interfacial tissue that gradually transitions in tissue type. The final aspect of this work was focused on enhancing the osteogenic potential of PDMS via functionalization with amine and phosphonate. Both amine and phosphonate moieties have demonstrated bioactivity. Thus, it was expected that these properties will be enhanced for amine and phosphonate functionalized PDMS. The subsequent incorporation of these PDMS-based macromers into the previously described PEG-DA scaffold system is expected to be valuable for osteochondral tissue regeneration.

  11. Design and validation of a compressive tissue stimulator with high-throughput capacity and real-time modulus measurement capability.

    PubMed

    Salvetti, David J; Pino, Christopher J; Manuel, Steven G; Dallmeyer, Ian; Rangarajan, Sanjeet V; Meyer, Tobias; Kotov, Misha; Shastri, V Prasad

    2012-03-01

    Mechanical stimulation has been shown to impact the properties of engineered hyaline cartilage constructs and is relevant for engineering of cartilage and osteochondral tissues. Most mechanical stimulators developed to date emphasize precision over adaptability to standard tissue culture equipment and protocols. The realization of mechanical characteristics in engineered constructs approaching native cartilage requires the optimization of complex variables (type of stimulus, regimen, and bimolecular signals). We have proposed and validated a stimulator design that focuses on high construct capacity, compatibility with tissue culture plastic ware, and regimen adaptability to maximize throughput. This design utilizes thin force sensors in lieu of a load cell and a linear encoder to verify position. The implementation of an individual force sensor for each sample enables the measurement of Young's modulus while stimulating the sample. Removable and interchangeable Teflon plungers mounted using neodymium magnets contact each sample. Variations in plunger height and design can vary the strain and force type on individual samples. This allows for the evaluation of a myriad of culture conditions and regimens simultaneously. The system was validated using contact accuracy, and Young's modulus measurements range as key parameters. Contact accuracy for the system was excellent within 1.16% error of the construct height in comparison to measurements made with a micrometer. Biomaterials ranging from bioceramics (cancellous bone, 123 MPa) to soft gels (1% agarose, 20 KPa) can be measured without any modification to the device. The accuracy of measurements in conjunction with the wide range of moduli tested demonstrate the unique characteristics of the device and the feasibility of using this device in mapping real-time changes to Young's modulus of tissue constructs (cartilage, bone) through the developmental phases in ex vivo culture conditions. PMID:21988089

  12. LOW-INTENSITY PULSED ULTRASOUND PROMOTES CHONDROGENIC PROGENITOR CELL MIGRATION VIA FOCAL ADHESION KINASE PATHWAY

    PubMed Central

    Jang, Kee W.; Ding, Lei; Seol, Dongrim; Lim, Tae-hong; Buckwalter, Joseph A.; Martin, James A.

    2014-01-01

    Low-intensity pulsed ultrasound (LIPUS) has been frequently studied for its beneficial effects on the repair of injured articular cartilage. Here, we hypothesized that these effects are due to stimulation of chondrogenic progenitor cell (CPC) migration toward injured areas in cartilage through focal adhesion kinase (FAK) activation. CPC chemotaxis in bluntly impacted osteochondral explants was examined by confocal microscopy and migratory activity of cultured CPCs was measured in trans-well and monolayer scratch assays. FAK activation by LIPUS was analyzed in cultured CPCs by western blot. LIPUS effects were compared with the effects of two known chemotactic factors; formylated-methionine peptides (fMLF), and high-mobility group box 1 (HMGB1) protein. LIPUS significantly enhanced CPC migration on explants and in cell culture assays. Phosphorylation of FAK at the kinase domain (Tyr 576/577) was maximized by 5 minute exposure to LIPUS at a dose of 27.5 mW/cm2 and at a frequency of 3.5 MHz. Treatment with fMLF, but not HMBG1 enhanced FAK activation to a degree similar to LIPUS, but neither fMLF nor HMGB1 enhanced the LIPUS effect. LIPUS-induced CPC migration was blocked by suppressing FAK phosphorylation with a Src family kinases (SFKs) inhibitor that blocks FAK phosphorylation. Our results imply that LIPUS might be utilized to promote cartilage healing by inducing the migration of CPCs to injured sites, which could delay or prevent the onset of post-traumatic osteoarthritis (PTOA). PMID:24612644

  13. Bioactive glass in tissue engineering.

    PubMed

    Rahaman, Mohamed N; Day, Delbert E; Bal, B Sonny; Fu, Qiang; Jung, Steven B; Bonewald, Lynda F; Tomsia, Antoni P

    2011-06-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  14. A Specialized Fibular Locking Plate for Lateral Malleolar Fractures.

    PubMed

    Yeo, Eui Dong; Kim, Hak Jun; Cho, Woo In; Lee, Young Koo

    2015-01-01

    We evaluated the outcomes and complications of a specialized fibular locking plate in the treatment of lateral malleolar fractures. The study included 27 patients (13 males and 14 females; mean age 46, range 16 to 73 years) with a minimum 1-year follow-up period. The study included 9 (33%) isolated lateral malleolar, 6 (23%) bimalleolar, 10 (37%) trimalleolar fractures, and 2 (7%) pilon fractures, all of which were treated using a specialized fibular locking plate for internal fixation. Bony union was monitored, and the patients' objective satisfaction was evaluated using the EQ-5D questionnaire (EuroQol Group). The patients were followed up after 1 year, and bony union was confirmed using a simple radiograph. The EQ-5D median ± standard deviation was 70 ± 15 (range 40 to 90) points at discharge, 80 ± 13 (range 40 to 90) at 6 weeks, 85 ± 11 (range 50 to 90) at 3 months, 90 ± 8 (range 60 to 90) at 6 months, and 90 ± 9 (range 70 to 95) at 1 year. Therefore, the EQ-5D score increased with time. No significant difference was found when stratified by sex or age (Mann-Whitney U test, p < .05). Eight complications (29%) developed: 1 superficial infection at the operative site, 1 case (3%) of osteomyelitis, 2 cases (7%) of an osteochondral lesion of the talus, and 5 cases (19%) of metallosis. A specialized fibular locking plate has the advantages of being an easy procedure, providing good patient satisfaction, and achieving complete bony union in all patients. However, additional complications developed compared with other well-known methods for fibular fracture treatment. PMID:26213160

  15. Distal Metaphyseal Ulnar Shortening Osteotomy: Technique, Pearls, and Outcomes

    PubMed Central

    Khouri, Joseph S.; Hammert, Warren C.

    2014-01-01

    Background Ulnar sided wrist pain is a commonly encountered complaint of the hand surgeon, and ulnar impaction is a common cause. Surgical treatment aims to reduce the force transmitted through the ulna and traditionally includes diaphyseal ulnar shortening osteotomy and the “wafer” procedure. These procedures have known shortcomings. We describe an alternative option known as the distal metaphyseal ulnar shortening osteotomy (DMUSO). Materials and Methods Retrospective review of eight procedures was undertaken to assess radiographic healing, objective measurements of wrist and forearm motion, grip and pinch strength, and subjective measures of Disabilities of the Arm, Shoulder, and Hand (DASH), Patient-Rated Wrist Evaluation (PRWE), and Michigan Hand Outcomes Questionnaire (MHQ) at a minimum of 12 months following surgery. Description of Technique A wedge osteotomy is made in the osteochondral region of the distal metaphysis of the ulna, and a headless compression screw is used for fixation. Results Five women and three men underwent DMUSO with average follow up at 13 months; the dominant wrist was affected in 7 of 8 patients. The affected wrist had less motion in all planes, and grip and pinch strength was also less in the affected wrist, but only wrist extension was significantly different from the contralateral side. These findings likely did not have an effect on the clinical outcome. Subjective outcomes included average DASH score of 13 (0–35), PRWE 19 (40–11), and MHQ score of 88 (85–100). Conclusions DMUSO is a viable option for patients with ulnar impaction syndrome. It requires intra-articular exposure of the distal radioulnar joint (DRUJ) but is less invasive then diaphyseal shortening. It permits early and reliable return of joint motion and function while avoiding the potential need for hardware removal by using a buried screw. PMID:25097810

  16. Loss of Tbx1 induces bone phenotypes similar to cleidocranial dysplasia.

    PubMed

    Funato, Noriko; Nakamura, Masataka; Richardson, James A; Srivastava, Deepak; Yanagisawa, Hiromi

    2015-01-15

    T-box transcription factor, TBX1, is the major candidate gene for 22q11.2 deletion syndrome (DiGeorge/ Velo-cardio-facial syndrome) characterized by facial defects, thymus hypoplasia, cardiovascular anomalies and cleft palates. Here, we report that the loss of Tbx1 in mouse (Tbx1(-/-)) results in skeletal abnormalities similar to those of cleidocranial dysplasia (CCD) in humans, which is an autosomal-dominant skeletal disease caused by mutations in RUNX2. Tbx1(-/-) mice display short stature, absence of hyoid bone, failed closure of fontanelle, bifid xiphoid process and hypoplasia of clavicle and zygomatic arch. A cell-type-specific deletion of Tbx1 in osteochondro-progenitor (Tbx1(OPKO)) or mesodermal (Tbx1(MKO)) lineage partially recapitulates the Tbx1(-/-) bone phenotypes. Although Tbx1 expression has not been previously reported in neural crest, inactivation of Tbx1 in the neural crest lineage (Tbx1(NCKO)) leads to an absence of the body of hyoid bone and postnatal lethality, indicating an unanticipated role of Tbx1 in neural crest development. Indeed, Tbx1 is expressed in the neural crest-derived hyoid bone primordium, in addition to mesoderm-derived osteochondral progenitors. Ablation of Tbx1 affected Runx2 expression in calvarial bones and overexpression of Tbx1 induced Runx2 expression in vitro. Taken together, our current studies reveal that Tbx1 is required for mesoderm- and neural crest-derived osteoblast differentiation and normal skeletal development. TBX1 mutation could lead to CCD-like bone phenotypes in human. PMID:25209980

  17. Regeneration of articular cartilage of the knee.

    PubMed

    Rodriguez-Merchan, E Carlos

    2013-04-01

    Cartilage therapy for focal articular lesions of the knee has been implemented for more than a decade, and it is becoming increasingly available. What do we know on the healing response of cartilage lesions? What do we know on the treatment of focal cartilage lesions of the knee and the prognostic factors involved? PubMed articles related to articular cartilage regeneration of the knee in clinical studies were searched from January 2006 to November 2012, using the following key words: articular cartilage, regeneration, clinical studies, and knee. A total of 44 reports were found. They showed the following possibilities for the treatment of focal lesions of the articular cartilage of the knee: cartilage regeneration and repair including cartilage reparation with gene-activated matrices, autologous chondrocyte implantation (ACI) and matrix-induced ACI (MACI), microfracture, osteochondral autograft transfer (mosaicplasty), biological approaches (scaffolds, mesenchymal stem cells-MSCs, platelet-rich plasma, growing factors-GF, bone morphogenetic proteins-BMPs, magnetically labeled synovium-derived cells-M-SDCs, and elastic-like polypeptide gels), osteotomies, stem-cell-coated titanium implants, and chondroprotection with pulsed electromagnetic fields. Untreated cartilage lesions on the femoral condyles had a superior healing response compared to those on the tibial plateaus, and in the patellofemoral joint. Clinical outcome regarding the treatment of medial defects is better than that of the lateral defects. Improvement from baseline was better for patients < or = 30 years compared with patients > or = 30 years. ACI, MACI, and mosaicplasty have shown similar results. The results of comparative clinical studies using ACI have shown some superiority over conventional microfracturing in medium or large defects and in long-term durability. Some biological methods such as scaffolds, MSCs, GF, M-SDCs, BMPs, and elastic-like polypeptide gels still need more research. PMID:23263546

  18. “Basket weave technique” for medial patellofemoral ligament reconstruction: Clinical outcome of a prospective study

    PubMed Central

    Kodkani, Pranjal S

    2016-01-01

    Background: Bone tunneling and implants with rigid fixations for medial patellofemoral ligament (MPFL) reconstruction are known to compromise results and are avoidable, especially in skeletally immature subjects. This study was to assess if these deficiencies were overcome with the technique devised by the author which avoids implants and bone tunnels. Results were assessed for complication rate and outcome. Materials and Methods: Fifty six knees of recurrent lateral patellar dislocation were treated in the past 49 months by MPFL reconstruction. Thirty nine were female and 17 male knees. The mean age was 20.6 years (range 9-48 years). Mean followup was 26 months. Five knees had previously failed stabilization procedures. Thirty one cases had Dejours Type A or B and 12 had Type C trochlear dysplasia. Arthroscopy was performed for associated injuries and loose bodies. Seven knees required loose body removal. Five knees underwent lateral retinacular release. Four knees had tibial tuberosity transfer. One knee had an associated anterior cruciate ligament reconstruction. An anatomical MPFL reconstruction was performed using hamstring autograft without the need for intraoperative fluoroscopy. Only soft tissue fixation was necessary with this newly devised technique and suturing. A rapid rehabilitation protocol was implemented with monthly followup until normalcy and 6 monthly thereafter. Results: All achieved full range of motion and normal mediolateral stability. There was no recurrence of dislocation. No major surgery related complications. One patella fracture at 8 months was due to a fall developed terminal restriction of flexion. Those in sports could return to their sporting activities (Tegner 1–9). Cases with osteochondral fractures had occasional pain that subsided in 1 year. Mean Kujala score improved from 64.3 to 99.69 with KOOS score near normal in all. Conclusion: This new method of MPFL reconstruction gives excellent results. It avoids complications related to bone tunneling and implants. It is a safe, effective, reliable and reproducible technique. PMID:26952121

  19. Of Mice, Men and Elephants: The Relation between Articular Cartilage Thickness and Body Mass

    PubMed Central

    Malda, Jos; de Grauw, Janny C.; Benders, Kim E. M.; Kik, Marja J. L.; van de Lest, Chris H. A.; Creemers, Laura B.; Dhert, Wouter J. A.; van Weeren, P. René

    2013-01-01

    Mammalian articular cartilage serves diverse functions, including shock absorption, force transmission and enabling low-friction joint motion. These challenging requirements are met by the tissue’s thickness combined with its highly specific extracellular matrix, consisting of a glycosaminoglycan-interspersed collagen fiber network that provides a unique combination of resilience and high compressive and shear resistance. It is unknown how this critical tissue deals with the challenges posed by increases in body mass. For this study, osteochondral cores were harvested post-mortem from the central sites of both medial and lateral femoral condyles of 58 different mammalian species ranging from 25 g (mouse) to 4000 kg (African elephant). Joint size and cartilage thickness were measured and biochemical composition (glycosaminoclycan, collagen and DNA content) and collagen cross-links densities were analyzed. Here, we show that cartilage thickness at the femoral condyle in the mammalian species investigated varies between 90 µm and 3000 µm and bears a negative allometric relationship to body mass, unlike the isometric scaling of the skeleton. Cellular density (as determined by DNA content) decreases with increasing body mass, but gross biochemical composition is remarkably constant. This however need not affect life-long performance of the tissue in heavier mammals, due to relatively constant static compressive stresses, the zonal organization of the tissue and additional compensation by joint congruence, posture and activity pattern of larger mammals. These findings provide insight in the scaling of articular cartilage thickness with body weight, as well as in cartilage biochemical composition and cellularity across mammalian species. They underscore the need for the use of appropriate in vivo models in translational research aiming at human applications. PMID:23437402

  20. Influence of Decreasing Nutrient Path Length on the Development of Engineered Cartilage

    PubMed Central

    Bian, L.; Angione, S.L.; Ng, K.W.; Lima, E.G.; Williams, D.Y.; Mao, D.Q.; Ateshian, G.A.; Hung, C.T.

    2012-01-01

    Objective Chondrocyte-seeded agarose constructs of 4 mm diameter (2.34 mm thickness) develop spatially inhomogeneous material properties with stiffer outer edges and a softer central core suggesting nutrient diffusion limitations to the central construct region1. The effects of reducing construct thickness and creating channels running through the depth of the thick constructs were examined. Methods In Study 1, the properties of engineered cartilage of 0.78mm (thin) or 2.34mm (thick) thickness were compared. In Study 2, a single nutrient channel (1 mm diameter) was created in the middle of each thick construct. In Study 3, the effects of channels on larger 10 mm diameter, thick constructs was examined. Results Thin constructs developed superior mechanical and biochemical properties than thick constructs. The channeled constructs developed significantly higher mechanical properties versus control channel-free constructs while exhibiting similar GAG and collagen content. Collagen staining suggested that channels resulted in a more uniform fibrillar network. Improvements in constructs of 10mm diameter were similarly observed. Conclusions This study demonstrated that more homogeneous tissue engineered cartilage constructs with improved mechanical properties can be achieved by reducing their thickness or incorporating macroscopic nutrient channels. Our data further suggests that these macroscopic channels remain open long enough to promote this enhanced tissue development while exhibiting the potential to refill with cell elaborated matrix with additional culture time. Together with reports that <3 mm defects in cartilage heal in vivo and that irregular holes are associated with clinically used osteochondral graft procedures, we anticipate that a strategy of incorporating macroscopic channels may aid the development of clinically-relevant engineered cartilage with functional properties. PMID:19022685

  1. [Arthroscopically assisted treatment of ankle fractures].

    PubMed

    Braunstein, M; Baumbach, S F; Böcker, W; Mutschler, W; Polzer, H

    2016-02-01

    Acute ankle fractures are one of the most common fractures in adults with an incidence of 0.1-0.2 % per year. Operative treatment by open reduction and internal fixation (ORIF) is the standard method of treatment for unstable or dislocated fractures. The main goal of the operation is the anatomical realignment of the joint and restoration of ankle stability; nevertheless, anatomical reduction does not automatically lead to favorable clinical results. According to several studies the mid-term and in particular the long-term outcome following operative treatment is often poor with residual symptoms including chronic pain, stiffness, recurrent swelling and ankle instability. There is growing evidence that this poor outcome might be related to occult intra-articular injuries involving cartilage and soft tissues. In recent studies the frequency of fracture-related osteochondral lesions was reported to be approximately 64 %. By physical examination, standard radiography or even computed tomography (CT), these intra-articular pathologies cannot be reliably diagnosed; therefore, many authors emphasize the value of ankle arthroscopy in acute fracture treatment as it has become a safe and effective diagnostic and therapeutic procedure. Arthroscopically assisted open reduction and internal fixation (AORIF) allows control of the reduction as well examination of all intra-articular structures. If necessary, intra-articular pathologies can be addressed by removing ruptured ligaments and loose bodies, performing chondroplasty or microfracturing. So far there is no evidence that supplementary ankle arthroscopy increases the complication rate. On the other hand, the positive effect of AORIF has also not been clearly documented; nevertheless, there are clear indications that arthroscopically assisted fracture treatment is beneficial, especially in complex fractures. PMID:26796120

  2. Assessing degeneration of human articular cartilage with ultra-short echo time (UTE) T2* mapping

    PubMed Central

    Williams, Ashley; Qian, Yongxian; Bear, David; Chu, Constance R.

    2010-01-01

    Objective To examine the sensitivity of ultra-short echo time (UTE) T2* mapping to collagen matrix degeneration in human articular cartilage. Methods MRI UTE-T2* maps and standard T2 maps were acquired on four human tibial plateau explants. Thirty-three osteochondral cores were harvested for polarized light microscopy (PLM), and composition analyses. Collagen matrix integrity was evaluated from PLM and histological images. Matrix integrity and composition was compared to standard T2 values and UTE-T2* values on a spatially registered basis. Results UTE-T2* values varied with matrix degeneration (p=0.008) and were lower in severely degraded cartilage compared to healthy tissue (p=0.012). A trend for higher UTE-T2* values in healthy tissue compared to mildly degenerate tissue (p=0.051) was detected. Standard T2 values were not found to vary with matrix degeneration (p=0.13) but tended to be higher in severely degraded cartilage compared to healthy tissue. UTE-T2* value variations were independent of type II collagen and glycosaminoglycan contents. UTE-T2* mapping of deep cartilage, adjacent to subchondral bone, was more robust than standard T2 mapping in this zone. Conclusion UTE-T2* mapping of articular cartilage is sensitive to matrix degeneration and detects short T2 signal, particularly in deep tissue, that is not well captured by standard T2 mapping. Correlation of UTE-T2* values and PLM indices supports the hypothesis that both may be sensitive to collagen microstructure. Further exploration of UTE-T2* mapping as a noninvasive tool to detect early articular cartilage degeneration is warranted. PMID:20170769

  3. Stem Cell Therapies for Knee Cartilage Repair: The Current Status of Preclinical and Clinical Studies

    PubMed Central

    Anderson, John A.; Little, Dianne; Toth, Alison P.; Moorman, Claude T.; Tucker, Bradford S.; Ciccotti, Michael G.; Guilak, Farshid

    2014-01-01

    Background Articular cartilage damage of the knee is common, causing significant morbidity worldwide. Many adult tissues contain cells that are able to differentiate into multiple cell types, including chondrocytes. These stem cells have gained significant attention over the past decade and may become frontline management for cartilage defects in the very near future. Purpose The role of stem cells in the treatment of knee osteochondral defects was reviewed. Recent animal and clinical studies were reviewed to determine the benefits and potential outcomes of using stem cells for cartilage defects. Study Design Literature review. Methods A PubMed search was undertaken. The key phrase “stem cells and knee” was used. The search included reviews and original articles over an unlimited time period. From this search, articles outlining animal and clinical trials were selected. A search of current clinical trials in progress was performed on the clinicaltrials.gov website, and “stem cells and knee” was used as the search phrase. Results Stem cells have been used in many recent in vitro and animal studies. A number of cell-based approaches for cartilage repair have progressed from preclinical animal studies into clinical trials. Conclusion The use of stem cells for the treatment of cartilage defects is increasing in animal and clinical studies. Methods of delivery of stem cells to the knee’s cartilage vary from direct injection to implantation with scaffolds. While these approaches are highly promising, there is currently limited evidence of a direct clinical benefit, and further research is required to assess the overall outcome of stem cell therapies for knee cartilage repair. PMID:24220016

  4. Acute Osteoclast Activity following Subchondral Drilling Is Promoted by Chitosan and Associated with Improved Cartilage Repair Tissue Integration

    PubMed Central

    Chen, G.; Sun, J.; Lascau-Coman, V.; Chevrier, A.; Marchand, C.; Hoemann, Caroline D.

    2011-01-01

    Objective: Cartilage-bone integration is an important functional end point of cartilage repair therapy, but little is known about how to promote integration. We tested the hypothesis that chitosan-stabilized blood clot implant elicits osteoclasts to drilled cartilage defects and promotes repair and cartilage-bone integration. Design: Bilateral trochlear defects in 15 skeletally mature rabbit knees were microdrilled and then treated with chitosan–glycerol phosphate (GP)/blood implant with fluorescent chitosan tracer and thrombin to accelerate in situ solidification or with thrombin alone. Chitosan clearance, osteoclast density, and osteochondral repair were evaluated at 1, 2, and 8 weeks at the outside, edge, and through the proximal microdrill holes. Results: Chitosan was retained at the top of the drill holes at 1 week as extracellular particles became internalized by granulation tissue cells at 2 weeks and was completely cleared by 8 weeks. Osteoclasts burst-accumulated at microdrill hole edges at 1 week, in new woven bone at the base of the drill holes at 2 weeks, and below endochondral cartilage repair at 8 weeks. Implants elicited 2-fold more osteoclasts relative to controls (P < 0.001), a more complete drill hole bone repair, and improved cartilage-bone integration and histological tissue quality. Treated and control 8-week cartilage repair tissues contained 85% collagen type II. After 8 weeks of repair, subchondral osteoclast density correlated positively with bone-cartilage repair tissue integration (P < 0.0005). Conclusions: Chitosan-GP/blood implant amplified the acute influx of subchondral osteoclasts through indirect mechanisms, leading to significantly improved repair and cartilage-bone integration without inducing net bone resorption. Osteoclasts are cellular mediators of marrow-derived cartilage repair integration. PMID:26069578

  5. Microsphere-Based Scaffolds Carrying Opposing Gradients of Chondroitin Sulfate and Tricalcium Phosphate

    PubMed Central

    Gupta, Vineet; Mohan, Neethu; Berkland, Cory J.; Detamore, Michael S.

    2015-01-01

    Extracellular matrix (ECM) components, such as chondroitin sulfate (CS) and tricalcium phosphate, serve as raw materials, and thus spatial patterning of these raw materials may be leveraged to mimic the smooth transition of physical, chemical, and mechanical properties at the bone-cartilage interface. We hypothesized that encapsulation of opposing gradients of these raw materials in high molecular weight poly(d,l-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds would enhance differentiation of rat bone marrow–derived stromal cells. The raw material encapsulation altered the microstructure of the microspheres and also influenced the cellular morphology that depended on the type of material encapsulated. Moreover, the mechanical properties of the raw material encapsulating microsphere-based scaffolds initially relied on the composition of the scaffolds and later on were primarily governed by the degradation of the polymer phase and newly synthesized ECM by the seeded cells. Furthermore, raw materials had a mitogenic effect on the seeded cells and led to increased glycosaminoglycan (GAG), collagen, and calcium content. Interestingly, the initial effects of raw material encapsulation on a per-cell basis might have been overshadowed by medium-regulated environment that appeared to favor osteogenesis. However, it is to be noted that in vivo, differentiation of the cells would be governed by the surrounding native environment. Thus, the results of this study demonstrated the potential of the raw materials in facilitating neo-tissue synthesis in microsphere-based scaffolds and perhaps in combination with bioactive signals, these raw materials may be able to achieve intricate cell differentiation profiles required for regenerating the osteochondral interface. PMID:26191526

  6. Investigation of Localized Delivery of Diclofenac Sodium from Poly(D,L-Lactic Acid-co-Glycolic Acid)/Poly(Ethylene Glycol) Scaffolds Using an In Vitro Osteoblast Inflammation Model

    PubMed Central

    Sidney, Laura E.; Heathman, Thomas R.J.; Britchford, Emily R.; Abed, Arif; Rahman, Cheryl V.

    2015-01-01

    Nonunion fractures and large bone defects are significant targets for osteochondral tissue engineering strategies. A major hurdle in the use of these therapies is the foreign body response of the host. Herein, we report the development of a bone tissue engineering scaffold with the ability to release anti-inflammatory drugs, in the hope of evading this response. Porous, sintered scaffolds composed of poly(D,L-lactic acid-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) were prepared with and without the anti-inflammatory drug diclofenac sodium. Analysis of drug release over time demonstrated a profile suitable for the treatment of acute inflammation with ∼80% of drug released over the first 4 days and a subsequent release of around 0.2% per day. Effect of drug release was monitored using an in vitro osteoblast inflammation model, comprised of mouse primary calvarial osteoblasts stimulated with proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Levels of inflammation were monitored by cell viability and cellular production of nitric oxide (NO) and prostaglandin E2 (PGE2). The osteoblast inflammation model revealed that proinflammatory cytokine addition to the medium reduced cell viability to 33%, but the release of diclofenac sodium from scaffolds inhibited this effect with a final cell viability of ∼70%. However, releasing diclofenac sodium at high concentrations had a toxic effect on the cells. Proinflammatory cytokine addition led to increased NO and PGE2 production; diclofenac-sodium-releasing scaffolds inhibited NO release by ∼64% and PGE2 production by ∼52%, when the scaffold was loaded with the optimal concentration of drug. These observations demonstrate the potential use of PLGA/PEG scaffolds for localized delivery of anti-inflammatory drugs in bone tissue engineering applications. PMID:25104438

  7. The Effects of Focal Articular Defects on Cartilage Contact Mechanics

    PubMed Central

    Gratz, Kenneth R.; Wong, Benjamin L.; Bae, Won C.; Sah, Robert L.

    2010-01-01

    Focal damage to articular cartilage is common in arthroscopy patients and may contribute to progressive tissue degeneration by altering the local mechanical environment. The effects of a focal defect, which may be oriented at various orientations relative to the subchondral bone, on the dynamics of cartilage contact and deformation are unclear. The objective of this study was to elucidate the effect of experimental full thickness focal defects, oriented at 80° or 100° relative to the subchondral bone, on intra-tissue strain and surface sliding of opposing cartilage surfaces during compression and stress relaxation. Pairs of intact bovine osteochondral blocks were compressed uniaxially by 20%, and allowed to stress relax. Tissue deformation was recorded by video microscopy. A full-thickness defect (with either 80° or 100° edges) was created in one block from each pair. Blocks were allowed to re-swell and retested. Defect edges were then re-cut with the opposite orientation, allowed to re-swell, and retested again. Stained nuclei were tracked by digital image correlation and used to quantify cartilage strains and surface sliding. The results indicated that loading of intact samples caused axial strain magnitudes that decreased with depth and relatively little sliding. With loading of samples containing defects, strain magnitudes were elevated in cartilage adjacent to, and opposing, defects. For samples with edge orientations of 100°, sliding magnitudes were increased over surfaces adjacent to defects. These local mechanical changes due to full-thickness articular cartilage defects may contribute to altered chondrocyte metabolism, tissue damage, or accelerated wear. PMID:18979528

  8. Arthroscopy of the subtalar joint and arthroscopic subtalar arthrodesis.

    PubMed

    Tasto, James P

    2006-01-01

    Subtalar arthroscopy has become a valuable adjunct to the tools used in lower extremity surgery. For the past 25 years, ankle arthroscopy has been in vogue for treating a variety of conditions. Subtalar arthroscopy has more treatment limitations and is more technically difficult to perform than ankle arthroscopy because of the anatomic confines and structure of the subtalar joint. Most procedures are performed on the posterior aspect of the subtalar joint. The subtalar joint is composed of three articulations (posterior, middle, and anterior facets) and is surrounded by a variety of intra-articular and extra-articular ligaments, whose anatomy must be fully understood before attempting this procedure. Subtalar arthroscopy may be indicated for diagnostic purposes and for débridement of synovial impingement syndromes in the sinus tarsi. It may be used to examine loose bodies or osteochondral lesions, to address fractures of the lateral process of the talus, and to evaluate subtalar instability to determine appropriate stabilization methods. Arthroscopic subtalar arthrodesis also has gained credibility over the past 10 years as an acceptable surgical procedure. Arthroscopic evaluation of subtalar instability is useful in planning the appropriate stabilization. Subtalar arthroscopy is usually performed with the patient in the lateral decubitus position without traction. Anterior and posterior portals as well as an accessory anterior portal are usually necessary to perform all of the above procedures. Because of the limited confines of the joint, care must be taken to prevent any articular cartilage damage. When performing subtalar arthroscopy in conjunction with ankle arthroscopy, the subtalar arthroscopy should be performed first to avoid excessive extravasation from the ankle arthroscopy, which could obscure entry to the subtalar joint. Complications of subtalar arthroscopy are similar to those encountered in ankle arthroscopy, such as damage to the sural and superficial peroneal nerves. PMID:16958488

  9. Talar Fractures and Dislocations: A Radiologist's Guide to Timely Diagnosis and Classification.

    PubMed

    Melenevsky, Yulia; Mackey, Robert A; Abrahams, R Brad; Thomson, Norman B

    2015-01-01

    The talus, the second largest tarsal bone, has distinctive imaging characteristics and injury patterns. The predominantly extraosseous vascular supply of the talus predisposes it to significant injury in the setting of trauma. In addition, the lack of muscular attachments and absence of a secondary blood supply can lead to subsequent osteonecrosis. Although talar fractures account for less than 1% of all fractures, they commonly result from high-energy trauma and may lead to complications and long-term morbidity if not recognized and managed appropriately. While initial evaluation is with foot and ankle radiographs, computed tomography (CT) is often performed to evaluate the extent of the fracture, displacement, comminution, intra-articular extension, and associated injuries. Talar fractures are divided by anatomic region: head, neck, and body. Talar head fractures can be treated conservatively if nondisplaced, warranting careful radiographic and CT evaluation to assess rotation, displacement, and extension into the neck. The modified Hawkins-Canale classification of talar neck fractures is most commonly used due to its simplicity, usefulness in guiding treatment, and prognostic value, as it correlates associated malalignment with risk of subsequent osteonecrosis. Isolated talar body fractures may be more common than previously thought. The Sneppen classification further divides talar body fractures into osteochondral talar dome, lateral and posterior process, and shear and crush comminuted central body fractures. Crush comminuted central body fractures carry a poor prognosis due to nonanatomic reduction, bone loss, and subsequent osteonecrosis. Lateral process fractures can be radiographically occult and require a higher index of suspicion for successful diagnosis. Subtalar dislocations are often accompanied by fractures, necessitating postreduction CT. Familiarity with the unique talar anatomy and injury patterns is essential for radiologists to facilitate appropriate and timely management. PMID:25969933

  10. Molecular changes after shockwave therapy in osteoarthritic knee in rats

    NASA Astrophysics Data System (ADS)

    Wang, C.-J.; Sun, Y.-C.; Wu, C.-T.; Weng, L.-H.; Wang, F.-S.

    2016-01-01

    This study investigated the molecular changes of DKK-1, MMP13, Wnt-5a and \\upbeta -catenin after extracorporeal shockwave therapy (ESWT) in anterior cruciate ligament transected (ACLT) osteoarthritic (OA) knee in rats. 27 male Spraque-Dawley rats were divided into three groups. Group I was the control one and received sham knee arthrotomy but no ACLT or ESWT. Group II underwent ACLT, but no ESWT. Group III underwent ACLT and received ESWT. The animals were killed at 12 weeks, and the harvested knee specimens were subjected to histopathological examination and immunohistochemical analysis. Radiographs of the knees were obtained at 0 and 12 weeks. At 12 weeks, radiographs of group II showed more arthritic changes with formation of osteochondral fragments, whereas very subtle arthritis was noted in groups I and III. In histopathological examination, group II showed a significant increase of Mankin score and a decrease of subchondral bone as compared to groups I and III. Group III showed a significant decrease of Mankin score and an increase of subchondral bone, with the data comparable to group I. In immunohistochemical analysis, group II showed significant increases of DKK-1 and MMP13 and decreases of Wnt-5a and \\upbeta -catenin in articular cartilage and subchondral bone as compared to groups I and III. Group III showed significant decreases of DKK-1 and MMP13 and increases of Wnt-5a and \\upbeta -catenin, with the data comparable to group I. In conclusion, the application of ESWT causes molecular changes that are consistent with the improvement in subchondral bone remodeling and chondroprotective effect in ACLT OA knees in rats.

  11. Bioactive glass in tissue engineering

    PubMed Central

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  12. Effects of optical beam angle on quantitative optical coherence tomography (OCT) in normal and surface degenerated bovine articular cartilage

    NASA Astrophysics Data System (ADS)

    Huang, Yan-Ping; Saarakkala, Simo; Toyras, Juha; Wang, Li-Ke; Jurvelin, Jukka S.; Zheng, Yong-Ping

    2011-01-01

    Quantitative measurement of articular cartilage using optical coherence tomography (OCT) is a potential approach for diagnosing the early degeneration of cartilage and assessing the quality of its repair. However, a non-perpendicular angle of the incident optical beam with respect to the tissue surface may cause uncertainty to the quantitative analysis, and therefore, significantly affect the reliability of measurement. This non-perpendicularity was systematically investigated in the current study using bovine articular cartilage with and without mechanical degradation. Ten fresh osteochondral disks were quantitatively measured before and after artificially induced surface degradation by mechanical grinding. The following quantitative OCT parameters were determined with a precise control of the surface inclination up to an angle of 10° using a step of 2°: optical reflection coefficient (ORC), variation of surface reflection (VSR) along the surface profile, optical roughness index (ORI) and optical backscattering (OBS). It was found that non-perpendicularity caused systematic changes to all of the parameters. ORC was the most sensitive and OBS the most insensitive to the inclination angle. At the optimal perpendicular angle, all parameters could detect significant changes after surface degradation (p < 0.01), except OBS (p > 0.05). Nonsignificant change of OBS after surface degradation was expected since OBS reflected properties of the internal cartilage tissue and was not affected by the superficial mechanical degradation. As a conclusion, quantitative OCT parameters are diagnostically potential for characterizing the cartilage degeneration. However, efforts through a better controlled operation or corrections based on computational compensation mechanism should be made to minimize the effects of non-perpendicularity of the incident optical beam when clinical use of quantitative OCT is considered for assessing the articular cartilage.

  13. Effect of high hydrostatic pressure on biological properties of extracellular bone matrix proteins.

    PubMed

    Diehl, Peter; Schmitt, Manfred; Schauwecker, Johannes; Eichelberg, Kay; Gollwitzer, Hans; Gradinger, Reiner; Goebel, Michael; Preissner, Klaus T; Mittelmeier, Wolfram; Magdolen, Ursula

    2005-08-01

    In orthopedic surgery, sterilization of bone used for reconstruction of osteoarticular defects caused by malignant tumors is carried out in various ways. At present, to devitalize tumor-bearing osteochondral segments, extracorporal irradiation or autoclaving is mainly used but both methods have substantial disadvantages, for instance, loss of biomechanical and biological integrity of the bone. In particular, after reimplantation, integration of the implant at the autograft-host junction is often impaired due to alteration of osteoinductivity as a result of its irradiation or autoclaving. As an alternative approach, high hydrostatic pressure (HHP) treatment of bone is suggested, a new technology which is in the preclinical testing stage, with the aim to inactivate tumor cells but leaving the biomechanical properties of bone, cartilage, and tendons intact. We investigated the influence of HHP on the major extracellular matrix (ECM) proteins, fibronectin (FN), vitronectin (VN), and type I collagen (Col-I), present in bone tissue, which are accountable for the biological properties within the bone. FN, VN, and Col-I were subjected to HHP < or = 600 MPa prior to coating of cell culture plates with these matrix proteins. Thereafter, the capacity of HHP-pretreated FN, VN, and Col-I to affect cell proliferation, cell adherence, and spreading of human primary osteoblast-like cells and the human osteosarcoma cell line Saos-2, was tested. Interestingly, even at HHP < or = 600 MPa, all three ECM proteins retained their biological properties because no significant changes were observed between HHP-treated and non-treated FN, VN, and Col-I regarding their biological properties to affect cell adherence, spreading, and proliferation. These data encourage further exploration of the potential of HHP to sterilize tumor-affected bone segments prior to reimplantation. While during this treatment eukaryotic cells including tumor cells will be irreversibly impaired, the bone's biomechanical properties and the biological properties of the ECM proteins FN, VN, and Col-I, respectively, are preserved. PMID:16012763

  14. Cartilage repair: 2013 Asian update.

    PubMed

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

    2013-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  16. Insight into the 3D-trabecular architecture of the human patella.

    PubMed

    Hoechel, Sebastian; Schulz, Georg; Müller-Gerbl, Magdalena

    2015-07-01

    The subchondral bone plate (SBP), a dynamic component of the osteochondral unit, shows functional adaptation to long-term loading by distribution of the mineral content in a manner best serving the mechanical demands. Since the received joint-load is transmitted into the trabecular system, the spongy bone also exhibits differences in strain energy density which models it for optimal support. To evaluate the regional variations in trabecular architecture, in accordance with the density distribution of the SBP revealing its long-term load intake, CT- and μCT-datasets of ten physiologic patellae were analysed for defined parameters of bony structure. For the SBP, the density distributions as well as area measurements were used. The trabecular architecture was described using parameters of bone morphology comprising the first 5mm (examined in 1mm steps) below the SBP. The obtained measurements are: Bone volume fraction (BV/TV); Bone surface density (BS/TV); Trabecular number (Tb.N); Trabecular separation (Tb.Sp); Trabecular thickness (Tb.Th); structure model index (SMI); and the Degree of anisotropy (DA). The evaluated architectural parameters varied within the trabecular system and showed an inhomogeneous distribution pattern. It proved to be distinctive with maxima of material and stability situated below areas of the highest long-term load intake. With increasing depth, the pattern of distribution was persistent but lessened in intensity. The parameters significantly correlated with the density distribution of the SBP within the first and second millimetres. With increasing depth down to the fifth millimetre, the coefficients of correlation decreased for all values. The trabecular network adapts to its mechanical needs and is therefore not homogenously built. Dependent upon the long-term load intake, the trabecular model optimizes the support with significant correlation to the density distribution of the SBP. PMID:25835353

  17. Hyperosmolarity normalises serum-induced changes to chondrocyte properties in a model of cartilage injury.

    PubMed

    Karim, A; Hall, A C

    2016-01-01

    Partial-thickness cartilage injuries do not heal effectively, potentially leading to degeneration as occurs in post-traumatic osteoarthritis (PTOA). The role of chondrocytes could be crucial in determining the nature of the repair; however, their response to this injury is poorly understood. We have utilised an in vitro bovine osteochondral partial-thickness scalpel injury model and determined chondrocyte properties at and distant from the injury in the presence/absence of (a) serum-free DMEM (340 mOsm), (b) synovial fluid DMEM (SF-DMEM), (c) foetal calf serum DMEM (FCS-DMEM), (d) hyperosmolar serum-free DMEM (600 mOsm), or (e) hyperosmolar FCS-DMEM for up to two weeks. Chondrocytes were fluorescently-labelled with 5-chloromethylfluorescein-diacetate (CMFDA)/propidium iodide (PI) for live/dead cells and imaged using confocal microscopy. Quantitative data were obtained on chondrocyte properties (cell volume, clusters, morphology) at and distant from the injury. In serum-free DMEM, chondrocyte morphology at the injury remained unaffected throughout culture. However, with SF-DMEM or FCS-DMEM the chondrocytes displayed an increase in volume (p < 0.0001), cluster formation (FCS; p < 0.01) and abnormal morphology (p < 0.001) compared to serum-free DMEM. Cluster formation and shape changes during FCS-DMEM culture were more pronounced than with SF-DMEM. SF-DMEM or FCS-DMEM stimulated these changes to chondrocytes at the injury with only small effects on distant cells. Hyperosmolarity inhibited the morphological and volume changes to chondrocytes induced by FCS-DMEM (p < 0.001) and the injured cartilage had the appearance of that in serum-free DMEM. Raised osmolarity may therefore have benefit in preserving the morphological phenotype of chondrocytes at the site of injury, and thus promote more effective integrative repair in partial-thickness cartilage injury. PMID:27021372

  18. Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1β and Mechanical Load

    PubMed Central

    Pohlig, Florian; Guell, Florian; Lenze, Ulrich; Lenze, Florian W.; Mühlhofer, Heinrich M. L.; Schauwecker, Johannes; Toepfer, Andreas; Mayer-Kuckuk, Philipp; von Eisenhart-Rothe, Rüdiger; Burgkart, Rainer; Salzmann, Gian M.

    2016-01-01

    Purpose In patients with osteoarthritis (OA), intraarticular injection of hyaluronic acid (HA) frequently results in reduced pain and improved function for prolonged periods of time, i.e. more than 6 months. However, the mechanisms underlying these effects are not fully understood. Our underlying hypothesis is that HA modifies the enzymatic breakdown of joint tissues. Methods To test this hypothesis, we examined osteochondral cylinders from 12 OA patients. In a bioreactor, these samples were stimulated by interleukin 1β (Il1ß) (2 ng/ml) plus mechanical load (2.0 Mpa at 0.5 Hz horizontal and 0.1 Hz vertical rotation), thus the experimental setup recapitulated both catabolic and anabolic clues of the OA joint. Results Upon addition of HA at either 1 or 3 mg/ml, we observed a significant suppression of expression of metalloproteinase (MMP)-13. A more detailed analysis based on the Kellgren and Lawrence (K&L) OA grade, showed a much greater degree of suppression of MMP-13 expression in grade IV as compared to grade II OA. In contrast to the observed MMP-13 suppression, treatment with HA resulted in a suppression of MMP-1 expression only at 1 mg/ml HA, while MMP-2 expression was not significantly affected by either HA concentration. Conclusion Together, these data suggest that under concurrent catabolic and anabolic stimulation, HA exhibits a pronounced suppressive effect on MMP-13. In the long-run these findings may benefit the development of treatment strategies aimed at blocking tissue degradation in OA patients. PMID:26934732

  19. Comparison of subjective lameness evaluation, force platforms and an inertial-sensor system to identify mild lameness in an equine osteoarthritis model.

    PubMed

    Donnell, J R; Frisbie, D D; King, M R; Goodrich, L R; Haussler, K K

    2015-11-01

    When mild lameness exists, agreement between clinicians is often controversial due to its subjective nature. The goal of the study was to compare subjective and objective methods to identify the presence of mild lameness using an established model of osteoarthritis (OA) in which OA was induced by creating a unilateral carpal osteochondral fragment (OCF) in the middle carpal joint of 16 horses. Subjective lameness evaluations (blinded and unblinded), force platforms (FP), and an inertial-sensor system (ISS) were used to detect forelimb lameness at four time points. Limbs identified as lame by each method were compared as well as compared with the OCF limb at each time point. Spearman correlations were calculated between all outcome parameters. Independent of time, blinded subjective evaluation (54%) and the ISS (60%) identified a higher percentage of horses as lame in the OCF limb compared to FP (40%). Blinded subjective evaluation and the ISS agreed which forelimb was lame more often (50%) compared with blinded subjective evaluation and the FP (38%). Induction of mild lameness within the OCF limb was supported by an increase in the frequency of horses considered lame by both subjective evaluations the ISS and a decrease (3.6%) in mean (among all horses) peak vertical force from baseline to post OCF induction. The percentage of horses identified as lame in the OCF limb, independent of time, was highest with the ISS (60%) followed by blinded subjective evaluation (51%) and the FP (42%). It was concluded that the best agreement was between subjective evaluation and the inertial-sensor system. PMID:26361749

  20. Bone fatigue and its implications for injuries in racehorses.

    PubMed

    Martig, S; Chen, W; Lee, P V S; Whitton, R C

    2014-07-01

    Musculoskeletal injuries are a common cause of lost training days and wastage in racehorses. Many bone injuries are a consequence of repeated high loading during fast work, resulting in chronic damage accumulation and material fatigue of bone. The highest joint loads occur in the fetlock, which is also the most common site of subchondral bone injury in racehorses. Microcracks in the subchondral bone at sites where intra-articular fractures and palmar osteochondral disease occur are similar to the fatigue damage detected experimentally after repeated loading of bone. Fatigue is a process that has undergone much study in material science in order to avoid catastrophic failure of engineering structures. The term 'fatigue life' refers to the numbers of cycles of loading that can be sustained before failure occurs. Fatigue life decreases exponentially with increasing load. This is important in horses as loads within the limb increase with increasing speed. Bone adapts to increased loading by modelling to maintain the strains within the bone at a safe level. Bone also repairs fatigued matrix through remodelling. Fatigue injuries develop when microdamage accumulates faster than remodelling can repair. Remodelling of the equine metacarpus is reduced during race training and accelerated during rest periods. The first phase of remodelling is bone resorption, which weakens the bone through increased porosity. A bone that is porous following a rest period may fail earlier than a fully adapted bone. Maximising bone adaptation is an important part of training young racehorses. However, even well-adapted bones accumulate microdamage and require ongoing remodelling. If remodelling inhibition at the extremes of training is unavoidable then the duration of exposure to high-speed work needs to be limited and appropriate rest periods instituted. Further research is warranted to elucidate the effect of fast-speed work and rest on bone damage accumulation and repair. PMID:24528139

  1. Design and Validation of a Compressive Tissue Stimulator with High-Throughput Capacity and Real-Time Modulus Measurement Capability

    PubMed Central

    Salvetti, David J.; Pino, Christopher J.; Manuel, Steven G.; Dallmeyer, Ian; Rangarajan, Sanjeet V.; Meyer, Tobias; Kotov, Misha

    2012-01-01

    Mechanical stimulation has been shown to impact the properties of engineered hyaline cartilage constructs and is relevant for engineering of cartilage and osteochondral tissues. Most mechanical stimulators developed to date emphasize precision over adaptability to standard tissue culture equipment and protocols. The realization of mechanical characteristics in engineered constructs approaching native cartilage requires the optimization of complex variables (type of stimulus, regimen, and bimolecular signals). We have proposed and validated a stimulator design that focuses on high construct capacity, compatibility with tissue culture plastic ware, and regimen adaptability to maximize throughput. This design utilizes thin force sensors in lieu of a load cell and a linear encoder to verify position. The implementation of an individual force sensor for each sample enables the measurement of Young's modulus while stimulating the sample. Removable and interchangeable Teflon plungers mounted using neodymium magnets contact each sample. Variations in plunger height and design can vary the strain and force type on individual samples. This allows for the evaluation of a myriad of culture conditions and regimens simultaneously. The system was validated using contact accuracy, and Young's modulus measurements range as key parameters. Contact accuracy for the system was excellent within 1.16% error of the construct height in comparison to measurements made with a micrometer. Biomaterials ranging from bioceramics (cancellous bone, 123 MPa) to soft gels (1% agarose, 20 KPa) can be measured without any modification to the device. The accuracy of measurements in conjunction with the wide range of moduli tested demonstrate the unique characteristics of the device and the feasibility of using this device in mapping real-time changes to Young's modulus of tissue constructs (cartilage, bone) through the developmental phases in ex vivo culture conditions. PMID:21988089

  2. Biomechanical evaluation of suture holding properties of native and tissue engineered articular cartilage

    PubMed Central

    DuRaine, GD; Arzi, B; Lee, JK; Lee, CA; Responte, DJ; Hu, JC; Athanasiou, KA

    2014-01-01

    Objective The purpose of this study was to determine suture-holding properties of tissue engineered neocartilage relative to native articular cartilage. To this end, suture pull-out strength was quantified for native articular cartilage and for neocartilages possessing various mechanical properties. Methods Suture holding properties were examined in vitro and in vivo. Neocartilage from bovine chondrocytes was engineered using two sets of exogenous stimuli resulting in neotissue of different biochemical compositions. Compressive and tensile properties and glycosaminoglycan, collagen, and pyridinoline cross-link contents were assayed (study 1). Suture pull-out strength was compared between neocartilage constructs, and bovine and leporine native cartilage. Uniaxial pull-out test until failure was performed after passing 6-0 Vicryl through each tissue (study 2). Subsequently, neocartilage was implanted into a rabbit model to examine short-term suture holding ability in vivo (study 3). Results Neocartilage glycosaminoglycan and collagen content per wet weight reached 4.55% ± 1.62% and 4.21 ± 0.77%, respectively. Tensile properties for neocartilage constructs reached 2.6 ± 0.77 MPa for Young’s modulus and 1.39 ± 0.63 MPa for ultimate tensile strength. Neocartilage reached ~33% of suture pull-out strength of native articular cartilage. Neocartilage cross-link content reached 50% of native values, and suture pull-out strength correlated positively with cross-link content (R2=0.74). Neocartilage sutured into rabbit osteochondral defects was successfully maintained for 3 weeks. Conclusion This study shows that pyridinoline cross-links in neocartilage may be vital in controlling suture pull-out strength. Neocartilage produced in vitro with one-third of native tissue pull-out strength appears sufficient for construct suturing and retention in vivo. PMID:24848644

  3. Morphological abnormalities in vitamin B6 deficient tarsometatarsal chick cartilage.

    PubMed

    Masse, P G; Colombo, V E; Gerber, F; Howell, D S; Weiser, H

    1990-09-01

    The aim of this study was to test the hypothesis that deficiency of vitamin B6 would produce morphological characteristics of osteochondral lathyrism. To accomplish this goal, morphological characteristics of chick cartilage in which lathyrism was produced by two separate dietary regimens was compared to morphological changes encountered in vitamin B6 deficiency. Vitamin B6 deficiency should reduce activity of lysyloxidase needed for producing intermolecular cross-links. The question to be addressed was: would this latter deficiency impair collagen morphological features and secondarily other structures indirectly by reducing collagen molecular assembly? Failure of cross-linking of collagen in the positive controls was related to a lack of functional aldehyde cross-link intermediates which are blocked by homocysteine and aminoacetonitrile. Day-old-male Lohmann chicks were fed adequate (6 mg/kg) or vitamin B6-deficient diets. Cross-link defects were induced by homocysteine-rich diets (0.6% w/w) or a diet containing aminoacetonitrile (0.1% w/w). Animals were sacrificed at 6 weeks of age and Ossa tarsalia articular cartilage specimens, as well as the proximal end of tarsometatarsus were dissected from the tibial metatarsal joint, a major weight-bearing site. Light microscopic observations revealed reduction of subarticular trabecular bone formation, concurrent with overexpansion of the hypertrophic cell zone. Ultrastructural electron microscopy observation of articular fibro-cartilage indicated significant thickening of collagen fibers in vitamin B6 deficient birds, as well as the positive controls in comparison to that of cage-matched control birds. It was concluded that vitamin B6 deficient cross-linking may be responsible for the observed delay in bone development and aforementioned cartilage histological alterations. PMID:2080430

  4. Subtalar arthroscopy using a 2.4-mm zero-degree arthroscope: indication, technical experience, and results.

    PubMed

    Siddiqui, Mashfiqul A; Chong, Keen Wai; Yeo, William; Rao, Mohana S; Rikhraj, Inderjeet S

    2010-08-01

    The subtalar joint is complex. With the advent of smaller diameter arthroscopes, subtalar arthroscopy has become an important diagnostic and therapeutic tool for subtalar joint disorders. The objective of this study was to evaluate the outcome of patients who underwent arthroscopy for subtalar joint disorders using a 2.4-mm zero-degree arthroscope. In this prospective study, 6 patients who underwent subtalar arthroscopy from September 2008 to January 2009 in the authors' institution were included. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot scores were recorded preoperatively and at 3 and 6 months postoperatively. Mean +/- SD age was 45.5 +/- 16.2 years (range, 27.5-63.2). Postoperative diagnosis included arthrofibrosis, osteoarthritis, and osteochondral disease of the subtalar joint. Mean +/- SD AOFAS scores improved from 49.67 +/- 18.83 (range, 22-76) to 67.33 +/- 14.92 (range, 53-91) at 3 months (P = .03) and 75 +/- 19.74 (range, 54-100) at 6 months (P = .004). Subtalar arthroscopy using the 2.4-mm zero-degree arthroscope shows promising results in the diagnosis and treatment of subtalar pathologies. Patients have a significant improvement in their AOFAS hindfoot scores as early as 3 months and continue to improve subsequently. Usage of the zero-degree arthroscope allows the "instrumentation hand" to maneuver more easily in space and perform the operative procedure without getting in the way of the "camera hand." It can also save on inventory costs for centers that already have the zero-degree arthroscope. The role of specialized imaging is still unclear. Diagnosis of sinus tarsi syndrome should be historical with direct visualization of the joint revealing exact etiology. PMID:20530192

  5. Identification of Cold-Temperature-Regulated Genes in Flavobacterium psychrophilum ▿

    PubMed Central

    Hesami, Shohreh; Metcalf, Devon S.; Lumsden, John S.; MacInnes, Janet I.

    2011-01-01

    Flavobacterium psychrophilum is the etiological agent of bacterial coldwater disease (BCWD) and rainbow trout fry syndrome (RTFS). It causes disease primarily in fresh water-reared salmonids, but other fish species can also be affected. A diverse array of clinical conditions is associated with BCWD, including tail rot (peduncle disease), necrotic myositis, and cephalic osteochondritis. Degradation of connective and muscular tissues by extracellular proteases is common to all of these presentations. There are no effective vaccines to prevent BCWD or RTFS, and antibiotics are often used to prevent and control disease. To identify virulence factors that might permit development of an efficacious vaccine, cDNA suppression subtractive hybridization (SSH) was used to identify cold-regulated genes in a virulent strain of F. psychrophilum. Genes predicted to encode a two-component system sensor histidine kinase (LytS), an ATP-dependent RNA helicase, a multidrug ABC transporter permease/ATPase, an outer membrane protein/protective antigen OMA87, an M43 cytophagalysin zinc-dependent metalloprotease, a hypothetical protein, and four housekeeping genes were upregulated at 8°C versus the level of expression at 20°C. Because no F. psychrophilum gene was known to be suitable as an internal standard in reverse transcription-quantitative real-time PCR (RT-qPCR) experiments, the expression stability of nine commonly used reference genes was evaluated at 8°C and 20°C. Expression of the 16S rRNA was equivalent at both temperatures, and this gene was used in RT-qPCR experiments to verify the SSH findings. With the exception of the ATCC 49513 strain, similar patterns of gene expression were obtained with 11 other representative strains of F. psychrophilum. PMID:21216906

  6. High seeding density of human chondrocytes in agarose produces tissue-engineered cartilage approaching native mechanical and biochemical properties.

    PubMed

    Cigan, Alexander D; Roach, Brendan L; Nims, Robert J; Tan, Andrea R; Albro, Michael B; Stoker, Aaron M; Cook, James L; Vunjak-Novakovic, Gordana; Hung, Clark T; Ateshian, Gerard A

    2016-06-14

    Animal cells have served as highly controllable model systems for furthering cartilage tissue engineering practices in pursuit of treating osteoarthritis. Although successful strategies for animal cells must ultimately be adapted to human cells to be clinically relevant, human chondrocytes are rarely employed in such studies. In this study, we evaluated the applicability of culture techniques established for juvenile bovine and adult canine chondrocytes to human chondrocytes obtained from fresh or expired osteochondral allografts. Human chondrocytes were expanded and encapsulated in 2% agarose scaffolds measuring ∅3-4mm×2.3mm, with cell seeding densities ranging from 15 to 90×10(6)cells/mL. Subsets of constructs were subjected to transient or sustained TGF-β treatment, or provided channels to enhance nutrient transport. Human cartilaginous constructs physically resembled native human cartilage, and reached compressive Young's moduli of up to ~250kPa (corresponding to the low end of ranges reported for native knee cartilage), dynamic moduli of ~950kPa (0.01Hz), and contained 5.7% wet weight (%/ww) of glycosaminoglycans (≥ native levels) and 1.5%/ww collagen. We found that the initial seeding density had pronounced effects on tissue outcomes, with high cell seeding densities significantly increasing nearly all measured properties. Transient TGF-β treatment was ineffective for adult human cells, and tissue construct properties plateaued or declined beyond 28 days of culture. Finally, nutrient channels improved construct mechanical properties, presumably due to enhanced rates of mass transport. These results demonstrate that our previously established culture system can be successfully translated to human chondrocytes. PMID:27198889

  7. ADAMTS-4 activity in synovial fluid as a biomarker of inflammation and effusion

    PubMed Central

    Roberts, S.; Evans, H.; Wright, K.; van Niekerk, L.; Caterson, B.; Richardson, J.B.; Kumar, K.H.S.; Kuiper, J.H.

    2015-01-01

    Summary Objective To evaluate the potential of ADAMTS-4 (aggrecanase -1) activity in synovial fluid (SF) as a biomarker of knee injury and joint disease. Design We have measured ADAMTS-4 activity in the synovial fluid of 170 orthopaedic patients with different degrees of joint pathology, using a commercial ADAMTS-4 fluorescence resonance energy transfer (FRET) substrate assay. Patients were classified at arthroscopy as (i) macroscopically normal, (ii) with an injury of the meniscus, anterior cruciate ligament or chondral/osteochondral defects or (iii) with osteoarthritis, and the influence of independent factors (age, patient group, effusion and synovial inflammation) on ADAMTS-4 activity levels was assessed. Results In most patients (106/170) ADAMTS-4 activity was undetectable; ADAMTS-4 ranged from 0 to 2.8 ng/mL in synovial fluid from patients with an injury, 0–4.1 ng/mL in osteoarthritic patients and 4.0–12.3 ng/mL in patients with large effusions. Four independent variables each significantly influenced ADAMTS-4 activity in synovial fluid (all P < 0.001): age (concordance = 0.69), presence of osteoarthritis (OA) (concordance = 0.66), level of effusion (concordance = 0.78) and inflammation (concordance = 0.68). Not only did effusion influence the amount of ADAMTS-4 activity most strongly, but it also did this in an ordered manner (P < 0.001). Conclusions The main finding of this study is that ADAMTS-4 levels in synovial fluid are most strongly correlated with inflammation and severity of effusion in the knee. Further study is required to determine if it could provide a useful tool to aid clinical diagnoses, indicate treatment, to monitor progression of joint degeneration or OA or alternatively the success of treatment. PMID:26003949

  8. Biomechanical evaluation of suture-holding properties of native and tissue-engineered articular cartilage.

    PubMed

    DuRaine, G D; Arzi, B; Lee, J K; Lee, C A; Responte, D J; Hu, J C; Athanasiou, K A

    2015-01-01

    The purpose of this study was to determine suture-holding properties of tissue-engineered neocartilage relative to native articular cartilage. To this end, suture pull-out strength was quantified for native articular cartilage and for neocartilages possessing various mechanical properties. Suture-holding properties were examined in vitro and in vivo. Neocartilage from bovine chondrocytes was engineered using two sets of exogenous stimuli, resulting in neotissue of different biochemical compositions. Compressive and tensile properties and glycosaminoglycan, collagen, and pyridinoline cross-link contents were assayed (study 1). Suture pull-out strength was compared between neocartilage constructs, and bovine and leporine native cartilage. Uniaxial pull-out test until failure was performed after passing 6-0 Vicryl through each tissue (study 2). Subsequently, neocartilage was implanted into a rabbit model to examine short-term suture-holding ability in vivo (study 3). Neocartilage glycosaminoglycan and collagen content per wet weight reached 4.55 ± 1.62% and 4.21 ± 0.77%, respectively. Tensile properties for neocartilage constructs reached 2.6 ± 0.77% MPa for Young's modulus and 1.39 ± 0.63 MPa for ultimate tensile strength. Neocartilage reached ~ 33% of suture pull-out strength of native articular cartilage. Neocartilage cross-link content reached 50% of native values, and suture pull-out strength correlated positively with cross-link content (R² = 0.74). Neocartilage sutured into rabbit osteochondral defects was successfully maintained for 3 weeks. This study shows that pyridinoline cross-links in neocartilage may be vital in controlling suture pull-out strength. Neocartilage produced in vitro with one-third of native tissue pull-out strength appears sufficient for construct suturing and retention in vivo. PMID:24848644

  9. Current state and use of biological adhesives in orthopedic surgery.

    PubMed

    Shah, Neil V; Meislin, Robert

    2013-12-01

    Bone and tissue adhesives are common and beneficial supplements to standard methods of musculoskeletal tissue suture repair. Knowledge and development of biologically derived or inspired adhesives useful in orthopedic surgery are rapidly advancing. Recent literature demonstrates the increased adjunct or primary use of biological adhesives in the repair of musculoskeletal soft tissues, chondral fractures, and osteochondral fractures. Adhesives offer more benefits and enhancements to tissue healing than current fixation methods afford, including improved biocompatibility, resorbability, and non-immunogenicity. Further investigation is required to determine the extent of the role that these bioadhesives can play in orthopedic surgery. The largest group of biologically derived adhesives and sealants is fibrin sealants, which include first- and second-generation commercially available fibrin sealants, autologous fibrin sealants, and variants. Other groups include gelatin-resorcin aldehydes, protein-aldehyde systems, collagen-based adhesives, polysaccharide- based adhesives, mussel adhesive proteins, and various biologically inspired or biomimetic glues. Potential uses include applications in orthopedic-related blood conservation, arthroplasty, articular cartilage disorders, sports medicine, spine surgery, trauma, and tumors. The development of an adhesive with universal application is likely unfeasible, given the unique characteristics of various musculoskeletal tissues. However, the literature demonstrates the overall underuse of adhesives and indicates the rising probability of the development of a successful variety of bioadhesives for use in orthopedic surgery. As a result of reading this article, physicians should be able to: 1. Describe the difference between adhesives and sealants. 2. Recognize fibrin adhesives commonly used in practice today and identify other biological adhesives with rising potential. 3. Analyze how fibrin sealants work relative to fibrin and fibrinogen. 4. Identify anatomical areas and techniques in which fibrin sealants are used. PMID:24579215

  10. Microsphere-Based Scaffolds Carrying Opposing Gradients of Chondroitin Sulfate and Tricalcium Phosphate.

    PubMed

    Gupta, Vineet; Mohan, Neethu; Berkland, Cory J; Detamore, Michael S

    2015-01-01

    Extracellular matrix (ECM) components, such as chondroitin sulfate (CS) and tricalcium phosphate, serve as raw materials, and thus spatial patterning of these raw materials may be leveraged to mimic the smooth transition of physical, chemical, and mechanical properties at the bone-cartilage interface. We hypothesized that encapsulation of opposing gradients of these raw materials in high molecular weight poly(d,l-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds would enhance differentiation of rat bone marrow-derived stromal cells. The raw material encapsulation altered the microstructure of the microspheres and also influenced the cellular morphology that depended on the type of material encapsulated. Moreover, the mechanical properties of the raw material encapsulating microsphere-based scaffolds initially relied on the composition of the scaffolds and later on were primarily governed by the degradation of the polymer phase and newly synthesized ECM by the seeded cells. Furthermore, raw materials had a mitogenic effect on the seeded cells and led to increased glycosaminoglycan (GAG), collagen, and calcium content. Interestingly, the initial effects of raw material encapsulation on a per-cell basis might have been overshadowed by medium-regulated environment that appeared to favor osteogenesis. However, it is to be noted that in vivo, differentiation of the cells would be governed by the surrounding native environment. Thus, the results of this study demonstrated the potential of the raw materials in facilitating neo-tissue synthesis in microsphere-based scaffolds and perhaps in combination with bioactive signals, these raw materials may be able to achieve intricate cell differentiation profiles required for regenerating the osteochondral interface. PMID:26191526

  11. Mechano growth factor (MGF) and transforming growth factor (TGF)-?3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model.

    PubMed

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

    2015-06-01

    Damaged cartilage has poor self-healing ability and usually progresses to scar or fibrocartilaginous tissue, and finally degenerates to osteoarthritis (OA). Here we demonstrated that one of alternative isoforms of IGF-1, mechano growth factor (MGF) acted synergistically with transforming growth factor ?3 (TGF-?3) embedded in silk fibroin scaffolds to induce chemotactic homing and chondrogenic differentiation of mesenchymal stem cells (MSCs). Combination of MGF and TGF-?3 significantly increased cell recruitment up to 1.8 times and 2 times higher than TGF-?3 did in vitro and in vivo. Moreover, MGF increased Collagen II and aggrecan secretion of TGF-?3 induced hMSCs chondrogenesis, but decreased Collagen I in vitro. Silk fibroin (SF) scaffolds have been widely used for tissue engineering, and we showed that methanol treated pured SF scaffolds were porous, similar to compressive module of native cartilage, slow degradation rate and excellent drug released curves. At 7 days after subcutaneous implantation, TGF-?3 and MGF functionalized silk fibroin scaffolds (STM) recruited more CD29+/CD44+cells (P<0.05). Similarly, more cartilage-like extracellular matrix and less fibrillar collagen were detected in STM scaffolds than that in TGF-?3 modified scaffolds (ST) at 2 months after subcutaneous implantation. When implanted into articular joints in a rabbit osteochondral defect model, STM scaffolds showed the best integration into host tissues, similar architecture and collagen organization to native hyaline cartilage, as evidenced by immunostaining of aggrecan, collagen II and collagen I, as well as Safranin O and Masson's trichrome staining, and histological evalution based on the modified O'Driscoll histological scoring system (P<0.05), indicating that MGF and TGF-?3 might be a better candidate for cartilage regeneration. This study demonstrated that TGF-?3 and MGF functionalized silk fibroin scaffolds enhanced endogenous stem cell recruitment and facilitated in situ articular cartilage regeneration, thus providing a novel strategy for cartilage repair. PMID:25818452

  12. Identification of cold-temperature-regulated genes in Flavobacterium psychrophilum.

    PubMed

    Hesami, Shohreh; Metcalf, Devon S; Lumsden, John S; Macinnes, Janet I

    2011-03-01

    Flavobacterium psychrophilum is the etiological agent of bacterial coldwater disease (BCWD) and rainbow trout fry syndrome (RTFS). It causes disease primarily in fresh water-reared salmonids, but other fish species can also be affected. A diverse array of clinical conditions is associated with BCWD, including tail rot (peduncle disease), necrotic myositis, and cephalic osteochondritis. Degradation of connective and muscular tissues by extracellular proteases is common to all of these presentations. There are no effective vaccines to prevent BCWD or RTFS, and antibiotics are often used to prevent and control disease. To identify virulence factors that might permit development of an efficacious vaccine, cDNA suppression subtractive hybridization (SSH) was used to identify cold-regulated genes in a virulent strain of F. psychrophilum. Genes predicted to encode a two-component system sensor histidine kinase (LytS), an ATP-dependent RNA helicase, a multidrug ABC transporter permease/ATPase, an outer membrane protein/protective antigen OMA87, an M43 cytophagalysin zinc-dependent metalloprotease, a hypothetical protein, and four housekeeping genes were upregulated at 8°C versus the level of expression at 20°C. Because no F. psychrophilum gene was known to be suitable as an internal standard in reverse transcription-quantitative real-time PCR (RT-qPCR) experiments, the expression stability of nine commonly used reference genes was evaluated at 8°C and 20°C. Expression of the 16S rRNA was equivalent at both temperatures, and this gene was used in RT-qPCR experiments to verify the SSH findings. With the exception of the ATCC 49513 strain, similar patterns of gene expression were obtained with 11 other representative strains of F. psychrophilum. PMID:21216906

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

    PubMed Central

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

    2013-01-01

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

  14. Safety of, and biological and functional response to, a novel metallic implant for the management of focal full-thickness cartilage defects: Preliminary assessment in an animal model out to 1 year.

    PubMed

    Kirker-Head, Carl A; Van Sickle, David C; Ek, Steve W; McCool, John C

    2006-05-01

    Focal full-thickness cartilage lesions of the human medial femoral condyle (MFC) can cause pain and functional impairment. Affected middle-aged patients respond unpredictably to existing treatments and knee arthroplasty may be required, prompting risk of revision. This study assesses the safety of, and biological and functional response to, a metallic resurfacing implant which may delay or obviate the need for traditional arthroplasty. The anatomic contour of the surgically exposed MFC of six adult goats was digitally mapped and an 11 mm diameter full-thickness osteochondral defect was created. An anchor-based Co-Cr resurfacing implant, matching the mapped articular contour, was implanted. Each goat's contralateral unoperated femorotibial joint was used as a control. Postoperative outcome was assessed by lameness examination, radiography, arthroscopy, synoviocentesis, necropsy, and histology up to 26 (n = 3) or 52 (n = 3) weeks. By postoperative week (POW) 4, goats demonstrated normal range of motion, no joint effusion, and only mild lameness in the operated limb. By POW 26 the animals were sound with only occasional very mild lameness. Arthroscopy at POW 14 revealed moderate synovial inflammation and a chondral membrane extending centrally across the implant surface. Radiographs at POWs 14 to 52 implied implant stability in the operated joints, as well as subchondral bone remodeling and mild exostosis formation in the operated and contralateral unoperated joints of some goats. By POW 26, histology revealed new trabecular bone abutting the implant. At POWs 26 and 52 MFC cartilage was metachromatic and intact in the operated and unoperated femorotibial joints. Proximal tibiae of some operated and unoperated limbs demonstrated limited subchondral bone remodeling and foci of articular cartilage fibrillation and thinning. The chondral membrane crossing the prosthesis possessed a metachromatic matrix containing singular and clustered chondrocytes. Our data imply the safety, biocompatibility, and functionality of the implant. Focal articular damage was documented in the operated joints at POWs 26 and 52, but lesions were much reduced over those previously reported in untreated defects. Expanded animal or preclinical human studies are justified. PMID:16609973

  15. Quantitative analysis of the impact of short-time high hydrostatic pressure on bone tumor-associated proteases.

    PubMed

    Diehl, Peter; Schauwecker, Johannes; Eichelberg, Kay; Gollwitzer, Hans; Magdolen, Ursula; Gerdesmeyer, Ludger; Mittelmeier, Wolfram; Schmitt, Manfred

    2007-04-01

    In orthopedic surgery, sterilization of bone used for reconstruction of osteoarticular defects caused by malignant tumors is carried out in various ways. At present, to devitalize tumor-bearing osteochondral segments, extracorporeal irradiation or autoclaving is mainly used, although both methods have substantial disadvantages, leading to a significant loss of biomechanical and biological integrity of the bone. As an alternative approach, a new technology to achieve bone sterilization, the high hydrostatic pressure (HHP) treatment of bone, has been suggested, which is currently being preclinically tested. This novel technique leads to the inactivation of tumor cells without impairing biomechanical properties of the bone, cartilage, or tendons. HHP may not only exert an effect on tumor and normal cells present in the bone but also on tumor-associated proteases released by these cells, which are conductive to tumor bone turnover. In order to investigate this, proteolytic key enzymes, e.g. MMP-9, uPA, t-PA, plasmin, trypsin, and thrombin were subjected to HHP

  16. Functionally graded scaffolds for the engineering of interface tissues using hybrid twin screw extrusion/electrospinning technology

    NASA Astrophysics Data System (ADS)

    Erisken, Cevat

    Tissue engineering is the application of the principles of engineering and life sciences for the development of biological alternatives for improvement or regeneration of native tissues. Native tissues are complex structures with functions and properties changing spatially and temporally, and engineering of such structures requires functionally graded scaffolds with composition and properties changing systematically along various directions. Utilization of a new hybrid technology integrating the controlled feeding, compounding, dispersion, deaeration, and pressurization capabilities of extrusion process with electrospinning allows incorporation of liquids and solid particles/nanoparticles into polymeric fibers/nanofibers for fabrication of functionally graded non-woven meshes to be used as scaffolds in engineering of tissues. The capabilities of the hybrid technology were demonstrated with a series of scaffold fabrication and cell culturing studies along with characterization of biomechanical properties. In the first study, the hybrid technology was employed to generate concentration gradations of beta-tricalcium phosphate (beta-TCP) nanoparticles in a polycaprolactone (PCL) binder, between two surfaces of nanofibrous scaffolds. These scaffolds were seeded with pre-osteoblastic cell line (MC3T3-E1) to attempt to engineer cartilage-bone interface, and after four weeks, the tissue constructs revealed formation of continuous gradations in extracellular matrix akin to cartilage-bone interface in terms of distributions of mineral concentrations and biomechanical properties. In a second demonstration of the hybrid technology, graded differentiation of stem cells was attempted by using insulin, a known stimulator of chondrogenic differentiation, and beta-glycerol phosphate (beta-GP), for mineralization. Concentrations of insulin and beta-GP in PCL were controlled to monotonically increase and decrease, respectively, along the length of scaffolds, which were then seeded with adipose derived stromal cells (h-ADSCs). Analysis of resulting tissue constructs revealed chondrocytic differentiation of h-ADSCs, with both the chondrocytic cell concentration and mineralization varying as a function of distributions of concentrations of insulin and beta-GP, respectively. The investigation also covered characterization of biomechanical properties of native bovine osteochondral tissue samples, which were then compared with biomechanical properties of tissue constructs at different stages of development. The hybrid technology developed in this thesis should provide another enabling platform for the fabrication of functionally graded scaffolds that aim to mimic the elegant gradations found in myriad native tissues.

  17. Surface modified PLGA/carbon nanofiber composite enhances articular chondrocyte functions

    NASA Astrophysics Data System (ADS)

    Park, Grace Eunseung

    Since articular cartilage has a limited self regeneration capability, alternative methods are needed for repairing cartilage defects. The purpose of the present in vitro study was to explore the effects of material surface properties and external stimulation on chondrocyte (cartilage-synthesizing cell) functions. Based on this information, a goal of this research was to propose a scaffold composite material for enhancing articular chondrocyte function. To improve functions of chondrocytes, material (namely, poly(lactic-co-glycolic acid); PLGA) surfaces were modified via chemical (NaOH) etching techniques. Chondrocytes were cultured on surface-modified 2-D PLGA films and 3-D PLGA tissue engineering scaffolds, which were created by a salt-leaching method. Carbon nanofibers were imprinted on PLGA matrices in an aligned pattern for controlled electrically-active surface features. Electrical stimulation was applied to expedite and enhance chondrocyte functions. Results demonstrated that both NaOH-treated 2-D and 3-D substrates enhanced chondrocyte functions (cell numbers as well as extracellular matrix production) compared to non-treated PLGA substrates. Furthermore, chondrocytes preferred to attach along the carbon nanofiber patterns imprinted on PLGA. Electrical stimulation also enhanced chondrocyte functions on carbon nanofiber/PLGA composites. Underlying material properties that may have enhanced chondrocyte functions include a more hydrophilic surface, surface energy differences due to the presence of carbon nanofibers, increased surface area, altered porosity, and a greater degree of nanometer roughness. Moreover, these altered surface properties positively influenced select protein adsorption that controlled subsequent chondrocyte adhesion. Collectively, this study provided a scaffold model for osteochondral defects that can be synthesized using the above techniques and a layer by layer approach to accommodate the property differences in each layer of natural cartilage. Specifically, these results suggest that the superficial zone, middle zone, and deep zone of cartilage should be composed of carbon nanofibers aligned parallel to the surface in PLGA, randomly oriented carbon nanofibers in PLGA, and carbon nanofibers aligned perpendicular to the surface in PLGA, respectively. Clearly, such scaffolds may ultimately enhance the efficacy of scaffolds used for articular cartilage repair.

  18. Analysis of the load on the knee joint and vertebral column with changes in squatting depth and weight load.

    PubMed

    Hartmann, Hagen; Wirth, Klaus; Klusemann, Markus

    2013-10-01

    It has been suggested that deep squats could cause an increased injury risk of the lumbar spine and the knee joints. Avoiding deep flexion has been recommended to minimize the magnitude of knee-joint forces. Unfortunately this suggestion has not taken the influence of the wrapping effect, functional adaptations and soft tissue contact between the back of thigh and calf into account. The aim of this literature review is to assess whether squats with less knee flexion (half/quarter squats) are safer on the musculoskeletal system than deep squats. A search of relevant scientific publications was conducted between March 2011 and January 2013 using PubMed. Over 164 articles were included in the review. There are no realistic estimations of knee-joint forces for knee-flexion angles beyond 50° in the deep squat. Based on biomechanical calculations and measurements of cadaver knee joints, the highest retropatellar compressive forces and stresses can be seen at 90°. With increasing flexion, the wrapping effect contributes to an enhanced load distribution and enhanced force transfer with lower retropatellar compressive forces. Additionally, with further flexion of the knee joint a cranial displacement of facet contact areas with continuous enlargement of the retropatellar articulating surface occurs. Both lead to lower retropatellar compressive stresses. Menisci and cartilage, ligaments and bones are susceptible to anabolic metabolic processes and functional structural adaptations in response to increased activity and mechanical influences. Concerns about degenerative changes of the tendofemoral complex and the apparent higher risk for chondromalacia, osteoarthritis, and osteochondritis in deep squats are unfounded. With the same load configuration as in the deep squat, half and quarter squat training with comparatively supra-maximal loads will favour degenerative changes in the knee joints and spinal joints in the long term. Provided that technique is learned accurately under expert supervision and with progressive training loads, the deep squat presents an effective training exercise for protection against injuries and strengthening of the lower extremity. Contrary to commonly voiced concern, deep squats do not contribute increased risk of injury to passive tissues. PMID:23821469

  19. Do Chondral Lesions of the Knee Correlate with Bone Tracer Uptake by Using SPECT/CT?

    PubMed

    Dordevic, Milos; Hirschmann, Michael T; Rechsteiner, Jan; Falkowski, Anna; Testa, Enrique; Hirschmann, Anna

    2016-01-01

    Purpose To evaluate the correlation of bone tracer uptake as determined with single photon emission computed tomography (SPECT)/computed tomography (CT) and the size and severity of chondral lesions detected with magnetic resonance (MR) imaging of the knee. Materials and Methods MR imaging and SPECT/CT images of 63 knee joints in 63 patients (mean age ± standard deviation, 49.2 years ± 12.7) with chondral or osteochondral lesions were prospectively collected and retrospectively analyzed after approval by the ethics committee. Chondral lesions were graded on MR images by using a modified Noyes grading scale (grade 0, intact; grade 1, fibrillations; grade 2, <50% defect; grade 3, >50% defect; and grade 4, grade three plus subchondral changes) and measured in two dimensions. Technetium 99m hydroxymethane diphosphonate SPECT/CT bone tracer uptake was volumetrically quantified by using validated software. Maximum values of each subchondral area (patellofemoral or medial and lateral femorotibial) were quantified, and a ratio was calculated in relation to a reference region in the femoral shaft, which represented the bone tracer uptake background activity. Grades and sizes of chondral lesions and bone tracer uptake were correlated by using an independent t test and analysis of variance (P < .05). Results Bone tracer uptake was low (mean relative uptake, 1.64 ± 0.95) in knees without any present chondral lesion. In knees with grade 3 and 4 chondral lesions, the relative ratio was significantly higher (3.62 ± 2.18, P = .002) than in knees with grade 1 and 2 lesions (2.95 ± 2.07). The larger the diameter of the chondral lesion, the higher the bone tracer uptake. Higher grades of chondral lesions (grades 3 and 4) larger than 4 cm(2) (4.96 ± 2.43) showed a significantly higher bone tracer uptake than smaller lesions (<1 cm(2), 2.72 ± 1.43 [P = .011]; and 1-4 cm(2), 3.28 ± 2.15 [P = .004]). Conclusion SPECT/CT findings significantly correlate with the degree and size of chondral lesions on MR images. Grade 3 and 4 chondral lesions of the knee, as well as larger lesions, correlate with a high bone tracer uptake. (©) RSNA, 2015. PMID:26162025

  20. Potential Utility of a Combined Approach with US and MR Arthrography to Image Medial Elbow Pain in Baseball Players.

    PubMed

    Roedl, Johannes B; Gonzalez, Felix M; Zoga, Adam C; Morrison, William B; Nevalainen, Mika T; Ciccotti, Michael G; Nazarian, Levon N

    2016-06-01

    Purpose To evaluate a combined imaging approach with both ultrasonography (US; conventional US and valgus stress US) and magnetic resonance (MR) arthrography in baseball players with medial elbow pain. Materials and Methods Institutional review board approval was obtained and the requirement for informed consent was waived. The study is compliant with HIPAA. Baseball players with medial elbow pain underwent US in addition to MR arthrography. Findings were assessed with each modality alone and both combined in this retrospective investigation. For the evaluation of ulnar collateral ligament (UCL) tears with stress US, the interval gapping of the medial elbow joint was measured between rest and valgus stress both at the injured and at the uninjured (contralateral) elbow. Surgical or arthroscopic correlation was available as the so-called gold standard. McNemar tests compared the accuracies of the imaging modalities. Results In this study, 144 baseball players had 191 findings of medial elbow pain, including 53 UCL tears. With stress US, joint gapping at the injured elbow greater than 1.0 mm compared with the contralateral elbow yielded a sensitivity, specificity, and accuracy of 96%, 81%, and 87%, respectively, for diagnosing UCL tears. With MR arthrography, the sensitivity, specificity, and accuracy for UCL tears were 81%, 91%, and 88%, respectively, and increased to 96% (P = .013, McNemar test), 99% (P = .023), and 98% (P < .001), respectively, when combined with US to a dual modality MR and US approach. For 31 patients with ulnar neuritis, the sensitivity, specificity, and accuracy increased from 74%, 92%, and 88%, respectively, with MR arthrography alone to 90% (P = .07, McNemar test), 100% (P < .001), and 98% (P < .001) combined with US. For the 59 myotendinous and the 48 osteochondral diagnoses, the sensitivity, specificity, and accuracy with MR arthrography alone were 93%, 93%, and 93%, and 94%, 98%, and 97%, respectively, with no additional diagnostic value from US. Conclusion The combined approach with both MR arthrography and US shows higher accuracy than each modality alone for the assessment of medial elbow pain. (©) RSNA, 2016. PMID:27183408

  1. Microscale Material Properties of Bone and the Mineralized Tissues of the Intervertebral Disc-Vertebral Body Interface

    NASA Astrophysics Data System (ADS)

    Paietta, Rachel C.

    The objective of this dissertation is to understand the influences of material structure on the properties, function and failure of biological connective tissues. Biological interfaces are becoming an increasingly studied system within mechanics and tissue engineering as a model for attaching dissimilar materials. The elastic modulus of bone (≈ 20 GPa) and cartilage (≈ 0.1-1 MPa) differ over orders of magnitude, which should intuitively create high stress concentrations and failure at the interface. Yet, these natural interface systems rarely fail in vivo, and the mechanism by which loads are transferred between tissues has not yet been established. Tissue quality is one major contributor to the mechanical behavior of bone and cartilage, and is defined by properties such as collagen orientation, mineral volume fraction, porosity and tissue geometry. These properties have yet to be established at the bone-cartilage interface in the spine, and the lack of quantitative data on material microstructure and behavior limits treatments and tissue engineering construct design. In this dissertation, second harmonic generation imaging, quantitative backscattered scanning electron imaging and nanoindentation are combined to characterize micrometer scale tissue quality and modulus in both bone and calcified cartilage. These techniques are utilized to: 1) determine the hierarchical micrometer to millimeter scale properties of lamellar bone, 2) quantify changes throughout development and aging at the human intervertebral disc-vertebral body junction, and 3) explore compressive fractures at this interface. This work is the first to provide quantitative data on the mineral volume fraction, collagen orientation and modulus from the same, undecalcified sections of tissue to corroborate tissue structure and mineralization and describe quantitative parameters of the interface. The principal findings from this work indicate that the underlying matrix, or collagen, organization in mineralized biological tissues and at the bone-cartilage interface plays an important mechanical role. Nanoindentation measurements in osteonal bone are affected by location within the lamellar structure, even though mineral volume fraction within a single osteon is relatively consistent compared to the differences observed between bone and calcified cartilage. While increasing mineral volume fraction contributes to increases in modulus in the calcified cartilage layer of the vertebral body-intervertebral disc interface, significant scatter remains. The collagenous matrix structure and type of collagen appear to have a significant influence on modulus as well. Collagen fibers of the disc mineralize adjacent to the bone of the vertebral body, and the persistence of this attachment zone from adolescence through senescence indicates that it likely serves a mechanical function. Fiber insertions into thick calcified cartilage regions likely create mechanically robust anchor points at the osteochondral interface.

  2. Ankle impingement: a review of multimodality imaging approach.

    PubMed

    Russo, A; Zappia, M; Reginelli, A; Carfora, M; D'Agosto, G F; La Porta, M; Genovese, E A; Fonio, P

    2013-08-01

    Ankle impingement is defined as entrapment of an anatomic structure that leads to pain and decreased range of motion of the ankle and can be classified as either soft tissue or osseous (Bassett et al. in J Bone Joint Surg Am 72:55-59, 1990). The impingement syndromes of the ankle are a group of painful disorders that limit full range of movement. Symptoms are due to compression of soft-tissues or osseous structures during particular movements (Ogilvie-Harris et al. in Arthroscopy 13:564-574, 1997). Osseous impingement can result from spur formation along the anterior margin of the distal tibia and talus or as a result of a prominent posterolateral talar process, the os trigonum. Soft-tissue impingement usually results from scarring and fibrosis associated with synovial, capsular, or ligamentous injury. Soft-tissue impingement most often occurs in the anterolateral gutter, the medial ankle, or in the region of the syndesmosis (Van den Bekerom and Raven in Knee Surg Sports Traumatol Arthrosc 15:465-471, 2007). The main impingement syndromes are anterolateral, anterior, anteromedial, posterior, and posteromedial impingement. These conditions arise from initial ankle injuries, which, in the subacute or chronic situation, lead to development of abnormal osseous and soft-tissue thickening within the ankle joint. The relative contributions of the osseous and soft-tissue abnormalities are variable, but whatever component is dominant there is physical impingement and painful limitation of ankle movement. Conventional radiography is usually the first imaging technique performer and allows assessment of any potential bone abnormality, particularly in anterior and posterior impingement. Computed tomography (CT) and isotope bone scanning have been largely superseded by magnetic resonance (MR) imaging. MR imaging can demonstrate osseous and soft-tissue edema in anterior or posterior impingement. MR imaging is the most useful imaging modality in evaluating suspected soft-tissue impingement or in excluding other ankle pathology such as an osteochondral lesion of the talus. MR imaging can reveal evidence of previous ligamentous injury and also can demonstrate thickened synovium, fibrosis, or adjacent reactive soft-tissue edema. Studies of conventional MR imaging have produced conflicting sensitivities and specificities in assessment of anterolateral impingement. CT and MR arthrographic techniques allow the most accurate assessment of the capsular recesses, albeit with important limitations in diagnosis of clinical impingement syndromes. In the majority of cases, ankle impingement is treated with conservative measures, with surgical debridement via arthroscopy or an open procedure reserved for patients who have refractory symptoms. In this article, we describe the clinical and potential imaging features, for the four main impingement syndromes of the ankle: anterolateral, anterior, anteromedial, posterior, and posteromedial impingement. PMID:23949938

  3. Subchondral bone changes and chondrogenic capacity of progenitor cells from subchondral bone in the collagenase-induced temporomandibular joints osteoarthritis rabbit model

    PubMed Central

    Wu, Guomin; Zhu, Songsong; Sun, Xiumei; Hu, Jing

    2015-01-01

    Purpose: The goals of this study were to characterize subchondral bone changes, and to determine biological activity characteristics of progenitor cell populations from subchondral bone in the collagenase-induced temporomandibular joint osteoarthritis (TMJOA) rabbit model. Greater understanding of such pathological changes occurring in TMJOA samples is critical in the future treatment modalities regarding cartilage protection and repair. Furthermore, the use of progenitor cell populations in various cartilage regeneration strategies proves to be a fruitful avenue for research and clinical applications. Materials and methods: Bone remodeling and anabolic activity of subchondral bone was evaluated by hematoxylin-eosin (H&E), Alcian blue-periodic acid-Schiff (AB-PAS) staining and immuohistochemical staining. The biological activity characteristics of progenitor cells were assessed by expressions of collagen type II, CD44, SOX-9 and MMP-9 by immunohistochemistry and Western blot analysis. Results: In most of the specimens, cartilage of the digested area displayed a reaction characterized by thickening of the cartilage cellular structure with retraction structure formation in the subchondral bone. Most of the specimens focuses on chondroid metaplasia were observed in the subchondral bone, promoting its remodeling, which could develop to endochondral ossification and increasing subchondral bone size. Meanwhile, immunohistochemistry analysis revealed that CD44 expressions in subchondral bone were most significantly increased in TMJOA at 2 weeks group (P < 0.01). And, at 4, 6 and 8 weeks groups, the osteochondral junction had completely disappeared by active subchondral bone remodeling, and collagen type II, CD44, SOX-9 and MMP-9 expressions in active subchondral bone region were significantly increased in TMJOA (P < 0.05). In addition, western blot analysis revealed that CD44 expression significantly emerged in subchondral bone region at 2 weeks group (P < 0.01). Meanwhile, SOX-9 expression emerged in all group, and the intensity was increased in the experimental groups (P < 0.05). Conclusion: Our results suggest that the beneficial activation of progenitor cells and bone marrow stem cells in subchondral bone at early stage of TMJOA played an important role on renovation and remodeling of subchondral bone. PMID:26617688

  4. Problems and pointers in osteochondrosis: Twenty years on.

    PubMed

    van Weeren, P René; Jeffcott, Leo B

    2013-07-01

    Twenty years ago a supplement of Equine Veterinary Journal was devoted to equine osteochondrosis (OC) and recognised the importance of this developmental disease to the equine industry. In the accompanying editorial several controversial issues were identified and a number of areas for further research were highlighted. Today, equine OC is still a major clinical problem, but the on-going research has resulted in much improved knowledge and understanding of this highly complicated disease. There is still conflicting evidence on the prevalence of OC due to the dynamic character of the condition, widely varying definitions in the literature, and the range of joints affected. Nevertheless there is now convincing evidence that early vascular damage, leading to chondronecrosis, is the major mechanism of onset. The aetiological factors that determine whether a horse will develop clinical signs of OC remain obscure and the complex nature of OC and its multi-factorial character has been clearly demonstrated by genetic studies. These have shown a multitude of loci on a variety of chromosomes linked to osteochondrotic phenotypes, depending on the type of manifestation of OC, the joint involved and the breed. The controversy surrounding the possible key role of copper in the pathogenesis of OC in the early 1990s has evolved into a more limited contribution to repair thus making it just one of the many environmental factors that may have an effect on the occurrence of OC, but not a decisive one. The semantic debate concerning the most appropriate nomenclature seems to have crystallised into a consensus on terminology at three levels: OC or osteochondritis dissecans (OCD) for the disturbance in the process of endochondral ossification, juvenile ostechondral conditions (JOCC) for all joint and growth plate related disorders, and developmental orthopaedic diseases (DOD) for the full range of skeletal conditions in young horses. Future progress in improved management of OC can be expected from more research on cellular and molecular processes and the influences that determine the process of endochondral ossification, the process of articular cartilage maturation, and from epidemiological studies quantifying the long-term effects of OC on health and performance. PMID:23639371

  5. Correlation between MRI and Arthroscopy in Diagnosis of Shoulder Pathology

    PubMed Central

    Bhonsle, Sachin; Mehta, Sonu

    2016-01-01

    Introduction Shoulder pain can cause significant pain, discomfort and reduce the ability to perform activities of daily living, thus making it the third most common cause of musculoskeletal consultation. The current gold standard diagnostic investigation is arthroscopy. MRI is a proved sensitive and accurate non-invasive tool in investigating shoulder pathology, but false and misleading results are equally reported. Aim The aim of the study is to compare the efficacy of MRI in diagnosing shoulder pathologies in comparison to arthroscopy, considering arthroscopy as the gold standard. Materials and Methods Thirty nine consecutive patients, between 18-80 years of age, presenting with chronic shoulder pain or instability of more than 6 weeks, or with clinical signs of impingement or tear were included in the study. MRI of the shoulder joint was done followed by shoulder arthroscopy. The data collected was analysed for the significant correlation between MRI of shoulder and arthroscopic findings by kappa statistics. Results Out of 39 patients, Rotator cuff (RC) tear was the most common pathology. MRI showed excellent sensitivity in the diagnosis of rotator cuff tears (0.91) and osteochondral defects (OCD), very good sensitivity for Bankart’s lesion (0.8) and had poor sensitivity to detect SLAP tear (0.15). MRI was specific for all shoulder pathologies. MRI detected RC tears with kappa score of 0.73, Bankart’s tear and OCD’s with kappa score of 0.83 and 1.0 respectively and SLAP lesion with kappa score of 0.14. The accuracy of MRI was highest in diagnosing OCD’s (1.0), followed by RC tear (0.9), Bankart’s tear (0.9) and accuracy was least in diagnosing SLAP lesion (0.7). False negative results were more than false positives. Conclusion The present study supports that MRI is effective in diagnosing rotator cuff tears, Bankart’s tear and ostechondral defects but was not found to be helpful in diagnosing SLAP lesions. MRI and arthroscopy have complimentary roles in the diagnosis of shoulder pathology. PMID:27042543

  6. Hallux limitus and hallux rigidus. Clinical examination, radiographic findings, and natural history.

    PubMed

    Camasta, C A

    1996-07-01

    Numerous clinical features of hallux limitus/rigidus have been previously reported as isolated entities based on individual case review or myopic observations. Few attempts have been made to synthesize a comprehensive natural history which correlates the inter-relationship of these findings. Frequently unrecognized or overlooked subtle clinical findings, such as shoe-wear patterns, hyperkeratoses locations, and gait disturbances, precede significant radiographic changes or painful degenerative arthritis by months to years. Recognition of these subtle clinical features will aid in establishing an early and accurate diagnosis, and provide the physician with an opportunity to institute treatment prior to the need for surgical reconstruction. Several conclusions can be made regarding the natural history of hallux rigidus. 1. Predisposing factors (pes planovalgus, uncompensated varus) lead to spastic contracture of the hallux (hallux equinus). 2. A shift in the axis of movement occurs within the first metatarsophalangeal joint, from centrally within the metatarsal head to plantarly at the level of the sesamoidophalangeal ligament. 3. Dorsal articular impingement of the proximal phalangeal base on the metatarsal head leads to either a chronic erosion of the dorsal metatarsal head (chondritis dissecans), or fracture through the subchondral bone plate (osteochondritis dissecans). 4. Progressive degenerative arthritis within the first metatarsophalangeal joint appears as joint space narrowing, dorsal osteophyte proliferation, subchondral cyst formation and sclerosis, and articular flattening. 5. Synovial effusion produces periarticular pain, resulting in chronic splinting of the hallux. 6. Auto-fusion of the metatarsophalangeal joint represents the end-stage progression of hallux rigidus. In addition to degeneration of the metatarsophalangeal joint, sesamoid degeneration further compounds joint immobility. 1. Sesamoid immobility from chronic spasm leads to traction proliferation of the sesamoid bones (hypertrophy). 2. Disuse osteopenia of the sesamoids is an indication of sesamoid-metatarsal degeneration, and parallels degenerative changes of the first metatarsophalangeal joint. 3. Proximal sesamoid retraction reflects the degree of hallux equinus. Metatarsus primus elevatus is a co-existant feature of hallux limitus and hallux rigidus. 1. Primary metatarsus primus elevatus is encountered in patients with a more proximal level of uncompensated varus, with hallux equinus occurring secondarily in an attempt to provide medial column support. 2. Secondary metatarsus primus elevatus results from the retrograde effects of hallux equinus on the first metatarsal, and occurs in patients with pes planovalgus. 3. Flexor stabilization syndrome of the hallux occurs in patients with pes planovalgus, and is analogous to a flexor stabilization hammertoe of the lesser digits. 4. Differentiation between primary and secondary metatarsus primus elevatus is made by evaluation of weight-bearing radiographs, comparing the standard lateral radiograph to a lateral radiograph using a forefoot block test, in which the digits are suspended off of the weight-bearing surface. PMID:8829034

  7. Comparison of Three Methods to Quantify Repair Cartilage Collagen Orientation

    PubMed Central

    Ross, Keir A.; Williams, Rebecca M.; Schnabel, Lauren V.; Mohammed, Hussni O.; Potter, Hollis G.; Bradica, Gino; Castiglione, Emme; Pownder, Sarah L.; Satchell, Patrick W.; Saska, Ryan A.

    2013-01-01

    Objective: The aim of this study was to determine if the noninvasive or minimally invasive and nondestructive imaging techniques of quantitative T2-mapping or multiphoton microscopy (MPM) respectively, could detect differences in cartilage collagen orientation similar to polarized light microscopy (PLM). It was hypothesized that MRI, MPM, and PLM would all detect quantitative differences between repair and normal cartilage tissue. Methods: Osteochondral defects in the medial femoral condyle were created and repaired in 5 mature goats. Postmortem, MRI with T2-mapping and histology were performed. T2 maps were generated and a mean T2 value was calculated for each region of interest. Histologic slides were assessed using MPM with measurements of autocorrelation ellipticity, and by PLM with application of a validated scoring method. Collagen orientation using each of the 3 modalities (T2-mapping, MPM, and PLM) was measured in the center of the repair tissue and compared to remote, normal cartilage. Results: MRI, MPM, and PLM were able to detect a significant difference between repair and normal cartilage (n = 5). The average T2 value was longer for repair tissue (41.43 9.81 ms) compared with normal cartilage (27.12 14.22 ms; P = 0.04); MPM autocorrelation ellipticity was higher in fibrous tissue (3.75 1.17) compared with normal cartilage (2.24 0.51; P = 0.01); the average PLM score for repair tissue was lower (1.6 1.02) than the score for remote normal cartilage (4.4 0.42; P = 0.002). The strongest correlation among the methods was between MRI and PLM (r = ?0.76; P = 0.01), followed by MPM and PLM (r = ?0.58; P = 0.08), with the weakest correlation shown between MRI and MPM (r = 0.35; P = 0.31). Conclusion: All 3 imaging methods quantitatively measured differences in collagen orientation between repair and normal cartilage, but at very different levels of resolution. PLM is destructive to tissue and requires euthanasia, but because MPM can be used arthroscopically, both T2-mapping and MPM can be performed in vivo, offering nondestructive means to assess collagen orientation that could be used to obtain longitudinal data in cartilage repair studies. PMID:26069654

  8. A history of lumbar disc herniation from Hippocrates to the 1990s.

    PubMed

    Truumees, Eeric

    2015-06-01

    In ancient times, a supernatural understanding of the syndrome of lumbar radiculopathy often involved demonic forces vexing the individual with often crippling pain. The ancient Greeks and Egyptians began to take a more naturalistic view and, critically, suspected a relationship between lumbar spinal pathology and leg symptoms. Relatively little then changed for those with sciatica until the classic works by Cotugno and Kocher arrived in the late 18th century. Early lumbar canal explorations were performed in the late 1800s and early 1900s by MacEwen, Horsley, Krause, Taylor, Dandy, and Cushing, among others. In these cases, when compressive pathologies were found and removed, the lesions typically were (mis-)identified as enchondromas or osteochondritis dissecans. To better understand the history, learn more about the first treatments of lumbar disc herniation, and evaluate the impact of the early influences on modern spine practice, searches of PubMed and Embase were performed using the search terms discectomy, medical history, lumbar spine surgery, herniated disc, herniated nucleus pulposus, sciatica, and lumbar radiculopathy. Additional sources were identified from the reference lists of the reviewed papers. Many older and ancient sources including De Ischiade Nervosa are available in English translations and were used. When full texts were not available, English abstracts were used. The first true, intentional discectomy surgery was performed by Mixter and Barr in 1932. Early on, a transdural approach was favored. In 1938, Love described the intralaminar, extradural approach. His technique, although modified with improved lighting, magnification, and retractors, remains a staple approach to disc herniations today. Other modalities such as chymopapain have been investigated. Some remain a part of the therapeutic armamentarium, whereas others have disappeared. By the 1970s, CT scanning after myelography markedly improved the clinical evaluation of patients with lumbar disc herniation. In this era, use of discectomy surgery increased rapidly. Even patients with very early symptoms were offered surgery. Later work, especially by Weber and Hakelius, showed that many patients with lumbar disc herniation would improve without surgical intervention. In the ensuing decades, the debate over operative indications and timing continued, reaching another pivotal moment with the 2006 publication of the initial results of Spine Patient Outcomes Research Trial. PMID:24752913

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

    PubMed Central

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

    2016-01-01

    Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1α) has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1α may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1α expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1α in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1α mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10−6 M) increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2α1) and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM) synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic marker genes including Mmp2, Mmp9, Mmp13, Adamts4 and Adamts5 was downregulated following Icariin treatment for 14 days. In a differentiation assay using bone marrow mesenchymal stem cells (MSCs) carrying HIF-1α floxed allele, the promotive effect of Icariin on chondrogenic differentiation is largely decreased following Cre recombinase-mediated deletion of HIF-1α in MSCs as indicated by Alcian blue staining for proteoglycan synthesis. In an alginate hydrogel 3D culture system, Icariin increases Safranin O positive (SO+) cartilage area. This phenotype is accompanied by upregulation of HIF-1α, increased proliferating cell nuclear antigen positive (PCNA+) cell numbers, SOX9+ chondrogenic cell numbers, and Col2 expression in the newly formed cartilage. Coincide with the micromass culture, Icariin treatment upregulates mRNA levels of Sox9, Col2α1, aggrecan and Col10α1 in the 3D cultures. We then generated alginate hydrogel 3D complexes incorporated with Icariin. The 3D complexes were transplanted in a mouse osteochondral defect model. ICRS II histological scoring at 6 and 12 weeks post-transplantation shows that 3D complexes incorporated with Icariin significantly enhance articular cartilage repair with higher scores particularly in selected parameters including SO+ cartilage area, subchondral bone and overall assessment than that of the controls. The results suggest that Icariin may inhibit PHD activity likely through competition for cellular iron ions and therefore it may serve as an HIF-1α activator to promote articular cartilage repair through regulating chondrocyte proliferation, differentiation and integration with subchondral bone formation. PMID:26841115

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

    PubMed

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

    2016-01-01

    Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1α) has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1α may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1α expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1α in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1α mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10-6 M) increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2α1) and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM) synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic marker genes including Mmp2, Mmp9, Mmp13, Adamts4 and Adamts5 was downregulated following Icariin treatment for 14 days. In a differentiation assay using bone marrow mesenchymal stem cells (MSCs) carrying HIF-1α floxed allele, the promotive effect of Icariin on chondrogenic differentiation is largely decreased following Cre recombinase-mediated deletion of HIF-1α in MSCs as indicated by Alcian blue staining for proteoglycan synthesis. In an alginate hydrogel 3D culture system, Icariin increases Safranin O positive (SO+) cartilage area. This phenotype is accompanied by upregulation of HIF-1α, increased proliferating cell nuclear antigen positive (PCNA+) cell numbers, SOX9+ chondrogenic cell numbers, and Col2 expression in the newly formed cartilage. Coincide with the micromass culture, Icariin treatment upregulates mRNA levels of Sox9, Col2α1, aggrecan and Col10α1 in the 3D cultures. We then generated alginate hydrogel 3D complexes incorporated with Icariin. The 3D complexes were transplanted in a mouse osteochondral defect model. ICRS II histological scoring at 6 and 12 weeks post-transplantation shows that 3D complexes incorporated with Icariin significantly enhance articular cartilage repair with higher scores particularly in selected parameters including SO+ cartilage area, subchondral bone and overall assessment than that of the controls. The results suggest that Icariin may inhibit PHD activity likely through competition for cellular iron ions and therefore it may serve as an HIF-1α activator to promote articular cartilage repair through regulating chondrocyte proliferation, differentiation and integration with subchondral bone formation. PMID:26841115