Osteochondritis dissecans of the capitellum is a well-recognized cause of elbow pain and disability in the adolescent athlete. This condition typically affects young athletes, such as throwers and gymnasts, involved in high-demand, repetitive overhead, or weightbearing activities. The true cause, natural history, and optimal treatment of osteochondritis dissecans of the capitellum remain unknown. Suspicion of this condition warrants investigation with
Champ L. Baker; Anthony A. Romeo
Osteochondral lesions of the talus are being recognized as an increasingly common injury. They are most commonly located postero-medially or antero-laterally, while centrally located lesions are uncommon. Large osteochondral lesions have significant biomechanical consequences and often require resurfacing with osteochondral autograft transfer, mosaicplasty, autologous chondrocyte implantation (or similar methods) or osteochondral allograft transplantation. Allograft procedures have become popular due to inherent advantages over other resurfacing techniques. Cartilage viability is one of the most important factors for successful clinical outcomes after transplantation of osteochondral allografts and is related to storage length and intra-operative factors. While there is abundant literature about osteochondral allograft transplantation in the knee, there are few papers about this procedure in the talus. Failure of non-operative management, initial debridement, curettage or microfractures are an indication for resurfacing. Patients should have a functional ankle motion, closed growth plates, absence of cartilage lesions on the tibial side. This paper reviews the published literature about osteochondral allograft transplantation of the talus focusing on indications, pre-operative planning, surgical approaches, postoperative management, results and complications of this procedure. PMID:25328456
Bisicchia, Salvatore; Rosso, Federica; Amendola, Annunziato
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)
DiStefano, Vincent J.
Critical-sized osteochondral defects are clinically challenging, with limited treatment options available. By engineering osteochondral grafts using a patient's own cells and osteochondral scaffolds designed to facilitate cartilage and bone regeneration, osteochondral defects may be treated with less complications and better long-term clinical outcomes. Scaffolds can influence the development and structure of the engineered tissue, and there is an increased awareness that osteochondral tissue engineering concepts need to take the in vivo complexities into account in order to increase the likelihood of successful osteochondral tissue repair. The developing trend in osteochondral tissue engineering is the utilization of multiphasic scaffolds to recapitulate the multiphasic nature of the native tissue. Cartilage and bone have different structural, mechanical, and biochemical microenvironments. By designing osteochondral scaffolds with tissue-specific architecture, it may be possible to enhance osteochondral repair within shorter timeframe. While there are promising in vivo outcomes using multiphasic approaches, functional regeneration of osteochondral constructs still remains a challenge. In this review, we provide an overview of in vivo osteochondral repair studies that have taken place in the past three years, and define areas which needs improvement in future studies. PMID:24293311
Jeon, June E; Vaquette, Cedryck; Klein, Travis J; Hutmacher, Dietmar W
BackgroundOsteochondral lesion of the talus (OLT) is a broad term used to describe an injury or abnormality of the talar articular cartilage and adjacent bone. A variety of treatment methods exist for OLT. The use of local Osteochondral talar autograft is an established treatment method for such articular cartilage defects. We present a series of patients treated this way for
Evangelos Evangelou; Thanos Badekas
An osteochondral lesion in the knee joint is caused by a focal traumatic osteochondral defect, osteochondritis dissecans, an isolated degenerative lesion, or diffuse degenerative disease. An osteochondral lesion with a cleft-like appearance accompanying medial meniscus injury is rare without trauma. We report the case of a 13-year-old boy who complained of right knee pain and swelling, with radiographic findings of an osteochondral defect. Arthroscopic inspection showed an osteochondral lesion in the medial condyle of the femur and tibial plateau accompanying a partial medial meniscus discoid tear. Partial meniscectomy was performed, and a microfracture procedure was carried out on the osteochondral defect. The patient was asymptomatic at 2 years' follow-up. This technique is a relatively easy, completely arthroscopic procedure that spares the bone and cartilage and has yielded a good clinical outcome in a skeletally immature patient who had an osteochondral lesion with a cleft-like appearance. PMID:24749028
Mine, Takatomo; Ihara, Koichiro; Kawamura, Hiroyuki; Date, Ryo; Chagawa, Kazuki
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
Seo, Seog-Jin; Mahapatra, Chinmaya; Singh, Rajendra K; Knowles, Jonathan C
The use of osteochondral allografts to treat focal osteochondral lesions continues to gain popularity, supported by long-term results. Clinicians must be knowledgeable concerning the possible risks of disease transmission, graft rejection, infection, and graft failure to advise the patient and obtain an informed consent. With advancing scientific and clinical research, future operative indications will likely continue to expand. A significant amount of literature regarding storage methods has recently been published; it is hoped that continued research will lead to techniques for prolonged graft storage to prevent availability concerns. PMID:19306735
Lattermann, Christian; Romine, Spencer E
... to or repetitive use of the joint (often sports-related). Some people with sporadic osteochondritis dissecans develop osteoarthritis in the affected ... personal genetic disease, syndrome, or condition should consult with a qualified healthcare ... a genetics professional in my area? in the Handbook.
\\u000a Osteochondrodysplasias like thanatophoric dysplasia, osteogenesis imperfecta, achondroplasia, and other genetic skeletal disorders\\u000a like fibrodysplasia ossificans progressiva are infrequently seen in clinical practice. In cases of sporadic achondroplasia\\u000a as well as in fibrodysplasia ossificans progressiva, there is a strong association with paternal age, a relationship that\\u000a is less evident in other genetic osteochondral diseases. No other constitutional or environmental factor has
Antonio Morales-Piga; Frederick S. Kaplan
This review provides a brief synopsis of the anatomy and physiology of the osteochondral interface, scaffold-based and non-scaffold based approaches for engineering both tissues independently as well as recent developments in the manufacture of gradient constructs. Novel manufacturing techniques and nanotechnology will be discussed with potential application in osteochondral interfacial tissue engineering. PMID:22677924
Castro, Nathan J; Hacking, S Adam; Zhang, Lijie Grace
This study describes a new method for the treatment of osteochondritis dissecans (OCD) in the medial talar dome. Ten cadaveric lower extremities were used to develop and evaluate a retrograde osteochondral grafting technique applying computer-assisted surgery. With the help of a computed tomography (CT)-based navigation system, a guide wire was placed from the lateral talar process into the posteromedial talar
Christian Hoser; Oliver Bichler; Reto Bale; Ralph Rosenberger; Michael Rieger; Peter Kovacs; Thomas Lang; Christian Fink
Treatment of symptomatic large cystic lesions of the talus has had mixed results. A technique of treatment using a cored osteochondral graft taken from the ipsilateral knee is presented. Preliminary results in ten consecutive patients show significant improvement in all patients with an average increase of 27 points in the AOFAS Hindfoot score. PMID:11428755
Scranton, P E; McDermott, J E
Background: There is a need to clarify the usefulness of and problems associated with cylindrical costal osteochondral autograft for reconstruction of large defects of the capitellum due to osteochondritis dissecans. Methods: Twenty-six patients with advanced osteochondritis dissecans of the humeral capitellum were treated with use of cylindrical costal osteochondral autograft. All were males with elbow pain and full-thickness articular cartilage lesions of ?15 mm in diameter. Clinical, radiographic, and magnetic resonance imaging outcomes were evaluated at a mean follow-up of thirty-six months (range, twenty-four to fifty-one months). Results: All patients had rapid functional improvement after treatment with costal osteochondral autograft and returned to their former activities, including sports. Five patients needed additional minor surgical procedures, including screw removal, loose body removal, and shaving of protruded articular cartilage. Mean elbow function, assessed with use of the clinical rating system of Timmerman and Andrews, was 111 points preoperatively and improved to 180 points at the time of follow-up and to 190 points after the five patients underwent the additional operations. Mean elbow motion was 126° of flexion with 16° of extension loss preoperatively and improved to 133° of flexion with 3° of extension loss at the time of follow-up. Osseous union of the graft on radiographs was obtained within three months in all patients. Revascularization of the graft depicted on T1-weighted magnetic resonance imaging and congruity of the reconstructed articular surface depicted on T2-weighted or short tau inversion recovery imaging were assessed at twelve and twenty-four months postoperatively. Functional recovery was good, and all patients were satisfied with the final outcomes. Conclusions: Cylindrical costal osteochondral autograft was useful for the treatment of advanced osteochondritis dissecans of the humeral capitellum. Functional recovery was rapid after surgery. Additional operations were performed for five of the twenty-six patients, whereas the remaining patients showed essentially full recovery within a year. All patients were satisfied with the results at the time of short-term follow-up. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID:22637205
Shimada, Kozo; Tanaka, Hiroyuki; Matsumoto, Taiichi; Miyake, Junichi; Higuchi, Haruhisa; Gamo, Kazushige; Fuji, Takeshi
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
Bates, J Tyler; Jacobs, John C; Shea, Kevin G; Oxford, Julia Thom
OBJECTIVES: Treatments for injured articular cartilage have not advanced to the point that efficient regeneration is possible. However, there has been an increase in the use of platelet-rich plasma for the treatment of several orthopedic disorders, including chondral injuries. Our hypothesis is that the treatment of chondral injuries with platelet gel results in higher-quality repair tissue after 180 days compared with chondral injuries not treated with gel. METHODS: A controlled experimental laboratory study was performed on 30 male rabbits to evaluate osteochondral injury repair after treatment with or without platelet gel. Osteochondral injuries were surgically induced in both knees of each rabbit at the medial femoral condyle. The left knee injury was filled with the platelet gel, and the right knee was not treated. Microscopic analysis of both knee samples was performed after 180 days using a histological grading scale. RESULTS: The only histological evaluation criterion that was not significantly different between treatments was metachromasia. The group that was treated with platelet gel exhibited superior results in all other criteria (cell morphology, surface regularity, chondral thickness and repair tissue integration) and in the total score. CONCLUSION: The repair tissue was histologically superior after 180 days in the study group treated with platelet gel compared with the group of untreated injuries.
Danieli, Marcus Vinicius; da Rosa Pereira, Hamilton; de Sa Carneiro, Carlos Augusto; Felisbino, Sergio Luiz; Deffune, Elenice
Image-Guided Techniques Improve the Short-term Outcome of Autologous Osteochondral Cartilage Repair), autologous chrondocyte implantation (ACI) (11) (12) (13) (14), and autologous osteochondral transplantation
, they are followed by cartilage grafting to repair discrete chondral lesions and ultimately total joint arthroplasty is autologous chondrocyte implantation. This cell therapy-based procedure for osteochondral defect repair
When conservative treatment is unsuccessful, there are many surgical options to treat patients with symptomatic chronic osteochondral lesions of the talus. The chosen treatment depends on the patient's symptoms, clinical examination findings, preoperative imaging results, and whether prior surgery was unsuccessful. It is important to be aware of treatment alternatives such as marrow stimulation, osteochondral autograft or allograft plugs, autologous chondrocyte implantation, and newer techniques currently being investigated outside the United States. PMID:20415394
Ferkel, Richard D; Scranton, Pierce E; Stone, James W; Kern, Brian S
The mechanical behavior of osteochondral defects was evaluated in this study with the intention of developing alternative procedures. Cylindrical pins (5.00 mm in diameter and in height) made of pHEMA hydrogel covered ultra-high molecular weight polyethylene (UHMWPE) or beta-tricalcium phosphate (beta-TCP) matrix were used. Ostoechondral defects were caused in the knees of adult dogs and the evaluation was carried out after a 9-month follow-up period. The mechanical behavior of the implants was evaluated by means of an indentation creep test that showed that the UHMWPE matrix maintained its viscoelastic behavior even after follow-up time, while the beta-TCP matrix osteochondral implants presented significant alterations. It is believed that the beta-TCP osteochondral implants were unable to withstand the load applied, causing an increase of complacency when compared to the UHMWPE osteochondral implants. Based on micro and macroscopic analysis, no significant wear was observed in either of the osteochondral implants when compared to the controls. However, morphological alterations, with fragmentation indices in the patella, were observed either due to friction with the hydrogel in the first postoperative months or due to forming of a dense conjunctive tissue. This wear mechanism caused on the counterface of the implant (patella) was observed, notwithstanding the osteochondral implant studied. PMID:18370946
Bavaresco, Vanessa P; Garrido, Luiz; Batista, Nilza A; Malmonge, Sônia M; Belangero, William D
Objectives Osteochondral injuries, if not treated adequately, often lead to severe osteoarthritis. Possible treatment options include refixation of the fragment or replacement therapies such as Pridie drilling, microfracture or osteochondral grafts, all of which have certain disadvantages. Only refixation of the fragment can produce a smooth and resilient joint surface. The aim of this study was the evaluation of an ultrasound-activated bioresorbable pin for the refixation of osteochondral fragments under physiological conditions. Methods In 16 Merino sheep, specific osteochondral fragments of the medial femoral condyle were produced and refixed with one of conventional bioresorbable pins, titanium screws or ultrasound-activated pins. Macro- and microscopic scoring was undertaken after three months. Results The healing ratio with ultrasound-activated pins was higher than with conventional pins. No negative heat effect on cartilage has been shown. Conclusion As the material is bioresorbable, no further surgery is required to remove the implant. MRI imaging is not compromised, as it is with implanted screws. The use of bioresorbable pins using ultrasound is a promising technology for the refixation of osteochondral fractures. PMID:23610699
Neumann, H.; Schulz, A. P.; Gille, J.; Klinger, M.; Jurgens, C.; Reimers, N.; Kienast, B.
The management of osteoarthritis (OA) remains challenging and controversial. Although several clinical options exist for the treatment of OA, regeneration of the damaged articular cartilage has proved difficult due to the limited healing capacity. With the advancements in tissue engineering and cell-based technologies over the past decade, new therapeutic options for patients with osteochondral lesions potentially exist. This review will focus on the feasibility of tissue-engineered biphasic scaffolds, which can mimic the native osteochondral complex, for osteochondral repair and highlight the recent development of these techniques toward tissue regeneration. Moreover, basic anatomy, strategy for osteochondral repair, the design and fabrication methods of scaffolds, as well as the choice of cells, growth factor, and materials will be discussed. Specifically, we focus on the latest preclinical animal studies using large animals and clinical trials with high clinical relevance. In turn, this will facilitate an understanding of the latest trends in osteochondral repair and contribute to the future application of such clinical therapies in patients with OA. PMID:24417741
Shimomura, Kazunori; Moriguchi, Yu; Murawski, Christopher D; Yoshikawa, Hideki; Nakamura, Norimasa
SUMMARY Several etiological theories have been proposed for the development of osteochondritis dissecans. Cartilage toxicity after fluoroquinolone use has been well documented in vitro. We present a case report of a 10-year-old child who underwent a prolonged 18-month course of ciprofloxacin therapy for chronic urinary tract infections. This patient later developed an osteochondritis dissecans lesion of the medial femoral condyle. We hypothesize that the fluoroquinolone therapy disrupted normal endochondral ossification, resulting in development of osteochondritis dissecans. The etiology of osteochondritis dissecans is still unclear, and this case describes an association between fluoroquinolone use and osteochondritis dissecans development. PMID:25228675
Jacobs, John; Shea, Kevin; Oxford, Julia; Carey, James
The treatment of osteochondral lesions of the talus has evolved with the development of improved imaging and arthroscopic techniques. However, the outcome of treatment for large cystic type-V lesions is poor, using conventional grafting, debridement or microfracture techniques. This retrospective study examined the outcomes of 50 patients with a cystic talar defect who were treated with arthroscopically harvested, cored osteochondral graft taken from the ipsilateral knee. Of the 50 patients, 45 (90%) had a mean good to excellent score of 80.3 (52 to 90) in the Karlsson-Peterson Ankle Score, at a mean follow-up of 36 months (24 to 83). A malleolar osteotomy for exposure was needed in 26 patients and there were no malleolar mal- or nonunions. One patient had symptoms at the donor site three months after surgery; these resolved after arthroscopic release of scar tissue. This technique is demanding with or without a malleolar osteotomy, but if properly performed has a high likelihood of success. PMID:16645106
Scranton, P E; Frey, C C; Feder, K S
Fresh osteochondral allograft (OCA) transplantation has been used to manage a wide spectrum of chondral and osteochondral knee disorders. Basic science and clinical studies support the safety and efficacy of the procedure. Transplantation of viable, mature hyaline cartilage into the affected area is an advantage of the procedure, which can be used to restore bone stock in complex or salvage scenarios. Indications for OCA transplantation in the knee include primary management of large chondral or osteochondral defects and salvage of previously failed cartilage repair. The procedure also can be used for complex biologic knee reconstruction in the setting of osteonecrosis, fracture malunion, or posttraumatic arthritis. Challenges associated with OCA transplantation include allograft storage and size matching, tissue availability, chondrocyte viability, the possibility of immunologic graft response, and a demanding surgical technique. Future research should focus on optimizing allograft viability and healing and refining current surgical indications and techniques. PMID:24486758
Sherman, Seth L; Garrity, Joseph; Bauer, Kathryn; Cook, James; Stannard, James; Bugbee, William
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
Daniel L. Cohen; Jeffrey I. Lipton; Lawrence J. Bonassar; Hod Lipson
In recent years there has been a burst of interest in the repair of articular cartilage defects. Fresh osteochondral (shell)allografting is one of several experimental procedures designed to repair full-thickness defects in young adults. This article describes the procedures used at our institution and contrasts these with the procedures at the two other centers, Mount Sinai Hospital in Toronto, Canada,
F. Richard Convery; Wayne H. Akeson; Marvin H. Meyers
Internal fixation of a traumatic osteochondral defect presents a challenge in terms of obtaining anatomic reduction, fixation,\\u000a and adequate compression for healing. Fixation with countersunk intraarticular screws, Herbert screws, bioabsorbable screws\\u000a and pins, mini-cancellous screws, and glue tissue adhesive have been reported with varying results. We present an alternative\\u000a fixation method used in two patients for femoral condylar defects that
Andrea L. Bowers; G. Russell Huffman
No single etiology regarding the cause of osteochondritis dissecans (OCD) lesions is unanimously accepted. This report documents a novel case of multiple OCD lesions affecting the left knee and a solitary defect of the right elbow in a patient with acquired human growth hormone (hGH) deficiency and supplementation. hGH deficiency and hormone replacement may be related to the development of OCD lesions. PMID:21222104
Hussain, Waqas M; Hussain, Haroon M; Hussain, Mohammed S; Ho, Sherwin S W
The definition "osteochondritis dissecans" of the talus improperly includes a variety of diseases involving the chondral surface of the talus dome and the relative subchondral bone. To investigate the CT diagnostic potentials in the study of these conditions, 35 patients complaining of a "painful ankle" were examined with plain radiography and axial and direct paracoronal CT over a 2-year period. Twelve patients were then examined with double contrast CT arthrography with air and iodated contrast agents. CT diagnostic accuracy was assessed evaluating the following parameters: the presence and extent of the subchondral bone fragment, the presence of residual bone fragment attachment at the lesion base or its intraarticular dislocation, the presence of subchondral bone cysts, of chondral surface lesions and, finally, of capsular and ligamentous damage. All the patients with CT findings of osteochondral conditions of the talus dome were submitted to arthroscopic examination/treatment and/or surgical arthrotomy. Baseline CT exams accurately depicted all the lesions, except for early (grade I) lesions. Moreover, the administration of intraarticular contrast agent (CT arthrography) increased the diagnostic accuracy in articular cartilage studies. Therefore, the authors believe baseline CT on the orthogonal planes to represent an effective tool for the staging of osteochondral talar lesions and for accurate treatment planning. PMID:9122454
Ragozzino, A; Rossi, G; Esposito, S; Giovine, S; Tuccillo, M
Posterior cruciate ligament (PCL) insertion-site osteochondral avulsions in children, particularly from the tibia, are not commonly seen by orthopaedic surgeons. Because of the rarity of these injuries, careful attention to the specific physical examination and imaging findings seen with these injuries is necessary so that the proper diagnosis can be made. Osteochondral avulsions of the PCL can be missed on plain radiographs in skeletally immature patients, and therefore magnetic resonance imaging is necessary for proper diagnosis. With this knowledge, clinicians can formulate treatment plans which can return their patients to activities while avoiding potential morbidity resulting from missed diagnoses or improper treatment. We report two rare cases of PCL insufficiency stemming from tibial insertion osteochondral avulsions. Both patients underwent subsequent open reduction and internal fixation of the avulsion using two different fixation methods (bioabsorbable anchors versus cannulated screw and washer) and have returned to full sporting activities. Electronic supplementary material The online version of this article (doi:10.1007/s11999-008-0373-6) contains supplementary material, which is available to authorized users. PMID:18648903
Pandya, Nirav K.; Janik, Luke; Chan, Gilbert
A report of a case of osteochondral fracture of the lateral femoral condyle in a patient doing a karate kick. The problems related to fixation of osteochondral fragments with protruding screws are highlighted and the suitability of Herbert screw fixation noted.
C E Mbubaegbu; A J Percy
People suffering from pain due to osteoarthritic or rheumatoidal changes in the joints are still waiting for a better treatment. Although some studies have achieved success in repairing small cartilage defects, there is no widely accepted method for complete repair of osteochondral defects. Also joint replacements have not yet succeeded in replacing of natural cartilage without complications. Therefore, there is room for a new medical approach, which outperforms currently used methods. The aim of this study is to show potential of using a tissue engineering approach for regeneration of osteochondral defects. The critical review of currently used methods for treatment of osteochondral defects is also provided. In this study, two kinds of hybrid scaffolds developed in Hutmacher's group have been analysed. The first biphasic scaffold consists of fibrin and PCL. The fibrin serves as a cartilage phase while the porous PCL scaffold acts as the subchondral phase. The second system comprises of PCL and PCL-TCP. The scaffolds were fabricated via fused deposition modeling which is a rapid prototyping system. Bone marrow-derived mesenchymal cells were isolated from New Zealand White rabbits, cultured in vitro and seeded into the scaffolds. Bone regenerations of the subchondral phases were quantified via micro CT analysis and the results demonstrated the potential of the porous PCL and PCL-TCP scaffolds in promoting bone healing. Fibrin was found to be lacking in this aspect as it degrades rapidly. On the other hand, the porous PCL scaffold degrades slowly hence it provides an effective mechanical support. This study shows that in the field of cartilage repair or replacement, tissue engineering may have big impact in the future. In vivo bone and cartilage engineering via combining a novel composite, biphasic scaffold technology with a MSC has been shown a high potential in the knee defect regeneration in the animal models. However, the clinical application of tissue engineering requires the future research work due to several problems, such as scaffold design, cellular delivery and implantation strategies. PMID:17931965
Swieszkowski, Wojciech; Tuan, Barnabas Ho Saey; Kurzydlowski, Krzysztof J; Hutmacher, Dietmar W
Summary Objective Normal cartilage is resistant to vascular invasion and anti-angiogenic protease inhibitors may contribute to its avascular status. We hypothesized that dysregulated expression of four key anti-angiogenic protease inhibitors may contribute to increased osteochondral vascularity in osteoarthritis (OA). Design Medial tibial plateaux from OA patients (n = 40) were compared with those from non-arthritic controls collected post-mortem (PM, n = 10). Immunohistochemistry was performed for protease inhibitors TIMP-1, TIMP-3, PAI-1 and SLPI and the pro-angiogenic factor vascular endothelial growth factor (VEGF). Immunoreactivity in articular chondrocytes was scored. Chondropathy was measured as a modified Mankin score, and osteochondral vascular density as number of channels crossing each mm of tidemark. Non-parametric analyses were used for all data. Results All protease inhibitors and VEGF were localised to chondrocytes near the articular surface, less often in the middle zone, and rarely to deep chondrocytes. Scores for VEGF, TIMP-1, TIMP-3, SLPI and PAI-1 were all increased in OA compared with PM, and higher scores were associated with greater chondropathy. Chondrocyte expression of VEGF was associated with higher osteochondral vascular density (r = 0.32, P < 0.05), whereas protease inhibitors were not. Conclusions The resistance of normal articular cartilage to vascular invasion may be more due to its matrix environment than ongoing protease inhibitor expression. Upregulation of protease inhibitors by superficial chondrocytes in OA may moderate the angiogenic effects of growth factors such as VEGF. However, failure of deep chondrocytes to express anti-angiogenic protease inhibitors may permit vascular invasion into the articular cartilage. PMID:20060952
Franses, R.E.; McWilliams, D.F.; Mapp, P.I.; Walsh, D.A.
Internal fixation of a traumatic osteochondral defect presents a challenge in terms of obtaining anatomic reduction, fixation, and adequate compression for healing. Fixation with countersunk intraarticular screws, Herbert screws, bioabsorbable screws and pins, mini-cancellous screws, and glue tissue adhesive have been reported with varying results. We present an alternative fixation method used in two patients for femoral condylar defects that achieved anatomic reduction with compression via a cruciate-shaped suture bridge construct tied down over a bony bridge. This fixation method allowed early passive range of motion and permitted high-quality MRI for followup of fracture healing and articular cartilage integrity. Arthroscopic examination of one of two patients at 6 months followup showed the gross appearance of a healed, anatomically reduced fracture. With 1 year followup for one patient and 2 years for the other, the patients have resumed activity as tolerated with full, painless range of motion at the knee. Longer-term outcomes are unknown. However, the suture bridge is an alternative means of fixation with encouraging early results for treatment of traumatic osteochondral fragments in the knee. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18584263
Bowers, Andrea L.
grafts have emerged as a promising treatment option for this debilitating condition. Currently for osteochondral interface tissue engineering. Introduction Osteoarthritis is the predominant form of arthritis1 Current treatment options for osteoarthritis include lavage, periosteal grafts, subchondral drilling
Linhardt, Robert J.
Background: Autologous osteochondral transplantation surgery requires an impact force on the graft that may cause chondrocyte death and matrix degradation. This study attempted to determine the degree to which this occurs in a rabbit model shortly after the procedure.Hypothesis: Impaction of a press-fit autologous osteochondral graft in vivo results in chondrocyte necrosis, apoptosis, and matrix degradation at early time points.Study
Lawrence V. Gulotta; Jonas R. Rudzki; David Kovacevic; Christopher C. T. Chen; Dejan Milentijevic; Riley J. Williams
Background: Autologous osteochondral transplantation procedures provide hyaline cartilage to the site of cartilage repair. It remains unknown whether these procedures restore native contact mechanics of the ankle joint.Purpose: This study was undertaken to characterize the regional and local contact mechanics after autologous osteochondral transplantation of the talus.Study Design: Controlled laboratory study.Methods: Ten fresh-frozen cadaveric lower limb specimens were used for
Ashraf M. Fansa; Christopher D. Murawski; Carl W. Imhauser; Joseph T. Nguyen; John G. Kennedy
This study shows that artificial super antiapoptotic FNK protein fused with a protein transduction domain (PTD-FNK) maintains the quality of osteochondral transplant by preventing chondrocyte death. Cylindrical osteochondral grafts were obtained from enhanced green fluorescent protein (EGFP)-expressing transgenic rats, in which living chondrocytes express green fluorescence, and submerged into medium containing PTD-FNK, followed by transplantation into cartilage defects of wild-type
Noriki Nakachi; Sadamitsu Asoh; Nobuyoshi Watanabe; Takashi Mori; Takashi Matsushita; Shinro Takai; Shigeo Ohta
No Tables CHAPTER 2 Table 2.1: Mechanical properties of condylar cartilage??.................................... 223 Table 2.2: Fibril/fiber dimensions and major collagen types in condylar cartilage.. 224 Table 2.3: Quantified extracellular matrix... and compressive properties of the mandibular condylar cartilage. The next phase was then to develop integrated osteochondral scaffolds and evaluate them for osteochondral tissue regeneration. The characterization stage provided important mechanical property...
The appropriate surgical technique for the treatment of unstable osteochondral lesions of the knee remains unclear and had been traditionally described with an open arthrotomy. Administration of bone grafting material in the knee may be performed for a variety of pathologic conditions, including unstable osteochondritis dissecans, traumatic osteochondral defects, or subchondral fracture nonunion, or for preparation of residual tunnels during revision anterior cruciate ligament reconstruction. Although various grafting materials have been described in the literature, cancellous autograft remains the gold standard for treatment safety and efficacy. We describe a successful technique for arthroscopic delivery of autogenous bone graft during fixation of unstable osteochondral lesions of the knee. When the indication for grafting is established, cancellous autograft is harvested from the proximal tibia, undergoes morcellation, and is soaked in bone marrow aspirate obtained through the harvest window. The bone graft is then packed into a modified tuberculin syringe. After arthroscopic preparation of the unstable osteochondral fragment and the respective donor surface, the tuberculin syringe is placed through a standard arthroscopy portal and the bone graft is introduced into the defect under direct visualization, followed by an appropriate osteochondral fixation technique. PMID:25126499
Espinoza, Chris; Ellis, Henry B; Wilson, Philip
Loose bodies are relatively common in the knee. On radiographs they can often be seen in the medial and lateral gutters, intercondylar notch, and the posterior compartment. At times an apparent loose body is not free to move in the knee because it has been covered by synovium and is no longer mobile. It is uncommon for an osteochondral loose body to become incorporated into meniscal tissue. We report a case of an apparent loose body becoming incorporated into the posterior horn and root of the medial meniscus. We are not aware that this condition has been previously reported. Because removing the entire loose body would have destabilized the posterior root of the medial meniscus, it is important to be aware of this potential occurrence. PMID:25251527
Jones, Christopher R; McMonagle, Joseph S; Garrett, William E
Contemporary methods of bone grafting osteochondral defects, in which the remaining overlying cartilage is relatively well preserved, have inherent problems. The bony defects are often saucer-shaped and the cylindrical graft may not fill the void, leaving areas of cartilage with no underlying scaffold and obviating early weight bearing. Furthermore, to obtain a proper fill of the defect, tamping of the graft can cause excessive pressure and disruption of the overlying cartilage. In an effort to address these concerns, the authors propose the use of a biological viscous paste of calcium sulfate that hardens within 5 minutes when injected in a retrograde fashion into the talus. This confers a mechanical advantage of complete cystic fill of the cyst which allows early weight bearing. Calcium sulfate acts as an osteoconductive material that incorporates into host bone within 8 weeks. Donor site morbidity is eliminated using this system. PMID:18549760
Kennedy, John G; Suero, Eduardo Manuel; O'Loughlin, Padhraig F; Brief, Andrew; Bohne, Walther H O
Three snow leopard (Uncia uncia) cubs, female and male siblings and an unrelated female, had lameness attributed to osteochondritis dissecans (OCD) lesions noted at 6, 8, and 10 mo of age, respectively. All cubs were diagnosed with OCD via radiographs. The sibling cubs both had lesions of the right lateral femoral condyles, while the unrelated cub had bilateral lesions of the lateral femoral condyles. Subsequently, OCD was confirmed in all three cases during surgical correction of the lateral femoral condyle lesions via lateral stifle arthrotomies, flap removal, and debridement of the defect sites. Histopathology also supported the diagnosis of OCD. Postoperatively, the sibling cubs developed seromas at the incision sites and mild lameness, which resolved within a month. To date, two cubs have been orthopedically sound, while one of the sibling cubs has developed mild osteoarthritis. OCD has rarely been reported in domestic felids, and to the authors' knowledge these are the first reported cases of OCD in nondomestic felids. PMID:22779240
Herrin, Kimberly Vinette; Allan, Graeme; Black, Anthony; Aliah, Rhonda; Howlett, Cameron Rolfe
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 ?-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
Pei, Yang; Fan, Jun-jun; Zhang, Xiao-qiang; Zhang, Zhi-yong; Yu, Min
We investigated the use of a commercial spectrocolorimeter and the application of two color models (L* a* b* colorimetric system and spectral reflectance distribution) to describe and quantify cartilage plugs in a rabbit model of osteochondral autografting. Osteochondral plugs were removed and then replaced in their original positions in Japanese white rabbits. The rabbits were sacrificed at 4 or 12
Koji Hattori; Kota Uematsu; Yohei Tanikake; Takashi Habata; Yasuhito Tanaka; Hiroshi Yajima; Yoshinori Takakura
The structure of an osteochondral biphasic scaffold is required to mimic native tissue, which owns a calcified layer associated with mechanical and separation function. The two phases of biphasic scaffold should possess efficient integration to provide chondrocytes and osteocytes with an independent living environment. In this study, a novel biphasic scaffold composed of a bony phase, chondral phase and compact layer was developed. The compact layer-free biphasic scaffold taken as control group was also fabricated. The purpose of current study was to evaluate the impact of the compact layer in the biphasic scaffold. Bony and chondral phases were seeded with autogeneic osteoblast- or chondrocyte-induced bone marrow stromal cells (BMSCs), respectively. The biphasic scaffolds-cells constructs were then implanted into osteochondral defects of rabbits’ knees, and the regenerated osteochondral tissue was evaluated at 3 and 6 months after surgery. Anti-tensile and anti-shear properties of the compact layer-containing biphasic scaffold were significantly higher than those of the compact layer-free biphasic scaffold in vitro. Furthermore, in vivo studies revealed superior macroscopic scores, glycosaminoglycan (GAG) and collagen content, micro tomograph imaging results, and histological properties of regenerated tissue in the compact layer-containing biphasic scaffold compared to the control group. These results indicated that the compact layer could significantly enhance the biomechanical properties of biphasic scaffold in vitro and regeneration of osteochondral tissue in vivo, and thus represented a promising approach to osteochondral tissue engineering. PMID:23382984
Cheng, Jian-Hua; Zhou, Wei; Xiong, Zhuo; Mu, Yun-Jing; Liu, Jian
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 bone-hydrogel 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 bone-hydrogel interface increased by 100% with the teZCC. Numerical predictions of the osteochondral defect treatment showed that the shear stress at the bone-hydrogel 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 bone-hydrogel interface and second, it reduces the stress at this interface. PMID:23706035
Hollenstein, Jérôme; Terrier, Alexandre; Cory, Esther; Chen, Albert C; Sah, Robert L; Pioletti, Dominique P
Several options exist for the treatment of osteochondral lesions of the talus. Particulated juvenile cartilage allograft transplantation (PJCAT) has become a viable treatment modality for osteochondral lesions of the talus that are not amenable to microfracture or for which microfracture has failed. Arthroscopic placement of this type of graft obviates the need for osteotomy or plafondplasty and does not prevent additional procedures from being performed through an anterior approach. Special instrumentation and setup are not required to perform this procedure. Our arthroscopic technique for placement of particulated juvenile cartilage into osteochondral lesions of the talus is described. Case series and outcomes after arthroscopic ankle PJCAT are currently not reported within the literature; however, it is believed that the outcomes are at least similar to those of open ankle PJCAT. PMID:25264516
Adams, Samuel B; Demetracopoulos, Constantine A; Parekh, Selene G; Easley, Mark E; Robbins, Justin
Several options exist for the treatment of osteochondral lesions of the talus. Particulated juvenile cartilage allograft transplantation (PJCAT) has become a viable treatment modality for osteochondral lesions of the talus that are not amenable to microfracture or for which microfracture has failed. Arthroscopic placement of this type of graft obviates the need for osteotomy or plafondplasty and does not prevent additional procedures from being performed through an anterior approach. Special instrumentation and setup are not required to perform this procedure. Our arthroscopic technique for placement of particulated juvenile cartilage into osteochondral lesions of the talus is described. Case series and outcomes after arthroscopic ankle PJCAT are currently not reported within the literature; however, it is believed that the outcomes are at least similar to those of open ankle PJCAT.
Adams, Samuel B.; Demetracopoulos, Constantine A.; Parekh, Selene G.; Easley, Mark E.; Robbins, Justin
Objective To assess the influence of osteochondral graft preservation techniques on post-transplant biomechanics of graft and host subchondral bone in the knee joint. Design An experimental animal model (sheep), specifically the weight-bearing articular surface of the medial femoral condyle of the knee joints. Intervention Each sheep received, in the ipsilateral knee, an allograft that was (a) frozen without dimethyl sulfoxide (DMSO), (b) snap-frozen in liquid nitrogen or (c) frozen with DMSO. The contralateral knee received an autograft that was (a) snap-frozen, (b) treated with DMSO or (c) left untreated (fresh). Main outcome measures Mechanical and material properties of bone, including maximal compression stress, modulus of elasticity and bone mineral ash content of subchondral bone cores (from the graft centre and surrounding host bone). Results No significant differences were found in the mechanical properties of the subchondral bone under the graft, but there were significant changes in surrounding bone. Bone surrounding the grafts that were snap-frozen or frozen without DMSO was significantly stronger than the normal control bone. However, bone surrounding fresh autografts and cryoprotected allografts was not significantly different from normal control bone. Conclusions The changes in the mechanical behaviour of the host bone may be associated with graft cell viability. The greater stiffness of the subchondral host bone may have consequences for long-term graft integrity and for the development of degenerative osteoarthritis. PMID:9627549
Wohl, Greg; Goplen, Gordon; Ford, Jason; Novak, Kelli; Hurtig, Mark; McPherson, Roger; McGann, Locksley; Schachar, Norman; Zernicke, Ronald F.
Purpose Retrospective review of high-resolution MR imaging features of talar dome osteochondral lesions and development of new classification\\u000a system based on these features.\\u000a \\u000a \\u000a \\u000a \\u000a Material and methods Over the past 7 years, 70 osteochondral lesions of the talar dome from 70 patients (49 males, 21 females, mean age 42 years,\\u000a range 15–62 years) underwent high-resolution MR imaging with a microscopy coil at 1.5 T. Sixty-one (87%) of
James Francis Griffith; Domily Ting Yi Lau; David Ka Wai Yeung; Margaret Wan Nar Wong
Although osteochondritis dissecans of the knee has been known for a long time, we still do not fully understand why it develops. This prompted us to present and describe an example of osteochondritis dissecans identified in the Osteological Collection of the Croatian Academy of Sciences and Arts. The case of osteochondritis dissecans described in this report was recovered from the Gluvine ku?e cemetery in the Dalmatian hinterland, approximately 28 km north-east of Split. A total of 77 graves were excavated and the individual exhibiting osteochondritis dissecans was recovered from grave number 16 that belongs to the younger phase of the cemetery that lasted during the second half of the 9th century A.D. Osteochondritis dissecans was noted in a subadult individual. The pathological changes consistent with osteochondritis dissecans are present on both medial femoral condyles. The lesion on the right femoral condyle is an oval crater-like defect with well defined margins and a porous floor of rough trabecular bone. The lesion on the left femoral condyle is basically, with two small provisions, identical to the one on the right side. The first is that it is slightly smaller, while the second is that unlike its antimere, it has a well preserved bone fragment that fits perfectly into the ostechondritic pit. Radiographic analyses of the femoral condyles support a diagnosis of osteochondritis dissecans and show a well-demarcated radiolucent defect in the articular surfaces of both joints surrounded by a thin sclerotic repair zone. According to the classification systems this degree of change corresponds to stage 3 or grade 3 osteochondritis dissecans--a detached but non-displaced fragment. Returning, for a second, to the opinion that prompted us to present this case, it is clear that during the last 1100 years there have been no significant morphological or radiological changes in the characteristics of osteochondritis dissecans. PMID:21086739
Slaus, Mario; Cicvara-Pe?ina, Tatjana; Lucijani?, Ivica; Pe?ina, Marko; Stilinovi?, Davor
Repairing osteochondral defects (OCD) remains a formidable challenge due to the high complexity of native osteochondral tissue and the limited self-repair capability of cartilage. Osteochondral tissue engineering is a promising strategy for the treatment of OCD. In this study, we fabricated a novel integrated trilayered scaffold using silk fibroin and hydroxyapatite by combining paraffin-sphere leaching with a modified temperature gradient-guided thermal-induced phase separation (TIPS) technique. This biomimetic scaffold is characterized by three layers: a chondral layer with a longitudinally oriented microtubular structure, a bony layer with a 3D porous structure and an intermediate layer with a dense structure. Live/dead and CCK-8 tests indicated that this scaffold possesses good biocompatibility for supporting the growth, proliferation, and infiltration of adipose-derived stem cells (ADSCs). Histological and immunohistochemical stainings and real-time polymerase chain reaction (RT-PCR) confirmed that the ADSCs could be induced to differentiate toward chondrocytes or osteoblasts in vitro at chondral and bony layers in the presence of chondrogenic- or osteogenic-induced culture medium, respectively. Moreover, the intermediate layer could play an isolating role for preventing the cells within the chondral and bony layers from mixing with each other. In conclusion, the trilayered and integrated osteochondral scaffolds can effectively support cartilage and bone tissue generation in vitro and are potentially applicable for OC tissue engineering in vivo. PMID:25210952
Ding, Xiaoming; Zhu, Meifeng; Xu, Baoshan; Zhang, Jiamin; Zhao, Yanhong; Ji, Shenglu; Wang, Lina; Wang, Lianyong; Li, Xiulan; Kong, Deling; Ma, Xinlong; Yang, Qiang
Cartilage defects of the hip cause significant pain and may lead to arthritic changes that necessitate hip replacement. We propose the use of fresh osteochondral allografts as an option for the treatment of such defects in young patients. Here we present the results of fresh osteochondral allografts for cartilage defects in 17 patients in a prospective study. The underlying diagnoses for the cartilage defects were osteochondritis dissecans in eight and avascular necrosis in six. Two had Legg-Calve-Perthes and one a femoral head fracture. Pre-operatively, an MRI was used to determine the size of the cartilage defect and the femoral head diameter. All patients underwent surgical hip dislocation with a trochanteric slide osteotomy for placement of the allograft. The mean age at surgery was 25.9 years (17 to 44) and mean follow-up was 41.6 months (3 to 74). The mean Harris hip score was significantly better after surgery (p < 0.01) and 13 patients had fair to good outcomes. One patient required a repeat allograft, one patient underwent hip replacement and two patients are awaiting hip replacement. Fresh osteochondral allograft is a reasonable treatment option for hip cartilage defects in young patients. Cite this article: Bone Joint J 2014;96-B(11 Supple A):11-16. PMID:25381401
Khanna, V; Tushinski, D M; Drexler, M; Backstein, D B; Gross, A E; Safir, O A; Kuzyk, P R
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
Fedorovich, Natalja E.; Schuurman, Wouter; Wijnberg, Hans M.; Prins, Henk-Jan; van Weeren, P. Rene; Malda, Jos; Dhert, Wouter J.A.
Osteochondral defects are frequent, painful, debilitating and expensive to treat, often resulting in poor results. The goal\\u000a of the present study was to synthesize and characterize a novel biocompatible and biodegradable hydrogel comprised of poly(ethylene\\u000a glycol), gelatin, and genipin, and examine the hydrogel as an injectable biomaterial in combination with a cyanoacrylate-based\\u000a surgical sealant for cartilage repair. An osteochondral knee
Natasa D. Miljkovic; Yen-Chih Lin; Mario Cherubino; Danielle Minteer; Kacey G. Marra
Background: Several methods are used to treat focal chondral and osteochondral defects on the weightbearing surfaces of synovial joints. Autologous osteochondral grafting is 1 option used to replace hyaline cartilage in the defect.Hypothesis: Mosaicplasty is effective in returning elite athletes to participation in sports.Study Design: Case series; Level of evidence, 4.Methods: In 3 institutes, 354 of 383 patients were followed
László Hangody; Jozsef Dobos; Eszter Balo; Gergely Panics; Istvan Berkes
Effective therapies for the regeneration of large osteochondral defects are still lacking; however, various approaches have\\u000a been used. We evaluated the efficacy of Escherichia coli-derived dimeric recombinant human BMP-2 (E-rhBMP-2) for the repair of large osteochondral defects in a rabbit model. Osteochondral\\u000a defects made in the femoral patellar groove of the knee were treated by transplanting gelatin sponges onto which
Yoshio Tokuhara; Shigeyuki Wakitani; Yuuki Imai; Amu Kawaguchi; Kenji Fukunaga; Mitsunari Kim; Yoshinori Kadoya; Kunio Takaoka
The primary objective of this study was to determine if magnetic resonance (MR) could accurately predict the arthroscopic stage of osteochondritis dissecans lesions of the knee and ankle. Twelve patients, who were indicated for arthroscopy on either clinical or radiographic findings, underwent an MR examination prior to arthroscopy. All scans were performed on a 0.35 T magnet using the same spin echo sequence: repetition time 1,000 ms and echo time 40 ms. Magnetic resonance scans were interpreted prospectively (D.W.N.) and retrospectively (J.S.) by the radiologists without knowledge of the arthroscopic findings. Both radiologists predicted the exact grade in 11 of 12 patients. A single Grade 2 lesion was called Grade 3 by both radiologists. An MR staging classification has been developed that allows accurate preoperative staging of osteochondritis dissecans lesions of the talus and knee. PMID:2398165
Nelson, D W; DiPaola, J; Colville, M; Schmidgall, J
Epiphyseal osteochondritis is a localized disorder in childhood. Vascular insufficiency is thought to be the most significant\\u000a etiologic factor. This study had been carried on Primary and Preparatory school children in Zagazig City and surrounding villages\\u000a in Sharkia Governorate, Egypt. Total number of studied children were 16,060, 7,380 males, 8,680 females. The mean age was\\u000a 11.41 ± 1.99. Our results showed that
Amany M. Abou El-Soud; Hala A. Gaballa; Manal Abdo Ali
Background: Magnetic resonance imaging (MRI) is a common clinical tool used to diagnose and monitor the progression and/or healing of osteochondritis dissecans of the knee. The purpose of this study was to systematically review the literature relative to the following questions: (1) Is MRI a valid, sensitive, specific, accurate, and reliable imaging modality to identify knee osteochondritis dissecans compared with arthroscopy? (2) Is MRI a sensitive tool that can be utilized to characterize lesion severity and stability of osteochondritis dissecans fragments in the knee? Methods: A systematic search was performed in December 2010 with use of PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), Scopus (from 1996), and EMBASE (from 1974) databases. Results: Seven studies, four Level-II and three Level-III investigations, met the specified inclusion criteria. No randomized controlled studies were identified. Because of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed. Conclusions: The limited available evidence, methodological inconsistencies in imaging techniques, and lack of standardized grading criteria used in current studies prevent clear conclusions regarding the diagnostic and specific staging equivalency of MRI with arthroscopy. However, available evidence supports the use of MRI to detect the stability or instability of the lesion. Given the benefits of the use of MRI as a noninvasive tool to diagnose, predict lesion progression, and assess clinical outcomes of treatment, there is a pressing need for high-level, systematic, sound, and thorough studies related to the clinical utility of MRI for assessing osteochondritis dissecans of the knee. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID:22637210
Quatman, Carmen E.; Quatman-Yates, Catherine C.; Schmitt, Laura C.; Paterno, Mark V.
There is a recognized and urgent need for improved treatment of articular cartilage defects. Tissue engineering of cartilage using a cell-scaffold approach has demonstrated potential to offer an alternative and effective method for treating articular defects. We have developed a unique, heterogeneous, osteochondral scaffold using the TheriFormTM three-dimensional printing process. The material composition, porosity, macroarchitecture, and mechanical properties varied throughout
Jill K Sherwood; Susan L Riley; Robert Palazzolo; Scott C Brown; Donald C Monkhouse; Matt Coates; Linda G Griffith; Lee K Landeen; Anthony Ratcliffe
Collagen hydrogel has been widely used for osteochondral repair, but its mechanical properties cannot meet the requirements of clinical application. Previous studies have shown that the addition of either polysaccharide or inorganic particles could reinforce the polymer matrix. However, their synergic effects on collagen-based hydrogel have seldom been studied, and the potential application of triple-phased composite gel in osteochondral regeneration has not been reported. In this study, nano-hydroxyapatite (nano-HA) reinforced collagen-alginate hydrogel (nHCA) was prepared by the in situ synthesis of nano-HA in collagen gel followed by the addition of alginate and Ca(2+). The properties of triple-phased nHCA hydrogel were studied and compared with pure collagen and biphasic gels, and the triple-phased composite of collagen-alginate-HA gels showed a superiority in not only mechanical but also biological features, as evidenced by the enhanced tensile and compressive modulus, higher cell viability, faster cell proliferation and upregulated hyaline cartilage markers. In addition, it was found that the synthesis process could also affect the properties of the triple-phased composite, compared to blend-mixing HCA. The in situ-synthesized nHCA hydrogel showed an enhanced tensile modulus, as well as enhanced biological features compared with HCA. Our study demonstrated that the nHCA composite hydrogel holds promise in osteochondral regeneration. The addition of alginate and nano-HA contribute to the increase in both mechanical and biological properties. This study may provide a valuable reference for the design of an appropriate composite scaffold for osteochondral tissue engineering. PMID:25358331
Zheng, Li; Jiang, Xianfang; Chen, Xuening; Fan, Hongsong; Zhang, Xingdong
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.
Becce, Fabio, E-mail: email@example.com [University of Lausanne, Department of Diagnostic and Interventional Radiology, Centre Hospitalier Universitaire Vaudois (Switzerland); Mouhsine, Elyazid [Clinique Hirslanden Bois-Cerf, Department of Orthopaedic Surgery (Switzerland); Mosimann, Pascal John; Anaye, Anass [University of Lausanne, Department of Diagnostic and Interventional Radiology, Centre Hospitalier Universitaire Vaudois (Switzerland); Letovanec, Igor [University Institute of Pathology, Centre Hospitalier Universitaire Vaudois (Switzerland); Theumann, Nicolas [University of Lausanne, Department of Diagnostic and Interventional Radiology, Centre Hospitalier Universitaire Vaudois (Switzerland)
Purpose: To analyze the mechanical effects of autogenous osteochondral grafting procedures on articular cartilage.Methods: The intensity, duration, and interval (indexes of stiffness, surface irregularity, and thickness) of the cartilage were assessed in a porcine model using an ultrasonic measurement system. In 7 of 12 knees, 6-mm-diameter plugs were harvested from the donor knees and grafted into 5-mm recipient holes at
Hiroshi Kuroki; Yasuaki Nakagawa; Koji Mori; Ken Ikeuchi; Takashi Nakamura
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
Lima, Eric G.; Chao, Pen-hsiu Grace; Ateshian, Gerard A.; Bal, B. Sonny; Cook, James L.; Vunjak-Novakovic, Gordana; Hung, Clark T.
Background Here we investigate the effect of millicurrent treatment on human chondrocytes cultivated in a collagen gel matrix and on human osteochondral explants. Methods Human chondrocytes from osteoarthritic knee joints were enzymatically released and transferred into a collagen type-I gel. Osteochondral explants and cell-seeded gel samples were cultivated in-vitro for three weeks. Samples of the verum groups were stimulated every two days by millicurrent treatment (3 mA, sinusoidal signal of 312 Hz amplitude modulated by two super-imposed signals of 0.28 Hz), while control samples remained unaffected. After recovery, collagen type-I, type-II, aggrecan, interleukin-1?, IL-6, TNF? and MMP13 were examined by immunohistochemistry and by real time PCR. Results With regard to the immunostainings 3 D gel samples and osteochondral explants did not show any differences between treatment and control group. The expression of all investigated genes of the 3 D gel samples was elevated following millicurrent treatment. While osteochondral explant gene expression of col-I, col-II and Il-1? was nearly unaffected, aggrecan gene expression was elevated. Following millicurrent treatment, IL-6, TNF?, and MMP13 gene expression decreased. In general, the standard deviations of the gene expression data were high, resulting in rarely significant results. Conclusions We conclude that millicurrent stimulation of human osteoarthritic chondrocytes cultivated in a 3 D collagen gel and of osteochondral explants directly influences cell metabolism. PMID:20691044
It is well accepted that natural tissue regeneration is unlikely to occur if the cells are not supplied with an extracellular matrix (ECM) substitute. With this goal, several different methodologies have been used to produce a variety of 3D scaffolds as artificial ECM substitutes suitable for bone and cartilage tissue engineering. Furthermore, osteochondral tissue engineering presents new challenges since the combination of scaffolding and co-culture requirements from both bone and cartilage applications is required in order to achieve a successful osteochondral construct. In this paper, an innovative processing route based on a chitosan particles aggregation methodology for the production of cartilage and osteochondral tissue engineering scaffolds is reported. An extensive characterization is presented including a morphological evaluation using Micro-Computed Tomography (microCT) and 3D virtual models built with an image processing software. Mechanical and water uptake characterizations were also carried out, evidencing the potential of the developed scaffolds for the proposed applications. Cytotoxicity tests show that the developed chitosan particles agglomerated scaffolds do not exert toxic effects on cells. Furthermore, osteochondral bilayered scaffolds could also be developed. Preliminary seeding of mesenchymal stem cells isolated from human adipose tissue was performed aiming at developing solutions for chondrogenic and osteogenic differentiation for osteochondral tissue engineering applications. PMID:16362204
B Malafaya, P P; Pedro, A J; Peterbauer, A; Gabriel, C; Redl, H; Reis, R L
The aim of this paper is to report on three cases of symptomatic osteochondritis dissecans of the humeral capitellum in adolescent gymnasts, two females and one male. In all the cases arthroscopic surgery was performed. During arthroscopy, loose osteochondral fragments were removed, the defect was debrided and microfractures were performed. All the three patients regained the full range of motion of the affected elbow, and returned to the high-level gymnastics within a period of 5 months. At 12 months follow-up, all the three patients remained symptomless and were participating in high-level gymnastics. A combination of arthroscopy and the microfracture technique is a reliable method with excellent short-term results in the treatment of the osteochondritis dissecans of the elbow. PMID:16217674
Bojani?, Ivan; Ivkovi?, Alan; Bori?, Igor
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
Dormer, Nathan H.; Singh, Milind; Zhao, Liang; Mohan, Neethu; Berkland, Cory J.; Detamore, Michael S.
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
In this study, a novel three-dimensional (3D) heterogeneous/bilayered scaffold was constructed to repair large defects in rabbit joints. The scaffold includes two distinct but integrated layers corresponding to the cartilage and bone components. The upper layer consists of gelatin, chondroitin sulphate and sodium hyaluronate (GCH), and the lower layer consists of gelatin and ceramic bovine bone (GCBB). The two form a 3D bilayered scaffold (GCH-GCBB), which mimics the natural osteochondral matrix for use as a scaffold for osteochondral tissue engineering. The purpose of this study was to evaluate the efficacy of this novel scaffold, combined with chondrocytes and bone marrow stem cells (BMSCs) to repair large defects in rabbit joints. Thirty-six large defects in rabbit femoral condyles were created; 12 defects were treated with the same scaffold combined with cells (group A); another 12 defects were treated with cell-free scaffolds (group B); the others were untreated (group C). At 6 and 12?weeks, in group A hyaline-like cartilage formation could be observed by histological examination; the newly formed cartilage, which stained for type II collagen, was detected by RT-PCR at high-level expression. Most of the GCBB was replaced by bone, while little remained in the underlying cartilage. At 36?weeks, GCBB was completely resorbed and a tidemark was observed in some areas. In contrast, groups B and C showed no cartilage formation but a great amount of fibrous tissue, with only a little bone formation. In summary, this study demonstrated that a novel scaffold, comprising a top layer of GCH, having mechanical properties comparable to native cartilage, and a bottom layer composed of GCBB, could be used to repair large osteochondral defects in joints. PMID:22777833
Deng, Tianzheng; Lv, Jing; Pang, Jianliang; Liu, Bing; Ke, Jie
Osteochondral defects represent a serious clinical problem. Although the cell-scaffold complexes have been reported to be effective for repairing osteochondral defects, a periosteal flap is frequently needed to arrest leakage of the implanted cells into the defect and to contribute to the secretion of cytokines to stimulate cartilage repair. The electrospun mesh mimicking the function of the flap assists tissue regeneration by preventing cell leakage and merits favorable outcomes in the cartilaginous region. In this study, an oriented poly(?-caprolactone) (PCL) fibrous membrane (OEM) was fabricated by electrospinning as a periosteal scaffold and then freeze-dried with a collagen type I and hyaluronic acid cartilage scaffold (CH) and finally, freeze-dried with a tricalcium phosphate (TCP) bone substratum. Scanning electron microscopic images show obvious microstructure formation of the trilayered scaffolds, and electrospun fibrous membranes have an oriented fibrous network structure for the periosteal phase. Also shown are opened and interconnected pores with well designed three-dimensional structure, able to be bound in the CH (chondral phase) and TCP (osseous phase) scaffolds. In vitro results showed that the OEM can promote the orientation of bone marrow mesenchymal stem cell (BMSCs) and BMSCs can penetrate into the CH and TCP. After successfully combining the BMSCs, the tissue-engineered cartilage which contained the OEM and TCP complex was successfully used to regenerate the osteochondral defects in the rabbit model with greatly improved repair effects. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1407-1414, 2014. PMID:24644257
Liu, Xudong; Liu, Shen; Liu, Shenghe; Cui, Wenguo
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.
Seebauer, Christian J., E-mail: firstname.lastname@example.org [Charite - Universitaetsmedizin Berlin, Center for Musculoskeletal Surgery (Germany); Bail, Hermann J., E-mail: email@example.com [Clinic Nuremberg, Department of Trauma and Orthopedic Surgery (Germany); Rump, Jens C., E-mail: firstname.lastname@example.org; Walter, Thula, E-mail: email@example.com; Teichgraeber, Ulf K. M., E-mail: firstname.lastname@example.org [Charite - Universitaetsmedizin Berlin, Department of Radiology (Germany)
Chondrolysis of the ankle is a very rare condition. We report a case of chondrolysis of the ankle following ankle arthroscopy and microfracture of the osteochondral lesion of the talar dome. The patient's symptoms were relieved after articulated distraction arthroplasty. PMID:24369518
Lui, Tun Hing
The range of joint-sparing treatments for advanced hallux rigidus is still very limited. The authors describe an osteochondral autograft transplantation technique combined with Lapidus arthrodesis as a novel method of obtaining a relatively symptom-free first metatarsophalangeal joint function in patients with hallux rigidus and first-ray elevation. PMID:24379451
Klos, Kajetan; Simons, Paul
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
Manferdini, C; Cavallo, C; Grigolo, B; Fiorini, M; Nicoletti, A; Gabusi, E; Zini, N; Pressato, D; Facchini, A; Lisignoli, G
Osteochondritis dissecans (OCD) represents an important clinical entity in orthopedic sports medicine. Once surgical intervention is required, retrograde drilling for OCD lesions remains technically challenging. A novel electromagnetic navigation system was developed to be a radiation-free navigation tool providing spatiotemporal real-time information to the surgeon without the need for a stationary patient tracker and without relevant setup and calibration times. The novel system was tested for arthroscopically assisted retrograde drilling of cadaveric OCD lesions of the knee and talus and compared with the gold standard fluoroscopy-guided retrograde drilling procedure in a controlled laboratory study setup. The novel method considerably improves on the standard operating procedure in terms of safety, operation time, and radiation exposure and will be available for further surgical indications. PMID:25370876
Hoffmann, Michael; Schroeder, Malte; Rueger, Johannes M
Near-infrared (NIR) spectroscopy has been used to assess hyaline cartilage quality in human and animal osteochondral tissues. However, due to the lack of NIR signal from bone phosphate and the relatively deep penetration depth of the radiation, the separate contributions of cartilage and bone to the spectral signatures have not been well defined. The objectives of the current study were (1) to improve the understanding of the contributions of bone and cartilage to NIR spectra acquired from osteochondral tissue and (2) to assess the ability of this nondestructive method to predict cartilage thickness and modified Mankin grade of human tibial plateau articular cartilage. Near-infrared spectra were acquired from samples of bovine bone and cartilage with varying thicknesses and from 22 tibial plateaus harvested from patients undergoing knee replacement surgery. The spectra were recorded from regions of the tibial plateaus with varying degrees of degradation, and the cartilage thickness and modified Mankin grade of these regions were assessed histologically. The spectra from bone and cartilage samples of known thicknesses were investigated to identify spectral regions that were distinct for these two tissues. Univariate and multivariate linear regression methods were used to correlate modified Mankin grade and cartilage thickness with NIR spectral changes. The ratio of the NIR absorbances associated with water at 5270 and 7085 cm(-1) was the best differentiator of cartilage and bone spectra. The NIR prediction models for thickness and Mankin grade calculated using partial least squares regression were more accurate than were univariate-based prediction models, with a root mean square errors of cross-validation of 0.42 mm (for thickness) and 1.3 (for modified Mankin grade). We conclude that NIR spectroscopy may be used to simultaneously assess articular cartilage thickness and modified Mankin grade, based in part on differences in spectral contributions from bone and cartilage. PMID:25197817
McGoverin, Cushla M; Lewis, Karl; Yang, Xu; Bostrom, Mathias P G; Pleshko, Nancy
Purpose Stickler syndrome is among the most common autosomal dominant connective tissue disorders but is often unrecognised and therefore not diagnosed by clinicians. Despite much speculation, the cause of osteochondrosis in general and osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) in particular remain unclear. Etiological understanding is essential. We describe a pair of family subjects presented with OCD and OSS as a symptom complex rather than a diagnosis. Methods Detailed clinical and radiographic examinations were undertaken with emphasis on the role of MRI imaging. Magnetic resonance imaging may allow early prediction of articular lesion healing potential in patients with Stickler syndrome. Results The phenotype of Stickler syndrome can be diverse and therefore misleading. The expectation that the full clinical criteria of any given genetic disorder such as Stickler syndrome will always be present can easily lead to an underestimation of these serious inheritable disorders. We report here two family subjects, a male proband and his aunt (paternal sister), both presented with the major features of Stickler syndrome. Tall stature with marfanoid habitus, astigmatism/congenital vitreous abnormality and submucus cleft palate/cleft uvula, and enlarged painful joints with early onset osteoarthritis. Osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) were the predominating joint abnormalities. Conclusion We observed that the nature of the articular and physeal abnormalities was consistent with a localised manifestation of a more generalised epiphyseal dysplasia affecting the weight-bearing joints. In these two patients, OCD and OSS appeared to be the predominant pathologic musculoskeletal consequences of an underlying Stickler's syndrome. It is empirical to consider generalised epiphyseal dysplasia as a major underlying causation that might drastically affect the weight-bearing joints. PMID:19193224
Al Kaissi, Ali; Klaushofer, Klaus; Grill, Franz
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
Saha, Sushmita; Kundu, Banani; Kirkham, Jennifer; Wood, David; Kundu, Subhas C.; Yang, Xuebin B.
Background: Focal articular cartilage lesions of the knee in young patients present a therapeutic challenge. Little information is available pertaining to the results after implantation of prolonged fresh grafts.Hypothesis: Prolonged fresh osteochondral allografts present a viable option for treating large full-thickness articular cartilage lesions.Study Design: Case series; Level of evidence, 4.Methods: This study presents the results of 25 consecutive patients
Patrick C. McCulloch; Richard W. Kang; Mohamed H. Sobhy; Jennifer K. Hayden; Brian J. Cole
Although several treatments for cartilage repair have been developed and used in clinical practice the last 20 years, little is known about the mechanisms that are involved in the formation of repair tissue after these treatments. Often, these treatments result in the formation of fibrocartilaginous tissue rather than normal articular cartilage. Because the repair tissue is inferior to articular cartilage in terms of mechanical properties and zonal organization of the extracellular matrix, complaints of the patient may return. The biological and functional outcome of these treatments should thus be improved. For this purpose, an in vitro model allowing investigation of the involved repair mechanisms can be of great value. We present the development of such a model. We used bovine osteochondral biopsies and created a system in which cartilage defects of different depths can be studied. First, our biopsy model was characterized extensively: we studied the viability by means of lactate dehydrogenase (LDH) excretion over time and we investigated expression of cartilage-related genes in osteochondral biopsies and compared it with conventional cartilage-only explants. After 28 days of culture, LDH was detected at low levels and mRNA could be retrieved. The expression of cartilage-related genes decreased over time. This was more evident in cartilage-only explants, indicating that the biopsy model provided a more stable environment. We also characterized the subchondral bone: osteoclasts and osteoblasts were active after 28 days of culture, which was indicated by tartrate acid phosphatase staining and alkaline phosphatase measurements, respectively, and matrix deposition during culture was visualized using calcein labeling. Second, the applicability of the model was further studied by testing two distinct settings: (1) implantation of chondrocytes in defects of different depths; (2) two different seeding strategies of chondrocytes. Differences were observed in terms of volume and integration of newly formed tissue in both settings, suggesting that our model can be used to model distinct conditions or even to mimic clinical treatments. After extensive characterization and testing of our model, we present a representative and reproducible in vitro model that can be used to evaluate new cartilage repair treatments and study mechanisms in a controlled and standardized environment. PMID:21875392
de Vries-van Melle, Marloes L.; Mandl, Erik W.; Kops, Nicole; Koevoet, Wendy J.L.M.; Verhaar, Jan A.N.
Polymer-coated 45S5 Bioglass(®) (BG)/chitosan-polycaprolactone (BG/CS-PCL) bilayered composite scaffolds were prepared via foam replication and freeze-drying techniques for application in osteochondral tissue engineering. The CS-PCL coated and uncoated BG scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The mechanical properties of the coated scaffolds were significantly improved in comparison to uncoated scaffolds. The bioactivity and biodegradation behavior of scaffolds were studied in simulated body fluid (SBF) for up to 28 days. The interface between the BG scaffold and the polymer coating layer was observed by SEM and a suitable interpenetration of the polymer into the scaffold struts was found. The effects of coated and uncoated BG scaffolds on MG-63 osteoblast-like cells were evaluated by cell viability, adhesion and proliferation. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4510-4518, 2014. PMID:24677705
Yao, Qingqing; Nooeaid, Patcharakamon; Detsch, Rainer; Roether, Judith A; Dong, Yanming; Goudouri, Ourania-Menti; Schubert, Dirk W; Boccaccini, Aldo R
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
van Bergen, Christiaan J A
Several studies have demonstrated a statistical association between management practices and juvenile osteochondral conditions (JOCC) in foals from birth to 6months of age, but this association has not been investigated in yearlings. The purpose of the current study was to determine the adjusted effects of management practices on the onset and evolution of JOCC in French yearlings. The study sample consisted of 259 yearlings born on 20 stud farms in Normandy. The breeding conditions of these horses were monitored from 6 to 17months. They were radiographed at 6 and 17months to determine their radiographic score (RS) and its evolution. Potential risk factors were investigated using univariate and multivariate analyses. The prevalence of JOCC was 48% at 6months and 42% at 17months. Between 6 and 17months, the RS changed (for better or worse) in 52% of yearlings. The main risk factors leading to deterioration in the RS were traumatic. 'Mixed housing' during winter, pastures with rough ground and a bad RS at 6months were significantly associated with deterioration in RS between 6 and 17months. In the multivariate analysis, the breed was not significantly associated with any evolution in the yearlings' RS. This study provides some indications on protective measures to prevent the worsening of JOCC lesions between 6 and 17months, a crucial period since it precedes the sale of yearlings and the beginning of training. PMID:23642463
Praud, Anne; Dufour, Barbara; Robert, Céline; Valette, Jean-Paul; Denoix, Jean-Marie; Crevier-Denoix, Nathalie
We reviewed 32 knees in 26 patients who had previously undergone arthroscopic debridement for symptomatic osteochondritis dissecans (OCD) of the knee. The patients were followed up at a minimum of 11 years following surgery and were evaluated clinically using the American Knee Society Clinical Rating Score. Additional evaluation was performed using the Hughston Scale to include radiographic assessment. The mean American Knee Society Score was 179 (out of 200), indicating good clinical function. Radiographically, however, only 29% scored excellent or good on the Hughston Scale. Younger patients with a small, stable (and therefore preserved), medial femoral condyle lesion had the best prognosis. Whilst more novel and complex options such as chondrocyte implantation are being assessed for the treatment of OCD, it is clear that within this study group careful debridement with removal of loose tissue can achieve good clinical results in the long term. There was however radiographic evidence of early degenerative joint disease in 17/24 (71%) of patients reviewed. Patients undergoing excision of OCD fragments did worse than those in whom the fragment was preserved, however the risk of further surgery is raised if a fragment is left in situ at initial surgery. PMID:17222556
Murray, J R D; Chitnavis, J; Dixon, P; Hogan, N A; Parker, G; Parish, E N; Cross, M J
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
Dormer, Nathan H.; Busaidy, Kamal; Berkland, Cory J.; Detamore, Michael S.
Palmar/plantar osteochondral fragments (POF) in fetlock joints commonly affect and influence the athletic performance of horses. In this study, we used the Equine SNP50 BeadChip® to perform a genome-wide association study of metatarsophalangeal POF in 176 Norwegian Standardbred trotter yearlings. Putative quantitative trait loci (QTL) for medial and/or lateral POF, and medial POF only were identified on ECA1, 2, 7, 9 and 31, whereas for lateral POF, only on ECA7, 11, 27 and X. The moderate number of QTL evidences a complex inheritance and suggests various genes controlling POF development in medial and lateral locations. PMID:23742657
Lykkjen, S; Dolvik, N I; McCue, M E; Rendahl, A K; Mickelson, J R; Rřed, K H
Articular cartilage has a limited capacity for self-repair in adult humans, and methods used to stimulate regeneration often result in re-growth of fibrous cartilage, which has lower durability. No current treatment option can provide complete repair. The possibility of growth factor delivery into the joint for cartilage regeneration after injury would be an attractive treatment option. A full thickness osteochondral defect of 4 mm in diameter and 2 mm deep was created by mechanical drilling in the medial femoral condyle in 20 female adult New Zealand White rabbits. In an attempt to improve regeneration a hyaluronic hydrogel system, with or without bone morphogenetic protein-2 (BMP-2) was delivered intraarticularly. The contralateral joint defect was treated with saline as control. Throughout the study, rabbits were clinically examined and after 12 (n = 6) or 24 (n = 9) weeks, the rabbits were euthanized and the joints evaluated by histology. The defects healed with fibrocartilage like tissue, and the filling of the defects ranged from less than 25% to complete. The healing of the defects varied both inter- and intra-group wise. Treatment with hyaluronan gel with or without BMP-2 had no effect on cartilage regeneration compared with controls. Instead, severe ectopic bone formation was found in seven joints treated with BMP-2. In conclusion, the present study shows that neither treatment with hyaluronic gel alone, nor in combination with BMP-2, improves the healing of an induced cartilage defect in rabbits. It further shows that BMP-2 can induce ectopic bone formation, which severely affects the functionality of the joint. PMID:23467490
Aulin, C; Jensen-Waern, M; Ekman, S; Hägglund, M; Engstrand, T; Hilborn, J; Hedenqvist, P
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
The transcriptional cofactor Jab1 controls cell proliferation, apoptosis, and differentiation in diverse developmental processes by regulating the activity of various transcription factors. To determine the role of Jab1 during early limb development, we developed a novel Jab1(flox/flox) ; Prx1-Cre conditional Knockout (cKO) mutant mouse model in which Jab1 was deleted in the osteochondral progenitor cells of the limb buds. Jab1 cKO mutant mice displayed drastically shortened limbs at birth. The short-limb defect became apparent in Jab1 cKO mutants at E15.5 and increasingly worsened thereafter. By E18.5, Jab1 cKO mutant mice exhibited significantly shorter limbs with: very few hypertrophic chondrocytes, disorganized chondrocyte columns, much smaller primary ossification centers, and significantly increased apoptosis. Real-time RT-PCR analysis showed decreased expression of Sox9, Col2a1, Ihh, and Col10a1 in Jab1 cKO mutant long bones, indicating impaired chondrogenesis. Furthermore, in a micromass culture model of early limb mesenchyme cells, alcian blue staining showed a significant decrease in chondrogenesis in Jab1 cKO limb bud cells. The expression of Sox9 and its downstream targets Col2a1 and Aggrecan, as well as BMP signaling downstream targets, Noggin, Id1, and Ihh, were significantly decreased in Jab1 cKO micromass cultures. Moreover, over-expression of SOX9 in Jab1 cKO micromass cultures partially restored Col2a1and Aggrecan expression. Jab1-deficient micromass cultures also exhibited decreased BMP signaling response and reduced BMP-specific reporter activity ex vivo. In summary, our study demonstrates that Jab1 is an essential regulator of early embryonic limb development in vivo, likely in part by co-activating Sox9 and BMP signaling. PMID:24604556
Bashur, Lindsay A; Chen, Dongxing; Chen, Zhijun; Liang, Bojian; Pardi, Ruggero; Murakami, Shunichi; Zhou, Guang
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-1?. 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 (??=?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
Objective To assess collagen network alterations occurring with flow and other abnormalities of articular cartilage at medial femoral condyle (MFC) sites repaired with osteochondral autograft (OATS) after 6 and 12 months, using quantitative polarized light microscopy (qPLM) and other histopathological methods Design The collagen network structure of articular cartilage of OATS-repaired defects and non-operated contralateral control sites were compared by qPLM analysis of parallelism index (PI), orientation angle (?) relative to the local tissue axes, and retardance (?) as a function of depth. qPLM parameter maps were also compared to ICRS and Modified O’Driscoll grades, and cell and matrix sub-scores, for sections stained with H&E and Safranin-O, and for Collagen-I and II Results Relative to non-operated normal cartilage, OATS-repaired regions exhibited structural deterioration, with low PI and more horizontal ?, and unique structural alteration in adjacent host cartilage: more aligned superficial zone, and reoriented deep zone lateral to the graft, and matrix disorganization in cartilage overhanging the graft. Shifts in ? and PI from normal site-specific values were correlated with histochemical abnormalities and co-localized with changes in cell organization/orientation, cloning, or loss, indicative of cartilage flow, remodeling, and deterioration, respectively Conclusions qPLM reveals a number of unique localized alterations of the collagen network in both adjacent host and implanted cartilage in OATS-repaired defects, associated with abnormal chondrocyte organization. These alterations are consistent with mechanobiological processes and the direction and magnitude of cartilage strain. PMID:23528954
Raub, CB; Hsu, SC; Chan, EF; Shirazi, R; Chen, AC; Chnari, E; Semler, EJ; Sah, RL
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 ?-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/?-TCP composites fabricated by 3D printing provides a feasible strategy for osteochondral tissue engineering application. PMID:25177697
Zhang, Weijie; Lian, Qin; Li, Dichen; Wang, Kunzheng; Hao, Dingjun; Bian, Weiguo; He, Jiankang; Jin, Zhongmin
Tissue engineering offers an alternative method that can overcome some of the existing drawbacks of current articular defect repair methods because articular cartilage has a limited capacity to respond to injury. The solution may lie in the design of a three-dimensional load-bearing scaffold. Here we describe the tissue engineering of an osteochondral construct by coculturing osteogenic cells and chondrogenic cells on a three-dimensional load-bearing bioresorbable polymer scaffold. Porous polycaprolactone scaffolds were designed and fabricated via fused deposition modeling. Osteogenic cells were seeded and precultured in one-half of the partitioned scaffolds. Chondrogenic cells were later seeded into the other half. The cell-seeded scaffolds were cultured in a coculture medium. Both cell types proliferated, migrated, linked in their scaffold compartments, and integrated at the interface. Osteoblasts and chondrocytes produced different extracellular matrices in each scaffold compartment. Mineralized nodules deposited in the osteogenic cell seeded compartment. High osteocalcin was detected in precultured osteogenic cell supernatant and high alkaline phosphatase was detected in the coculture supernatant of osteochondral constructs. This study suggests that a tissue-engineered osteochondral construct with a three-dimensional polycaprolactone scaffold has the potential for osteochondral defect repair. PMID:14511474
Cao, Tong; Ho, Kee-Hai; Teoh, Swee-Hin
Background Osteochondral autograft transfer (OAT) aims at restoring normal articular cartilage surface geometry and articular contact mechanics. To date, no studies have evaluated the contact mechanics of the canine stifle following OAT. Additionally, there are no studies that evaluated the role of the meniscus in contact mechanics following OAT in human or canine femorotibial joints. The objective of this study was to measure the changes in femorotibial contact areas (CA), mean contact pressure (MCP) and peak contact pressure (PCP) before and after osteochondral autograft transplantation (OAT) of a simulated lateral femoral condylar cartilage defect with an intact lateral meniscus and following lateral meniscectomy. Results With an intact lateral meniscus, creation of an osteochondral defect caused a decrease in MCP and PCP by 11% and 30%, respectively, compared to the intact stifle (p?0.01). With an intact meniscus, implanting an osteochondral graft restored MCP and PCP to 96% (p?=?0.56) and 92% (p?=?0.41) of the control values. Lateral meniscectomy with grafting decreased CA by 54% and increased PCP by 79% compared to the intact stifle (p?0.01). Conclusions OAT restored contact pressures in stifles with a simulated lateral condylar defect when the meniscus was intact. The lateral meniscus has a significant role in maintaining normal contact pressures in both stifles with a defect or following OAT. Meniscectomy should be avoided when a femoral condylar defect is present and when performing OAT. PMID:23522348
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 ?-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/?-TCP composites fabricated by 3D printing provides a feasible strategy for osteochondral tissue engineering application.
Li, Dichen; Wang, Kunzheng; Hao, Dingjun; Bian, Weiguo; He, Jiankang; Jin, Zhongmin
It is easy to overlook osteochondral lesions (OCLs) of the ankle in patients with chronic lower limb pain, such as complex regional pain syndrome (CRPS) or thromboangiitis obliterans (TAO, Buerger's disease). A 57-year-old woman diagnosed with type 1 CRPS, and a 58-year-old man, diagnosed with TAO, complained of tactile and cold allodynia in their lower legs. After neurolytic lumbar sympathethic ganglion block and titration of medications for neuropathic pain, each subject could walk without the aid of crutches. However, they both complained of constant pain on the left ankle during walking. Focal tenderness was noted; subsequent imaging studies revealed OCLs of her talus and his distal tibia, respectively. Immediately after percutaneous osteoplasties, the patients could walk without ankle pain. It is important to consider the presence of a hidden OCL in chronic pain patients that develop weight-bearing pain and complain of localized tenderness on the ankle. PMID:23614079
Ri, Hyun Su; Lee, Dong Heon
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
Batista, N. A.; Rodrigues, A. A.; Bavaresco, V. P.; Mariolani, J. R. L.; Belangero, W. D.
Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints. PMID:24668595
Ley, C J; Ekman, S; Hansson, K; Björnsdóttir, S; Boyde, A
Previous studies have shown that disruption of von Hippel-Lindau gene (Vhl) coincides with activation of hypoxia-inducible factor ? (HIF?) signaling in bone cells and plays an important role in bone development, homeostasis, and regeneration. It is known that activation of HIF1? signaling in mature osteoblasts is central to the coupling between angiogenesis and bone formation. However, the precise mechanisms responsible for the coupling between skeletal angiogenesis and osteogenesis during bone remodeling are only partially elucidated. To evaluate the role of Vhl in bone homeostasis and the coupling between vascular physiology and bone, we generated mice lacking Vhl in osteochondral progenitor cells (referred to as Vhl cKO mice) at postnatal and adult stages in a tamoxifen-inducible manner and changes in skeletal morphology were assessed by micro-computed tomography (µCT), histology, and bone histomorphometry. We found that mice with inactivation of Vhl in osteochondral progenitor cells at the postnatal stage largely phenocopied that of mice lacking Vhl in mature osteoblasts, developing striking and progressive accumulation of cancellous bone with increased microvascular density and bone formation. These were accompanied with a significant increase in osteoblast proliferation, upregulation of differentiation marker Runx2 and osteocalcin, and elevated expression of vascular endothelial growth factor (VEGF) and phosphorylation of Smad1/5/8. In addition, we found that Vhl deletion in osteochondral progenitor cells in adult bone protects mice from aging-induced bone loss. Our data suggest that the VHL-mediated signaling in osteochondral progenitor cells plays a critical role in bone remodeling at postnatal/adult stages through coupling osteogenesis and angiogenesis. © 2014 American Society for Bone and Mineral Research. PMID:23999831
Weng, Tujun; Xie, Yangli; Huang, Junlan; Luo, Fengtao; Yi, Lingxian; He, Qifen; Chen, Di; Chen, Lin
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
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; Helder, Marco N
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
Smyth, Niall A; Murawski, Christopher D; Haleem, Amgad M; Hannon, Charles P; Savage-Elliott, Ian; Kennedy, John G
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
Jin-Hyung Shim; Jung-Seob Lee; Jong Young Kim; Dong-Woo Cho
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.
Shim, Jin-Hyung; Lee, Jung-Seob; Kim, Jong Young; Cho, Dong-Woo
Objective The articular cartilage of autologous osteochondral grafts is typically different in structure and function from local host cartilage and thereby presents a remodeling challenge. The hypothesis of this study was that properties of the articular cartilage of trochlear autografts and adjacent femoral condyle are associated with the 3-D geometrical match between grafted and contralateral joints at 6 and 12 months after surgery. Design Autografts were transferred unilaterally from the lateral trochlea (LT) to the medial femoral condyle (MFC) in adult Spanish goats. Operated and contralateral Non-Operated joints were harvested at 6 and 12 months, and analyzed by indentation testing, micro-computed tomography, and histology to compare (1) histological indices of repair, (2) 3-D structure (articular surface deviation, bone-cartilage interface deviation, cartilage thickness), (3) indentation stiffness, and (4) correlations between stiffness and 3-D structure. Results Cartilage deterioration was present in grafts at 6 months and more severe at 12 months. Cartilage thickness and normalized stiffness of Operated MFC were lower than Non-Operated MFC within the graft and proximal adjacent host regions. Operated MFC articular surfaces were recessed relative to Non-Operated MFC and exhibited lower cartilage stiffness with increasing recession. Sites with large bone-cartilage interface deviations, both proud and recessed, were associated with recessed articular surfaces and low cartilage stiffness. Conclusion The effectiveness of cartilage repair by osteochondral grafting is associated with the match of 3-D cartilage and bone geometry to the native osteochondral structure. PMID:24224069
Chan, Elaine F.; Liu, I-Ling; Semler, Eric J.; Aberman, Harold M.; Simon, Timothy M.; Chen, Albert C.; Truncale, Kate G.; Sah, Robert L.
Treatment options for damaged articular cartilage are limited due to its lack of vasculature and its unique viscoelastic properties. This study was the first to fabricate a hyaluronan (HA)-polyethylene copolymer for potential use in the replacement of articular cartilage and repair of osteochondral defects. Amphiphilic graft copolymers consisting of HA and high-density polyethylene (HA-co-HDPE) were fabricated with 10, 28 and 50 wt.% HA. Dynamic mechanical analysis was used to assess the effect of varying constituent weight ratios on the viscoelastic properties of HA-co-HDPE materials. The storage moduli of HA-co-HDPE copolymers ranged from 2.4 to 15.0 MPa at physiological loading frequencies. The viscoelastic properties of the HA-co-HDPE materials were significantly affected by varying the wt.% of HA and/or crosslinking of the HA constituent. Cytotoxicity and the ability of the materials to support mineralization were evaluated in the presence of bone marrow stromal cells. HA-co-HDPE materials were non-cytotoxic, and calcium and phosphorus were present on the surface of the HA-co-HDPE materials 2 weeks after osteogenic differentiation of the bone marrow stromal cells. This study is the first to measure the viscoelastic properties and osseocompatibility of HA-co-HDPE for potential use in orthopedic applications. PMID:21095243
Oldinski, Rachael A; Ruckh, Timothy T; Staiger, Mark P; Popat, Ketul C; James, Susan P
Most living tissues are viscoelastic in nature. Self-repair due to the dissipation of energy by reversible bonds prevents the rupture of the molecular backbone in these tissues. Recent studies, therefore, have aimed to synthesize biomaterials that approximate the mechanical performance of biological materials with self-recovery properties. We report an environmentally friendly method for the development of ionotropically cross-linked viscoelastic chitosan gels with a modulus comparable to that of living tissues. The strain recovery property was found to be highest for the gels with the lowest cross-linking density. The force-displacement curve showed significant hysteresis due to the presence of reversible bonds in the cross-linked gels. Nanoindentation studies demonstrated the creep phenomenon for the cross-linked chitosan gels. Creep, hysteresis, and plasticity index confirmed the viscoelastic behavior of the cross-linked gels. The viscoelastic gels were implanted at osteochondral defect sites to assess the tissue regeneration ability. In vivo results demonstrated early cartilage formation and woven bone deposition for defects filled with the gels compared to nontreated defects. PMID:24971647
Ghosh, Paulomi; Rameshbabu, Arun Prabhu; Dhara, Santanu
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=6–7. 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
Miller, Rachel E.; Grodzinsky, Alan J.; Vanderploeg, Eric J.; Lee, Christina; Ferris, Dora J.; Barrett, Myra F.; Kisiday, John D.; Frisbie, David D.
Biomaterials/scaffolds. Design of bioactive, multiphasic PCL/collagen type I and type II-PCL-TCP/collagen composite scaffolds for functional tissue engineering of osteochondral repair tissue by using electrospinning and FDM techniques.
Current clinical therapies for traumatic or chronic injuries involving osteochondral tissue result in temporary pain reduction and filling of the defect but with biomechanically inferior repair tissue. Tissue engineering of osteochondral repair tissue using autologous cells and bioactive biomaterials has the potential to overcome the current limitations and results in native-like repair tissue with good integration capabilities. For this reason, we applied two modem biomaterial design techniques, namely, electrospinning and fused deposition modeling (FDM), to produce bioactive poly(epsilon-caprolactone)/collagen (PCL/Col) type I and type II-PCL-tri-calcium phosphate (TCP)/Col composites for precursor cell-based osteochondral repair. The application of these two design techniques (electrospinning and FDM) allowed us to specifically produce the a suitable three-dimensional (3D) environment for the cells to grow into a particular tissue (cartilage and bone) in vitro prior to in vivo implantation. We hypothesize that our new designed biomaterials, seeded with autologous bone marrow-derived precursor cells, in combination with bioreactor-stimulated cell-culture techniques can be used to produce clinically relevant osteochondral repair tissue. PMID:18085205
Schumann, Detlef; Ekaputra, Andrew K; Lam, Christopher X F; Hutmacher, Dietmar W
Effects of bilayer gelatin/?-tricalcium phosphate sponges loaded with mesenchymal stem cells, chondrocytes, bone morphogenetic protein-2, and platelet rich plasma on osteochondral defects of the talus in horses.
Osteochondrosis (OC) is a common and clinically important joint disorder in horses. However, repair of the OC region is difficult because of the avascular nature of cartilage. This study aimed to evaluate the efficacy of bilayer gelatin/?-tricalcium phosphate (GT) sponges loaded with mesenchymal stem cells (MSCs), chondrocytes, bone morphogenetic protein-2 (BMP-2), and platelet rich plasma (PRP) for the repair of osteochondral defects of the talus in horses. Full-thickness osteochondral defects were created on both the lateral trochlear ridges of the talus (n = 6). In the test group, a basic GT sponge loaded with MSCs and BMP-2 (MSC/BMP2/GT) was inserted into the lower part of the defect, and an acidic GT sponge loaded with chondrocyte, MSCs, and PRP (Ch/MSC/PRP/GT) was inserted into the upper part of the defect. In the control group, the defect was treated only with bilayer GT sponges. Repair of osteochondral defects was assessed by radiography, quantitative computed tomography (QCT), and macroscopic and histological evaluation. The test group showed significantly higher radiographic, QCT, macroscopic, and histological scores than the control group. This study demonstrated that the bilayer scaffolds consisting of Ch/MSC/PRP/GT for the chondrogenic layer and MSC/BMP2/GT for the osteogenic layer promoted osteochondral regeneration in an equine model. The bilayer scaffolds described here may be useful for treating horses with OC. PMID:24054973
Seo, Jong-Pil; Tanabe, Takafumi; Tsuzuki, Nao; Haneda, Shingo; Yamada, Kazutaka; Furuoka, Hidefumi; Tabata, Yasuhiko; Sasaki, Naoki
This study was aimed to develop an ECM-derived biphasic scaffold and to investigate its regeneration potential loaded with BM-MSCs in repair of large, high-load-bearing osteochondral defects of the canine femoral head. The scaffolds were fabricated using cartilage and bone ECM as a cartilage and bone layer, respectively. Osteochondral constructs were fabricated using induced BM-MSCs and the scaffold. Osteochondral defects (11?mm diameter × 10?mm depth) were created on femoral heads of canine and treated with the constructs. The repaired tissue was evaluated for gross morphology, radiography, histological, biomechanics at 3 and 6 months after implantation. Radiography revealed that femoral heads slightly collapsed at 3 months and severely collapsed at 6 months. Histology revealed that some defects in femoral heads were repaired, but with fibrous tissue or fibrocartilage, and femoral heads with different degrees of collapse. The bone volume fraction was lower for subchondral bone than normal femoral bone at 3 and 6 months. Rigidity was lower in repaired subchondral bone than normal femoral bone at 6 months. The ECM-derived, biphasic scaffold combined with induced BM-MSCs did not successfully repair large, high-load-bearing osteochondral defects of the canine femoral head. However, the experience can help improve the technique of scaffold fabrication and vascularization. PMID:24737955
Qiang, Yang; Yanhong, Zhao; Jiang, Peng; Shibi, Lu; Quanyi, Guo; Xinlong, Ma; Qun, Xia; Baoshan, Xu; Bin, Zhao; Aiyuan, Wang; Li, Zhang; Wengjing, Xu; Chao, Zeng
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
Santo, Vitor E.; Mano, Joao F.; Reis, Rui L.
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
Santo, Vítor E.; Mano, Joăo F.; Reis, Rui L.
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
Seo, Sung-Suk; Park, Joo-Yeon; Kim, Hae-Jin; Yoon, Ji-Wook; Park, Sang-Hyun; Kim, Kyung-Hoon
The OATS technique is one of several cartilage repair procedures that exhibits promising short- to intermediate-term results in the surgical management of OLTs. Although the OATS procedure is generally reserved for salvage of failed debridement and drilling, some investigators are suggesting that it may have applications in primary surgical management of OLTs, particularly those that are associated with subchondral cysts. Long-term outcome of the OATS procedure for OLTs is not yet available. PMID:12911241
Easley, Mark E; Scranton, Pierce E
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
Bojanic, Ivan; Smoljanovic, Tomislav; Dokuzovic, Stjepan
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
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
Krych, Aaron J.; Wanivenhaus, Florian; Ng, Kenneth W.; Doty, Stephen; Warren, Russell F.
Regeneration of cartilage defects can be accelerated by localized delivery of appropriate growth factors (GFs) from scaffolds. In the present study we analysed the in vitro and in vivo release rates and delivery efficacies of transforming growth factor-?1 (TGF?1) and bone morphogenetic protein-2 (BMP-2) from a bilayered system, applied for osteochondral defect repair in a rabbit model. A bone-orientated, porous PLGA cylinder was overlaid with GF containing PLGA microspheres, dispersed in an alginate matrix. Four microsphere formulations were incorporated: (a) blank ones; (b) microspheres containing 50 ng TGF?1; (c) microspheres containing 2.5 µg BMP-2; and (d) microspheres containing 5 µg BMP-2. Release kinetics and tissue distributions were determined using iodinated ((125) I) GFs. Bioactivity of in vitro released BMP-2 and TGF?1 was confirmed in cell-based assays. In vivo release profiles indicated good GF release control. 20% of BMP-2 and 15% of TGF?1 were released during the first day. Virtually the total dose was delivered at the end of week 6. Significant histological differences were observed between untreated and GF-treated specimens, there being especially relevant short-term outcomes with 50 ng TGF?1 and 5 µg BMP-2. Although the evaluation scores for the newly formed cartilage did not differ significantly, 5 µg BMP-2 gave rise to higher quality cartilage with improved surface regularity, tissue integration and increased collagen-type II and aggrecan immunoreactivity 2 weeks post-implantation. Hence, the bilayered system controlled GF release rates and led to preserved cartilage integrity from 12 weeks up to at least 24 weeks. PMID:22733683
Reyes, R; Delgado, A; Sánchez, E; Fernández, A; Hernández, A; Evora, C
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 ?CT 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
Pallante-Kichura, Andrea L; Cory, Esther; Bugbee, William D; Sah, Robert L
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
Muhammad Abdul Wajid; Muhammad Idrees Shah; Mohsin-e-Azam; Tashfeen Ahmad
al.178 used such a material to fabricate six different stratified porosity patterns (Table 2.1). Blocks of higher porosity were fabricated by burnout of polyethylene particles or polyurethane sponges from dried bioglass mixtures. Low porosity samples... fluid (SBF). The interfaces between porous regions were well integrated morphologically, and testing did not indicate that this area was a specific structural weakness. Incubation of the high porosity stratified constructs from sponge replication in SBF...
Dormer, Nathan Henry
Articular cartilage that is damaged or diseased often requires surgical intervention to repair the tissue; therefore, tissue engineering strategies have been developed to aid in cartilage regeneration. Tissue engineering approaches often require the integration of cells, biomaterials, and growth factors to direct and support tissue formation. A variety of cell types have been isolated from adipose, bone marrow, muscle, and skin tissue to promote cartilage regeneration. The interaction of cells with each other and with their surrounding environment has been shown to play a key role in cartilage engineering. In tissue engineering approaches, biomaterials are commonly used to provide an initial framework for cell recruitment and proliferation and tissue formation. Modifications of the properties of biomaterials, such as creating sites for cell binding, altering their physicochemical characteristics, and regulating the delivery of growth factors, can have a significant influence on chondrogenesis. Overall, the goal is to completely restore healthy cartilage within an articular cartilage defect. This chapter aims to provide information about the importance of cell–biomaterial interactions for the chondrogenic differentiation of various cell populations that can eventually produce functional cartilage matrix that is indicative of healthy cartilage tissue. PMID:21975954
Kim, Kyobum; Yoon, Diana M.; Mikos, Antonios G.
for articular cartilage repair Clark T. Hunga, *, Eric G. Limaa , Robert L. Maucka , Erica Takia , Michelle A, for the repair of focal lesions and damage to the articular surface. These approaches include tissue adhesives (Ahsan et al., 1999; Harper, 1988), enzymatic treatments (Caplan et al., 1997), laser solder welding
Lu, Helen H.
rabbits compared to the blood clot in untreated controls. Methods: Three microdrill hole defects, 1.4 mm-computed tomography, histomorphometry and stereology for bone and soft tissue repair. Results: All 3 implants filled
In syndromic craniosynostosis, such as Crouzon syndrome, midfacial hypoplasia can cause exophthalmos and concave facial profile. Though midfacial hypoplasia in Crouzon syndrome patients can be treated with midface advancement, known as a Le Fort II or Le Fort III osteotomy, such method can change nasal appearance and frequently fails to achieve class I occlusion after surgery. This report presents a case of an aesthetically and functionally successful midfacial augmentation using rib and cartilage graft along with orthognathic surgery (Le fort I and bilateral sagittal split ramus osteotomy) for patients with Crouzon syndrome. The patient was a 21-year-old male with Crouzon syndrome, who had undergone augmentation rhinoplasty 2 years ago. His main issues were midfacial retrusion and mild anterior open bite and cross bite and, furthermore, did not want any change in his nasal appearance. To augment midfacial volume, rib bone graft was inserted on the inferior orbital rim and costal cartilage graft was done on the zygomatic area. The costal osteocartilage was fixed with titanium screws. Additionally, Le Fort I osteotomy and bilateral sagittal split ramus osteotomy were done to treat the anterior open bite and cross bite. The maxillary segment was advanced 2 mm and posteriorly impacted 2.5 mm. Then, 5 mm of mandibular setback was done and the maxillomandibular segment was rotated clockwise. Finally, genioplasty with 5-mm advancement was done to compensate for the chin retrusion after performing the mandibular setback. The operation took 425 minutes and estimated blood loss was 500 mL. After 6 months since surgery, the patient had convex facial profile and class I occlusion. For the patient with mild midface hypoplasia, good nasal profile, and malocclusion, rib bone graft along with Le Fort I and bilateral sagittal ramus osteotomy can be a good surgical modality. PMID:25153066
Song, Hyunsuk; Park, Myong Chul; Lee, Il Jae; Park, Dong Ha
A syndrome of brachydactyly (absence of some middle or distal phalanges), aplastic or hypoplastic nails, symphalangism (ankylois of proximal interphalangeal joints), synostosis of some carpal and tarsal bones, craniosynostosis, and dysplastic hip joints is reported in five members of an Italian family. It may represent a previously undescribed autosomal dominant trait.
V Ventruto; R Di Girlamo; B Festa; A Romano; G Sebastio; L Sebastio
Degenerative diseases, such as osteoarthritis, and traumatic injuries are both prominent causes of cartilage defects. Due to its avascular nature, adult human cartilage displays limited capacity for regeneration. Current ...
Saatchi, Sanaz, 1980-
integration and proteoglycan staining was observed. Only the rhFGF18 defects showed pericellular type VI collagen staining with positive type II collagen and reduced positive type I collagen staining. The majority of defects in the control and BMP-7 groups...
Getgood, Alan; Henson, Frances; Skelton, Carrie; Brooks, Roger; Guehring, Hans; Fortier, Lisa A.; Rushton, Neil
for cartilage focal lesions with promising initial results are autologous osteochondral grafting procedures online 17 October 2005 Abstract Biological integration of cartilage grafts with subchondral bone remains is important in regenerating the osteochondral interface on tissue-engineered osteochondral grafts. We describe
Lu, Helen H.
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
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
Background: Intact articular cartilage tissue is used clinically in the form of osteochondral allografts and experimentally as explants in modeling the physiologic behavior of chondrocytes in their native extracellular matrix. Long-term maintenance of allograft tissue is challenging.Hypothesis: By carefully modulating the preservation environment, it may be possible to preserve osteochondral allograft tissue over the long term while maintaining its original
Liming Bian; Aaron M. Stoker; Kevin M. Marberry; Gerard A. Ateshian; James L. Cook; Clark T. Hung
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
Covell, D. Jeff; Lattermann, Christian
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
Triche, Rachel; Mandelbaum, Bert R
Objective Repair of articular cartilage defects of knee to restore a pain-free joint function. Indications Full-thickness chondral or osteochondral posttraumatic lesions and osteochondritis dissecans defects that have not been successfully repaired with methods such as debridement, drilling, and microfracturing. Contraindications Osteoarthritis. Rheumatoid arthritis. Surgical Technique During arthroscopy, the cartilage lesion is evaluated, and cartilage slices weighing 200-300 mg are harvested
\\u000a The most important clinical indications for magnetic resonance imaging (MRI) are assessment of cartilage in osteoarthritis\\u000a (OA), chronic or acute osteochondral injury including sports injuries, osteochondritis dissecans, chondromalacia patellae,\\u000a and inflammatory arthropathies (in particular before invasive therapy). In addition dedicated cartilage imaging is required\\u000a after invasive cartilage repair procedures or conservative therapies, including pharmacological therapies, to monitor treatment\\u000a effect. MR
Thomas M. Link
A subchondral cyst of the talus frequently occurs with an osteochondral lesion of the talar dome. Debridement, curettage, and bone grafting through the articular defect was frequently the recommended treatment in reported studies for a massive cyst. We report a case of a massive cyst of the talar body with a small osteochondral lesion of the talar dome. Our patient was successfully treated by curettage and bone grafting of the cyst using posterior ankle arthroscopy, with minimal disruption of the articular surface of the talar dome. PMID:23643665
Lui, Tun Hing
Glenoid bone loss is a significant risk factor for failure after arthroscopic shoulder stabilization. Multiple options are available to reconstruct this bone loss, including coracoid transfer, iliac crest bone graft, and osteoarticular allograft. Each technique has strengths and weaknesses. Coracoid grafts are limited to anterior augmentation and, along with iliac crest, do not provide an osteochondral reconstruction. Osteochondral allografts do provide a cartilage source but are challenged by the potential for graft rejection, infection, cost, and availability. We describe the use of a distal clavicular osteochondral autograft for bony augmentation in cases of glenohumeral instability with significant bone loss. This graft has the advantages of being readily available and cost-effective, it provides an autologous osteochondral transplant with minimal donor-site morbidity, and it can be used in both anterior and posterior bone loss cases. The rationale and technical aspects of arthroscopic performance will be discussed. Clinical studies are warranted to determine the outcomes of the use of the distal clavicle as a graft in shoulder instability. PMID:25264509
Tokish, John M; Fitzpatrick, Kelly; Cook, Jay B; Mallon, William J
Glenoid bone loss is a significant risk factor for failure after arthroscopic shoulder stabilization. Multiple options are available to reconstruct this bone loss, including coracoid transfer, iliac crest bone graft, and osteoarticular allograft. Each technique has strengths and weaknesses. Coracoid grafts are limited to anterior augmentation and, along with iliac crest, do not provide an osteochondral reconstruction. Osteochondral allografts do provide a cartilage source but are challenged by the potential for graft rejection, infection, cost, and availability. We describe the use of a distal clavicular osteochondral autograft for bony augmentation in cases of glenohumeral instability with significant bone loss. This graft has the advantages of being readily available and cost-effective, it provides an autologous osteochondral transplant with minimal donor-site morbidity, and it can be used in both anterior and posterior bone loss cases. The rationale and technical aspects of arthroscopic performance will be discussed. Clinical studies are warranted to determine the outcomes of the use of the distal clavicle as a graft in shoulder instability.
Tokish, John M.; Fitzpatrick, Kelly; Cook, Jay B.; Mallon, William J.
To evaluate articular cartilage repair tissue after biological cartilage repair, we propose a new technique of non-invasive, high-resolution magnetic resonance imaging (MRI) and define a new classification system. For the definition of pertinent variables the repair tissue of 45 patients treated with three different techniques for cartilage repair (microfracture, autologous osteochondral transplantation, and autologous chondrocyte transplantation) was analyzed 6 and
Stefan Marlovits; Gabriele Striessnig; Christoph T. Resinger; Silke M. Aldrian; Vilmos Vecsei; Herwig Imhof; Siegfried Trattnig
Symptomatic chondral defects may be repaired by arthroscopic lavage and debridement, marrow stimulation,osteochondral graft transfer, autologous chondrocyte implantation, or osteoarticular allograft transplantation. The procedural selection may be made easier by a knowledge of the factors influencing prognosis. These factors include defect size, patient age, acuteness of injury, and activity level. Predisposing causes for chondral injuries such as instability, axial or
Ankle osteoarthritis is often a result of an injury, and severe degeneration is treated by arthrodesis or arthroplasty. Osteochondral lesions of the talus may be traumatic or atraumatic, and arthroscopic assessment and treatment may be needed. Ankle impingement can often be treated arthroscopically by removal of impingement lesions. Instability of the ankle sometimes responds to physiotherapy, but may require ligament
There is growing recognition of the importance of nutritional factors in the maintenance of bone and joint health, and that nutritional imbalance combined with endocrine abnormalities may be involved in the pathogenesis of osteoarthritis (OA) and osteochondritis dissecans (OCD). Despite this, dietary programs have played a secondary role in the management of these connective tissue disorders. Articular cartilage is critically
Robert Goggs; Anne Vaughan-Thomas; Peter D. Clegg; Stuart D. Carter; John F. Innes; Ali Mobasheri; Mehdi Shakibaei; Wolfgang Schwab; Carolyn A. Bondy
Traumatic patella alta in children occurs either distal to the patellar tendon as a tibial tubercle apophyseal fracture or proximally as an osteochondral sleeve fracture of the inferior patellar pole. Acute surgical exploration in a pediatric case of a knee extensor mechanism rupture revealed both proximal and distal (bipolar) patellar tendon pathology. PMID:7790483
Berg, E E
chondral defects may pro- gress in size, leading to degenerative arthritis.4,20,24,37 There are numerous treatment options for focal chon- dral defects, each having advantages and disadvantages.6,7 Abrasion. Clinical Relevance: Osteochondral transplantation may be a viable treatment option; however, long
having access to bone marrow, thus improving existing bone marrow-stimulation procedures. BST that use cartilage and/or bone grafts,5,6 and (3) those that attempt to elicit a healing re- sponse from implanta- tion, osteochondral grafting (either autologous or alloge- neic), or bone marrow stimulation
The study aimed to investigate the prognosis of osteochondral affection (e.?g., osteochondritis dissecans (OCD), cartilage lesions, fractures and bone edema in the elbows of high-performance gymnasts (n=30) compared to prognosis results with athletes not undergoing excessive stress on the upper extremity (n=29). The study also tested a novel isotropic 3D-FSE-sequence (CUBE) technique as an early diagnostic modality. Standard protocol was used to conduct the MRI examinations, which were then compared to results from the CUBE - sequence. The gymnast group (p=0.012) presented a significantly higher prevalence of complaints in the elbow joint compared to the other athlete group. Furthermore, osteochondral lesions in MRIs appeared more frequently in the group of gymnasts (n=10, 33%, p=0.033), including 7 cases (23%) of OCD. In the control athlete group 2 asymptomatic cases of OCD and one case of bone edema were detected. The MRI investigation with the CUBE - sequence showed similar results as the standard MRI protocol in terms of the diagnosis sensitivity. The current study indicates that juvenile gymnasts are at a higher risk for osteochondral lesions of the elbow than athletes without excessive stress on the upper extremities. PMID:24863726
Dexel, J; Marschner, K; Beck, H; Platzek, I; Wasnik, S; Schuler, M; Nasreddin, A; Kasten, P
Objective To investigate the MR characteristics of SONK-like (spontaneous osteonecrosis of the knee) subchondral abnormalities in the adult atraumatic knee and to recategorize these patients into two subgroups: a subacute to chronic process associated with osteoarthritis and an acute process associated with insufficiency fractures. Design We retrospectively examined the knee MRIs of 39 patients with non-specific interpretations of osteochondral abnormalities.
R. Richard Ramnath; Susan V. Kattapuram
As the popularity and intensity of children's athletics have increased, so has the risk for knee injuries. Fractures of the tibial eminence may be treated operatively or nonoperatively depending on fracture classification, but arthrofibrosis is a potentially significant complication. Anterior cruciate ligament rupture presents treatment challenges as regards the optimal timing and method of reconstruction. A number of novel reconstructive techniques have been developed to minimize risks to the physes in this population. Recent studies have focused on the prognosis, surgical indications, and operative techniques for osteochondritis dissecans in children. A number of authors have also sought to better-define the optimal diagnostic testing and management of patellar dislocation. In this review, we provide an update on current concepts for tibial eminence fractures, anterior cruciate ligament injuries, osteochondritis dissecans of the knee, and patellar dislocation in young athletes. PMID:24045503
Beck, Nicholas A; Patel, Neeraj M; Ganley, Theodore J
A two-year-old, 97 kg, male neutered English Mastiff was evaluated for left pelvic limb lameness of five months duration localized to the stifle joint. Following radiographic, computed tomographic and arthroscopic examination, the lameness was subsequently diagnosed as being caused by primary synovial osteochondromatosis. In total, 194 osteochondral bodies were removed using arthroscopy in combination with a mini-arthrotomy. Histology and immunohistochemistry of the loose osteochondral fragments confirmed the diagnosis with a moderately high degree of differentiation and low cellularity. Nuclear staining for Ki-67 revealed decreasing differentiation and increasing cellularity in the fragments. At the 13 months telephone follow-up the owner reported that the dog was free from lameness and had a vastly improved function compared with preoperative levels, although mild lameness did occasionally occur. This is the first report of computed tomography, arthroscopy and immunohistochemistry confirming a case of primary synovial osteochondromatosis in a dog. PMID:22286965
Smith, T J; Baltzer, W I; Löhr, C; Stieger-Vanegas, S M
There are numerous techniques for the surgical management of thumb carpometacarpal (CMC) joint arthritis. The four senior\\u000a authors of this study employ three such techniques: trapeziectomy with hematoma distraction arthroplasty, hemitrapeziectomy\\u000a with osteochondral allograft, and ligament reconstruction tendon interposition (LRTI). This study examines the three commonly\\u000a utilized procedures at a single institution. This study examines the 10-year experience from 1995–2005
Min J. Park; Greg Lichtman; Jennifer B. Christian; Jennifer Weintraub; James Chang; Vincent R. Hentz; Amy L. Ladd; Jeffrey Yao
AIM: To investigate donor site’s area histological and immunohistochemical knee cartilage appearances after resurfacing iatrogenic defects with biosynthetic plugs orautografts. METHODS: Thirty New Zealand White rabbits were used in this study. A full-thickness cylindrical defect of 4.5 mm (diameter) × 7 mm (depth) was created with a hand drill in the femoral groove of every animal. In Group A (n = 10) the defect of the donor site was repaired with a biosynthetic osteochondral plug, in Group B (n = 10) with an osteochondral autograft, while in Group C (control group of 10) rabbits were left untreated. RESULTS: Twenty-four weeks postoperatively, smooth articular cartilage was found macroscopically in some trocleas’ surfaces; in all others, an articular surface with discontinuities was observed. Twenty-eight out of 30 animals were found with predominantly viable chondrocytes leaving the remaining two -which were found only in the control group- with partially viable chondrocytes. However, histology revealed many statistical differences between the groups as far as the International Cartilage Repair Society (ICRS) categories are concerned. Immunofluoresence also revealed the presence of collagen II in all specimens of Group B, whereas in Group A collagen II was found in less specimens. In Group C collagen IIwas not found. CONCLUSION: The matrix, cell distribution, subchondral bone and cartilage mineralization ICRS categories showed statistically differences between the three groups. Group A was second, while group B received the best scores; the control group got the worst ICRS scores in these categories. So, the donor site area, when repairing osteochondral lesions with autografting systems, is better amended with osteochondral autograft rather than bone graft substitute implant.
Intzoglou, Konstantinos S; Mastrokalos, Dimitrios S; Korres, Dimitrios S; Papaparaskeva, Kleo; Koulalis, Dimitrios; Babis, George C
A procedure based on multifactorial evaluation of the most important clinical and X-ray signs was suggested to differentiate between secondary bone chondrosarcoma and such benign lesions as chondroma and osteochondrous exostosis. The analysis included 100 patients with secondary bone chondrosarcoma and 36 of those with benign lesions. The study used complex parameters derived from two, three or four simple ones. The method described assured a 95% credibility of differential diagnosis. PMID:2305571
Petrovichev, N N; Karata, D I; Glazkova, T G; Spiridonova, T A; Khmelev, O N; Zatsepin, S T; Lipkin, S I
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.
Nurmio, Mirja, E-mail: Mirja.Nurmio@utu.fi [Department of Physiology, University of Turku (Finland); Department of Pediatrics, University of Turku (Finland); Joki, Henna, E-mail: Henna.Joki@utu.fi [Department of Cell Biology and Anatomy, University of Turku (Finland); Kallio, Jenny, E-mail: Jenny.Kallio@utu.fi [Department of Physiology, University of Turku (Finland); Maeaettae, Jorma A., E-mail: email@example.com [Department of Cell Biology and Anatomy, University of Turku (Finland); Department of Turku Center for Disease Modeling, University of Turku (Finland); Vaeaenaenen, H. Kalervo, E-mail: firstname.lastname@example.org [Department of Cell Biology and Anatomy, University of Turku (Finland); Toppari, Jorma, E-mail: Jorma.Toppari@utu.fi [Department of Physiology, University of Turku (Finland); Department of Pediatrics, University of Turku (Finland); Jahnukainen, Kirsi, E-mail: Kirsi.Jahnukainen@utu.fi [Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institutet and University Hospital, Stockholm (Sweden); Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Helsinki (Finland); Laitala-Leinonen, Tiina, E-mail: email@example.com [Department of Cell Biology and Anatomy, University of Turku (Finland)
The effect of intravenous administration of gadolinium diethylenetriamine-pentaacetic acid (Gd-DTPA) on MR images was studied in vitro, using pathologic osteochondral specimens removed during surgery for total endoprosthesis, and in vivo, on a group of volunteers. In ex vivo specimens, lesions of different shape having lower T1 were detected which corresponded to areas with depleted proteoglycans found histologically. In vivo experiments
Siegfried Trattnig; Vladim??r Mly?arik; Martin Breitenseher; Monika Huber; Alexander Zembsch; Thomas Rand; Herwig Imhof
ObjectiveLocal malignant bone tumor excision followed by pasteurization and subsequent reimplantation is a unique technique for reconstruction after resection of primary bone sarcomas. The purpose of this investigation was to assess the normal and abnormal long-term radiographic findings of intercalary and osteo-chondral pasteurized bone graft\\/implant composite.Design and patientsThe long-term radiographic findings of pasteurized bone grafts used in reconstruction after resection
Adel Refaat Ahmed; Jun Manabe; Noriyoshi Kawaguchi; Seiichi Matsumoto; Yasushi Matsushita
We present a case report of a 15-year-old kendo (Japanese fencing) player who suffered a stress fracture of the ulnar styloid process. Exercise of the kendo requires the athlete to flex his non-dominant wrist repeatedly in an ulnar direction, and causes the disorder. Excision of the osteochondral fragment relieved the symptoms. This lesion is likely to occur with other sports or activities which demand similar motion of the wrists. PMID:11677673
Itadera, E; Ichikawa, N; Hashizume, H; Inoue, H
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
Levato, Riccardo; Visser, Jetze; Planell, Josep A; Engel, Elisabeth; Malda, Jos; Mateos-Timoneda, Miguel A
It is well established that irregular bursae can form adjacent to an osteochondroma (bursa exostotica) as a result of mechanical irritation and that these bursae can be complicated by inflammation, hemorrhage, or infection. Bursal chondromatosis is a rare complication, with only seven published cases in the literature according to our searches. We present the case of a 53-year-old female who presented with slowly progressive left hip/thigh pain and was found to have an osteochondroma arising from the lesser trochanter with numerous ossified bodies in the adjacent soft tissues. MRI demonstrated osteochondral bodies in a fluid-filled bursa adjacent to the osteochondroma, with several of the bodies noted to be fairly displaced from the osteochondroma cartilaginous cap. At surgery, the osteochondroma was removed and numerous bodies of varying sizes were excised, some of which were noted to be adherent to the bursal lining and others that were separated/distant from the cartilage cap. The question arises as to whether this process represents bursal chondromatosis resulting from benign neoplasia of cells lining the abnormal bursa, "cartilage shedding" from the osteochondromatous cap, or both. The purpose in presenting this case is to introduce a rare complication of an osteochondroma, demonstrate that soft tissue calcification and osteochondral densities displaced from an underlying osteochondroma are not always the result of sarcomatous degeneration, and provide support for the theory that cells lining a bursa in a nonphysiologic location can undergo benign neoplasia with subsequent formation of osteochondral bodies. PMID:25001874
Gould, Elaine S; Baker, Kevin S; Huang, Mingqian; Khan, Fazel; Hoda, Syed
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
Myers, K. R.; Sgaglione, N. A.; Grande, D. A.
The elbow joint is one of the feline appendicular joints most commonly and severely affected by degenerative joint disease. The macroscopic and histopathological lesions of the elbow joints of 30 adult cats were evaluated immediately after euthanasia. Macroscopic evidence of degenerative joint disease was found in 22 of 30 cats (39 elbow joints) (73.33% cats; 65% elbow joints), and macroscopic cartilage erosion ranged from mild fibrillation to complete ulceration of the hyaline cartilage with exposure of the subchondral bone. Distribution of the lesions in the cartilage indicated the presence of medial compartment joint disease (most severe lesions located in the medial coronoid process of the ulna and medial humeral epicondyle). Synovitis scores were mild overall and correlated only weakly with macroscopic cartilage damage. Intra-articular osteochondral fragments either free or attached to the synovium were found in 10 joints. Macroscopic or histologic evidence of a fragmented coronoid process was not found even in those cases with intra-articular osteochondral fragments. Lesions observed in these animals are most consistent with synovial osteochondromatosis secondary to degenerative joint disease. The pathogenesis for the medial compartmentalization of these lesions has not been established, but a fragmented medial coronoid process or osteochondritis dissecans does not appear to play a role. PMID:24476939
Freire, M; Meuten, D; Lascelles, D
The paper reviews current knowledge on conservative versus surgical options for the treatment of osteochondrosis entities in the horse. Clinical and radiographic signs of each significant osteochondrosis entity in the horse are presented, followed by the value of conservative treatment versus arthroscopic surgery options as well as the results for each option with the various entities. The entities presented in detail include, osteochondritis dissecans (OCD) of the femoropatellar, tarsocrural, metacarpophalangeal and metatarsophalangeal, and glenohumural articulations. The various treatment options for subchondral cystic lesions of the medial femoral condyle are detailed with evidence for the value of various treatments and subchondral cystic lesions in other locations are briefly reviewed. PMID:23746868
McIlwraith, C Wayne
This article reviews the anatomy of the physis and the most common classification of injuries or fractures through the physis. The common apophyseal injuries of Osgood-Schlatter, Severs disease and iliac apophysitis, are reviewed in addition to a review of the most common osteochondritides, including Panner's disease and Osteochondritis Dessicans of the femur and talus. An understanding of these is key to diagnosis and treatment of adolescent musculoskeletal injuries. This article also reviews slipped capital femoral epiphysis, little leaguer's elbow, anterior cruciate and collateral ligament injuries, patella problems, ankle sprains and several common fractures in children. PMID:9469924
Kaeding, C C; Whitehead, R
Magnetic resonance (MR) imaging was performed in 60 patients with ankle pain who were suspected of having various soft-tissue or osseous abnormalities. Results of conventional radiographs had been normal or inconclusive. Soft-tissue disorders depicted by MR imaging included tendon and ligament tears, tendinitis, tenosynovitis, and plantar fasciitis. Osseous conditions demonstrated by MR imaging included osteochondritis dessicans, infarcts, bone bruises, stress fractures, tarsal coalition, and osteoid osteoma. The authors believe that MR imaging is useful in the assessment of a variety of painful ankle disorders. PMID:1852934
Kier, R; McCarthy, S; Dietz, M J; Rudicel, S
An 8-mo-old captive male reticulated giraffe (Giraffa camelopardalis reticulata) developed an acute lameness (grade IV/V) of the right forelimb, with swelling of the metacarpophalangeal joint. A traumatic injury was suspected based on clinical, radiographic, and arthroscopic evaluation. Several abnormalities were identified arthroscopically, including synovitis, cartilage damage, and an osteochondral fragment. Medial collateral ligament damage was also suspected based on radiographic evaluation. Arthroscopy provided a means of diagnosis and treatment of the abnormalities identified. The lameness in this giraffe resolved within 6 wk following arthroscopic surgery. PMID:10572867
Radcliffe, R M; Turner, T A; Radcliffe, C H; Radcliffe, R W
Campomelic dysplasia is a rare hereditary congenital osteochondral dysplasia characterized by abnormal bowing of the lower limbs, sex reversal in males, and other skeletal and extraskeletal abnormalities. It is usually fatal in the neonatal period because of respiratory insufficiency. The diagnosis is usually difficult because of its rare presentation and the prognosis is poor. We present such a case in a 1-month-old child with typical skeletal abnormalities, whose presentation was unusual because of later presentation of respiratory distress and lack of genitourinary abnormalities. PMID:24800790
Jain, Vineet; Sen, Biswaroop
X-ray studies were made of both elbows of 162 boys in the 9 to 14 year age group, divided into three categories: Pitchers, non-pitchers, and a control group who had never played organized baseball. Changes involving the medial epicondylar epiphysis and opposing articular surfaces of the capitulum and head of radius in the throwing arm appeared to be in direct proportion to the amount and type of throwing. The most striking changes were in the arms of pitchers. Some degree of accelerated growth, separation and fragmentation of the medial epicondylar epiphyses was noted in the throwing arm of all 80 pitchers in the study. Five cases of traumatic osteochondritis of the capitulum and head of radius, and one case of juvenile osteochondritis of the head of the radius were also found among the pitchers. Better medical supervision and stress on prevention are needed, especially in the Southern California area where climatic conditions favor prolonged seasons and throwing practice the year around. ImagesFigure 1 (Case 1).Figure 2 (Case 2).Figure 3 (Case 3).Figure 4 (Case 4).Figure 5 (Case 6).Figure 6 (Case 6).Figure 7 (Case 9).Figure 7 (Case 9).Figure 8 (Case 11). PMID:14254967
Adams, Joel E.
The uppermost superficial surface layer of articular cartilage, the ‘lamina splendens’ which provides a very low friction lubrication surface in articular joints, was investigated using atomic force microscopy (AFM). Complementary specimens were also observed under SEM at ?10 °C without dehydration or sputter ion coating. Fresh adult pig osteochondral specimens were prepared from the patellas of pig knee joints and digested with the enzymes, hyaluronidase, chondroitinase ABC and alkaline protease. Friction coefficients between a pyrex glass plate and the osteochondral specimens digested by enzymes as well as natural (undigested) specimens were measured, using a thrust collar apparatus. Normal saline, hyaluronic acid (HA) and a mixture of albumin, globulin, HA (AGH) were used as lubrication media. The surface irregularities usually observed in SEM studies were not apparent under AFM. The articular cartilage surface was resistant to hyaluronidase and also to chondroitinase ABC, but a fibrous structure was exhibited in alkaline protease enzymes-digested specimens. AFM analysis revealed that the thickness of the uppermost superficial surface layer of articular cartilage was between 800 nm and 2 ?m in adult pig articular cartilage. The coefficient of friction (c.f.) was significantly higher in chondroitinase ABC and alkaline protease enzymes digested specimens. Generally, in normal saline lubrication medium, c.f. was higher in comparison to HA and AGH lubrication media. The role of the uppermost, superficial surface layer of articular cartilage in the lubrication mechanism of joints is discussed. PMID:11554503
KUMAR, P.; OKA, M.; TOGUCHIDA, J.; KOBAYASHI, M.; UCHIDA, E.; NAKAMURA, T.; TANAKA, K.
Magnetic Resonance Imaging (MRI) is the preferred modality of choice to image epiphyseal lesions. It provides excellent soft tissue resolution and extent of disease. A wide spectrum of tumor and tumor like lesions can involve the epiphysis. Early and accurate diagnosis as well as appropriate management of epiphyseal lesions is critical as these conditions may lead to disabling complications such as, limb length discrepancy, angular or joint surface deformities and secondary osteoarthritis. In this article, we discuss the role of conventional sequences, such as T1W, fluid sensitive T2W and intravenous (IV) Gadolinium enhanced sequences as well as the additional value of problem solving MRI sequences such as, chemical shift and diffusion weighted imaging. Based on the imaging findings on various MRI sequences and lesion characteristics, a systematic approach directed to the diagnoses of epiphyseal lesions is presented and discussed. MRI features of clinically and biopsy proven examples of the epiphyseal lesions, such as osteomyelitis, intra-osseous abscess, infiltrative malignancy, metastases, transient osteoporosis, subchondral insufficiency fracture, avascular necrosis, osteochondral fracture, osteochondritis dissecans, eosinophilic granuloma and geode are demonstrated. Using this systematic approach, the reader will be able to better characterize epiphyseal lesions with a potential to positively affect patient management. PMID:23102949
Thawait, Shrey K; Thawait, Gaurav K; Frassica, Frank J; Andreisek, Gustav; Carrino, John A; Chhabra, Avneesh
Human mesenchymal stem cells (MSCs), which can generate both osteoblasts and chondrocytes, represent an ideal resource for orthopaedic repair using tissue-engineering approaches. One major difficulty for the development of osteochondral constructs using undifferentiated MSCs is that serum is typically used in culture protocols to promote differentiation of the osteogenic component, whereas existing chondrogenic differentiation protocols rely on the use of serum-free conditions. In order to define conditions which could be compatible with both chondrogenic and osteogenic differentiation in a single bioreactor, we have analysed the efficiency of new biphasic differentiation regimes based on transient serum exposure followed by serum-free treatment. MSC differentiation was assessed either in serum-free medium or with a range of transient exposure to serum, and compared to continuous serum-containing treatment. Although osteogenic differentation was not supported in the complete absence of serum, marker expression and extensive mineralization analyses established that 5 days of transient exposure triggered a level of differentiation comparable to that observed when serum was present throughout. This initial phase of serum exposure was further shown to support the successful chondrogenic differentiation of MSCs, comparable to controls maintained in serum-free conditions throughout. This study indicates that a culture based on temporal serum exposure followed by serum-free treatment is compatible with both osteogenic and chondrogenic differentiation of MSCs. These results will allow the development of novel strategies for osteochondral tissue engineering approaches using MSCs for regenerative medicine. PMID:23161724
France, L A; Scotchford, C A; Grant, D M; Rashidi, H; Popov, A A; Sottile, V
Background Osteochondral interface regeneration is challenging for functional and integrated cartilage repair. Various layered scaffolds have been used to reconstruct the complex interface, yet the influence of the permeability of the layered structure on cartilage defect healing remains largely unknown. Methods We designed and fabricated a novel bilayered scaffold using articular cartilage extracellular matrix (ACECM) and hydroxyapatite (HAp), involving a porous, oriented upper layer and a dense, mineralised lower layer. By optimising the HAp/ACECM ratio, differing pore sizes and porosities were obtained simultaneously in the two layers. To evaluate the effects of permeability on cell behaviour, rabbit chondrocytes were seeded. Results Morphological observations demonstrated that a gradual interfacial region was formed with pore sizes varying from 128.2?±?20.3 to 21.2?±?3.1 ?m. The permeability of the bilayered scaffold decreased with increasing compressive strain and HAp content. Mechanical tests indicated that the interface was stable to bearing compressive and shear loads. Accordingly, the optimum HAp/ACECM ratio (7 w/v%) in the layer to mimic native calcified cartilage was found. Chondrocytes could not penetrate the interface and resided only in the upper layer, where they showed high cellularity and abundant matrix deposition. Conclusions Our findings suggest that a bilayered scaffold with low permeability, rather than complete isolation, represents a promising candidate for osteochondral interface tissue engineering. PMID:24950704
Clinical manual tests refer to increased ankle stiffness in children immobilized due to hip osteochondritis. The aim of the present study was to investigate musculo-articular stiffness via different techniques in immobilized children to confirm or not and quantify these observations. Ankle stiffness was quantified monthly during the long immobilization period in three diseased children and compared to healthy age-matched children. Sinusoidal perturbations were used to evaluate musculo-articular (MA) stiffness of the ankle plantar-flexors. The stiffness index (SI(MA-EMG)) was the slope of the linear relationship between angular stiffness and plantar-flexion torque normalized with electromyographic activity of the triceps surae (TS). The stiffness of the ankle plantar-flexors was also indirectly evaluated using the TS electromechanical delay (EMD). SI(MA-EMG) was greater for diseased children, and this higher stiffness was confirmed by the higher EMD values found in these immobilized children. Furthermore, both parameters indicated that ankle stiffness continues to increase through immobilization period. This study gives a quantitative evaluation of ankle stiffness changes through the immobilization period imposed to children treated for hip osteochondritis. The use of EMD measurement to indirectly evaluate these stiffness changes is also validated. This study shed for the first time some light into the patterns of muscle modifications following immobilization in children. PMID:20189829
Grosset, Jean-François; Lapole, Thomas; Mora, Isabelle; Verhaeghe, Martine; Doutrellot, Pierre-Louis; Pérot, Chantal
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 scaffold’s 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 scaffold’s 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
Elder, Steven; Gottipati, Anuhya; Zelenka, Hilary; Bumgardner, Joel
In this work, injectable, biodegradable hydrogel composites of crosslinked oligo(poly(ethylene glycol) fumarate) (OPF) and gelatin microparticles (MPs) were utilized to fabricate a bilayered osteochondral construct. Rabbit marrow mesenchymal stem cells (MSCs) were encapsulated with transforming growth factor-?3 (TGF-?3)-loaded MPs in the chondrogenic layer and cocultured with cells of different periods of osteogenic preculture (0, 3, 6 and 12 days) in the osteogenic layer to investigate the effects of TGF-?3 delivery and coculture on the proliferation and differentiation of cells in both layers. The results showed that, in the chondrogenic layer, TGF-?3 significantly stimulated chondrogenic differentiation of MSCs. Additionally, cells of various osteogenic preculture periods in the osteogenic layer, along with TGF-?3, enhanced gene expression for MSC chondrogenic markers to different extents. In the osteogenic layer, cells maintained their alkaline phosphatase activity during the coculture; however, mineralization was delayed by the presence of TGF-?3. Overall, this study demonstrated the fabrication of bilayered hydrogel composites that mimic the structure and function of osteochondral tissue, along with the application of these composites as cell and growth factor carriers, while illustrating that encapsulated cells of different degrees of osteogenic differentiation can significantly influence the chondrogenic differentiation of cocultured progenitor cells in both the presence and absence of chondrogenic growth factors. PMID:20197126
Guo, Xuan; Liao, Jiehong; Park, Hansoo; Saraf, Anita; Raphael, Robert M.; Tabata, Yasuhiko; Kasper, F. Kurtis; Mikos, Antonios G.
Introduction Mesenchymal stem cells (MSCs) are an attractive cell source for cartilage and bone tissue engineering given their ability to differentiate into chondrocytes and osteoblasts. However, the common origin of these two specialized cell types raised the question about the identification of regulatory pathways determining the differentiation fate of MSCs into chondrocyte or osteoblast. Methods Chondrogenesis, osteoblastogenesis, and adipogenesis of human and mouse MSC were induced by using specific inductive culture conditions. Expression of promyelocytic leukemia zinc-finger (PLZF) or differentiation markers in MSCs was determined by RT-qPCR. PLZF-expressing MSC were implanted in a mouse osteochondral defect model and the neotissue was analyzed by routine histology and microcomputed tomography. Results We found out that PLZF is not expressed in MSCs and its expression at early stages of MSC differentiation is the mark of their commitment toward the three main lineages. PLZF acts as an upstream regulator of both Sox9 and Runx2, and its overexpression in MSC enhances chondrogenesis and osteogenesis while it inhibits adipogenesis. In vivo, implantation of PLZF-expressing MSC in mice with full-thickness osteochondral defects resulted in the formation of a reparative tissue resembling cartilage and bone. Conclusions Our findings demonstrate that absence of PLZF is required for stemness maintenance and its expression is an early event at the onset of MSC commitment during the differentiation processes of the three main lineages. PMID:24564963
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
Carmalt, James L; Borg, Hanna; Näslund, Hans; Waldner, Cheryl
In this study, we report adaptation of Raman spectroscopy for arthroscopy of joint tissues using a custom-built fiber optic probe. Differentiation of healthy and damaged tissue or examination of subsurface tissue, such as subchondral bone, is a challenge in arthroscopy because visual inspection may not provide sufficient contrast. Discrimination of healthy versus damaged tissue may be improved by incorporating point spectroscopy or hyperspectral imaging into arthroscopy where contrast is based on molecular structure or chemical composition. Articular joint surfaces of knee cadaveric human tissue and tissue phantoms were examined using a custom-designed Raman fiber optic probe. Fiber-optic Raman spectra were compared against reference spectra of cartilage, subchondral bone and cancellous bone collected using Raman microspectroscopy. In fiber-optic Raman spectra of the articular surface, there was an effect of cartilage thickness on recovery of signal from subchondral bone. At sites with intact cartilage, the bone mineralization ratio decreased but there was a minimal effect in the bone mineral chemistry ratios. Tissue phantoms were prepared as experimental models of the osteochondral interface. Raman spectra of tissue phantoms suggested that optical scattering of cartilage has a large effect on the relative cartilage and bone signal. Finite element analysis modeling of light fluence in the osteochondral interface confirmed experimental findings in human cadaveric tissue and tissue phantoms. These first studies demonstrate proof of principle for Raman arthroscopic measurement of joint tissues and provide a basis for future clinical or animal model studies. PMID:21359366
Esmonde-White, Karen A.; Esmonde-White, Francis W.L.; Morris, Michael D.
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
Hutchinson, Mark R; Ireland, Mary Lloyd
The management of osteoarthritis of the shoulder in young, active patients is a challenge, and the optimal treatment has yet to be completely established. Many of these patients wish to maintain a high level of activity, and arthroplasty may not be a practical treatment option. It is these patients who may be excellent candidates for joint-preservation procedures in an effort to avoid or delay joint replacement. Several palliative and restorative techniques are currently optional. Joint debridement has shown good results and a combination of arthroscopic debridement with a capsular release, humeral osteoplasty, and transcapsular axillary nerve decompression seems promising when humeral osteophytes are present. Currently, microfracture seems the most studied reparative treatment modality available. Other techniques, such as autologous chondrocyte implantation and osteochondral transfers, have reportedly shown potential but are currently mainly still investigational procedures. This paper gives an overview of the currently available joint preserving surgical techniques for glenohumeral osteoarthritis. PMID:22536514
van der Meijden, Olivier A; Gaskill, Trevor R; Millett, Peter J
We evaluated the curative efficacy of a gelatin ?-tricalcium phosphate (?-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 ?-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 ?-TCP sponge at the lesion site. PMID:24155448
Tsuzuki, Nao; Seo, Jong-pil; Yamada, Kazutaka; Haneda, Shingo; Furuoka, Hidefumi; Tabata, Yasuhiko; Sasaki, Naoki
We evaluated the curative efficacy of a gelatin ?-tricalcium phosphate (?-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 ?-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 ?-TCP sponge at the lesion site. PMID:24155448
Tsuzuki, Nao; Seo, Jong-pil; Yamada, Kazutaka; Haneda, Shingo; Furuoka, Hidefumi; Tabata, Yasuhiko; Sasaki, Naoki
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
Schoffl, Volker; Kupper, Thomas
We describe a patient with a giant cell tumor in the talar head and neck of the left foot who was diagnosed as having osteochondritis dissecans and treated with arthroscopic drilling in this same location 3 years earlier. Giant cell tumors can be confused with several conditions, including giant cell reparative granulomas, brown tumors, and aneurysmal bone cysts. Giant cell tumors of bone typically occur in the epiphysis of long bones, including the distal femur and proximal tibia. They are uncommonly found in the small bones of the foot or ankle, and talar involvement is rare. Despite this rarity, the radiographic appearance and clinical signs of talar lesions should be considered in the differential diagnosis of nontraumatic conditions in the foot. PMID:17507533
Selek, Hakan; Ozer, Hamza; Turanli, Sacit; Erdem, Ozlem
Encephalitozoon cuniculi is an obligate intracellular microsporidian parasite that can result in clinical and subclinical infection in many species. In the present study, a serological survey was conducted using samples from 105 horses in the state of New Jersey; 49 of the samples were obtained from clinically abnormal animals. Five or 4.8% of 105 serum samples were found to demonstrate reactivity by ELISA with titers of 1:64 to 1:1,024. One of the samples was obtained from a clinically normal horse. Clinical signs and diagnoses from the other animals included lameness, colic, osteochondritis dissecans, and fever. All clinical issues were resolved with hospitalization and treatment without the institution of E. cuniculi-focused therapy. This is the first report on the detection of E. cuniculi antibodies in horses in the USA. PMID:24802871
Cray, Carolyn; Perritt, Emily; Hughes, Cynthia; Belgrave, Rodney L
This case report aims at highlighting the different effects on subchondral bone regeneration of two different biomaterials in the same patient, in addition to bone marrow derived cell transplantation (BMDCT) in ankle. A 15-year-old boy underwent a first BMDCT on a hyaluronate membrane to treat a deep osteochondral lesion (8?mm). The procedure failed: subchondral bone was still present at MRI. Two years after the first operation, the same procedure was performed on a collagen membrane with DBM filling the defect. After one year, AOFAS score was 100 points, and MRI showed a complete filling of the defect. The T2 mapping MRI after one year showed chondral tissue with values in the range of hyaline cartilage. In this case, DBM and the collagen membrane were demonstrated to be good biomaterials to restore subchondral bone: this is a critical step towards the regeneration of a healthy hyaline cartilage. PMID:23936705
Context: Medial impingement syndrome of the ankle is common in the athletic population. A marginal osteophyte on the leading edge of the medial talar facet and a corresponding “kissing” osteophyte on the tibia, in front of the medial malleolus, may abut and cause pain and limited dorsiflexion. Background: Palpation of the talar osteophyte and standard imaging—especially, the oblique view of the foot—are useful in making the diagnosis. Surgical removal of the osteophyte may be necessary. Conclusions: Ankle impingement is commonly seen in running and jumping sports, especially if the athlete has a subtle cavus foot. It may be associated with ankle instability, osteochondritis dissecans of the talus, and stress fractures of the foot. PMID:23015980
Ankle arthroscopy is a useful technique, especially for intra-articular problems and osteocartilagenous lesions. Indications for this diagnostic and therapeutic technique include: ankle sprain unresponsive to the usual course of treatment, complaints of intermittent locking, pain and clicking, limitation of motion, and painful conditions with no obvious etiology (especially in a worker's compensation beneficiary). A review of arthroscopic, radiographic, and clinical data of all patients undergoing ankle arthroscopy at our center provided the following diagnoses: talar dome osteochondral fractures, loose bodies, accessory ossicles, talar dome cyst with loose bodies, and chronic synovitis. The anatomy of ankle arthroscopy is demanding; while the technique incorporates the same instrumentation as is used for knee arthroscopy, awareness of the neurovascular structures is essential to avoid complications. Although infrequent, complications can include sinus tract formation, sensory nerve damage, synovitis, infection, instrument breakage, and calf compartment syndromes due to extravasation of irrigation fluid. PMID:3050810
Barber, F A; Britt, B T; Ratliff, H W; Sutker, A N
Rotational dislocations of patella, which involve rotation of the patella around a horizontal or vertical axis are rare. These rotational dislocations of patella are difficult to reduce by close methods. These dislocations can have associated osteochondral and retinacular injury. We report a case of a 20-year-old male who presented with swelling and pain in the right knee following a motor cycle accident. Radiological evaluation using the computed tomography revealed a patellar dislocation with a concomitant Hoffa fracture. Patella was rotated around the vertical axis and was incarcerated into the Hoffa fracture. This is a very rare injury and first of its kind to be reported. The difficulties in diagnosis, mechanism of injury and management have been discussed. We feel closed reduction of such an injury is likely to fail and open reduction is recommended. PMID:25298564
Soraganvi, Prasad C; Narayan Gowda, Bs; Rajagopalakrishnan, Ramakanth; Gavaskar, Ashok S
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
Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J.; Warren, Russell F.; Doyle, Maureen; Rodeo, Scott A.
This review was conducted as a complementary study to our review "Current concepts in the treatment of cartilage damage. A review", in this same Journal, on promising new strategies in the treatment of cartilage defects. The established treatments such as osteochondral implants, bone marrow stimulation techniques and chondrogeneic cell implantations, besides advantages, have drawbacks that have led to seek new strategies such as scaffold materials. Matrix-associated chondrocyte implantation, hyaluronan-based scaffolds, tissue-engineered collagen matrices seeded with autologous chondrocytes and encapsulation of autologous chondrocytes in poly(ethylene glycol) diacrylate (PEGDA) seem to be less invasive and have a good performance. In this review we describe benefits and disadvantages of the new procedures of cartilage regeneration by scaffolding materials such as PEGDA. PMID:25338410
Musumeci, Giuseppe; Loreto, Carla; Castorina, Sergio; Imbesi, Rosa; Leonardi, Rosalia; Castrogiovanni, Paola
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.
Beltran, J.; Noto, A.M.; Mosure, J.C.; Weiss, K.L.; Zuelzer, W.; Christoforidis, A.J.
Elbow arthroscopic surgery can now effectively treat a variety of conditions that affect athletes. Advances in instrumentation, increased surgeon familiarity, and expanded indications have led to significant growth in elbow arthroscopic surgery in the past few decades. While positioning, portal placement, and specific instruments may vary among surgeons, anatomic considerations guide surgical approaches to minimize neurovascular compromise. Arthroscopic procedures vary in difficulty, and surgeons should follow stepwise advancement with experience. Removal of loose bodies, debridement of synovial plicae, and debridement of the extensor carpi radialis brevis for lateral epicondylitis are considered simple procedures for novice elbow arthroscopic surgeons. More advanced procedures include management of osteochondritis dissecans, valgus extension overload in the throwing athlete, and capsular release. With proper technique, a variety of athletic elbow conditions can be treated arthroscopically with predictable results and minimal morbidity. PMID:23572098
Byram, Ian R; Kim, H Mike; Levine, William N; Ahmad, Christopher S
Additive manufacturing (AM) is a broad term encompassing 3D printing and several other varieties of material processing, which involve computer-directed layer-by-layer synthesis of materials. As the popularity of AM increases, so to do expectations of the medical therapies this process may offer. Clinical requirements and limitations of current treatment strategies in bone grafting, spinal arthrodesis, osteochondral injury and treatment of periprosthetic joint infection are discussed. The various approaches to AM are described, and the current state of clinical translation of AM across these orthopedic clinical scenarios is assessed. Finally, we attempt to distinguish between what AM may offer orthopedic surgery from the hype of what has been promised by AM. PMID:25159068
Gibbs, David Mr; Vaezi, Mohammad; Yang, Shoufeng; Oreffo, Richard Oc
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
Sillanpää, Petri J; Mäenpää, Heikki M
Patellar dislocation is a common knee injury with mainly lateral dislocations, leading to ruptures of the medial patellofemoral ligament in most of the cases. Reliable data and prognostic factors for stability of the patellofemoral joint and satisfaction of the patient after either conservative or operative treatment have not been established yet. Until now, there are no randomized controlled trials for recurrent patellar dislocation at all. As a synopsis of the randomized controlled trials about first-time patellar dislocation, no significant difference between operative and conservative management is evident. This applies to both children and adolescents as well as to adults. There is a clear tendency towards first-line conservative therapy after traumatic patellar dislocation. Operative treatment is only required in case of accompanying injuries like osteochondral fractures or in case of recurrent dislocations. Further prospective randomized controlled trials with standardized operative and conservative treatment and patient cohorts of sufficient size are necessary in the future. PMID:22527955
Petri, M; Krettek, C; Jagodzinski, M
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 (6–8 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 vivo–labeling procedures. The in vivo–labeled 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 vivo–labeled MSC transplants and unlabeled control transplants were compared by using t tests. MR data were correlated with histopathologic results. Results: In vivo–labeled MSCs demonstrated significantly higher ferumoxytol uptake compared with ex vivo–labeled cells. With electron microscopy, iron oxide nanoparticles were localized in secondary lysosomes. In vivo–labeled 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 vivo–labeling procedures. © RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130858/-/DC1 PMID:23850832
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
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
Boyce, Mary K.; Trumble, Troy N.; Carlson, Cathy S.; Groschen, Donna M.; Merritt, Kelly A.; Brown, Murray P.
Application of new biological treatments in orthopaedics is controversial nowadays. Surgeons and practitioners know how difficult can be to choose a solution for chondral injuries. Joint damages are from little contusions, osteochondral fractures, avascular necrosis, osteochondritis and degenerative processes like osteoarthritis and rheumatisms. All mentioned have a common problem: the lack of regenerating hyaline cartilage by themselves. Recently, PRP have been used to treat early moderate chondropathies. Here we show the preliminary results of 30 patients affected by chondropathy of the knee after 6 months treated with a single intrarticular injection of PRP. Thirty patients, 18-65 years old, with a diagnosis of I to III Outerbridge chondropathy in the knee, pain for more than 3 months following conservative treatment and no bone axial defect, were treated with one intraarticular injection of PRP (GPS mini set, BIOMET), after written consent and Ethic and Legal Committee approval. VAS and KOOS scores were evaluated before PRP injection and at 1, 3 and 6 months after the treatment. ANOVA with repeated measures using the SPSS showed significantly better results in term of KOOS and VAS scores at 1, 3 and 6 months respect to the pre-injection value (p less than 0,05) We think that PRP treatment is a promising alternative for the treatment of knee chondropathy; however its efficacy has to be demonstrated with more clinical works, with longer follow up and with greater number of patients, even with controlled and randomized trials. In our study only one injection of PRP has been able to allow a clinical improvement, suggesting the possibility to avoid multiple injections protocols, and consequently reducing the health expenses. Until the efficacy of PRP will not be definitely demonstrated, surgeon should be very prudent in indications. PMID:23648201
Torrero, J I; Aroles, F; Ferrer, D
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
Oka, M; Ushio, K; Kumar, P; Ikeuchi, K; Hyon, S H; Nakamura, T; Fujita, H
Introduction Total subtalar dislocation without fracture of the ankle is a rare clinical entity; it is usually due to a traumatic high-energy mechanism. Standard treatment is successful closed reduction under general anesthesia followed by non-weight bearing and ankle immobilization with a below-knee cast for 6 weeks. Case presentation We present the case of a 30-year-old Moroccan woman who was involved in a road traffic accident. She subsequently received a radiological assessment that objectified a total subtalar dislocation without fracture of her ankle. She was immediately admitted to the operating theater where an immediate reduction was performed under sedation, and immobilization in a plaster boot was adopted for 8 weeks. The management of this traumatic lesion is discussed in the light of the literature. Conclusions Medial subtalar dislocation is a rare dislocation and is not commonly seen as a sports injury because it requires transfer of a large amount of kinetic energy. The weaker talocalcaneal and talonavicular ligaments often bear the brunt of the energy and are more commonly disrupted, compared to the relatively stronger calcaneonavicular ligament. Urgent reduction is important, and closed reduction under general anesthesia is usually successful, often facilitated by keeping the knee in flexion to relax the gastrocnemius muscle. Long-term sequelae include talar avascular necrosis and osteochondral fracture, as well as chronic instability and pain. PMID:25240955
INTRODUCTION Chondral and osteochondral lesions of the knee are notoriously difficult to treat due to the poor healing capacity of articular cartilage and the hostile environment of moving joints, ultimately causing disabling pain and early osteoarthritis. There are many different reconstructive techniques used currently but few are proven to be of value. However, some have been shown to produce a better repair with hyaline-like cartilage rather than fibrocartilage. METHODS A systematic search of all available online databases including PubMed, MEDLINE® and Embase™ was undertaken using several keywords. All the multiple treatment options and methods available were considered. These were summarised and the evidence for and against them was scrutinised. RESULTS A total of 460 articles were identified after cross-referencing the database searches using the keywords. These revealed that autologous and matrix assisted chondrocyte implantation demonstrated both ‘good to excellent’ histological results and significant improvement in clinical outcomes. CONCLUSIONS Autologous and matrix assisted chondrocyte implantation have been shown to treat symptomatic lesions successfully with significant histological and clinical improvement. There is, however, still a need for further randomised clinical trials, perfecting the type of scaffold and the use of adjuncts such as growth factors. A list of recommendations for treatment and the potential future trends of managing these lesions are given. PMID:22943326
Perera, JR; Gikas, PD; Bentley, G
The treatment of the painful osteomyelitis in patients with SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) is often a problem. A 53-year-old woman had experienced palmo-plantar pustular skin lesions for four years, and in the past two years complained about progressive breath-and movement-dependent pain of the sternum. On examination she had extensive palmoplantar pustules and a painful swelling in the area of the right sternoclavicular joint. The three-phase bone scintigraphy showed a strong focal enrichment in the right sternoclavicular joint and at the transition from the manubrium to the corpus sterni suggesting active osteo-chondritis. Initially prednisolone and ibuprofen were administered, but only the skin changes regressed. The strong sternal pain decreased only after infusion of 4 mg zoledronic acid over three days. In a follow-up examination after five months the patient was still free of pain. The bisphosphonates inhibit osteoclastic activity and lead to long-lasting improvement of osteo-articular complaints in the SAPHO syndrome. PMID:18266863
Just, Alexander; Adams, Sabine; Brinkmeier, Thomas; Barsegian, Vahé; Lorenzen, Johannes; Schilling, Fritz; Frosch, Peter
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
Ahmad, Christopher S; Vitale, Mark A
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
Ye, Ken; Felimban, Raed; Traianedes, Kathy; Moulton, Simon E.; Wallace, Gordon G.; Chung, Johnson; Quigley, Anita; Choong, Peter F. M.; Myers, Damian E.
Posttraumatic disorders of the ankle are a common cause of chronic pain. Magnetic resonance imaging (MRI) has proved to be highly useful in clarifying a wide spectrum of underlying lesions which frequently cannot be detected on radiographs. Even if the assessment of the lateral collateral ligaments of the ankle is not regarded as a primary indication for MRI, it allows the diagnosis of subchondral contusions or cysts, anterolateral impingement syndrome, sinus tarsi syndrome, osteochondral fractures and osteochondrosis dissecans of the talus (ODT),which may not be detected with other imaging modalities. A 42 year old female patient suffered from persisting non-specific pain following an inversion trauma 4 months previously. MRI enabled the detection of an ODT which was not diagnosed on plain radiographs and which was verified upon arthroscopy. A superficial cartilage defect, as shown arthroscopically,was not delineated using MRI. Our observations indicate that MRI may be useful in patients with unclear persisting pain following ankle trauma and that it may contribute to the early detection of lesions which require surgical intervention. PMID:12658342
Wirth, S; Wieser, A; Witt, S N; Mutschler, W; Reiser, M
Three-dimensional printing (3DP) is a rapid prototyping 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 and chitosan 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 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
Lee, Ju-Yeon; Choi, Bogyu; Wu, Benjamin; Lee, Min
Polymer-ceramic composites obtained as the result of a mineralization process hold great promise for the future of tissue engineering. Simulated body fluids (SBFs) are widely used for the mineralization of polymer scaffolds. In this work an exhaustive study with the aim of optimizing the mineralization process on a poly(L-lactic acid) (PLLA) macroporous scaffold has been performed. We observed that when an air plasma treatment is applied to the PLLA scaffold its hydroxyapatite nucleation ability is considerably improved. However, plasma treatment only allows apatite deposition on the surface of the scaffold but not in its interior. When a 5 wt % of synthetic hydroxyapatite (HAp) nanoparticles is mixed with PLLA a more abundant biomimetic hydroxyapatite layer grows inside the scaffold in SBF. The morphology, amount, and composition of the generated biomimetic hydroxyapatite layer on the pores' surface have been analyzed. Large mineralization times are harmful to pure PLLA as it rapidly degrades and its elastic compression modulus significantly decreases. Degradation is retarded in the composite scaffolds because of the faster and extensive biomimetic apatite deposition and the role of HAp to control the pH. Mineralized scaffolds, covered by an apatite layer in SBF, were implanted in osteochondral lesions performed in the medial femoral condyle of healthy sheep. We observed that the presence of biomimetic hydroxyapatite on the pore's surface of the composite scaffold produces a better integration in the subchondral bone, in comparison to bare PLLA scaffolds. PMID:23152082
Deplaine, H; Lebourg, M; Ripalda, P; Vidaurre, A; Sanz-Ramos, P; Mora, G; Prósper, F; Ochoa, I; Doblaré, M; Gómez Ribelles, J L; Izal-Azcárate, I; Gallego Ferrer, G
Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization would contribute to the commercialization or industrialization of this technology. Vitrification has been thought to be a promising method for successful preservation of articular cartilage (AC), but high concentration cryoprotectants (CPAs) are used which may cause high cellular toxicity. An effective way to reduce CPA toxicity is to increase CPA concentration gradually while the temperature is lowered. Understanding the mechanism of CPA permeation at subzero temperatures is important for designing the cryopreservation protocol. In this research, the permeation of dimethyl sulfoxide (Me(2)SO) in ovine AC at subzero temperatures was studied experimentally. Pretreated AC discs were exposed in Me(2)SO solutions for different time (0, 5, 15, 30, 50, 80, and 120 min) at three temperature levels (-10, -20, and -30 °C). The Me(2)SO concentration within the tissue was determined by ultraviolet (UV) spectrophotometry. The diffusion coefficients were estimated to be 0.85×10(-6), 0.48×10(-6), and 0.27×10(-6) cm(2)/s at -10, -20, and -30 °C, respectively, and the corresponding activation energy was 29.23 kJ/mol. Numerical simulation was performed to compare two Me(2)SO addition protocols, and the results demonstrated that the total loading duration could be effectively reduced with the knowledge of permeation kinetics. PMID:22374614
Zhang, Shao-Zhi; Yu, Xiao-Yi; Chen, Guang-Ming
Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization would contribute to the commercialization or industrialization of this technology. Vitrification has been thought to be a promising method for successful preservation of articular cartilage (AC), but high concentration cryoprotectants (CPAs) are used which may cause high cellular toxicity. An effective way to reduce CPA toxicity is to increase CPA concentration gradually while the temperature is lowered. Understanding the mechanism of CPA permeation at subzero temperatures is important for designing the cryopreservation protocol. In this research, the permeation of dimethyl sulfoxide (Me2SO) in ovine AC at subzero temperatures was studied experimentally. Pretreated AC discs were exposed in Me2SO solutions for different time (0, 5, 15, 30, 50, 80, and 120 min) at three temperature levels (?10, ?20, and ?30 °C). The Me2SO concentration within the tissue was determined by ultraviolet (UV) spectrophotometry. The diffusion coefficients were estimated to be 0.85×10?6, 0.48×10?6, and 0.27×10?6 cm2/s at ?10, ?20, and ?30 °C, respectively, and the corresponding activation energy was 29.23 kJ/mol. Numerical simulation was performed to compare two Me2SO addition protocols, and the results demonstrated that the total loading duration could be effectively reduced with the knowledge of permeation kinetics. PMID:22374614
Zhang, Shao-zhi; Yu, Xiao-yi; Chen, Guang-ming
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.
Steinert, Marian; Kratz, Marita; Jaedicke, Volker; Hofmann, Martin R.; Jones, David B.
The articular hyaline cartilage of synovial joints has a very limited capacity for repair after injury. In contrast, the mandibular condylar cartilage of the temporomandibular joint possesses as intrinsic potential for regeneration. This study aimed to test the hypothesis that cultured allografts of mandibular condylar cartilage could be used to promote biological repair of injured orthotopic joint surfaces. Using a primate animal model, cultures of mandibular condylar cartilage cells were grafted into surgically created defects in a recipient hyaline cartilage joint surface. Articular wound healing was assessed macroscopically and histologically over a postoperative period of 52 weeks. Mandibular condylar cartilage cells scheduled for allogenous transplantation were initially characterised in vitro. Expansion of primary colonies in organ culture provided the allogenic cellular material for in vivo grafting. Grafting of osteochondral articular wounds with 5-week cultures of mandibular cartilage cells led to wound regeneration with complete reconstitution of articular surface continuity by 52 weeks. There was novel synthesis of cartilage collagens and sulphated glycosaminoglycans within the repair tissue and no evidence of immunological rejection. Healing of grafted defects was thought to occur by a combination of donor cell proliferation and ingress of host mesenchymal cells. In contrast, grafted control wounds underwent largely fibrous repair with incomplete articular regeneration. In conclusion, transplanted allografts of cultured mandibular condylar cartilage appeared to have the ability, in this primate model, to promote cartilaginous repair and regeneration of orthotopic articular wounds. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:9038492
Girdler, N. M.
The biomechanical function of articular cartilage relies crucially on its integration with both the subchondral bone and the wider continuum of cartilage beyond the directly loaded contact region. This study was aimed at visualizing, at the microanatomical level, the deformation response of cartilage including that of the non-directly loaded continuum. Cartilage-on-bone samples from bovine patellae were loaded in static compression until a near-equilibrium deformation was achieved, and then chemically fixed in this deformed state. Full-depth cartilage–bone sections, incorporating the indentation profile and beyond, were studied in their fully hydrated state using differential interference contrast microscopy. Morphometric measurements of the indented profile were used in combination with a force analysis of the tangential layer to investigate the extent to which the applied force is attenuated in moving away from the directly loaded region. This study provides microscopic evidence of a structure-related response in the transitional zone of the cartilage matrix. It is manifested as an intense chevron-type shear discontinuity arising from the constraints provided by both the strain-limiting articular surface and the osteochondral attachment. The discontinuity persists well into the non-directly loaded continuum of cartilage and is proposed as a force attenuation mechanism. The structural and biomechanical analyses presented in this study emphasize the important role of the complex microanatomy of cartilage, highlighting the interconnectivity and optimal recruitment of the load-bearing elements throughout the zonally differentiated cartilage depth. PMID:17062019
Thambyah, Ashvin; Broom, Neil
Abstract Hyaline cartilage displays a limited regenerative potential. Consequently, therapeutic approaches have been developed to treat focal cartilage lesions. Larger-sized lesions are commonly treated by osteochondral grafting/mosaicplasty, autologous chondrocyte implantation (ACI) or matrix-induced chondrocyte implantation (MACI). As an alternative cell source to chondrocytes, multipotent mesenchymal stem cells (MSCs) are regarded a promising option. We therefore investigated the feasibility of predifferentiating human MSCs incorporated in hydrogels clinically applied for MACI (CaReS®). MSC-laden hydrogels were cast and cultured over 10 days in a defined chondrogenic differentiation medium supplemented with TGF-?1. This was followed by an 11-day culture in TGF-?1 free media. After 21 days, considerable contraction of the hydrogels was observed. Histochemistry showed cells of a chondrocyte-like morphology embedded in a proteoglycan-rich extracellular matrix. Real-time polymerase chain reaction (RT-PCR) analysis showed the expression of chondrogenic marker genes, such as collagen type II and aggrecan. In summary, we demonstrate that chondrogenic differentiation of human mesenchymal stem cells embedded in collagen type I hydrogels can be induced under the influence of TGF-?1 over a period of 10 days. PMID:24803605
Fensky, Florian; Reichert, Johannes C; Traube, Andrea; Rackwitz, Lars; Siebenlist, Sebastian; Nöth, Ulrich
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
Baghaban Eslaminejad, Mohamadreza; Malakooty Poor, Elham
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
Bodó, Gábor; Vásárhelyi, Gábor; Hangody, László; Módis, László
Direct gene transfer strategies are of promising value to treat articular cartilage defects. Here, we tested the ability of a recombinant adeno-associated virus (rAAV) SOX9 vector to enhance the repair of cartilage lesions in vivo. The candidate construct was provided to osteochondral defects in rabbit knee joints vis-ŕ-vis control (lacZ) vector treatment and to cells relevant of the repair tissue (mesenchymal stem cells, chondrocytes). Efficient, long-term transgene expression was noted within the lesions (up to 16 weeks) and in cells in vitro (21 days). Administration of the SOX9 vector was capable of stimulating the biological activities in vitro and over time in vivo. SOX9 treatment in vivo was well tolerated, leading to improved cartilage repair processes with enhanced production of major matrix components. Remarkably, application of rAAV SOX9 delayed premature terminal differentiation and hypertrophy in the newly formed cartilage, possible due to contrasting effects of SOX9 on RUNX2 and ?-catenin osteogenic expression in this area. Most strikingly, SOX9 treatment improved the reconstitution of the subchondral bone in the defects, possibly due to an increase in RUNX2 expression in this location. These findings show the potential of direct rAAV gene delivery as an efficient tool to treat cartilage lesions. PMID:23149825
Cucchiarini, Magali; Orth, Patrick; Madry, Henning
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
Paoluzzi, Luca; Pieper, Jeroen; de Wijn, Joost R.; van Blitterswijk, Clemens A.
The purpose of this study was to describe a safer and more anatomical technique of MPFL reconstruction and to report the short-term results. The subjects included 20 patients with patellar dislocation with a mean age of 23. The operation was performed using a double-looped autogenous semitendinosus tendon graft. Two small bone tunnels were made at the medial edge of the patella, mimicking the wide patellar insertion of the MPFL and a bone tunnel was made at the femoral insertion site. The free ends of the graft attached to the patella and the loop end was fixed to the femoral side. Five patients were available for follow-up interviews by telephone and the remaining 15 were directly examined by physical examination and radiographic evaluation at 2 years or longer postoperatively. The average follow-up period was 30 months. Re-dislocation or patellar fracture was not seen in any patients. The average Kujala's score was 96 with a range from 84 to 100. Six patients were classified as excellent and 14 as good, according to the Crosby and Insall grading system. Radiographically, narrowing of the patellofemoral joint space was observed in 2 cases with previous osteochondral fracture out of those who were directly examined. The dual tunnel MPFL reconstruction produces favorable results in subjective and functional assessment of outcome without complications. PMID:20684880
Toritsuka, Yukiyoshi; Amano, Hiroshi; Mae, Tatsuo; Uchida, Ryohei; Hamada, Masayuki; Ohzono, Kenji; Shino, Konsei
Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into "pieces of the puzzle" in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as "cogs in a wheel" of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the "cogs" ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxanthoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature. PMID:21852556
Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert
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.
Liu, Xiaohua; Jin, Xiaobing; Ma, Peter X.
In tissue engineering, the physical and chemical properties of the scaffold mediates cell behavior, including regeneration. Thus a strategy that permits rapid screening of cell-scaffold interactions is critical. Herein, we have prepared eight "hybrid" hydrogel scaffolds in the form of continuous gradients such that a single scaffold contains spatially varied properties. These scaffolds are based on combining an inorganic macromer (methacrylated star polydimethylsiloxane, PDMSstar-MA) and organic macromer (poly(ethylene glycol)diacrylate, PEG-DA) as well as both aqueous and organic fabrication solvents. Having previously demonstrated its bioactivity and osteoinductivity, PDMSstar-MA is a particularly powerful component to incorporate into instructive gradient scaffolds based on PEG-DA. The following parameters were varied to produce the different gradients or gradual transitions in: (1) the wt.% ratio of PDMSstar-MA to PEG-DA macromers, (2) the total wt.% macromer concentration, (3) the number average molecular weight (Mn) of PEG-DA and (4) the Mn of PDMSstar-MA. Upon dividing each scaffold into four "zones" perpendicular to the gradient, we were able to demonstrate the spatial variation in morphology, bioactivity, swelling and modulus. Among these gradient scaffolds are those in which swelling and modulus are conveniently decoupled. In addition to rapid screening of cell-material interactions, these scaffolds are well suited for regeneration of interfacial tissues (e.g. osteochondral tissues) that transition from one tissue type to another. PMID:23707502
Bailey, Brennan M; Nail, Lindsay N; Grunlan, Melissa A
Objectives Matrix-assisted autologous chondrocyte transplantation (MACT) has been developed and applied in the clinical practice in the last decade to overcome most of the disadvantages of the first generation procedures. The purpose of this systematic review is to document and analyse the available literature on the results of MACT in the treatment of chondral and osteochondral lesions of the knee. Methods All studies published in English addressing MACT procedures were identified, including those that fulfilled the following criteria: 1) level I-IV evidence, 2) measures of functional or clinical outcome, 3) outcome related to cartilage lesions of the knee cartilage. Results The literature analysis showed a progressively increasing number of articles per year. A total of 51 articles were selected: three randomised studies, ten comparative studies, 33 case series and five case reports. Several scaffolds have been developed and studied, with good results reported at short to medium follow-up. Conclusions MACT procedures are a therapeutic option for the treatment of chondral lesions that can offer a positive outcome over time for specific patient categories, but high-level studies are lacking. Systematic long-term evaluation of these techniques and randomised controlled trials are necessary to confirm the potential of this treatment approach, especially when comparing against less ambitious traditional treatments. PMID:23610698
Kon, E.; Filardo, G.; Di Matteo, B.; Perdisa, F.; Marcacci, M.
The mechanisms and completeness of equine articular cartilage repair were studied in ten horses over a nine month period. Large (15 mm square) and small (5 mm square) full-thickness lesions were made in weight bearing and nonweight bearing areas of the radiocarpal, middle carpal and femoropatellar joints. The horses were euthanized in groups of two 1, 2.5, 4, 5 and 9 months later. Gross pathology, microradiography, and histopathology were used to evaluate qualitative aspects of articular repair. Computer assisted microdensitometry of safranin-O stained cartilage sections was used to quantitate cartilage matrix proteoglycan levels. Structural repair had occurred in most small defects at the end of nine months by a combination of matrix flow and extrinsic repair mechanisms. Elaboration of matrix proteoglycans was not complete at this time. Statistically better healing occurred in small weight bearing lesions, compared to large or nonweight bearing lesions. Synovial and perichondrial pannus interfered with healing of osteochondral defects that were adjacent to the cranial rim of the third carpal bone. Clinical and experimental experience suggests that these lesions are unlikely to heal, whereas similar lesions in the radiocarpal and femoropatellar joints had satisfactory outcomes. Observations made in this study support the use of early postoperative ambulation, passive flexion of operated joints, and recuperative periods of up to a year for large cartilage defects. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. Fig. 11. PMID:3349393
Hurtig, M B; Fretz, P B; Doige, C E; Schnurr, D L
In tissue engineering, the physical and chemical properties of the scaffold mediates cell behavior including regeneration. Thus, a strategy that permits rapid screening of cell-scaffold interactions is critical. Herein, we have prepared eight “hybrid” hydrogel scaffolds in the form of continuous gradients such that a single scaffold contains spatially varied properties. These scaffolds are based on combining an inorganic macromer [methacrylated star polydimethylsiloxane, PDMSstar-MA] and organic macromer [poly(ethylene glycol)diacrylate, PEG-DA] as well both aqueous and organic fabrication solvents. Having previously demonstrated its bioactivity and osteoinductivity, PDMSstar-MA is a particularly powerful component to incorporate into instructive gradient scaffolds based on PEG-DA. The following parameters were varied to produce the different gradients or gradual transitions in: (1) the wt% ratio of PDMSstar-MA to PEG-DA macromers, (2) the total wt% macromer concentration, (3) the number average molecular weight (Mn) of PEG-DA and (4) the Mn of PDMSstar-MA. Upon dividing each scaffold into four “zones” perpendicular to the gradient, we were able to demonstrate the spatial variation in morphology, bioactivity, swelling and modulus. Among these gradient scaffolds are those in which swelling and modulus are conveniently decoupled. In addition to rapid screening of cell-material interactions, these scaffolds are well-suited for regeneration of interfacial tissues (e.g. osteochondral tissues) that transition from one tissue type to another. PMID:23707502
Bailey, Brennan M.; Nail, Lindsay N.; Grunlan, Melissa A.
There are typical causes for carpal tunnel syndromes as well as a series of rare causes. Furthermore, the clinical image can also be untypical. This report is about a 59-year-old female patient with an untypical clinical symptomatology and with a rare cause: there was no major pain during the night or in the morning, no paraesthesias and no impairment of the fine motor skills, nevertheless, there were rapid paraesthesias and pain in the first three fingers of the right hand immediately after hyperextension of the wrist. Although the discomforts had already existed for 2 years they were not recognised properly because they were untypical and incomplete and neurography was negative. 3 years later in a renewed examination X-ray pictures of the carpus were taken and a 4 x 6 x 8 mm big ossicle on the ground of the carpal canal was found, the computed tomography and the intraoperative situs confirmed the image. The histology gave the diagnosis of a loose osteochondral body. Postoperatively the patient was quickly was free of the symptoms. PMID:18629762
Stocker, R L; Neuhold, N
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
Steinert, Marian; Kratz, Marita; Jaedicke, Volker; Hofmann, Martin R; Jones, David B
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 0.5 Hz with amplitude of 0.25 MPa for 1 h. 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
Wolff, Katherine J; Ramakrishnan, Prem S; Brouillette, Marc J; Journot, Brice J; McKinley, Todd O; Buckwalter, Joseph A; Martin, James A
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
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
Correia, S. I.; Pereira, H.; Silva-Correia, J.; Van Dijk, C. N.; Espregueira-Mendes, J.; Oliveira, J. M.; Reis, R. L.
First-time patellar dislocation typically occurs with twisting knee motions, during which the medial ligamentous stabilizers rupture, and the patella strikes against the lateral femoral condyle. The typical injury pattern is a tear of the medial patellofemoral ligament (MPFL) and bone bruises of the patella and the lateral femoral condyle. Additionally, complex injuries to bone, cartilage, and ligaments may occur. The ensuing loss of medial restraint favors future patellar dislocations, especially if additional risk factors are present. Recurrent patellar dislocations usually occur in individuals with anatomic variants of the patellar stabilizers, such as trochlear dysplasia, patella alta, and lateralization of the tibial tuberosity. Magnetic resonance (MR) imaging is reliable in identifying risk factors for chronic patellar instability and in assessing knee joint damage associated with patellar dislocation. MR imaging can thus provide important information for individually tailored treatment. Patients with primary patellar dislocation without severe internal derangement who lack major risk factors can be treated conservatively. Patients with pronounced ligamentous tears or large osteochondral lesions require prompt surgery. In addition, surgical correction of anatomic variants will help reduce the potential for chronic instability. The most common procedures, in addition to MPFL reconstruction, include trochleoplasty, medialization of the tibial tuberosity, and medial capsular plication. For comprehensive assessment of patellar dislocation, a radiologist should be able to identify typical injury patterns, know standard methods to assess risk factors for patellar instability, and be familiar with surgical options. PMID:20631363
Diederichs, Gerd; Issever, Ahi S; Scheffler, Sven
Nell-1, first identified by its overexpression in synostotic cranial sutures, is a novel osteoinductive growth and differentiation factor. To further define Nell-1's role in craniofacial patterning, we characterized defects of the ENU-induced Nell-1-deficient (END) mice, focusing on both intramembranous and endochondral cranial bones. Results showed that calvarial bones of neonatal END mice were reduced in thickness and density, with a phenotype resembling calvarial cleidocraniodysplasia. In addition, a global reduction in osteoblast markers was observed, including reductions in Runx2, alkaline phosphatase, and osteocalcin. Remarkably, detailed analysis of endochondral bones showed dysplasia as well. The chondrocranium in the END mouse showed enrichment for early, proliferating Sox9? chondrocytes, whereas in contrast markers of chondrocytes maturation were reduced. These data suggest that Nell-1 is an important growth factor for regulation of osteochondral differentiation, by regulating both Runx2 and Sox9 expression within the calvarium. In summary, Nell-1 is required for normal craniofacial membranous and endochondral skeletal development. PMID:22337375
Zhang, Xinli; Ting, Kang; Pathmanathan, Dharmini; Ko, Theodore; Chen, Weiwei; Chen, Feng; Lee, Haofu; James, Aaron W; Siu, Ronald K; Shen, Jia; Culiat, Cymbeline T; Soo, Chia
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
Chung, Eun Ji; Qiu, Hongjin; Kodali, Pradeep; Yang, Scott; Sprague, Stuart M.; Hwong, James; Koh, Jason; Ameer, Guillermo A.
A major task of contemporary medicine and dentistry is restoration of human tissues and organs lost to diseases and trauma. A decade-long intense effort in tissue engineering has provided the proof of concept for cell-based replacement of a number of individual tissues such as the skin, cartilage, and bone. Recent work in stem cell-based in vivo restoration of multiple tissue phenotypes by composite tissue constructs such as osteochondral and fibro-osseous grafts has demonstrated probable clues for bioengineered replacement of complex anatomical structures consisting of multiple cell lineages such as the synovial joint condyle, tendon-bone complex, bone-ligament junction, and the periodontium. Of greater significance is a tangible contribution by current attempts to restore the structure and function of multitissue structures using cell-based composite tissue constructs to the understanding of ultimate biological restoration of complex organs such as the kidney or liver. The present review focuses on recent advances in stem cell-based composite tissue constructs and attempts to outline challenges for the manipulation of stem cells in tailored biomaterials in alignment with approaches potentially utilizable in regenerative medicine of human tissues and organs. PMID:15929124
Rahaman, Mohamed N; Mao, Jeremy J
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
Baghaban Eslaminejad, Mohamadreza; Malakooty Poor, Elham
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.
Bailey, Brennan Margaret
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.
Huang, Yan-Ping; Saarakkala, Simo; Toyras, Juha; Wang, Li-Ke; Jurvelin, Jukka S.; Zheng, Yong-Ping
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
Gratz, Kenneth R.; Wong, Benjamin L.; Bae, Won C.; Sah, Robert L.
Targeting and differentiating stem cells at sites of injury and repair is an exciting and promising area for disease treatment and reparative medicine. We have investigated remote magnetic field activation of magnetic nanoparticle-tagged mechanosensitive receptors on the cell membrane of human bone marrow stromal cells (HBMSCs) for use in osteoprogenitor cell delivery systems and activation of differentiation in vitro and in vivo toward an osteochondral lineage. HBMSC-labeled with magnetic beads coated with antibodies or peptides to the transmembrane ion channel stretch activated potassium channel (TREK-1) or arginine–glycine–aspartic acid were cultured in monolayer or encapsulated into polysaccharide alginate/chitosan microcapsules. Upregulation in gene expression was measured in magnetic particle-labeled HBMSCs in response to TREK-1 activation over a short period (7 days) with an increase in mRNA levels of Sox9, core binding factor alpha1 (Cbfa1), and osteopontin. Magnetic particle-labeled HBMSCs encapsulated into alginate chitosan capsules were exposed to magnetic forces both in vitro and in vivo intermittently for 21 days. After 21 days the encapsulated, magnetic particle-labeled HBMSCs in vivo were viable as evidenced by extensive cell tracker green fluorescence. The mechanical stimulation of HBMSCs labeled with TREK-1 magnetic nanoparticle receptors enhanced expression of type-1 collagen in vitro with increases in proteoglycan matrix, core binding factor alpha1 (Cbfa1) and collagen synthesis, and extracellular matrix production and elevated the expression of type-1 and type-2 collagen in vivo. Additionally, the magnetically remote stimulation of HBMSCs labeled with magnetic nanoparticle arginine–glycine–aspartic acid considerably enhanced proteoglycan and collagen synthesis and extracellular matrix production and elevated the expression of type-1 and type-2 collagen in vivo and in vitro. Osteogenic mechanosensitive receptor manipulation by magnetic nanotechnology can induce the differentiation of osteoprogenitor cell populations toward an osteogenic lineage. These cell manipulation strategies offer tremendous therapeutic opportunities in soft and hard tissue repair. PMID:20504072
Kanczler, Janos M; Sura, Harpul S; Magnay, Julia; Green, David; Oreffo, Richard O C; Dobson, Jon P; El Haj, Alicia J
Cartilage regeneration with cell therapy following arthroscopic surgery could be used in racehorses with intra-articular fractures (IAF) and osteochondritis dissecans (OCD). The aims of this study were to investigate the origin and multipotency of stromal cells in the synovial fluid (SF) of horses with intra-articular injury and synovitis, and to provide a new strategy for regeneration of lost articular cartilage. Mesenchymal stromal cells were isolated from SF of horses with IAF and OCD. Multipotency was analysed by RT-PCR for specific mRNAs and staining for production of specific extracellular matrices after induction of differentiation. The total number of SF-derived mesenchymal stromal cells reached >1?×?10(7) by the fourth passage. SF-derived cells were strongly positive (>90% cells positive) for CD44, CD90 and major histocompatibility complex (MHC) class I, and moderately positive (60-80% cells positive) for CD11a/CD18, CD105 and MHC class II by flow cytometry. SF-derived cells were negative for CD34 and CD45. Under specific nutrient conditions, SF-derived cells differentiated into osteogenic, chondrogenic, adipogenic and tenogenic lineages, as indicated by the expression of specific marker genes and by the production of specific extracellular matrices. Chondrogenic induction in culture resulted in a change in cell shape to a 'stone-wall' appearance and formation of a gelatinous sheet that was intensely stained with Alcian blue. SF may be a novel source of multipotent mesenchymal stem cells with the ability to regenerate chondrocytes. PMID:25151209
Murata, D; Miyakoshi, D; Hatazoe, T; Miura, N; Tokunaga, S; Fujiki, M; Nakayama, K; Misumi, K
In initial work, we developed a 14-day culture protocol under potential GMP, chemically defined conditions to generate chondroprogenitors from human embryonic stem cells (hESCs). The present study was undertaken to investigate the cartilage repair capacity of these cells. The chondrogenic protocol was optimized and validated with gene expression profiling. The protocol was also applied successfully to two lines of induced pluripotent stem cells (iPSCs). Chondrogenic cells derived from hESCs were encapsulated in fibrin gel and implanted in osteochondral defects in the patella groove of nude rats, and cartilage repair was evaluated by histomorphology and immunocytochemistry. Genes associated with chondrogenesis were upregulated during the protocol, and pluripotency-related genes were downregulated. Aggregation of chondrogenic cells was accompanied by high expression of SOX9 and strong staining with Safranin O. Culture with PluriSln1 was lethal for hESCs but was tolerated by hESC chondrogenic cells, and no OCT4-positive cells were detected in hESC chondrogenic cells. iPSCs were also shown to generate chondroprogenitors in this protocol. Repaired tissue in the defect area implanted with hESC-derived chondrogenic cells was stained for collagen II with little collagen I, but negligible collagen II was observed in the fibrin-only controls. Viable human cells were detected in the repair tissue at 12 weeks. The results show that chondrogenic cells derived from hESCs, using a chemically defined culture system, when implanted in focal defects were able to promote cartilage repair. This is a first step in evaluating these cells for clinical application for the treatment of cartilage lesions. PMID:25273540
Cheng, Aixin; Kapacee, Zoher; Peng, Jiang; Lu, Shibi; Lucas, Robert J; Hardingham, Timothy E; Kimber, Susan J
We recently have reported on a novel ankylosis gene that is closely linked to the Enpp1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) gene on chromosome 10. Here, we have discovered novel mutant mice in a Jcl:ICR closed colony with ankylosis in the toes of the forelimbs at about 3 weeks of age. The mutant mice exhibited rigidity in almost all joints, including the vertebral column, which increased with age. These mice also showed hypogrowth with age after 16 weeks due to a loss of visceral fat, which may have been caused by poor nutrition. Histological examination and soft X-ray imaging demonstrated the ectopic ossification of various joints in the mutant mice. In particular, increased calcium deposits were observed in the joints of the toes, the carpal bones and the vertebral column. We sequenced all exons and exon/intron boundaries of Enpp1 in the normal and mutant mice, and identified a G-to-T substitution (c.259+1G>T) in the 5? splice donor site of intron 2 in the Enpp1 gene of the mutant mice. This substitution led to the skipping of exon 2 (73 bp), which generated a stop codon at position 354 bp (amino acid 62) of the cDNA (p.V63Xfs). Nucleotide pyrophosphohydrolase (NPPH) activity of ENPP1 in the mutant mice was also decreased, suggesting that Enpp1 gene function is disrupted in this novel mutant. The mutant mice reported in this study will be a valuable animal model for future studies of human osteochondral diseases and malnutrition. PMID:24770645
Takabayashi, Shuji; Seto, Shintaro; Katoh, Hideki
The use of radiofrequency devices has become widespread for surgical ablation procedures. When ablation devices have been deployed in treatment settings requiring tissue preservation like débridement chondroplasty, adoption has been limited due to the collateral damage caused by these devices in healthy tissue surrounding the treatment site. Ex vivo radiofrequency mediated débridement chondroplasty was performed on osteochondral specimens demonstrating surface fibrillation obtained from patients undergoing knee total joint replacement. Three radiofrequency systems designed to perform débridement chondroplasty were tested each demonstrating different energy delivery methods: monopolar ablation, bipolar ablation, and non-ablation energy. Treatment outcomes were compared with control specimens as to clinical endpoint and histopomorphic characteristics. Fibrillated cartilage was removed in all specimens; however, the residual tissue remaining at the treatment site displayed significantly different characteristics attributable to radiofrequency energy delivery method. Systems that delivered ablation-based energies caused tissue necrosis and collateral damage at the treatment site including corruption of cartilage Superficial and Transitional Zones; whereas, the non-ablation system created a smooth articular surface with Superficial Zone maintenance and without chondrocyte death or tissue necrosis. The mechanism of radiofrequency energy deposition upon tissues is particularly important in treatment settings requiring tissue preservation. Ablation-based device systems can cause a worsened state of articular cartilage from that of pre-treatment. Non-ablation energy can be successful in modifying/preconditioning tissue during débridement chondroplasty without causing collateral damage. Utilizing a non-ablation radiofrequency system provides the ability to perform successful débridement chondroplasty without causing additional articular cartilage tissue damage and may allow for other cartilage intervention success. PMID:20721322
Ganguly, Kumkum; McRury, Ian D; Goodwin, Peter M; Morgan, Roy E; Auge II, Wayne K
ACL reconstruction in adolescents undergoing or being beyond the final growth spurt can be performed as in adults without major concern of growth disturbance. Whereas for the young athlete with wide-open physis a lot of controversy still exists about the technical aspect of the procedure to minimise the risk of growth disturbance. Between 10/1997 and 10/2002 31 children graded Tanner stage 1 or 2 (median age 11 years) with an intraligamental rupture of the anterior cruciate ligament were enrolled. Seventeen patients with coexisting intraarticular damage (meniscus, osteochondral flake) underwent transphsyeal reconstruction of the ACL with the use of an autogenous semitendinosus tendon graft, whereas 14 patients without coexisting pathologies received a nonoperative regime. Growth disturbance, functional and radiographic outcome could be evaluated in 28 patients at a median of 70 months after initial treatment. No patient had clinical or radiological evidence for varus/valgus malalignment or leg length discrepancy. The mean of subsequent body growth within the study population was 20.3 cm. Patients operated on revealed significant (P < 0.05) better clinical (KT-1000 side-to-side difference, pivot shift) and functional results according to the IKDC (median, 95 vs. 87), Lysholm (median, 93 vs. 84) and the Tegner score. More than half of the conservatively treated patients (58%) had subsequent surgery due to persistent instability. Transphyseal reconstruction of intraligamental ACL ruptures with an autologous ST graft yielded superior clinical results if compared to a nonoperative treatment in immature prepubescent patients being Tanner stage 1 and 2. PMID:20130837
Streich, Nikolaus A; Barié, Alexander; Gotterbarm, Tobias; Keil, Maximilian; Schmitt, Holger
Eighteen female New Zealand White rabbits (3.9?±?0.4?kg) were anaesthetized with sufentanil-midazolam by intravenous infusion (SUF-MID, n?=?9) or isoflurane (ISO, n?=?9) for bilateral creation of an osteochondral defect in the medial femur condyle. Subcutaneous premedication with 0.1?mg/kg medetomidine and anaesthesia induction by intravenous infusion of 1.1?µg/kg sufentanil and 0.2?mg/kg midazolam were identical in both groups. During surgery (60?min), the effects on respiratory and circulatory variables serum lactate, total protein and blood glucose were examined. Intermittent positive pressure ventilation (IPPV) was initiated if apnoea lasted>30?s or if end-tidal CO2 ?8?kPa. The righting reflex was lost in 3?min. IPPV was necessary during most of the anaesthesia for most of the rabbits. Maintenance doses during surgery were 2.0?µg/kg/h sufentanil and 0.4?mg/kg/h midazolam, and 1.4% isoflurane, respectively. Mean arterial blood pressure (MAP) was higher in group SUF-MID than group ISO during surgery (63?±?12 vs 50?±?8?mmHg). In group ISO the heart rate was higher during surgery than before anaesthesia (197?±?26 vs 158?±?40 bpm) as was blood glucose (9?±?2 vs 12?±?3?mmol/L). Serum lactate levels remained unchanged whereas total protein decreased in both groups. Time to recover from anaesthesia did not differ between groups (20?min). Intravenous sufentanil-midazolam infusion provided surgical anaesthesia with a higher MAP than isoflurane anaesthesia. The protocol can be useful in situations in which gas anaesthesia cannot be used or in animals with limited cardiovascular reserves. However, IPPV is necessary. PMID:24464922
Hedenqvist, Patricia; Edner, Anna; Jensen-Waern, Marianne
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
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
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
Martig, S; Chen, W; Lee, P V S; Whitton, R C
Background The differences of mechanical and histological properties between cartilage covered by menisci and uncovered by menisci may contribute to the osteoarthritis after meniscectomy and these differences are not fully understood. The purpose of this study is to investigate potential differences in the mechanical and histological properties, and in particular the collagen architecture, of the superficial cartilage layer and subchondral bone between regions covered and uncovered by menisci using immature knee. Methods Osteochondral plugs were obtained from porcine tibial cartilage that was either covered or uncovered by menisci. Investigation of the thickness, mechanical properties, histology, and water content of the cartilage as well as micro-computed tomography analysis of the subchondral bone was performed to compare these regions. Collagen architecture was also assessed by using scanning electron microscopy. Results Compared to the cartilage uncovered by menisci, that covered by menisci was thinner and showed a higher deformity to compression loading and higher water content. In the superficial layer of cartilage in the uncovered regions, collagen fibers showed high density, whereas they showed low density in covered regions. Furthermore, subchondral bone architecture varied between the 2 regions, and showed low bone density in covered regions. Conclusions Cartilage covered by menisci differed from that uncovered in both its mechanical and histological properties, especially with regards to the density of the superficial collagen layer. These regional differences may be related to local mechanical environment in normal condition and indicate that cartilage covered by menisci is tightly guarded by menisci from extreme mechanical loading. Our results indicate that immature cartilage degeneration and subchondral microfracture may occur easily to extreme direct mechanical loading in covered region after meniscectomy. PMID:24669849
In the US and northern Europe, the prevalence of pregnant syphilitic women is estimated at .1-.6%, while in South Africa it was 7.6% in 1982. In 1978, there 108 cases in the US which increased to 268 reported cases in 1985. The increase of congenital syphilis (CS) by 25% from 1985 to 1988 was attributed to the spread of crack cocaine in the US. The rate was 10.5 cases/100,000 live births in the US during this period, a 21% increase. In contrast, in the Netherlands there were 2.5 cases/100,000 live births during 1982-85. Clinical symptoms appear 3 weeks after birth, but some are present at birth such as hepatosplenomegaly, bloated abdomen, cutaneous lesions, and nasal discharge turning into purulent rhinitis. Anemia occurs in 90% of children with CS. Generalized lymphadenopathy, splenomegaly with hepatomegaly, and syphilitic hepatitis may also occur. Syphilitic skeletal abnormalities include osteochondritis, periostitis, osteomyelitis, and osteitis. Meningovascular syphilis produces nervous system effects. CS complications include nephrotic syndrome and acute glomerulonephritis. Ocular abnormalities are caused by treponemes found in the cornea, sclera, uvea, retina and the optic nerve. Chorioretinitis and iridocyclitis are common ocular lesions. The pathogen Treponema pallidum can be diagnosed by dark field microscopy, by immunofluorescence, or by histopathological examination of silver-stained preparations. Pregnancy women with syphilis are treated with penicillin although failures have been reported after single or 2 or 3 in administrations of 2.4 MU benzathine penicillin and after giving tetracycline in 3rd trimester pregnancy. The CDC recommendation for treating infants with CS is iv 50,000 U/kg penicillin G every 8-12 hours for 10-14 days or im 50,000 U procaine penicillin once daily for 10-14 days. Single administration of 50,000 U/kg benzathine penicillin is recommended for newborn children whose mothers have been treated with erythromycin. PMID:1616961
Boot, J M; Oranje, A P; de Groot, R; Tan, G; Stolz, E
This study investigated the cellular and molecular changes which occur in cartilage from adults with femoral neck fracture (FNF) and osteoarthritis (OA), and explored the similarities in hip cartilage obtained from elderly patients and patients with early OA. Femoral heads were retrieved from 23 female patients undergoing total hip arthroplasty (THA). This group included 7 healthy patients with FNF (hFNF), 8 elderly adults with FNF (eFNF), and 8 elderly patients with hip OA (OA). After high-field MRI T2 mapping, osteochondral plugs were harvested from the weight-bearing area of femoral heads for subsequent macroscopic, histologic, and immunochemical evaluation. Additionally, the contents of cartilage matrix were analyzed, and gene expression was detected. The surface of cartilage from hFNF and eFNF patients appeared smooth, regular, and elastic, whereas it showed irregularities, thinning, and defects in OA patients. Elevated T2 values and decreased accumulation of glycosaminoglycans (GAGs) were detected in cartilage from eFNF patients. Furthermore, type I collagen accumulation was slightly increased and type X collagen concentration was obviously elevated in eFNF patients; however, type II collagen distribution and the contents and anisotropy of collagen fibrils in eFNF patients showed no significant changes. Consistent with histology and immunohistochemical results, aggrecan was downregulated and type X collagen was upregulated, while collagens types I and II showed no significant changes in eFNF patients. The cellular and molecular characteristics of hip cartilage in eFNF patients who showed no symptoms of OA were similar to those in patients with mild OA. Thus, eFNF cartilage can serve as a comparative specimen for use in studies investigating early OA. PMID:25400727
Wei, Bo; Gu, Qiangrong; Li, Dong; Yan, Junwei; Guo, Yang; Mao, Fengyong; Xu, Yan; Zang, Fengchao; Wang, Liming
It is widely accepted that canonical Wnt (cWnt) signaling is required for the differentiation of osteoprogenitors into osteoblasts. Furthermore, tumor-derived secretion of the cWnt-antagonist Dickkopf-1 (Dkk-1) is known to cause bone destruction, inhibition of repair and metastasis in many bone malignancies, but its role in osteosarcoma (OS) is still under debate. In this study, we examined the role of Dkk-1in OS by engineering its overexpression in the osteochondral sarcoma line MOS-J. Consistent with the known role of Dkk-1 in osteoblast differentiation, Dkk-1 inhibited osteogenesis by the MOSJ cells themselves and also in surrounding tissue when implanted in vivo. Surprisingly, Dkk-1 also had unexpected effects on MOSJ cells in that it increased proliferation and resistance to metabolic stress in vitro and caused the formation of larger and more destructive tumors than controls upon orthotopic implantation. These effects were attributed in part to upregulation of the stress response enzyme and cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1). Direct inhibition of ALDH1 reduced viability under stressful culture conditions, whereas pharmacological inhibition of cWnt or overexpression of ALDH1 had a protective effect. Furthermore, we observed that ALDH1 was transcriptionally activated in a c-Jun-dependent manner through a pathway consisting of RhoA, MAP-kinase-kinase-4 and Jun N-terminal Kinase (JNK), indicating that noncanonical planar cell polarity-like Wnt signaling was the mechanism responsible. Together, our results therefore demonstrate that Dkk-1 enhances resistance of OS cells to stress by tipping the balance of Wnt signaling in favor of the non-canonical Jun-mediated Wnt pathways. In turn, this results in transcriptional activation of ALDH1 through Jun-responsive promoter elements. This is the first report linking Dkk-1 to tumor stress resistance, further supporting the targeting of Dkk-1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells. PMID:24577091
Krause, U; Ryan, D M; Clough, B H; Gregory, C A
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
van Weeren, P René; Jeffcott, Leo B
Cartilage degeneration of the knee joint is considered to be a largely mechanically driven process. We conducted a microstructural and histomorphometric analysis of subchondral bone samples of intact cartilage and in samples with early and higher- grade arthritic degeneration to compare the different states and correlate the findings with the condition of hyaline cartilage. These findings will enable us to evaluate changes in biomechanical properties of subchondral bone during the evolution of arthritic degeneration, for which bone density alone is an insufficient parameter. From a continuous series of 80 patients undergoing implantation of total knee endoprosthesis 30 osteochondral samples with lesions macroscopically classified as ICRS grade 1b (group A) and 30 samples with ICRS grade 3a or 3b lesions (group B) were taken. The bone samples were assessed by 2D histomorphometry (semiautomatic image analysis system) and 3D microstructural analysis (high-resolution micro-CT system). The cartilage was examined using the semiquantitative real-time PCR gene expression of collagen type I and II and aggrecan. Both histomorphometry and microstructural and biomechanical analysis of subchondral bone in groups A and B consistently revealed progressive changes of both bone and cartilage compared with healthy controls. The severity of cartilage degeneration as assessed by RT PCR was significantly correlated with BV/TV (Bone Volume Fraction), Tb.Th (Trabecular Thickness) showed a slight increase. Tb.N (Trabecular Number), Tb.Sp (Trabecular separation) SMI (Structure Model Index), Conn.D (Connectivity Density) and DA (Degree of Anisotropy) were inversely correlated. We saw sclerotic transformation and phagocytic reticulum cells. Bone volume fraction decreased with an increasing distance from the cartilage with the differences compared with healthy controls becoming greater in more advanced cartilage damage. The density of subchondral bone alone is considered an unreliable parameter for classifying changes evolving over time. The progressive damage of subchondral bone seen in the present study correlates well with cartilage changes. Trabecular orientation is also impaired, which explains the changes in biomechanical parameters and the inadequate load transfer and excessive loading of cartilage. Besides subchondral bone density, which in turn correlates with cartilage thickness, other parameters such as structure model index and grade of anisotropy best reflect mechanical properties such as Young modulus, compressive strength, tensile stress, and failure energy. However, it remains unclear whether the mechanical interaction of the mineralized subchondral tissues with articular cartilage works vice versa. The possibility of a biochemical signalling from the degenerating cartilage via the synovial fluid and bone- cartilage crosstalks via subchondral pores may indeed explain a certain depth-dependency of subchondral bone changes. PMID:24828695
Lahm, Andreas; Kasch, Richard; Spank, Heiko; Erggelet, Christoph; Esser, Jan; Merk, Harry; Mrosek, Eike
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.
Park, Grace Eunseung
The development of bioengineered cartilage for replacement of damaged articular cartilage has gained momentum in recent years. One such approach has been developed in the Kandel lab, whereby cartilage is formed by seeding primary articular chondrocytes on the top surface of a porous biodegradable calcium polyphosphate (CPP) bone substitute, permitting anchorage of the tissue within the pores of the substrate; however, the interfacial shear properties of the tissue-substrate interface of these biphasic constructs are 1 to 2 orders of magnitude lower than the native cartilage-subchondral bone interface. To overcome this limitation, a strategy was devised to generate a zone of calcified cartilage (ZCC), thereby mimicking the native architecture of the osteochondral junction; however, the ZCC was located slightly above the cartilage-CPP interface. Thus, it was hypothesized that polyphosphate released from the CPP substrate and accumulating in the tissue inhibits the formation of the ZCC at the tissue-substrate interface. Based on this information, a strategy was devised to generate biphasic constructs incorporating a properly located ZCC. This approach involved the application of a thin calcium phosphate film to the surfaces of porous CPP via a sol-gel procedure, thereby limiting the accumulation of polyphosphate in the cartilaginous tissue. This modification to the substrate surface did not negatively impact the quality of the in vitro-formed cartilage tissue or the ZCC. Interfacial shear testing of biphasic constructs demonstrated significantly improved interfacial shear properties in the presence of a properly located ZCC. These studies also led to the observation that chondrocytes produce endogenous polyphosphate and that its levels in deep zone cartilage appear inversely related to mineral deposition within the tissue. Using an in vitro model of cartilage calcification, it was demonstrated that polyphosphate levels are modulated in part by the inhibitory effects of fibroblast growth factor 18 on exopolyphosphatase activity in the tissue. Polyphosphate also appears to act in a feedback loop to control exopolyphosphatase activity. Interestingly, polyphosphate also exhibits positive effects on cartilage matrix accumulation. The potential implication of polyphosphate in the maintenance of articular cartilage homeostasis is intriguing and must be investigated further.
Background Slipped capital femoral epiphysis (SCFE), causing posterior and inferior displacement and retroversion of the femoral head, is a well-recognized etiology for femoroacetabular impingement (FAI) and can lead to premature arthritis in the young adult. The treatment of malunited SCFE remains controversial. Surgical dislocation and subcapital correction osteotomy (SCO) has been described as a powerful method to correct the proximal femoral deformity. Methods Between January 2003 and January 2010, 11 patients (12 hips) with closed femoral physes and symptomatic FAI from malunited SCFE were treated with surgical dislocation and SCO. We performed a retrospective review of patient histories, physical exams, operative findings, and pre and postoperative anteroposterior (AP) and groin lateral (GLat) radiographs. Mean follow-up was 61 months. Results There were 4 female and 7 male patients with an average age of 15 years at the time of SCO. On the AP radiograph the mean inferior femoral head displacement (AP epiphyseal-neck angle) was significantly improved (-26° to -6°, p<0.001). On the groin lateral radiograph the mean posterior femoral head displacement (Lateral epiphyseal-neck angle) was significantly improved (-45° to -3°, p<0.001). The mean alpha angle was also significantly improved on both views (AP: 85° to 56°, P<0.001; GLat: 85° to 46°, p<0.001). Operative findings included one femoral osteochondral defect, 8 Outerbridge grade 3-4 acetabular cartilage lesions, and 10 labral lesions. Significant improvement of the mean Harris hip score (HHS) was seen at latest follow-up (54 to 77, p=0.016). Complications occurred in 4 of the 12 cases with AVN in two patients, a worse postoperative HHS in one patient, and failure of fixation treated successfully with revision open reduction internal fixation in one patient. Conclusions Subcapital correction osteotomy as an adjunct to surgical dislocation and osteochondroplasty can be used to correct the deformity of the proximal femur associated with malunited SCFE. Normalization of proximal femoral anatomy may postpone progression to severe osteoarthritis and thus delay the need for arthroplasty in this young patient population. However, surgeons and patients should be aware that the risks of this procedure in this population are significant. PMID:23653020
Anderson, Lucas A.; Gililland, Jeremy; Pelt, Christoper; Peters, Christopher L.
Background: Ankle sprains may damage both the lateral ligaments of the hindfoot and the osteochondral tissue of the ankle joint. When nonoperative treatment fails, operative approaches are indicated to restore both native motion patterns at the hindfoot and ankle joint contact mechanics. The goal of the present study was to determine the effect of lateral ligament injury, repair, and reconstruction on ankle joint contact mechanics and hindfoot motion patterns. Methods: Eight cadaveric specimens were tested with use of robotic technology to apply combined compressive (200-N) and inversion (4.5-Nm) loads to the hindfoot at 0° and 20° of plantar flexion. Contact mechanics at the ankle joint were simultaneously measured. A repeated-measures experiment was designed with use of the intact condition as control, with the other conditions including sectioned anterior talofibular and calcaneofibular ligaments, the Broström and Broström-Gould repairs, and graft reconstruction. Results: Ligament sectioning decreased contact area and caused a medial and anterior shift in the center of pressure with inversion loads relative to those with the intact condition. There were no significant differences in inversion or coupled axial rotation with inversion between the Broström repair and the intact condition; however, medial translation of the center of pressure remained elevated after the Broström repair relative to the intact condition. The Gould modification of the Broström procedure provided additional support to the hindfoot relative to the Broström repair, reducing inversion and axial rotation with inversion beyond that of intact ligaments. There were no significant differences in center-of-pressure excursion patterns between the Broström-Gould repair and the intact ligament condition, but this repair increased contact area beyond that with the ligaments intact. Graft reconstruction more closely restored inversion motion than did the Broström-Gould repair at 20° of plantar flexion but limited coupled axial rotation. Graft reconstruction also increased contact areas beyond the lateral ligament-deficient conditions but altered center-of-pressure excursion patterns relative to the intact condition. Conclusions: No lateral ankle ligament reconstruction completely restored native contact mechanics of the ankle joint and hindfoot motion patterns. Clinical Relevance: Our results provide a rationale for conducting long-term, prospective, comparative, in vivo studies to assess the impact of altered mechanics following lateral ligament injury, and its nonoperative and operative treatment, on the development of ankle osteoarthritis. PMID:20962188
Prisk, Victor R.; Imhauser, Carl W.; O'Loughlin, Padhraig F.; Kennedy, John G.
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
Camasta, C A
Background Chronic lateral ankle instability often accompanies intra-articular lesions, and arthroscopy is often useful in diagnosis and treatment of intra-articular lesions. Methods Preoperative magnetic resonance imaging (MRI) examinations and arthroscopic findings were reviewed retrospectively and compared in 65 patients who underwent surgery for chronic lateral ankle instability from January 2006 to January 2010. MR images obtained were assessed by two radiologists, and the inter- and intra-observer reliability was calculated. American Orthopedic Foot and Ankle Society (AOFAS) and visual analogue scale (VAS) scores were evaluated. Results Abnormalities of the anterior talofibular ligament (ATFL) were found in all 65 (100%) cases. In arthroscopy examinations, 33 (51%) cases had talar cartilage lesions, and 3 (5%) cases had 'tram-track' cartilage lesion. Additionally, 39 (60%) cases of synovitis, 9 (14%) cases of anterior impingement syndrome caused by osteophyte, 14 (22%) cases of impingement syndrome caused by fibrotic band and tissue were found. Sensitivity of MRI examination for each abnormality was: ATFL, 60%; osteochondral lesion of talus (OLT), 46%; syndesmosis injury, 21%; synovitis, 21%; anterior impingement syndrome caused by osteophyte, 22%. Paired intra-observer reliability was measured by a kappa statistic of 0.787 (95% confidence interval [CI], 0.641 to 0.864) for ATFL injury, 0.818 (95% CI, 0.743 to 0.908) for OLT, 0.713 (95% CI, 0.605 to 0.821) for synovitis, and 0.739 (95% CI, 0.642 to 0.817) for impingement. Paired inter-observer reliability was measured by a kappa statistic of 0.381 (95% CI, 0.241 to 0.463) for ATFL injury, 0.613 (95% CI, 0.541 to 0.721) for OLT, 0.324 (95% CI, 0.217 to 0.441) for synovitis, and 0.394 (95% CI, 0.249 to 0.471) for impingement. Mean AOFAS score increased from 64.5 to 87.92 (p < 0.001) when there was no intra-articular lesion, from 61.07 to 89.04 (p < 0.001) in patients who had one intra-articular lesion, and from 61.12 to 87.6 (p < 0.001) in patients who had more than two intra-articular lesions. Conclusions Although intra-articular lesion in patients with chronic lateral ankle instability is usually diagnosed with MRI, its sensitivity and inter-observer reliability are low. Therefore, arthroscopic examination is strongly recommended because it improved patients' residual symptoms and significantly increased patient satisfaction. PMID:23205239
Kim, Hyoung Soo; Chung, Soo Tai; Yoo, Jeong Hyun; Park, Jai Hyung; Kim, Joo Hak; Hyung, Jae Won
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.
Background We have developed crosslinked salmon-derived atelocollagen sponge, which has a denaturation temperature of 47 degrees Celsius. The purpose of this study is to evaluate the fundamental in vivo efficacy of the osteogenic protein (OP) -1 containing salmon-derived collagen sponge disc (SCS) on cartilage regeneration, using a rabbit model. Methods A total of 24 rabbits were used in this study. In each animal, a full-thickness osteochondral defect was created in each femoral trochlea. Then, each 12 rabbits were randomly divided into the two groups. In Group I, an OP1-SCS disc was implanted into the defect in the right knee. In Group II, a SCS disc without OP-1 was implanted into the defect in the right knee. A control group of 12 rabbits was assembled from randomly-selected left knees from among the first two groups. In Group-III, we applied no treatment for a defect in the left knee to obtain the untreated control. All rabbits were sacrificed at 12 weeks after surgery. In each group, 10 animals were used for histological and immunohistological evaluations, and the remaining 2 were used for real-time polymerase chain reaction (PCR) analyses. Results In Group I, a regenerated cartilage tissue rich in proteoglycan and type-2 collagen was found at 12 weeks, although the width was thicker than that of Group II. In Group II, the defect was filled with thick inhomogeneous tissues, including cartilage, fibrous, and bone tissues at 12 weeks. Concerning the gross observation and histological scores at 12 weeks, the ANOVA showed significant differences (p?0.0001, and p?0.0001, respectively). The post-hoc test indicated that the gross observation and histological scores of Group I was significantly greater than those of Groups II (p?=?0.035, and p?=?0.0104, respectively) and III (p?0.0001, and p?0.0001, respectively), while Group II was significantly greater than Group III (p?=?0.0069, and p?=?0.005, respectively). The real time PCR analysis showed that gene expression of type-2 collagen and aggrecan of Group I was greater than that of Group II. Conclusions The present study clearly demonstrated that the implantation of the OP1-SCS disc without any cultured cells may induce spontaneous hyaline-like cartilage regeneration to greater degrees than implantation of only the salmon-derived collagen sponge disc. PMID:23721417