The Role of Immunologic Response in Fresh Osteochondral Allografting of the Knee
The American Journal of Sports Medicine (Impact Factor: 4.36). 02/2014; 42(4). DOI: 10.1177/0363546513518733
BACKGROUND:Osteochondral allografting, a restorative treatment option for articular cartilage lesions in the knee, involves transplantation of fresh osteochondral tissue with no tissue matching. Although retrieval studies have not consistently shown evidence of immunologic response, development of anti-human leukocyte antigen class I cytotoxic antibodies has been observed in allograft recipients. HYPOTHESIS:Postallograft antibody formation is related to graft size and may affect clinical outcome. STUDY DESIGN:Case-control study; Level of evidence, 3. METHODS:This study retrospectively compared 42 antibody-positive postallograft patients with 42 antibody-negative patients. Groups were matched for age, sex, and body mass index but not intra-articular disease severity. Seventeen patients (20%) were lost to follow-up. Of the remaining 67 patients (33 antibody-positive and 34 antibody-negative), average follow-up time was 50.3 months (range, 24-165 months). Mean age was 38.1 years (range, 15-68 years) with 58% being male. Graft area was categorized as small (<5 cm(2)), medium (5-10 cm(2)), or large (>10 cm(2)). Graft survival and Knee Society function scores were used to measure clinical outcome. RESULTS:Of the 84 patients, 80 had graft area data. Of 27 patients with large graft area, 19 (70%) had positive postoperative antibody screens, compared with 1 of 16 (6%) with small graft area (P < .001). Graft survival rates in the antibody-positive and antibody-negative groups were 64% and 79%, respectively (P = .152). Mean postoperative Knee Society function scores in surviving antibody-positive and antibody-negative groups were 88.3 and 84.6 points, respectively (P = .482). CONCLUSION:Antibody development after fresh, non-tissue-matched osteochondral allograft transplants in the knee appears related to graft size. No difference was observed in clinical outcome between groups. Graft survival is multifactorial, and the effect that the immunologic response has on clinical outcome merits further investigation.
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ABSTRACT: Cartilage matrix is a promising material for cartilage regeneration given the evidence supporting its chondroinductive character. The “raw materials” of cartilage matrix can serve as building blocks and signals for tissue regeneration. These matrices can be created by chemical or physical processing: physical methods disrupt cellular membranes and nuclei but may not fully remove all cell components and DNA, whereas chemical methods combined with physical methods are effective in fully decellularizing such materials. It is important to delineate between the sources of the cartilage matrix, that is, derived from matrix in vitro or from native tissue, and then to further characterize the cartilage matrix based on the processing method, decellularization or devitalization. With these distinctions, four types of cartilage matrices exist: decellularized native cartilage (DCC), devitalized native cartilage (DVC), decellularized cell-derived matrix (DCCM), and devitalized cell-derived matrix (DVCM). One currently marketed cartilage matrix device is decellularized, although trends in patents suggest additional decellularized products may be available in the future. To identify the most relevant source and processing for cartilage matrix, testing needs to include targeting the desired application, optimizing delivery of the material, identify relevant FDA regulations, assess availability of materials, and immunogenic properties of the product.Advanced Healthcare Materials 07/2014; 4(1). DOI:10.1002/adhm.201400165 · 5.80 Impact Factor
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ABSTRACT: Osteochondral allograft (OCA) transplantation is a single-stage technique that transfers viable, mature hyaline cartilage and subchondral bone into size-matched chondral or osteochondral defects. Over the last decade, improvements in allograft storage, harvest, and surgical technique have resulted in encouraging clinical results. Recent clinical success in high demand patient populations has generated a significant amount of interest in OCA transplantation as a primary treatment for a wide spectrum of large cartilage lesions, including post-traumatic defects, osteochondritis dissecans, and focal osteonecrosis. OCA transplantation is also indicated as a salvage procedure following failure of other cartilage repair techniques. The use of OCA, however, is limited by donor availability and size matching, disease transmission and screening, chondrocyte viability, and a demanding surgical technique. This review discusses the basic science, clinical evaluation, and indications for OCA transplantation, with a focus on surgical technique, rehabilitation, and clinical outcomes in the knee.Operative Techniques in Orthopaedics 08/2014; 24(4). DOI:10.1053/j.oto.2014.05.007
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ABSTRACT: Xenogeneic or allogeneic chondrocytes hold great potential to build up new cartilage in vivo. However, immune rejection is a major concern for the utility of universal donor-derived cells. In order to verify the reported immune privilege of chondrocytes in vivo, the aim of this study was to assess engraftment of human articular chondrocytes (HAC) in minipig knee cartilage defects and their contribution to cartilage regeneration. HAC were transplanted matrix-assisted within two hydrogels into full-thickness cartilage defects of minipigs or implanted ectopically into immune deficient mice to assess redifferentiation capacity. At 2 and 4 weeks after surgery, cell-persistence and host cell invasion were monitored by species-specific in situ hybridization and RT-PCR. Early tissue regeneration was evaluated by histomorphometry and a modified O'Driscoll score. HAC capable of successful in vivo chondrogenic redifferentiation persisted at ectopic sites for 4 weeks in both carrier materials. Early defect regeneration involved extensive host cell invasion and a decline of HAC to less than 5 % of initial cell numbers in 6/12 defects within 2 weeks. Few clusters of persisting HAC within collagen type II-rich tissue were surrounded by porcine macrophages. Four weeks after cell transplantation, most of the defects contained well-integrated cell-rich tissue free of human cells with no apparent difference between hydrogel carriers. In summary, HAC failed to engraft in porcine articular cartilage defects despite their ability for successful in vivo redifferentiation. The co-localization of macrophages to hydrogel-implanted HAC suggests active graft rejection without evidence for an immune-privileged status of xenogeneic chondrocytes in a large animal joint.Cell and Tissue Research 08/2014; 358(3). DOI:10.1007/s00441-014-1982-x · 3.57 Impact Factor
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