In vivo efficacy of fresh versus frozen osteochondral allografts in the goat at 6 months is associated with PRG4 secretion

The long‐term efficacy of osteochondral allografts is due to the presence of viable chondrocytes within graft cartilage. Chondrocytes in osteochondral allografts, especially those at the articular surface that normally produce the lubricant proteoglycan‐4 (PRG4), are susceptible to storage‐associated death. The hypothesis of this study was that the loss of chondrocytes within osteochondral grafts leads to decreased PRG4 secretion, after graft storage and subsequent implant. The objectives were to determine the effect of osteochondral allograft treatment (FROZEN vs. FRESH) on secretion of functional PRG4 after (i) storage, and (ii) 6 months in vivo in adult goats. FROZEN allograft storage reduced PRG4 secretion from cartilage by ～85% compared to FRESH allograft storage. After 6 months in vivo, the PRG4‐secreting function of osteochondral allografts was diminished with prior FROZEN storage by ～81% versus FRESH allografts and by ～84% versus non‐operated control cartilage. Concomitantly, cellularity at the articular surface in FROZEN allografts was ～96% lower than FRESH allografts and non‐operated cartilage. Thus, the PRG4‐secreting function of allografts appears to be maintained in vivo based on its state after storage. PRG4 secretion may be not only a useful marker of allograft performance, but also a biological process protecting the articular surface of grafts following cartilage repair. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 880–886, 2013     

Time Course of Biological Activity in Fresh Murine Osteochondral Allografts Paralleled to the Recipient's Immune Response

The use of fresh osteochondral allografts is a popular approach to treat articular cartilage lesions. Immunological reactions of the recipient elicited by the allograft's osseous portion, however, frequently result in their deterioration. So far, little emphasis has been put on describing morphology and biological activity in fresh allografts and paralleling these to the immunological processes triggered in the host. Therefore, in the present study murine neonatal femora, serving as osteochondral grafts, were transplanted as fresh isografts (controls) or allografts (the latter in non- or presensitized mice) and retrieved after 2, 5, 10, and 20 days. It was shown that (1) in isografts active bone cells (osteoblasts, osteoclasts) were present, the bone marrow was repopulated with hematopoietic cells, the diaphysis increased in length, and no specific immunological reaction by the recipient was evoked. (2) Allografts transplanted into nonsensitized hosts initially appeared similar as isografts, but activated T lymphocytes at the transplantation site preceded loss of active bone cells within the graft and development of fibrosis within the marrow cavity. (3) In allografts transplanted into presensitized recipients, severe deterioration of the graft was observed with very few active bone cells, accompanied by an invasion of T lymphocytes and fibrosis in the marrow cavity already in early stages.

Similar to vital organ transplantation, the function of cells within osteochondral allografts is severely impaired after being recognized by the immune system. Therefore, emphasis has to be placed on the development of procedures preserving cartilage biology while reducing the antigenicity of the allograft's osseous portion.     

Time course of biological activity in fresh murine osteochondral allografts paralleled to the recipient's immune response.

The use of fresh osteochondral allografts is a popular approach to treat articular cartilage lesions. Immunological reactions of the recipient elicited by the allograft's osseous portion, however, frequently result in their deterioration. So far, little emphasis has been put on describing morphology and biological activity in fresh allografts and paralleling these to the immunological processes triggered in the host. Therefore, in the present study murine neonatal femora, serving as osteochondral grafts, were transplanted as fresh isografts (controls) or allografts (the latter in non- or presensitized mice) and retrieved after 2, 5, 10, and 20 days. It was shown that (1) in isografts active bone cells (osteoblasts, osteoclasts) were present, the bone marrow was repopulated with hematopoietic cells, the diaphysis increased in length, and no specific immunological reaction by the recipient was evoked. (2) Allografts transplanted into nonsensitized hosts initially appeared similar as isografts, but activated T lymphocytes at the transplantation site preceded loss of active bone cells within the graft and development of fibrosis within the marrow cavity. (3) In allografts transplanted into presensitized recipients, severe deterioration of the graft was observed with very few active bone cells, accompanied by an invasion of T lymphocytes and fibrosis in the marrow cavity already in early stages. Similar to vital organ transplantation, the function of cells within osteochondral allografts is severely impaired after being recognized by the immune system. Therefore, emphasis has to be placed on the development of procedures preserving cartilage biology while reducing the antigenicity of the allograft's osseous portion.     

The fate of articular cartilage after transplantation of fresh and cryopreserved tissue-antigen-matched and mismatched osteochondral allografts in dogs

The long-term success of massive osteochondral allografts depends not only on the incorporation of the transplanted articular cartilage. Osteochondral allografts are immunogenic, and, once an immune response is stimulated by exposure to donor cellular antigens, the cartilage becomes vulnerable to direct injury by cytotoxic antibodies or by lymphocytes, or to indirect injury by inflammatory mediators and enzymes induced by the immune response. To clarify the role of histocompatibility antigen-matching on the health of transplanted articular cartilage, we orthotopically implanted canine leukocyte antigen-matched and mismatched proximal osteochondral allografts of the radius, both fresh and cryopreserved, in beagles. Four groups of dogs received: (1) canine leukocyte antigen-mismatched frozen allografts, (2) canine leukocyte antigen-mismatched fresh allografts, (3) canine leukocyte antigen-matched fresh allografts, or (4) canine leukocyte antigen-matched frozen allografts. In twelve of the dogs, the contralateral leg was subjected to a sham operation, and in ten of the dogs, the proximal part of the radius was removed and replaced as an autogenous graft control. All animals were followed for eleven months after the operation and then were killed. The cartilage of the grafts was evaluated grossly, histologically, and biochemically. The biochemical analysis consisted of measurement of dry weight, content of glycosaminoglycan and hydroxyproline, and galactosamine-to-glucosamine ratios. Analyses of variance were used to study the effect of tissue antigen-matching and freezing on degradation of cartilage. During the study, no dog had grossly obvious clinical abnormalities, all host-graft interfaces healed, and no joints dislocated. The gross appearance of the cartilage was normal for both the joints that had an autogenous graft and those that were subjected to the sham operation. The cartilage of all allografts was thinned, dull, and roughened. The synovial membrane of all of the joints that had been operated on was mildly fibrotic and hyperplastic, but only that of the dogs that had an allograft was severely fibrotic and hyperplastic and demonstrated an inflammatory response. The inflammatory response was most severe in joints that had received a fresh canine leukocyte antigen-mismatched allograft. Invasive pannus was more frequent in joints that had received a fresh graft, particularly those that had received a canine leukocyte antigen-mismatched allograft, and cartilage was sometimes eroded to subchondral bone. Freezing was harmful to the cartilage. Very few cells survived the freezing procedure, and frozen grafts received s significantly worse histological scores had significantly less glycosaminoglycans and had a lower ratio of galactosamine to glucosamine than fresh grafts.     

Repair of cartilage lesions using biological implants. A comparative histological and biomechanical study in goats

We report the experimental use of three different biological implants to restore articular surface defects: glutaraldehyde-fixed bovine meniscal xenograft, glutaraldehyde-fixed bovine costal cartilage xenograft, and viable osteochondral allografts. The grafts were implanted in the knees of 19 goats who were allowed free-field activity and were studied for up to one year. The natural articular surfaces of meniscal fibrocartilage provided excellent articular surfaces at all times. Equally good articular surfaces were restored by host tissue growth covering costal cartilage grafts at six months, but by 12 months this surface had degenerated. The majority of the allografts survived and integrated with the host at six months, but many showed signs of failure at 12 months. Only three out of seven ungrafted defects healed completely at six months and the healed surfaces were degenerating at 12 months.     

Articular cartilage injuries

The acute and repetitive impact and torsional joint loading that occurs during participation in sports can damage articular surfaces causing pain, joint dysfunction, and effusions. In some instances, this articular surface damage leads to progressive joint degeneration. Three classes of chondral and osteochondral injuries can be identified based on the type of tissue damage and the repair response: (1) damage to the joint surface that does not cause visible mechanical disruption of the articular surface, but does cause chondral damage and may cause subchondral bone injury; (2) mechanical disruption of the articular surface limited to articular cartilage; and (3) mechanical disruption of articular cartilage and subchondral bone. In most instances, joints can repair damage that does not disrupt the articular surface if they are protected from additional injury. Mechanical disruption of articular cartilage stimulates chondrocyte synthetic activity, but it rarely results in repair of the injury. Disruption of subchondral bone stimulates chondral and bony repair, but it rarely restores an articular surface that duplicates the biologic and mechanical properties of normal articular cartilage. In selected patients, surgeons have used operative treatments including penetrating subchondral bone, soft tissue grafts, and cell transplants and osteochondral autografts and allografts to restore articular surfaces after chondral injuries. Experimental studies indicate that use of artificial matrices and growth factors also may promote formation of a new joint surface. However, an operative treatment of an articular surface injury that will benefit patients must not just provide a new joint surface, it must produce better long-term joint function than would be expected if the injury was left untreated or treated by irrigation and debridement alone. Therefore, before selecting a treatment for a patient with an articular cartilage injury, the surgeon should define the type of injury and understand its likely natural history.     

The viability of articular cartilage in fresh osteochondral allografts after clinical transplantation

The articular cartilage of four fresh osteochondral allografts was biopsied after transplantation, and its viability was studied by autoradiography. The biopsy specimens were labeled with both 3H-cytidine, for newly synthesized ribonucleic acid, and 35S-sulphate, for newly synthesized proteoglycans. The cartilage of a lateral humeral condylar graft at twelve months had 96 to 99 per cent labeled chondrocytes, the articular cartilage of a medial femoral condylar graft at twenty-four months showed 69 to 78 per cent labeled chondrocytes, and the cartilage of a medial tibial-plateau graft at forty-one months had 90 per cent labeled cells. At six years, a lateral tibial-plateau graft had 37 per cent labeled chondrocytes.     

Qualitative Histological Evaluation of Photooxidized Bovine Osteochondral Grafts in Rabbits: A Pilot Study

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

Magnetic resonance imaging of hyaline cartilage regeneration in neocartilage graft implantation

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

Cryopreservation of osteochondral allografts: dimethyl sulfoxide promotes angiogenesis and immune tolerance in mice

BACKGROUND: Although transplantation of cryopreserved bone allografts has become a routine procedure in orthopaedic surgery, biological and immunological impairment remains an unsolved problem that causes clinical failures. Experimental and clinical evidence has indicated that bone grafts that are revascularized early remain viable and contribute to union at the recipient site. Unprotected cryopreservation, used in most bone banks to reduce graft antigenicity, is associated with complete loss of graft viability, potentially contributing to graft failure. The differences in the survival of various cell types during cryopreservation with use of dimethyl sulfoxide, particularly the increased sensitivity of leukocytes to fast freezing, has resulted in a new approach to modulate immunogenicity. On the basis of this concept, it was proposed that a reduction in the immune response and enhanced revascularization of osteochondral allografts could be achieved by rapid cryopreservation with dimethyl sulfoxide. To test this hypothesis, angiogenesis and immune tolerance were quantified in a murine model with use of intravital microscopy. METHODS: Fresh osteochondral tissue and osteochondral tissue that had been cryopreserved with and without dimethyl sulfoxide was transplanted into dorsal skinfold chambers as isografts and as allografts in presensitized and nonsensitized recipient mice. To quantify angiogenesis, the onset of hemorrhages in the vicinity of the grafts and the revascularization of the grafts were determined by means of intravital fluorescence microscopy. To determine the recipient's intravascular immune response to the grafts, the leukocyte-endothelium interaction was assessed on the twelfth day after transplantation. RESULTS: Nine of nine fresh isografts were revascularized at a mean (and standard deviation) of 57 +/- 33 hours, eight of nine isografts that had been cryopreserved with dimethyl sulfoxide were revascularized at 98 +/- 50 hours, and zero of nine isografts that had been cryopreserved without dimethyl sulfoxide were revascularized. Seven of seven fresh allografts were revascularized at 53 +/- 6 hours, and ten of ten allografts that had been cryopreserved with dimethyl sulfoxide were revascularized at 82 +/- 29 hours. However, signs of revascularization faded in four of the seven fresh allografts whereas reperfusion was maintained in the majority (seven) of the ten grafts frozen in the presence of dimethyl sulfoxide. Similar to the findings associated with unprotected frozen isografts, zero of ten unprotected frozen allografts were revascularized. None of the allografts that had been transplanted into presensitized recipients were revascularized, regardless of whether they had been implanted fresh (nine grafts) or had been implanted after protected (eight grafts) or unprotected (nine grafts) freezing. Quantification of the leukocyte-endothelium interaction revealed a reduction in the intravascular immune response to frozen allografts (both protected and unprotected) compared with fresh allografts. CONCLUSION: Osteochondral allografts that had been pretreated by cryopreservation with dimethyl sulfoxide demonstrated improved angiogenesis induction and enhanced immune tolerance compared with unprotected frozen grafts. A selective reduction in donor passenger leukocytes is the proposed mechanism underlying this phenomenon. Clinical Relevance: In the absence of presensitization, cryopreservation with dimethyl sulfoxide appears to reduce the immune response to allografts and to enhance their revascularization; in the presence of presensitization, alternatives to allograft transplantation should be considered since the allografts will be exposed to a deleterious immune response.     

Autologous osteochondral mosaicplasty for treatment of a posttraumatic defect of the lateral tibial plateau: a case report with two-year follow-up

Posttraumatic osteochondral defects following a tibial plateau fracture are common and a serious complication that may lead to the development of posttraumatic arthrosis. Successful reconstruction of the tibial plateau must include restoration of limb alignment, repair of bone defects, restoration of the articular cartilage, and preservation of the menisci. When osteochondral defects are present, the use of bulk bone grafts to restore the original articular surface anatomy of the tibial plateau is difficult due to incongruity between the graft and the original joint surface. Recognizing this, an autologous osteochondral transplantation utilizing the mosaic technique was performed successfully on a 32-year-old male alpine skier with a posttraumatic osteochondral defect following a tibial plateau fracture. At 2 years postsurgery, the patient had regained the capacity to perform most activities of daily living and to participate in sports. Clinical examination revealed an improvement of the Lysholm score from 48 points to 72 points.     

Changes in subchondral bone in cartilage resurfacing--an experimental study in sheep using different types of osteochondral grafts

OBJECTIVE: This article addresses the subchondral bone integrity in cartilage resurfacing by comparing fresh, untreated auto-, xeno-, and photooxidized osteochondral allo- and xenografts. Photooxidation was expected to improve mechanical stability of the osteochondral grafts through an improved linkage of the collagen fibers within the bone matrix. DESIGN: Untreated auto- and xenografts and with photooxidation pretreated allo- and xenografts were surgically implanted in femoral condyles of sheep (n=40). After 2, 6, 12 and 18 months results were evaluated histologically using non-decalcified bone embedded in acrylic resin. Qualitative evaluation was performed with emphasis on bone matrix, biomechanical stability of graft anchorage, formation of cystic lesions, and bone resorption and formation. Quantitative evaluation of the total subchondral bone area was conducted histomorphometrically. Statistical analysis (factorial ANOVA test) was used to compare differences between groups with respect to the percentage of bone matrix and fibrous tissue per section. RESULTS: Subchondral bone resorption was fastest in untreated, fresh autografts, followed by photooxidized allografts, untreated, fresh xenografts and last pretreated photooxidized xenografts. Cystic lesions were seen in all types of grafts, but were most pronounced at 6 months in autografts and least in photooxidized grafts. Cyst-like lesions had subsided substantially in the untreated auto- and photooxidized xenografts, if no graft dislocation occurred during the healing period. Mononuclear cell infiltration and an increase in the presence of multinuclear cells were observed at 2 months, mostly in untreated autografts, followed by photooxidized allo- and untreated xenografts. They were much higher in numbers compared to photooxidized grafts, at least in the early specimens at 2 months. Graft stability was linked to the rate of bone resorption. CONCLUSION: Substantial resorption of the subchondral bone, involving the development of cyst-like lesions, lead to dislocation and finally to cartilage matrix degradation of the grafts. The process of photooxidation decreased the speed of bone resorption in osteochondral grafts and, thus, improved graft stability and cartilage survival. These results suggest that the remodeling of the subchondral bone of the host and the graft within the first 6 months is an important factor in graft stability and overall results of cartilage resurfacing.     

Prolonged-fresh preservation of intact whole canine femoral condyles for the potential use as osteochondral allografts.

Defects in articular cartilage are often repaired with fresh osteochondral grafts. While fresh allografts provide viable chondrocytes, logistic limitations require surgical implantation within seven days of graft harvest. Here, we provide information on cold preservation of whole intact osteochondral materials that retains cartilage cell viability and function, and histologic and biochemical integrity for 28 days. Canine femoral condyles were obtained and stored at 4 degrees C for 14, 21 or 28 days. At the end of the storage period, cartilage was assessed for cell viability, 35S uptake, proteoglycan content and histologic parameters. The most noticeable histologic change was reduced Safranin-O near the cartilage surface with 14 days of cold preservation, but had recovered with 21 and 28 days. Cartilage thicknesses did not vary significantly. Cell viability was >95% at 14 days, 75-98% at 21 days and reduced to 65-90% at 28 days. Cell function measures showed that the level of 35SO4 incorporation was suppressed in samples stored at 4 degrees C. However, no significant differences were seen among groups at 14, 21 or 28 days of cold preservation. This data has implications for tissue banking protocols for osteochondral allograft material obtained for transplantation suggesting that cold preserved allograft material be implanted within 28 days.     

Articular cartilage transplantation. Clinical results in the knee

Between December 1983 and August 1991, 55 consecutive patients (55 knees) who underwent articular cartilage transplantation to their damaged knees were enrolled in the study. Average followup was 75 months (range, 11-147 months). Eight-two percent were younger than 45 years of age. Patients were evaluated through an 18-point scale, with 6 points each allocated to pain, range of motion, and function. An excellent knee was pain free, had full range of motion, and permitted unlimited activity. A good knee allowed full time employment and moderate activity. Eleven of 15 (73%) allografts transplanted 10 or more years ago were still good or excellent at the time of last followup. Overall, 45 of 55 (76%) knees that received the transplants were rated good or excellent. Specifically, 36 of 43 (84%) patients with unipolar transplants regained normal use of their resurfaced knee. The results after bipolar resurfacing were less encouraging, with only six of 12 (50%) knees rated good or excellent. The described technique of osteochondral shell allograft resurfacing of the knee capitalize on the different healing potentials of bone and cartilage by transplanting the viable articular cartilage organ in its entirety along with just enough of the underlying bone to allow for graft incorporation through creeping substitution. The results support the use of fresh osteochondral shell allograft transplantation for the treatment of large, full thickness articular cartilage defects to the medial or lateral femoral condyles and to the patella.     

Development of transplanted fetal bones: differences between isografts and allografts in mice

Allogeneic bone from bone banks frequently is used when large skeletal defects have to be bridged in orthopaedic surgery. Beside immunologic rejection of the graft, the loss in osteogenic potential caused by bone banking procedures may be a major reason for limited clinical success. Similar problems as described for bone have occurred with cartilage and osteochondral transplants. Improving the properties of allogenic bone so that its biologic activity becomes comparable to autologous bone could be substantially beneficial for the outcome of allograft transplantation. To dissect the steps involved in the integration of a fetal osteochondral graft as it matures to bone, the current study compared the development and biologic function of metatarsals from 18-day-old fetal mice freshly transplanted in three different immunologic settings. Morphologic assessment of (1) isografts and (2) allografts in nonsensitized hosts 12 days after transplantation revealed that the grafts bear an intrinsic potential to develop after transplantation. In allografts in nonsensitized hosts, however, a slight alteration in biologic activity as compared with isografts could be detected already in this early phase after transplantation by in situ hybridization for messenger ribonucleic acids encoding extracellular matrix proteins. (3) In contrast to isografts and allografts in nonsensitized hosts, morphologic features and biologic function of allografts transplanted to presensitized hosts were altered severely.     

Reconstruction of skeletal deficits at the knee. A comprehensive osteochondral transplant program

From 1971 to 1982, 110 osteochondral transplants with follow-up evaluation were performed for treatment of skeletal deficits caused by degenerative, traumatic, and neoplastic diseases largely involving the knee joint. Seventy-eight small-fragment fresh allografts were transplanted for repair of old tibial plateau osteochondral fractures, osteonecrosis, and unicompartmental osteoarthritis. Thirty-two large-fragment grafts were performed following en bloc excision of bone tumors. Of these, 22 were allografts, three were vascularized fibular autografts, and seven were a combination of allografts and vascularized fibular autografts. In this large-fragment group, three grafts have been removed for tumor recurrence, two for infection, and one for a stress fracture. The results of these transplants have proved particularly rewarding in the old plateau fractures, for traumatic loss of bone and cartilage (osteonecrosis), and after en bloc excision of giant cell tumors.     

FRESH OSTEOCHONDRAL ALLOGRAFTS: A 6–10-YEAR REVIEW

Background : In young patients with limited articular cartilage damage, osteochondral allografts may offer an alternative to total joint replacement. The survival of chondrocytes after transplantation and the correlation with clinical outcomes was studied. Methods : Between March 1987 and September 1990, nine patients received fresh osteochondral allografts. Three patients received tibial plateau transplants, three received patellar transplants, two received proximal interphalangeal joints and the remaining patient received segmental femoral head allograft. Patient ages ranged from 16–51 years (mean = 30). They have been followed in prospective manner for up to 10 years with clinical, radiographic and histopathological review during that period. Results : Early histological analyses demonstrated preservation of hyaline cartilage. Subsequent analyses from the periphery of some grafts demonstrated chondrocyte death and change from hyaline cartilage to fibrocartilage, but one specimen taken from the centre of tibial plateau graft, nine years after transplantation, demonstrated viable chondrocytes. The three tibial plateau recipients improved at clinical level from an average pre-operative score of 73 (HSS 0–200) to postoperative average of 174 points. Two of those patients receiving patellar allografts improved from 91 points to 181 points on average. The third patella allograft recipient underwent total knee replacement 18 months post-transplantation. The patella was not resurfaced. The proximal interphalangeal joint transplants failed and the femoral head allograft has been lost to follow-up. Conclusions : The clinical success of the tibial plateau and patellar allografts, irrespective of the histological results, has resulted in the formulation of code of specific indications for this operation. Future enthusiasm, although buoyed by the possibility of long-term chondrocyte viability and good clinical results, must be tempered by the ever-present risk of disease transmission.     

Editorial Commentary: Are We Really Ready to Talk About Sports After Osteochondral Allograft Transplantation?

When it comes to return to high-level sports participation, articular cartilage surgical treatment outcomes were historically abysmal, whereas osteochondral allografts have allowed return to sport at rates as high as 88%. However, although osteochondral allograft transplantation effectively reconstructs the damaged articular surface in affected knees, the grafts themselves do nothing to re-establish normal joint homeostasis, resulting in high reoperation rates. Return to sport should require recovery of nearly normal motion and strength, as well as magnetic resonance imaging showing intact cartilage, bony incorporation, and no effusion. These milestones typically occur at 6 months. Persistent joint inflammation and reactivity remain a vexing issue, and long-term durability is of significant concern. In the future, a goal could be to develop biological therapies that could modulate the joint inflammation and catabolism associated with articular cartilage injury.