Chondrogenesis in Repair of Articular Cartilage Defects by Free Periosteal Grafts in Rabbits

The origin of the cartilaginous tissue in articular defects after periosteal grafting was studied histologically in 6-month-old rabbits. The grafts were taken from the tibia and transplanted to artificial defects in the femoral articular cartilage. An isolating Nucleopore filter^®, hindering the penetration of cells, was placed between the graft and the cancellous bone, in order to trace the origin of the proliferating cells. The histological results revealed that the cartilage tissue which proliferated in the defect originated from the periosteal graft and not from the subchondral bone. The effect of the depth of the defect was studied by making a superficial and deep part in the defect. Cartilage tissue was found in both parts of the defect, though there was less in the more superficial defect.     

Repair of articular cartilage defects with cultured chondrocytes in Atelocollagen gel

We attempted to repair full-thickness articular cartilage defects in rabbit knee joints with allogeneic cultured chondrocytes embedded in Atelocollagen gel. An articular cartilage defect was created on the patellar groove of the femur. The defect was filled with chondrocytes cultured in the collagen gel and covered with periosteal flap (G group). In three other experimental groups, the same defects were transplanted with chondrocytes in monolayer culture with periosteal flap (M group), periosteal graft only (P group), or left empty (E group). At 4, 12, and 24 weeks after operation, the reparative tissue was analyzed macroscopically and histologically. At 4 weeks after operation, the surfaces of the reparative tissue were smooth, and the defects were filled with reparative tissues that resembled hyaline cartilage in all four groups. However, the reparative tissues degenerated gradually with time in the M, P, and E groups. In contrast, in the G group, the reparative tissue retained its thickness, and there was a steady integration of the grafted tissue into the adjacent normal cartilage at 24 weeks after operation. The results suggest that transplantation of allogeneic chondrocytes cultured in Atelocollagen gel is effective in repairing an articular cartilage defect.     

Filling the bone defect with osteogenic material

In this experimental study with bone defects, we focussed on the one hand on external and internal osteogenic callus formation after filling the defect and on the other on the osteochondrogenic differentiation capacity of 4-day-old fibrous-like callus grafts and 12-day-old woven bone grafts in an osteogenic environment. A standard cortical bone defect of the femur was created in 95 young rats. The defect was filled with a cortical bone graft and 4- and 12-day-old callus grafts. The grafts were transplanted as such or in Nucleopore chambers. Follow-up was done at 1, 2, 3 and 6 weeks. The osteochondrogenic tissue formed was studied histologically and histomorphometrically. The results suggest that the filling of the bone defect had no influence on the primary external and internal osteogenic callus formation at 1 and 2 weeks. At 3 and 6 weeks in the chamber groups the persisting internal bridging woven bone was converted into more compact lamellar bone whereas periosteal callus remained at the edges of the defect. In the other groups at 3 and 6 weeks the normal shape of the cortex was reconstituting. Four-day-old fibrous-like callus formed bone in the Nucleopore chamber, indicating that fibrous-like callus tissue at 4 days contains osteogenic cells. Twelve-day-old callus consisting of woven bone was partially differentiated to cartilage, showing that woven bone contains cells capable of chondrogenic differentiation.     

Hyaline cartilage degenerates after autologous osteochondral transplantation.

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

Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel

In an attempt to repair articular cartilage, allograft articular chondrocytes embedded in collagen gel, were transplanted into full-thickness defects in rabbit articular cartilage. Twenty-four weeks after the transplantation, the defects were filled with hyaline cartilage, specifically synthesising Type II collagen. These chondrocytes were autoradiographically proven to have originated from the transplanted grafts. Assessed histologically the success rate was about 80%, a marked improvement over the results reported in previous studies on chondrocyte transplantation without collagen gel. By contrast, the defects without chondrocyte transplantation healed with fibrocartilage. Immunological enhancement induced by transplanted allogenic chondrocytes or collagen was not significant at eight weeks after treatment, so far as shown by both direct and indirect blastformation reactions. Thus, allogenic transplantation of isolated chondrocytes embedded in collagen gel appears to be one of the most promising methods for the restoration of articular cartilage.     

Embryonic stem cells form articular cartilage, not teratomas, in osteochondral defects of rat joints

Embryonic stem (ES) cells are considered to be a potential tool for repairing articular cartilage defects, but so far it has been impossible to cause these cells to differentiate into chondrocytes exclusively, either in vivo or in vitro. To explore a potential new cell source of cell transplantation for articular cartilage defects, we transplanted ES cells into articular cartilage defects in immunosuppressed rats. ES cells (AB2.2 or CCE cells) were transplanted into articular cartilage defects in the patellar groove of immunosuppressed rats treated with cyclosporine. The cells were histologically observed until 8 weeks after transplantation. To determine whether the repair tissue in the defect in the AB2.2-transplanted group was derived from the transplanted cells, the neomycin-resistant gene, which had been transfected into AB2.2 cells but does not exist in rat cells, was used for detection. The cells produced cartilage, resulting in repair of the defects from 4 weeks until 8 weeks after the transplantation without forming any teratomas. The neomycin-resistant gene was detected in every sample, demonstrating that the repair tissue in the AB2.2-transplanted group was derived from the transplanted AB2.2 cells. The environment of osteochondral defects is chondrogenic for ES cells. ES cells may thus be a potential tool for repairing articular cartilage defects.     

Repair of articular cartilage defects with cultured chondrocytes on polysulphonic membrane: experimental studies in rabbits

INTRODUCTION: Autologous osteochondral transplantation is one method that can be used to create hyaline or hyaline-like repair in a defect area. The purpose of the present study was to repair full-thickness articular cartilage defects in 9 rabbit knee joints with autologous cultured chondrocytes. METHODS: An articular cartilage defect was created on the patellar groove of the femur. The defect was filled with chondrocytes cultured in vitro and placed into the knee on a polysulphonic membrane. At 8 weeks after the operation, the reparative tissue was analyzed macroscopically and histologically. RESULTS: At 8 weeks after the operation, the surfaces of the reparative tissue were smooth, and the defects were filled with mature hyaline cartilage in 5 cases. In 2 cases, the reparative hyaline cartilage was immature and there was worse integration of grafted tissue into the adjacent normal cartilage. In 2 cases, the surface of the grafted area was irregular, and the reparative tissue was disintegrated and incompletely differentiated. CONCLUSION: The results suggest that transplantation of autologous chondrocytes cultured in vitro and placed into the knee on polysulphonic membrane is effective in repairing an articular cartilage defect.     

Tissue engineered cartilage repair using cryopreserved and noncryopreserved chondrocytes

The objective of this study was to reconstruct full thickness cartilage defects in rabbit knees with in vitro engineered cartilage tissue based on noncryopreserved and cryopreserved chondrocytes in polymer fleece scaffolds. Osteochondral defects in rabbits were filled with polymer cylinders with noncryopreserved or cryopreserved allogeneic chondrocytes and compared with empty defects and defects filled with polymers alone. The defects were evaluated macroscopically and histologically 4 and 12 weeks after surgery. Transplant samples were graded using a semiquantitative score system. Successful healing was defined as complete integration of a hyalinelike and structurally intact cartilage into the defect and occurred in 71% of the group with noncryopreserved chondrocytes after 4 weeks and 100% of the rabbit knees after 12 weeks, whereas hyalinelike cartilage was seen in 71% of the group with cryopreserved chondrocytes after 4 weeks, and in 85% after 12 weeks. No newly formed cancellous bone was present in the subchondral bone. In the control groups, no cartilagelike tissue was seen. Transplantation of chondrocytes in polymer fleece constructs is a suitable approach for joint cartilage repair. Noncryopreserved chondrocytes are preferred to cryopreserved chondrocytes because of their regenerative potential. In vitro engineered cartilage offers broad opportunities for optimization of cartilage transplantation based on the controlled use of morphogenic and biologically active factors such as transforming growth factor-beta and bone morphogenetic proteins.     

Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2)

BACKGROUND: Damaged articular cartilage has a limited ability to repair. Operative removal of damaged cartilage and penetration into the subchondral bone to allow population of the defect with progenitor cells can result in filling of the defect with repair tissue. However, this repair tissue often degenerates over time because of its inability to withstand the mechanical forces to which it is subjected. We previously reported that recombinant human bone morphogenetic protein-2 (rhBMP-2) improves the repair of full-thickness defects of cartilage as long as six months postoperatively. We have now extended that study to examine the quality of the repair tissue at one year. METHODS: Full-thickness defects of cartilage were created in the trochlear groove of twenty-five adult New Zealand White rabbits. Eight defects were left empty, eight were filled with a collagen sponge, and nine were filled with a collagen sponge impregnated with five micrograms of rhBMP-2. The animals were killed at fifty-two weeks postoperatively, and the gross appearance of the healed defect was assessed. The repair tissue was examined histologically and was evaluated, according to a grading scale, by four individuals who were blinded with respect to the treatment. The tissue sections were immunostained with antibodies against type-I collagen, type-II collagen, aggrecan, and link protein. The residence time of the rhBMP-2 in the cartilage defect was evaluated in vivo with use of scintigraphic imaging of radiolabeled protein. RESULTS: One year after a single implantation of a collagen sponge containing five micrograms of rhBMP-2, the defects had a significantly better histological appearance than the untreated defects (those left empty or filled with a collagen sponge). The histological features that showed improvement were integration at the margin, cellular morphology, architecture within the defect, and reformation of the tidemark. The total scores were also better for the defects treated with rhBMP-2 than for the untreated defects, but in no instance was the repair tissue identical to normal articular cartilage. The thickness of the cartilage in the defects treated with rhBMP-2 was 70 percent that of the normal cartilage, an observation that was identical to that at twenty-four weeks postoperatively. Immunostaining demonstrated significantly less type-I collagen in the defects treated with rhBMP-2 than in the untreated defects. Immunostaining for other matrix components showed no difference among the treatment groups. The mean residence time of rhBMP-2 in the cartilage defects was eight days with an elimination half-life of 5.6 days. Detectable amounts of rhBMP-2 were present as long as fourteen days after implantation. CONCLUSIONS: The problems associated with operative repair of cartilage include the formation of fibrocartilage rather than normal articular cartilage and the degeneration of that repair tissue over time. Our results demonstrate that the addition of rhBMP-2 to the operative site after creation of a full-thickness defect results in an improvement in the histological appearance and composition of the extracellular matrix at one year postoperatively. If these experimental results translate directly to the clinical situation, it is possible that the addition of rhBMP-2 to existing operative treatments for the repair of cartilage may improve the repair process and may help to maintain the integrity of the repair tissue.     

Die Implantation von matrixfreien dreidimensionalen Knorpeltransplantaten in standardisierte Knorpeldefekte am Schafskniegelenk

The goal of the current investigation was to make a comparative analysis of regenerative tissue after autologous de novo cartilage transplantation on the femoral condyles of sheep after a chondral defect. One chondral defect measuring 4 mm in diameter was placed in the center of one medial femoral condyle of each of 48 Suffolk sheep. Twelve defects were left to heal spontaneously, 16 defects were covered with periosteal flaps, and 20 defects were filled with autologous de novo cartilage graft. Macroscopic and microscopic assessments were performed at 26 and at 52 weeks. Regeneration was significantly better (p<0.05) in the transplant group than in the control groups at both 26 weeks and 52 weeks. The differences were most evident in the grade of defect filling, cartilage stability, cell distribution, and matrix assessments. Transplantation of immature, autologous de novo cartilage leads to qualitatively better regeneration both macro- and microscopically than does periosteal flap placement alone. The transplanted, immature cartilage tissue undergoes maturation in vivo. The regenerated tissue has hyaline-like features.     

Repair of rabbit articular surfaces with allografts of chondrocytes embedded in collagen gels

In an attempt to restore articular cartilage, allogeneic articular chondrocytes embedded in collagen gels were transplanted onto full-thickness defects in rabbit articular cartilage. Within 24 weeks after the transplantation, the defects were filled with hyaline cartilage, specifically synthesizing type II collagen. These chondrocytes were autoradiographically proven to be originated from the originally transplanted chondrocytes. As histologically assessed, success rate was about 80%, a marked improvement over the results (40% success rate) in previous studies reporting chondrocyte transplantation without collagen gels. On the other hand, the defects without chondrocyte transplantation healed with fibrocartilaginous tissue more than 24 weeks after treatment. Immunological enhancement induced by transplanted allogeneic chondrocytes or collagen was not significant for eight weeks after treatment, so far as shown by both direct and indirect blastformation reactions. Thus, allogeneic transplantation of isolated chondrocytes embedded in collagen gels appears to be one of the most promising methods for the restoration of articular cartilage.     

Rib perichondrial grafts for the repair of full-thickness articular-cartilage defects. A morphological and biochemical study in rabbits

The purpose of this study was to investigate the use of perichondrial grafts in articular cartilage defects and to characterize the newly formed cartilage. In a rabbit model, rib perichondrium was used to repair full-thickness defects in the femoral condyle. The quality of repair was then evaluated histologically and biochemically at six and twelve weeks after grafting. Unacceptable results were obtained in 50 per cent of the rabbits. These failures were due to condylar fracture in 20 per cent, failure of graft attachment in 20 per cent, and infection in 10 per cent. The technique of grafting must be improved to increase the percentage of successful grafts in which neocartilage with a relatively normal chemical composition fills the articular cartilage defect. Successful grafts proliferate to fill the full-thickness defect with neocartilage, which has biochemical characteristics that are similar to those of hyaline cartilage.     

Articular cartilage repair using tissue engineering technique--novel approach with minimally invasive procedure

Articular cartilage has very limited potential to spontaneously heal, because it lacks vessels and is isolated from systemic regulation. Although there have been many attempts to treat articular cartilage defects, such as drilling, microfracture techniques, soft tissue grafts or osteochondral grafts, no treatment has managed to repair the defects with long-lasting hyaline cartilage. Recently, a regenerative medicine using a tissue engineering technique for cartilage repair has been given much attention in the orthopedic field. In 1994, Brittberg et al. introduced a new cell technology in which chondrocytes expanded in monolayer culture were transplanted into the cartilage defect of the knee. As a second generation of chondrocyte transplantation, since 1996 we have been performing transplantation of tissue-engineered cartilage made ex vivo for the treatment of osteochondral defects of the joints. This signifies a concept shift from cell transplantation to tissue transplantation made ex vivo using tissue engineering techniques. We have reported good clinical results with this surgical treatment. However, extensive basic research is vital to achieve better clinical results with this tissue engineering technique. This article describes our recent research using a minimally invasive tissue engineering technique to promote cartilage regeneration.     

Xeno-implantation of pig chondrocytes into rabbit to treat localized articular cartilage defects: an animal model

Articular cartilage has only a limited ability to regenerate. The transplantation of autologous chondrocytes is currently used to treat focal defects in human articular cartilage, although use of organs, tissues, or cells from different species is being investigated as an alternative treatment. The object of this study was to use xeno-transplantation of cultured pig chondrocytes for the repair of rabbit chondral defects, and to analyze the significance of tissue rejection in this animal model. Partial chondral defects, including removal of cartilage tissue and a part of the subchondral bone, were created in the lateral femoral condyles of 30 adult New Zealand White rabbits. A periosteal flap was sutured to the native cartilage with the cambium layer facing the defect. As a control, culture medium was injected into the defect void of one group of rabbits while in a treatment group, chondrocytes, isolated from normal femoral pig cartilage, were injected into the defect void. All rabbits were killed by 24 weeks. Macroscopic changes of the cartilage were analyzed using Mankin's score. The distal femoral portion was studied histologically using hematoxylin and eosin, alcian blue, toluidine blue, and Mason's trichrome. Pig cells and pig genetic material were detected in the neo-synthesized tissue by immunohistochemical detection of SLA-II-DQ and polymerase chain reaction analysis of the gene SLA-II-DQB. The synovial membrane was studied histologically by hematoxylin and eosin staining. In the control group, on average, less than 25 percent of the chondral defect was filled. The repair tissue had an irregular surface with few cells similar to chondrocytes or fibroblasts and a minimal formation of extracellular matrix. In the treatment group, the chondral defect was approximately 90 percent filled with good integration between the neo-synthesized cartilage and the native cartilage. The repair tissue had a smooth surface with cells similar to chondrocytes and a hyaline-like extracellular matrix. The neo-synthesized cartilage was morphologically similar to hyaline cartilage. Importantly, there were no signs of graft-vs.-host rejections or infiltration by immune cells. In the neo-synthesized tissue, pig genetic material was detected in 27 +/- 5 percent of all cells. These cells containing pig genetic material were distributed throughout the neo-synthesized cartilage. We conclude that the xeno-transplantation of chondrocytes could be an alternative method for the repair of articular cartilage defects.     

培养软骨移植修复关节软骨缺损的实验研究

目的：为探讨一种新的关节软骨缺损修复方法。方法：将体外培养２周形成软骨样组织,移植修复兔关节软骨全层缺损。于移植术后２、４、８周分别行功能评价、大体形态及组织学检查。结果：全部实验兔于术后２周内恢复正常活动。２周时移植修复组织由非成熟透明软骨组成。４周时部分移植组出现成熟透明软骨。８周时移植组关节软骨缺损全部由成熟透明软骨充填修复,修复组织与邻近关节软骨融合。培养软骨移植修复关节软骨全层缺损明显优于自身修复（Ｐ＜００１）。结论：本实验提示使用具有高有丝分裂率的软骨细胞,经离心管培养形成骺软骨样组织,植入关节软骨全层缺损后,软骨细胞生长良好,逐渐成熟和转化,能发挥良好的修复作用。     

Chondrocyte transplantation in PGLA/polydioxanone fleece

The transplantation of chondrogenic cells in a supportive carrier structure proved to be a promising alternative for the treatment of cartilage defects. In the study presented we focused on the transplantation of allogeneic chondrocytes in a biodegradable polymer scaffold (PGLA/Polydioxanon) in articular cartilage defects in a rabbit defect model. Isolated allogeneic chondrocytes embedded in a PGLA polymer scaffold were transplanted into osteochondrogenic defects of the patellar groove and compared with empty defects and transplants of polymer scaffolds without cells. The histological and histochemical analysis was performed after 4 and 12 weeks. The transplant integration and the architecture of the newly formed cartilage were evaluated with a semiquantitative score. After 4 weeks the development of a hyaline-like cartilage tissue of the cell-polymer-transplants was observed, after 12 weeks the defects were nearly completely filled with hyaline-like cartilage. The biodegradation of the polymer construct did not affect the histological structure of the transplant area. Defects of the groups with empty defect and polymer transplants without cells revealed no or insufficient healing indices. The study demonstrated that biodegradable polymers served as suitable carriers for the chondrocyte transplantation, which is due to the in-vitro establishment of a semi-solid cartilage transplant and the resulting effective transplant fixation into the defect. In-vivo the polymer cell transplants seem to provide a supportive microenvironment for the development of hyaline cartilage. The controlled release of morphogenic factors or bioactive molecules and the use of pluripotent mesenchymal progenitor cells opens new perspectives for the optimization of cartilage repair procedures.     

微粒骨膜-三维支架修复大面积关节软骨缺损

目的 探讨微粒骨膜-三维支架修复大面积关节软骨缺损的有效性和可行性.方法 于兔股骨滑车关节面制作直径4.5 mm深达软骨下骨板的全层软骨缺损模型,缺损处随机行自体微粒骨膜-纤维蛋白混凝物、单纯纤维蛋白"浇铸"移植.分别于术后3 h、4 d及1、2、4、8、12、24周取材,行大体观察、苏木素.伊红(HE)、Masson及藏红花(safranin-0)染色组织学检查,并进行组织学评分半定量分析.结果 微粒骨膜.三维支架制备简便.微粒骨膜被均匀种植于纤维蛋白三维支架中,可随意"浇铸"充填骨软骨缺损,移植物不易脱落,手术1次完成.术后微粒骨膜在缺损空间内全方位迅速增殖、分化、分泌基质完成缺损骨软骨修复.新生软骨具有与周围正常软骨基本一致的厚度、细胞形态及排列、基质胶原及蛋白多糖染色,且与周边软骨及软骨下骨结合良好.术后4、8、12及24周,两组组织学评分差异有统计学意义(P<0.05).结论 该方法能简单高效地构建工程化组织复合体,随意浇铸充填软骨缺损,完成较大面积关节软骨缺损的生物性修复.     

The effect of fibroblast growth factor-2 on autologous osteochondral transplantation

In this study, we performed a mechanical analysis of the effect of fibroblast growth factor-2 (FGF-2) on autologous osteochondral transplantation in a rabbit model. A full-thickness cartilage defect (diameter: 5 mm; depth: 5 mm) made in the right femoral condyle was treated with osteochondral transplantation using an osteochondral plug (diameter: 6 mm; depth: 5 mm) taken from the left femoral condyle. The animals were divided into three groups: Group I, the defect was filled with 0.1 ml of gelatin hydrogel containing 1 microg of FGF-2; Group II, the defect was filled with 0.1 ml of gelatin hydrogel only; Group III, the defect was left untreated. Thereafter, osteochondral plugs were transplanted and the transplanted osteochondral grafts were evaluated mechanically and histologically at postoperative weeks 1, 3, 8 and 12. The structural property of the osteochondral graft was significantly greater in Group I than in Groups II and III at postoperative week 3. Histological analysis at 3 weeks revealed a tendency towards increased subchondral bone trabeculae in Group I compared with the other groups. Autologous osteochondral grafts transplanted with gelatin hydrogel containing FGF-2 acquired adequate stiffness at an early postoperative phase.     

自体软骨细胞团块植入修复兔陈旧性关节软骨缺损的实验研究

目的 观察自体软骨细胞团块植入对兔关节软骨缺损的修复作用. 方法 24只成年新西兰大白兔48侧膝关节,随机分为三组(n=16)并制备双膝关节股骨滑车软骨缺损模型.空白对照组无特殊处理,骨膜移植组将骨膜覆盖缺损并缝合于缺损两侧的股骨髁上,实验组将自体软骨细胞团块植入缺损中.术后3、6个月分别取材(n=8),进行大体和组织学观察,修复组织行Wakitani评分并进行比较. 结果实验组共成功取材11个缺损关节,9个为透明软骨修复,2个因植入细胞生长状态差未修复;骨膜移植组修复组织为纤维软骨或纤维组织,修复组织薄,基质异染弱;空白对照组仅有少量纤维组织填充缺损底部.修复组织Wakitani评分:实验组3.82分,骨膜移植组6.71分,空白对照组9.23分,差异有统计学意义(F=5.96,P=0.00). 结论自体软骨细胞团块植入能较好修复关节软骨缺损,修复的质量与植入细胞的质量有关.     

Restoration of arthritic cartilage defects using autologous chondrocytes transplantation is superior to cartilage-paste graft in rabbits

This study compared the articular cartilage repair potential of cultured chondrocytes transplantation with bone-cartilage paste-graft in the resurfacing of full-thickness defects without breaching of the subchondral bone plate in rabbit knees. A 5 x 5-mm articular cartilage defect was created in the patellar groove of the femur. Three months following creation, the defect was filled with cultured autologous chondrocytes (group 1) or bone-cartilage paste (group 2). A control group of untreated defects was followed for 1 year. The reparative tissue was analyzed macroscopically, histologically, and by immunohistochemistry 3-12 months post-transplantation. The surfaces of the reparative tissue in group 1 were smooth, and the defects were filled with reparative tissue that resembled hyaline cartilage. The composition of the repair tissue more closely resembled cartilage, as demonstrated by cartilage-specific stains. In contrast, the reparative tissue in group 2 was fibrous and exhibited markers of mesenchymal stem cells and bone formation. Transplantation of cultured chondrocytes into a full-thickness defect in the rabbit generates a biologic substitute tissue that resembles native articular cartilage with living cells capable of synthesizing the surrounding cartilage matrix. In contrast, analysis of the healing response to the paste-graft technique failed to show cartilage-like characteristics. This information may be clinically applicable to direct the use of these treatments in chondral injuries.