Enhanced repair of large osteochondral defects using a combination of artificial cartilage and basic fibroblast growth factor

The purpose of this study was to examine the efficacy of a combination of artificial cartilage and basic fibroblast growth factor (bFGF) for the repair of large osteochondral defects. The artificial cartilage was a three-dimensional fabric (3-DF) composed of an ultra-high molecular weight polyethylene fiber with a triaxial three-dimensional structure. We implanted 3-DF impregnated with type I collagen gel containing 500 ng of bFGF (bFGF-treated group) or 3-DF impregnated with type I collagen gel alone (non-treated group) into a large full-thickness osteochondral defect (6 x 6 x 3 mm) of the patellar groove of rabbits. The defect area was examined grossly, histologically and biomechanically 4-48 weeks after surgery. Bone ingrowth into and around the 3-DF was evaluated with micro-computed tomography (micro-CT). Addition of bFGF to the 3-DF greatly accelerated cartilage formation on the articular surface and subchondral bone formation into and around the 3-DF, and improved biomechanical properties. These findings suggest that a combination of artificial cartilage and bFGF is clinically useful in cases involving large osteochondral defects.     

Role of insulin like growth factor-I in repair response in immature cartilage

OBJECTIVE: The purpose of this study was to investigate the effects of exogenous local Insulin like growth factor-I (IGF-I) on the repair of full-thickness articular cartilage defects in immature rabbits. DESIGN: Thirty-six skeletally immature New Zealand rabbits between 6 and 8 weeks old were used. A single defect, 3.5-mm-wide by 4-mm-deep full-thickness articular cartilage defect in the medial femoral condyle, was created. The defect was either filled with a collagen sponge or with a collagen sponge impregnated with 5 mug of recombinant IGF-I. The animals were sacrificed at 4, 8 or 12 weeks, and the repair tissue was examined macroscopically and histologically. Repair tissue was also examined immunohistochemically for the presence of type-I collagen, type-II collagen and PCNA at all weeks. RESULTS: Newly formed tissue in all of the defects in the IGF-I group had the gross, histological and histochemical appearance of a smooth, intact hyaline articular cartilage. The average total scores on the histological grading scale were significantly better (p<0.05) for the defects treated with recombinant IGF-I at all time points. Immunostaining with an antibody against type-II collagen showed the diffuse presence of the repair cartilage in the IGF-I treated defects. The control groups demonstrated minimum staining with type-II collagen antibody. CONCLUSIONS: These findings suggest that repair of full-thickness immature cartilage defects can be enhanced by recombinant IGF-I.     

组织工程软骨与柚皮苷联合修复兔膝关节软骨缺损的组织学证实

背景：目前临床上虽有多种方法用于治疗软骨缺损,但没有从根本上解决关节软骨缺损修复问题。 目的：通过组织学研究进一步评价柚皮苷结合组织工程软骨修复兔关节软骨缺损的效果。 方法：取兔骨髓间充质干细胞体外增殖后,复合于改建后的脱细胞真皮基质载体上,制成组织工程软骨,植入到兔膝关节软骨缺损,并以柚皮苷汤灌胃,于 4,8周后分别对修复组织进行苏木精-伊红、Masson三色染色、甲苯胺蓝染色、Ⅱ型胶原染色、Ⅹ型胶原染色等组织学检查。 结果与结论：术后8周, 柚皮苷结合干细胞复合体组缺损处修复组织变成乳白色,半透明光滑组织,缺损修复组织与周围正常软骨已基本难区分,表面光滑。组织学检查发现修复缺损处基本为新生软骨填充。结果证实,柚皮苷结合组织工程软骨能提高家兔膝关节软骨缺损的修复质量。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

转化生长因子β1与骨形态发生蛋白2联合修复膝关节软骨损伤

目的 通过探讨转化生长因子β1(TGF-β1)和骨形态发生蛋白2(BMP-2)联合使用对兔膝关节全层关节软骨的修复作用,为关节软骨损伤的治疗提供参考依据.方法 取8只6月龄健康家兔,随机分成两组,每组4只.在无菌条件下,于兔双侧膝关节股骨内外侧髁关节负重面制备直径3mm、深2mm全层关节软骨缺损,用胶原海绵填充或将胶原...     

凝胶包埋骨髓基质干细胞复合脱钙骨基质修复关节软骨缺损简

目的探索Ⅱ型胶原凝胶包埋的自体骨髓基质干细胞（BMSCs）接于同种异体脱钙骨基质（DBM）材料修复兔关节软骨缺损的效果。方法15只健康成年新西兰大白兔,雌雄不限,体质量约3．0kg,兔龄6。9个月;以Urist方法制作同种异体DBM材料。以Ⅱ型胶原蛋白配制水凝胶．以水凝胶包埋兔BMSCs并接种于同种异体DBM材料,构建组织工程复合物。在新西兰大白兔股骨髁关节面制造软骨缺损。分组进行修复。将健康成年新西兰大白兔27只（雌雄不限,体质量约2．5kg．兔龄3～4个月）共54侧膝关节随机分为Ⅱ型胶原／DBM／BMSCs修复组（实验组）、Ⅱ型胶原／DBM修复组（实验对照组）及空白对照组。于术后4周、8周及12周各处死9只动物,取材对修复组织进行大体及组织学观察,根据Wakitani法对修复组织进行评分．数据输入SPSS11．5软件进行统计学分析,比较各组的评分差异是否具有统计学意义。结果实验组Ⅱ型胶原／DBM／BMSCs植入后形成透明软骨样修复．表面光滑平坦,与周围软骨及软骨下骨结合良好;实验对照组Ⅱ型胶原／DBM植入后有部分软骨样修复：而空白对照组仅有少量纤维性修复。根据组织学评分标准,实验组组织学评分为（20．25±1．64）分,高于实验对照组[（7．46±1．29）分]及空白对照组[（6．00±2．09）分]。结论Ⅱ型胶原自体BMSCs复合同种异体DBM支架材料修复全层关节软骨缺损的效果良好,是一种修复软骨缺损的行之有效的方法。     

Repair of articular cartilage defect by cell transplantation

Full-thickness articular cartilage defects are a major clinical problem; however, at present there is no treatment that is widely accepted to regeneratively repair these lesions. The current therapeutic approach is to drill or abrade the base of the defect to expose the bone marrow with its cells and growth factors. This usually results in a repaired tissue of fibrocartilage that functions poorly in the loaded joint environment. Recently, autologous cultured chondrocyte transplantation and mosaic plasty were explored. We can repair small articular cartilage defects using these methods, although their effectiveness is still controversial. We have reported that transplantation of allogeneic chondrocytes embedded in collagen gels or allogeneic chondrocytes cultured in collagen gels could repair articular cartilage defect in a rabbit model. We also reported that autologous culture-expanded bone marrow mesenchymal cell transplantation could repair articular cartilage defect in a rabbit model. This procedure offers expedient clinical use, given that autologous bone marrow cells are easily obtained and can be culture-expanded. We transplanted autologous culture-expanded bone marrow cells into the cartilage defect of the osteoarthritic knee joint on 11 patients at the time of high tibial osteotomy. As early as 6.8 weeks after transplantation, the defect was covered with white soft tissue, in which slight metachromasia was histologically observed. Thirty-three weeks after transplantation, the repaired tissue had hardened. Histologically, repaired tissues showed stronger metachromasia and a partial hyaline cartilage-like appearance. This procedure may prove a promising method by which to repair articular cartilage defects.     

自体脂肪间充质干细胞复合人脐带Wharton胶支架修复兔膝关节软骨缺损****◇

背景：脐带Wharton胶富含透明质酸,糖胺多糖及胶原等,成分与天然软骨细胞外基质类似,因此由人脐带提取的Wharton胶很可能是一种较为理想的软骨组织工程支架材料。 目的：评价自体脂肪间充质干细胞复合人脐带Wharton胶支架修复兔膝关节软骨缺损的效果。 方法：将终浓度为1010 L -1、成软骨方向诱导后的兔自体脂肪间充质干细胞与人脐带Wharton胶支架复合,继续培养1周构建组织工程软骨,对兔膝关节全层软骨缺损进行修复(实验组),并与单纯支架修复的对照组及空白组进行比较。术后3个月对修复组织行大体观察、组织学检测、糖胺多糖、总胶原定量检测及生物力学测定。 结果与结论：实验组的缺损多为透明软骨修复,对照组以纤维组织修复为主,空白组无明显组织修复。提示脂肪间充质干细胞作为软骨组织工程种子细胞具有可行性;实验构建的组织工程软骨能有效的修复关节软骨缺损,人脐带Wharton胶可作为软骨组织工程良好的支架材料。     

Localization of Carboxy-terminal Type II Procollagen Peptide (pCOL-II-C) and Type II Collagen in the Repair Tissue of Full-thickness Articular Cartilage Defect

It is well established that a full-thickness articular cartilage defect is repaired with a fibrocartilaginous tissue of which cells are derived from undifferentiated mesenchymal stem cells in the bone marrow. To characterize the repair tissue immunohistochemically, full-thickness defects were created in rabbit knee joints, and the repair tissues immunostained at 3, 6, and 12 weeks after surgery. Well characterized polyclonal antibody against carboxy-terminal type II procollagen peptide (pCOL-II-C) and monoclonal antibody against type II collagen were used to evaluate the repair tissue with regard to the metabolism of type II collagen. lmmunohistochemistry revealed that pCOL-II-C was localized in or around most of the repair cells obtained at 3 and 6 weeks after surgery, while type II collagen distributed mainly in the pericellular matrix of metaplastic round-shaped repair cells. The results suggest that the repair cells taken at the early stage of the repair process of the defect could originally have more activity of type II collagen synthesis.     

Cross-linked type I and type II collagenous matrices for the repair of full-thickness articular cartilage defects--a study in rabbits

The physico-chemical properties of collagenous matrices may determine the tissue response after insertion into full-thickness articular cartilage defects. In this study, cross-linked type I and type II collagen matrices, with and without attached chondroitin sulfate, were implanted into full-thickness defects in the femoral trochlea of adolescent rabbits. The tissue response was evaluated 4 and 12 weeks after implantation by general histology and two semi-quantitative histological grading systems. Four weeks after implantation, type I collagenous matrices were completely filled with cartilage-like tissue. By contrast, type II collagenous matrices revealed predominantly cartilaginous tissue only at the superficial zone and at the interface of the matrix with the subchondral bone, leaving large areas of the matrix devoid of tissue. Attachment of chondroitin sulfate appeared to promote cellular ingrowth and cartilaginous tissue formation in both types of collagen matrices. Twelve weeks after implantation, the differences between the matrices were less pronounced. The deep parts of the subchondral defects were largely replaced by new bone with a concomitant degradation of the matrices. The original cartilage contours in defects with type I collagen-based matrices were repaired with fibro-cartilaginous tissue. Defects containing type II matrices showed an increase in the amount of superficial cartilage-like tissue. The original contour, however, was not completely restored in all animals, occasionally leaving a central depression or fissure. It is concluded that different types of collagen matrices induce different tissue responses in full-thickness articular cartilage defects. Type I collagen-based matrices are superior to guide progenitor cells from a subchondral origin into the defect. In type II collagen-based matrices cell migration is less, but invading cells are directed into a chondrocyte phenotype. Based on these observations it is suggested that a composite matrix consisting of a deep layer of type I collagen and a more superficial layer of type II collagen may be the matrix of choice for cartilage regeneration.     

In vivo cultivation of human articular chondrocytes in a nude mouse-based contained defect organ culture model

The nude mouse model is an established method to cultivate and investigate tissue engineered cartilage analogues under in vivo conditions. One limitation of this common approach is the lack of appropriate surrounding articular tissues. Thus the bonding capacity of cartilage repair tissue cannot be evaluated. Widely applied surgical techniques in cartilage repair such as conventional and three-dimensional autologous chondrocyte implantation (ACI) based on a collagen gel matrix cannot be included into nude mouse studies, since their application require a contained defect. The aim of this study is to apply an organ culture defect model for the in vivo cultivation of different cell-matrix-constructs.Cartilage defects were created on osteochondral specimens which had been harvested from 10 human knee joints during total knee replacement. Autologous chondrocytes were isolated from the cartilage samples and cultivated in monolayer until passage 2. On each osteochondral block defects were treated either by conventional ACI or a collagen gel seeded with autologous chondrocytes, including a defect left empty as a control. The samples were implanted into the subcutaneous pouches of nude mice and cultivated for six weeks. After retrieval, the specimens were examined histologically, immunohistochemically and by cell morphology quantification.In both, ACI and collagen gel based defect treatment, a repair tissue was formed, which filled the defect and bonded to the adjacent tissues. The repair tissue was immature with low production of collagen type II. In both groups redifferentiation of chondrocytes remained incomplete. Different appearances of interface zones between the repair tissue and the adjacent cartilage were found.The presented contained defect organ culture model offers the possibility to directly compare different types of clinically applied biologic cartilage repair techniques using human articular tissues in a nude mouse model.     

The influence of transforming growth factor beta1 on mesenchymal cell repair of full-thickness cartilage defects

To repair full-thickness articular cartilage defects in rabbit knees, we transplanted periosteal cells in a fibrin gel and determined the influence of transforming growth factor beta (TGF-beta) in vitro. Alginate served as a temporary supportive matrix component and was removed prior to transplantation. The defects were analyzed macroscopically, histologically, and electron microscopically, and evaluated with a semi-quantitative score system. Periosteal cell transplants showed a chondrogenic differentiation, which results in the development of embryonic-like cartilage tissue after 4 weeks and complete resurfacing of the patellar groove after 12 weeks. In the control groups, no repair was observed. Under the influence of TGF-beta1 we observed a reduction of the cartilage layer, whereas the osteochondral integration and the zonal architecture were improved. Periosteal cell-beads are stable cartilage transplants and have stiffness and elasticity enough for easy and sufficient transplant fixation. Further investigations are necessary to optimize the application of TGF-beta1 for cartilage repair.     

Resurfacing potential of heterologous chondrocytes suspended in fibrin glue in large full-thickness defects of femoral articular cartilage: an experimental study in the goat.

A large full-thickness articular-cartilage defect was created in the medial femoral condyle of 32 adult goats. The defects were xenografted with isolated rabbit chondrocytes suspended in fibrin glue. Sham operated goats, where only a standardized defect was created, were used as controls. Results of cartilage repair were assessed after 3, 8, 13, 26 and 52 weeks. The repair tissue was evaluated macroscopically, histologically and biochemically. Results indicated that xenografted rabbit chondrocytes survived the transplantation and maintained their potential to produce matrix in fibrin glue, particularly if they were located in a non-weight-bearing area. In terms of an immunological reaction to xenografted chondrocytes, only mild signs of synovitis were observed in both groups and rejection of transplanted cells did not occur. From 3 weeks gradually progressive resolvement of the fibrin glue was observed with subsequent replacement by fibrous tissue. Initially xenografted defects histologically showed better tendency for cartilage regeneration, however, 52 weeks after surgery no significant differences could be detected in the repair tissue of both groups macroscopically, histologically and on biochemical scoring. The amount of collagen type II in the newly synthesized matrix was 75% 1 year after surgery. This study shows that isolated heterologous chondrocytes can be used for transplantation in articular cartilage defects, however, fibrin glue does not offer enough biomechanical support to the cells to maintain its function as a three-dimensional scaffold.     

Osteochondral repair using the combination of fibroblast growth factor and amorphous calcium phosphate/poly(L-lactic acid) hybrid materials

A novel amorphous calcium phosphate (ACP)/poly(L-lactic acid) (PLLA) material, which can experience morphological variations in the microstructure is supposed to be a suitable candidate as scaffold for cartilage tissue-engineering. The purpose of this study was to evaluate the efficacy of this scaffold combined with basic fibroblast growth factor (bFGF) to repair articular cartilage defects in a rabbit model. Forty-two osteochondral defects created in the femoral condyles were (a) left untreated, (b) treated by PLLA combined with bFGF, or (c) ACP/PLLA loaded with bFGF. The treatment of PLLA incorporated with bFGF improved defect filling compared with that left untreated, while the regenerated tissue was mainly fibrocartilage and showed little bone formation with only a small amount of collagen type II (Col II) and no aggrecan gene message measured. When implanted with ACP/PLLA and bFGF, most of the defects were filled with a well-established layer of cartilage tissue with abundance of cartilaginous extracellular matrix accumulation observed. Positive immunohistochemical staining of Col II was observed. High levels of Col II and aggrecan message were also detected by RT-PCR. These results indicate the feasibility of using the combination of ACP/PLLA with bFGF for cartilage repair.     

Repairing large porcine full-thickness defects of articular cartilage using autologous chondrocyte-engineered cartilage

Large full-thickness defects of articular cartilage remain a major challenge to orthopedic surgeons because of unsatisfactory results of current therapy. Many methods, such as chondrectomy, drilling, cartilage scraping, arthroplasty, transplantation of chondrocytes, periosteum, perichondrium, as well as cartilage and bone, have been tried to repair articular cartilage defects. However, the results are far from satisfactory. In this study, we applied a tissue-engineering approach to the repair of articular cartilage defects of knee joints in a porcine model. Using isolated autologous chondrocytes, polyglycolic acid (PGA), and Pluronic, we have successfully in vivo-engineered hyaline cartilage and repaired articular cartilage defects. The surface of the repaired defects appeared smooth at 24 weeks postrepair. Histological examination demonstrated a typical hyaline cartilage structure with ideal interface healing between the engineered cartilage and the adjacent normal cartilage and underlying cancellous bone. In addition, glycosaminoglycan (GAG) levels in the engineered cartilage reached 80% of that found in native cartilage at 24 weeks postrepair. Biomechanical analysis at 24 weeks demonstrated that the biomechanical properties of the tissue-engineered cartilage were improved compared with those at an earlier stage. Thus, the results of this study may provide insight into the clinical repair of articular cartilage defects.     

Extracellular matrix composition of full-thickness defect repair tissue is little influenced by exercise in rat articular cartilage.

Full-thickness articular cartilage defects in the femoral condyles of adult rats were examined four and eight weeks after injury. Quantitative polarized light microscopic analysis showed that birefringence of the tissue in the central repair area increased more in rats exercised on a treadmill. Glycosaminoglycan content in the repair tissue was also higher than in the intermittent active motion group at four weeks after injury, but by eight weeks the levels were similar in both groups. No normal-looking articular cartilage was formed in the lesions, and only in one animal type II collagen was observed in the superficial zone of repair tissue. No 3B3(-) antigenicity of the proteoglycans was seen during repair. In conclusion, exercise minimally modified the repair of full-thickness articular cartilage defects in adult rats. The repair in the exercised group may occur slightly faster in the early stages but no difference was seen at the eight week time interval between the exercised and the intermittently active group.     

Evaluation of three-dimensional scaffolds prepared from poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) for growth of allogeneic chondrocytes for cartilage repair in rabbits

Articular cartilage repair using tissue engineering approach generally requires the use of an appropriate scaffold architecture that can support the formation of cartilage tissue. In this investigation, the potential of three-dimensional scaffolds made of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) was evaluated in rabbit articular cartilage defect model. Engineered PHBHHx cartilage constructs inoculated in vitro with rabbit chondrocytes for 30 days were examined. Subsequently the constructs inoculated with chondrocytes for 10 days were selected for transplantation into rabbits. After 16 weeks of in vivo implantation, both the engineered cartilage constructs and the bare scaffolds were found to be filled the defects with white cartilaginous tissue, with the engineered constructs showing histologically good subchondral bone connection and better surrounding cartilage infusion. Owing to pre-seeded chondrocytes in the PHBHHx scaffolds, better surface integrality and more accumulation of extracellular matrix (ECM) including type II collagen and sGAG were achieved in the engineered cartilage constructs. The repaired tissues possessed an average compressive modulus of 1.58MPa. For comparison, the defects without repair treatments still showed defects with fibrous tissues. These results demonstrated that PHBHHx is a useful material for cartilage tissue engineering.     

Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem cells in an injectable, in situ, cross-linked synthetic extracellular matrix

A co-cross-linked synthetic extracellular matrix (sECM) composed of chemically modified hyaluronic acid and gelatin was used as a cell delivery vehicle for osteochondral defect repair in a rabbit model. A full-thickness defect was created in the patellar groove of the femoral articular cartilage in each of 2 rabbit joints, and 4 experimental groups were assigned (12 rabbits/group): untreated control, autologous mesenchymal stem cells (MSCs) only, sECM only, and MSCs + sECM. The sECM hydrogels were allowed to cross-link in the defect in situ. Rabbits were sacrificed at 4, 8, and 12 weeks post-surgery, and cartilage repair was evaluated and scored. In the controls, defects were filled with fibrous tissue. In the MSC-only group, hyaline-like cartilage filled the peripheral area of the defect, but the center was filled with fibrous tissue. In the sECM-only group, hyaline cartilage with zonal architecture filled the defect at 12 weeks, but an interface between repaired and adjacent host cartilage was evident. In the MSCs + sECM group, defects were completely filled with elastic, firm, translucent cartilage at 12 weeks and showed superior integration of the repair tissue with the normal cartilage. The sECM delivers and retains MSCs, and the injectable cell-seeded sECM could be delivered arthroscopically in the clinic.     

Extracellular Matrix Composition of Full-Thickness Defect Repair Tissue is Little Influenced by Exercise in Rat Articular Cartilage

Full-thickness articular cartilage defects in the femoral condyles of adult rats were examined four and eight weeks after injury. Quantitative polarized light microscopic analysis showed that birefringence of the tissue in the central repair area increased more in rats exercised on a treadmill. Glycosaminoglycan content in the repair tissue was also higher than in the intermit-tent active motion group at four weeks after injury, but by eight weeks the levels were similar in both groups. No normal-looking articular cartilage was formed in the lesions, and only in one animal type II collagen was observed in the superficial zone of repair tissue. No 3B3(-) antigenicity of the proteoglycans was seen during repair. In conclusion, exercise minimally modified the repair of full-thickness articular cartilage defects in adult rats. The repair in the exercised group may occur slightly faster in the early stages but no difference was seen at the eight week time interval between the exercised and the intermittently active group.     

Use of a biphasic graft constructed with chondrocytes overlying a beta-tricalcium phosphate block in the treatment of rabbit osteochondral defects

To evaluate the ability of a biphasic construct to repair osteochondral defects in articular cartilage, plugs made of chondrocytes in collagen gel overlying a resorbable porous beta-tricalcium phosphate (TCP) block were implanted into defects in rabbit knees. The repair tissue was evaluated at 8, 12, and 30 weeks. Eight weeks after implantation of the biphasic construct, histologic examination showed hyaline-like cartilage formation that was positive for safranin O and type II collagen. At 12 weeks, most of the beta-TCP was replaced by bone, with a small amount remaining in the underlying cartilage. In the cell-seeded layer, the newly formed middle and deep cartilage adjacent to the subchondral bone stained with safranin O, but no staining was observed in the superficial layer. In addition, cell morphology was distinctly different from the deep levels of the reparative cartilage, with hypertrophic cells at the bottom of the cartilaginous layer. At 30 weeks, beta-TCP had completely resorbed and a tidemark was observed in some areas. In contrast, controls (defects filled with a beta-TCP block alone) showed no cartilage formation but instead had subchondral bone formation. These findings indicate that beta-TCP-supported chondrocytes in collagen gel can partially repair isolated articular cartilage osteochondral defects.     

Kinetic study of the replacement of porcine small intestinal submucosa grafts and the regeneration of meniscal-like tissue in large avascular meniscal defects in dogs.

Porcine small intestinal submucosa (SIS) was used to replace large, avascular defects in the medial menisci of dogs. Twelve dogs received SIS grafts and 3 dogs were left untreated as controls. Dogs were evaluated at 4, 8, and 12 weeks by means of lameness scoring and ultrasonography. Dogs were sacrificed at 1, 6, or 12 weeks after implantation, and the tissue at the site of meniscal resection was evaluated for gross and histologic appearance, cross-sectional and surface area, and collagen types I and II. The femoral and tibial condyles were assessed for articular cartilage damage. Control dogs were significantly more lame than grafted dogs 8 and 12 weeks after instrumentation. Grafted dogs' replacement tissue appeared meniscal-like when evaluated grossly and ultrasonographically 12 weeks after instrumentation. The amount of replacement tissue was significantly greater in both cross-sectional and surface area for grafted dogs than for controls at all time points. Histologically, the SIS biomaterial could be identified in all grafted dogs at 1 week post-implantation, but in none at 6 weeks post-implantation. Subjectively, grafted dogs' replacement tissue was histologically superior to that of controls with respect to tissue type, organization, and architecture. Collagen types I and II immunoreactivity in grafted menisci were similar to that of normal menisci. Control dogs had significantly more articular cartilage damage than grafted dogs. SIS appears to induce regeneration of meniscal-like tissue in large, avascular meniscal defects in dogs, resulting in superior clinical function and articular cartilage protection compared to ungrafted controls.