hIGF-I基因增强Mosaicplasty技术重建膝负重区大面积骨软骨复合缺损实验研究

目的研究hIGF-I基因增强组织工程提高Mosaicplasty修复大面积骨软骨缺损的修复质量，改善骨软骨的整合。 方法制造山羊膝关节股骨髁大面积骨软骨缺损模型，使用自制Mosaicplasty器械，植入2 mm直径骨软骨柱镶嵌充填缺损，以hIGF-I基因转染的骨髓基质干细胞复合可注射藻酸钙凝胶填充残余缺损。同时设立未转染hIGF-I基因的骨髓基质干细胞组、Mosaicplasty组和对照组。术后4 w、8 w、16 w处死动物，行大体观察、光镜、电镜观察，磁共振检查比较修复效果。 结果骨软骨缺损在16 w时IGF-I基因增强Mosaicplasty组移植物固定牢固，关节面平滑，移植物间界限消失，新生软骨组织类似于正常软骨，4~16 w修复效果逐渐改善，优于其他各组。光镜观察见移植的骨软骨生长良好，与新生软骨组织紧密相连，新生的软骨细胞排列规整，细胞外基质分布均一。对照组无明显修复。MRI观察类似大体观察结果。 结论使用转染hIGF-I基因的骨髓基质干细胞复合可注射藻酸钙凝胶可促进Mosaicplasty后骨软骨的整合，改善其修复效果。     

自体骨髓基质干细胞辅助Mosaicplasty技术促进骨软骨缺损修复整合

目的探讨以基于骨髓基质干细胞(BMSCs)的组织工程技术与自体骨软骨柱镶嵌移植术(Mosaicplasty)相结合的方法修复骨软骨及促进缺损间隙的整合效果。方法12只中国山羊于术前2周抽取骨髓,体外培养自体BMSCs。术中以自制器械分别制造山羊双后肢股骨内髁负重区直径5 mm、深3 mm的复合骨软骨缺损各一处。在Mosaicplasty技术填充缺损后,即以动物自体BMSCs与透明质酸凝胶相复合,注射填充于左后肢骨软骨柱之间及与周围组织的间隙内,右后肢单纯自体骨软骨柱移植作为对照组。术后第4、8、16周分别取材进行组织学、组织化学及蛋白聚糖含量等检测。比较16周时两组的缺损区惨复软骨组织与正常软骨的蛋白聚糖含量。结果两组自体骨软骨柱移植软骨均以透明软骨存活,与周围正常软骨间无明显差异。实验组骨软骨柱的间隙内可见新生软骨修复,组织学表现与周围正常软骨相同。交界区整合良好,间隙消失;对照组各时间点软骨间的间隙为纤维组织或纤维软骨填充,仍有间隙存留。移植软骨的基质、实验组骨软骨柱间隙内的新生软骨基质及Ⅱ型胶原免疫组化染色均为阳性。蛋白聚糖含量比较显示,对照组骨软骨柱间隙内新生组织的蛋白聚糖含量均低于正常软骨和实验组,差异有显著性意义(P< 0．05)。结论基于BMSCs的组织工程技术结合Mosaicplasty技术,可以有效地促进骨软骨缺损间隙的整合,改善修复效果好,有望成为一种理想的促进骨软骨缺损修复的方法。     

骨形态形成蛋白修复大面积关节软骨缺损的实验研究

将骨形态形成蛋白(BMP)用于大面积关节软骨缺损的修复,探讨应用方法,观察修复效果。在51只成年兔股骨的髌髁关节面上制造5mm×10mm的骨软骨缺损,深3～5mm。缺损内分别填充骨形态形成蛋白和纤维蛋白粘合剂复合物(BMP/FS)、BMP、FS,植入物均用自体游离骨膜覆盖,并设单纯骨膜覆盖缺损组和空白对照组。术后2、4、8、12周对缺损修复情况行大体和组织学观察。结果显示:BMP/FS组,8周时软骨下骨再生已完成,12周表层新生软骨组织结构接近正常,修复效果明显优于其它组。     

自体骨软骨和半月板移植修复负重关节骨软骨缺损

本文就非负重区关节面软骨和坐月板移植能否负重作一实验研究。取51只1.1～1.2kg未成熟兔,在全麻下从膝关节内侧切开,暴露股骨内髁,在关节面负重中心钻孔造成直径3mm,深2mm的骨软骨缺损。组Ⅰ为自然修复组,缺损处无任何组织覆盖;组Ⅱ为骨软骨移植组,缺损处用髌股关节面的骨软骨充填;组Ⅲ为半月板纤维软骨移植组,缺损处用外侧半月板充填。全部动物术后不     

单纯骨软骨镶嵌成形术与联合组织工程方法治疗急性骨软骨缺损的对比研究

目的 对比研究单纯骨软骨镶嵌成形术与联合组织工程方法 及联合未转染基因的BMSCs-藻酸钙修复急性骨软骨缺损的效果. 方法 对携带hTGF-β,的重组腺病毒转染BMSCs(hTGF-β转染组)、采用携带Lac-Z报告基因的重组腺病毒(Adv-βgal)转染BMSCs(Adv-βgal转染组)及未转染BMSCs(未转染空白对照组)进行Westernblot检测hTGF-β1、Col Ⅱ及Aggrecan表达.将雄性6月龄崇明山羊18只,体重22～25 kg,随机分为A、B、C组(n=6).取B、C组自体骨髓进行BMSCs分离、培养,传至第3代.B组细胞行hTGF-β,重组腺病毒转染.3组动物于双后肢股骨内髁负重区采用骨钻制各直径5 mm、长3 mm的缺损,A组采用自体骨软骨柱修复:B组修复材料同A组,并同时将5 mL转染hTGF-β1的BMSCs藻酸钠混合液注入空隙,加入CaCl2产生凝胶;C组:修复方法 同B组,采用未转染hTGF-β1的自体BMSCs藻酸钠混合液.术后观察山羊一般情况,于术后12周及24周取材,行大体及组织学观察,并参照O'Driscoll,Keeley and Salter组织形态学评分标准进行评分;术后24周行免疫组织化学及透射电镜观察. 结果 转染后5 d,hTGF-β1转染组细胞hTGF-β1、Col Ⅱ及Aggrecan表达均显著强于Adv-βgal转染组及未转染空白对照组.术后动物均存活至实验完成,伤口Ⅰ期愈合.大体观察B组修复组织边界模糊,移植修复区域表面光滑;A、C组软骨间空隙有裂隙存在.组织学观察A组软骨间空隙区纤维软骨样组织修复、纤维组织填充或相邻软骨增生;B组修复软骨细胞排列规律,交界区整合良好;C组软骨间的空隙区见纤维软骨样组织,存在裂隙.各时间点B组组织学评分均高于A、C组,C组高于A组,差异均有统计学意义(P<0.05);B组12周与24周差异有统计学意义(P<0.05).术后24周免疫组织化学示B组软骨间修复组织染色以软骨细胞和陷窝周围明显,A、C组呈淡染.透射电镜观察示B组修复组织可见典犁软骨细胞,A、C组见平行或交错排列的胶原纤维束. 结论 骨软骨镶嵌成形术联合组织工程方法 可解决单纯骨软骨镶嵌成形术残留缺损愈合不良及软骨间整合不良的问题.     

骨形态形成蛋白复合纤维蛋白载体修复全厚关节软骨缺损的实验研究

目的：用骨形态形成蛋白（BMP）复合纤维蛋白载体修复创伤性全厚关节软骨缺损,方法：60只新西兰家兔,体重2．5－3kg,雌雄不限,随机分为5组,每侧股骨髌髁关节面低速电钻钻一直径为4mm全厚关节软骨缺损,一侧缺损填充BMP／FS,对照侧缺损填充单纯FS,单纯BMP和空白组,膝关节不做固定,允许笼中自由活动,术后2,4,8,12周空气栓塞分批处死动物,大体观,组织学切片HE染色,S－100蛋白免疫组化染色和透射电镜观察实验结果,结果：术后4周,BMP／HF填充的部分关节软骨缺损由类透明软骨修复,术后8周,实验组缺损大部分由类透明软骨修复,而对照组则由纤维软骨或纤维组织修复,术后12周,实验组修复组织主要是透明软骨或类透明软骨,修复面较平整光滑,与周围组织愈合良好,但部分修复软骨面变薄,纤维化。结论：BMP／FS复合物促进了关节软骨的早期修复,并且最终的修复组织更接受正常的关节软骨,但术后12周修复的关节软骨出现退行性改变。     

骨形态形成蛋白修复大面积关节软骨缺损的实验研究

将骨形态形成骨蛋白用于大面积关节软骨缺损的修复，探讨应用方法，观察修复效果。在５１只成年兔股骨的髌髁关节面上制造５ｍｍ×１０ｍｍ的骨软骨缺损，深３－５ｍｍ。缺损内分别填充骨形态形成蛋白和纤维蛋白粘合剂复合物，ＢＭＰ，ＦＳ，植入物均用自体游离骨膜覆盖，并设单独骨膜覆盖缺损组和空白对照组。     

孔数不同的软骨下骨钻孔术对兔软骨缺损修复的影响

目的：为了观察软骨缺损的修复过程，比较不同数目钻孔术对软骨缺损的修复效果。方法：用中国白兔２４只，在股骨关节面造成６ｍｍ×８ｍｍ全层软骨缺损，分别施行１０孔及５孔钻孔术，术后４、８周取材，做组织学及电镜观察，并进行评估。结果：（１）１０孔、５孔和对照组的优势修复组织分别以类透明软骨，类透明软骨加纤维软骨和纤维组织为主。（２）修复组织厚度１０孔及５孔无显著差异。（３）修复组织覆盖缺损的面积，１０孔＞５孔＞对照组。初步结论：软骨下骨钻孔可修复关节软骨全层缺损；多孔比少孔修复好；非钻孔的缺损修复效果较差。     

兔自体松质骨颗粒修复关节软骨损伤

目的研究兔自体松质骨颗粒在膝关节软骨损伤处移植后能够诱导软骨组织生成、促进关节软骨损伤修复的现象。方法 12只新西兰大白兔麻醉后在兔的右侧膝关节股骨远端内、外侧髁负重区用电钻分别造成直径、深度均为3 mm的骨软骨缺损创面,取同侧髂骨松质骨,制成直径约为1 mm松质骨颗粒植入股骨内侧髁软骨缺损处,作为实验组,外侧髁软骨缺损不做处理作为对照组。术后12周进行膝关节大体观察、病理切片染色,评估关节软骨损伤的修复情况。结果兔膝关节实验组软骨缺损处被新生软骨填充,软骨面光滑,组织切片染色显示有关节软骨形成。对照组缺损创面仍然凹陷,仅在缺损边缘有少量软骨生长。结论兔自体松质骨颗粒在膝关节软骨损伤处能够诱导软骨生成,促进关节软骨的修复,是一种良好的关节软骨损伤修复方法。     

"双相"组织工程软骨修复兔关节骨软骨缺损

目的探讨“双相”异体骨基质明胶（bonematrixgelatin,BMG）作为组织工程软骨载体,与同体骨髓间充质干细胞（marrowmesenchymalstemcells,MSCs）结合,构建组织工程软骨修复兔关节骨软骨缺损的效果。方法4月龄新西兰兔32只,雌雄不限,体重2～3kg。①体外实验：取5只新西兰兔,处死后取髂骨和四肢骨,制备一侧松质骨,一侧皮质骨的“双相”异体BMG载体,扫描电镜观察。另取新西兰兔18只,抽取骨髓,分离MSCs并诱导成软骨分化;将诱导而来的软骨前体细胞与“双相”BMG载体复合构建组织工程软骨,分别于1、3和5周取材行Masson、PAS染色和扫描电镜观察。②体内实验：将抽取骨髓的18只及余下的9只新西兰兔制成双侧股骨内髁骨软骨缺损模型,将前期制备的组织工程软骨同体植入18只兔的右股骨内髁骨软骨缺损（A组）,左侧缺损移植异体BMG（B组）,其余9只双侧软骨缺损未予处理作为空白对照（C组）,分别于术后1、3和6个月取材,行大体、组织学和Ⅱ型胶原mRNA原位杂交观察,改良Wakitani法评分,比较各组修复效果差异。结果①体外实验：“双相”BMG松质骨面孔隙大小100-800μm,细胞于其中增生,形成富含细胞的软骨层;皮质骨面孔隙大小10～40pm,细胞层状覆盖于其表面,可作为起支撑作用的软骨下骨。②体内实验：A组术后1个月即可重建关节骨软骨缺损;修复软骨在观察期内逐渐变薄,但在6个月内始终保持关节面及软骨下骨结构完整。B、C组未能修复缺损,缺损周边软骨磨损加剧。改良Wakitani评分显示A组在3个时间点的各项评分结果,除6个月软骨厚度外,其它指标均优于B、C组,且差异有统计学意义（P〈0．01）。Ⅱ型胶原mRNA原位杂交显示,A组缺损区修复组织中细胞阳性染色率明显高于B、C组,且差异有统计学意义（P〈0．01）。结论“双相”异体BMG可作为组织工程软骨载体材料,其结合自体MSCs诱导的软骨前体细胞制备的组织工程软骨,可修复兔关节软骨和软骨下骨。     

Mosaicplasty: long-term follow-up

The successful treatment of chondral and osteochondral defects of the weightbearing surfaces is a challenge for orthopaedic surgeons. Autologous osteochondral transplantation is one method that can be used to create a hyaline or hyaline-like repair in the defect area. Ten years of clinical experience with autologous osteochondral mosaicplasty are described. Clinical scores, imaging techniques, arthroscopy, histological examination of biopsy samples, and cartilage stiffness measurements were used to evaluate the clinical outcomes and quality of the transplanted cartilage in a total of 831 patients who underwent mosaicplasty. According to our investigations, good-to-excellent results were achieved in 92% of the patients treated with femoral condylar implantations, in 87% of those treated with tibial resurfacing, in 79% of those treated with patellar and/or trochlear mosaicplasties, and in 94% of those treated with talarprocedures. Long-term donor-site disturbances, which were assessed using the Bandi score, showed that patients had 3% morbidity after mosaicplasty. Sixty-nine of 83 patients who were followed arthroscopically showed congruent gliding surfaces, histological evidence of the survival of the transplanted hyaline cartilage, and fibrocartilage filling of the donor sites. Four deep infections and 36 painful postoperative hemarthroses were experienced as complications arising from the surgical procedures. On the basis of both these promising results and also those of other similar studies, autologous osteochondral mosaicplasty would appears to be an alternative for the treatment of small and medium-sized focal chondral and osteochondral defects of the weightbearing surfaces of the knee and other weightbearing synovial joints.     

Repair of porcine articular cartilage defect with a biphasic osteochondral composite.

Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with beta-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone.     

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.     

A morphologic,biochemical, and biomechanical assessment of short-term effects of osteochondral autograft plug transfer in an animal model

Purpose: The objective of this study was to assess the short-term changes that occur after an osteochondral autograft plug transfer from the femoral trochlea to the medial femoral condyle in a goat model. Type of Study: Articular cartilage repair animal study. Methods: Six adult male goats were used in this study. Two 4.5-mm osteochondral plugs were transferred from the superolateral femoral trochlea to 2 recipient sites in the central portion of the medial femoral condyle for a survival period of 12 weeks. Postmortem, the global effects of the procedure were assessed by gross morphologic inspection and by analyzing the synovial DNA for inflammatory response. The recipient sites were also evaluated histologically and biomechanically. Metabolic activity was determined by ³⁵SO₄ uptake, and viability was assessed using a live/dead stain and by confocal laser microscopy. Results: There was no evidence of significant gross morphologic or histologic changes in the operative knee as a result of the osteochondral donor or recipient sites. The patella, tibial plateau, and medial meniscus did not show any increased degenerative changes as a result of articulating against the donor or recipient sites of the osteochondral autografts. Analysis of synovial DNA revealed no inflammatory response. Biomechanically, 6- to 7-fold greater stiffness was noted in the cartilage of the transferred plugs compared with the control medial femoral condyle. Furthermore, on histologic examination, the healing subchondral bone interface at the recipient site had increased density. Glycosaminoglycan synthesis as determined by ³⁵SO₄ uptake was upregulated in the transplanted cartilage plug relative to the contralateral control, showing a repair response at the site of implantation. And finally, confocal microscopy showed 95% viability of the transferred plugs in the medial femoral condyle region. Conclusions: Our findings demonstrate the ability to successfully transfer an osteochondral autograft plug with maintenance of chondrocyte cellular viability. The transferred cartilage is stiffer than the control medial femoral condyle cartilage, and there is concern regarding the increased trabecular mass in the healing subchondral plate, but these do not result in increased degenerative changes of the opposing articular surfaces in the short term.Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 17, No 8 (October), 2001: pp 856–863     

Observations of subchondral plate advancement during osteochondral repair: a histomorphometric and mechanical study in the rabbit femoral condyle

OBJECTIVE: The subchondral plate and its reconstitution has been an under-researched aspect of articular cartilage repair. The extent to which the subchondral plate is restored by natural healing remains controversial. This study aimed to quantify advancement of subchondral bone during repair of an osteochondral defect, and to examine the effect of subchondral bone height on the quality of articular surface repair. DESIGN: Osteochondral defects, 3mm diameter by 3mm deep, were made by controlled drilling through the articular surface into the subchondral bone in femoral condyles of 33 rabbits. The repair response was examined at 8, 16 and 32 weeks (n=14, 12 and 7, respectively) post surgery. The specimens were subjected to mechanical testing, radiography, histology and histomorphometrology using an image analysis system. RESULTS: At 8 weeks, the level of reparative subchondral bone was 0.79+/-0.36 mm below the native tidemark. By 16 weeks, reformed subchondral plate was irregular, showing that 76.5% of the plate had extended beyond the native tidemark (0.13+/-0.05 mm) whilst 16.9% of the plate remained below (0.19+/-0.15 mm). The repaired surface non-osseous layer became thinner than the adjacent cartilage (0.23+/-0.08 vs 0.38+/-0.11 mm, P<0.05). This persisted up to 32 weeks. The repaired surface layers showed disappearance of safranin-O staining, increased separation splits at the boundary, and eventual degradation. General histological scores were similar across 8, 16 and 32 weeks although the scores of defect filling and restoration of osteochondral junction were decreased from 8 to 16 weeks. Mechanically, repaired defects had lower contact pressure and greater indentation than the normal controls at all time (P<0.05). Indentations of the cartilage adjacent to the defects were also greater than the normal at 8 and 32 weeks (P<0.05). CONCLUSION: The reparative subchondral bone advanced beyond the level of the native subchondral plate by 16 weeks in osteochondral defects of the rabbit femoral condyles. The presence of an advanced and irregular subchondral plate was associated with degradation of repaired articular surface. Abnormal subchondral plate is likely one of the major factors in influencing the long-term outcome of articular cartilage repair.     

Autologous osteochondral grafting in the knee: indication,results, and reflections

The use of multiple autologous osteochondral plugs (mosaicplasty) for repair of articular cartilage defects is a well-accepted technique. Since 1995, the authors have used mosaicplasty to treat more than 110 patients with cartilage defects of the knee, hip, and ankle. The first 52 consecutive patients who had mosaicplasty of the knee and have an average followup of 37 months (range, 24-56 months) were examined. Indications for surgical treatment were osteochondritis dissecans, acute trauma, and posttraumatic lesions of the femorotibial joint, femoropatellar maltracking with recurrent episodes of patella dislocations, and distinct femoropatellar arthrosis. Preoperatively, cartilage defects were classified as International Cartilage Repair Society Grade III lesions in 23 patients and Grade IV lesions in 29 patients. Two years after surgery, an increased level of knee function was found in 86% of the patients. At the latest followup, improved knee function was observed in 92% of the patients. In four patients, reoperation was necessary because of graft failure. Complications and reoperation rate were related to large surface lesions. Autologous osteochondral transplantation is a valid option for the treatment of full-thickness osteochondral defects. However, the method is limited by the defect size and the number of plugs to be taken at the donor site.     

Transplantation of tissue-engineered osteochondral plug using cultured chondrocytes and interconnected porous calcium hydroxyapatite ceramic cylindrical plugs to treat osteochondral defects in a rabbit model

Abstract:  The purpose of this study was to evaluate the macroscopic and histological results of transplanting a tissue-engineered composite plug made of tissue-engineered cartilage and interconnected porous calcium hydroxyapatite ceramics (IP-CHA) with a very high porosity of 94.9% to treat osteochondral defects. Twelve 12-week-old male Japanese white rabbits were used. Fresh articular cartilage slices were taken, and isolated chondrocytes (2 × 10⁶ cells) were embedded in atelocollagen gel. They were seeded on the top of IP-CHA plugs and cultured for 2 weeks. These tissue-engineered composite plugs were transplanted into the osteochondral defects in the patellar grooves (the experimental group). In the control group, the defects were treated with composite plugs without chondroytes. Twelve weeks after transplantation in the experimental group, the defects were repaired with cartilage-like tissue with good subchondral bone formation histologically. Histological scores in the experimental group were significantly better than those in the control group. This study clearly showed the defects that had been treated with tissue-engineered composite plugs.     

Contact pressure comparison of proud osteochondral autograft plugs versus proud synthetic plugs

Osteochondral autograft transfer is an accepted treatment for chondral and osteochondral defects of the knee. Synthetic plugs may eventually be used for primary treatment of defects. Currently they are largely used for osteochondral donor site backfill. Placement of osteochondral or synthetic plugs proud leads to articulating surface incongruity, increases in contact pressure, and potential for both plug and opposing surface degenerative change. We conducted a biomechanical study of human cadaver knees to determine whether differences exist in the contact pressure of osteochondral autograft plugs placed proud versus synthetic plugs placed proud. Ten human cadaveric knees were used (20 condyles). Contact pressure was measured with Tekscan sensor technology (South Boston, Massachusetts) with both static and cyclical loads (of 250 and 500 cycles) created by an MTS Bionix system (Eden Prairie, Minnesota) under the following conditions: native articular cartilage, surgically created defect (7-mm diameter), 1-mm proud osteochondral autograft, and 1-mm proud synthetic graft. Proud osteochondral autograft plugs resulted in a 21.4% increase in peak contact pressure over surrounding native articular cartilage versus a 4.9% increase with proud synthetic plugs. Synthetic plugs compressed their structure and subsided versus subchondral bone collapse with compressive load in osteochondral autograft plugs. Proud osteochondral autograft plugs have significantly higher peak contact pressures than proud synthetic plugs when placed for treatment of chondral and osteochondral defects in the knee.     

Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study

BACKGROUND: Full-thickness defects measuring 3 mm in diameter have been commonly used in studies of rabbits to evaluate new procedures designed to improve the quality of articular cartilage repair. These defects initially heal spontaneously. However, little information is available on the characteristics of repair of larger defects. The objective of the present study was to define the characteristics of repair of 6-mm full-thickness osteochondral defects in the adult Spanish goat. METHODS: Full-thickness osteochondral defects measuring 6 x 6 mm were created in the medial femoral condyle of the knee joint of adult female Spanish goats. The untreated defects were allowed to heal spontaneously. The knee joints were removed, and the defects were examined at ten time-intervals, ranging from time zero (immediately after creation of the defect) to one year postoperatively. The defects were examined grossly, microradiographically, histologically, and with magnetic resonance imaging and computed tomography. RESULTS: The 6-mm osteochondral defects did not heal. Moreover, heretofore undescribed progressive, deleterious changes occurred in the osseous walls of the defect and the articular cartilage surrounding the defect. These changes resulted in a progressive increase in the size of the defect, the formation of a large cavitary lesion, and the collapse of both the surrounding subchondral bone and the articular cartilage into the periphery of the defect. Resorption of the osseous walls of the defect was first noted by one week, and it was associated with extensive osteoclastic activity in the trabecular bone of the walls of the defect. Flattening and deformation of the articular cartilage at the edges of the defect was also observed at this time. By twelve weeks, bone resorption had transformed the surgically created defect into a larger cavitary lesion, and the articular cartilage and subchondral bone surrounding the defect had collapsed into the periphery of the defect. By twenty-six weeks, bone resorption had ceased and the osseous walls of the lesion had become sclerotic. The cavitary lesion did not become filled in with fibrocartilage. Instead, a cystic lesion was found in the center of most of the cavitary lesions. Only a thin layer of fibrocartilage was present on the sclerotic osseous walls of the defect. Specimens examined at one year postoperatively showed similar characteristics. CONCLUSIONS: Full-thickness osteochondral defects, measuring 6 mm in both diameter and depth, that are created in the medial femoral condyle of the knee joint of adult Spanish goats do not heal spontaneously. Instead, they undergo progressive changes resulting in resorption of the osseous walls of the defect, the formation of a large cavitary lesion, and the collapse of the surrounding articular cartilage and subchondral bone. CLINICAL RELEVANCE: As surgeons apply new reparative procedures to larger areas of full-thickness articular cartilage loss, we believe that it is important to consider the potential deleterious effects of a "zone of influence" secondary to the creation of a large defect in the subchondral bone. When biologic and synthetic matrices with or without cells or bioactive factors are placed into surgically created osseous defects, the osseous walls serve as shoulders to protect and stabilize the preliminary repair process. It is important to protect the repair process until biologic incorporation occurs and the chondrogenic switch turns the cells on to synthesize an articular-cartilage-like matrix. It takes a varying period of time to fill a large, surgically created bone defect underlying a chondral surface. The repair of such a defect requires bone synthesis and the reestablishment of a subchondral plate with a tidemark transition to the new overlying articular surface. The prevention of secondary changes in the surrounding bone and articular cartilage and the durability of the new reparative tissue making up the articulating surface are issues that must be addressed in future studies.