Solchaga L A, Yoo J U, Lundberg M, Dennis J E, Huibregtse B A, Goldberg V M, Caplan A I
Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, Ohio 44106-7080, USA.
J Orthop Res. 2000 Sep;18(5):773-80. doi: 10.1002/jor.1100180515.
Articular cartilage in adults has limited ability for self-repair. Some methods devised to augment the natural healing response stimulate some regeneration, but the repair is often incomplete and lacks durability. Hyaluronan-based polymers were tested for their ability to enhance the natural healing response. It is hypothesized that hyaluronan-based polymers recreate an embryonic-like milieu where host progenitor cells can regenerate the damaged articular surface and underlying bone. Osteochondral defects were made on the femoral condyles of 4-month-old rabbits and were left empty or filled with hyaluronan-based polymers. The polymers tested were ACP sponge, made of crosslinked hyaluronan, and HYAFF-11 sponge, made of benzylated hyaluronan. The rabbits were killed 4 and 12 weeks after surgery, and the condyles were processed for histology. All 12-week defects were scored with a 29-point scale, and the scores were compared with a Kruskall-Wallis analysis of variance on ranks. Untreated defects filled with bone tissue up to or beyond the tidemark, and the noncalcified surface layer varied from fibrous to hyaline-like tissue. Four weeks after surgery, defects treated with ACP exhibited bone filling to the level of the tidemark and the surface layer was composed of hyaline-like cartilage well integrated with the adjacent cartilage. At 12 weeks, the specimens had bone beyond the tidemark that was covered with a thin layer of hyaline cartilage. Four weeks after surgery, defects treated with HYAFF-11 contained a rim of chondrogenic cells at the interface of the implant and the host tissue. In general, the 12-week defects exhibited good bone fill and the surface was mainly hyaline cartilage. Treated defects received significantly higher scores than untreated defects (p < 0.05), and ACP-treated defects scored significantly higher than HYAFF-11-treated defects (p < 0.05). The introduction of these hyaluronan-based polymers into defects provides an appropriate scaffolding and favorable microenvironment for the reparative process. Further work is required to fully assess the long-term outcome of defects treated with these polymers.
成人关节软骨的自我修复能力有限。为增强自然愈合反应而设计的一些方法能刺激一定程度的再生，但修复往往不完整且缺乏持久性。基于透明质酸的聚合物被测试其增强自然愈合反应的能力。据推测，基于透明质酸的聚合物能重建类似胚胎的微环境，在此环境中宿主祖细胞可使受损的关节表面和下方骨骼再生。在4月龄兔的股骨髁上制造骨软骨缺损，缺损处不做处理或填充基于透明质酸的聚合物。所测试的聚合物为交联透明质酸制成的ACP海绵和苄基化透明质酸制成的HYAFF-11海绵。术后4周和12周处死兔子，对髁进行组织学处理。所有12周的缺损用29分制评分，评分采用Kruskal-Wallis秩方差分析进行比较。未经处理的缺损被骨组织填充至潮线或超过潮线，非钙化表层从纤维组织到类透明软骨组织不等。术后4周，用ACP处理的缺损骨填充至潮线水平，表层由与相邻软骨良好整合的类透明软骨组成。12周时，标本在潮线以外有骨组织，表面覆盖一层薄的透明软骨。术后4周，用HYAFF-11处理的缺损在植入物与宿主组织界面处有一圈软骨生成细胞。总体而言，12周的缺损显示出良好的骨填充，表面主要为透明软骨。经处理的缺损得分显著高于未经处理的缺损（p < 0.05），且ACP处理的缺损得分显著高于HYAFF-11处理的缺损（p < 0.05）。将这些基于透明质酸的聚合物引入缺损为修复过程提供了合适的支架和有利的微环境。需要进一步开展工作以全面评估用这些聚合物处理缺损的长期结果。
