Buma Pieter, Pieper Jeroen S, van Tienen Tony, van Susante Job L C, van der Kraan Peter M, Veerkamp Jacques H, van den Berg Wim B, Veth Rene P H, van Kuppevelt Toin H
Orthopedic Research Laboratory, Department of Orthopedics, University Medical Center Nijmegen, P.O. Box 9101, The Netherlands.
Biomaterials. 2003 Aug;24(19):3255-63. doi: 10.1016/s0142-9612(03)00143-1.
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.
胶原基质的物理化学性质可能决定其植入全层关节软骨缺损后引发的组织反应。在本研究中,将交联的I型和II型胶原基质(有无硫酸软骨素附着)植入青春期兔股骨滑车的全层缺损处。通过常规组织学和两种半定量组织学分级系统对植入后4周和12周的组织反应进行评估。植入后4周,I型胶原基质完全被类软骨组织填充。相比之下,II型胶原基质仅在表层区域以及基质与软骨下骨的界面处显示出主要为软骨组织,基质的大片区域无组织生长。硫酸软骨素的附着似乎促进了两种胶原基质中的细胞向内生长和软骨组织形成。植入后12周,基质之间的差异不太明显。软骨下缺损的深部大部分被新骨替代,同时基质发生降解。基于I型胶原基质的缺损处,其原始软骨轮廓由纤维软骨组织修复。含有II型基质的缺损处表层类软骨组织数量增加。然而,并非所有动物的原始轮廓都完全恢复,偶尔会留下中央凹陷或裂隙。得出的结论是,不同类型的胶原基质在全层关节软骨缺损中引发不同的组织反应。基于I型胶原的基质在引导软骨下来源的祖细胞进入缺损方面更具优势。在基于II型胶原的基质中,细胞迁移较少,但侵入细胞会向软骨细胞表型分化。基于这些观察结果,建议由深层I型胶原和较表层II型胶原组成的复合基质可能是软骨再生的首选基质。