Development‐associated differences in integrative cartilage repair: Roles of biosynthesis and matrix

Abstract

A recurring problem in tissue transplantation therapies for articular cartilage defects is the lack of integration between the implant and the host cartilage. Previous studies have shown that in vitro integration between explants of calf cartilage is markedly higher than that between fetal cartilage, despite similarly high levels of deposition of newly synthesized collagen. The aim of this study was to determine if cellular biosynthesis and extracellular matrix each contribute to these development-associated differences in integrative repair in vitro. The approach taken was to examine integration between specific combinations of cartilage explants that were apposed for two weeks. The cartilage matrix showed different propensities for repair, as integration of calf live cartilage to calf devitalized cartilage was greater than that of calf live cartilage to fetal devitalized cartilage. An inhibiting factor appeared to be present in fetal cartilage matrix since guanidine treatment of fetal devitalized cartilage was able to enhance its integration. The difference between integration to living cartilage and integration to devitalized cartilage, for calf and fetal tissue, indicated that the biosynthetic contribution to integration by calf cartilage was greater than the biosynthetic contribution by fetal cartilage. Thus, the increasing level of integration between fetal and fetal cartilage, fetal and calf cartilage, and calf and calf cartilage appeared to reflect both biosynthetic and matrix differences. Therapeutic strategies to enhance integration to cartilage may thus target both the extracellular components and the cellular biosynthetic activities of implants and host cartilage.

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

“…An important step in evaluating novel cell sources for defect repair is to demonstrate integration of newly developing tissue with native cartilage, as the synthesis of matrix by cells can affect the strength of cartilage integration (43)(44)(45). We found that sorted and expanded iPSCderived cells seeded in agarose were effective at filling the defect with cartilaginous matrix that integrated well with the surrounding cartilage.…”

Injectable and Photopolymerizable Tissue-Engineered Auricular Cartilage Using Poly(Ethylene Glycol) Dimethacrylate Copolymer Hydrogels

“…Integration of neocartilage with recipient tissue appears to be dependent on viable cells at the interface of integration, even in only one of the two apposing surfaces. 26,27 The adhesive strength of cartilage integration has been correlated with collagen synthesis and deposition. 28 Investigating the integrative properties of the PEGDM-based neocartilage, we found that the engineered hydrogels can support the integration of the engineered cartilage with existing native cartilage.…”

Translation from Research to Applications

“…Structural and functional integration with host tissues is essential for long-term functionality of implants. 38,39 For quantitative analysis of integration of tissue engineered constructs, there are already available in vitro models. 40 For implant integration, which is a cell-regulated process, ultrastructural integration of secreted matrix components is necessary.…”