Abstract

Extracellular matrix (ECM)-based biomaterials are promising candidates in cartilage tissue engineering by simulating the native microenvironment to regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) without exogenous growth factors. The biological properties of ECM scaffolds are primarily depended on the original source, which would directly influence the chondrogenic effects of the ECM materials. Despite the expanding investigations on ECM scaffolds in recent years, the selection of optimized ECM materials in cartilage regeneration was less reported. In this study, we harvested and compared the articular cartilage ECM from newborn, juvenile and adult rabbits. The results demonstrated the significant differences in the mechanical strength, sulphated glycosaminoglycan and collagen contents of the different aged ECM, before and after decellularization. Consequently, different compositional and mechanical properties were shown in the three ECM-based collagen hydrogels, which exerted age-dependent chondrogenic inducibility. In general, both in vitro and in vivo results suggested that the newborn ECM promoted the most chondrogenesis of BMSCs but led to severe matrix calcification. In contrast, BMSCs synthesized the lowest amount of cartilaginous matrix with minimal calcification with adult ECM. The juvenile ECM achieved the best overall results in promoting chondrogenesis of BMSCs and preventing matrix calcification. Together, this study provides important information to our current knowledge in the design of future ECM-based biomaterials towards a successful repair of articular cartilage.

中文翻译：

---

不同年龄软骨ECM对BMSCs体外和体内软骨形成的影响

摘要

基于细胞外基质（ECM）的生物材料通过模拟天然微环境来调节不含间充质生长因子的骨髓间充质干细胞（BMSC）的软骨分化，有望成为软骨组织工程中的候选材料。ECM支架的生物学特性主要取决于原始来源，这将直接影响ECM材料的软骨形成作用。尽管近年来对ECM支架的研究不断扩大，但在软骨再生中选择最佳ECM材料的报道却很少。在这项研究中，我们收获并比较了新生兔，幼兔和成年兔的关节软骨ECM。结果表明机械强度存在显着差异，脱细胞前后不同年龄的ECM的硫酸化糖胺聚糖和胶原蛋白含量。因此，在三种基于ECM的胶原蛋白水凝胶中显示出不同的成分和机械性能，这些凝胶水凝胶具有年龄依赖性的成软骨诱导性。一般而言，两者体外和体内结果表明，新生儿ECM促进了BMSC的大多数软骨形成，但导致了严重的基质钙化。相反，BMSCs用成人ECM合成的软骨基质量最少，钙化程度最低。幼年ECM在促进BMSC软骨形成和预防基质钙化方面取得了最佳的总体效果。总之，这项研究为我们成功设计关节软骨的未来基于ECM的生物材料提供了重要的信息。