Chen Jiaqing, Li Yijiang, Wang Bin, Yang Jiabei, Heng Boon Chin, Yang Zheng, Ge Zigang, Lin Jianhao
Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, P. R. China.
J Mater Chem B. 2018 Jan 28;6(4):675-687. doi: 10.1039/c7tb02132a. Epub 2018 Jan 15.
Growth factors, such as TGF-β and BMPs, play key roles in the chondrogenic differentiation of mesenchymal stem cells (MSCs) and cartilage regeneration in vivo. Nevertheless, there are some technical challenges in delivering exogenous growth factors in vivo, such as burst release and loss of bioactivity. In this study, TGF-β1 affinity peptides were incorporated within porous chitosan scaffolds to enhance cartilage regeneration. Significant upregulation of gene expression levels of Sox9, Col II and AGG during chondrogenic differentiation of MSCs in vitro, were positively correlated with increasing amounts of TGF-β1 affinity peptides incorporated within the chitosan scaffolds. The results of ectopic implantation of scaffolds in nude mice showed that incorporation of TGF-β1 affinity peptides and preloading of TGF-β1 synergistically enhanced ectopic cartilage formation at both high and low cell densities. Furthermore, in a rabbit osteochondral defect model, implantation of chitosan scaffolds incorporated with TGF-β1 affinity peptides (CHI-PEP) could significantly promote cartilage regeneration, even in the absence of exogenous growth factors and seeded cells. Notably, inflammation and cartilage degeneration were markedly alleviated in the CHI-PEP group. Hence, incorporation of TGF-β1 affinity peptide within the chitosan sponge scaffold significantly enhanced articular cartilage regeneration.
生长因子，如转化生长因子-β（TGF-β）和骨形态发生蛋白（BMPs），在间充质干细胞（MSCs）的软骨形成分化及体内软骨再生中发挥关键作用。然而，在体内递送外源性生长因子存在一些技术挑战，如突发释放和生物活性丧失。在本研究中，将TGF-β1亲和肽掺入多孔壳聚糖支架中以增强软骨再生。在体外MSCs软骨形成分化过程中，Sox9、II型胶原（Col II）和聚集蛋白聚糖（AGG）基因表达水平显著上调，这与壳聚糖支架中掺入的TGF-β1亲和肽数量增加呈正相关。支架在裸鼠体内异位植入的结果表明，掺入TGF-β1亲和肽和预加载TGF-β1在高细胞密度和低细胞密度下均协同增强了异位软骨形成。此外，在兔骨软骨缺损模型中，植入掺入TGF-β1亲和肽的壳聚糖支架（CHI-PEP）即使在没有外源性生长因子和接种细胞的情况下也能显著促进软骨再生。值得注意的是，CHI-PEP组的炎症和软骨退变明显减轻。因此，在壳聚糖海绵支架中掺入TGF-β1亲和肽可显著增强关节软骨再生。
