Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, PR China.
Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, PR China.
Colloids Surf B Biointerfaces. 2024 Sep;241:114011. doi: 10.1016/j.colsurfb.2024.114011. Epub 2024 Jun 1.
Hyaline cartilage regeneration will bring evangel to millions of people suffered from cartilage diseases. However, uncontrollable cartilage fibrosis and matrix mineralization are the primary causes of cartilage regeneration failure in many tissue engineering scaffolds. This study presents a new attempt to avoid endochondral ossification or fibrosis in cartilage regeneration therapy by establishing biochemical regulatory area. Here, SOX9 expression plasmids are assembled in cellulose gels by chitosan gene vectors to fabricate SOX9+ functionalized scaffolds. RT-qPCR, western blot and biochemical analysis all show that the SOX9 reinforcement strategy can enhance chondrogenic specific proteins expression and promote GAG production. Notably, the interference from SOX9 has resisted osteogenic inducing significantly, showing an inhibition of COL1, OPN and OC production, and the inhibition efficiency was about 58.4 %, 22.8 % and 76.9 % respectively. In vivo study, implantation of these scaffolds with BMSCs can induce chondrogenic differentiation and resist endochondral ossification effectively. Moreover, specific SOX9+ functionalized area of the gel exhibited the resistance to matrix mineralization, indicating the special biochemical functional area for cartilage regeneration. These results indicate that this strategy is effective for promoting the hyaline cartilage regeneration and avoiding cartilage fibrosis, which provides a new insight to the future development of cartilage regeneration scaffolds.
透明软骨再生将为数百万患有软骨疾病的人带来福音。然而，在许多组织工程支架中，不可控的软骨纤维化和基质矿化是软骨再生失败的主要原因。本研究通过建立生化调节区，对软骨再生治疗中避免软骨内骨化或纤维化提出了新的尝试。在这里，通过壳聚糖基因载体将 SOX9 表达质粒组装在纤维素凝胶中，以制备 SOX9+功能化支架。RT-qPCR、western blot 和生化分析均表明，SOX9 增强策略可以增强软骨特异性蛋白的表达并促进 GAG 的产生。值得注意的是，SOX9 的干扰显著抵抗成骨诱导，表现出对 COL1、OPN 和 OC 产生的抑制，抑制效率分别约为 58.4%、22.8%和 76.9%。体内研究表明，这些支架与 BMSCs 共植入可以有效诱导软骨分化并抵抗软骨内骨化。此外，凝胶中具有特定 SOX9+功能的区域表现出对基质矿化的抗性，表明存在用于软骨再生的特殊生化功能区。这些结果表明，该策略可有效促进透明软骨再生并避免软骨纤维化，为软骨再生支架的未来发展提供了新的思路。
