Li Guanglong, Gao Fei, Yang Donglei, Lin Lu, Yu Weijun, Tang Jiaqi, Yang Ruhan, Jin Min, Gu Yuting, Wang Pengfei, Lu Eryi
Department of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, China.
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200127, China.
Bioact Mater. 2024 Sep 4;42:241-256. doi: 10.1016/j.bioactmat.2024.08.035. eCollection 2024 Dec.
Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/β-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.
生物活性水凝胶材料在骨组织工程领域具有巨大的应用潜力。然而,制备能够模拟天然骨细胞外基质(ECM)的功能性水凝胶仍然是一项挑战,因为它们需要提供机械支撑并体现促进血管生成和骨生成的生理信号。受ECM特性的启发,我们构建了一种双组分复合水凝胶,它由甲基丙烯酰化明胶(GelMA)和脱氧核糖核酸(DNA)的互穿聚合物网络组成。在复合水凝胶中,GelMA网络作为机械和生物稳定性的骨架,而DNA网络实现动态功能(如应力松弛),从而促进细胞增殖和成骨分化。此外,功能性适体(Apt19S和AptV)易于附着在DNA网络上,以募集骨髓间充质干细胞(BMSCs)并实现负载的血管内皮生长因子向血管生成的持续释放。我们的结果表明,复合水凝胶能够促进BMSCs的黏附,通过激活黏着斑激酶(FAK)/磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/β-连环蛋白信号通路促进成骨分化,并最终增强血管化骨再生。这项研究表明,GelMA和DNA的多功能复合水凝胶能够成功模拟天然骨ECM的生物学功能,在修复骨缺损方面具有巨大潜力。
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