Gan Qi, Chen Lina, Bei Ho-Pan, Ng Sze-Wing, Guo Han, Liu Guoqiang, Pan Hao, Liu Changsheng, Zhao Xin, Zheng Zijian
Laboratory for Advanced Interfacial Materials and Devices, School of Fashion and Textiles, The Hong Kong Polytechnic University, Kowloon, 99077, Hong Kong Special Administrative Region of China.
Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
Bioact Mater. 2023 Jan 12;24:551-562. doi: 10.1016/j.bioactmat.2022.12.029. eCollection 2023 Jun.
Preservation of growth factor sensitivity and bioactivity (e.g., bone morphogenetic protein-2 (BMP-2)) post-immobilization to tissue engineering scaffolds remains a great challenge. Here, we develop a stable and soft surface modification strategy to address this issue. BMP-2 (a model growth factor) is covalently immobilized onto homogeneous poly (glycidyl methacrylate) (PGMA) polymer brushes which are grafted onto substrate surfaces (Au, quartz glass, silica wafer, or common biomaterials) via surface-initiated atom transfer radical polymerization. This surface modification method multiplies the functionalized interfacial area; it is simple, fast, gentle, and has little effect on the loaded protein owing to the cilia motility. The immobilized BMP-2 (i-BMP-2) on the surface of homogeneous PGMA polymer brushes exhibits excellent bioactivity (⁓87% bioactivity of free BMP-2 and 20%-50% higher than scaffolds with free BMP-2 ), with conformation and secondary structure well-preserved after covalent immobilization and ethanol sterilization. Moreover, the osteogenic activity of i-BMP-2 on the nanoline pattern (PGMA-poly (N-isopropylacrylamide)) shows ⁓110% bioactivity of free BMP-2. This is superior compared to conventional protein covalent immobilization strategies in terms of both bioactivity preservation and therapeutic efficacy. PGMA polymer brushes can be used to modify surfaces of different tissue-engineered scaffolds, which facilitates immobilization of growth factors, and accelerates repair of a wide range of tissue types.
固定到组织工程支架后生长因子敏感性和生物活性（例如骨形态发生蛋白-2（BMP-2））的保留仍然是一个巨大的挑战。在此，我们开发了一种稳定且柔软的表面修饰策略来解决这个问题。BMP-2（一种典型的生长因子）通过表面引发的原子转移自由基聚合共价固定到接枝在基底表面（金、石英玻璃、硅片或常见生物材料）上的均相聚甲基丙烯酸缩水甘油酯（PGMA）聚合物刷上。这种表面修饰方法增加了功能化界面面积；它简单、快速、温和，并且由于纤毛运动对负载的蛋白质影响很小。均相PGMA聚合物刷表面固定的BMP-2（i-BMP-2）表现出优异的生物活性（约为游离BMP-2生物活性的87%，比带有游离BMP-2的支架高20%-50%），在共价固定和乙醇灭菌后其构象和二级结构得到良好保留。此外，i-BMP-2在纳米线图案（PGMA-聚（N-异丙基丙烯酰胺））上的成骨活性显示约为游离BMP-2生物活性的110%。在生物活性保留和治疗效果方面，这比传统的蛋白质共价固定策略更优越。PGMA聚合物刷可用于修饰不同组织工程支架的表面，这有利于生长因子的固定，并加速多种组织类型的修复。
