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Photopatterned biomolecule immobilization to guide three-dimensional cell fate in natural protein-based hydrogels [Applied Biological Sciences]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2021-01-26 , DOI: 10.1073/pnas.2014194118
Ivan Batalov 1, 2 , Kelly R Stevens 2, 3, 4 , Cole A DeForest 2, 3, 5, 6, 7
Affiliation  

Hydrogel biomaterials derived from natural biopolymers (e.g., fibrin, collagen, decellularized extracellular matrix) are regularly utilized in three-dimensional (3D) cell culture and tissue engineering. In contrast to those based on synthetic polymers, natural materials permit enhanced cytocompatibility, matrix remodeling, and biological integration. Despite these advantages, natural protein-based gels have lagged behind synthetic alternatives in their tunability; methods to selectively modulate the biochemical properties of these networks in a user-defined and heterogeneous fashion that can drive encapsulated cell function have not yet been established. Here, we report a generalizable strategy utilizing a photomediated oxime ligation to covalently decorate naturally derived hydrogels with bioactive proteins including growth factors. This bioorthogonal photofunctionalization is readily amenable to mask-based and laser-scanning lithographic patterning, enabling full four-dimensional (4D) control over protein immobilization within virtually any natural protein-based biomaterial. Such versatility affords exciting opportunities to probe and direct advanced cell fates inaccessible using purely synthetic approaches in response to anisotropic environmental signaling.



中文翻译:


光图案生物分子固定指导天然蛋白质水凝胶中的三维细胞命运[应用生物科学]



源自天然生物聚合物(例如纤维蛋白、胶原蛋白、脱细胞细胞外基质)的水凝胶生物材料经常用于三维(3D)细胞培养和组织工程。与基于合成聚合物的材料相比,天然材料可以增强细胞相容性、基质重塑和生物整合。尽管有这些优点,天然蛋白质凝胶在可调节性方面仍落后于合成替代品。以用户定义的异质方式选择性调节这些网络的生化特性以驱动封装细胞功能的方法尚未建立。在这里,我们报告了一种可推广的策略,利用光介导的肟连接,用包括生长因子在内的生物活性蛋白共价修饰天然衍生的水凝胶。这种生物正交光功能化很容易适用于基于掩模和激光扫描的光刻图案,从而能够对几乎任何基于天然蛋白质的生物材料内的蛋白质固定进行全面的四维(4D)控制。这种多功能性提供了令人兴奋的机会来探测和指导高级细胞命运,这是使用纯合成方法响应各向异性环境信号而无法实现的。

更新日期:2021-01-20
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