Department of Chemical Engineering, University of Washington, Seattle, WA 98105.
Department of Bioengineering, University of Washington, Seattle, WA 98105.
Proc Natl Acad Sci U S A. 2021 Jan 26;118(4). doi: 10.1073/pnas.2014194118.
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.
水凝胶生物材料来源于天然生物聚合物（如纤维蛋白、胶原蛋白、去细胞细胞外基质），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，天然材料具有更好的细胞相容性、基质重塑和生物整合性。尽管具有这些优势，但天然蛋白基水凝胶在可调节性方面落后于合成替代品；尚未建立方法以用户定义和异质的方式选择性调节这些网络的生化特性，从而可以驱动被包裹细胞的功能。在这里，我们报告了一种利用光介导肟键合的可推广策略，通过共价键将生物活性蛋白（包括生长因子）修饰到天然衍生的水凝胶上。这种生物正交光功能化易于适应掩模和激光扫描光刻图案化，从而可以在几乎任何天然蛋白基生物材料内实现对蛋白质固定的全四维（4D）控制。这种多功能性为探索和指导先进的细胞命运提供了令人兴奋的机会，这些细胞命运是纯粹的合成方法无法实现的，可响应各向异性环境信号。
