Photopatterned biomolecule immobilization to guide three-dimensional cell fate in natural protein-based hydrogels
Photopatterned biomolecule immobilization to guide three-dimensional cell fate in natural protein-based hydrogels
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DOI：
10.1073/pnas.2014194118
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发表时间：
2021-01-26
影响因子：
11.1
通讯作者：
DeForest, Cole A.
中科院分区：
文献类型：
--
作者：
Batalov, Ivan;Stevens, Kelly R.;DeForest, Cole A.
衍生自天然生物聚合物的水凝胶生物材料（例如，纤维蛋白、胶原、脱细胞的细胞外基质）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那些相比，天然材料允许增强的细胞相容性、基质重塑和生物整合。尽管有这些优点，天然蛋白质凝胶在其可调性方面落后于合成替代品;以用户定义的和异质的方式选择性地调节这些网络的生化特性的方法尚未建立，该方法可以驱动封装的细胞功能。在这里，我们报告了一个可推广的策略，利用光介导的肟连接共价修饰天然衍生的水凝胶与生物活性蛋白，包括生长因子。这种生物正交光功能化很容易适用于基于掩模的和激光扫描光刻图案化，使得能够对几乎任何天然蛋白质基生物材料内的蛋白质固定进行全四维（4D）控制。这种多功能性提供了令人兴奋的机会，以探测和指导先进的细胞命运无法使用纯合成的方法，以响应各向异性的环境信号。
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.