Chemists, biologists, and material scientists alike have long sought to control protein presentation, orientation, and activity within biomaterials to dictate reaction catalysis, biological signaling, and cell-fate specification. Such control is most typically achieved through the installation of reactive chemical handles onto proteins that govern static or dynamic biomacromolecule-material associations. Though convenient, stochastic functionalization strategies often yield ill-defined protein samples with severely diminished activity. In contrast, site-selective methodologies permit the controlled installation of material-interacting handles onto fragile proteins while preserving native structure and function. Here, we review methods that afford chemical, regioselective, and site-specific modification of proteins, emphasizing those that have found utility in the creation of functional biomaterials. We discuss cutting-edge strategies involving small-molecule-based labeling, genetic engineering, and chemoenzymatic reactions that provide precise control over the extent and location of protein modification. We assess the progress and look to the future in exploiting these functional proteins to create next-generational biomaterials for tissue engineering, therapeutic, and fundamental biological applications.

化学家，生物学家和材料科学家等长期以来一直在寻求控制生物材料中蛋白质的呈递，方向和活性，以决定反应催化，生物信号传导和细胞命运规范。这种控制通常是通过在控制静态或动态生物大分子-材料结合的蛋白质上安装反应性化学手柄来实现的。尽管很方便，但是随机功能化策略通常会产生活性大大降低的不确定蛋白质样品。相反，位点选择方法允许在保持天然结构和功能的同时，将与材料相互作用的手柄可控地安装在易碎的蛋白质上。在这里，我们回顾了可以对蛋白质进行化学，区域选择性和位点特异性修饰的方法，强调那些在功能性生物材料的创造中发现有用的物质。我们讨论了涉及基于小分子的标记，基因工程和化学酶反应的尖端策略，这些策略可提供对蛋白质修饰范围和位置的精确控制。我们评估这些功能蛋白的开发进展，并展望未来，以开发用于组织工程，治疗和基础生物学应用的下一代生物材料。