Hydrogel biomaterials have a wide range of potential clinical applications, including augmentation of wound closure, acute induction of hemostasis, and local drug delivery. Key determinants of hydrogel efficacy include the strength, degree of tissue-material interaction, drug release capacity as well as material biocompatibility. Canonical hydrogel biomaterials, however, are limited by a trade-off among performance criteria that are largely governed by the efficiency of tissue-material interactions. One emergent strategy to improve hydrogel clinical performance is application-specific material design, with the goal of leveraging both local soft tissue surface chemistry and environmental factors to promote tissue-material interactions.