This study presents a novel approach to constructing evolving biointerfaces using granule-releasing hydrogels, which can transition from monolithic to focal interfaces. These hydrogels, composed of gelatin and chitosan, are responsive to biological environments and can be shaped into various macroscopic forms such as bandages and bioelectronics-gel hybrids. The granules, embedded within the hydrogel, can be released and form focal bio-adhesions ex vivo and in vivo, enhancing tissue regeneration and biomedical device manipulation. The granule-releasing hydrogels have been successfully applied to treat ulcerative colitis, heal skin wounds, and reduce myocardial infarctions. Additionally, they improve the performance of flexible cardiac electrophysiology mapping devices. The study demonstrates the potential of these evolving biointerfaces in expanding the application domains of traditional monolithic or focal biointerfaces, offering a more dynamic and less invasive approach to disease diagnosis and treatment.This study presents a novel approach to constructing evolving biointerfaces using granule-releasing hydrogels, which can transition from monolithic to focal interfaces. These hydrogels, composed of gelatin and chitosan, are responsive to biological environments and can be shaped into various macroscopic forms such as bandages and bioelectronics-gel hybrids. The granules, embedded within the hydrogel, can be released and form focal bio-adhesions ex vivo and in vivo, enhancing tissue regeneration and biomedical device manipulation. The granule-releasing hydrogels have been successfully applied to treat ulcerative colitis, heal skin wounds, and reduce myocardial infarctions. Additionally, they improve the performance of flexible cardiac electrophysiology mapping devices. The study demonstrates the potential of these evolving biointerfaces in expanding the application domains of traditional monolithic or focal biointerfaces, offering a more dynamic and less invasive approach to disease diagnosis and treatment.