Immunocompatible Elastomer With Enhanced Fibrous Capsule‐Resistance and Elasticity by Water‐Induced Surface Phase Reconfiguration.

Abstract Integrating surface and bulk heterogeneity enables synergistic optimization of implantable biomaterials, harmonizing surface‐tissue interactions with the mechanical integrity of the bulk. However, achieving this heterogeneity within a single material remains a significant challenge. Here, a strategy to engineer spontaneously generated heterogeneous surface and bulk structures within a material is introduced. The resulting material is termed phase‐separation and underwater reconfiguration‐enhanced (PURE) elastomers. PURE elastomers integrate the high elasticity of the bulk with superior immunocompatibility at the surface. By de novo designing the immunomodulatory and alkyl acrylate monomer structures, this is regulated that the copolymer's spatial configurations, ultimately influencing its condensed structure. Tuning the alkyl side chain length facilitates the formation of a distinctive phase‐separation pattern in elastomers that accommodates large deformations, resulting in excellent toughness and low hysteresis. Moreover, this phase structure supports a water‐induced surface phase reconfiguration, aligning with in vivo applications. This reconfiguration enriches immunomodulatory groups at the material surface, significantly enhancing immunocompatibility. Consequently, these elastomers exhibit extremely low fibrotic capsule formation for up to one year in mice and two months in non‐human primates. This findings introduce a class of durable, fibrosis‐resistant materials and establish a new strategy for designing heterogeneous polymeric elastomers with broad biomedical applicability.