Biomimetic Coacervate Coatings: From Phase Separation Fundamentals to Advanced Biomedical Applications

This review systematically elucidates the rapidly evolving field of biomimetic coacervate coatings, bridging the fundamental thermodynamic principles of liquid–liquid phase separation (LLPS) with advanced biomedical translations. While conventional surface modifications for medical implants frequently fail to maintain structural and functional integrity within dynamic, wet physiological environments, biomimetic coacervation inspired by natural underwater adhesive mechanisms offers a highly versatile, conformable, and robust interfacial strategy. Here, we analyze the critical physicochemical driving forces governing coacervate formation, emphasizing the synergistic interplay of electrostatic, hydrophobic, hydrogen-bonding, and cation–π interactions. We comprehensively discuss diverse macromolecular design principles utilizing marine-derived biopolymers, synthetic or recombinant polypeptides, and hybrid organic–inorganic condensates, alongside key architectural orchestration methodologies including direct deposition, in situ triggerable coacervation, and layer-by-layer (LbL) assembly. Furthermore, we evaluate multi-functional clinical translations, highlighting breakthroughs in wet tissue sealing, bone repair, localized stimuli-responsive drug or nucleic acid delivery, anti-biofouling medical device coatings, and regenerative cell–material interfaces. Ultimately, this review underscores the profound potential of biomimetic coacervates as a cornerstone platform for next-generation multifunctional medical devices and personalized regenerative medicine.