Biomolecular coacervation-mediated materials: Phase states, phase transitions, and biomedical applications.

Abstract

Biomolecular coacervation is increasingly recognized as a phase-evolution process, including liquid-liquid phase separation (LLPS), resulting in metastable liquid-like states, and phase transitions that give rise to gel-like states or solid-like states. These coacervate phase states exhibit distinct structural, dynamic and mechanical characteristics, making biomolecular coacervation regulation a powerful design strategy to engineer biomaterials for a broad range of biomedical applications. In this review, we first summarize the classification of LLPS and the typical molecular driving forces. We then discuss the phase evolution of coacervates, with particular emphasis on LLPS, liquid-to-gel and liquid-to-solid transitions, the characteristics of liquid-like, gel-like and solid-like states, and the intrinsic molecular and environmental factors that regulate these processes. Finally, we examine how distinct phase-state properties govern the biomedical functions of coacervation-mediated materials, with representative applications in drug delivery, bioreactors, bioinspired adhesion and tissue engineering scaffolds. Hopefully, this review could provide a unified framework for understanding coacervation-mediated materials as programmable biomolecular coacervate systems and for guiding their rational design in biomedical applications.