Bioconvergence of sound-guided and supramolecular assembly strategies to create peptide-protein composite hydrogels with predictable shape-to-function features

Abstract

Purely protein-based hydrogels are widely used in tissue engineering for their biomimicry and biocompatibility, yet remain challenging to tailor with precision and predictability at biological and mechanical levels. To overcome this, synthetic self-assembling peptide amphiphiles (PAs) offer opportunities for supramolecular customization, both as single-phase materials and co-assembled with proteins to create hybrid nanocomposites with emerging functionalities. Similarly, contactless, sound-guided bioassembly techniques using liquid-phase hydrogel precursors are emerging as strategic tools for obtaining structured and functional hydrogels. Leveraging these advances, here a fast, contactless, one-pot bioassembly strategy merging supramolecular PA self-assembly with sound-guided patterning to fabricate hybrid peptide-protein hydrogels with programmable shape-to-function features is presented. Using fibrin as proof-of-concept, material performance is biologically enhanced by incorporating growth factor-binding PAs, while inorganic microparticles are embedded and spatially organized via acoustic fields to tune mechanical properties. This strategy allows predictable tuning of composite stiffness and architecture by adjusting sound wave frequency, with acoustic fields guiding material organization from micro-to-macroscale. Composite hydrogels result highly permissive to cell infiltration in vitro and versatile platform to tune immune cell-material interactions. This modular biofabrication platform integrating supramolecular and sound-guided processes can be generalized to other building blocks opening unique opportunities for scalable, tunable, and hierarchically-organized biomaterials.