Maneuvering the mineralization of self-assembled peptide nanofibers for designing mechanically-stiffened self-healable composites toward bone-mimetic ECM

Abstract

Extracellular matrix (ECM) elasticity remains a crucial parameter to determine cell–material interactions (viz. adhesion, growth, and differentiation), cellular communication, and migration that are essential to tissue repair and regeneration. Supramolecular peptide hydrogels with their 3-dimensional porous network and tuneable mechanical properties have emerged as an excellent class of ECM-mimetic biomaterials with relevant dynamic attributes and bioactivity. Here, we demonstrate the design of minimalist amyloid-inspired peptide amphiphiles, C_nPA (n = 6, 8, 10, 12) with tuneable peptide nanostructures that are efficiently biomineralized and cross-linked using bioactive silicates. Such hydrogel composites, C_nBG exhibit excellent mechanical attributes and possess excellent self-healing abilities and collagen-like strain-stiffening ability as desired for bone ECM mimetic scaffold. The composites exhibited the formation of a hydroxyapatite mineral phase upon incubation in a simulated body fluid that rendered mechanical stiffness akin to the hydroxyapatite-bridged collagen fibers to match the bone tissue elasticity eventually. In a nutshell, peptide nanostructure-guided temporal effects and mechanical attributes demonstrate C₈BG to be an optimal composite. Finally, such constructs feature the potential for adhesion, proliferation of U2OS cells, high alkaline phosphatase activity, and osteoconductivity.