Biomaterial functionalization with triple-helical peptides for tissue engineering

In the growing field of tissue engineering, providing cells in biomaterials with the adequate biological cues represents an increasingly important challenge. Yet, biomaterials with excellent mechanical properties are often biologically inert to many cell types. To address this issue, researchers resort to functionalization, i.e. the surface modification of a biomaterial with active molecules or substances. Functionalization notably aims to replicate the native cellular microenvironment provided by the extracellular matrix, and in particular by collagen, its major component. As our understanding of biological processes regulating cell behavior increases, functionalization with biomolecules binding cell surface receptors constitutes a promising strategy. Among these, triple-helical peptides (THPs) that reproduce the architectural and biological properties of collagen are especially attractive. Indeed, THPs containing binding sites from the native collagen sequence have successfully been used to guide cell response by establishing cell-biomaterial interactions. Notably, the GFOGER motif recognizing the collagen-binding integrins is extensively employed as a cell adhesive peptide. In biomaterials, THPs efficiently improved cell adhesion, differentiation and function on biomaterials designed for tissue repair (especially for bone, cartilage and heart), vascular graft fabrication, wound dressing, drug delivery or immunomodulation. This review describes the key characteristics of THPs, their effect on cells when combined to biomaterials and their strong potential as biomimetic tools for regenerative medicine. Statement of significance This review article describes how triple-helical peptides constitute efficient tools to improve cell-biomaterial interactions in tissue engineering. Triple helical peptides are bioactive molecules that mimic the architectural and biological properties of collagen. They have been successfully used to specifically recognize cell-surface receptors and provide cells seeded on biomaterials with controlled biological cues. Functionalization with triple-helical peptides has enabled researchers to improve cell function for regenerative medicine applications, such as tissue repair. However, despite encouraging results, this approach remains limited and under-exploited, and most functionalization strategies reported in the literature rely on biomolecules that are unable to address collagen-binding receptors. This review will assist researchers in selecting the correct tools to functionalize biomaterials, in efforts to guide cellular response. (C) 2022 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc.