Supramolecular-Covalent Peptides Self-Assembly: From Design to Regenerative Medicine and Beyond

The field of supramolecular peptides self-assembly has undergone outstanding growth since the early 1990s after the serendipitously discovery by Shuguang Zhang of an ionic self-complementary peptide as a repeating segment in a yeast protein. From then on, the field expanded at an accelerating pace and these self-assembled materials have become an integral part of a broad plethora of designer supramolecular nanomaterials useful for different applications ranging from 3D tissue cell cultures, regenerative medicine, up to optoelectronics. However, the supramolecular peptide based-nanomaterials available thus far for regenerative medicine still lack the dynamic complexity found in the biological structures that mediate regeneration. Indeed, self-assembling peptide (SAPs) suffer from poor mechanical stability, losing mechanical properties at low strains. Just like the extracellular matrix (ECM) of living systems, the chemical structure of the SAP-biomaterials should concurrently contain non-covalent and covalent bonds, bringing, respectively, infinite and finite lifetimes of interactions to obtain a reversibly dynamic matrix. In this review, will be highlighted the major advantages and current limitations of SAP-based biomaterials, and it will be discussed the most widely used strategies for precisely tune their mechanical properties (stiffness, resilience, strain-failure, stress resistance), describing recent and promising approaches in tissue engineering, regenerative medicine, and beyond.