Modulating the Gelation Properties of Self-Assembling Peptide Amphiphiles

Abstract

Peptide amphiphiles (PAs) are self-assembling molecules that form interwoven nanofiber gel networks. They have gained a lot of attention because of their excellent biocompatibility, adaptable peptide structure that allows for specific biochemical functionality, and nanofibrous assembly that mimics natural tissue formation. However, variations in molecule length, charge, and intermolecular bonding between different bioactive PAs cause contrasting mechanical properties. This potentially limits cell-delivery therapies because scaffold durability is needed to withstand the rigors of clinician handling and transport to wound implant sites. Additionally, the mechanical properties have critical influence on cellular behavior, as the elasticity and stiffness of biomaterials have been shown to affect cell spreading, migration, contraction, and differentiation. Several different PAs have been synthesized, each endowed with specific cellular adhesive ligands for directed biological response. We have investigated mechanical means for modulating and stabilizing the gelation properties of PA hydrogels in a controlled manner. A more stable, biologically inert PA (PA-S) was synthesized and combined with each of the bioactive PAs. Molar ratio (M(r) = PA/PA-S) combinations of 3:1, 1:1, and 1:3 were tested. All PA composites were characterized by observed nanostructure and rheological analysis measuring viscoelasticity. It was found that the PAs could be combined to successfully control and stabilize the gelation properties, allowing for a mechanically tunable scaffold with increased durability. Thus, the biological functionality and natural degradability of PAs can be provided in a more physiologically relevant microenvironment using our composite approach to modulate the mechanical properties, thereby improving the vast potential for cell encapsulation and other tissue engineering applications.