Tunable Macroscopic\nAlignment of Self-Assembling Peptide\nNanofibers

Abstract

Progress in the design and synthesis of nanostructured\nself-assembling\nsystems has facilitated the realization of numerous nanoscale geometries,\nincluding fibers, ribbons, and sheets. A key challenge has been achieving\ncontrol across multiple length scales and creating macroscopic structures\nwith nanoscale organization. Here, we present a facile extrusion-based\nfabrication method to produce anisotropic, nanofibrous hydrogels using\nself-assembling peptides. The application of shear force coinciding\nwith ion-triggered gelation is used to kinetically trap supramolecular\nnanofibers into aligned, hierarchical macrostructures. Further, we\ndemonstrate the ability to tune the nanostructure of macroscopic hydrogels\nthrough modulating phosphate buffer concentration during peptide self-assembly.\nIn addition, increases in the nanostructural anisotropy of fabricated\nhydrogels are found to enhance their strength and stiffness under\nhydrated conditions. To demonstrate their utility as an extracellular\nmatrix-mimetic biomaterial, aligned nanofibrous hydrogels are used\nto guide directional spreading of multiple cell types, but strikingly,\nincreased matrix alignment is not always correlated with increased\ncellular alignment. Nanoscale observations reveal differences in cell–matrix\ninteractions between variably aligned scaffolds and implicate the\nneed for mechanical coupling for cells to understand nanofibrous alignment\ncues. In total, innovations in the supramolecular engineering of self-assembling\npeptides allow us to decouple nanostructure from macrostructure and\ngenerate a gradient of anisotropic nanofibrous hydrogels. We anticipate\nthat control of architecture at multiple length scales will be critical\nfor a variety of applications, including the bottom-up tissue engineering\nexplored here.