Functionalization of Two-Component Gelatinous Peptide/Reactive Oligomer Hydrogels with Small Molecular Amines for Enhanced Cellular Interaction

A platform of two-component cross-linked hydrogel (cGEL) based on gelatinous peptides and anhydride-containing cross-linkers (oPNMA, oPDMA) is extended for use in peripheral nerve regeneration. Hybrid composites with bio-/chemical cues for enhanced biophysical and biochemical properties were fabricated by covalently grafting small molecular, heterobifunctional amines including the nerve growth factor mimetic LM11A-31 to the oligomeric cross-linkers prior to hydrogel formation. The cytocompatibility and growth-supportive conditions within the matrix are confirmed for pristine and modified hydrogels using L929 mouse fibroblasts and human adipose-derived stem cells (hASCs). For hASCs, cell behavior depends on the type of cross-linker and integrated amine. In a subsequent step, neonatal rat Schwann cells (SCs) are seeded on pristine and functionalized cGEL to investigate the materials' capabilities to support SC growth and morphology. Within all formulations, cell viability, adherence, and cell extension are maintained though the cell elongation and orientation vary compared to the two-dimensional control. It is possible to merge adjustable two-component hydrogels with amines as biochemical signals, leading to improved nervous cell proliferation and activity. This indicates the potential of tunable bioactive cGEL as biomaterials in nerve implants, suggesting their use as a foundational component for nerve conduits.