Supramolecular Nano-Assembly of Melatonin-Conjugated Peptide as a Multifunctional Scaffold for Wound Healing Applications

Wounds are one of the major socioeconomic challenges globally, mainly arising from trauma, surgery, burns, and infections. In many cases, prolonged recovery time leads to complications and requires a multifunctional approach that can target tissue regeneration and prevents infection. The supramolecular assembly of peptides yield well-defined nanoassemblies that resemble the extracellular matrix and influence cellular interactions. The peptide-based systems allow structural fine-tuning, high biocompatibility, and the ability to incorporate bioactive signals. Despite advances in peptide-based supramolecular gels for wound treatment, multifunctional peptide-based scaffolds remain relatively unexplored. In this work, we have designed a melatonin-conjugated amphiphilic peptide that self-assembles into a viscoelastic, nanofibrous gel with antibacterial and wound-healing functions. The amphiphilic nanofibers effectively disrupted bacterial membranes, and conjugated melatonin enhanced the antioxidant activity and promoted M1 to M2 macrophage polarization. The structural and biological properties of the self-assembled gel provide a promising multifunctional platform for wound management.