GelMA-based peptide conjugated hydrogel with antifibrotic modulation and antibiofilm activity

Excessive fibrosis and implant-associated infections remain major challenges in wound healing and post-surgical tissue repair, often resulting in impaired regeneration and long-term complications. Although gelatin methacryloyl (GelMA) hydrogels are widely used in regenerative medicine due to their biocompatibility and tunable physicochemical properties, they intrinsically lack antifibrotic and antibacterial functionality. Herein, we report a dual-functional GelMA-based hydrogel (GelMA-AMP/AFP) achieved by the covalent co-conjugation of an antifibrotic peptide (DR8) and a broad-spectrum antimicrobial peptide (P9-4), enabling simultaneous regulation of fibrotic responses and bacterial colonization within a single biomaterial platform. The peptide-functionalized GelMA hydrogels preserved their porous microarchitecture, mechanical integrity, and swelling behavior while providing a sustained peptide release profile over 14 days. In a TGF-β1-induced in vitro fibrotic fibroblast model, the dual-functional hydrogel significantly suppressed fibroblast proliferation and migration, reduced collagen deposition, and downregulated key profibrotic markers, including COL1A1, ACTA2, FN1, and TGF-β1, at both gene and protein levels. In parallel, the same GelMA-AMP/AFP platform effectively inhibited bacterial adhesion and biofilm formation by multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA), without inducing cytotoxicity. This study reports a GelMA-based biomaterial to simultaneously integrate covalently conjugated antifibrotic and antimicrobial peptides, thereby achieving concurrent suppression of fibrosis and inhibition of biofilm formation within a single material system, in vitro. By combining complementary biological functionalities without compromising material properties, this study presents a chemically driven strategy for multifunctional biomaterial design. This strategy may provide a useful foundation for future studies targeting advanced wound dressings, post-surgical adhesion prevention, and infection-prone tissue repair, pending further in vivo validation.