Polyglutamic Acid‐Based Injectable Hydrogel: Design, Fabrication, and Evaluation in Accelerating Infected Wound Repair

ABSTRACT Hydrogels have emerged as promising candidates for infected wound repair owing to their injectability and in situ gelation properties. In this study, an injectable, in situ forming hydrogel, PGBP, was designed and fabricated based on polyglutamic acid (PGA), and its efficacy in accelerating infected wound healing was evaluated. The PGB polymer was synthesized via amidation of PGA with N‐methacryloyl‐1,6‐hexanediamine (MHB), followed by crosslinking with 4‐arm‐PEG‐SH through Michael addition to form PGBP. The resulting hydrogel exhibited a porous three‐dimensional network, high swelling capacity and water retention, excellent blood compatibility, and suitable mechanical properties for wound coverage. When loaded with amikacin (Ami), the Ami@PGBP hydrogel demonstrated potent in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus , along with a sustained drug release profile. Moreover, PGBP significantly enhanced the cellular antioxidant capacity of RAW 264.7 cells, scavenged free radicals (DPPH, ABTS, and •OH), reduced the expression of pro‐inflammatory cytokines (IL‐1β, IL‐6, TNF‐α), and promoted the migration of co‐cultured RAW264.7 and C166 cells. In a murine full‐thickness infected wound model, Ami@PGBP treatment accelerated wound closure, promoted re‐epithelialization and collagen deposition, facilitated skin appendage regeneration, and markedly downregulated both local and systemic inflammatory markers. In vivo biosafety assessments confirmed the hydrogel's biocompatibility and complete biodegradation within 15 days, with no observed adverse effects. Therefore, Ami@PGBP exhibits considerable potential as a multifunctional, safe, and effective dressing for the management of infected wounds.