A PHMB-Functionalized Fully Absorbable Synthetic Matrix as a Novel Alternative to Biologics: Balancing Antibacterial Efficacy, Tissue Repair, and Safety

Effective management of acute, complex, and chronic wounds requires constructs that simultaneously support tissue repair and provide sustained infection control. Biologic-derived materials, despite their regenerative potential, are limited by insufficient long-term antibacterial activity and susceptibility to enzymatic degradation. To overcome these limitations, a fully absorbable synthetic matrix composed of electrospun composite fibers functionalized with polyhexamethylene biguanide (PHMB) (hereafter, PHMB Matrix) was developed to mimic extracellular matrix architecture while enabling durable antibacterial performance. Quantitative assessment per AATCC 100 demonstrated robust broad-spectrum efficacy (>99.99% reduction) against six clinically relevant Gram-positive and Gram-negative pathogens, with potency retained after 15 months of real-time aging. The matrix's interconnected fibrous architecture enables a controlled, biphasic PHMB release coordinated with biodegradation, sustaining antibacterial protection throughout a 28-day healing period. In porcine full-thickness wound models, the PHMB Matrix achieved 63.53% ± 12.0% wound area reduction by Day 22, demonstrating accelerated mid-phase healing compared to an antibacterial collagen control (<i>p</i> < 0.05 on Day 22), with both treatments achieving comparable near-complete closure by Day 28. Pharmacokinetic analysis confirmed localized drug enrichment with negligible systemic exposure. These findings establish the PHMB-functionalized synthetic matrix as a safe, effective, fully absorbable alternative to biologic-derived materials for soft tissue repair, offering sustained antibacterial efficacy and a favorable safety profile.