Development of antimicrobial peptide loaded PVA-based nanofibrous matrix to combat bacterial wound infection

Abstract

Wound infections caused by antibiotic resistant bacterial strains, present a significant challenge in healthcare worldwide due to the uncontrolled use of antibiotics. A promising alternative to conventional antibiotics is antimicrobial peptides (AMPs) that provide potent, broad spectrum antibacterial activity with a reduced likelihood of resistance development due to their action mechanism. This research focuses on developing and evaluating AMP loaded PVA nanofibrous matrix as an innovative approach to treating these infections. AMPs extracted from corn seeds, were stabilized within PVA nanofibers through in situ incorporation facilitated by dopamine, resulting in robust and stable nanofibrous matrices. Physical and chemical characterizations, including FTIR, XRD, and tensile test, indicated that the 2:1-PVA/AMP formulation offered superior structural integrity with a tensile strength of 3.2 ± 0.3 MPa, making it the an effective option for further testing. This formulation showed a significant zone of inhibition (ZOI) of 19 ± 0.3 mm against Staphylococcus aureus, 16 ± 0.3 mm against Escherichia coli, 48 ±0.1 mm against Proteus spp., and 16 ± 0.1 mm against Pseudomonas aeruginosa, outperforming the 1:1-PVA/AMP. Comparatively, ceftazidime (CAZ) showed no antibacterial activity across all tested strains. Hemocompatibility assessments revealed that all PVA/AMP samples exhibited a hemolysis ratio below 3%, confirming their safety for blood contact. In vivo experiments using an infected wound model in mice demonstrated that the 2:1-PVA/AMP nanofibers significantly accelerated wound healing, with markedly reduced pus formation and superior tissue regeneration compared to both the control and PVA/CAZ groups. Histological analysis showed a marked reduction in the epithelial gap and enhanced re-epithelialization, with 87 ± 2% wound closure observed by day 14, compared to 44 ± 1% in the PVA/CAZ group. Additionally, a significant reduction in inflammatory cell infiltration was observed in the 2:1-PVA/AMP group which indicates better management of infection and inflammation. This contributed to more effective tissue regeneration compared to both the control and PVA/CAZ groups. These results underscore the potential of AMP loaded PVA nanofibers as a superior alternative to conventional antibiotic treatments in wound care, particularly for managing infections caused by antibiotic resistant bacteria.