Antimicrobial Effect of Nitric Oxide Releasing Hydrogels on Staphylococcus Aureus Derived Proteases

Abstract The skin serves as a crucial barrier against environmental insults and invading pathogens. However, traumatic injury or skin disorder can compromise this barrier function, leasing to bacterial colonization and infection of the wound with microorganisms such as Staphylococcus aureus, which are normally present on healthy skin. The secretion of bacterial proteases such as V8 protease from S. aureus can disturb the equilibrium between extracellular matrix degradation and deposition during wound healing resulting in loss of barrier integrity. We report the feasibility of a nitric oxide (NO) releasing poly‐ε‐lysine (pεK) hydrogel to prevent loss of barrier function caused by V8 proteases. The fabrication and characterization of the pεK hydrogel and NO releasing properties in biologically relevant media are reported. The NO‐releasing pεK hydrogel have demonstrated bactericidal activity against a clinical isolate of S. aureus in complex physiological media and concurrently reduce the catalytic activity of secreted V8 protease. Moreover, pεK hydrogels are cytocompatible with keratinocytes and dermal fibroblasts. In contrast, Penicillin G loaded pεK hydrogels showed excellent antimicrobial efficacy but did not affect V8 catalytic activity. This demonstrates that NO‐releasing pεK hydrogels hold potential as an effective treatment for infected wounds reducing the microbial burden and inactivating bacterial secreted proteases.