Microneedles for Enhanced Bacterial Pathogen Inactivation and Accelerated Wound Healing

Abstract

Bacterial wound infections are a significant socioeconomic concern in the modern healthcare industry owing to increased morbidity, prolonged hospital stay, and mortality. Bacterial infectious agents that colonize the wound bed develop biofilms, acting as a physical barrier that prevents the effective penetration of topical antimicrobials. Further, bacteria in such infectious wounds express a wide range of virulence factors promoting intercellular transmigration and host cell invasion complicating the treatment regimen. To address this need, a water-dissolvable poly-vinyl pyrrolidine (PVP), calcium peroxide (CPO) infused microneedle structure (denoted as PVP/CPO MN) for effective transdermal delivery of antimicrobial payload deep into the tissues is developed. Fluid exudate from the wound bed dissolves the PVP/CPO MN enabling the release of CPO deep into the infected wound bed. A slow catalytic decomposition of CPO results in the sustained release of reactive oxygen species (ROS) deep within the infected wound inhibiting the inter- and intracellular pathogens. Here, a systematic study of microneedle fabrication and sterilization after complete packaging is conducted to ensure scalability and safe applicability while maintaining mechanical and antibacterial properties. In vitro, antibacterial efficacy of the microneedles is validated against two common wound pathogens, Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). Moreover, the PVP/CPO MN exhibited significant efficacy in eradicating both extracellular and intracellular bacterial populations within an in vivo porcine wound model. Additionally, the microneedle technology facilitated a faster wound healing, with approximate to 30% increase compared to control and a 15% improvement over conventional silver dressing. This study presents a novel approach utilizing dissolving microneedles loaded with calcium peroxide (CPO) for eradicating both intercellular and intracellular pathogens in infected wounds. Through systematic in vitro and in vivo experiments, the microneedles demonstrate effective antibacterial properties against P. aeruginosa and S. aureus, leading to accelerated wound healing. The technology showcases promising potential for clinical translation in wound care practice. image