Antimicrobial prosthetic liner for preventing residual limb infection

About This Grant

PROJECT SUMMARY Residual limb infection is a significant complication following major lower limb amputation, with occurrence rates ranging from approximately 3.9% to 12.9%, depending on the location. These infections often result from contamination at the contact points between the skin and the prosthetic liner, a soft interface material that cushions and protects the residual limb within the prosthesis. Severe infections may require surgical interventions, such as debridement or revision amputations, and can even lead to death. Existing prevention measures, including regular liner cleaning, vigilant wound monitoring, and prophylactic antibiotics, have shown limited efficacy. Furthermore, the use of antibiotics contributes to several adverse outcomes, most notably the promotion of antimicrobial resistance in pathogens. Conventional liner materials promote excessive sweating and poor heat dissipation, creating an ideal warm, moist environment that fosters bacterial growth. This highlights the urgent need for an innovative liner fabric that inherently prevents infections without relying on antibiotics. We propose to address this need by manufacturing liner fabric using polymers derived from chitosan, a natural polysaccharide known for its inherent antibacterial properties and biocompatibility. We have engineered an antimicrobial liner fabric (ALF) consisting of chitosan nanofibers intertwined with medical-grade polyurethane nanofibers. Our preliminary results indicate that chemically modified chitosan nanofibers exhibit pronounced and sustained in vitro activity against both Gram-positive and Gram-negative pathogens, while remaining non- cytotoxic. Our manufacturing approach utilizes high-rate electrospinning technology, which is industrially viable and adaptable to existing large-scale manufacturing equipment. The objective of this Phase I proposal is to demonstrate the antibacterial and antibiofilm effectiveness of the ALF against common pathogens found on residual limbs and to assess its feasibility as an inner, skin-contact layer of prosthetic liners. This objective will be achieved through three specific aims: (1) optimize the formulation of the ALF to improve its antibacterial and antibiofilm efficacy; (2) validate the mechanical durability and biocompatibility of the proof-of-concept liner; and (3) demonstrate the performance and antimicrobial efficacy of the proof-of-concept liner under simulated wear and cleaning conditions. The successful completion of this Phase I proposal will result in a proof-of-concept liner incorporating the best-performing ALF laminated with optimized silicone support. This liner will then be optimized and prepared for safety and efficacy clinical trials in a Phase II effort. We predict that our ALF will transform prosthetic liner technology for patients with major limb loss, positioning it to secure a substantial share of the U.S. prosthetic liner market, which was valued at approximately $88 million in 2023.