Antimicrobial Peptide Treatment to Combat Wound Biofilm

ABSTRACT The long term goal of this work is to develop a treatment for chronic wounds that will prevent wound biofilm and facilitate healingChronic wounds affect approximatelymillion patients in the US with annual treatment cost up to $billionDespite high treatment costsapproximatelyof patients will not heal using existing interventions and many wounds progress to serious infectionsincluding amputationsThe involvement of drug resistant organisms and multispecies biofilms is gaining recognition as an important factor in wound chronicityThere are currently no therapeutic options to address these issuesNew therapeutics are urgently needed to reduce painimprove functional outcomesand improve quality of life for those with chronic woundsThe goal of this work is to develop an antimicrobial wound treatment based on an engineered cationic antimicrobial peptide called ASPthat is effective against biofilm and conducive to healingASPdisplays potent activity against biofilms of both gram positive and gram negative bacteriaincluding multi drug resistant organismsDROsover a broad range of pH and in the presence of proteinsChitosan hydrogels containing ASPwill be developed for primary wound application to establish feasibility for efficacy and safety using both in vitro and animal modelsThe composition of hydrogels developed will be tailored to achieve a duration of ASPrelease exceedingdayswhich will be measured by RP HPLCThe efficacy of hydrogels will be established first using in vitro biofilm models where challenge durations will extend overday periods and biofilms tested will include methicillin resistant Staphylococcus aureusMRSAAcinetobacter baumanniiand Pseudomonas aeruginosaThe hydrogels will be evaluated for biocompatibility using direct contact cytotoxicity assaysThese assays will be conducted for both primary human dermal fibroblasts and keratinocytesFinallyboth safety and efficacy of the ASPHydrogel will be evaluated using a porcine model of excisional MRSA wound infectionThis model will be utilized to conduct an early dose range evaluationA commercial silver based product will be included for comparison in both the in vitro an animal studiesSuccessful completion of this project will demonstrate feasibility for an ASPHydrogel that provides broad spectrum antibiofilm coverage and overcomes the biocompatibility and cytotoxicity limitations associated with silver and other antiseptic productsIf successfulthis product will have a significant impact on reducing morbidity and improving the quality of life of patients with chronic wounds PROJECT NARRATIVE The goal of this project is to develop a product that will be used to treat chronic and infected woundsThe product will fill a critical gap in the need for antimicrobial treatments that are biocompatible and supportive of healingIf successfulthe product is expected to have a substantial impact on the treatment and quality of life of patients with chronic wounds by reducing infectionpainamputation risksand treatment costs