This project aims to develop the ideal bandage that provides antimicrobial, anti-inflammatory and analgesic activity locally to the site of wounds infected with biofilms of multi-drug resistant Pseudomonas aeruginosa, listed as a serious threat by the Centers for Disease Control and Prevention. Ibuprofen delivered locally to wounds has been shown to act both as an anti-inflammatory and an analgesic. Silver has been incorporated into commercially available wound dressings due to its potent, broad spectrum antimicrobial activity, although the high local concentrations impede wound healing through toxicity to human cells. Preliminary data demonstratepotentantimicrobialandanti-inflammatoryactivityofanovelsilversaltofibuprofen(Ag+IBU)that will be loaded into electrospun scaffolds of the Food and Drug Administration (FDA)-approved polymer, poly(caprolactone) (PCL) functionalized with collagen to promote wound healing. N-acetyl cysteine (NAC), an FDA-approved therapeutic that abrogates silver toxicity will also be loaded into the PCL membranes. The project addresses thehypotheses that electrospun PCL membranes functionalized with collagen and loaded with Ag+IBU and NAC will provide superior antimicrobial and wound healing efficacy compared with a commercially-available silver-based bandage. The following aims will address these hypotheses: 1. fabricate and evaluate the capacity of Ag+IBU/NAC-loaded, collagen-functionalized PCL scaffolds to enhance cell adhesion and migration, eradicate P. aeruginosa biofilms, and preserve fibroblasts, in vitro, and 2. determine the localized therapeutic concentrations, wound healing ability, and antimicrobial activity of Ag+IBU/NAC- loaded,collagen-functionalizedPCLscaffoldscomparedwithfreedrugandcommerciallyavailableAg+loaded bandages,invivo.ThesestudieswillbethefirsttouseN-acetylcysteinetoabrogatesilvertoxicityandthefirst to assess the wound healing activity of bandages loaded with the novel antimicrobial, anti-inflammatory, and analgesicsmallmolecule,silveribuprofen.
The goal of this project is to develop the ideal bandage that provides antimicrobial, anti-inflammatory and analgesic activity locally to the site of wounds infected with biofilms of multi-drug resistant Pseudomonas aeruginosa.Ibuprofendeliveredlocallytowoundshasbeenshowntoactbothasananti-inflammatoryandan analgesic. Silver has been incorporated into commercially available wound dressings due to its potent, broad spectrumantimicrobialactivity,althoughthehighlocalconcentrationsimpedewoundhealingthroughtoxicityto humancells.Anovelsilversaltofibuprofenwillbeco-loadedintoelectrospunscaffoldswithN-acetylcysteine, an FDA-approved therapeutic that abrogates silver toxicity, and the wound healing properties compared with commerciallyavailablesilver-loadedbandages.