Wound healing has been studied extensively on the skin and particularly following intestinal injury. Intestinal wound healing efficiency is highly sensitive to environmental factors, especially the microbiome, where specific microbial community structures or supplementation with probiotic bacteria enhances the wound healing process. However, little is known about how the oral microbiome affects ONF wound healing. We directly address this gap in knowledge and show preliminary data that creating an ONF in a murine model results in marked changes in the microbiome composition with the complete disappearance of certain microbes and blooms of other bacterial taxa.Thus, our overall hypothesis is that the oral commensal microbiome exerts positive modulatory influences on oral wound healing and may limit ONF formation. Discovering specific bacterial taxa within the oral cavity or wound tissue that positively influence healing will be essential information for the characterization of an eubiotic oral microbiome for wound healing. Our experiments will also generate critical information for clinicians about the prudent use of antibiotics after cleft palate surgery and the effects of depleting the oral microbiome during healing. We will also substantiate the approach of the repletion of the oral commensal bacteria using hydrogel technology as the vehicle to enhance oral wound healing. Together, these studies will yield critical data to inform new therapeutic modalities to lower the prevalence of ONFs following cleft palate surgery.