The NIH Diversity Supplement is to support a budding post-doctoral research scientist to focuse on advancing the research initiated in the parent R01 project (Grant: R01DE031812, titled: Angiogenic and anti-microbial supports for pulp regeneration), which investigates novel angiogenic and anti-microbial hydrogels for use in regenerative endodontics. The central aim of this supplement is to support this candidate in evaluating the interactions between these hydrogels and cellular receptors, improving the understanding of material-cell interactions, and demonstrating the hydrogel's preclinical efficacy in an inflamed large animal model, essential for progressing toward FDA approval. The Supplemental Project Aims are to Evaluate Material-Cell Receptor Binding: Aim 1: the candidate will utilize computational modeling and in vitro assays to investigate the binding properties between the angiogenic peptide hydrogel SLan and the VEGFR2 receptor. By assessing the molecular dynamics of peptide interactions with bacterial membranes and VEGF receptors, this work will provide critical data on the angiogenic potential of the hydrogel system. Aim 2: Inflamed Revascularization Model: In collaboration with endodontic and pulp biology experts (Co-I), the candidate will conduct in vivo experiments in a porcine model of pulp infection. These studies will assess the hydrogel's ability to regenerate vascularized soft tissue following pulpectomy, simulating real-world clinical conditions of pulp inflammation. Key outcomes will include the degree of root thickening, root lengthening, and vascularized tissue regeneration, determined by both radiographic and histological analyses. Aim 3: FDA Pre-Investigational New Drug (pre-IND) Application: the candidate will work with the team to navigate the regulatory pathway required for an IND application. This will include synthesizing the hydrogel peptides under good manufacturing practices (GMP), compiling quality assurance and chemistry, manufacturing, and controls (CMC) documentation, and engaging in pre-IND meetings with the FDA. Successful completion will establish a foundation for human clinical trials in regenerative endodontics. Expected Impact: This research aims to deliver a novel, off-the-shelf, injectable hydrogel capable of regenerating vascularized pulp tissue, providing a significant advancement over current endodontic treatments. If successful, this technology will drastically reduce the failure rates associated with conventional root canal procedures and provide a more cost-effective, accessible solution for dental care worldwide. Through this diversity supplement, the candidate will play a crucial role in advancing this groundbreaking translational research.