Biomimetic Nitric Oxide and Hydroxyapatite Duo for Advanced Direct Pulp Capping - PROJECT SUMMARY Direct pulp capping (DPC) offers an effective vital pulp therapy (VPT) for managing minimal, asymptomatic pulp exposures, with the potential to prevent disease progression and reduce the need for invasive procedures such as root canals, extractions, and extensive prosthetics. Current DPC materials, such as bioceramics and calcium silicates, show limitations in providing bioactive functions essential for pulp healing, including vascularization, mineralized barrier formation, and antimicrobial/anti-inflammatory effects. To overcome these limitations, we propose a novel biomimetic nitric oxide and hydroxyapatite (NO-HA) duo, utilizing a sequential application of NO-releasing peptide amphiphiles (PA-NO) gel and HA-fortified peptide amphiphiles (PA-HA) gel. Our team’s preliminary data indicate that PA-NO has robust antibacterial, anti- inflammatory, pro-angiogenic, and stem cell differentiation capabilities. Additionally, HA provides dimensional stability due to its low solubility, calcium and phosphate tunability, resorption resistance, and radiopacity, potentially supporting dentinogenic differentiation of dental pulp stem cells when used alongside NO. Therefore, we hypothesized that the biomimetic NO-HA duo would synergistically enhance bioactive and physical-mechanical barrier functions, providing a promising DPC solution for VPT. PA-NO will initiate repair by promoting vascularization and delivering antimicrobial and anti-inflammatory effects, while PA-HA will function as a mineralized barrier to stabilize the pulp-dentin interface and support dentinogenesis. In Aim 1, we will 1) characterize PA-HA’s physical-mechanical properties including viscoelasticity, compressive strength, solubility, and marginal adaptation, and 2) evaluate PA-NO’s bioactive functions for vascularization, dentinogenic differentiation, mineralization, and inflammation. In Aim 2, we will assess the feasibility and efficacy of the NO-HA duo in a rat pulp exposure model. The proposed biomimetic NO-HA duo aims to 1) support pulp-dentin repair through vascular network formation and dentinogenic response and 2) establish a stable, mineralized barrier with clinically relevant physical-mechanical properties. This preclinical study represents the first application of engineered NO and HA as bioactive DPC materials and will provide critical evidence for designing future large-scale studies and clinical trials. The biomimetic NO- HA duo could enable pulp-dentin repair while preserving tooth vitality, reducing invasive and irreversible tooth loss, and enhancing patient outcomes, with implications for cost savings and advancements in dental pulp regeneration.
