Commercialization of the Vital-Dent Regenerative Pulp Therapy - PROJECT SUMMARY/ABSTRACT Over half of all children severely hurt their teeth through physical injury or carious legion, resulting in the performance of 4.7M endodontic procedures per year in the pediatric and young adult population. Maintenance of vital pulp in the tooth is critical for the ability to fight future infections, prevent fracture, and retain the tooth, particularly for immature permanent teeth without fully developed roots. Existing treatment options include non- vital therapies, such as apexification and root canal therapy, vital pulp therapies, which preserve some existing pulp but do not maintain vital pulp throughout the dental canal, and revascularization therapy, which suffers from high rates of adverse events. Treatment with Vital-Dent, a hydrogel material that supports the regeneration of vital pulp tissue for the restoration of pulp throughout the dental canal, will increase tooth retention and promote resistance to fracture and infection. Vital-Dent is an acellular, drug-free hydrogel that provides obturation and pulp regeneration for regenerative endodontic procedures. Vital-Dent consists of two biopolymers (porcine derived gelatin with added unfractionated heparin) and photoinitiator dissolved in saline. The liquid hydrogel precursor is placed into the pulp canal and then is photocrosslinked. The hydrogel works as a barrier to influx of blood into the treated tooth root, inhibiting the acute inflammatory response to thrombus formation, with the gelatin supporting cellular migration into the hydrogel from the periapical space. The heparin supplement promotes swelling of the gelatin hydrogel to ensure the full obturation and the barrier function. The extensive testing completed to date demonstrates the regeneration of pulp tissue and maintenance of tooth vitality with Vital-Dent. Phase I results showed that Vital-Dent doubled the incidence of apex closure relative to revascularization. This is the paramount outcome for pediatric indications, as continued tooth development greatly increases tooth survival. The work proposed here represents a significant step towards bringing Vital-Dent to the clinic. The Vital-Dent manufacturing process will be scaled up and the product formulation will be optimized to include cGMP precursor biomacromolecules while maintaining the equivalent physical properties and biocompatibility of the final hydrogel. This aim will result in the manufacture of a fully cGMP-compliant batch of Vital-Dent. The mechanical and functional properties of the final Vital-Dent formulation will be characterized, and an in vivo study will evaluate the effectiveness of Vital-Dent. Finally, we will perform biocompatibility testing to assess for cytotoxicity, sensitization potential, irritation, and acute and subacute toxicity. The proposed studies have been designed to support the filing for FDA clearance of Vital- Dent, a critical step towards adoption of Vital-Dent.
