Over 15 million root canal treatments (RCT) are performed yearly in the United States to treat deep caries and dental pulp infection. This procedure however, removes both the diseased and healthy pulp, leading to tooth devitalization. Furthermore, RCTs are associated with a high incidence of reinfection and dentin fracture, reduced sensitivity and eventual tooth loss. Thus there is an unmet clinical need for alternative endodontic therapies that can preserve tooth vitality and ensure long term dental health. The strategy of vital endodontic therapy explored in this thesis centers on the design of a bioactive scaffold that guides host cell homing while providing antibiotic release, in effect harnessing the intrinsic repair potential of the native pulp while simultaneously eliminating residual bacteria that can cause recurrent infection.

Specifically, a bioactive polyethylene glycol fibrinogen (PEG-fibrinogen) hydrogel is optimized to support host cell infiltration, maintain dental pulp cell phenotype, and enable pulp regeneration. Ciprofloxacin, a clinically relevant antibiotic for RCT, is incorporated into PEG-fibrinogen to prevent infection. The scaffold and culturing parameters optimized in vitro using either explant or a tooth slice model includes fibrinogen, poly(ethylene glycol) diacrylate (PEGDA) and photoinitiator concentration, as well as cell source and density. In addition, dose-dependent antibiotic effects on both anaerobic bacteria isolated from deep caries and healthy pulp cells are evaluated. The collective findings of this thesis demonstrate that a cell-instructive hydrogel comprised of a fibrinogen backbone and cross-linked with difunctional poly(ethylene glycol) side chains supports pulp cell viability, phenotypic morphology, and host cell migration. Furthermore, increasing pulp cell density promotes cell biosynthesis and a higher fibrinogen concentration is found to enhance collagen deposition. Photoinitiator and PEGDA concentrations have been optimized to enhance hydrogel mechanical properties and gel degradation, while supporting pulp cell phenotype. An optimal antibiotic dosage in the hydrogel has been identified that significantly reduces bacteria count from infected dental pulp without harmful side effects on dental pulp cell phenotype and host cell migration.

In summary, this thesis focuses on the design of a bioactive hydrogel-based scaffold with antibiotic release that can induce dental pulp regeneration without the addition of cells and stimuli such as growth factors and minimize post-therapy infection. The innovative scaffold design strategy presented here lays the foundation for the development of vital endodontic therapy that harnesses pulp self-repair and sustains long-term tooth function.