Biomimetics for Dentin Regeneration

DESCRIPTION: This project seeks to develop a commercially viable substitute therapy for existing vital pulp therapy, root canal, root repair and apexification procedures. The proposed new therapy is based on novel developments in synthetic polymers for tissue engineering. New methods of polymerization yield fibers or sheets of poly (acids) with controllably-sized interconnecting pores. Additionally biologically active signaling molecules such as morphogens, growth or angiogenic factors and/or a thin layer of carbonated hydroxyapatite crystals and/or cells can be added. These new scaffolds have been demonstrated to serve multiple functions including direct stimulation of bone formation (mineralized version) and controlled release of signaling molecules from mineralized or non-mineralized scaffolds. Herein we propose to determine the capacity of this new material to induce reparative dentinogenesis in vitro and in vivo models of odontoblast differentiation and reparative dentin formation. Mineralized and non-mineralized scaffolds will be tested with and without allogeneic stem cells cultured from dental pulp and gingiva. The rationale for this study derives from our data that experimental protein and ex vivo gene therapies induce both bone and dentin regeneration. Hence it is deemed likely that a simpler approach using a material without additional biological agents might also induce reparative dentinogenesis. AIIogeneic pulp and gingival cells, isolated using methods demonstrated to produce "stem" cells, attached to the mineralized scaffold will be compared to the "neat" scaffold. These experiments will employ our published model of reversible pulpitis induced in adult ferret teeth. If successful these experiments could lead to efficacy tests in non-human primate models of reparative dentinogenesis (Phase II), human clinical trials and commercialization.