This collaborative seed project between Drs. Hartgerink and D'Souza is designed to acquire initial data and lay the groundwork for a biomimetic, nanostructured tissue engineering approach to dental reconstruction.

It harnesses the expertise of the Hartgerink lab in the design, synthesis and characterization of novel nanostructured scaffolds for tissue engineering and the expertise of the D'Souza lab in the handling and characterization of SHED dental stem cells. We will utilize peptide amphiphile nanofibers as a novel scaffold to promote the proliferation and differentiation of dental stem cells. Peptide-amphiphiles (PA) self-assemble into nanofibers which can display one or more cell adhesion ligands and can degrade in a cell responsive fashion. These fibers form a gel that entraps cells in a three dimensional matrix simply by mixing the PA with a suspension of cells in culture media. This eliminates the need for complicated seeding protocols necessary with other tissue engineering scaffolds. Previously PAs have been used successfully to support the growth of a number of cell lines, including dental pulp fibroblasts. The goal of this seed grant is to optimize peptide-amphiphile nanofiber gels with respect to cell-adhesion ligands, degradation profile and mechanical properties to support the growth and differentiation of dental stem cells. This is broken into three aims: Correlation ofcell viability to peptide-arnphiphile nanojiber adhesive ligand density. Correlation ofcell migration and cell proliferation to presence and concentration of peptide-amphiphile nanojiber enzyme mediated degradation sequence. Assessment ofcell differentiation with respect to adhesive ligand density and nanojiber degradation. This is a critical first step in engineering fully functional dental tissues. Success of this seed grant will help to establish PA nanofibers as a powerful and versatile scaffold for tissue engineering and will help to address a fundamental question of the importance of nano-structural control compared to simple chemical presentation. This is coupled with the clear clinical need for advanced therapies for dental repair and replacement which has recently been highlighted by the NIH Craniofacial Diseases and Skeletal Branch.