| Summary: | Dental caries and traumatic impact are two major causes of destruction of dental soft and mineralized tissues that affect a large segment of the population and pose major public health concerns. Conventional treatment strategies rely on mere replacement with bioinert filling materials. Hence, a critical need exists for biology-based therapeutic approaches to restore damaged dental tissues to their original form and function. Recent developments in tissue engineering, material sciences and stem cell research offer considerable potential to impact dental therapies. A customized scaffolding system laden with bioactive factors could deliver dental stem cells to the site of injury. An applicable scaffold should be biocompatible and biodegradable, accommodate cells, incorporate growth and differentiation factors, and allow for injection into small defects. Synthetic peptide hydrogels are particularly interesting in all these aspects. Our pilot study demonstrated their compatibility with two dental stem cell lines. In Specific Aim 1, peptide sequences were developed to further optimize the system for cell proliferation and spreading. In Specific Aim 2, the gels were modified to incorporate bioactive molecules and growth factors for cell differentiation and vasculogenesis. Release profiles were established, and cell culture studies demonstrated the induction of cellular differentiation. For Specific Aim 3, the generated material was utilized in an animal model, where constructs of cell- and growth-factor-laden gels in standardized dentin cylinders were transplanted into immunocompromised mice. Soft connective tissue formation and new blood vessel formation could be observed, along with localized collagen deposits, indicating beginning dentin formation. In summary, the objective of this research was to modify and optimize peptide-based hydrogels in order to develop a novel tissue engineering approach for the regeneration of dental tissues.
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