Therapeutic management of bone loss in the craniofacial region as a consequence of trauma, surgery or congenital malformations presents a clinical challenge. Cleft palate is the second most common congenital deformity in the United States that occurs with an incidence of 1 in 700. Regeneration of bone in the hard palate region is essential to restore proper maxillofacial growth. Of several approaches stem cell based strategies are promising to regenerate of bone. Our long term goal is to regenerate bone and restore the normal craniofacial growth. Successful regeneration of bone requires the use of appropriate stem cells, scaffolds and growth supporting molecules. Human gingiva derived mesenchymal stem cells (HGMSCs) are excellent source, as they are obtained with a minimally invasive technique, highly proliferative with minimal risk of immune-rejection. Puramatrix is a nanofibrous self-assembled peptide hydrogel that facilitates HGMSCs proliferation and differentiation. Bone morphogenic protein2 (BMP2) is a potent growth factor used clinically for bone tissue formation. Due their short half-life, high levels of BMP2 are used in clinical management for bone regeneration. However, use of excessive BMP-2 can have adverse effects on normal craniofacial development.
This project aims to establish a cell-scaffold system with optimized concentrations of BMP2 to regenerate bone. Our hypothesis is GMSCs embedded in the Puramatrix will facilitate bone regeneration with minimal use of BMP2. In the proposed project we intend to i) establish the optimal dose of BMP2 in vitro in vivo. Various doses of BMP2 will be added to Puramatrix scaffold impregnated with or without GMSCs and injected subcutaneously in rats and the bone formation will be assessed. The results of the present study can be used to develop optimized strategies and evolve novel approaches for repair and regeneration of bone, especially bony voids of cleft palate.