Research Project
8392335
DESCRIPTION (provided by applicant): Calvarial reconstruction continues to present challenges for surgeons. Although the gold standard for restoration of the skull is autologous bone, particularly from the removed flap, substitutes are often necessary due to the flap becoming infected or infiltrated with tumor tissue. Other challenges to the use of the removed flap include age, difficulties with storage, surgery timing, and anatomical conditions. Therefore, the surgeon often relies on alloplastic materials such as titanium mesh, which can be easily shaped, has a modulus of elasticity similar to bone, and is biocompatible. However, titanium mesh does not provide the cells or growth factors needed to stimulate bone regeneration. One approach for bone regeneration is the combination of a scaffold with osteogenic cells to accelerate healing by reducing the need for endogenous cell migration and proliferation at the implant site. Adipose-derived and bone marrow-derived mesenchymal stem cells (ASCs and BMSCs, respectively) have shown potential to support bone growth in multiple models of bone defects and craniofacial reconstruction. Currently, ASCs and BMSCs are purified through culture expansion or through tedious negative or positive selections with antibodies. The difficulty achieving therapeutic numbers of cells and the complicated processing steps involved in their isolation have limited the use of stem cells in the clinic. To address this unmet need, Affinergy used phage display screening to identify peptide sequences that bind stem cells with high affinity. In this application, we propose to test the feasibility of modifying the surface of titanium with this peptide to improve the capture and retention of stem cells. The technology will significantly improve outcomes for oral and craniomaxillofacial surgeries with titanium implants. PUBLIC HEALTH RELEVANCE: Calvarial reconstruction continues to present challenges for surgeons. One proposed solution is the use of adult stem cells to augment bone regeneration; however, the use of stem cells has been limited by the low frequency of the cells in tissue. In this application, we propose to develop a titanium implant that can capture and retain adult stem cells to improve clinical outcomes.
