D. Khalil1, R. Bakshi1, L. Wang1, S. Zhou1, K. Rezzadeh1, A. Hokugo1, R. Jarrahy1 1David Geffen School of Medicine at UCLA,Department Of Surgery,Los Angeles, CA, USA
Introduction: Current commontechniques for repairing full thickness calvarial defects include autologous bone grafting and the use of alloplastic implants, both of which have significant limitations. In this study, we investigate a novel alternative approach to bone repair based on tissue engineering principles. Specifically, we examine the ability of nanoscale peptide amphiphile gels (PAs) engineered tocontrolrelease of VEGF to recruit circulating stem cells to a site of bone regeneration and to help facilitate large-scale bone healing by BMP-2.
Methods: Chemotactic functional scaffolds (CFS) were fabricated by combining collagen sponges with PAs to which VEGF was bound. The in vitro chemotactic activity of these constructs was evaluated by measuring human mesenchymal stem cell (hMSC) movement across a semipermeable membrane when exposed to the CFS. In vivo,CFS function was assessed by implantation of scaffolds into dorsal subcutaneous pockets in rodentsand analysis of migration of peripherally injected hMSCs to the CFS. Large-scale rodent cranial bone defectswas created. CFS and other control materials were implanted and bone regeneration was evaluated.
Results: Migration of hMSCs through semipermeable membranes was significantly greater in scaffolds exposed to CFS compared to control scaffolds (P<0.05). In vivo chemotaxis was evidenced by migration of circulating DiR-tagged hMSCs to the CFS. Successful bone regeneration was noted in the defects treated with CFS.
Conclusion: Our observations suggest that this bioengineered construct successfully acts as a chemo-attractantfor circulating hMSCs, likely due to controlled release of VEGF from the CFS. The CFS may play a role in the future design of clinically relevant bone graft substitutes.?