Dual Peptide DPI-VTK Enhances Bone Regeneration

Objectives: Functionalizing biomaterials to interact with cells is one of the key challenges of tissue engineering. Through phage display, we have identified the apatite binding peptide sequence VTKHLNQISQSY (VTK) and the mesenchymal stem cell (MSC) binding peptide sequence DPIYALSWSGMA (DPI). By combining these peptide sequences into the dual-peptide DPI-VTK, we have enhanced the attachment of iPS derived MSCs to mineralized PLGA scaffolds. Peptide coated scaffolds had increased seeding density and cell proliferation compared to controls, as well as increased volume fraction of bone regeneration in an ectopic transplant model. Our hypothesis is that the incorporation of VTK-DPI peptides on the surface of MSC-seeded mineral coated PLGA scaffolds will result in superior bone regeneration compared to non-peptide coated scaffolds in a critical-size calvarial bone defect model.
Methods: Scaffolds with a diameter of 5 mm were fabricated using solvent casting and particulate leaching followed by mineralization with simulated body fluid. The scaffolds were then incubated with a solution of the peptides followed by cell seeding with iPS derived MSCs. A 5 mm critical-size bone defect was created in the calvarium of nude mice (3 mice for each group) and the scaffolds were placed in the defect and the wound was closed with sutures. Animals were sacrificed and the transplants analyzed with microcomputed tomography and histology.



Results: DPI-VTK coated scaffolds resulted in greater bone volume and quality compared to controls.
Conclusions: Our data supports the role of DPI-VTK in enhancing bone regeneration. This work demonstrates the potential clinical applications of DPI-VTK for bone grafting procedures in fields such as dentistry and orthopedic surgery.