Functionalization of Mineralized Biomaterials With Peptide DPI-VTK for Bone Regeneration

Objectives: There is much interest in developing synthetic biomaterials that can replace traditional autografts and allografts for craniofacial bone grafting, but modifying such materials to interact with living cells remains a key challenge. Incorporating bioactive molecules such as peptides into biomaterials is a key strategy for enhancing regeneration. Our laboratory created the dual-functional DPI-VTK peptide sequence GGDPIYALSWSGMAGGGSVTKHLNQISQSY that contains both a mesenchymal stem cell (MSC) binding domain and a mineral-binding domain. DPI-VTK is advantageous over other peptides such as RGD and P15 due to its specificity for MSCs and high absorption onto hydroxyapatite. Preliminary data has shown that DPI-VTK coated scaffolds are capable of bone regeneration in an ectopic subcutaneous transplant model. Our hypothesis is that the functionalization of mineralized materials with DPI-VTK peptides can enhance the regeneration of craniofacial bone defects.

Methods: PLGA scaffolds were fabricated using solvent casting and particulate leaching and mineralized in simulated body fluid. Mineralized scaffolds were coated with peptides (4 groups: DPI-VTK, P15, RGD, no peptide) and seeded with human MSCs. Scaffolds were then placed in a 5 mm diameter calvarial defect in immunocompromised mice (n=4 per group). After 8 weeks of healing, the animals were sacrificed and the regenerated bone defects analyzed with microcomuted tomography and microscopy.
Results: Using a flow mineralization process, we were able to achieve BV/TV values of 0.109±0.018 with homogenous surface coating on the scaffolds. In-vivo data shows enhanced bone regeneration for DPI-VTK functionalized scaffolds versus controls.
Conclusions: Our data shows that DPI-VTK can enhance bone tissue engineering. Future studies will involve investigation of the effect of DPI-VTK on the longterm survival of transplanted cells, migration of host cells into scaffold, and the mechanism of DPI-VTK's affinity for MSCs. Ultimately, this work demonstrates the potential clinical applications of DPI-VTK for craniofacial bone regeneration.