Cell and Material-Specific Phage Display Peptides Increase iPS-MSC Mediated Bone and Vasculature Formation In Vivo

Biomimetically designed materials matching the chemical and mechanical properties of tissue support higher mesenchymal stem cell (MSC) adhesion. However, directing cell-specific attachment and ensuring uniform cell distribution within the interior of 3D biomaterials remain key challenges in healing critical sized defects. Previously, a phage display derived MSC-specific peptide (DPIYALSWSGMA, DPI) was combined with a mineral binding sequence (VTKHLNQISQSY, VTK) to increase the magnitude and specificity of MSC attachment to calcium-phosphate biomaterials in 2D. This study investigates how DPI-VTK influences quantity and uniformity of iPS-MSC mediated bone and vasculature formation in vivo. There is greater bone formation in vivo when iPS-MSCs are transplanted on bone-like mineral (BLM) constructs coated with DPI-VTK compared to VTK (p < 0.002), uncoated BLM (p < 0.037), acellular BLM/DPI-VTK (p < 0.003), and acellular BLM controls (p < 0.01). This study demonstrates, for the first time, the ability of non-native phage-display designed peptides to spatially control uniform cell distribution on 3D scaffolds and increase the magnitude and uniformity of bone and vasculature formation in vivo. Taken together, the study validates phage display as a novel technology platform to engineer non-native peptides with the ability to drive cell specific attachment on biomaterials, direct bone regeneration, and engineer uniform vasculature in vivo.