"Designing Cell-Responsive Scaffolds for Bone Regeneration"
Each year, over two million bone grafting procedures are performed worldwide. While patient-derived bone grafts are the standard, donor shortages and complications underscore the need for engineered alternatives. Biodegradable polyesters like polycaprolactone are promising scaffold materials due to their mechanical properties and ability to be 3D printed into patient-specific geometries. However, polycaprolactone exhibits a slow degradation rate compared to that of new bone formation, and the lack of signals to promote blood vessel growth limits its effectiveness in supporting regeneration. Here, peptide–polyester conjugates were designed to create scaffolds that respond directly to cellular activity. Peptides incorporated into polyester backbones allow scaffolds to degrade when cleaved by cellular proteases and release signals only when specific cells are active. Fluorescence spectroscopy was used to evaluate scaffold behavior. Scaffolds containing protease-sensitive peptides showed significantly faster degradation than controls, confirming sequence-specific, cell-mediated resorption. Scaffolds functionalized with a vascular endothelial growth factor-mimetic peptide were successfully 3D printed, and preliminary release studies are underway. These peptide-polyester systems offer a versatile framework for scaffolds that dynamically interact with cells, advancing regenerative materials designed for clinically relevant bone repair.