Crosslinked Gelatin‐Polycaprolactone Scaffolds: Balancing Biocompatibility and Inflammatory Response for Tissue Engineering Applications

ABSTRACT The integration of biomaterials in tissue engineering faces challenges due to the host's inflammatory response, which can compromise scaffold biocompatibility. Polycaprolactone (PCL) is approved by the Food and Drug Administration (FDA) for certain medical devices but lacks universal acceptance as a standalone biomaterial due to its hydrophobic nature and low bioactivity. Combining PCL with natural polymers like gelatin has been shown to improve hydrophilicity, biocompatibility, and cellular interactions. However, gelatin's instability in aqueous environments requires crosslinking for sustained performance. In this study, three‐dimensional (3D) porous PCL scaffolds were fabricated using the solvent casting and particle leaching (SCPL) technique, then functionalized with gelatin. Stabilization was achieved through chemical crosslinking (EDC/NHS) and physical crosslinking (UV radiation). The scaffolds were characterized in terms of morphology, porosity, wettability, and microhardness, and biologically evaluated in vitro with human fetal osteoblasts (hFOB) and in vivo in a subcutaneous implantation model in Wistar rats. Results confirmed stable gelatin incorporation without compromising porosity. Enhanced hydrophilicity, surface resistance, and improved cellular adhesion, viability, and proliferation were observed in vitro. Histological analysis in vivo showed no adverse inflammatory responses. These findings suggest that functionalizing PCL scaffolds with crosslinked gelatin is a promising strategy for regenerative medicine applications.