Decoupling Bioactivity and Processability: RGD Click-Functionalized Coatings for a 3D-Printed PCL Scaffold

The development of functionalized scaffolds with enhanced bioactivity remains a key challenge in bone tissue engineering (BTE). Here, we present a modular strategy to functionalize the surface of 3D-printed poly(ε-caprolactone) (PCL) scaffolds using an RGD-functionalized PCL derivative. A three-step synthesis introduced maleimide groups along the PCL backbone, enabling covalent conjugation of a thiol-containing peptide. The resulting polymer (PCL-AE-L) was applied via dip-coating, preserving the scaffold architecture and mechanical integrity while ensuring homogeneous surface coverage. Subsequent bioconjugation with the thiol-modified RGD peptide to obtain PCL@RGD scaffolds imparts enhanced cell-adhesive properties. Each functionalization step was confirmed by NMR, FTIR, DSC, GPC, and SEM-EDX analyses. Coating stability was demonstrated under simulated culture conditions. In vitro assays using SAOS-2 cells showed improved cell adhesion and mineralization of PCL@RGD compared to controls. This approach decouples bioactivity enhancement from the printing process and enables customizable surface functionalization, offering a versatile platform for developing next-generation scaffolds for regenerative medicine.