Surface-Biofunctionalized Dual-Purpose Scaffolds that Minimize Growth Factor Dependency for Stem Cell Expansion and Delivery

The clinical potential of mesenchymal stromal/stem cells (MSCs) is limited by the mismatch between their low abundance in adult tissue and the high doses required for treatment. Conventional cell expansion systems that rely on repeated supplementation with labile, soluble growth factors are inefficient and costly. Moreover, the majority of transplanted MSCs exhibit poor survival post-delivery, undermining therapeutic outcomes and exacerbating cell supply challenges. Three-dimensional (3D) polymeric scaffolds, with high surface-area-to-volume ratios, offer a promising strategy for enhancing both cell expansion and delivery. However, their bioinert nature and limited functionalization options have hindered translation. Here, we present a dual-purpose macroporous polycaprolactone (PCL) scaffold, homogeneously activated using long-lived surface-embedded radicals, to enable the one-step covalent immobilization of fibroblast growth factor 2 (FGF2) throughout its internal architecture. This approach preserves the degradability of PCL, while enhancing FGF2 stability and bioavailability. The resulting biofunctional scaffold supports labor-efficient, spatially uniform MSC expansion with a 99% reduction in FGF2 usage, compared to serial cultures on planar surfaces in FGF2-supplemented media. In addition, when used as a cell delivery vehicle, the scaffold enhances MSC survival and retention after implantation. The generation of such multifunctional 3D materials has broad implications for improving the feasibility, accessibility, and impact of cell therapies and offers a blueprint for the robust, cost-effective biofunctionalization of other biomedically relevant porous materials.