Cyclodextrin–Epichlorohydrin–Cyanoguanidine Polymer for Resveratrol Delivery to Enhance Human Chondrocyte Function in Cartilage Repair

High Resolution Image Download MS PowerPoint Slide Water-soluble β-cyclodextrin–epichlorohydrin polymers (CDPs) are widely used in drug delivery and regenerative medicine. Herein, we report a novel β-cyclodextrin–epichlorohydrin–cyanoguanidine polymer (CDPC) for resveratrol (RES) delivery in cartilage repair. Cyanoguanidine (CyG), a nitrogen-rich compound remaining nonprotonated at physiological pH, was incorporated at varying CyG/β-CD ratios to modulate the polymer properties. Structural characterization was performed by NMR, FT-IR, and CHN analyses. Compared with CDP, CDPC exhibited enhanced RES encapsulation that was attributed to additional intramolecular interactions. Dynamic light scattering revealed nanosized complexes (18 nm for CDPC/RES vs 4 nm for CDP/RES) with a near-neutral surface charge. CDPC showed intrinsic antioxidant activity, which was further enhanced upon RES loading. Both CDP and CDPC were cytocompatible and were efficiently internalized by human chondrocytes. Moreover, the CDP/RES and CDPC/RES systems improved the chondrocyte metabolic activity and extracellular matrix deposition, highlighting their potential as promising carriers for cartilage repair and regeneration.