Incorporation of Magnesium Ions into an Aptamer-Functionalized ECM Bioactive Scaffold for Articular Cartilage Regeneration

The regeneration and reconstruction of articular cartilage (AC) after a defect are often difficult. The key to the treatment of AC defects lies in regeneration of the defect site and regulation of the inflammatory response. In this investigation, a bioactive multifunctional scaffold was formulated using the aptamer Apt19S as a mediator for mesenchymal stem cell (MSC)-specific recruitment and the enhancement of cellular chondrogenic and inflammatory regulation through the incorporation of Mg²⁺. Apt19S, which can recruit MSCs in vitro and in vivo, was chemically conjugated to a decellularized cartilage extracellular matrix (ECM)-lysed scaffold. The results from in vitro experiments using the resulting scaffold demonstrated that the inclusion of Mg²⁺ could stimulate not only the chondrogenic differentiation of synovial MSCs but also the increased polarization of macrophages toward the M2 phenotype. Additionally, Mg²⁺ inhibited NLRP3 inflammasome activation, thereby decreasing chondrocyte pyroptosis. Subsequently, Mg²⁺ was incorporated into the bioactive multifunctional scaffold, and the resulting scaffold promoted cartilage regeneration in vivo. In conclusion, this study confirms that the combination of Mg²⁺ and aptamer-functionalized ECM scaffolds is a promising strategy for AC regeneration based on in situ tissue engineering and early inflammatory regulation.