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 Mg. 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 Mg could stimulate not only the chondrogenic differentiation of synovial MSCs but also the increased polarization of macrophages toward the M2 phenotype. Additionally, Mg inhibited NLRP3 inflammasome activation, thereby decreasing chondrocyte pyroptosis. Subsequently, Mg 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 Mg and aptamer-functionalized ECM scaffolds is a promising strategy for AC regeneration based on in situ tissue engineering and early inflammatory regulation.