MXene-Based Cartilage-Adhesive Microspheres for Photothermal-Controlled Hydrophobic Drug Release and Mesenchymal Stem Cell Delivery in Osteoarthritis

Intra-articular drug injection is an effective treatment for osteoarthritis (OA). However, the rapid clearance of drugs from the joint cavity results in low drug utilization and suboptimal therapeutic outcomes. This study describes MXene-based cartilage-adhesive microspheres for photothermal-controlled hydrophobic drug release and bone marrow mesenchymal stem cell (BMSC) delivery. Nano cationic amylose (NCA) was obtained by modifying amylose with glycidyltrimethylammonium chloride (GTAC), and hydrophobic drug Kartogenin (KGN) was encapsulated in the hydrophobic helical cavity of NCA through ultrasonic treatment, resulting in nano cationic amylose@KGN complexes (NCA@KGN). HAMA/MXene-NCA@KGN (H/M-NCA@KGN) microspheres were prepared using a microfluidic device. These microspheres exhibited excellent biocompatibility, effectively adhered to the cartilage surface, and carried BMSCs. H/M-NCA@KGN microspheres demonstrated photothermal-controlled release of the hydrophobic drug KGN. Notably, KGN promoted the differentiation of BMSCs into chondrocytes, thereby improving the loss of extracellular matrix in joint cartilage. Additionally, appropriate thermal stimulation induced the expression of heat shock protein 70 (HSP70) in OA chondrocytes, providing a protective effect and delaying the progression of OA. H/M-NCA@KGN microspheres enable controlled hydrophobic drug release and stem cell delivery for potential OA treatment applications.