Acoustic manipulation and intracellular drug release promote bone marrow mesenchymal stem cells to repair articular cartilage defect

Bone marrow mesenchymal stem cells (BMSCs) possess multidirectional differentiation potential and are regarded as a promising approach for the treatment of cartilage defects. However, how to aggregate and adsorb BMSCs to the injured sites of cartilage and promote their directional differentiation into chondrocytes has always been a key issue to be solved. Here, we fabricated Kartogenin (KGN)-loaded PLGA nanobubbles (KGN-NBs) and swallowed them into BMSCs, obtaining KGN-NBs-containing BMSCs (KGN-NBs@BMSCs). Also, we designed a polylactic acid (PLA) acoustically response scaffold which can produce local sound field under low intensity ultrasound irradiation, and capture KGN-NBs@BMSCs to aggregate on the surface of scaffold. More importantly, KGN could be intracellularly released from KGN-NBs under a short burst of high-energy burst ultrasound irradiation, greatly promoting chondrogenic differentiation of BMSCs and favoring to repair articular cartilage defect. Our study provides a new strategy for the treatment of cartilage defects. Schematic design of PLA acoustically response scaffolds for repair cartilage defects. KGN-NBs were prepared and swallowed by BMSCs and obtained KGN-NBs@BMSCs). PLA scaffolds were implanted into the cartilage defect, and then KGN-NBs@BMSCs cells were injected into the site. After exposure to low intensity ultrasound irradiation (US1), PLA scaffolds produced circumferential acoustic trapping force to capture KGN-NBs@BMSCs cells and make them adhere to the scaffold. Subsequently, KGN-NBs in KGN-NBs@BMSCs were destructed after exposure to short high-power acoustic stimulation (US2) for intracellularly releasing KGN, greatly promoting the differentiation of BMSCs into chondrocytes and helping the recovery of cartilage defects. • Kartogenin (KGN) could be encapsulated into PLGA nanobubbles (KGN-NBs) and the resulting KGN-NBs could be uptaken into BMSCs, obtaining KGN-NBs-containing BMSCs (KGN-NBs@BMSCs). • Acoustically responsive scaffold was designed which could produce local sound field under low intensity ultrasound irradiation, and capture KGN-NBs@BMSCs to aggregate on the surface of scaffold. • Kartogenin (KGN) could be intracellularly released from KGN-NBs under a short high-energy burst ultrasound irradiation, greatly promoting chondrogenic differentiation of BMSCs.