Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Encapsulated in M2 Macrophage Cell Membrane Targeted to Inhibit Joint Periprosthetic Inflammation

Periprosthetic osteolysis (PPOL) is a serious complication following total joint replacement surgery, and exploring treatments for this complication is of significant societal importance. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos, Exos) have diverse cellular functions, such as inhibiting osteoclast formation, suppressing inflammation progression, and promoting M2 macrophage polarization. However, standalone Exosomes are easily recognized and phagocytosed by the immune system, have a short half-life, and lack specificity. This study is based on the homing effect possessed by M2 macrophages under the regulation of various factors. By combining this with cell membrane encapsulation technology and embedding BMSC-Exos within the membrane of M2 macrophages (M2M-Exos), the aim is to inhibit inflammation and treat PPOL. It was found that M2M-Exos can target the PPOL area, enhancing the therapeutic effects of the BMSC-Exos and reducing wear particle-induced cranial osteolysis. Additionally, M2M-Exos provide immune camouflage through the cell membrane, allowing the BMSC-Exos to evade clearance by the mononuclear macrophage system in the body. Therefore, the study demonstrates the targeting ability of M2M-Exos and their unique role in preventing PPOL. These biomimetic nanoparticles establish a targeted nanodrug delivery system for PPOL treatment.