Targeted therapy for peri-prosthetic osteolysis using macrophage membrane-encapsulated human urine-derived stem cell extracellular vesicles

Aseptic loosening of the prosthesis is a severe complication after joint replacement. It is of great prac-tical significance and social value to discover the prevention and treatment strategies for this condition. Exosomes from urine-derived stem cells (Exos) have great potential in promoting bone repair, reconstruc-tion, and regulating bone metabolism. However, they are easily eliminated by macrophages and incapable of targeting the osteolysis zone. In this study, based on macrophage homing into periprosthetic oste-olysis region and cell membrane encapsulating nanotechnology, exosomes from urine-derived stem cells were encapsulated with macrophage membrane (MM) to prevent periprosthetic osteolysis. We found that macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be tar-geted delivery to the osteolysis zone and enhance the therapeutic effectiveness of Exos, which alleviated wear particles-induced calvarial osteolysis. Furthermore, MM-Exos could provide immunological camou-flage and allow the Exos to avoid phagocytosis by macrophages and stimulate cellular uptake by bone marrow-derived stem cells (BMSCs). Therefore, we demonstrated the unique ability of the macrophage membrane as a targeted transport of exosomes from urine-derived stem cells for the prevention and treatment of periprosthetic osteolysis. These biomimetic nanoparticles provided a new therapeutic exo-some delivery system for preventing wear particles-induced osteolysis.Statement of Significance Macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effect of Exos on peri-prosthetic osteolysis prevention. MM-Exos could allow the Exos to avoid phagocytosis by macrophages and promote the uptake of Exos by BMSCs. (c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

In this study, exosomes from urine-derived stem cells were encapsulated with macrophage membrane to achieve targeted delivery to the osteolysis zone and enhance therapeutic effectiveness. The macrophage membrane encapsulated exosomes could avoid phagocytosis by macrophages and promote cellular uptake by BMSCs.