biostudies-literatureMa TNational Natural Science Foundation of ChinaZhejiang Province Natural Science Foundation171-188https://www.ebi.ac.uk/biostudies/studies/S-EPMC12005309biostudies-literatureUnknown50The onset of periprosthetic osteolysis is mediated by wear particles following artificial arthroplasty. This manifests as a disturbed bone metabolism microenvironment, characterized by insufficient osteogenesis and angiogenesis, and enhanced osteoclastic activity. To target and remodel the homeostatic environment of bone metabolism in the sterile region around the prosthesis, we successfully pioneered the proposal and construction of a fused exosome (f-exo) system with M2 macrophage-derived exosomes (M2-exo) and urine-derived stem cell exosomes (USC-exo). The results demonstrate that f-exo effectively combines the osteolysis region-targeting capabilities of M2-exo with the bone metabolic homeostasis modulation effects of two exosomes (M2-exo and USC-exo), thereby achieving a significantly Bioactive materialsFused exosomal targeted therapy in periprosthetic osteolysis through regulation of bone metabolic homeostasis.PMC1200530982272452LQN25H0600098220273382372414Yang YHu YZhang ZXie JLiu QMa TNan JLiu GfalseFused exosomal targeted therapy in periprosthetic osteolysis through regulation of bone metabolic homeostasis.The onset of periprosthetic osteolysis is mediated by wear particles following artificial arthroplasty. This manifests as a disturbed bone metabolism microenvironment, characterized by insufficient osteogenesis and angiogenesis, and enhanced osteoclastic activity. To target and remodel the homeostatic environment of bone metabolism in the sterile region around the prosthesis, we successfully pioneered the proposal and construction of a fused exosome (f-exo) system with M2 macrophage-derived exosomes (M2-exo) and urine-derived stem cell exosomes (USC-exo). The results demonstrate that f-exo effectively combines the osteolysis region-targeting capabilities of M2-exo with the bone metabolic homeostasis modulation effects of two exosomes (M2-exo and USC-exo), thereby achieving a significantly 2025-01-01T00:00:00Z2025 Aug2025-07-08T03:11:35.256Z2025-07-08T03:11:35.256ZS-EPMC120053094024818810.1016/j.bioactmat.2025.04.006