PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis

  • J Nanobiotechnology. 2023 Oct 31;21(1):398. doi: 10.1186/s12951-023-02177-7.
Jie Xie  1 Yihe Hu  1 Weiping Su  2 Sijie Chen  3 Jiahao Wang  4 Shuailong Liang  4 Mingyu Chen  3 Haoyi Wang  4 Tianliang Ma  5
Affiliations
  • 1. Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2. Department of Orthopaedics, The 3rd Xiangya Hospital, Central South University, Changsha, China.
  • 3. Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, China.
  • 4. Department of Orthopedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
  • 5. Department of Orthopedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China. [email protected].
Abstract

The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of Reactive Oxygen Species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis.

Keywords
Aseptic loosening; Exosomes; Human umbilical cord derived mesenchymal stem cells; PLGA; Periprosthetic osteolysis.
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