Modifying MSCs-derived EVs with esterase-responsive and charge-reversal cationic polymers enhances bone regeneration

Yihan Chen; Bang Li; Mukeshimana Christelle; Nshimiyimana Eugene; Wenjia Han; Hong Zhou; Nasha Qiu; Hengguo Zhang; Jianguang Xu

doi:10.1016/j.isci.2024.110801

Modifying MSCs-derived EVs with esterase-responsive and charge-reversal cationic polymers enhances bone regeneration

iScience. 2024 Aug 23;27(9):110801. doi: 10.1016/j.isci.2024.110801. eCollection 2024 Sep 20.

Authors

Yihan Chen^{1

2}, Bang Li¹, Mukeshimana Christelle¹, Nshimiyimana Eugene¹, Wenjia Han¹, Hong Zhou³, Nasha Qiu⁴, Hengguo Zhang¹, Jianguang Xu¹

Affiliations

¹ College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Anhui, China.
² Restorative Dental Sciences, Endodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, P.R. China.
³ Department of Cell and Biology, College of Life Sciences, Anhui Medical University, Anhui, China.
⁴ The Center for Integrated Oncology and Precision Medicine, Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou First People's Hospital, Hangzhou, China.

Abstract

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) for the treatment of bone defects have been widely reported as a cell-free therapy because of their appropriate stability and biocompatibility. However, EV isolation is expensive and time-consuming. We developed a method of modifying EVs derived from bone marrow MSCs (BMSCs) via the cationic polymer (ERP) with characteristics of charge reversal and esterase response (ERP-EVs). When simply mixing BMSCs-EVs with ERP at a 1:1 ratio, ERP-EVs significantly enhanced the osteogenesis of BMSCs. More EVs were released by ERP in BMSCs than in fibroblasts, realizing the selective release. Last, ERP-EVs were loaded on an nHA/CS-MS scaffold and showed enhanced bone regeneration on rat calvarial bone defects in vivo. In general, this study provided an effective strategy to improve cellular uptake and selective release of BMSCs-EVs in bone-related cells, which had great potential to accelerate the clinical practice of BMSCs-EVs-based bone defect repair.

Keywords: Bioengineering; Biological sciences; Biomaterials; Drug delivery system.