文献类型：期刊文献

英文题名：Exosomal mRNAs for Angiogenic-Osteogenic Coupled Bone Repair

作者：Ma, Yifan[1,2];Sun, Lili[3,4];Zhang, Jingjing[2];Chiang, Chi-ling[2];Pan, Junjie[2];Wang, Xinyu[2];Kwak, Kwang Joo[5];Li, Hong[2];Zhao, Renliang[6,7];Rima, Xilal Y.[2];Zhang, Chi[8];Zhang, Anan[3,4];Liu, Yutong[3,4];He, Zirui[3,4];Hansford, Derek[1];Reategui, Eduardo[2];Liu, Changsheng[3,4];Lee, Andrew S.[9,10];Yuan, Yuan[2,3,4];Lee, Ly James[1,2]

机构：[1]Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA;[2]Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA;[3]East China Univ Sci & Technol, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai 200237, Peoples R China;[5]Spot Biosyst Ltd, Palo Alto, CA 94305 USA;[6]Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Orthoped Surg, Shanghai 200233, Peoples R China;[7]Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Shanghai Inst Microsurg Extrem, Shanghai 200233, Peoples R China;[8]Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA;[9]Peking Univ Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Shenzhen 518055, Peoples R China;[10]Shenzhen Bay Lab, Inst Canc Res, Shenzhen 518132, Peoples R China

年份：2023

卷号：10

期号：33

外文期刊名：ADVANCED SCIENCE

收录：;EI(收录号：20234214923086);WOS:【SCI-EXPANDED(收录号:WOS:001084204200001)】；

基金：This work was partially supported by the National Natural Science Foundation of China (NSFC 32271401 and NSFC 31971264), Basic Science Center Project of National Natural Science Foundation of China (T2288102), and Outstanding Technical Leader of Shanghai in 2022.

语种：英文

外文关键词：PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel; small extracellular vesicles carrying therapeutic mRNAs and associated microRNAs; track-etched membrane-based nanoelectroporation (TM-nanoEP); vascular endothelial growth factor A (VEGF-A); bone morphogenetic protein 2 (BMP-2) mRNAs coupled angiogenic-osteogenic regeneration

摘要：Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic-osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs. This study describes an easily scalable and cost-effective method to produce abundant therapeutic small extracellular vesicles (t-sEVs) carrying a cocktail of functional mRNAs (VEGF-A and BMP-2) within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel cage for coupling bone regeneration in rats that have challenging femur critical-size defects.image