Soft tissue defects from trauma or surgery remain challenging to repair due to poor regenerative capacity and fibrosis. Adipose tissue-derived small extracellular vesicles (sEVs) have emerged as promising agents for promoting adipogenesis and driving adipose tissue regeneration, offering significant potential for soft tissue defect repair. This study aimed to establish a novel cell-free strategy by integrating sEVs with decellularized adipose tissue hydrogel (sEVs@DAT) for adipose tissue regeneration and elucidate the underlying mechanisms. We identified that sEVs derived from both white adipose tissue (sEV-WAT) and brown adipose tissue (sEV-BAT) promoted mitochondrial metabolism and adipogenic differentiation of adipose-derived stem cells (ASCs) in vitro. Furthermore, the sEVs@DAT supported anti-inflammatory macrophage polarization, and significantly improved adipose tissue formation and vascularization in vivo. Transcriptomic profiling identified Senp2 as a key mRNA cargo enriched in both sEVs types. Functional studies revealed that knockdown of Senp2 impaired sEVs-induced mitochondrial activity, adipogenic gene expression, and ERK/AKT phosphorylation. These findings presented a cell-free therapeutic approach for adipose tissue engineering by integrating bioactive sEVs with a biocompatible scaffold, offering a translationally promising approach for soft tissue reconstruction over traditional cell-based therapies.
基金:
China Postdoctoral Science Foundation [2024M752300]; Research and Develop Program, West China Hos-pital of Stomatology Sichuan University [RD-03-202405]
第一作者机构:[1]Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China[2]Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China[3]Sichuan Univ, West China Hosp Stomatol, Minist Educ, Engn Res Ctr Oral Translat Med, Chengdu 610041, Peoples R China[4]Sichuan Univ, West China Hosp Stomatol, Natl Engn Lab Oral Regenerat Med, Chengdu 610041, Peoples R China[5]Sichuan Univ, West China Hosp Stomatol, Dept Oral & Maxillofacial Surg, Chengdu 610041, Peoples R China
通讯作者:
通讯机构:[1]Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China[2]Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China[3]Sichuan Univ, West China Hosp Stomatol, Minist Educ, Engn Res Ctr Oral Translat Med, Chengdu 610041, Peoples R China[4]Sichuan Univ, West China Hosp Stomatol, Natl Engn Lab Oral Regenerat Med, Chengdu 610041, Peoples R China[5]Sichuan Univ, West China Hosp Stomatol, Dept Oral & Maxillofacial Surg, Chengdu 610041, Peoples R China[6]Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Sichuan Clin Res Ctr Canc, Dept Head & Neck Surg,Sichuan Canc Ctr, Chengdu 610040, Sichuan, Peoples R China
推荐引用方式(GB/T 7714):
Hong Pengyu,Yuan Shengmeng,Yang Jian,et al.Combining small extracellular vesicles with decellularized adipose tissue hydrogel for the construction of tissue-engineered adipose[J].MATERIALS & DESIGN.2025,256:doi:10.1016/j.matdes.2025.114331.
APA:
Hong, Pengyu,Yuan, Shengmeng,Yang, Jian,Cao, Zhiwei,Sun, Xiangyun...&Pan, Jian.(2025).Combining small extracellular vesicles with decellularized adipose tissue hydrogel for the construction of tissue-engineered adipose.MATERIALS & DESIGN,256,
MLA:
Hong, Pengyu,et al."Combining small extracellular vesicles with decellularized adipose tissue hydrogel for the construction of tissue-engineered adipose".MATERIALS & DESIGN 256.(2025)