Adipose-Derived Mesenchymal Stem Cell-Derived Exosomes Biopotentiated Extracellular Matrix Hydrogels Accelerate Diabetic Wound Healing and Skin Regeneration

被引:148
作者
Song, Yanling [1 ]
You, Yuchan [1 ]
Xu, Xinyi [1 ]
Lu, Jingyi [1 ]
Huang, Xiajie [1 ]
Zhang, Jucong [1 ]
Zhu, Luwen [1 ]
Hu, Jiahao [1 ]
Wu, Xiaochuan [1 ]
Xu, Xiaoling [2 ]
Tan, Weiqiang [3 ]
Du, Yongzhong [1 ,3 ,4 ,5 ]
机构
[1] Zhejiang Univ, Inst Pharmaceut, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China
[2] Zhejiang Shuren Univ, Shulan Int Med Coll, Hangzhou 310015, Zhejiang, Peoples R China
[3] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Plast Surg, Hangzhou 310016, Zhejiang, Peoples R China
[4] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Pharm, Hangzhou 310016, Zhejiang, Peoples R China
[5] Zhejiang Univ, Jinhua Inst, Innovat Ctr Translat Pharm, Jinhua 321299, Peoples R China
关键词
adipose-derived mesenchymal stem cells; diabetic wounds; exosomes; extracellular matrix hydrogel; wound healing; PREVENT MUSCLE DAMAGE; VESICLES; SERUM;
D O I
10.1002/advs.202304023
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
Wound healing is an urgent clinical challenge, particularly in the case of chronic wounds. Traditional approaches to wound healing have limited therapeutic efficacy due to lengthy healing times, risk of immune rejection, and susceptibility to infection. Recently, adipose-derived mesenchymal stem cell-derived exosomes (ADSC-exos) have emerged as a promising modality for tissue regeneration and wound repair. In this study, the development of a novel extracellular matrix hydrogel@exosomes (ECM@exo) is reported, which entails incorporation of ADSC-exos into an extracellular matrix hydrogel (ECM hydrogel). This solution forms a hydrogel at physiological temperature (& AP;37 & DEG;C) upon local injection into the wound site. ECM@exo enables sustained release of ADSC-exos from the ECM hydrogel, which maintains high local concentrations at the wound site. The ECM hydrogel displays good biocompatibility and biodegradability. The in vivo and in vitro results demonstrate that ECM@exo treatment effectively reduces inflammation and promotes angiogenesis, collagen deposition, cell proliferation, and migration, thereby accelerating the wound healing process. Overall, this innovative therapeutic approach offers a new avenue for wound healing via a biological hydrogel with controlled exosome release. In this research, the authors construct an injectable extracellular matrix (ECM) hydrogel by encapsulating exosomes derived from ADSCs, which can provide a sustained release of exosomes in the wound site. This strategy enhances cell proliferation, angiogenesis, collagen deposition, and reduces inflammation, which accelerates wound healing and remodels the normal physiological structure of the skin in normal and diabetic wound models.image
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页数:14
相关论文
共 59 条
[1]
Extracellular Vesicle-Based Hydrogels for Wound Healing Applications [J].
Amengual-Tugores, Andreu Miquel ;
Raez-Meseguer, Carmen ;
Forteza-Genestra, Maria Antonia ;
Monjo, Marta ;
Ramis, Joana M. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (04)
[2]
Anti-inflammatory and M2 macrophage polarization-promoting effect of mesenchymal stem cell-derived exosomes [J].
Arabpour, Maedeh ;
Saghazadeh, Amene ;
Rezaei, Nima .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2021, 97
[3]
Potential Applications of Nanomaterials and Technology for Diabetic Wound Healing [J].
Bai, Que ;
Han, Kai ;
Dong, Kai ;
Zheng, Caiyun ;
Zhang, Yanni ;
Long, Qianfa ;
Lu, Tingli .
INTERNATIONAL JOURNAL OF NANOMEDICINE, 2020, 15 :9717-9743
[4]
Extracellular matrix particle-glycosaminoglycan composite hydrogels for regenerative medicine applications [J].
Beachley, Vince ;
Ma, Garret ;
Papadimitriou, Chris ;
Gibson, Matt ;
Corvelli, Michael ;
Elisseeff, Jennifer .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2018, 106 (01) :147-159
[5]
Hormesis: Wound healing and keratinocytes [J].
Calabrese, Edward J. ;
Dhawan, Gaurav ;
Kapoor, Rachna ;
Agathokleous, Evgenios ;
Calabrese, Vittorio .
PHARMACOLOGICAL RESEARCH, 2022, 183
[6]
miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts their In-Vivo Angiogenic Potential [J].
Cavallari, Claudia ;
Figliolini, Federico ;
Tapparo, Marta ;
Cedrino, Massimo ;
Trevisan, Alessandra ;
Positello, Lorenza ;
Rispoli, Pietro ;
Solini, Anna ;
Migliaretti, Giuseppe ;
Camussi, Giovanni ;
Brizzi, Maria Felice .
SCIENTIFIC REPORTS, 2020, 10 (01)
[7]
Serum-derived extracellular vesicles (EVs) impact on vascular remodeling and prevent muscle damage in acute hind limb ischemia [J].
Cavallari, Claudia ;
Ranghino, Andrea ;
Tapparo, Marta ;
Cedrino, Massimo ;
Figliolini, Federico ;
Grange, Cristina ;
Giannachi, Valentina ;
Garneri, Paolo ;
Deregibus, Maria Chiara ;
Collino, Federica ;
Rispoli, Pietro ;
Camussi, Giovanni ;
Brizzi, Maria Felice .
SCIENTIFIC REPORTS, 2017, 7
[8]
Exosomes from human adipose-derived stem cells promote proliferation and migration of skin fibroblasts [J].
Choi, Eun Wook ;
Seo, Min Koo ;
Woo, Eun Young ;
Kim, Suk Hyung ;
Park, Eun Joo ;
Kim, Sue .
EXPERIMENTAL DERMATOLOGY, 2018, 27 (10) :1170-1172
[9]
Managing Diabetic Foot Ulcers: Pharmacotherapy for Wound Healing [J].
Dixon, Danielle ;
Edmonds, Michael .
DRUGS, 2021, 81 (01) :29-56
[10]
Ferreira Andrea da Fonseca, 2018, Bioengineering-Basel, V6, P4, DOI [10.3390/bioengineering6010004, 10.3390/bioengineering6010004]