ADSC-exo@MMP-PEG smart hydrogel promotes diabetic wound healing by optimizing cellular functions and relieving oxidative stress

Jiang, Tao; Liu, Siju; Wu, Zihan; Li, Qianyun; Ren, Sen; Chen, Jing; Xu, Xiang Xi; Wang, Cheng; Lu, Cuifen; Yang, Xiaofan; Chen, Zhenbing

doi:10.1016/j.mtbio.2022.100365

Cited by 51 publications

(56 citation statements)

References 52 publications

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“…It was veri ed that the Keap1/Nrf2 signaling pathway was impaired and the level of Keap1 protein was down-regulated, both in diabetic human and animal models [14]. In wound healing treatment, our research team had researched that the synthetic ADSC-exo@MMP-PEG hydrogel could alleviate the H 2 O 2 -induced oxidative stress and improve the impaired wound healing in diabetes mice [15] and the thermosensitive niobium carbide (Nb 2 C)-based hydrogel (Nb 2 C@Gel) with antioxidative and antimicrobial activity could promote wound healing by attenuating ROS levels [16]. Simu's research indicated that the oxidative stress could be decreased by activating Nrf2, which makes ROS elimination and nitric oxide generation [17].…”

Section: Discussionmentioning

confidence: 99%

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Xiang

Chen

Jiang

et al. 2022

Preprint

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Diabetic wound, as a serious complication of diabetes mellitus (DM), leads to persistent infection, amputation and even death. Prolonged oxidative stress has been widely recognized as the main cause of diabetic wound and is considered as hopeful therapeutic target. In the present study, Keap1/Nrf2 signaling was confirmed to be activated in streptozotocin (STZ)-induced diabetic mice and methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVEC). Knockdown of Keap1 by siRNA attenuated the raised Keap1 level, promoted the nuclear transfer of Nrf2, and then facilitated the expression of HO-1, an antioxidant protein. Then the milk-derived exosomes (mEXOs) were developed as a novel, efficient and non-toxic siRNA carrier. SiRNA-Keap1 (siKeap1) was loaded into mEXOs through ultrasonic technique, which promoted HUVEC proliferation, migration and relieved oxidative stress in MGO-treated HUVEC. In the meantime, the injection of mEXOs-siKeap1 significantly accelerated the diabetic wound healing with enhanced collagen formation and neovascularization in mice models. Totally, the present study puts forward a potential treatment for diabetic wound and proved the feasibility of mEXOs as a scalable, biocompatible, and cost-effective siRNA delivery system.

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Section: Discussionmentioning

confidence: 99%

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Xiang

Chen

Jiang

et al. 2022

Preprint

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“…The high concentration of Exos in large doses of injection will result in waste, and the operation will become more complicated in low doses of multiple injections. 21,59…”

Section: Challenges and Improving Strategiesmentioning

confidence: 99%

“…Thus, the challenges of extracting MSCs from elderly patients for therapeutic purposes can be overcome; (3) reducing some effects of continuous laboratory manipulation induced on genetic or epigenetic changes in regenerative function based on a longer life span, higher proliferative capacity, shorter doubling time, later in vitro senescence, and prolonged maintenance of phenotype; (4) no ethical issues compared with embryonic stem cells; (5) pain relieving properties. 17–23…”

Section: Introductionmentioning

confidence: 99%

“…(5) pain relieving properties. [17][18][19][20][21][22][23] In wound healing management, ADMSC-based stem cell therapy has shown good results with regards to cell recruitment, angiogenesis, extracellular matrix remodeling and nerve regeneration, [24][25][26][27] especially autologous stem cell transplantation. [28][29][30] In spite of this, the lack of standardized doses or protocols, the heterogeneity of clinical trials, immune incompatibility, chromosome variation, and metabolic disorders, particularly metabolic disorders in diabetic patients can reduce the function of autologous cells and increase the risk of complications, thus limiting its application to a large extent.…”

Section: Introductionmentioning

confidence: 99%

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Advances in microRNA from adipose-derived mesenchymal stem cell-derived exosome: focusing on wound healing

Ling

Lei

et al. 2022

J. Mater. Chem. B

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“…Exosomes have been delivered via PEG hydrogels for cutaneous wound healing [ 47 , 171 ]. Additionally, macrophages adopt polarization states in response to the local microenvironment [ 47 ].…”

Section: Synthetic Biopolymer Scaffolds For Therapeutic Ev Deliverymentioning

confidence: 99%

Biomaterials and Extracellular Vesicle Delivery: Current Status, Applications and Challenges

Leung

Shirazi

Cooper

et al. 2022

Cells

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In this review, we will discuss the current status of extracellular vesicle (EV) delivery via biopolymeric scaffolds for therapeutic applications and the challenges associated with the development of these functionalized scaffolds. EVs are cell-derived membranous structures and are involved in many physiological processes. Naïve and engineered EVs have much therapeutic potential, but proper delivery systems are required to prevent non-specific and off-target effects. Targeted and site-specific delivery using polymeric scaffolds can address these limitations. EV delivery with scaffolds has shown improvements in tissue remodeling, wound healing, bone healing, immunomodulation, and vascular performance. Thus, EV delivery via biopolymeric scaffolds is becoming an increasingly popular approach to tissue engineering. Although there are many types of natural and synthetic biopolymers, the overarching goal for many tissue engineers is to utilize biopolymers to restore defects and function as well as support host regeneration. Functionalizing biopolymers by incorporating EVs works toward this goal. Throughout this review, we will characterize extracellular vesicles, examine various biopolymers as a vehicle for EV delivery for therapeutic purposes, potential mechanisms by which EVs exert their effects, EV delivery for tissue repair and immunomodulation, and the challenges associated with the use of EVs in scaffolds.

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ADSC-exo@MMP-PEG smart hydrogel promotes diabetic wound healing by optimizing cellular functions and relieving oxidative stress

Cited by 51 publications

References 52 publications

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Advances in microRNA from adipose-derived mesenchymal stem cell-derived exosome: focusing on wound healing

Biomaterials and Extracellular Vesicle Delivery: Current Status, Applications and Challenges

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