Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles

Neutrophil extracellular traps(NETs)have been considered a significant unfavorable factor for wound healing in diabetes,but the mechanisms remain unclear.The therapeutic application of small extracellular vesicles(sEVs)derived from mesenchymal stem cells(MSCs)has received considerable attention for their properties.Hypoxic preconditioning is reported to enhance the therapeutic potential of MSC-derived sEVs in regenerative medicine.Therefore,the aim of this study is to illustrate the detailed mechanism of NETs in impairment of diabetic wound healing and develop a promising NET-targeting treatment based on hypoxic pretreated MSC-derived sEVs(Hypo-sEVs).Excessive NETs were found in diabetic wounds and in high glucose(HG)-induced neutrophils.Further research showed that high concentration of NETs impaired the function of fibroblasts through activating endoplasmic reticulum(ER)stress.Hypo-sEVs efficiently promoted diabetic wound healing and reduced the excessive NET formation by transferring miR-17-5p.Bioinformatic analysis and RNA interference experiment revealed that miR-17-5p in Hypo-sEVs obstructed the NET formation by targeting TLR4/ROS/MAPK pathway.Additionally,miR-17-5p overexpression decreased NET formation and overcame NET-induced impairment in fibroblasts,similar to the effects of Hypo-sEVs.Overall,we identify a previously unrecognized NET-related mechanism in diabetic wounds and provide a promising NET-targeting strategy for wound treatment.

MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing by targeting IRAK1

Unhealable diabetic wounds need to be addressed with the help of newer,more efficacious strategies.Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment.Here,the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch(SFP)were demonstrated to promote diabetic wound healing.Silk fibroin binding peptide(SFBP)was screened through phage display,and SFBP-Gluc-MS2(SGM)and pac-miR146a-pac fusion protein were constructed.The designed exosomes(SGM-Exos,miR146a-Exos,and SGM-miR146a-Exos)were isolated from the engineered placental mesenchymal stem cells(PMSCs)transduced with SGM or/and pac-miR146a-pac protein.Gluc signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of SGM-Exo.Moreover,the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in miR146a-Exos.Superior to untreated,SGM-miR146a-Exo-only treated,and SFP-only treated groups,SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation,collagen deposition,and neovascularization.The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment.Here,we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.

Remote monitoring contributes to preventing overwork-related events in health workers on the COVID-19 frontlines

Fighting on the frontlines against the coronavirus disease 2019(COVID-19)pandemic,health workers are at high risk of virus infection and overwork-related sudden death and disorders including cardiovascular diseases and stress.When we noted the increase of overwork-related sudden deaths in physicians and nurses in the first 2 weeks after lockdown of Wuhan,we organized the‘Touching Your Heart’program by remote monitoring,aiming to protect health workers from overwork-related disorders through integrated volunteer work by physicians and medical engineering researchers from Wuhan Huoshenshan Hospital,Nanjing Medical University,and Tiangong University.By remotely monitoring the health conditions of the medical aid team working atWuhan Huoshenshan Hospital,the programsuccessfully helped in avoiding severe overwork-related events.The results from our program should be used to remind frontline health workers around the world to take precautions against overworked-related severe events,and showthat precision monitoring is effective in improving work efficiency and maintaining a sustainable workforce during emergency situations like a pandemic.