Burn wound healing is a multifaceted process often complicated by excessive inflammation and impaired ker-atinocyte function,both of which are key factors contributing to delayed healing.In this study we screened the ...Burn wound healing is a multifaceted process often complicated by excessive inflammation and impaired ker-atinocyte function,both of which are key factors contributing to delayed healing.In this study we screened the key miRNA regulating the epithelialization process under oxidative stress conditions through high-throughput sequencing.We identified that miR-192-5p was significantly upregulated in both oxidative stress models of keratinocytes and burn wound tissues,with detrimental effects on keratinocyte proliferation,migration,and apoptosis.Inhibition of miR-192-5p enhanced epidermal cell function by upregulating olfactomedin-4(OLFM4),a key gene associated with cell proliferation,adhesion and migration.To optimize delivery and therapeutic efficacy,we engineered MSC-derived exosomes loaded with antagomiR-192-5p(ant-192;Final content:2 nmol per wound;Loading efficiency:35.22±0.34%)and then encapsulated into a composite hydrogel composed of GelMA and MXene(Ti3C2Tx)nanosheets,forming a multifunctional dressing(Exo-ant-192@M-Gel).It achieved sustained release of ant-192,delay its degradation,and exert anti-inflammatory properties,thus promoting epithelization and burn wound healing.This study offered a novel therapeutic approach for burn wound closure.展开更多
Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns.It takes~24 h for tri-gas incubator to achieve steady cell hypoxia,which fails to recapitulate ultr...Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns.It takes~24 h for tri-gas incubator to achieve steady cell hypoxia,which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion(IR)injury.Inspired from the structure of native intestinal villi,we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on coaxial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold.The chip was featured on:(i)eight times the oxygen exchange efficiency compared with the conventional device,tri-gas incubator,(ii)implantation of intestinal organoid reproducing all types of intestinal epithelial cells,and(iii)bio-responsiveness to hypoxia and reoxygenation(HR)by presenting metabolism disorder,inflammatory reaction,and cell apoptosis.Strikingly,it was found for the first time that Olfactomedin 4(Olfm4)was the most significantly downregulated gene under a rapid HR condition by sequencing the RNA from the organoids.Mechanistically,OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation,thus it could be used as a therapeutic target.Altogether,this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo,and sets an example of next-generation multisysteminteractive organoid chip for finding precise therapeutic targets of IR injury.展开更多
基金supported by the National Key R&D Program of China(2024YFA1108401)the National Nature Science Foundation of China(81930057)+7 种基金Shanghai Rising Star Program(22QA1411700,24YF2758700)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-076)the National Nature Science Foundation of China(82372512,82372513,82072170 and 81772076)Shanghai Top Pri-ority Research Center Project(2023ZZ02013)Basic medical research project of Changhai Hospital(2023YQ02)Changhong talent plan of Changhai HospitalDeep Blue Talent Project of Naval Medical Univer-sityClinical Medical Research of Changhai Hospital(2024LYC06).
文摘Burn wound healing is a multifaceted process often complicated by excessive inflammation and impaired ker-atinocyte function,both of which are key factors contributing to delayed healing.In this study we screened the key miRNA regulating the epithelialization process under oxidative stress conditions through high-throughput sequencing.We identified that miR-192-5p was significantly upregulated in both oxidative stress models of keratinocytes and burn wound tissues,with detrimental effects on keratinocyte proliferation,migration,and apoptosis.Inhibition of miR-192-5p enhanced epidermal cell function by upregulating olfactomedin-4(OLFM4),a key gene associated with cell proliferation,adhesion and migration.To optimize delivery and therapeutic efficacy,we engineered MSC-derived exosomes loaded with antagomiR-192-5p(ant-192;Final content:2 nmol per wound;Loading efficiency:35.22±0.34%)and then encapsulated into a composite hydrogel composed of GelMA and MXene(Ti3C2Tx)nanosheets,forming a multifunctional dressing(Exo-ant-192@M-Gel).It achieved sustained release of ant-192,delay its degradation,and exert anti-inflammatory properties,thus promoting epithelization and burn wound healing.This study offered a novel therapeutic approach for burn wound closure.
基金the National Natural Science Foundation of China(82270595,82272237,82072223,32171402)the China Postdoctoral Science Foundation(BX20220393,2022M723891)+2 种基金the General Program of Medical Research from the Jiangsu Commission of Health(M2020052)the Jiangsu Key Research and Development Plan(BE2021727)Jiangsu Provincial Medical Innovation Center(CXZX202217).
文摘Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns.It takes~24 h for tri-gas incubator to achieve steady cell hypoxia,which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion(IR)injury.Inspired from the structure of native intestinal villi,we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on coaxial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold.The chip was featured on:(i)eight times the oxygen exchange efficiency compared with the conventional device,tri-gas incubator,(ii)implantation of intestinal organoid reproducing all types of intestinal epithelial cells,and(iii)bio-responsiveness to hypoxia and reoxygenation(HR)by presenting metabolism disorder,inflammatory reaction,and cell apoptosis.Strikingly,it was found for the first time that Olfactomedin 4(Olfm4)was the most significantly downregulated gene under a rapid HR condition by sequencing the RNA from the organoids.Mechanistically,OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation,thus it could be used as a therapeutic target.Altogether,this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo,and sets an example of next-generation multisysteminteractive organoid chip for finding precise therapeutic targets of IR injury.
