Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impede...Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impeded by their low viability and efficiency after grafting in vivo.Nitric oxide(NO)is beneficial in promoting stem cell bioactivity,but whether it can function effectively in vivo is still largely unknown.In this study,we bioprinted an efficient biological scaffold loaded with ADSCs and NO(3D-ADSCs/NO)to evaluate its biological efficacy in promoting severe burn wound healing.The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting.Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells(HUVECs).Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition.Notably,immunohistochemistry of CD31 suggested an increase in neovascularization,supported by the upregulation of vascular endothelial growth factor(VEGF)mRNA in ADSCs in the 3D biosystem.These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway.This scaffold may be considered a promising strategy for healing severe burns.展开更多
Adipose mesenchymal stem cell(ADMSC)-derived exosomes(ADMSC-Exos)have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns.However,the low yield,easy loss after direc...Adipose mesenchymal stem cell(ADMSC)-derived exosomes(ADMSC-Exos)have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns.However,the low yield,easy loss after direct coating,and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing.And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques,especially in exosome-releasing hydrogel system.Therefore,we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing,namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid(HA).In this project,we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional(2D)plate culture(2D-Exos),microcarrier culture(2.5D-Exos),and 3D-printed microfiber culture(3D-Exos).Results showed that compared with 2D-Exos and 2.5D-Exos,3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly.Additionally,3D-Exos had stronger angiogenesis-promoting effects in tube formation of(HUVECs)cells.Moreover,we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos,including accelerated burn wound healing rate and better collagen remodeling.The study findings reveal that the HA-loaded,controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing,while concurrently introducing a facile application approach.This system markedly bolsters the exosomal loading efficiency,provides a robust protective milieu,and potentiates the inherent biological functionalities of the exosomes.Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future,and a novel strategy for healing severe burns.展开更多
Joint contracture is a fibrotic complication induced by joint immobilization and trauma,which is characterized as excessive myofibroblast proliferation in joint capsule.The treatments of joint contracture are unsatisf...Joint contracture is a fibrotic complication induced by joint immobilization and trauma,which is characterized as excessive myofibroblast proliferation in joint capsule.The treatments of joint contracture are unsatisfied and patients are suffered from joint dysfunction.Our previous study has shown that curcumin can inhibit myofibroblast proliferation in vitro,but the major challenge is the low aqueous solubility and biological activity of curcumin.In this study,hyaluronic acid-curcumin(HA-Cur)conjugate was synthesized to suppress myofibroblasts in joint contracture.Cells were isolated from the joint capsules of joint contracture patients and induced to active myofibroblasts by transforming growth factor-b(TGF-b).The anti-fibrotic function and mechanisms of HA-Cur were investigated by immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(PCR),methylation-specific PCR,western blot,transwell migration assay and proliferation assay.Results showed that 30 lM HA-Cur significantly attenuated the fibrotic functions of myofibroblast in joint contracture in vitro by regulating the methylation of prostaglandin E receptor 2(PTGER2)and inhibiting TGF-b signaling.This may provide a mechanism for the treatment of joint contracture,and provide a molecular target PTGER2 for therapy during the pathogenesis of joint contracture.展开更多
基金This work was supported by the Natural Science Foundation of Guangdong Province,China(No.2017A030313889)This work was partly supported by National Natural Science Foundation of China(No.81772368)the Science and Technology Planning Project of Guangdong Province(No.2017B090912007).
文摘Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impeded by their low viability and efficiency after grafting in vivo.Nitric oxide(NO)is beneficial in promoting stem cell bioactivity,but whether it can function effectively in vivo is still largely unknown.In this study,we bioprinted an efficient biological scaffold loaded with ADSCs and NO(3D-ADSCs/NO)to evaluate its biological efficacy in promoting severe burn wound healing.The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting.Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells(HUVECs).Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition.Notably,immunohistochemistry of CD31 suggested an increase in neovascularization,supported by the upregulation of vascular endothelial growth factor(VEGF)mRNA in ADSCs in the 3D biosystem.These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway.This scaffold may be considered a promising strategy for healing severe burns.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2021A1515220120)the Natural Science Foundation of China(grant no.52075285).
文摘Adipose mesenchymal stem cell(ADMSC)-derived exosomes(ADMSC-Exos)have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns.However,the low yield,easy loss after direct coating,and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing.And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques,especially in exosome-releasing hydrogel system.Therefore,we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing,namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid(HA).In this project,we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional(2D)plate culture(2D-Exos),microcarrier culture(2.5D-Exos),and 3D-printed microfiber culture(3D-Exos).Results showed that compared with 2D-Exos and 2.5D-Exos,3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly.Additionally,3D-Exos had stronger angiogenesis-promoting effects in tube formation of(HUVECs)cells.Moreover,we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos,including accelerated burn wound healing rate and better collagen remodeling.The study findings reveal that the HA-loaded,controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing,while concurrently introducing a facile application approach.This system markedly bolsters the exosomal loading efficiency,provides a robust protective milieu,and potentiates the inherent biological functionalities of the exosomes.Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future,and a novel strategy for healing severe burns.
基金grants from National Natural Science Foundation of China[81772368 and 81802184]Natural Science Foundation of Guangdong Province[2017A030310226]+1 种基金the Guangdong Traditional Chinese Medicine Bureau Research Fund[20181061]Medical Research Foundation of Guangdong[A2017003].
文摘Joint contracture is a fibrotic complication induced by joint immobilization and trauma,which is characterized as excessive myofibroblast proliferation in joint capsule.The treatments of joint contracture are unsatisfied and patients are suffered from joint dysfunction.Our previous study has shown that curcumin can inhibit myofibroblast proliferation in vitro,but the major challenge is the low aqueous solubility and biological activity of curcumin.In this study,hyaluronic acid-curcumin(HA-Cur)conjugate was synthesized to suppress myofibroblasts in joint contracture.Cells were isolated from the joint capsules of joint contracture patients and induced to active myofibroblasts by transforming growth factor-b(TGF-b).The anti-fibrotic function and mechanisms of HA-Cur were investigated by immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(PCR),methylation-specific PCR,western blot,transwell migration assay and proliferation assay.Results showed that 30 lM HA-Cur significantly attenuated the fibrotic functions of myofibroblast in joint contracture in vitro by regulating the methylation of prostaglandin E receptor 2(PTGER2)and inhibiting TGF-b signaling.This may provide a mechanism for the treatment of joint contracture,and provide a molecular target PTGER2 for therapy during the pathogenesis of joint contracture.
