3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing

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.

Hyaluronic acid-curcumin conjugate suppresses the fibrotic functions of myofibroblasts from contractive joint by the PTGER2 demethylation

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.