Successful wound healing depends on the reconstruction of proper tissue homeostasis,particularly in the posttraumatic inflammatory tissue microenvironment.Diabetes jeopardizes tissues’immune homeostasis in cutaneous ...Successful wound healing depends on the reconstruction of proper tissue homeostasis,particularly in the posttraumatic inflammatory tissue microenvironment.Diabetes jeopardizes tissues’immune homeostasis in cutaneous wounds,causing persistent chronic inflammation and cytokine dysfunction.Previously,we developed an autologous regeneration factor(ARF)technology to extract the cytokine composite from autologous tissue to restore immune homeostasis and promote wound healing.However,treatment efficacy was significantly compromised in diabetic conditions.Therefore,we proposed that a combination of melatonin and ARF,which is beneficial for proper immune homeostasis reconstruction,could be an effective treatment for diabetic wounds.Our research showed that the utilization of melatonin-mediated ARF biogel(AM gel)promoted diabetic wound regeneration at a more rapid healing rate.RNA-Seq analysis showed that AM gel treatment could restore more favorable immune tissue homeostasis with unique inflammatory patterning as a result of the diminished intensity of acute and chronic inflammation.Currently,AM gel could be a novel and promising therapeutic strategy for diabetic wounds in clinical practice through favorable immune homeostatic reconstructions in the tissue microenvironment and proper posttraumatic inflammation patterning.展开更多
The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proof reading.Below is the corrected funding statement in Acknowledgment SECTION This work was supported by t...The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proof reading.Below is the corrected funding statement in Acknowledgment SECTION This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.81902189,81772354,82002303,31570980),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),National Key Research and Development Plan(2018YFC1105103).展开更多
The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by th...The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).展开更多
The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from t...The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells.Human umbilical vein endothelial cell-derived decellularized extracellular matrix(HdECM),which contains a collection of angiocrine biomolecules,has recently been demonstrated to mediate endothelial cells(ECs)-osteoprogenitors(OPs)crosstalk.We employed the HdECM to create a PCL(polycaprolactone)/fibrin/HdECM(PFE)hybrid scaffold.We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk,resulting in vascularized bone regeneration.Following implantation in a rat femoral bone defect,the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography(μ-AG)and micro-computational tomography(μ-CT).Based on the immunofluorescence studies,PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors.In addition,superior osseointegration was observed by a direct host bone-PCL interface,which was likely attributed to the formation of type H vessels.The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration.It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels,which could compensate for the inherent biological inertness of synthetic polymers.展开更多
Regardless of the advancement of synthetic bone substitutes,allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases.Nevertheless,the stringent devitalization proc...Regardless of the advancement of synthetic bone substitutes,allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases.Nevertheless,the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure.Hence,improving osseointegration and transplantation efficiency remains important.The alteration of bone tissue microenvironment(TME)to facilitate osseointegration has been generally recognized.However,the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging.To address this concern,an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment.The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique.The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated.In the animal test,superior osseointegration between Mg-enriched graft and host bone was found,whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation.Furthermore,the bony in-growth appeared on magnesium-enriched allograft bone was significant higher.The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells.Lastly,our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.展开更多
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.81772354,81902189,82072409)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002)+3 种基金Science Technology Project of Guangzhou City(201804010185)Natural Science Foundation of Guangdong Province(2019A1515012020)Science and Technology Innovation Project of Foshan City(1920001000025)National Young Thousand-Talent Scheme to Zhang Zhi-Yong.
文摘Successful wound healing depends on the reconstruction of proper tissue homeostasis,particularly in the posttraumatic inflammatory tissue microenvironment.Diabetes jeopardizes tissues’immune homeostasis in cutaneous wounds,causing persistent chronic inflammation and cytokine dysfunction.Previously,we developed an autologous regeneration factor(ARF)technology to extract the cytokine composite from autologous tissue to restore immune homeostasis and promote wound healing.However,treatment efficacy was significantly compromised in diabetic conditions.Therefore,we proposed that a combination of melatonin and ARF,which is beneficial for proper immune homeostasis reconstruction,could be an effective treatment for diabetic wounds.Our research showed that the utilization of melatonin-mediated ARF biogel(AM gel)promoted diabetic wound regeneration at a more rapid healing rate.RNA-Seq analysis showed that AM gel treatment could restore more favorable immune tissue homeostasis with unique inflammatory patterning as a result of the diminished intensity of acute and chronic inflammation.Currently,AM gel could be a novel and promising therapeutic strategy for diabetic wounds in clinical practice through favorable immune homeostatic reconstructions in the tissue microenvironment and proper posttraumatic inflammation patterning.
文摘The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proof reading.Below is the corrected funding statement in Acknowledgment SECTION This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.81902189,81772354,82002303,31570980),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),National Key Research and Development Plan(2018YFC1105103).
文摘The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).
基金This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201001)+3 种基金Science Technology Project of Guangzhou City(2019ZD15)Collegiate Innovation and Entrepreneurship Education Project of Guangzhou City(2019PT104)Science and Technology Innovation Project of Foshan City(1920001000025)and National Young Thousand-Talent Scheme to Zhang Zhi-Yong.
文摘The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells.Human umbilical vein endothelial cell-derived decellularized extracellular matrix(HdECM),which contains a collection of angiocrine biomolecules,has recently been demonstrated to mediate endothelial cells(ECs)-osteoprogenitors(OPs)crosstalk.We employed the HdECM to create a PCL(polycaprolactone)/fibrin/HdECM(PFE)hybrid scaffold.We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk,resulting in vascularized bone regeneration.Following implantation in a rat femoral bone defect,the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography(μ-AG)and micro-computational tomography(μ-CT).Based on the immunofluorescence studies,PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors.In addition,superior osseointegration was observed by a direct host bone-PCL interface,which was likely attributed to the formation of type H vessels.The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration.It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels,which could compensate for the inherent biological inertness of synthetic polymers.
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.81902189,81772354,82002303,31570980)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201001)+6 种基金National Key Research and Development Plan(2018YFC1105103)Research Grant Council General Research Funds(RGC GRF)(17214516)Shenzhen Science and Technology Innovation Funding(JCYJ20160429190821781 and JCYJ2016429185449249)Science Technology Project of Guangzhou City(201804010185)Science and Technology Innovation Project of Foshan City(1920001000025)Scientific Research Foundation of PEKING UNIVERSITY SHENZHEN HOSPITAL KYQD(2021064)National Young Thousand-Talent Scheme to Zhang Zhi-Yong.
文摘Regardless of the advancement of synthetic bone substitutes,allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases.Nevertheless,the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure.Hence,improving osseointegration and transplantation efficiency remains important.The alteration of bone tissue microenvironment(TME)to facilitate osseointegration has been generally recognized.However,the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging.To address this concern,an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment.The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique.The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated.In the animal test,superior osseointegration between Mg-enriched graft and host bone was found,whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation.Furthermore,the bony in-growth appeared on magnesium-enriched allograft bone was significant higher.The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells.Lastly,our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.