AIMTo investigate the influence of He-Ne lasers on scar formation in the filtration canal after trabeculectomy in a rabbit model, as well as to explore the mechanisms for preventing scar formation when using He-Ne las...AIMTo investigate the influence of He-Ne lasers on scar formation in the filtration canal after trabeculectomy in a rabbit model, as well as to explore the mechanisms for preventing scar formation when using He-Ne lasers in vivo.展开更多
Electrical stimulation has recently received attention as noninvasive treatment in skin wound healing with its outstanding biological property for clinical setting.However,the complexity of equipment for applying appr...Electrical stimulation has recently received attention as noninvasive treatment in skin wound healing with its outstanding biological property for clinical setting.However,the complexity of equipment for applying appropriate electrical stimulation remains an ongoing challenge.Here,we proposed a strategy for skin scar inhibition by providing electrical stimulation via a multilayer stacked electret(MS-electret),which can generate direct current(DC)electric field(EF)without any power supply equipment.In addition,the MS-electret can easily control the intensity of EFs by simply stacking electret layers and maintain stable EF with the surface potential of 3400 V over 5 days owing to the injected charges on the electret surface.We confirmed inhibition of type 1 collagen andα-SMA expression of human dermal fibroblasts(hDFs)by 90%and 44%in vitro,indicating that the transition of hDFs to myofibroblasts was restricted by applying stable electrical stimulation.We further revealed a 20%significant decrease in the ratio of myofibroblasts caused by the MS-electret in vivo.These findings present that the MS-electret is an outstanding candidate for effective skin scar inhibition with a battery-free,physiological electrical microenvironment,and noninvasive treatment that allows it to prevent external infection.展开更多
AIM:To investigate the efficacy and safety of Honghua preserved amniotic membrane(AM)for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.METHODS:Totally 36 rabbits(...AIM:To investigate the efficacy and safety of Honghua preserved amniotic membrane(AM)for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.METHODS:Totally 36 rabbits(36 eyes)were randomly divided into 3 groups:the experimental group(ocular trabeculectomy in combination with Honghua preserved AM transplantation),the control group(ocular trabeculectomy surgery in combination with AM implantation),and the blank group(single trabeculectomy).Clinical observations[including intraocular pressure(IOP),filtering blebs and complications],MassonTrichrome staining,real-time quantitative reverse transcription-polymerase chain reaction(real-time PCR),Western blot were performed on different time points(D1,D7,D14,D21 and D56)after the surgery.RESULTS:After operated for 14d,there were statistically significant differences in the filtering blebs compared to the situation before operation(P【0.05),whereas no statistically difference on that among three groups(P】0.05).After 21d,the IOP of experimental group was lowest(P【0.05).There was significant difference between control group and blank group(P【0.05).On postoperative D14,the mean number of fibroblasts in the experimental group was significantlylower(40.6±10.2)compared to those in the control group(54.4±10.8)and blank group(68.2±11.6)(P【0.05,respectively).The mean numbers of the macrophage in the experimental and control groups were respcitively significantly lower versus the blank group(P【0.05,P【0.05,respectively).Compared to that in blank group,the level of transforming growth factor-β(TGF-β1)expression in sclera and conjunctival areas was reduced in the experimental and control groups on protein and mRNA level(P【0.05),but not significant difference between these two groups(P】0.05).CONCLUSION:The trabeculectory surgery with Honghua preserved AM can control IOP,sustain the functional filtration bleb,inhibit the proliferation of fibroblasts and open the filtrating pathway on the rabbit glaucoma models.展开更多
AIM: To investigate the antifibrotic effect of the freeze-dried bilayered fibrin-binding amniotic membrane as a drug delivery system on glaucoma surgery in rabbit model. The aim of this study was to prepare a novel lo...AIM: To investigate the antifibrotic effect of the freeze-dried bilayered fibrin-binding amniotic membrane as a drug delivery system on glaucoma surgery in rabbit model. The aim of this study was to prepare a novel local delivery system for the sustained and controllable release of 5-Fu. METHODS: Twenty-four Japanese white rabbits were randomized into three groups: the experimental group (ocular trabeculectomy in combination with 5-Fu loaded freeze-dried bilayered fibrin-binding amniotic membrane transplantation), the control group (ocular trabeculectomy in combination with 5-Fu) and the blank group (single trabeculectomy). HE staining, massion staining and immunohistochemistry for alpha -SMA were performed on days 7, 14, 21 and 30 following surgery. The concentration of 5-Fu in rabbit aqueous humor was examined by high performance liquid chromatography (HPLC) 3 days after the surgery. RESULTS: Statistical differences were noted in intraocular pressure among groups on day 7, 14, 21 and 30 following surgery. Histology further demonstrated that trabeculectomy in combination with freeze-dried bilayered fibrin-binding amniotic membrane yielded well wound healing and no scar formation and was beneficial for long term effect. CONCLUSION: HPLC showed a good slow-release effect with freeze-dried bilayered fibrin-binding amniotic membrane.展开更多
Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord ...Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury. In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3 K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3 K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3 K/AKT/mTOR pathway.展开更多
Reactive astrogliosis occurs after central nervous system（CNS） injuries whereby resident astrocytes form rapid responses along a graded continuum. Following CNS lesions, na？ve astrocytes are converted into reactive...Reactive astrogliosis occurs after central nervous system（CNS） injuries whereby resident astrocytes form rapid responses along a graded continuum. Following CNS lesions, na？ve astrocytes are converted into reactive astrocytes and eventually into scar-forming astrocytes that block axon regeneration and neural repair. It has been known for decades that scarring development and its related extracellular matrix molecules interfere with regeneration of injured axons after CNS injury, but the cellular and molecular mechanisms for controlling astrocytic scar formation and maintenance are not well known. Recent use of various genetic tools has made tremendous progress in better understanding genesis of reactive astrogliosis. Especially, the latest experiments demonstrate environment-dependent plasticity of reactive astrogliosis because reactive astrocytes isolated from injured spinal cord form scarring astrocytes when transplanted into injured spinal cord, but revert in retrograde to naive astrocytes when transplanted into naive spinal cord. The interactions between upregulated type I collagen and its receptor integrin β1 and the N-cadherin-mediated cell adhesion appear to play major roles for local astrogliosis around the lesion. This review centers on the environment-dependent plasticity of reactive astrogliosis after spinal cord injury and its potential as a therapeutic target.展开更多
Scar formation can be effectively prevented when the proportion of collagen type Ⅰ(Col Ⅰ)/type Ⅲ(Col Ⅲ)is reduced.Unlike Col Ⅲ,recombinant human collagen type Ⅲ chain(RHC Ⅲ chain)does not possess a triple helic...Scar formation can be effectively prevented when the proportion of collagen type Ⅰ(Col Ⅰ)/type Ⅲ(Col Ⅲ)is reduced.Unlike Col Ⅲ,recombinant human collagen type Ⅲ chain(RHC Ⅲ chain)does not possess a triple helical structure.This study aimed to elucidate the capacity of fibroblasts to uptake RHC Ⅲ chain,reduce the Col Ⅰ/Col Ⅲ ratio and determine its effects on wound healing and scar.RHC Ⅲ chain demonstrates qualified cell compatibility.In cell experiments,immunofluorescence and western blot(WB)analyses revealed an increase in the polyhistidine tag level,indicating that RHC Ⅲ chain in internalized by these cells.Transmission electron microscopy showed increased intracellular phagocytic activity,indicating that RHC Ⅲ chain enters fibroblasts by endocytosis.The immunofluorescence and WB showed that Col Ⅲ synthesis enhanced,and Col Ⅰ/Col Ⅲ ratio reduced.However,the polyhistidine tag disappeared with time,indicating that RHC Ⅲ chain degraded within cells and then synthesized into Col Ⅲ.The content of newly synthesized Col Ⅲ increases,but real-time fluorescence quantitative showed a decrease in Col Ⅲ related gene content suggests the formation of negative feedback.However,due to the sufficient raw materials,the amount of Col Ⅲ synthesis is still increasing,leading to the reduction of the ratio of type Ⅰ collagen/type Ⅲ collagen,which beneficial to wound healing and reduce scar hyperplasia.In animal experiments,the SD rat full-thickness skin defect model of wound suggests that RHC Ⅲ chain also takes effect through endocytosis and ultimately promotes wound healing.The rabbit ear scar model suggests that RHC Ⅲ chain inhibits scar proliferation by reducing the ratio of Col Ⅰ/Col Ⅲ.In summary,RHC Ⅲ chain was endocytosed by fibroblasts to promote native Col Ⅲ synthesis,as well as promote wound healing and reduce scar hyperplasia.展开更多
Cross-linking agents are frequently used to restore corneal properties after decellularization,and it is especially important to select an appropriate method to avoid excessive cross-linking.In addition,how to promote...Cross-linking agents are frequently used to restore corneal properties after decellularization,and it is especially important to select an appropriate method to avoid excessive cross-linking.In addition,how to promote wound healing and how to improve scar formation require further investigation.To ensure the safety and efficacy of animal-derived products,we designed bioartificial corneas(BACs)according to the criteria for Class III medical devices.Our BACs do not require crosslinking agents and increase mechanical strength via self-cross-linking of aldehyde-modified hyaluronic acid(AHA)and carboxymethyl chitosan(CMC)on the surface of decellularized porcine corneas(DPCs).The results showed that the BACs had good biocompatibility and transparency,and the modification enhanced their antibacterial and anti-inflammatory properties in vitro.Preclinical animal studies showed that the BACs can rapidly regenerate the epithelium and restore vision within a month.After 3 months,the BACs were gradually filled with epithelial,stromal,and neuronal cells,and after 6 months,their transparency and histology were almost normal.In addition,side effects such as corneal neovascularization,conjunctival hyperemia,and ciliary body hyperemia rarely occur in vivo.Therefore,these BACs show promise for clinical application for the treatment of infectious corneal ulcers and as a temporary covering for corneal perforations to achieve the more time.展开更多
Bacterial infection and scar formation remain primary challenges in wound healing.To address these issues,we developed a decellularized pomelo peel(DPP)functionalized with an adhesive PVA-TSPBA hydrogel and antibacter...Bacterial infection and scar formation remain primary challenges in wound healing.To address these issues,we developed a decellularized pomelo peel(DPP)functionalized with an adhesive PVA-TSPBA hydrogel and antibacterial gallic acid/copper MOFs.The hybrid wound dressing demonstrates favorable biocompatibility.It does not impede the proliferation of fibroblasts or immune cells and can stimulate fibroblast migration,endothelial angiogenesis,and M2 macrophage polarization.Additionally,the dressing can scavenge reactive oxygen species(ROS)and provide antioxidant effects.Furthermore,DPP+MOF@Gel effectively inhibits the viability of S.aureus and E.coli in vitro and in vivo.The histological observations revealed enhanced granulation tissue formation,re-epithelialization,and angiogenesis in the DPP+MOF@Gel group compared to other groups.The local immune response also shifted from a pro-inflammatory to a pro-regenerative status with DPP+MOF@Gel treatment.The skin incision stitching experiment further exhibits DPP+MOF@Gel could reduce scar formation during wound healing.Taken together,the hybrid DPP+MOF@Gel holds great promise for treating bacteria-infected skin wounds and inhibiting scar formation during wound healing.展开更多
Chronic wounds are wounds that cannot heal properly due to various factors,such as underlying diseases,infection or reinjury,and improper healing of skin wounds and ulcers can cause a serious economic burden.Numerous ...Chronic wounds are wounds that cannot heal properly due to various factors,such as underlying diseases,infection or reinjury,and improper healing of skin wounds and ulcers can cause a serious economic burden.Numerous studies have shown that extracellular vesicles(EVs)derived from stem/progenitor cells promote wound healing,reduce scar formation and have significant advantages over traditional treatment methods.EVs are membranous particles that carry various bioactive molecules from their cellular origins,such as cytokines,nucleic acids,enzymes,lipids and proteins.EVs can mediate cell-to-cell communication and modulate various physiological processes,such as cell differentiation,angiogenesis,immune response and tissue remodelling.In this review,we summarize the recent advances in EV-based wound healing,focusing on the signalling pathways that are regulated by EVs and their cargos.We discuss how EVs derived from different types of stem/progenitor cells can promote wound healing and reduce scar formation by modulating the Wnt/β-catenin,phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin,vascular endothelial growth factor,transforming growth factorβand JAK-STAT pathways.Moreover,we also highlight the challenges and opportunities for engineering or modifying EVs to enhance their efficacy and specificity for wound healing.展开更多
基金Supported by the Natural Science Foundation of Hubei Province,China(No.2007ABA108)
文摘AIMTo investigate the influence of He-Ne lasers on scar formation in the filtration canal after trabeculectomy in a rabbit model, as well as to explore the mechanisms for preventing scar formation when using He-Ne lasers in vivo.
基金National Research Foundation of Korea(NRF),Grant/Award Numbers:2021R1A4A1032782,2022R1C1C1008831Korean Fund for Regenerative Medicine(KFRM),Grant/Award Number:21A0102L1-12Postdoctoral Research Program of Sungkyunkwan University。
文摘Electrical stimulation has recently received attention as noninvasive treatment in skin wound healing with its outstanding biological property for clinical setting.However,the complexity of equipment for applying appropriate electrical stimulation remains an ongoing challenge.Here,we proposed a strategy for skin scar inhibition by providing electrical stimulation via a multilayer stacked electret(MS-electret),which can generate direct current(DC)electric field(EF)without any power supply equipment.In addition,the MS-electret can easily control the intensity of EFs by simply stacking electret layers and maintain stable EF with the surface potential of 3400 V over 5 days owing to the injected charges on the electret surface.We confirmed inhibition of type 1 collagen andα-SMA expression of human dermal fibroblasts(hDFs)by 90%and 44%in vitro,indicating that the transition of hDFs to myofibroblasts was restricted by applying stable electrical stimulation.We further revealed a 20%significant decrease in the ratio of myofibroblasts caused by the MS-electret in vivo.These findings present that the MS-electret is an outstanding candidate for effective skin scar inhibition with a battery-free,physiological electrical microenvironment,and noninvasive treatment that allows it to prevent external infection.
基金Supported by the National Natural Science Foundation of China(No.81160118)Clinical Medicine Research Special-purpose Foundation of China(No.L2012052)+3 种基金Science and Technology Foundation of Jiangxi Province(No.20111BBG70026-2)Jiangxi Province Youth Science Foundation(No.20114BAB215036)Science and Technology Platform Construction Project of Jiangxi Province(No.2013-116)Health Department Tradition Chinese Medicine Science and Technology Foundation(No.2012A087)
文摘AIM:To investigate the efficacy and safety of Honghua preserved amniotic membrane(AM)for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.METHODS:Totally 36 rabbits(36 eyes)were randomly divided into 3 groups:the experimental group(ocular trabeculectomy in combination with Honghua preserved AM transplantation),the control group(ocular trabeculectomy surgery in combination with AM implantation),and the blank group(single trabeculectomy).Clinical observations[including intraocular pressure(IOP),filtering blebs and complications],MassonTrichrome staining,real-time quantitative reverse transcription-polymerase chain reaction(real-time PCR),Western blot were performed on different time points(D1,D7,D14,D21 and D56)after the surgery.RESULTS:After operated for 14d,there were statistically significant differences in the filtering blebs compared to the situation before operation(P【0.05),whereas no statistically difference on that among three groups(P】0.05).After 21d,the IOP of experimental group was lowest(P【0.05).There was significant difference between control group and blank group(P【0.05).On postoperative D14,the mean number of fibroblasts in the experimental group was significantlylower(40.6±10.2)compared to those in the control group(54.4±10.8)and blank group(68.2±11.6)(P【0.05,respectively).The mean numbers of the macrophage in the experimental and control groups were respcitively significantly lower versus the blank group(P【0.05,P【0.05,respectively).Compared to that in blank group,the level of transforming growth factor-β(TGF-β1)expression in sclera and conjunctival areas was reduced in the experimental and control groups on protein and mRNA level(P【0.05),but not significant difference between these two groups(P】0.05).CONCLUSION:The trabeculectory surgery with Honghua preserved AM can control IOP,sustain the functional filtration bleb,inhibit the proliferation of fibroblasts and open the filtrating pathway on the rabbit glaucoma models.
基金Natural Science Foundation of Hubei Province, China (No.2008cda055)
文摘AIM: To investigate the antifibrotic effect of the freeze-dried bilayered fibrin-binding amniotic membrane as a drug delivery system on glaucoma surgery in rabbit model. The aim of this study was to prepare a novel local delivery system for the sustained and controllable release of 5-Fu. METHODS: Twenty-four Japanese white rabbits were randomized into three groups: the experimental group (ocular trabeculectomy in combination with 5-Fu loaded freeze-dried bilayered fibrin-binding amniotic membrane transplantation), the control group (ocular trabeculectomy in combination with 5-Fu) and the blank group (single trabeculectomy). HE staining, massion staining and immunohistochemistry for alpha -SMA were performed on days 7, 14, 21 and 30 following surgery. The concentration of 5-Fu in rabbit aqueous humor was examined by high performance liquid chromatography (HPLC) 3 days after the surgery. RESULTS: Statistical differences were noted in intraocular pressure among groups on day 7, 14, 21 and 30 following surgery. Histology further demonstrated that trabeculectomy in combination with freeze-dried bilayered fibrin-binding amniotic membrane yielded well wound healing and no scar formation and was beneficial for long term effect. CONCLUSION: HPLC showed a good slow-release effect with freeze-dried bilayered fibrin-binding amniotic membrane.
基金supported by the National Key R&D Program of China,No.2020YFC2008502 (to QW)the National Natural Science Foundation of China,No. 82172534 (to QW)。
文摘Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury. In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3 K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3 K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3 K/AKT/mTOR pathway.
基金supported by research grants to SL from NIH(1R01NS079432 and 1R01EY024575)Shriners Research Foundation(SHC-86300-PHI,SHC-86200-PHI-16 and SHC-85100)
文摘Reactive astrogliosis occurs after central nervous system（CNS） injuries whereby resident astrocytes form rapid responses along a graded continuum. Following CNS lesions, na？ve astrocytes are converted into reactive astrocytes and eventually into scar-forming astrocytes that block axon regeneration and neural repair. It has been known for decades that scarring development and its related extracellular matrix molecules interfere with regeneration of injured axons after CNS injury, but the cellular and molecular mechanisms for controlling astrocytic scar formation and maintenance are not well known. Recent use of various genetic tools has made tremendous progress in better understanding genesis of reactive astrogliosis. Especially, the latest experiments demonstrate environment-dependent plasticity of reactive astrogliosis because reactive astrocytes isolated from injured spinal cord form scarring astrocytes when transplanted into injured spinal cord, but revert in retrograde to naive astrocytes when transplanted into naive spinal cord. The interactions between upregulated type I collagen and its receptor integrin β1 and the N-cadherin-mediated cell adhesion appear to play major roles for local astrogliosis around the lesion. This review centers on the environment-dependent plasticity of reactive astrogliosis after spinal cord injury and its potential as a therapeutic target.
基金supported by the Science and Technology Action Innovation Plan of Shanghai[23QB1401000,24S11901800]the Young Innovative Talents Project of Zhejiang Health Science and Technology Plan[2022RC237]+3 种基金Medical and Health Science and Technology Project of Hangzhou[B20200432]Special Policy for Shanghai University Science and Technology Park-Science and Technology Innovation Special Fund[2021-HSD-8-1-004]Epidemic-related projects of the Special Policy for Science and Technology Park Around Shanghai UniversitySpecial Fund for Promoting High-Quality Development in Shanghai-Key Fields of Industrial Strategy Technology Research-Biomedical Special Topic[SY2022008].
文摘Scar formation can be effectively prevented when the proportion of collagen type Ⅰ(Col Ⅰ)/type Ⅲ(Col Ⅲ)is reduced.Unlike Col Ⅲ,recombinant human collagen type Ⅲ chain(RHC Ⅲ chain)does not possess a triple helical structure.This study aimed to elucidate the capacity of fibroblasts to uptake RHC Ⅲ chain,reduce the Col Ⅰ/Col Ⅲ ratio and determine its effects on wound healing and scar.RHC Ⅲ chain demonstrates qualified cell compatibility.In cell experiments,immunofluorescence and western blot(WB)analyses revealed an increase in the polyhistidine tag level,indicating that RHC Ⅲ chain in internalized by these cells.Transmission electron microscopy showed increased intracellular phagocytic activity,indicating that RHC Ⅲ chain enters fibroblasts by endocytosis.The immunofluorescence and WB showed that Col Ⅲ synthesis enhanced,and Col Ⅰ/Col Ⅲ ratio reduced.However,the polyhistidine tag disappeared with time,indicating that RHC Ⅲ chain degraded within cells and then synthesized into Col Ⅲ.The content of newly synthesized Col Ⅲ increases,but real-time fluorescence quantitative showed a decrease in Col Ⅲ related gene content suggests the formation of negative feedback.However,due to the sufficient raw materials,the amount of Col Ⅲ synthesis is still increasing,leading to the reduction of the ratio of type Ⅰ collagen/type Ⅲ collagen,which beneficial to wound healing and reduce scar hyperplasia.In animal experiments,the SD rat full-thickness skin defect model of wound suggests that RHC Ⅲ chain also takes effect through endocytosis and ultimately promotes wound healing.The rabbit ear scar model suggests that RHC Ⅲ chain inhibits scar proliferation by reducing the ratio of Col Ⅰ/Col Ⅲ.In summary,RHC Ⅲ chain was endocytosed by fibroblasts to promote native Col Ⅲ synthesis,as well as promote wound healing and reduce scar hyperplasia.
基金supported by National Science Fund for Distinguished Young Scholars(No.31625011)the National Key Research and Development Program(No.2016YFC1101100).
文摘Cross-linking agents are frequently used to restore corneal properties after decellularization,and it is especially important to select an appropriate method to avoid excessive cross-linking.In addition,how to promote wound healing and how to improve scar formation require further investigation.To ensure the safety and efficacy of animal-derived products,we designed bioartificial corneas(BACs)according to the criteria for Class III medical devices.Our BACs do not require crosslinking agents and increase mechanical strength via self-cross-linking of aldehyde-modified hyaluronic acid(AHA)and carboxymethyl chitosan(CMC)on the surface of decellularized porcine corneas(DPCs).The results showed that the BACs had good biocompatibility and transparency,and the modification enhanced their antibacterial and anti-inflammatory properties in vitro.Preclinical animal studies showed that the BACs can rapidly regenerate the epithelium and restore vision within a month.After 3 months,the BACs were gradually filled with epithelial,stromal,and neuronal cells,and after 6 months,their transparency and histology were almost normal.In addition,side effects such as corneal neovascularization,conjunctival hyperemia,and ciliary body hyperemia rarely occur in vivo.Therefore,these BACs show promise for clinical application for the treatment of infectious corneal ulcers and as a temporary covering for corneal perforations to achieve the more time.
基金financially supported by the National Natural Science Foundation of China(grant no.82102334 to S.Chen,grant no.82272204 to J.Pan,grant no.82360446 to W.Wan)Wenzhou Science and Technology Major Project(grant no.ZY2022026 to S.Chen)+2 种基金Pioneer”and“Leading Goose”R&D Program of Zhejiang(grant no.2023C03084 to J.Pan)Foundation of Health Commission of Jiangxi Province(Grant No.202210603 to W.Wan)the“Thousand Talents Plan”of Jiangxi Province Introduces and Trains Innovative and Entrepreneurial High-level Talents(jxsq2023201027).
文摘Bacterial infection and scar formation remain primary challenges in wound healing.To address these issues,we developed a decellularized pomelo peel(DPP)functionalized with an adhesive PVA-TSPBA hydrogel and antibacterial gallic acid/copper MOFs.The hybrid wound dressing demonstrates favorable biocompatibility.It does not impede the proliferation of fibroblasts or immune cells and can stimulate fibroblast migration,endothelial angiogenesis,and M2 macrophage polarization.Additionally,the dressing can scavenge reactive oxygen species(ROS)and provide antioxidant effects.Furthermore,DPP+MOF@Gel effectively inhibits the viability of S.aureus and E.coli in vitro and in vivo.The histological observations revealed enhanced granulation tissue formation,re-epithelialization,and angiogenesis in the DPP+MOF@Gel group compared to other groups.The local immune response also shifted from a pro-inflammatory to a pro-regenerative status with DPP+MOF@Gel treatment.The skin incision stitching experiment further exhibits DPP+MOF@Gel could reduce scar formation during wound healing.Taken together,the hybrid DPP+MOF@Gel holds great promise for treating bacteria-infected skin wounds and inhibiting scar formation during wound healing.
基金supported by grants from the National Natural Science Foundation of China(81902784)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004)+2 种基金Fund of Sichuan Provincial Department of Science and Technology(2022YFSY0058)the Research Funding(RCDWJS 2020-20)Research and Development Program(RD-02-202002)fromWest China School/Hospital of Stomatology Sichuan University.
文摘Chronic wounds are wounds that cannot heal properly due to various factors,such as underlying diseases,infection or reinjury,and improper healing of skin wounds and ulcers can cause a serious economic burden.Numerous studies have shown that extracellular vesicles(EVs)derived from stem/progenitor cells promote wound healing,reduce scar formation and have significant advantages over traditional treatment methods.EVs are membranous particles that carry various bioactive molecules from their cellular origins,such as cytokines,nucleic acids,enzymes,lipids and proteins.EVs can mediate cell-to-cell communication and modulate various physiological processes,such as cell differentiation,angiogenesis,immune response and tissue remodelling.In this review,we summarize the recent advances in EV-based wound healing,focusing on the signalling pathways that are regulated by EVs and their cargos.We discuss how EVs derived from different types of stem/progenitor cells can promote wound healing and reduce scar formation by modulating the Wnt/β-catenin,phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin,vascular endothelial growth factor,transforming growth factorβand JAK-STAT pathways.Moreover,we also highlight the challenges and opportunities for engineering or modifying EVs to enhance their efficacy and specificity for wound healing.
