Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy aft...Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.展开更多
Background: Wound healing is a process of cell-cell interaction and cell-extracellular matrix interaction. Dermal multipotent stem cells (dMSCs) have the abilities to promote survival and wound healing, but the potent...Background: Wound healing is a process of cell-cell interaction and cell-extracellular matrix interaction. Dermal multipotent stem cells (dMSCs) have the abilities to promote survival and wound healing, but the potential function of dMSCs in wound healing, particularly in the initiation of wound repair, has not been fully understood. Methods: dMSCs and fibroblasts were isolated from neonatal rat dermis and were further purified and expanded. The cell cycles were determined with flow cytometry, while the radiosensitivity was measured by MTT assay. Rats were wounded with a 7-cm incision on the back skin and the wound fluids were collected by inserting two pieces of sterile polyvinyl alcohol sponge (1 cmin diameter and0.4 cmin thickness) subcutaneously into the dorsum of each rat through the midline of incision on the 1st, 2nd, 3rd and 4th day after incision. The effects of wound fluids on the proliferation of dMSCs and fibroblasts were measured with MTT assays. dMSC’s abilities of adhesion and attachment and its migration in response to wound fluids collected on the 1st day after incision were explored by measuring the percentage of floating cells and the cells migrated into wounding area in vitro, respectively. Results: The isolated dMSCs were morphologically homogenous and highly proliferative. Most of the cultured dMSCs were quiescent with few apoptotic cells. Compared with fibroblasts, dMSCs were more sensitive to radiation and more proliferative in response to wound fluids, especially to the wound fluids collected on the 1st day after wounding. Moreover, their abilities to attach, adhere and migrate were significantly enhanced with the early-phase wound fluids. Conclusions: As primitive stem cells, dMSCs are very responsive to wound fluids, which suggests dMSCs’ important role in wound healing, especially in initiating wound repair.展开更多
Studies on a variety of highly regenerative tissues, including the central nervous system(CNS) in non-mammalian vertebrates, have consistently demonstrated that tissue damage induces the formation of an ionic curren...Studies on a variety of highly regenerative tissues, including the central nervous system(CNS) in non-mammalian vertebrates, have consistently demonstrated that tissue damage induces the formation of an ionic current at the site of injury. These injury currents generate electric fields(EF) that are 100-fold increased in intensity over that measured for uninjured tissue. In vitro and in vivo experiments have convincingly demonstrated that these electric fields(by their orientation, intensity and duration) can drive the migration, proliferation and differentiation of a host of cell types. These cellular behaviors are all necessary to facilitate regeneration as blocking these EFs at the site of injury inhibits tissue repair while enhancing their intensity promotes repair. Consequently, injury-induced currents, and the EFs they produce, represent a potent and crucial signal to drive tissue regeneration and repair. In this review, we will discuss how injury currents are generated, how cells detect these currents and what cellular responses they can induce. Additionally, we will describe the growing evidence suggesting that EFs play a key role in regulating the cellular response to injury and may be a therapeutic target for inducing regeneration in the mammalian CNS.展开更多
Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung d...Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung diseases, such as idiopathic pulmonary fibrosis (IPF). In this study, we have investigated the paracrine effect of differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC) wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM) which contain cell secretory factors were collected at different time points of differentiation. CM were then tested onin vitro?wound repair model with human type II AEC line, A549 cells (AEC). Our study demonstrated that CM originated from undifferentiated hESC significantly inhibited AEC wound repair when compared to the control. Whereas, CM originated from Activin-directed hESC differentiated cell population demonstrated a differential reparative effect on AEC wound repair model. CM obtained from Day-11 of differentiation significantly enhanced AEC wound repair in comparison to CM collected from pre- and post-Day-11 of differentiation. Day-11 CM enhanced AEC wound repair through significant stimulation of cell migration and cell proliferation. RT-PCR and immunocytochemistry confirmed that Day-11 CM was originated form a mixed population of endodermal/mesodermal differentiated hESC. This report suggests a putative paracrine-mediated epithelial injury healing mechanism by hESC secreted products, which is valuable in the development of novel stem cell-based therapeutic strategies.展开更多
Foreign body reactions induced by macrophages often cause delay or failure of wound healing in the application of tissue engineering scaffolds.This study explores the application of nanosilver(NAg)to reduce foreign bo...Foreign body reactions induced by macrophages often cause delay or failure of wound healing in the application of tissue engineering scaffolds.This study explores the application of nanosilver(NAg)to reduce foreign body reactions during scaffold transplantation.An NAg hybrid collagen-chitosan scaffold(NAg-CCS)was prepared using the freeze-drying method.The NAg-CCS was implanted on the back of rats to evaluate the effects on foreign body reactions.Skin tissue samples were collected for histological and immunological evaluation at variable intervals.Miniature pigs were used to assess the effects of NAg on skin wound healing.The wounds were photographed,and tissue samples were collected for molecular biological analysis at different time points post-transplantation.NAg-CCS has a porous structure and the results showed that it could release NAg constantly for two weeks.The NAg-CCS group rarely developed a foreign body reaction,while the blank-CCS group showed granulomas or necrosis in the subcutaneous grafting experiment.Both matrix metalloproteinase-1(MMP-1)and tissue inhibitor of metalloproteinase-1(TIMP-1)were reduced significantly in the NAg-CCS group.The NAg-CCS group had higher interleukin(IL)-10 and lower IL-6 than the blank CCS group.In the wound healing study,M1 macrophage activation and inflammatory-related proteins inducible nitric oxide synthase(iNOS),IL-6,and interferon-(IFN-)were inhibited by NAg.In contrast,M2 macrophage activation and proinflammatory proteins(arginase-1),major histocompatibility complex-II(MHC-II),and found in inflammatory zone-1(FIZZ-1)were promoted,and this was responsible for suppressing the foreign body responses and accelerating wound healing.In conclusion,dermal scaffolds containing NAg suppressed the foreign body reaction by regulating macrophages and the expression of inflammatory cytokines,thereby promoting wound healing.展开更多
Current treatments for full-thickness skin injuries are still unsatisfactory due to the lack of hierarchically stimulated dressings that can integrate the rapid hemostasis,inflammation regulation,and skin tissue remod...Current treatments for full-thickness skin injuries are still unsatisfactory due to the lack of hierarchically stimulated dressings that can integrate the rapid hemostasis,inflammation regulation,and skin tissue remodeling into the one system instead of single-stage boosting.In this work,a multilayer-structured bioactive glass nanopowder(BGN@PTE)is developed by coating the poly-tannic acid andε-polylysine onto the BGN via facile layer-by-layer assembly as an integrative and multilevel dressing for the sequential management of wounds.In comparison to BGN and poly-tannic acid coated BGN,BGN@PTE exhibited the better hemostatic performance because of its multiple dependent approaches to induce the platelet adhesion/activation,red blood cells(RBCs)aggregation and fibrin network formation.Simultaneously,the bioactive ions from BGN facilitate the regulation of the inflammatory response while the poly-tannic acid and antibacterialε-polylysine prevent the wound infection,promoting the wound healing during the inflammatory stage.In addition,BGN@PTE can serve as a reactive oxygen species scavenger,alleviate the oxidation stress in wound injury,induce the cell migration and angiogenesis,and promote the proliferation stage of wound repair.Therefore,BGN@PTE demonstrated the significantly higher wound repair capacity than the commercial bioglass dressing Dermlin™.This multifunctional BGN@PTE is a potentially valuable dressing for full-thickness wound management and may be expected to extend to the other wounds therapy.展开更多
The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we att...The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-guest hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-guest hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.展开更多
Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or contusions.As such injuries are common to all human groups,they may at times represent a serious socioeconomic burden.Currently,increas...Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or contusions.As such injuries are common to all human groups,they may at times represent a serious socioeconomic burden.Currently,increasing numbers of studies have focused on the role of mesenchymal stem cell(MSC)-derived extracellular vesicles(EVs)in skin wound repair.As a cell-free therapy,MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy.Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures,including the regeneration of vessels,nerves,and hair follicles.In addition,MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization,wound angiogenesis,cell proliferation,and cell migration,and by inhibiting excessive extracellular matrix production.Additionally,these structures can serve as a scaffold for components used in wound repair,and they can be developed into bioengineered EVs to support trauma repair.Through the formulation of standardized culture,isolation,purification,and drug delivery strategies,exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair.In conclusion,MSCderived EV-based therapies have important application prospects in wound repair.Here we provide a comprehensive overview of their current status,application potential,and associated drawbacks.展开更多
The mucin 1(MUC1)gene emerged in mammals to afford protection of barrier epithelial tissues from the external environment.MUC1 encodes a transmembrane C-terminal(MUC1-C)subunit that is activated by loss of homeostasis...The mucin 1(MUC1)gene emerged in mammals to afford protection of barrier epithelial tissues from the external environment.MUC1 encodes a transmembrane C-terminal(MUC1-C)subunit that is activated by loss of homeostasis and induces inflammatory,proliferative,and remodeling pathways associated with wound repair.As a consequence,chronic activation of MUC1-C promotes lineage plasticity,epigenetic reprogramming,and carcinogenesis.In driving cancer progression,MUC1-C is imported into the nucleus,where it induces NF-κB inflammatory signaling and the epithelial-mesenchymal transition(EMT).MUC1-C represses gene expression by activating(i)DNA methyltransferase 1(DNMT1)and DNMT3b,(ii)Polycomb Repressive Complex 1(PRC1)and PRC2,and(iii)the nucleosome remodeling and deacetylase(NuRD)complex.PRC1/2-mediated gene repression is counteracted by the SWI/SNF chromatin remodeling complexes.MUC1-C activates the SWI/SNF BAF and PBAF complexes in cancer stem cell(CSC)models with the induction of genome-wide differentially accessible regions and expressed genes.MUC1-C regulates chromatin accessibility of enhancer-like signatures in association with the induction of the Yamanaka pluripotency factors and recruitment of JUN and BAF,which promote increases in histone activation marks and opening of chromatin.These and other findings described in this review have uncovered a pivotal role for MUC1-C in integrating lineage plasticity and epigenetic reprogramming,which are transient in wound repair and sustained in promoting CSC progression.展开更多
Wound repair,as one of the most intricate biological mechanisms,is essential to ensure the formation and integrity of the skin barrier.However,multiple factors can cause delays and severe debilitating effects in wound...Wound repair,as one of the most intricate biological mechanisms,is essential to ensure the formation and integrity of the skin barrier.However,multiple factors can cause delays and severe debilitating effects in wound repair,which bring serious challenges.Metal elements such as calcium,copper,iron,and zinc serve irreplaceable roles in various regulatory pathways of the human body and directly or indirectly affect the orderly wound repair process.Biomaterials have proven to be an attractive strategy that can be applied to wound repair and have excellent potential to induce skin regeneration.In recent decades,with in-depth research on the regulatory mechanisms of metal elements involved in wound repair,metal-based biomaterials have been widely reported.Metal-based zero-dimensional(0D)biomaterials such as Angstrom-scale metallic materials and metal quantum dots,metal-based one-dimensional(1D)biomaterials such as nanorods,nanowires and nanofibers,metal-based two-dimensional(2D)biomaterials such as nanofilms and nanosheets,and metal-based three-dimensional(3D)biomaterials such as nanoframes have achieved remarkable results,which provide great support for accelerated wound repair.In this review,we systematically investigated the advances and impacts of various metal-based biomaterial platforms for wound repair to provide valuable guidance for future breakthroughs in wound treatment.展开更多
To report the methods and effect of axial pattern flap on lower limb in repairing deep wounds of heels by using color Doppler flow imaging (CDFI) technique so as to solve the ever before problems that the vessel can n...To report the methods and effect of axial pattern flap on lower limb in repairing deep wounds of heels by using color Doppler flow imaging (CDFI) technique so as to solve the ever before problems that the vessel can not be displayed in designing axial flap.Methods Suitable axial flaps on lower limbs were selected according to the character of the wounds.There were 25 flaps including 10 cases of the distal-based sural neurovascular flap,nine medial sole flap and six medial leg flap.All the axial pattern flaps were designed on the basis of traditional design ways before operation;then,CDFI appliance with high resolution was used to examine the starting spot,exterior diameter,trail and length of the flap’s major artery.The flaps were redesigned according to the results of CDFI and transferred to cover the wounds.In the meantime,both the results of operation and examination were compared.Results The major artery’s starting spot,exterior diameter,trail and anatomic layers were displayed clearly,in consistency with the results of operation.The flaps survived completely and recovered well,with perfect appearance,color and arthral function.Conclusion CDFI is a simple,macroscopic and atraumatic method for designing the axial pattern flap on lower limb,can provide more scientific and accurate evidence for preoperative determination of flap transplantation and is worthy of clinical application.10 refs,4 figs,2 tabs.展开更多
Objective To discuss the application of medial planta island flaps pedicled with anterior tibial artery perforator in front of inner malleolus for repairing small wounds around ankle Methods From Jan. 2005 to Jun. 200...Objective To discuss the application of medial planta island flaps pedicled with anterior tibial artery perforator in front of inner malleolus for repairing small wounds around ankle Methods From Jan. 2005 to Jun. 2009,10 cases with small wounds around ankle展开更多
BACKGROUND The diabetic foot is a common cause of disability and death,and comorbid foot infections usually lead to prolonged hospitalization,high healthcare costs,and a significant increase in amputation rates.And mo...BACKGROUND The diabetic foot is a common cause of disability and death,and comorbid foot infections usually lead to prolonged hospitalization,high healthcare costs,and a significant increase in amputation rates.And most diabetic foot trauma is complicated by lower extremity arteriopathy,which becomes an independent risk factor for major amputation in diabetic foot patients.AIM To establish the efficacy and safety of endovascular revascularization(ER)combined with vacuum-assisted closure(VAC)for the treatment of diabetic foot.METHODS Clinical data were collected from 40 patients with diabetic foot admitted to the Second Affiliated Hospital of Soochow University from April 2018 to April 2022.Diabetic foot lesions were graded according to Wagner’s classification,and blood flow to the lower extremity was evaluated using the ankle-brachial index test and computerized tomography angiography of the lower extremity arteries.Continuous subcutaneous insulin infusion pumps were used to achieve glycemic control.Lower limb revascularization was facilitated by percutaneous transluminal balloon angioplasty(BA)or stenting.Wounds were cleaned by nibbling debridement.Wound granulation tissue growth was induced by VAC,and wound repair was performed by skin grafting or skin flap transplantation.RESULTS Of the 35 cases treated with lower limb revascularization,34 were successful with a revascularization success rate of 97%.Of these,6 cases underwent stenting after BA of the superficial femoral artery,and 1 received popliteal artery stent implantation.In the 25 cases treated with infrapopliteal artery revascularization,39 arteries were reconstructed,7 of which were treated by drug-coated BA and the remaining 32 with plain old BA.VAC was performed in 32 wounds.Twenty-four cases of skin grafting and 2 cases of skin flap transplantation were performed.Two patients underwent major amputations,whereas 17 had minor amputations,accounting for a success limb salvage rate of 95%.CONCLUSION ER in combination with VAC is a safe and effective treatment for diabetic foot that can significantly improve limb salvage rates.The use of VAC after ER simplifies and facilitates wound repair.展开更多
目的:探究重组贻贝粘蛋白水凝胶敷料(Recombined mussel adhesive protein hydrogel dressing,Rmaphd)在点阵CO_(2)激光治疗面部痤疮萎缩性瘢痕术后创面修复中的应用效果。方法:选择2022年6月-2023年2月面部痤疮萎缩性瘢痕患者117例,分...目的:探究重组贻贝粘蛋白水凝胶敷料(Recombined mussel adhesive protein hydrogel dressing,Rmaphd)在点阵CO_(2)激光治疗面部痤疮萎缩性瘢痕术后创面修复中的应用效果。方法:选择2022年6月-2023年2月面部痤疮萎缩性瘢痕患者117例,分为Rmaphd组、重组人表皮生长因子(Recombinant human epidermal growth factor,rhEGF)组和对照组,每组39例,三组均给予点阵CO_(2)激光术治疗,术后分别给予Rmaphd、rhEGF及生理盐水处理,比较三组疗效、ECCA评分、症状持续时间以及生活质量评分。结果:Rmaphd组和rhEGF组总有效率分别为92.31%和94.87%,均高于对照组76.92%(P<0.05),术后ECCA评分低于对照组(P<0.05),术后疼痛、红斑、痂皮持续时间短于对照组(P<0.05),Acne-QoL各指标得分优于对照组(P<0.05);上述各临床Rmaphd组与rhEGF组差异无统计学意义(P>0.05)。结论:Rmaphd用于点阵CO_(2)激光治疗面部痤疮萎缩性瘢痕术后创面修复疗效显著,具备在临床上辅助激光治疗术后修复的应用潜力。展开更多
文摘Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.
文摘Background: Wound healing is a process of cell-cell interaction and cell-extracellular matrix interaction. Dermal multipotent stem cells (dMSCs) have the abilities to promote survival and wound healing, but the potential function of dMSCs in wound healing, particularly in the initiation of wound repair, has not been fully understood. Methods: dMSCs and fibroblasts were isolated from neonatal rat dermis and were further purified and expanded. The cell cycles were determined with flow cytometry, while the radiosensitivity was measured by MTT assay. Rats were wounded with a 7-cm incision on the back skin and the wound fluids were collected by inserting two pieces of sterile polyvinyl alcohol sponge (1 cmin diameter and0.4 cmin thickness) subcutaneously into the dorsum of each rat through the midline of incision on the 1st, 2nd, 3rd and 4th day after incision. The effects of wound fluids on the proliferation of dMSCs and fibroblasts were measured with MTT assays. dMSC’s abilities of adhesion and attachment and its migration in response to wound fluids collected on the 1st day after incision were explored by measuring the percentage of floating cells and the cells migrated into wounding area in vitro, respectively. Results: The isolated dMSCs were morphologically homogenous and highly proliferative. Most of the cultured dMSCs were quiescent with few apoptotic cells. Compared with fibroblasts, dMSCs were more sensitive to radiation and more proliferative in response to wound fluids, especially to the wound fluids collected on the 1st day after wounding. Moreover, their abilities to attach, adhere and migrate were significantly enhanced with the early-phase wound fluids. Conclusions: As primitive stem cells, dMSCs are very responsive to wound fluids, which suggests dMSCs’ important role in wound healing, especially in initiating wound repair.
文摘Studies on a variety of highly regenerative tissues, including the central nervous system(CNS) in non-mammalian vertebrates, have consistently demonstrated that tissue damage induces the formation of an ionic current at the site of injury. These injury currents generate electric fields(EF) that are 100-fold increased in intensity over that measured for uninjured tissue. In vitro and in vivo experiments have convincingly demonstrated that these electric fields(by their orientation, intensity and duration) can drive the migration, proliferation and differentiation of a host of cell types. These cellular behaviors are all necessary to facilitate regeneration as blocking these EFs at the site of injury inhibits tissue repair while enhancing their intensity promotes repair. Consequently, injury-induced currents, and the EFs they produce, represent a potent and crucial signal to drive tissue regeneration and repair. In this review, we will discuss how injury currents are generated, how cells detect these currents and what cellular responses they can induce. Additionally, we will describe the growing evidence suggesting that EFs play a key role in regulating the cellular response to injury and may be a therapeutic target for inducing regeneration in the mammalian CNS.
文摘Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung diseases, such as idiopathic pulmonary fibrosis (IPF). In this study, we have investigated the paracrine effect of differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC) wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM) which contain cell secretory factors were collected at different time points of differentiation. CM were then tested onin vitro?wound repair model with human type II AEC line, A549 cells (AEC). Our study demonstrated that CM originated from undifferentiated hESC significantly inhibited AEC wound repair when compared to the control. Whereas, CM originated from Activin-directed hESC differentiated cell population demonstrated a differential reparative effect on AEC wound repair model. CM obtained from Day-11 of differentiation significantly enhanced AEC wound repair in comparison to CM collected from pre- and post-Day-11 of differentiation. Day-11 CM enhanced AEC wound repair through significant stimulation of cell migration and cell proliferation. RT-PCR and immunocytochemistry confirmed that Day-11 CM was originated form a mixed population of endodermal/mesodermal differentiated hESC. This report suggests a putative paracrine-mediated epithelial injury healing mechanism by hESC secreted products, which is valuable in the development of novel stem cell-based therapeutic strategies.
基金supported by the Zhejiang Province Key Research and Development Program(No.2019C03083)the Zhejiang Provincial Basic Public Welfare Research Program(No.LGF19H150008)the National Natural Science Foundation of China(Nos.81601681 and 81871558).
文摘Foreign body reactions induced by macrophages often cause delay or failure of wound healing in the application of tissue engineering scaffolds.This study explores the application of nanosilver(NAg)to reduce foreign body reactions during scaffold transplantation.An NAg hybrid collagen-chitosan scaffold(NAg-CCS)was prepared using the freeze-drying method.The NAg-CCS was implanted on the back of rats to evaluate the effects on foreign body reactions.Skin tissue samples were collected for histological and immunological evaluation at variable intervals.Miniature pigs were used to assess the effects of NAg on skin wound healing.The wounds were photographed,and tissue samples were collected for molecular biological analysis at different time points post-transplantation.NAg-CCS has a porous structure and the results showed that it could release NAg constantly for two weeks.The NAg-CCS group rarely developed a foreign body reaction,while the blank-CCS group showed granulomas or necrosis in the subcutaneous grafting experiment.Both matrix metalloproteinase-1(MMP-1)and tissue inhibitor of metalloproteinase-1(TIMP-1)were reduced significantly in the NAg-CCS group.The NAg-CCS group had higher interleukin(IL)-10 and lower IL-6 than the blank CCS group.In the wound healing study,M1 macrophage activation and inflammatory-related proteins inducible nitric oxide synthase(iNOS),IL-6,and interferon-(IFN-)were inhibited by NAg.In contrast,M2 macrophage activation and proinflammatory proteins(arginase-1),major histocompatibility complex-II(MHC-II),and found in inflammatory zone-1(FIZZ-1)were promoted,and this was responsible for suppressing the foreign body responses and accelerating wound healing.In conclusion,dermal scaffolds containing NAg suppressed the foreign body reaction by regulating macrophages and the expression of inflammatory cytokines,thereby promoting wound healing.
基金This work was supported by the Special Support Program for High Level Talents of Shaanxi Province of China,the key R&D plan of Shaanxi Province of China(grant No.2021GXLH-Z-052)State Key Laboratory for Manufacturing Systems Engineering of China(grant No.sklms2021006)Young Talent Support Plan of Xi’an Jiaotong University of China(grant No.QY6J003).
文摘Current treatments for full-thickness skin injuries are still unsatisfactory due to the lack of hierarchically stimulated dressings that can integrate the rapid hemostasis,inflammation regulation,and skin tissue remodeling into the one system instead of single-stage boosting.In this work,a multilayer-structured bioactive glass nanopowder(BGN@PTE)is developed by coating the poly-tannic acid andε-polylysine onto the BGN via facile layer-by-layer assembly as an integrative and multilevel dressing for the sequential management of wounds.In comparison to BGN and poly-tannic acid coated BGN,BGN@PTE exhibited the better hemostatic performance because of its multiple dependent approaches to induce the platelet adhesion/activation,red blood cells(RBCs)aggregation and fibrin network formation.Simultaneously,the bioactive ions from BGN facilitate the regulation of the inflammatory response while the poly-tannic acid and antibacterialε-polylysine prevent the wound infection,promoting the wound healing during the inflammatory stage.In addition,BGN@PTE can serve as a reactive oxygen species scavenger,alleviate the oxidation stress in wound injury,induce the cell migration and angiogenesis,and promote the proliferation stage of wound repair.Therefore,BGN@PTE demonstrated the significantly higher wound repair capacity than the commercial bioglass dressing Dermlin™.This multifunctional BGN@PTE is a potentially valuable dressing for full-thickness wound management and may be expected to extend to the other wounds therapy.
基金supported by the National Natu-ral Science Foundation of China (T2288101,31971266,82272152,22075087)Guangdong Basic and Applied Basic Research Foundation (2022A1515011925)the Key Research and Development Program of Guangzhou (202007020002).
文摘The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-guest hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-guest hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.
基金supported by the National Key Research and Development Project Intergovernmental Cooperation in Science and Technology of China(2018YFE0126900)the Key R&D Program of Lishui City(2021ZDYF12)the National Natural Science Foundation of China(82271629)。
文摘Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or contusions.As such injuries are common to all human groups,they may at times represent a serious socioeconomic burden.Currently,increasing numbers of studies have focused on the role of mesenchymal stem cell(MSC)-derived extracellular vesicles(EVs)in skin wound repair.As a cell-free therapy,MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy.Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures,including the regeneration of vessels,nerves,and hair follicles.In addition,MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization,wound angiogenesis,cell proliferation,and cell migration,and by inhibiting excessive extracellular matrix production.Additionally,these structures can serve as a scaffold for components used in wound repair,and they can be developed into bioengineered EVs to support trauma repair.Through the formulation of standardized culture,isolation,purification,and drug delivery strategies,exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair.In conclusion,MSCderived EV-based therapies have important application prospects in wound repair.Here we provide a comprehensive overview of their current status,application potential,and associated drawbacks.
基金Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant numbers CA97098,CA166480 and CA233084 awarded to D.Kufe。
文摘The mucin 1(MUC1)gene emerged in mammals to afford protection of barrier epithelial tissues from the external environment.MUC1 encodes a transmembrane C-terminal(MUC1-C)subunit that is activated by loss of homeostasis and induces inflammatory,proliferative,and remodeling pathways associated with wound repair.As a consequence,chronic activation of MUC1-C promotes lineage plasticity,epigenetic reprogramming,and carcinogenesis.In driving cancer progression,MUC1-C is imported into the nucleus,where it induces NF-κB inflammatory signaling and the epithelial-mesenchymal transition(EMT).MUC1-C represses gene expression by activating(i)DNA methyltransferase 1(DNMT1)and DNMT3b,(ii)Polycomb Repressive Complex 1(PRC1)and PRC2,and(iii)the nucleosome remodeling and deacetylase(NuRD)complex.PRC1/2-mediated gene repression is counteracted by the SWI/SNF chromatin remodeling complexes.MUC1-C activates the SWI/SNF BAF and PBAF complexes in cancer stem cell(CSC)models with the induction of genome-wide differentially accessible regions and expressed genes.MUC1-C regulates chromatin accessibility of enhancer-like signatures in association with the induction of the Yamanaka pluripotency factors and recruitment of JUN and BAF,which promote increases in histone activation marks and opening of chromatin.These and other findings described in this review have uncovered a pivotal role for MUC1-C in integrating lineage plasticity and epigenetic reprogramming,which are transient in wound repair and sustained in promoting CSC progression.
基金supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China(2018ZX10301402)International Cooperation and Exchange of the National Natural Science Foundation of China(51820105004)+2 种基金General program of the National Natural Science Foundation of China(51973243)General program of Guangdong Natural Science Foundation(2020A1515010983)the Fundamental Research Funds for the Central Universities(191gzd35).
文摘Wound repair,as one of the most intricate biological mechanisms,is essential to ensure the formation and integrity of the skin barrier.However,multiple factors can cause delays and severe debilitating effects in wound repair,which bring serious challenges.Metal elements such as calcium,copper,iron,and zinc serve irreplaceable roles in various regulatory pathways of the human body and directly or indirectly affect the orderly wound repair process.Biomaterials have proven to be an attractive strategy that can be applied to wound repair and have excellent potential to induce skin regeneration.In recent decades,with in-depth research on the regulatory mechanisms of metal elements involved in wound repair,metal-based biomaterials have been widely reported.Metal-based zero-dimensional(0D)biomaterials such as Angstrom-scale metallic materials and metal quantum dots,metal-based one-dimensional(1D)biomaterials such as nanorods,nanowires and nanofibers,metal-based two-dimensional(2D)biomaterials such as nanofilms and nanosheets,and metal-based three-dimensional(3D)biomaterials such as nanoframes have achieved remarkable results,which provide great support for accelerated wound repair.In this review,we systematically investigated the advances and impacts of various metal-based biomaterial platforms for wound repair to provide valuable guidance for future breakthroughs in wound treatment.
文摘To report the methods and effect of axial pattern flap on lower limb in repairing deep wounds of heels by using color Doppler flow imaging (CDFI) technique so as to solve the ever before problems that the vessel can not be displayed in designing axial flap.Methods Suitable axial flaps on lower limbs were selected according to the character of the wounds.There were 25 flaps including 10 cases of the distal-based sural neurovascular flap,nine medial sole flap and six medial leg flap.All the axial pattern flaps were designed on the basis of traditional design ways before operation;then,CDFI appliance with high resolution was used to examine the starting spot,exterior diameter,trail and length of the flap’s major artery.The flaps were redesigned according to the results of CDFI and transferred to cover the wounds.In the meantime,both the results of operation and examination were compared.Results The major artery’s starting spot,exterior diameter,trail and anatomic layers were displayed clearly,in consistency with the results of operation.The flaps survived completely and recovered well,with perfect appearance,color and arthral function.Conclusion CDFI is a simple,macroscopic and atraumatic method for designing the axial pattern flap on lower limb,can provide more scientific and accurate evidence for preoperative determination of flap transplantation and is worthy of clinical application.10 refs,4 figs,2 tabs.
文摘Objective To discuss the application of medial planta island flaps pedicled with anterior tibial artery perforator in front of inner malleolus for repairing small wounds around ankle Methods From Jan. 2005 to Jun. 2009,10 cases with small wounds around ankle
文摘BACKGROUND The diabetic foot is a common cause of disability and death,and comorbid foot infections usually lead to prolonged hospitalization,high healthcare costs,and a significant increase in amputation rates.And most diabetic foot trauma is complicated by lower extremity arteriopathy,which becomes an independent risk factor for major amputation in diabetic foot patients.AIM To establish the efficacy and safety of endovascular revascularization(ER)combined with vacuum-assisted closure(VAC)for the treatment of diabetic foot.METHODS Clinical data were collected from 40 patients with diabetic foot admitted to the Second Affiliated Hospital of Soochow University from April 2018 to April 2022.Diabetic foot lesions were graded according to Wagner’s classification,and blood flow to the lower extremity was evaluated using the ankle-brachial index test and computerized tomography angiography of the lower extremity arteries.Continuous subcutaneous insulin infusion pumps were used to achieve glycemic control.Lower limb revascularization was facilitated by percutaneous transluminal balloon angioplasty(BA)or stenting.Wounds were cleaned by nibbling debridement.Wound granulation tissue growth was induced by VAC,and wound repair was performed by skin grafting or skin flap transplantation.RESULTS Of the 35 cases treated with lower limb revascularization,34 were successful with a revascularization success rate of 97%.Of these,6 cases underwent stenting after BA of the superficial femoral artery,and 1 received popliteal artery stent implantation.In the 25 cases treated with infrapopliteal artery revascularization,39 arteries were reconstructed,7 of which were treated by drug-coated BA and the remaining 32 with plain old BA.VAC was performed in 32 wounds.Twenty-four cases of skin grafting and 2 cases of skin flap transplantation were performed.Two patients underwent major amputations,whereas 17 had minor amputations,accounting for a success limb salvage rate of 95%.CONCLUSION ER in combination with VAC is a safe and effective treatment for diabetic foot that can significantly improve limb salvage rates.The use of VAC after ER simplifies and facilitates wound repair.
文摘目的:探究重组贻贝粘蛋白水凝胶敷料(Recombined mussel adhesive protein hydrogel dressing,Rmaphd)在点阵CO_(2)激光治疗面部痤疮萎缩性瘢痕术后创面修复中的应用效果。方法:选择2022年6月-2023年2月面部痤疮萎缩性瘢痕患者117例,分为Rmaphd组、重组人表皮生长因子(Recombinant human epidermal growth factor,rhEGF)组和对照组,每组39例,三组均给予点阵CO_(2)激光术治疗,术后分别给予Rmaphd、rhEGF及生理盐水处理,比较三组疗效、ECCA评分、症状持续时间以及生活质量评分。结果:Rmaphd组和rhEGF组总有效率分别为92.31%和94.87%,均高于对照组76.92%(P<0.05),术后ECCA评分低于对照组(P<0.05),术后疼痛、红斑、痂皮持续时间短于对照组(P<0.05),Acne-QoL各指标得分优于对照组(P<0.05);上述各临床Rmaphd组与rhEGF组差异无统计学意义(P>0.05)。结论:Rmaphd用于点阵CO_(2)激光治疗面部痤疮萎缩性瘢痕术后创面修复疗效显著,具备在临床上辅助激光治疗术后修复的应用潜力。