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
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
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
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
As the body’s integumentary system,the skin is vulnerable to injuries.The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality.To this end,multiple tissue-resident cells ...As the body’s integumentary system,the skin is vulnerable to injuries.The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality.To this end,multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue.Such temporally-and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation.In this context,regulatory T cells(Tregs)hold a key role in balancing immune homeostasis and mediating cutaneous wound healing.A comprehensive understanding of Tregs’multifaceted field of activity may help decipher wound pathologies and,ultimately,establish new treatment modalities.Herein,we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair.Further,we discuss how Tregs operate during fibrosis,keloidosis,and scarring.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
Bacterial infections and excessive oxidative stress seriously hinder the healing of skin wounds.Traditional wound dressings can only serve as physical barriers and lack active molecules essential for actively promotin...Bacterial infections and excessive oxidative stress seriously hinder the healing of skin wounds.Traditional wound dressings can only serve as physical barriers and lack active molecules essential for actively promoting wound healing.Herein,an antibacterial and antioxidant liquid metal inorganic active material is developed for wound repair through in situ polymerization of chitosan/acrylic acid precursor solution initiated by tannic acid-coated liquid metal nanoparticles,without extra initiators and ultraviolet (UV) light.The tannic acid component enables the inorganic active material to exhibit antioxidant property,which can remove 90% of free radicals and relieve cellular oxidative stress.The chitosan component endows the inorganic active material with antibacterial property,effectively inhibiting the growth of Staphylococcus aureus and Escherichia coli (killing ratio: 90%).In vivo experiment demonstrates that this inorganic active material can promote the healing of Staphylococcus aureus-infected wound,achieving a closure rate of 98.16% on the 9th day.Meanwhile,this inorganic active material exhibits good electrical conductivity,enabling timely and stable monitoring of human joint movements.This work offers a simple strategy for developing multifunctional inorganic active material,which holds great potential for wound repair and motion monitoring.展开更多
<strong>Background: </strong>This is still a public problem that needs to be solved urgently: chronic and refractory wound healing with long course and complex pathological mechanism. At present, there is ...<strong>Background: </strong>This is still a public problem that needs to be solved urgently: chronic and refractory wound healing with long course and complex pathological mechanism. At present, there is still a lack of effective clinical treatment. This study, therefore, aims at exploring moist exposed burn therapy/moist exposed burn ointment (MEBT/MEBO) combined with Zhuang medicine detoxification in the treatment of chronic refractory wound healing. <strong>Methodology: </strong>100 SPF Wistar rats were randomly divided into blank control group, model control group, MEBO group, Zhuang medicine group and Combined group, with 20 rats in each group. Open wound model was established in blank control group, and chronic refractory wound model was established in other groups. Black control group and model control group were given food and water freely, MEBO group was given dressing change once a day, Zhuang medicine group was given intragastric administration once a day, and combined group was given dressing change and intragastric administration once a day. The effective rate of wound healing was observed after 12 days of continuous intervention. <strong>Conclusion: </strong>Skin regeneration medical technique combined with Zhuang medicine poison theory can effectively reduce the symptoms of bleeding and exudation, reduce the area of wound, shorten the healing time of wound, and achieve physiological healing of wound. It has a good effect on chronic refractory wound.展开更多
Generally, wounds are of two categories, such as chronic and acute. Chronic wounds takes time to heal when compared to the acute wounds. Chronic wounds include vasculitis, non healing ulcer, pyoderma gangrenosum, and ...Generally, wounds are of two categories, such as chronic and acute. Chronic wounds takes time to heal when compared to the acute wounds. Chronic wounds include vasculitis, non healing ulcer, pyoderma gangrenosum, and diseases that cause ischemia. Chronic wounds are rapidly increasing among the elderly population with dysfunctional valves in their lower extremity deep veins, ulcer, neuropathic foot and pressure ulcers. The process of the healing of wounds has several steps with the involvement of immune cells and several other cell types. There are many evidences supporting the hypothesis that apoptosis of immune cells is involved in the wound healing process by ending inflammatory condition. It is also involved in the resolution of various phases of tissue repair. During final steps of wound healing most of the endothelial cells, macrophagesand myofibroblasts undergo apoptosis or exit from the wound, leaving a mass that contains few cells and consists mostly of collagen and other extracellular matrix proteins to provide strength to the healing tissue. This review discusses the various phases of wound healing both in the chronic and acute wounds especially during diabetes mellitus and thus support the hypothesis that the oxidative stress, apoptosis, connexins and other molecules involved in the regulation of chronic wound healing in diabetes mellitus and gives proper understanding of the mechanisms controlling apoptosis and tissue repair during diabetes and may eventually develop therapeutic modalities to fasten the healing process in diabetic patients.展开更多
●AIM:To explore netrin-1 functions on corneal epithelium in vitro and in vivo.●METHODS:In vitro the human corneal epithelial(HCE)cells were treated with serum free DMEM-F12 basic media containing 0,50,100,200,300,50...●AIM:To explore netrin-1 functions on corneal epithelium in vitro and in vivo.●METHODS:In vitro the human corneal epithelial(HCE)cells were treated with serum free DMEM-F12 basic media containing 0,50,100,200,300,500,800,and 1000 ng/mL of netrin-1,respectively.The cells viability was detected by cell counting kit-8(CCK-8).The wound-healing assay was applied to assess the migration proficiency of HCE cells.Flow cytometry was used to analyze the cell-cycle distribution and apoptosis.In vivo,normal c57(6 wk)mice were demarcated with a trephine in the middle of the cornea to produce a 3-mm circular wound.Mice corneas were inflicted no epithelium with a 3-mm wound displayed,but remained the limbal epithelium intact.A blunt scalpel blade was used to remove the corneal epithelian cells,followed by topical netrin-1 application(200 ng/mL),and the group treated by PBS as control.The treated group was injected netrin-1 into the normal c57 mice inferior subconjunctival 4 h before trauma.Mouse corneal inflammation and neovascularization were observed under slit lamp microscope.The apoptosis of corneal cells was determined by TUNEL staining.●RESLUTS:A concentration of 200 ng/mL netrin-1 enhanced 25%of the HCE viability.The relative migration rates were 76.3%and 100%in control and netrin-1 treated group after cultured 72 h.Treated with netrin-1(200 ng/mL)decreased the apoptosis of HCE cells,as well as decreased their percentage from 19.3%±0.57%to 12.7%±0.42%of the total.The remaining wound area was 1.22 mm2 in control group but 0.22 mm2 in the netrin-1 treated group.Exogenous Netrin-1 inhibits apoptosis of corneal epithelial cells of c57 mice.TUNEL-positive cells at the epithelial layer of the corneas of the control and netrin-1 treated c57 mice at 24 h after wounding were 43.3%and 16.7%respectively.●CONCLUSION:Netrin-1 can reduce HCE apoptosis as well as promote its proliferation and migration.Topical application of netrin-1 promotes the injuryed cornea epithelial wound repair and inhibits apoptosis of corneal epithelial cells.These findings may offer potential therapies to repair the defects of corneal epithelial based on netrin-1.展开更多
The repair of wounded tissue during postnatal life could be associated with the upregulation of some functions characteristic of the initial phases of embryonic development. The focusing of these recapitulated systemi...The repair of wounded tissue during postnatal life could be associated with the upregulation of some functions characteristic of the initial phases of embryonic development. The focusing of these recapitulated systemic functions in the interstitial space of the injured tissue is established through a heterogeneous endothelial barrier which has excretory-secretory abilities which in turn,would induce a gastrulation-like process. The repair of adult tissues using upregulated embryonic mechanisms could explain the universality of the inflammatory response against injury,regardless of its etiology. However,the early activation after the injury of embryonic mechanisms does not always guarantee tissue regeneration since their long-term execution is mediated by the host organism.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 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.
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 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.
文摘As the body’s integumentary system,the skin is vulnerable to injuries.The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality.To this end,multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue.Such temporally-and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation.In this context,regulatory T cells(Tregs)hold a key role in balancing immune homeostasis and mediating cutaneous wound healing.A comprehensive understanding of Tregs’multifaceted field of activity may help decipher wound pathologies and,ultimately,establish new treatment modalities.Herein,we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair.Further,we discuss how Tregs operate during fibrosis,keloidosis,and scarring.
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
基金supported by the National Natural Science Foundation of China (Nos.52222214,52372274,22388101,22020102003,22125701)the National Key Research and Development Program of China (No.2020YFA0908900)+4 种基金the Natural Science Foundation of Jilin Province,China (Nos.20240101175JC,20210101366JC)the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (No.2022QNRC001)the Beijing Natural Science Foundation,China (No.2244071)the Xiangfu Lab Research Project,China (No.XF012022C0200)the Funding from China Postdoctoral Science Foundation (No.2022M721802).
文摘Bacterial infections and excessive oxidative stress seriously hinder the healing of skin wounds.Traditional wound dressings can only serve as physical barriers and lack active molecules essential for actively promoting wound healing.Herein,an antibacterial and antioxidant liquid metal inorganic active material is developed for wound repair through in situ polymerization of chitosan/acrylic acid precursor solution initiated by tannic acid-coated liquid metal nanoparticles,without extra initiators and ultraviolet (UV) light.The tannic acid component enables the inorganic active material to exhibit antioxidant property,which can remove 90% of free radicals and relieve cellular oxidative stress.The chitosan component endows the inorganic active material with antibacterial property,effectively inhibiting the growth of Staphylococcus aureus and Escherichia coli (killing ratio: 90%).In vivo experiment demonstrates that this inorganic active material can promote the healing of Staphylococcus aureus-infected wound,achieving a closure rate of 98.16% on the 9th day.Meanwhile,this inorganic active material exhibits good electrical conductivity,enabling timely and stable monitoring of human joint movements.This work offers a simple strategy for developing multifunctional inorganic active material,which holds great potential for wound repair and motion monitoring.
文摘<strong>Background: </strong>This is still a public problem that needs to be solved urgently: chronic and refractory wound healing with long course and complex pathological mechanism. At present, there is still a lack of effective clinical treatment. This study, therefore, aims at exploring moist exposed burn therapy/moist exposed burn ointment (MEBT/MEBO) combined with Zhuang medicine detoxification in the treatment of chronic refractory wound healing. <strong>Methodology: </strong>100 SPF Wistar rats were randomly divided into blank control group, model control group, MEBO group, Zhuang medicine group and Combined group, with 20 rats in each group. Open wound model was established in blank control group, and chronic refractory wound model was established in other groups. Black control group and model control group were given food and water freely, MEBO group was given dressing change once a day, Zhuang medicine group was given intragastric administration once a day, and combined group was given dressing change and intragastric administration once a day. The effective rate of wound healing was observed after 12 days of continuous intervention. <strong>Conclusion: </strong>Skin regeneration medical technique combined with Zhuang medicine poison theory can effectively reduce the symptoms of bleeding and exudation, reduce the area of wound, shorten the healing time of wound, and achieve physiological healing of wound. It has a good effect on chronic refractory wound.
文摘Generally, wounds are of two categories, such as chronic and acute. Chronic wounds takes time to heal when compared to the acute wounds. Chronic wounds include vasculitis, non healing ulcer, pyoderma gangrenosum, and diseases that cause ischemia. Chronic wounds are rapidly increasing among the elderly population with dysfunctional valves in their lower extremity deep veins, ulcer, neuropathic foot and pressure ulcers. The process of the healing of wounds has several steps with the involvement of immune cells and several other cell types. There are many evidences supporting the hypothesis that apoptosis of immune cells is involved in the wound healing process by ending inflammatory condition. It is also involved in the resolution of various phases of tissue repair. During final steps of wound healing most of the endothelial cells, macrophagesand myofibroblasts undergo apoptosis or exit from the wound, leaving a mass that contains few cells and consists mostly of collagen and other extracellular matrix proteins to provide strength to the healing tissue. This review discusses the various phases of wound healing both in the chronic and acute wounds especially during diabetes mellitus and thus support the hypothesis that the oxidative stress, apoptosis, connexins and other molecules involved in the regulation of chronic wound healing in diabetes mellitus and gives proper understanding of the mechanisms controlling apoptosis and tissue repair during diabetes and may eventually develop therapeutic modalities to fasten the healing process in diabetic patients.
基金Supported by the National Natural Science Foundation of China(No.81300729,No.81160118,No.81460092,No.81660158)Natural Science Foundation of Fujian Province(No.2015J05170).
文摘●AIM:To explore netrin-1 functions on corneal epithelium in vitro and in vivo.●METHODS:In vitro the human corneal epithelial(HCE)cells were treated with serum free DMEM-F12 basic media containing 0,50,100,200,300,500,800,and 1000 ng/mL of netrin-1,respectively.The cells viability was detected by cell counting kit-8(CCK-8).The wound-healing assay was applied to assess the migration proficiency of HCE cells.Flow cytometry was used to analyze the cell-cycle distribution and apoptosis.In vivo,normal c57(6 wk)mice were demarcated with a trephine in the middle of the cornea to produce a 3-mm circular wound.Mice corneas were inflicted no epithelium with a 3-mm wound displayed,but remained the limbal epithelium intact.A blunt scalpel blade was used to remove the corneal epithelian cells,followed by topical netrin-1 application(200 ng/mL),and the group treated by PBS as control.The treated group was injected netrin-1 into the normal c57 mice inferior subconjunctival 4 h before trauma.Mouse corneal inflammation and neovascularization were observed under slit lamp microscope.The apoptosis of corneal cells was determined by TUNEL staining.●RESLUTS:A concentration of 200 ng/mL netrin-1 enhanced 25%of the HCE viability.The relative migration rates were 76.3%and 100%in control and netrin-1 treated group after cultured 72 h.Treated with netrin-1(200 ng/mL)decreased the apoptosis of HCE cells,as well as decreased their percentage from 19.3%±0.57%to 12.7%±0.42%of the total.The remaining wound area was 1.22 mm2 in control group but 0.22 mm2 in the netrin-1 treated group.Exogenous Netrin-1 inhibits apoptosis of corneal epithelial cells of c57 mice.TUNEL-positive cells at the epithelial layer of the corneas of the control and netrin-1 treated c57 mice at 24 h after wounding were 43.3%and 16.7%respectively.●CONCLUSION:Netrin-1 can reduce HCE apoptosis as well as promote its proliferation and migration.Topical application of netrin-1 promotes the injuryed cornea epithelial wound repair and inhibits apoptosis of corneal epithelial cells.These findings may offer potential therapies to repair the defects of corneal epithelial based on netrin-1.
文摘The repair of wounded tissue during postnatal life could be associated with the upregulation of some functions characteristic of the initial phases of embryonic development. The focusing of these recapitulated systemic functions in the interstitial space of the injured tissue is established through a heterogeneous endothelial barrier which has excretory-secretory abilities which in turn,would induce a gastrulation-like process. The repair of adult tissues using upregulated embryonic mechanisms could explain the universality of the inflammatory response against injury,regardless of its etiology. However,the early activation after the injury of embryonic mechanisms does not always guarantee tissue regeneration since their long-term execution is mediated by the host organism.