Skeletal stem/progenitor cell(SSPC)senescence is a major cause of decreased bone regenerative potential with aging,but the causes of SSPC senescence remain unclear.In this study,we revealed that macrophages in calluse...Skeletal stem/progenitor cell(SSPC)senescence is a major cause of decreased bone regenerative potential with aging,but the causes of SSPC senescence remain unclear.In this study,we revealed that macrophages in calluses secrete prosenescent factors,including grancalcin(GCA),during aging,which triggers SSPC senescence and impairs fracture healing.Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair.Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence.Mechanistically,GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction,resulting in cellular senescence.Depletion of Plxnb2 in SSPCs impaired fracture healing.Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice.Thus,our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence,and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.展开更多
Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address ...Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin regeneration.However,the use of stem cells in skin regeneration presents several challenges.Recently,stem cells and biomaterials have been identified as crucial components of the wound-healing process.Combination therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable attention.Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the ECM.These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing.This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine functions.Additionally,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.展开更多
In this editorial,we comment on an article by Liao et al published in the current issue of the World Journal of Diabetes.We focus on the clinical significance of tibial transverse transport(TTT)as an effective treatme...In this editorial,we comment on an article by Liao et al published in the current issue of the World Journal of Diabetes.We focus on the clinical significance of tibial transverse transport(TTT)as an effective treatment for patients with diabetic foot ulcers(DFU).TTT has been associated with tissue regeneration,improved blood circulation,reduced amputation rates,and increased expression of early angiogenic factors.Mechanistically,TTT can influence macrophage polarization and growth factor upregulation.Despite this potential,the limitations and conflicting results of existing studies justify the need for further research into its optimal application and development.These clinical implications highlight the efficacy of TTT in recalcitrant DFU and provide lasting stimuli for tissue re-generation,and blood vessel and bone marrow improvement.Immunomodu-lation via systemic responses contributes to its therapeutic potential.Future studies should investigate the underlying molecular mechanisms to enhance our understanding and the efficacy of TTT.This manuscript emphasizes the potential of TTT in limb preservation and diabetic wound healing and suggests avenues for preventive measures against limb amputation in diabetes and peripheral artery disease.Here,we highlight the clinical significance of the TTT and its importance in healing DFU to promote the use of this technique in tissue regeneration.展开更多
Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of f...Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.展开更多
Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses w...Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses who were admitted to our hospital(Xinghua City People’s Hospital)from May 2022 to May 2023 were selected and randomly divided into two groups,a control group(30 cases)and a study group(31 cases).Both groups received surgical treatment.The control group received conventional treatment and warm water fumigation,sitz bath,and surgical dressing change after surgery,while the research group received XFHM based on the control group.XFHM was taken orally and replaced with warm water for fumigation and sitz bathing.Both groups received treatment for 4 weeks but discontinued sitz bathing after 2 weeks.Various clinical indicators between the two groups were compared.Results:The total clinical effective rate and wound recovery rate of the study group were higher than that of the control group.There were differences in the wound pain scores,surrounding tissue edema,and wound secretions at different time points.Both groups experienced wound pain.The scores of wound pain,surrounding tissue edema,and wound secretions of the study group were lower than those of the control group,7 and 14 days after surgery.The serum interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)levels,and pH values of the study group were lower than those of the control group 10 days after surgery(P<0.05).Conclusion:The application of XFHM for treating cutaneous infections and promoting wound healing in patients with perianal abscesses improved the treatment outcome,alleviated clinical symptoms,and promoted healing.展开更多
In the new urban construction,the concept of healing environment is helpful to promote the physical and mental health of the urban public.By combing the relevant theories of health and environment,such as stress relie...In the new urban construction,the concept of healing environment is helpful to promote the physical and mental health of the urban public.By combing the relevant theories of health and environment,such as stress relief theory,attention recovery theory,biophilia design,evidence-based design,etc.and using field research methods,the functional layout,slow walking environment,public space,healing environment and healing architecture of Dongheyan area were analyzed,and the design strategies of healing environment were put forward for the slow walking environment and public space in Dongheyan area based on all aspects of problems and attributes of the area.展开更多
Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain int...Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.展开更多
Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H ...Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.展开更多
S Background Music therapy is a promising complementary intervention for addressing various mental health conditions.Despite evidence of the beneficial effects of music,the acoustic features that make music effective ...S Background Music therapy is a promising complementary intervention for addressing various mental health conditions.Despite evidence of the beneficial effects of music,the acoustic features that make music effective in therapeutic contexts remain elusive.Aims This study aimed to identify and validate distinctive acoustic features of healing music.Methods We constructed a healing music dataset(HMD)based on nominations from related professionals and extracted 370 acoustic features.Healing-distinctive acoustic features were identified as those that were(1)independent from genre within the HMD,(2)significantly different from music pieces in a classical music dataset(CMD)and(3)similar to pieces in a five-element music dataset(FEMD).We validated the identified features by comparing jazz pieces in the HMD with a jazz music dataset(JMD).We also examined the emotional properties of the features in a Chinese affective music system(CAMS).Results The HMD comprised 165 pieces.Among all the acoustic features,74.59%shared commonalities across genres,and 26.22%significantly differed between the HMD classical pieces and the CMD.The equivalence test showed that the HMD and FEMD did not differ significantly in 9.46%of the features.The potential healing-distinctive acoustic features were identified as the standard deviation of the roughness,mean and period entropy of the third coefficient of the mel-frequency cepstral coefficients.In a three-dimensional space defined by these features,HMD's jazz pieces could be distinguished from those of the JMD.These three features could significantly predict both subjective valence and arousal ratings in the CAMS.Conclusions The distinctive acoustic features of healing music that have been identified and validated in this study have implications for the development of artificial intelligence models for identifying therapeutic music,particularly in contexts where access to professional expertise may be limited.This study contributes to the growing body of research exploring the potential of digital technologies for healthcare interventions.展开更多
Objective:To investigate the in vitro antioxidant and wound healing properties of the hydroethanolic extract of Sargassum polycystum,and elucidate the mechanism of its wound healing activity.Methods:Human dermal fibro...Objective:To investigate the in vitro antioxidant and wound healing properties of the hydroethanolic extract of Sargassum polycystum,and elucidate the mechanism of its wound healing activity.Methods:Human dermal fibroblast and HaCaT cells were used to evaluate the proliferation by sulforhodamine B and dsDNA assay after treatment with Sargassum polycystum extracts.Scratch wound healing and phalloidin-rhodamine staining were employed to observe migratory activity and filopodia formation,respectively.Western blot and real-time RT-PCR assays were performed to determine the protein and gene expressions related to wound healing activities.Results:The phytochemical analysis found a higher level of flavonoid than phenolic compound in Sargassum polycystum extracts.In human dermal fibroblast cells,Sargassum polycystum extracts at 50 and 100μg/mL significantly increased fibroblast proliferation and the gene expressions of hyaluronic acid synthase 1(HAS1),HAS2,HAS3,collagen type 1 alpha 1 chain(COL1A1),collagen type 3 alpha 1 chain(COL3A1),and elastin.The phosphorylation of Akt,ERK1/2,and p38 MAPK was also significantly upregulated after treatment with Sargassum polycystum extracts.Additionally,50 and 100μg/mL of the extracts prominently enhanced the proliferation,migration,and filopodia formation of HaCaT cells,as well as the protein levels of pFAK/FAK,pSrc/Src,pAkt/Akt,pERK1/2/ERK1/2,Rac1 and Cdc42.Conclusions:Sargassum polycystum extracts show promising wound healing activities in human dermal fibroblasts and keratinocytes.展开更多
Objective:To synthesize zinc oxide nanoparticles(ZnONPs)and evaluate their antibacterial and wound healing effects against wounds infected with methicillin-resistant Staphylococcus aureus(MRSA).Methods:ZnONPs were pre...Objective:To synthesize zinc oxide nanoparticles(ZnONPs)and evaluate their antibacterial and wound healing effects against wounds infected with methicillin-resistant Staphylococcus aureus(MRSA).Methods:ZnONPs were prepared by sol-gel method and characterized by X-ray diffraction(XRD)analysis and scanning electron microscopy(SEM).A total of 18 rabbits were divided into three groups:the ZnONPs group,the gentamicin group and the control group.A wound of 3 cm^(2) was inflicted on each rabbit and contaminated with MRSA inoculum.Treatment was started from the fourth day post-surgery.Wound healing,microbiological analysis,and histopathological analysis were performed to assess the efficacy of ZnONPs ointment.Results:XRD analysis confirmed the hexagonal wurtzite structure of the ZnONPs with an average crystallite size of 29.23 nm.SEM revealed discoid-shaped ZnONPs with a rough surface and an average size of 48.36 nm.Energy-dispersive X-ray analysis confirmed the purity of ZnONPs.Moreover,the particle size ranged from 100-700 nm with a high agglomeration trend.Treatment with ZnONPs promoted MRSA-infected wound healing.In addition,ZnONPs showed a good antibacterial effect as evidenced by a dose-dependent increase in the zone of inhibition.Conclusions:ZnONPs accelerate the healing of MRSA-infected wounds.Therefore,it can be explored for the treatment of MRSA infection.展开更多
Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and th...Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve(B.breve).A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing.The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography(micro-CT).Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay(ELISA).The senescence and biological functions were tested in oral mucosal stem cells(OMSCs)treated with sunitinib.Ligated loop experiments were used to investigate the effect of oral B.breve.Neutralizing antibody for interleukin-10(IL-10)was used to prove the critical role of IL-10 in the pro-healing process derived from B.breve.Results showed that sunitinib caused oral mucosal wound healing impairment in mice.In vitro,sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation,migration,and differentiation.Oral administration of B.breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells(DCs)-derived IL-10.IL-10 reversed cellular senescence caused by sunitinib in OMSCs,and IL-10 neutralizing antibody blocked the ameliorative effect of B.breve on oral mucosal wound healing under sunitinib treatment conditions.In conclusion,sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B.breve could improve wound healing impairment via intestinal DCs-derived IL-10.展开更多
Diabetes mellitus is a global public health concern affecting an estimated 537 million people,and patients with diabetes are more susceptible to developing chronic wounds^([1,2]).The wound healing process is often aff...Diabetes mellitus is a global public health concern affecting an estimated 537 million people,and patients with diabetes are more susceptible to developing chronic wounds^([1,2]).The wound healing process is often affected by various factors,including infection,tissue hypoxia,necrosis,exudates,and excessive inflammatory cytokines^([3]).Presently,there is no effective treatment for refractory wound healing,and the development of new techniques and therapeutic strategies is urgently required for patients with diabetes who have chronic wounds.展开更多
Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and polyadenylation.Most mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative pol...Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and polyadenylation.Most mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative polyadenylation(APA)isoforms that have the same coding region but distinct 3′untranslated regions(UTRs).The 3′UTR contains motifs that regulate m RNA metabolism;thus,changing the 3′UTR length via APA can significantly affect gene expression.Endochondral ossification is a central process in bone healing,but the impact of APA on gene expression during this process is unknown.Here,we report the widespread occurrence of APA,which impacts multiple pathways that are known to participate in bone healing.Importantly,the progression of endochondral ossification involves global 3′UTR shortening,which is coupled with an increased abundance of shortened transcripts relative to other transcripts;these results highlight the role of APA in promoting gene expression during endochondral bone formation.Our mechanistic studies of transcripts that undergo APA in the fracture callus revealed an intricate regulatory network in which APA enhances the expression of the collagen,type I,alpha 1(Col1a1)and Col1a2 genes,which encode the 2 subunits of the abundantly expressed protein collagen 1.APA exerts this effect by shortening the 3′UTRs of the Col1a1 and Col1a2 m RNAs,thus removing the binding sites of mi R-29a-3p,which would otherwise strongly promote the degradation of both transcripts.Taken together,our study is the first to characterize the crucial roles of APA in regulating the 3′UTR landscape and modulating gene expression during fracture healing.展开更多
The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion r...The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion resistance,titanium–niobium alloys have the potential to become a new generation of internal fixation materials for fractures.However,the role and mechanism of titanium–niobium alloys on promoting fracture healing are still undefined.Therefore,in this study,we systematically evaluated the bone-enabling properties of Ti45Nb via in vivo and in vitro experiments.In vitro,we found that Ti45Nb has an excellent ability to promote MC3T3-E1 cell adhesion and proliferation without obvious cytotoxicity.Alkaline phosphatase(ALP)activity and alizarin red staining and semiquantitative analysis showed that Ti45Nb enhanced the osteogenic differentiation of MC3T3-E1 cells compared to the Ti6Al4V control.In the polymerase chain reaction experiment,the expression of osteogenic genes in the Ti45Nb group,such as ALP,osteopontin(OPN),osteocalcin(OCN),type 1 collagen(Col-1)and runt-related transcription factor-2(Runx2),was significantly higher than that in the control group.Meanwhile,in the western blot experiment,the expression of osteogenic-related proteins in the Ti45Nb group was significantly increased,and the expression of PI3K–Akt-related proteins was also higher,which indicated that Ti45Nb might promote fracture healing by activating the PI3K–Akt signaling pathway.In vivo,we found that Ti45Nb implants accelerated fracture healing compared to Ti6Al4V,and the biosafety of Ti45Nb was confirmed by histological evaluation.Furthermore,immunohistochemical staining confirmed that Ti45Nb may promote osteogenesis by upregulating the PI3K/Akt signaling pathway.Our study demonstrated that Ti45Nb exerts an excellent ability to promote fracture healing as well as enhance osteoblast differentiation by activating the PI3K/Akt signaling pathway,and its good biosafety has been confirmed,which indicates its clinical translation potential.展开更多
The process of wound healing is routinely evaluated by histological evaluation in the clinic,which may cause scarring and secondary injury.Reflectance confocal microscopy(RCM)represents a noninvasive,real-time imaging...The process of wound healing is routinely evaluated by histological evaluation in the clinic,which may cause scarring and secondary injury.Reflectance confocal microscopy(RCM)represents a noninvasive,real-time imaging technique that allows in vivo evaluation of the skin.Traditional RCM was wide-probe-based,which limited its application on uneven and covered skin.In this study,we report the development of a portable reflectance confocal microscope(PRCM)in which all components were assembled in a handheld shell.Although the size and weight of the PRCM were reduced based on the use of a microelectromechanical system,the resolution was kept at 0.91μm,and the field of view of the system was 343μm×532μm.When used in vivo,the PRCM was able to visualize cellular and nuclear morphology for both mouse and human skin.PRCM evaluations were then performed on wounds after topically applied mesenchymal stem cells(MSCs)or saline treatment.The PRCM allowed visualization of the formation of collagen bundles,re-epithelization from the wound edge to the wound bed,and hair follicle regeneration,which were consistent with histological evaluations.Therefore,we offer new insights into monitoring the effects of topically applied MSCs on the process of wound healing by using PRCM.This study illustrates that the newly developed PRCM represents a promising device for real-time,noninvasive monitoring of the dynamic process of wound healing,which demonstrates its potential to diagnose,monitor,or predict disease in clinical wound therapy.展开更多
BACKGROUND Rapid wound healing remains a pressing clinical challenge,necessitating studies to hasten this process.A promising approach involves the utilization of human umbilical cord mesenchymal stem cells(hUC-MSCs)d...BACKGROUND Rapid wound healing remains a pressing clinical challenge,necessitating studies to hasten this process.A promising approach involves the utilization of human umbilical cord mesenchymal stem cells(hUC-MSCs)derived exosomes.The hypothesis of this study was that these exosomes,when loaded onto a gelatin sponge,a common hemostatic material,would enhance hemostasis and accelerate wound healing.AIM To investigate the hemostatic and wound healing efficacy of gelatin sponges loaded with hUC-MSCs-derived exosomes.METHODS Ultracentrifugation was used to extract exosomes from hUC-MSCs.Nanoparticle tracking analysis(NTA),transmission electron microscopy(TEM),and western blot techniques were used to validate the exosomes.In vitro experiments were performed using L929 cells to evaluate the cytotoxicity of the exosomes and their impact on cell growth and survival.New Zealand rabbits were used for skin irritation experiments to assess whether they caused adverse skin reactions.Hemolysis test was conducted using a 2%rabbit red blood cell suspension to detect whether they caused hemolysis.Moreover,in vivo experiments were carried out by implanting a gelatin sponge loaded with exosomes subcutaneously in Sprague-Dawley(SD)rats to perform biocompatibility tests.In addition,coagulation index test was conducted to evaluate their impact on blood coagulation.Meanwhile,SD rat liver defect hemostasis model and full-thickness skin defect model were used to study whether the gelatin sponge loaded with exosomes effectively stopped bleeding and promoted wound healing.RESULTS The NTA,TEM,and western blot experimental results confirmed that exosomes were successfully isolated from hUC-MSCs.The gelatin sponge loaded with exosomes did not exhibit significant cell toxicity,skin irritation,or hemolysis,and they demonstrated good compatibility in SD rats.Additionally,the effectiveness of the gelatin sponge loaded with exosomes in hemostasis and wound healing was validated.The results of the coagulation index experiment indicated that the gelatin sponge loaded with exosomes had significantly better coagulation effect compared to the regular gelatin sponge,and they showed excellent hemostatic performance in a liver defect hemostasis model.Finally,the full-thickness skin defect healing experiment results showed significant improvement in the healing process of wounds treated with the gelatin sponge loaded with exosomes compared to other groups.CONCLUSION Collectively,the gelatin sponge loaded with hUC-MSCs-derived exosomes is safe and efficacious for promoting hemostasis and accelerating wound healing,warranting further clinical application.展开更多
Impaired wound healing presents great health risks to diabetics.Encouragingly,the current clinical successfully found out meaningful method to repair wound tissue,and stem cell therapy could be an effective method for...Impaired wound healing presents great health risks to diabetics.Encouragingly,the current clinical successfully found out meaningful method to repair wound tissue,and stem cell therapy could be an effective method for diabetic wound healing with its ability to accelerate wound closure and avoid amputation.This minireview aims at introducing stem cell therapy for facilitating tissue repair in diabetic wounds,discussing the possible therapeutic mechanism and clinical application status and problems.展开更多
BACKGROUND Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing.Previous studies have indicated that antler reserve mesenchyme(RM)cells and their conditioned medium im...BACKGROUND Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing.Previous studies have indicated that antler reserve mesenchyme(RM)cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages.AIM To develop hydrogels from the antler RM matrix(HARM)and evaluate the effect on wound healing.METHODS We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin.Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application.RESULTS The results showed that HARM accelerated wound healing rate and reduced scar formation.Also,HARM stimulated the regeneration of cutaneous appendages and blood vessels,and reduced collagen fiber aggregation.Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site.The levels of fetal wound healing-related genes,including Collagen III and TGFβ3 treated with HARM were all increased,while the expression levels of Collagen I,TGFβ1,and Engrailed 1 were decreased in the healing.Moreover,the number of stem cells was increased in the fetal-like niche created by HARM,which may contribute to the regeneration of cutaneous appendages.CONCLUSION Overall,we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds.We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing,and thus pave the way for HARM to be developed for the clinic use.展开更多
BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the eff...BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.展开更多
基金This work was supported by the National Key R&D Program of China(Project No.2019YFA0111900 to C.J.L.and Y.J.,2022YFC3601900 to G.H.L.,2022YFC3601903 to X.H.L.,and 2022YFC3601905)the National Natural Science Foundation of China(Grant Nos.82261160397,82272560,81922017 to C.J.L.and 81930022,91749105 to X.H.L.)+3 种基金the NSFC/RGC Joint Research Scheme,the Research Grants Council(UGC)of the Hong Kong Special Administrative Region and the National Natural Science Foundation of China(NSFC/RGC Project No.N_CUHK483/22 to Y.J.)the Hunan Provincial Science and Technology Department(2023JJ30896 to C.J.L.)the Key Research and Development Program of Hunan Province(2022SK2023 to C.J.L.)the Science and Technology Innovation Program of Hunan Province(2023RC1027 to C.J.L.,2022RC1009 to J.W,and 2022RC3075 to C.Z.).
文摘Skeletal stem/progenitor cell(SSPC)senescence is a major cause of decreased bone regenerative potential with aging,but the causes of SSPC senescence remain unclear.In this study,we revealed that macrophages in calluses secrete prosenescent factors,including grancalcin(GCA),during aging,which triggers SSPC senescence and impairs fracture healing.Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair.Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence.Mechanistically,GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction,resulting in cellular senescence.Depletion of Plxnb2 in SSPCs impaired fracture healing.Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice.Thus,our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence,and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2020-I2M-C&T-A-004National High Level Hospital Clinical Research Funding,No.2022-PUMCH-A-210,No.2022-PUMCH-B-041,and No.2022-PUMCH-C-025and National Key R&D Program of China,No.2020YFE0201600.
文摘Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin regeneration.However,the use of stem cells in skin regeneration presents several challenges.Recently,stem cells and biomaterials have been identified as crucial components of the wound-healing process.Combination therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable attention.Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the ECM.These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing.This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine functions.Additionally,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.
基金Supported by Grants of the Korea Research Foundation,an NRF Grant Funded by the Korea Government,No.NRF-2023R1A2C3003717.
文摘In this editorial,we comment on an article by Liao et al published in the current issue of the World Journal of Diabetes.We focus on the clinical significance of tibial transverse transport(TTT)as an effective treatment for patients with diabetic foot ulcers(DFU).TTT has been associated with tissue regeneration,improved blood circulation,reduced amputation rates,and increased expression of early angiogenic factors.Mechanistically,TTT can influence macrophage polarization and growth factor upregulation.Despite this potential,the limitations and conflicting results of existing studies justify the need for further research into its optimal application and development.These clinical implications highlight the efficacy of TTT in recalcitrant DFU and provide lasting stimuli for tissue re-generation,and blood vessel and bone marrow improvement.Immunomodu-lation via systemic responses contributes to its therapeutic potential.Future studies should investigate the underlying molecular mechanisms to enhance our understanding and the efficacy of TTT.This manuscript emphasizes the potential of TTT in limb preservation and diabetic wound healing and suggests avenues for preventive measures against limb amputation in diabetes and peripheral artery disease.Here,we highlight the clinical significance of the TTT and its importance in healing DFU to promote the use of this technique in tissue regeneration.
文摘Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.
文摘Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses who were admitted to our hospital(Xinghua City People’s Hospital)from May 2022 to May 2023 were selected and randomly divided into two groups,a control group(30 cases)and a study group(31 cases).Both groups received surgical treatment.The control group received conventional treatment and warm water fumigation,sitz bath,and surgical dressing change after surgery,while the research group received XFHM based on the control group.XFHM was taken orally and replaced with warm water for fumigation and sitz bathing.Both groups received treatment for 4 weeks but discontinued sitz bathing after 2 weeks.Various clinical indicators between the two groups were compared.Results:The total clinical effective rate and wound recovery rate of the study group were higher than that of the control group.There were differences in the wound pain scores,surrounding tissue edema,and wound secretions at different time points.Both groups experienced wound pain.The scores of wound pain,surrounding tissue edema,and wound secretions of the study group were lower than those of the control group,7 and 14 days after surgery.The serum interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)levels,and pH values of the study group were lower than those of the control group 10 days after surgery(P<0.05).Conclusion:The application of XFHM for treating cutaneous infections and promoting wound healing in patients with perianal abscesses improved the treatment outcome,alleviated clinical symptoms,and promoted healing.
基金the National Natural Science Foundation of China(52278045).
文摘In the new urban construction,the concept of healing environment is helpful to promote the physical and mental health of the urban public.By combing the relevant theories of health and environment,such as stress relief theory,attention recovery theory,biophilia design,evidence-based design,etc.and using field research methods,the functional layout,slow walking environment,public space,healing environment and healing architecture of Dongheyan area were analyzed,and the design strategies of healing environment were put forward for the slow walking environment and public space in Dongheyan area based on all aspects of problems and attributes of the area.
文摘Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.
基金supported by the National Natural Science Foundation of China (Grant Nos.81874006,82172399,81902222,82060395,81902277,82072504,82000845)the Hunan Province Natural Science Foundation of China (Grant Nos.2020JJ4928,2020JJ4897,2021JJ30038,2021JJ40492)the Independent Exploration and Innovation Project of Central South University (Grant Nos.2020zzts255)。
文摘Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.
基金supported by the National Natural Science Foundation of China(62101324)the Shanghai Sailing Program(20YF1442000)+2 种基金the Academic Leader of the Health Discipline of Shanghai Municipal Health Commission(2022XD025)the Qihang Program of Shanghai Mental Health Center(2020-QH-01)the Hospital Program of Shanghai Mental Health Center(2020-YJ01)。
文摘S Background Music therapy is a promising complementary intervention for addressing various mental health conditions.Despite evidence of the beneficial effects of music,the acoustic features that make music effective in therapeutic contexts remain elusive.Aims This study aimed to identify and validate distinctive acoustic features of healing music.Methods We constructed a healing music dataset(HMD)based on nominations from related professionals and extracted 370 acoustic features.Healing-distinctive acoustic features were identified as those that were(1)independent from genre within the HMD,(2)significantly different from music pieces in a classical music dataset(CMD)and(3)similar to pieces in a five-element music dataset(FEMD).We validated the identified features by comparing jazz pieces in the HMD with a jazz music dataset(JMD).We also examined the emotional properties of the features in a Chinese affective music system(CAMS).Results The HMD comprised 165 pieces.Among all the acoustic features,74.59%shared commonalities across genres,and 26.22%significantly differed between the HMD classical pieces and the CMD.The equivalence test showed that the HMD and FEMD did not differ significantly in 9.46%of the features.The potential healing-distinctive acoustic features were identified as the standard deviation of the roughness,mean and period entropy of the third coefficient of the mel-frequency cepstral coefficients.In a three-dimensional space defined by these features,HMD's jazz pieces could be distinguished from those of the JMD.These three features could significantly predict both subjective valence and arousal ratings in the CAMS.Conclusions The distinctive acoustic features of healing music that have been identified and validated in this study have implications for the development of artificial intelligence models for identifying therapeutic music,particularly in contexts where access to professional expertise may be limited.This study contributes to the growing body of research exploring the potential of digital technologies for healthcare interventions.
基金funded by Prince of Songkla University(Grant No.SCI6302160S)。
文摘Objective:To investigate the in vitro antioxidant and wound healing properties of the hydroethanolic extract of Sargassum polycystum,and elucidate the mechanism of its wound healing activity.Methods:Human dermal fibroblast and HaCaT cells were used to evaluate the proliferation by sulforhodamine B and dsDNA assay after treatment with Sargassum polycystum extracts.Scratch wound healing and phalloidin-rhodamine staining were employed to observe migratory activity and filopodia formation,respectively.Western blot and real-time RT-PCR assays were performed to determine the protein and gene expressions related to wound healing activities.Results:The phytochemical analysis found a higher level of flavonoid than phenolic compound in Sargassum polycystum extracts.In human dermal fibroblast cells,Sargassum polycystum extracts at 50 and 100μg/mL significantly increased fibroblast proliferation and the gene expressions of hyaluronic acid synthase 1(HAS1),HAS2,HAS3,collagen type 1 alpha 1 chain(COL1A1),collagen type 3 alpha 1 chain(COL3A1),and elastin.The phosphorylation of Akt,ERK1/2,and p38 MAPK was also significantly upregulated after treatment with Sargassum polycystum extracts.Additionally,50 and 100μg/mL of the extracts prominently enhanced the proliferation,migration,and filopodia formation of HaCaT cells,as well as the protein levels of pFAK/FAK,pSrc/Src,pAkt/Akt,pERK1/2/ERK1/2,Rac1 and Cdc42.Conclusions:Sargassum polycystum extracts show promising wound healing activities in human dermal fibroblasts and keratinocytes.
文摘Objective:To synthesize zinc oxide nanoparticles(ZnONPs)and evaluate their antibacterial and wound healing effects against wounds infected with methicillin-resistant Staphylococcus aureus(MRSA).Methods:ZnONPs were prepared by sol-gel method and characterized by X-ray diffraction(XRD)analysis and scanning electron microscopy(SEM).A total of 18 rabbits were divided into three groups:the ZnONPs group,the gentamicin group and the control group.A wound of 3 cm^(2) was inflicted on each rabbit and contaminated with MRSA inoculum.Treatment was started from the fourth day post-surgery.Wound healing,microbiological analysis,and histopathological analysis were performed to assess the efficacy of ZnONPs ointment.Results:XRD analysis confirmed the hexagonal wurtzite structure of the ZnONPs with an average crystallite size of 29.23 nm.SEM revealed discoid-shaped ZnONPs with a rough surface and an average size of 48.36 nm.Energy-dispersive X-ray analysis confirmed the purity of ZnONPs.Moreover,the particle size ranged from 100-700 nm with a high agglomeration trend.Treatment with ZnONPs promoted MRSA-infected wound healing.In addition,ZnONPs showed a good antibacterial effect as evidenced by a dose-dependent increase in the zone of inhibition.Conclusions:ZnONPs accelerate the healing of MRSA-infected wounds.Therefore,it can be explored for the treatment of MRSA infection.
基金supported by the Clinical Medicine Plus X-Young Scholars Project of Peking University of the Fundamental Research Funds for the Central Universities (PKU2023LCXQ035)the Chinese Academy of Medical Sciences Central Public-Interest Scientific Institution Basal Research Fund (2022-JKCS-27)+3 种基金the National clinical key discipline construction project (PKUSSNKP-202114)China Postdoctoral Science Foundation (2022M720289)Chinese Stomatological Association Clinical Research Fund (CSA-SIS2022-01)National Natural Science Foundation of China (82301024)
文摘Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve(B.breve).A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing.The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography(micro-CT).Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay(ELISA).The senescence and biological functions were tested in oral mucosal stem cells(OMSCs)treated with sunitinib.Ligated loop experiments were used to investigate the effect of oral B.breve.Neutralizing antibody for interleukin-10(IL-10)was used to prove the critical role of IL-10 in the pro-healing process derived from B.breve.Results showed that sunitinib caused oral mucosal wound healing impairment in mice.In vitro,sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation,migration,and differentiation.Oral administration of B.breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells(DCs)-derived IL-10.IL-10 reversed cellular senescence caused by sunitinib in OMSCs,and IL-10 neutralizing antibody blocked the ameliorative effect of B.breve on oral mucosal wound healing under sunitinib treatment conditions.In conclusion,sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B.breve could improve wound healing impairment via intestinal DCs-derived IL-10.
文摘Diabetes mellitus is a global public health concern affecting an estimated 537 million people,and patients with diabetes are more susceptible to developing chronic wounds^([1,2]).The wound healing process is often affected by various factors,including infection,tissue hypoxia,necrosis,exudates,and excessive inflammatory cytokines^([3]).Presently,there is no effective treatment for refractory wound healing,and the development of new techniques and therapeutic strategies is urgently required for patients with diabetes who have chronic wounds.
基金National Institutes of Health(NIH)R01 DK121327 to R.A.E。
文摘Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and polyadenylation.Most mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative polyadenylation(APA)isoforms that have the same coding region but distinct 3′untranslated regions(UTRs).The 3′UTR contains motifs that regulate m RNA metabolism;thus,changing the 3′UTR length via APA can significantly affect gene expression.Endochondral ossification is a central process in bone healing,but the impact of APA on gene expression during this process is unknown.Here,we report the widespread occurrence of APA,which impacts multiple pathways that are known to participate in bone healing.Importantly,the progression of endochondral ossification involves global 3′UTR shortening,which is coupled with an increased abundance of shortened transcripts relative to other transcripts;these results highlight the role of APA in promoting gene expression during endochondral bone formation.Our mechanistic studies of transcripts that undergo APA in the fracture callus revealed an intricate regulatory network in which APA enhances the expression of the collagen,type I,alpha 1(Col1a1)and Col1a2 genes,which encode the 2 subunits of the abundantly expressed protein collagen 1.APA exerts this effect by shortening the 3′UTRs of the Col1a1 and Col1a2 m RNAs,thus removing the binding sites of mi R-29a-3p,which would otherwise strongly promote the degradation of both transcripts.Taken together,our study is the first to characterize the crucial roles of APA in regulating the 3′UTR landscape and modulating gene expression during fracture healing.
基金This work was supported by the National Natural Science Foundation of China(Nos.81972058,81902194 and 82202680)the Science and Technology Commission of Shanghai Municipality(No.22YF1422900)+3 种基金the Shanghai Municipal Key Clinical Specialty,China(No.shslczdzk06701)the National Facility for Translational Medicine(Shanghai),China(No.TMSZ-2020-207)the Shanghai Engineering Research Center of Orthopedic Innovative Instruments and Personalized Medicine Instruments and Personalized Medicine(No.19DZ2250200)the Key R&D Program of Ningxia,China(Nos.2020BCH01001 and 2021BEG02037).
文摘The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion resistance,titanium–niobium alloys have the potential to become a new generation of internal fixation materials for fractures.However,the role and mechanism of titanium–niobium alloys on promoting fracture healing are still undefined.Therefore,in this study,we systematically evaluated the bone-enabling properties of Ti45Nb via in vivo and in vitro experiments.In vitro,we found that Ti45Nb has an excellent ability to promote MC3T3-E1 cell adhesion and proliferation without obvious cytotoxicity.Alkaline phosphatase(ALP)activity and alizarin red staining and semiquantitative analysis showed that Ti45Nb enhanced the osteogenic differentiation of MC3T3-E1 cells compared to the Ti6Al4V control.In the polymerase chain reaction experiment,the expression of osteogenic genes in the Ti45Nb group,such as ALP,osteopontin(OPN),osteocalcin(OCN),type 1 collagen(Col-1)and runt-related transcription factor-2(Runx2),was significantly higher than that in the control group.Meanwhile,in the western blot experiment,the expression of osteogenic-related proteins in the Ti45Nb group was significantly increased,and the expression of PI3K–Akt-related proteins was also higher,which indicated that Ti45Nb might promote fracture healing by activating the PI3K–Akt signaling pathway.In vivo,we found that Ti45Nb implants accelerated fracture healing compared to Ti6Al4V,and the biosafety of Ti45Nb was confirmed by histological evaluation.Furthermore,immunohistochemical staining confirmed that Ti45Nb may promote osteogenesis by upregulating the PI3K/Akt signaling pathway.Our study demonstrated that Ti45Nb exerts an excellent ability to promote fracture healing as well as enhance osteoblast differentiation by activating the PI3K/Akt signaling pathway,and its good biosafety has been confirmed,which indicates its clinical translation potential.
基金the National Key Research andDevelopment Program of China(No.2021YFA1101100)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16020807)+3 种基金the Major Innovative Research Team of Suzhou,China(No.ZXT2019007)Suzhou Institute of Biomedical Engineering and Technology(SIBET)Jilin City Science and Technology Cooperation Project(No.E0550104)Science and Technology Innovation Talents in Universities of Henan Province and Doctor of Entrepreneurship and Innovation Program of Jiangsu Province in the year of 2020.
文摘The process of wound healing is routinely evaluated by histological evaluation in the clinic,which may cause scarring and secondary injury.Reflectance confocal microscopy(RCM)represents a noninvasive,real-time imaging technique that allows in vivo evaluation of the skin.Traditional RCM was wide-probe-based,which limited its application on uneven and covered skin.In this study,we report the development of a portable reflectance confocal microscope(PRCM)in which all components were assembled in a handheld shell.Although the size and weight of the PRCM were reduced based on the use of a microelectromechanical system,the resolution was kept at 0.91μm,and the field of view of the system was 343μm×532μm.When used in vivo,the PRCM was able to visualize cellular and nuclear morphology for both mouse and human skin.PRCM evaluations were then performed on wounds after topically applied mesenchymal stem cells(MSCs)or saline treatment.The PRCM allowed visualization of the formation of collagen bundles,re-epithelization from the wound edge to the wound bed,and hair follicle regeneration,which were consistent with histological evaluations.Therefore,we offer new insights into monitoring the effects of topically applied MSCs on the process of wound healing by using PRCM.This study illustrates that the newly developed PRCM represents a promising device for real-time,noninvasive monitoring of the dynamic process of wound healing,which demonstrates its potential to diagnose,monitor,or predict disease in clinical wound therapy.
基金the National Key R&D Program of China,No.2018YFA0108304the National Natural Science Foundation of China,No.81771721 and 81971505the Innovation Project of Guangxi Graduate Education,No.YCBZ2022004 and YCBZ2022045。
文摘BACKGROUND Rapid wound healing remains a pressing clinical challenge,necessitating studies to hasten this process.A promising approach involves the utilization of human umbilical cord mesenchymal stem cells(hUC-MSCs)derived exosomes.The hypothesis of this study was that these exosomes,when loaded onto a gelatin sponge,a common hemostatic material,would enhance hemostasis and accelerate wound healing.AIM To investigate the hemostatic and wound healing efficacy of gelatin sponges loaded with hUC-MSCs-derived exosomes.METHODS Ultracentrifugation was used to extract exosomes from hUC-MSCs.Nanoparticle tracking analysis(NTA),transmission electron microscopy(TEM),and western blot techniques were used to validate the exosomes.In vitro experiments were performed using L929 cells to evaluate the cytotoxicity of the exosomes and their impact on cell growth and survival.New Zealand rabbits were used for skin irritation experiments to assess whether they caused adverse skin reactions.Hemolysis test was conducted using a 2%rabbit red blood cell suspension to detect whether they caused hemolysis.Moreover,in vivo experiments were carried out by implanting a gelatin sponge loaded with exosomes subcutaneously in Sprague-Dawley(SD)rats to perform biocompatibility tests.In addition,coagulation index test was conducted to evaluate their impact on blood coagulation.Meanwhile,SD rat liver defect hemostasis model and full-thickness skin defect model were used to study whether the gelatin sponge loaded with exosomes effectively stopped bleeding and promoted wound healing.RESULTS The NTA,TEM,and western blot experimental results confirmed that exosomes were successfully isolated from hUC-MSCs.The gelatin sponge loaded with exosomes did not exhibit significant cell toxicity,skin irritation,or hemolysis,and they demonstrated good compatibility in SD rats.Additionally,the effectiveness of the gelatin sponge loaded with exosomes in hemostasis and wound healing was validated.The results of the coagulation index experiment indicated that the gelatin sponge loaded with exosomes had significantly better coagulation effect compared to the regular gelatin sponge,and they showed excellent hemostatic performance in a liver defect hemostasis model.Finally,the full-thickness skin defect healing experiment results showed significant improvement in the healing process of wounds treated with the gelatin sponge loaded with exosomes compared to other groups.CONCLUSION Collectively,the gelatin sponge loaded with hUC-MSCs-derived exosomes is safe and efficacious for promoting hemostasis and accelerating wound healing,warranting further clinical application.
基金Supported by The National Natural Science Foundation of China,No.82171604。
文摘Impaired wound healing presents great health risks to diabetics.Encouragingly,the current clinical successfully found out meaningful method to repair wound tissue,and stem cell therapy could be an effective method for diabetic wound healing with its ability to accelerate wound closure and avoid amputation.This minireview aims at introducing stem cell therapy for facilitating tissue repair in diabetic wounds,discussing the possible therapeutic mechanism and clinical application status and problems.
基金Supported by the Natural Science Foundation of Jilin Province,No.YDZJ202301ZYTS508National Natural Science Foundation of China,No.U20A20403+2 种基金Doctoral Research Start-Up Fund of Changchun Sci-Tech University,No.202303Young Scientific and Technological Talents Support Project of Jilin Province,No.QT202203Strategic Research and Consulting Project of Chinese Academy of Engineering,No.JL2022-05.
文摘BACKGROUND Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing.Previous studies have indicated that antler reserve mesenchyme(RM)cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages.AIM To develop hydrogels from the antler RM matrix(HARM)and evaluate the effect on wound healing.METHODS We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin.Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application.RESULTS The results showed that HARM accelerated wound healing rate and reduced scar formation.Also,HARM stimulated the regeneration of cutaneous appendages and blood vessels,and reduced collagen fiber aggregation.Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site.The levels of fetal wound healing-related genes,including Collagen III and TGFβ3 treated with HARM were all increased,while the expression levels of Collagen I,TGFβ1,and Engrailed 1 were decreased in the healing.Moreover,the number of stem cells was increased in the fetal-like niche created by HARM,which may contribute to the regeneration of cutaneous appendages.CONCLUSION Overall,we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds.We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing,and thus pave the way for HARM to be developed for the clinic use.
基金Supported by the Hospital Research Fund,No.SDFEYBS1805,No.SDFEYGJ2013 and No.XKTJ-HRC20210015Suzhou Science and Technology Development Project,No.SYS2020105,No.SKJY2021078 and No.2022SS43+2 种基金the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLZD2021002CNNC Elite Talent Program2022 State Key Laboratory of Radiological Medicine and Radiation Protection jointly built by Province and Ministry,No.GZK1202244.
文摘BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.
