Prior to his initial diagnosis, a 21-year-old male had been experiencing facial acne for two years and had been treated by a doctor in private practice. The patient visited our department because the clinical manifest...Prior to his initial diagnosis, a 21-year-old male had been experiencing facial acne for two years and had been treated by a doctor in private practice. The patient visited our department because the clinical manifestations of mandibular acne did not improve. At the time of initial examination, telangiectasia (TE), post-inflammatory erythema (PIE), post-inflammatory hyperpigmentation (PIH), atrophic scars (ASs), and a hypertrophic scar (HS) with induration were observed on the right neck. We diagnosed this as an acne vulgaris complication. HS lesions were topically treated by injecting triamcinolone acetonide, and the patient was prescribed 8.1 g/day of oral Saireito (Japanese herb). Adapalene benzoyl peroxide gel and topical tacrolimus hydrate ointment were used to treat PIE and TE. Both HSs and PIE improved;however, TE and AS did not improve. Currently, the patient is under observation. We consider this to be a very rare concurrent occurrence of diverse complications of acne vulgaris, and present the following case study.展开更多
Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein...Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。展开更多
Objective To study the relation of the mRNA and protein expression of CyclinA and p21cip1 in different stages hypertrophic scar fibroblast (FB) with its cell cycle,so as to provide theoretical evidence for interventio...Objective To study the relation of the mRNA and protein expression of CyclinA and p21cip1 in different stages hypertrophic scar fibroblast (FB) with its cell cycle,so as to provide theoretical evidence for intervention therapy of展开更多
Objective:To study the anti-hypertrophic scar effect of the six-herb Chinese medicine composition(SCMC) ointment on the rabbit ear hypertrophic scar models.Methods:The optimal formulation of SCMC ointment matrix was s...Objective:To study the anti-hypertrophic scar effect of the six-herb Chinese medicine composition(SCMC) ointment on the rabbit ear hypertrophic scar models.Methods:The optimal formulation of SCMC ointment matrix was screened by the orthogonal designs and a series of evaluation tests.The SCMC ointment was prepared through emulsifying method.The rabbit ear hypertrophic scar models were established and used to investigate the anti-hypertrophic scar effect of SCMC ointment.Results:Our results demonstrated that all the quality control indications of the SCMC ointment met the requirements.Anti-hypertrophic scar activity results showed that all the rabbit ear scar tissues appeared different degrees of shrink and fading,and took an unobvious but palpable shift from hard to soft texture with the low,middle and high concentration SCMC ointments treatments in vivo.Additionally,on 21 st day the scar area and thickness in different concentrations of SCMC ointment groups were significantly reduced than control group,in a concentration-dependent manner.The immunohistochemical results also indicated that the SCMC ointment had good anti-hypertrophic scar properties and could inhibit hypertrophic scar formation.Conclusion:The SCMC ointment could improve the blood circulation condition of hypertrophic scar tissues.Our research has demonstrated the Chinese medicine composition ointment with good antihypertrophic scar properties that could be used to treat hypertrophic scars.Meanwhile,it provides a theoretical basis for further clinical application.展开更多
There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic diseases....There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic diseases.This is particularly true for clinicians who deal with Asian and African patients because these ethnicities are highly prone to these diseases.By contrast,Caucasians are less likely to develop keloids and hypertrophic scars,and if they do,the scars tend not to be severe.This ethnic disparity also means that countries vary in terms of their differential diagnostic algorithms.The lack of clear treatment guidelines also means that primary care physicians are currently applying a hotchpotch of treatments,with uneven outcomes.To overcome these issues,the Japan Scar Workshop(JSW)has created a tool that allows clinicians to objectively diagnose and distinguish between keloids,hypertrophic scars,and mature scars.This tool is called the JSW Scar Scale(JSS)and it involves scoring the risk factors of the individual patients and the affected areas.The tool is simple and easy to use.As a result,even physicians who are not accustomed to keloids and hypertrophic scars can easily diagnose them and judge their severity.The JSW has also established a committee that,in cooperation with outside experts in various fields,has prepared a Consensus Document on keloid and hypertrophic scar treatment guidelines.These guidelines are simple and will allow even inexperienced clinicians to choose the most appropriate treatment strategy.The Consensus Document is provided in this article.It describes(1)the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors,(2)the general treatment algorithms for keloids and hypertrophic scars at different medical facilities,(3)the rationale behind each treatment for keloids and hypertrophic scars,and(4)the body site-specific treatment protocols for these scars.We believe that this Consensus Document will be helpful for physicians from all over the world who treat keloids and hypertrophic scars.展开更多
Once scar tissues mature,it is impossible for the surrounding tissue to regenerate normal dermal tissue.Therefore,it is essential to understand the fundamental mechanisms and establish effective strategies to inhibit ...Once scar tissues mature,it is impossible for the surrounding tissue to regenerate normal dermal tissue.Therefore,it is essential to understand the fundamental mechanisms and establish effective strategies to inhibit aberrant scar formation.Hypertrophic scar formation is considered a result of the imbalance between extracellular matrix synthesis and degradation during wound healing.However,the underlying mechanisms of hypertrophic scar development are poorly understood.The purpose of this review was to outline the management in the early stage after wound healing to prevent hypertrophic scar formation,focusing on strategies excluding therapeutic agents of internal use.Treatment aimed at molecular targets,including cytokines,will be future options to prevent and treat hypertrophic scars.More basic studies and clinical trials,including combination therapy,are required to investigate the mechanisms and prevent hypertrophic scar formation.展开更多
Hypertrophic scar(HS)is an undesirable skin abnormality following deep burns or operations.Although intralesional multi-injection with the suspension of triamcinolone acetonide(TA)and 5-fluorouracil(5-Fu)has exhibited...Hypertrophic scar(HS)is an undesirable skin abnormality following deep burns or operations.Although intralesional multi-injection with the suspension of triamcinolone acetonide(TA)and 5-fluorouracil(5-Fu)has exhibited great promise to HS treatment in clinical,the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy.Besides,the traditional injection with great pain is highly dependent on the skill of the experts,which results in poor compliance.Herein,a bilayer dissolving microneedle(BMN)containing TA and 5-Fu(TA-5-Fu-BMN)with biphasic release profile was designed for HS therapy.Equipped with several micro-scale needle tips,the BMN could be self-pressed into the HS with uniform drug distribution and less pain.Both in vitro permeation and in vivo HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property.Subsequently,the rabbit ear HS model was established to assess therapeutic efficacy.The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition.It was also found that the value of scar elevation index was ameliorated to a basal level,together with the downregulation of mRNA and protein expression of Collagen I(Col I)and transforming growth factor-β1(TGF-β1)after application of TA-5-Fu-BMN.In conclusion,the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior.展开更多
Hypertrophic scars(HTS)are caused by dermal injuries such as trauma and burns to the deep dermis,which are red,raised,itchy and painful.They can cause cosmetic disfigurement or contractures if craniofacial areas or mo...Hypertrophic scars(HTS)are caused by dermal injuries such as trauma and burns to the deep dermis,which are red,raised,itchy and painful.They can cause cosmetic disfigurement or contractures if craniofacial areas or mobile region of the skin are affected.Abnormal wound healing with more extracellular matrix deposition than degradation will result in HTS formation.This review will introduce the physiology of wound healing,dermal HTS formation,treatment and difference with keloids in the skin,and it also review the current advance of molecular basis of HTS including the involvement of cytokines,growth factors,and macrophages via chemokine pathway,to bring insights for future prevention and treatment of HTS.展开更多
Background:MicroRNA-101(miR-101)is a tumor suppressor microRNA(miRNA)and its loss is associated with the occurrence and progression of various diseases.However,the biological function and target of miR-101 in the path...Background:MicroRNA-101(miR-101)is a tumor suppressor microRNA(miRNA)and its loss is associated with the occurrence and progression of various diseases.However,the biological function and target of miR-101 in the pathogenesis of hypertrophic scars(HS)remains unknown.Methods:We harvested HS and paired normal skin(NS)tissue samples from patients and cultured their fibroblasts(HSF and NSF,respectively).We used quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),fluorescence in situ hybridization(FISH),enzyme-linked immunosorbent assays(ELISA)and Western blot analyses to measure mRNA levels and protein expression of miR-101,enhancer of zeste homolog 2(EZH2),collagen 1 and 3(Col1 and Col3)andα-smooth muscle actin(α-SMA)in different in vitro conditions.We also used RNA sequencing to evaluate the relevant signaling pathways and bioinformatics analysis and dual-luciferase reporter assays to predict miR-101 targets.We utilized a bleomycin-induced fibrosis mouse model in which we injected miR-101 mimics to evaluate collagen deposition in vivo.Results:We found low expression of miR-101 in HS and HSF compared to NS and NSF.Overexpressing miR-101 decreased Col1,Col3 andα-SMA expression in HSF.We detected high expression of EZH2 in HS and HSF.Knockdown of EZH2 decreased Col1,Col3 andα-SMA in HSF.Mechanistically,miR-101 targeted the 3-untranslated region(3UTR)of EZH2,as indicated by the decreased expression of EZH2.Overexpressing EZH2 rescued miR-101-induced collagen repression.MiR-101 mimics effectively suppressed collagen deposition in the bleomycin-induced fibrosis mouse model.Conclusions:Our data reveal that miR-101 targets EZH2 in HS collagen production,providing new insight into the pathological mechanisms underlying HS formation.展开更多
Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to ...Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to lose efficacy over prolonged applications.Traditional Chinese medicine(TCM)offers as a promising candidate to treat pathological scars.A large number of TCMs have been studied to show anti-scarring effect,however,the natural barrier of the skin impedes their penetration,lowering its therapeutic efficacy.Herein,we reported the use of dissolvable hyaluronic acid(HA)microneedles(MNs)as a vehicle to aid the transdermal delivery of therapeutic agent,a model TCM called shikonin for the treatment of hypertrophic scars.Here,shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration,making its dosage controllable during the fabrication process.The therapeutic effect of the shikonin MNs was studied in vira using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction.Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes(i.e.,TGFβ1,FAP-αand COL1 A1).Furthermore,we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.展开更多
Background:Hypertrophic scars are one of the main complications that affect the quality of life of patients after burns.Many methods have been shown to be effective in the treatment of hypertrophic scars,such as ablat...Background:Hypertrophic scars are one of the main complications that affect the quality of life of patients after burns.Many methods have been shown to be effective in the treatment of hypertrophic scars,such as ablative fractional CO_(2) laser(AFCL)and platelet-rich plasma(PRP).However,there are few studies on the effect of the combined application of these measures.The purpose of this study was to explore the therapeutic effect of AFCL combined with PRP on hypertrophic burn scars.Methods:A retrospective clinical observation study was conducted on 50 patients with hypertrophic burn scars.The AFCL+PRP group included 31 patients who received AFCL combined with PRP treatment;the AFCL group included 19 patients who received AFCL treatment only.The University of North Carolina 4P Scar Scale(UNC4P)and the Vancouver Scar Scale(VSS)scores that were collected before each treatment were used as indicators of the effectiveness of the previous treatment.The scores recorded at the second,fourth and seventh months were analysed.Results:The demographic data of the 2 groups were not significantly different.Before treatment,therewas no difference in the UNC4P and VSS scores between the 2 groups.Therewas a significant decline in the UNC4P and VSS total scores over 6 months in both groups(p<0.05)and scores in the 2 groups were comparable after 3 and 6 months(p<0.05).UNC4P scores in the AFCL+PRP group decreased from a mean of 8.26 to 2.61(p<0.05)with a concomitant drop in VSS scores from a mean of 11.74 to 6.06(p<0.01).In the AFCL group UNC4P and VSS scores decreased from 7.68 to 4.63(p<0.05)and from 10.89 to 8.16(p<0.05),respectively.The sub-items of these 2 assessments were analysed and the results suggest that AFCL combined with PRP can comprehensively improve scarring.Conclusions:This study shows that PRP is an effective adjunct for AFCL in the treatment of hypertrophic burn scars and that the combination of PRP and AFCL proved to be more useful than AFCL alone.This combination may be a new and effective clinical practice for the treatment of scars.However,larger and higher-level clinical studies are still needed to determine its efficacy and possible mechanisms.展开更多
Background:The aim of this review was to explore the existing body of literature focusing on the intralesional treatments of keloids and hypertrophic scars.Methods:A comprehensive systematic review of related articles...Background:The aim of this review was to explore the existing body of literature focusing on the intralesional treatments of keloids and hypertrophic scars.Methods:A comprehensive systematic review of related articles was conducted across multiple databases.Article selection was limited to those published in the English language between 1950 and 2014.Search terms for the on-line research were"scar(s),""keloid(s),""hypertrophic,""injection,""intralesional,"and"treatment".Results:The initial search returned 2548 published articles.After full text review,the final search yielded 11 articles that met inclusion criteria.A total of 14 patient samples in 11 articles were collected.The most frequent intralesional injection treatment studied was triamcinolone(n=5),fol owed by bleomycin(n=3),5-fluorouracil(n=2),verapamil(n=2),cryosurgery,and collagenase.The scar height reduction for all but one study was demonstrated,with acceptable complication and recurrence rate.Only three articles reported a follow-up period longer than 18 months,and only two studies used standardized outcome criteria with a quantitative scale.Conclusions:Although many treatment options have already been described in the literature,there is no universal y accepted treatment resulting in permanent hypertrophic or keloid scar ablation.The lack of adequately long-term powered randomized control ed trials does not permit to establish definitive conclusions with implications for routine clinical practice.Level of展开更多
Background:Hypertrophic scars(HS)represent one of the most common clinical challenges due to unsatisfactory therapeutic results.HS formation is associated with the abnormal activation of fibroblasts and their excessiv...Background:Hypertrophic scars(HS)represent one of the most common clinical challenges due to unsatisfactory therapeutic results.HS formation is associated with the abnormal activation of fibroblasts and their excessive fibrotic behavior.Glycolysis dysregulation has been shown to participate in the incidence and progression of various fibrotic diseases and shows potential as a means of controlling HS formation.This work aimed to discuss the impact of augmented glycolysis on HS and to propose a method for controlling HS formation through glycolysis regulation.Methods:Here,augmented glycolysis was confirmed together with enhanced fibrotic activity in both HS fibroblasts(HFs)and HS tissues,and the suppression of glycolysis also attenuated fibroblast activation.We also introduced IR780,a heptamethine cyanine dye,to regulate glycolysis for the control of HS formation.Results:In vitro,cell studies indicated that IR780 significantly down-regulated glycolysis and suppressed the fibrotic activity of HFs.In vivo,the intralesional injection of IR780 into rabbit HS models led to the downregulation of glycolysis and the control of HS formation.Furthermore,IR780 accumulated preferentially in activated fibroblasts in both in vitro and in vivo studies,and thus specifically downregulated glycolysis and efficiently controlled fibrosis by targeting activated fibroblasts.Conclusions:This work identified a strategy for controlling fibrosis and HS formation from the perspective of glycolysis regulation with IR780 targeting of activated fibroblasts.展开更多
The therapeutic interventions of human hypertrophic scars(HHS)remain puzzle largely due to the lack of accepted models.Current HHS models are limited by their inability to mimic native scar architecture and associated...The therapeutic interventions of human hypertrophic scars(HHS)remain puzzle largely due to the lack of accepted models.Current HHS models are limited by their inability to mimic native scar architecture and associated pathological microenvironments.Here,we create a 3D functional HHS model by preformed cellular aggregates(PCA)bioprinting,firstly developing bioink from scar decellularized extracellular matrix(ECM)and alginate-gelatin(Alg-Gel)hydrogel with suitable physical properties to mimic the microenvironmental factors,then pre-culturing patient-derived fibroblasts in this bioink to preform the topographic cellular aggregates for sequent printing.We confirm the cell aggregates preformed in bioink displayed well defined aligned structure and formed functional scar tissue self-organization after bioprinting,hence showing the potential of creating HHS models.Notably,these HHS models exhibit characteristics of early-stage HHS in gene and protein expression,which significantly activated signaling pathway related to inflammation and cell proliferation,and recapitulate in vivo tissue dynamics of scar forming.We also use the in vitro and in vivo models to define the clinically observed effects to treatment with concurrent anti-scarring drugs,and the data show that it can be used to evaluate the potential therapeutic target for drug testing.The ideal humanized scar models we present should prove useful for studying critical mechanisms underlying HHS and to rapidly test new drug targets and develop patient-specific optimal therapeutic strategies in the future.展开更多
The formation of hypertrophic scars (HSs) is a fibroproliferative disorder of abnormal wound healing. HSs usually characterize excessive proliferation of fibroblasts, abnormal deposition of extracellular matrix (ECM) ...The formation of hypertrophic scars (HSs) is a fibroproliferative disorder of abnormal wound healing. HSs usually characterize excessive proliferation of fibroblasts, abnormal deposition of extracellular matrix (ECM) during wound healing, associated with cosmetic, functional, and psychological problems. Owing to the role of ECM proteins in scar formation, we comparatively analyzed matrix proteins secreted by normal skin fibroblasts (NSFs) and HS fibroblasts (HSFs). The acetone-extracted secreted proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and identified by mass spectrometry (MS). Based on Go annotation of MS data, the profiling of ECM proteins was established and scar-related proteins have been screened out. The functions of several ECM proteins identified by MS have been discussed, such as collagens I, VI, XII, fibronectin, decorin, lumican, and protein procollagen C endopeptidase enhancer 1 (PCPE-1). Among them, the MS result of PCPE-1 was supported by Western blotting that PCPE-1 from HSFs were significantly upregulated than that from NSFs. It is suggested that PCPE-1 could be a potential target for scar treatment. The exploration of scar related proteins may provide new perspectives on understanding the mechanism of scar formation and open a new way to scar treatment and prevention.展开更多
Background:A hypertrophic scar is a unique fibrotic disease that only exists in humans.Despite advances in burn care and rehabilitation,as well as progress in the management during these decades,the hypertrophic scar ...Background:A hypertrophic scar is a unique fibrotic disease that only exists in humans.Despite advances in burn care and rehabilitation,as well as progress in the management during these decades,the hypertrophic scar remains hard to cure following surgical methods and drugs for treatment.In this study,we are looking forward to finding the multitude of possible traumatic mechanisms and the underlying molecular signal ways in the formation of the hypertrophic scar.Methods:We used isobaric tags for relative and absolute quantitation(iTRAQ)labeling technology,followed by high-throughput 2D LC-MS/MS,to determine relative quantitative differential proteins between the hypertrophic scar and normal skin tissue.Results:A total of 3166 proteins were identified with a high confidence(≥95%confidence).And,a total of 89 proteins were identified as the differential proteins between the hypertrophic scar and normal skin,among which 41 proteins were up-regulated and 48 proteins were down-regulated in the hypertrophic scar.GO-Analysis indicated the up-regulated proteins were involved in extracellular matrix,whereas the down-regulated proteins were involved in dynamic junction and structural molecule activity.Conclusions:In our study,we demonstrate 89 proteins present differently in the hypertrophic scar compared to normal skin by iTRAQ technology,which might indicate the pathologic process of hypertrophic scar formation and guide us to propose new strategies against the hypertrophic scar.展开更多
Photodynamic therapy(PDT)is an emerging therapeutic strategy for hypertrophic scars(HS),which is heavily dependent on reactive oxygen species(ROS)generation.However,the unsatisfactory delivery and excitation of 5-amin...Photodynamic therapy(PDT)is an emerging therapeutic strategy for hypertrophic scars(HS),which is heavily dependent on reactive oxygen species(ROS)generation.However,the unsatisfactory delivery and excitation of 5-aminolevulinic acid(ALA,a commercial photosensitizer in dermatology)result in an insufficient ROS generation,and thus limit the clinical application of PDT treating HS(HS-PDT).Consequently,sophisticated transdermal co-delivery nanoethosomes(named A/A-ES)with ALA and Au nanotriangles(AuNTs)in cores are prepared via an in-situ seed-mediated growth method,and then applied to improve HS-PDT through localized surface plasmon resonance(LSPR)-enhanced ROS generation.A/A-ES display a satisfactory performance in co-delivery in HS tissue with sufficient protoporphyrin IX production and LSPR effect in cytoplasm,which is beneficial for ALA excitation as well as ROS generation.In vitrolvivo studies reveal that A/A-ES significantly improve HS-PDT in promoting to fibroblast apoptosis and collagen remodeling through LSPR-enhanced ROS generation.Therefore,this study provides a feasible strategy that integrates transdermal delivery and LSPR to enable the beneficial effects of HS-PDT through boosting the delivery and excitation of ALA.展开更多
Numerous studies have shown that macrophages can orchestrate the microenvironment from the early stage of wound healing to the later stages of scar formation.However,few reviews have highlighted the significance of ma...Numerous studies have shown that macrophages can orchestrate the microenvironment from the early stage of wound healing to the later stages of scar formation.However,few reviews have highlighted the significance of macrophages during the formation of abnormal scars.The purpose of this reviewwas to outline the polarization of macrophages from early to late stage of pathological scar formation,focusing on spatiotemporal diversity of M1 and M2 macrophages.In this review,the role of macrophages in the formation of hypertrophic scars and keloids is summarized in detail.First,an increased number of M2 cells observed before injuries are significantly associated with susceptibility to abnormal scar pathogenesis.Second,decreased expression of M1 at the early stage and delayed expression of M2 at the late stage results in pathological scar formation.Third,M2 cells are highly expressed at both the margin and the superficial region,which is consistent with the invasive property of keloids.Finally,this review helps to characterize strategies for the prediction and prevention of pathological scar formation.展开更多
Background:Hypertrophic scars are skin fibrotic diseases,characterized by fibroblast hyperprolif-eration and excessive accumulation of extracellular matrix.However,topical drug application for hypertrophic scars are u...Background:Hypertrophic scars are skin fibrotic diseases,characterized by fibroblast hyperprolif-eration and excessive accumulation of extracellular matrix.However,topical drug application for hypertrophic scars are unsatisfactory.The purpose of this study was to explore the permeability of silk nanofiber hydrogels(SNFs)loaded with rhodamine 6G(R6G)and rhodamine 110(R110)mediated by CO_(2)fractional laser irradiation into hypertrophic scar tissues.Methods:In this work,R6G and R110 were chosen as hydrophilic and hydrophobic model molecules.They were loaded inside SNFs.In vivo rabbit ear hypertrophic scars were treated with CO_(2)fractional laser irradiation and then R6G/R110-laden SNFs were applied to the scars to evaluate their synergetic effect on drug penetration efficiency.Their permeability was quantified by fluorescence intensity and measured by confocal laser scanning microscopy on days 1,3,5 and 7.More specifically,the thermal coagulation zone(CZ)and its surrounding area(peri-CZ)caused by the thermal coagulation of the laser were discussed separately.Results:Our data indicated that the SNFs promoted the penetration of R6G but not that of R110 in the peri-CZ on day 1 when combined with laser irradiation.Interestingly,both R6G and R110 were abundant in the CZ and remained stable on days 1,3 and 5.Moreover,rapid re-epithelialization hindered the long-term permeability of both drugs.Conclusion:Combining CO_(2)fractional laser irradiation with SNF drug delivery could improve the efficiency of hydrophilic drug delivery within 24 h before total re-epithelialization.展开更多
文摘Prior to his initial diagnosis, a 21-year-old male had been experiencing facial acne for two years and had been treated by a doctor in private practice. The patient visited our department because the clinical manifestations of mandibular acne did not improve. At the time of initial examination, telangiectasia (TE), post-inflammatory erythema (PIE), post-inflammatory hyperpigmentation (PIH), atrophic scars (ASs), and a hypertrophic scar (HS) with induration were observed on the right neck. We diagnosed this as an acne vulgaris complication. HS lesions were topically treated by injecting triamcinolone acetonide, and the patient was prescribed 8.1 g/day of oral Saireito (Japanese herb). Adapalene benzoyl peroxide gel and topical tacrolimus hydrate ointment were used to treat PIE and TE. Both HSs and PIE improved;however, TE and AS did not improve. Currently, the patient is under observation. We consider this to be a very rare concurrent occurrence of diverse complications of acne vulgaris, and present the following case study.
基金the National Natural Science Foundation of China(grant no.81872219)Science and Technology Project of Hunan Provincial Health Commission(grant no.B2015-040)+2 种基金Major Scientific and Technological Projects in Hunan Province(grant no.2019SK1010)2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant(grant nos.2020LKSFG18B,2020LKSFG02E)Guangdong University Innovation Team Project(grant no.2021KCXTD047).
文摘Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。
文摘Objective To study the relation of the mRNA and protein expression of CyclinA and p21cip1 in different stages hypertrophic scar fibroblast (FB) with its cell cycle,so as to provide theoretical evidence for intervention therapy of
基金supported by grants from Academic Talent Project of Guizhou Provincial Department of Science and Technology (Qiankehe Platform Talent[2017]5735-28)the Doctorial Startup Foundation of Guizhou University of Traditional Chinese Medicine (2016-3043-043160011)+5 种基金Guizhou discipline construction project (GNYL[2017]008)the National Key Research and Development Program of China (2018YFC1708100)University Students Chinese Medicine Preparation Innovation and Entrepreneurship Studio (Qiangaojiaofa[2017]158)Program for University Students Innovation and Entrepreneurship Plan of Guizhou University of Traditional Chinese Medicine (GZY Dachuanghe (2018) 30)Guizhou Province Top Major Chinese Medicine (Qianjiaogaofa[2017]158)Guizhou High-Level Innovative Talents Training Program (Qiankehe[2015]4032)。
文摘Objective:To study the anti-hypertrophic scar effect of the six-herb Chinese medicine composition(SCMC) ointment on the rabbit ear hypertrophic scar models.Methods:The optimal formulation of SCMC ointment matrix was screened by the orthogonal designs and a series of evaluation tests.The SCMC ointment was prepared through emulsifying method.The rabbit ear hypertrophic scar models were established and used to investigate the anti-hypertrophic scar effect of SCMC ointment.Results:Our results demonstrated that all the quality control indications of the SCMC ointment met the requirements.Anti-hypertrophic scar activity results showed that all the rabbit ear scar tissues appeared different degrees of shrink and fading,and took an unobvious but palpable shift from hard to soft texture with the low,middle and high concentration SCMC ointments treatments in vivo.Additionally,on 21 st day the scar area and thickness in different concentrations of SCMC ointment groups were significantly reduced than control group,in a concentration-dependent manner.The immunohistochemical results also indicated that the SCMC ointment had good anti-hypertrophic scar properties and could inhibit hypertrophic scar formation.Conclusion:The SCMC ointment could improve the blood circulation condition of hypertrophic scar tissues.Our research has demonstrated the Chinese medicine composition ointment with good antihypertrophic scar properties that could be used to treat hypertrophic scars.Meanwhile,it provides a theoretical basis for further clinical application.
文摘There has been a long-standing need for guidelines on the diagnosis and treatment of keloids and hypertrophic scars that are based on an understanding of the pathomechanisms that underlie these skin fibrotic diseases.This is particularly true for clinicians who deal with Asian and African patients because these ethnicities are highly prone to these diseases.By contrast,Caucasians are less likely to develop keloids and hypertrophic scars,and if they do,the scars tend not to be severe.This ethnic disparity also means that countries vary in terms of their differential diagnostic algorithms.The lack of clear treatment guidelines also means that primary care physicians are currently applying a hotchpotch of treatments,with uneven outcomes.To overcome these issues,the Japan Scar Workshop(JSW)has created a tool that allows clinicians to objectively diagnose and distinguish between keloids,hypertrophic scars,and mature scars.This tool is called the JSW Scar Scale(JSS)and it involves scoring the risk factors of the individual patients and the affected areas.The tool is simple and easy to use.As a result,even physicians who are not accustomed to keloids and hypertrophic scars can easily diagnose them and judge their severity.The JSW has also established a committee that,in cooperation with outside experts in various fields,has prepared a Consensus Document on keloid and hypertrophic scar treatment guidelines.These guidelines are simple and will allow even inexperienced clinicians to choose the most appropriate treatment strategy.The Consensus Document is provided in this article.It describes(1)the diagnostic algorithm for pathological scars and how to differentiate them from clinically similar benign and malignant tumors,(2)the general treatment algorithms for keloids and hypertrophic scars at different medical facilities,(3)the rationale behind each treatment for keloids and hypertrophic scars,and(4)the body site-specific treatment protocols for these scars.We believe that this Consensus Document will be helpful for physicians from all over the world who treat keloids and hypertrophic scars.
文摘Once scar tissues mature,it is impossible for the surrounding tissue to regenerate normal dermal tissue.Therefore,it is essential to understand the fundamental mechanisms and establish effective strategies to inhibit aberrant scar formation.Hypertrophic scar formation is considered a result of the imbalance between extracellular matrix synthesis and degradation during wound healing.However,the underlying mechanisms of hypertrophic scar development are poorly understood.The purpose of this review was to outline the management in the early stage after wound healing to prevent hypertrophic scar formation,focusing on strategies excluding therapeutic agents of internal use.Treatment aimed at molecular targets,including cytokines,will be future options to prevent and treat hypertrophic scars.More basic studies and clinical trials,including combination therapy,are required to investigate the mechanisms and prevent hypertrophic scar formation.
基金supported by the National Natural Science Foundation of China[grant No.81803466]the Research and Development Plan for Key Areas in Guangdong Province[grant No.2019B020204002]the National Science and Technology Major Program[grant No.2017zx09101001].
文摘Hypertrophic scar(HS)is an undesirable skin abnormality following deep burns or operations.Although intralesional multi-injection with the suspension of triamcinolone acetonide(TA)and 5-fluorouracil(5-Fu)has exhibited great promise to HS treatment in clinical,the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy.Besides,the traditional injection with great pain is highly dependent on the skill of the experts,which results in poor compliance.Herein,a bilayer dissolving microneedle(BMN)containing TA and 5-Fu(TA-5-Fu-BMN)with biphasic release profile was designed for HS therapy.Equipped with several micro-scale needle tips,the BMN could be self-pressed into the HS with uniform drug distribution and less pain.Both in vitro permeation and in vivo HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property.Subsequently,the rabbit ear HS model was established to assess therapeutic efficacy.The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition.It was also found that the value of scar elevation index was ameliorated to a basal level,together with the downregulation of mRNA and protein expression of Collagen I(Col I)and transforming growth factor-β1(TGF-β1)after application of TA-5-Fu-BMN.In conclusion,the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior.
基金Authors gratefully acknowledge the support from Li Ka Shine Sino-Canadian Exchange Program(ZZ).This work was also funded by University Hospital foundation from University of Alberta and the Firefighters'Burn Trust Fund
文摘Hypertrophic scars(HTS)are caused by dermal injuries such as trauma and burns to the deep dermis,which are red,raised,itchy and painful.They can cause cosmetic disfigurement or contractures if craniofacial areas or mobile region of the skin are affected.Abnormal wound healing with more extracellular matrix deposition than degradation will result in HTS formation.This review will introduce the physiology of wound healing,dermal HTS formation,treatment and difference with keloids in the skin,and it also review the current advance of molecular basis of HTS including the involvement of cytokines,growth factors,and macrophages via chemokine pathway,to bring insights for future prevention and treatment of HTS.
基金supported by the National Natural Science Foundation of China(81772071 to DHH).
文摘Background:MicroRNA-101(miR-101)is a tumor suppressor microRNA(miRNA)and its loss is associated with the occurrence and progression of various diseases.However,the biological function and target of miR-101 in the pathogenesis of hypertrophic scars(HS)remains unknown.Methods:We harvested HS and paired normal skin(NS)tissue samples from patients and cultured their fibroblasts(HSF and NSF,respectively).We used quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),fluorescence in situ hybridization(FISH),enzyme-linked immunosorbent assays(ELISA)and Western blot analyses to measure mRNA levels and protein expression of miR-101,enhancer of zeste homolog 2(EZH2),collagen 1 and 3(Col1 and Col3)andα-smooth muscle actin(α-SMA)in different in vitro conditions.We also used RNA sequencing to evaluate the relevant signaling pathways and bioinformatics analysis and dual-luciferase reporter assays to predict miR-101 targets.We utilized a bleomycin-induced fibrosis mouse model in which we injected miR-101 mimics to evaluate collagen deposition in vivo.Results:We found low expression of miR-101 in HS and HSF compared to NS and NSF.Overexpressing miR-101 decreased Col1,Col3 andα-SMA expression in HSF.We detected high expression of EZH2 in HS and HSF.Knockdown of EZH2 decreased Col1,Col3 andα-SMA in HSF.Mechanistically,miR-101 targeted the 3-untranslated region(3UTR)of EZH2,as indicated by the decreased expression of EZH2.Overexpressing EZH2 rescued miR-101-induced collagen repression.MiR-101 mimics effectively suppressed collagen deposition in the bleomycin-induced fibrosis mouse model.Conclusions:Our data reveal that miR-101 targets EZH2 in HS collagen production,providing new insight into the pathological mechanisms underlying HS formation.
基金support from Singapore Agency for Science,Technology and Research(A*STAR)Science and Engineering Research Council Additive Manufacturing for Biological Materials(AMBM)program(A18A8b0059,Singapore)City University of Hong Kong(#9610472,China)+1 种基金General Research Fund(GRF)from University Grant Committee of Hong Kong(UGC)Research Grant Council(RGC)(#9042951,China)NSFC/RGC Joint Research Scheme(N_City U118/20,China)
文摘Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to lose efficacy over prolonged applications.Traditional Chinese medicine(TCM)offers as a promising candidate to treat pathological scars.A large number of TCMs have been studied to show anti-scarring effect,however,the natural barrier of the skin impedes their penetration,lowering its therapeutic efficacy.Herein,we reported the use of dissolvable hyaluronic acid(HA)microneedles(MNs)as a vehicle to aid the transdermal delivery of therapeutic agent,a model TCM called shikonin for the treatment of hypertrophic scars.Here,shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration,making its dosage controllable during the fabrication process.The therapeutic effect of the shikonin MNs was studied in vira using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction.Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes(i.e.,TGFβ1,FAP-αand COL1 A1).Furthermore,we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.
基金supported by the National Nature Science Foundation of China(81701899)the Youth Incubation Plan of the Military Medical Science and Technology(16QNP091)+1 种基金the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-076)the high level achievement cultivation plan of the Naval Medical University(2018-CGPZ-B03).
文摘Background:Hypertrophic scars are one of the main complications that affect the quality of life of patients after burns.Many methods have been shown to be effective in the treatment of hypertrophic scars,such as ablative fractional CO_(2) laser(AFCL)and platelet-rich plasma(PRP).However,there are few studies on the effect of the combined application of these measures.The purpose of this study was to explore the therapeutic effect of AFCL combined with PRP on hypertrophic burn scars.Methods:A retrospective clinical observation study was conducted on 50 patients with hypertrophic burn scars.The AFCL+PRP group included 31 patients who received AFCL combined with PRP treatment;the AFCL group included 19 patients who received AFCL treatment only.The University of North Carolina 4P Scar Scale(UNC4P)and the Vancouver Scar Scale(VSS)scores that were collected before each treatment were used as indicators of the effectiveness of the previous treatment.The scores recorded at the second,fourth and seventh months were analysed.Results:The demographic data of the 2 groups were not significantly different.Before treatment,therewas no difference in the UNC4P and VSS scores between the 2 groups.Therewas a significant decline in the UNC4P and VSS total scores over 6 months in both groups(p<0.05)and scores in the 2 groups were comparable after 3 and 6 months(p<0.05).UNC4P scores in the AFCL+PRP group decreased from a mean of 8.26 to 2.61(p<0.05)with a concomitant drop in VSS scores from a mean of 11.74 to 6.06(p<0.01).In the AFCL group UNC4P and VSS scores decreased from 7.68 to 4.63(p<0.05)and from 10.89 to 8.16(p<0.05),respectively.The sub-items of these 2 assessments were analysed and the results suggest that AFCL combined with PRP can comprehensively improve scarring.Conclusions:This study shows that PRP is an effective adjunct for AFCL in the treatment of hypertrophic burn scars and that the combination of PRP and AFCL proved to be more useful than AFCL alone.This combination may be a new and effective clinical practice for the treatment of scars.However,larger and higher-level clinical studies are still needed to determine its efficacy and possible mechanisms.
文摘Background:The aim of this review was to explore the existing body of literature focusing on the intralesional treatments of keloids and hypertrophic scars.Methods:A comprehensive systematic review of related articles was conducted across multiple databases.Article selection was limited to those published in the English language between 1950 and 2014.Search terms for the on-line research were"scar(s),""keloid(s),""hypertrophic,""injection,""intralesional,"and"treatment".Results:The initial search returned 2548 published articles.After full text review,the final search yielded 11 articles that met inclusion criteria.A total of 14 patient samples in 11 articles were collected.The most frequent intralesional injection treatment studied was triamcinolone(n=5),fol owed by bleomycin(n=3),5-fluorouracil(n=2),verapamil(n=2),cryosurgery,and collagenase.The scar height reduction for all but one study was demonstrated,with acceptable complication and recurrence rate.Only three articles reported a follow-up period longer than 18 months,and only two studies used standardized outcome criteria with a quantitative scale.Conclusions:Although many treatment options have already been described in the literature,there is no universal y accepted treatment resulting in permanent hypertrophic or keloid scar ablation.The lack of adequately long-term powered randomized control ed trials does not permit to establish definitive conclusions with implications for routine clinical practice.Level of
基金supported by National Natural Science Foundation of China(82172222 and 82102328)ShanghaiMunicipal Education Commission-Gaofeng Clinical Medicine Grant Support(20152227)+3 种基金ClinicalMulti-Disciplinary Team Research Program of ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(2017-1-007)Cross Research Project of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYJC202009)Shanghai Health Industry Clinical Research Special Project(20204Y0443)Shanghai Municipal Key Clinical Specialty(shslczdzk00901).
文摘Background:Hypertrophic scars(HS)represent one of the most common clinical challenges due to unsatisfactory therapeutic results.HS formation is associated with the abnormal activation of fibroblasts and their excessive fibrotic behavior.Glycolysis dysregulation has been shown to participate in the incidence and progression of various fibrotic diseases and shows potential as a means of controlling HS formation.This work aimed to discuss the impact of augmented glycolysis on HS and to propose a method for controlling HS formation through glycolysis regulation.Methods:Here,augmented glycolysis was confirmed together with enhanced fibrotic activity in both HS fibroblasts(HFs)and HS tissues,and the suppression of glycolysis also attenuated fibroblast activation.We also introduced IR780,a heptamethine cyanine dye,to regulate glycolysis for the control of HS formation.Results:In vitro,cell studies indicated that IR780 significantly down-regulated glycolysis and suppressed the fibrotic activity of HFs.In vivo,the intralesional injection of IR780 into rabbit HS models led to the downregulation of glycolysis and the control of HS formation.Furthermore,IR780 accumulated preferentially in activated fibroblasts in both in vitro and in vivo studies,and thus specifically downregulated glycolysis and efficiently controlled fibrosis by targeting activated fibroblasts.Conclusions:This work identified a strategy for controlling fibrosis and HS formation from the perspective of glycolysis regulation with IR780 targeting of activated fibroblasts.
基金supported in part by the National Nature Science Foundation of China(81830064,81721092,32000969,82002056)Key Support Program for Growth Factor Research(SZYZ-TR-03)+3 种基金Chinese PLA General Hospital for Military Medical Innovation Research Project(CX-19026)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)the Military Medical Research and Development Projects(AWS17J005)National Key Research and Development Program of China(2018YFA0108700,2017YFA0105602).
文摘The therapeutic interventions of human hypertrophic scars(HHS)remain puzzle largely due to the lack of accepted models.Current HHS models are limited by their inability to mimic native scar architecture and associated pathological microenvironments.Here,we create a 3D functional HHS model by preformed cellular aggregates(PCA)bioprinting,firstly developing bioink from scar decellularized extracellular matrix(ECM)and alginate-gelatin(Alg-Gel)hydrogel with suitable physical properties to mimic the microenvironmental factors,then pre-culturing patient-derived fibroblasts in this bioink to preform the topographic cellular aggregates for sequent printing.We confirm the cell aggregates preformed in bioink displayed well defined aligned structure and formed functional scar tissue self-organization after bioprinting,hence showing the potential of creating HHS models.Notably,these HHS models exhibit characteristics of early-stage HHS in gene and protein expression,which significantly activated signaling pathway related to inflammation and cell proliferation,and recapitulate in vivo tissue dynamics of scar forming.We also use the in vitro and in vivo models to define the clinically observed effects to treatment with concurrent anti-scarring drugs,and the data show that it can be used to evaluate the potential therapeutic target for drug testing.The ideal humanized scar models we present should prove useful for studying critical mechanisms underlying HHS and to rapidly test new drug targets and develop patient-specific optimal therapeutic strategies in the future.
基金We would like to thank Dr. Peter Mose Larsen for his kind suggestion to the experimental design and data analysis. This work was supported by the grants NSFC(2010ZX09401-306-4-5, 30973116 and 81171809)"863"project(2012AA020504)the State Key Laboratory Funding(SKLZZ201012)
文摘The formation of hypertrophic scars (HSs) is a fibroproliferative disorder of abnormal wound healing. HSs usually characterize excessive proliferation of fibroblasts, abnormal deposition of extracellular matrix (ECM) during wound healing, associated with cosmetic, functional, and psychological problems. Owing to the role of ECM proteins in scar formation, we comparatively analyzed matrix proteins secreted by normal skin fibroblasts (NSFs) and HS fibroblasts (HSFs). The acetone-extracted secreted proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and identified by mass spectrometry (MS). Based on Go annotation of MS data, the profiling of ECM proteins was established and scar-related proteins have been screened out. The functions of several ECM proteins identified by MS have been discussed, such as collagens I, VI, XII, fibronectin, decorin, lumican, and protein procollagen C endopeptidase enhancer 1 (PCPE-1). Among them, the MS result of PCPE-1 was supported by Western blotting that PCPE-1 from HSFs were significantly upregulated than that from NSFs. It is suggested that PCPE-1 could be a potential target for scar treatment. The exploration of scar related proteins may provide new perspectives on understanding the mechanism of scar formation and open a new way to scar treatment and prevention.
文摘Background:A hypertrophic scar is a unique fibrotic disease that only exists in humans.Despite advances in burn care and rehabilitation,as well as progress in the management during these decades,the hypertrophic scar remains hard to cure following surgical methods and drugs for treatment.In this study,we are looking forward to finding the multitude of possible traumatic mechanisms and the underlying molecular signal ways in the formation of the hypertrophic scar.Methods:We used isobaric tags for relative and absolute quantitation(iTRAQ)labeling technology,followed by high-throughput 2D LC-MS/MS,to determine relative quantitative differential proteins between the hypertrophic scar and normal skin tissue.Results:A total of 3166 proteins were identified with a high confidence(≥95%confidence).And,a total of 89 proteins were identified as the differential proteins between the hypertrophic scar and normal skin,among which 41 proteins were up-regulated and 48 proteins were down-regulated in the hypertrophic scar.GO-Analysis indicated the up-regulated proteins were involved in extracellular matrix,whereas the down-regulated proteins were involved in dynamic junction and structural molecule activity.Conclusions:In our study,we demonstrate 89 proteins present differently in the hypertrophic scar compared to normal skin by iTRAQ technology,which might indicate the pathologic process of hypertrophic scar formation and guide us to propose new strategies against the hypertrophic scar.
基金This study was supported by China Postdoctoral Science Foundation(Nos.2017M620159 and 2019T120345)National Natural Science Foundation of China(Nos.81772098 and 81801917),Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(No.20152227)+3 种基金Cross Research Project of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(No.JYJC202009)Shanghai Health Industry Clinical Research Special Project(No.20204Y0443)Shanghai Municipal Key Clinical Specialty(shslczdzk00901)Scientific Research Foundation of Shanghai Municipal Commission of Health and Family Planning(No.20154Y002).
文摘Photodynamic therapy(PDT)is an emerging therapeutic strategy for hypertrophic scars(HS),which is heavily dependent on reactive oxygen species(ROS)generation.However,the unsatisfactory delivery and excitation of 5-aminolevulinic acid(ALA,a commercial photosensitizer in dermatology)result in an insufficient ROS generation,and thus limit the clinical application of PDT treating HS(HS-PDT).Consequently,sophisticated transdermal co-delivery nanoethosomes(named A/A-ES)with ALA and Au nanotriangles(AuNTs)in cores are prepared via an in-situ seed-mediated growth method,and then applied to improve HS-PDT through localized surface plasmon resonance(LSPR)-enhanced ROS generation.A/A-ES display a satisfactory performance in co-delivery in HS tissue with sufficient protoporphyrin IX production and LSPR effect in cytoplasm,which is beneficial for ALA excitation as well as ROS generation.In vitrolvivo studies reveal that A/A-ES significantly improve HS-PDT in promoting to fibroblast apoptosis and collagen remodeling through LSPR-enhanced ROS generation.Therefore,this study provides a feasible strategy that integrates transdermal delivery and LSPR to enable the beneficial effects of HS-PDT through boosting the delivery and excitation of ALA.
文摘Numerous studies have shown that macrophages can orchestrate the microenvironment from the early stage of wound healing to the later stages of scar formation.However,few reviews have highlighted the significance of macrophages during the formation of abnormal scars.The purpose of this reviewwas to outline the polarization of macrophages from early to late stage of pathological scar formation,focusing on spatiotemporal diversity of M1 and M2 macrophages.In this review,the role of macrophages in the formation of hypertrophic scars and keloids is summarized in detail.First,an increased number of M2 cells observed before injuries are significantly associated with susceptibility to abnormal scar pathogenesis.Second,decreased expression of M1 at the early stage and delayed expression of M2 at the late stage results in pathological scar formation.Third,M2 cells are highly expressed at both the margin and the superficial region,which is consistent with the invasive property of keloids.Finally,this review helps to characterize strategies for the prediction and prevention of pathological scar formation.
基金support from the Natural Science Foundation of Shanghai Project(19ZR1430200).
文摘Background:Hypertrophic scars are skin fibrotic diseases,characterized by fibroblast hyperprolif-eration and excessive accumulation of extracellular matrix.However,topical drug application for hypertrophic scars are unsatisfactory.The purpose of this study was to explore the permeability of silk nanofiber hydrogels(SNFs)loaded with rhodamine 6G(R6G)and rhodamine 110(R110)mediated by CO_(2)fractional laser irradiation into hypertrophic scar tissues.Methods:In this work,R6G and R110 were chosen as hydrophilic and hydrophobic model molecules.They were loaded inside SNFs.In vivo rabbit ear hypertrophic scars were treated with CO_(2)fractional laser irradiation and then R6G/R110-laden SNFs were applied to the scars to evaluate their synergetic effect on drug penetration efficiency.Their permeability was quantified by fluorescence intensity and measured by confocal laser scanning microscopy on days 1,3,5 and 7.More specifically,the thermal coagulation zone(CZ)and its surrounding area(peri-CZ)caused by the thermal coagulation of the laser were discussed separately.Results:Our data indicated that the SNFs promoted the penetration of R6G but not that of R110 in the peri-CZ on day 1 when combined with laser irradiation.Interestingly,both R6G and R110 were abundant in the CZ and remained stable on days 1,3 and 5.Moreover,rapid re-epithelialization hindered the long-term permeability of both drugs.Conclusion:Combining CO_(2)fractional laser irradiation with SNF drug delivery could improve the efficiency of hydrophilic drug delivery within 24 h before total re-epithelialization.
