Inflammation and cutaneous nervous system involvement in hypertrophic scarring

This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation.

Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking

BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.

Role of HLA-DR and CD1a molecules in pathogenesis of hypertrophic scarring and keloids

Keyword: hypertrophic scars · keloids · HLA DR · CD1a

A Case Report of Concurrent Acne-Related Occurrence Complications: Telangiectasia, Post-Inflammatory Erythema, Post-Inflammatory Hyperpigmentation, and Atrophic and Hypertrophic Scars

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.

Understanding wound healing in obesity

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.

Inhibition effects of a negative electret 5-FU patch on the growth of a hypertrophic scar

In this study,the hypertrophic scar（HS） model in rats was established.5-fluorouracil（5-FU）patch,-1000 V and-2000 V polypropylene（PP） electret 5-FU patches were prepared and applied onto the wound.The in vitro permeation experiment was performed using the Franz diffusion cell system to determine the permeation cumulative amount and retention amount of5-FU through/in scar skin.The inhibition effect of negative electret on growth of HS was studied by hematoxylin-eosin（HE） staining,Masson staining and the immunohistologicall methods.The permeation study indicated that a negative electret could enhance the permeation and retention of 5-FU through and in scar skin respectively.HE staining and Masson staining indicated a better effect for-1000 V and-2000 V electret 5-FU patches on HS inhibition after28 d post-wounding compared with 5-FU patch.The immunohistological study showed much more reduced expressions of collegan type I,collegan type III,TGF-β1 and HSP47 in scar tissue after application of negative electret 5-FU patches than those of 5-FU patch.A negative electret5-FU patch may be advantageous for HS treatment.

NON-LINEAR SPECTRAL IMAGING MICROSCOPY STUDIES OF HUMAN HYPERTROPHIC SCAR

Skin scar is unique to humans,the major significant negative outcome sustained after thermal injuries,traumatic injuries,and surgical procedures.Hypertrophic scar in human skin is investigated using non-linear spectral imaging microscopy.The high contrast images and spectroscopic intensities of collagen and elastic fibers extracted from the spectral imaging of normal skin tissue,and the normal skin near and far away from the hypertrophic scar tissues in a 10-year-old patient case are obtained.The results show that there are apparent differences in the morphological structure and spectral characteristics of collagen and elastic fibers when comparing the normal skin with the hypertrophic scar tissue.These differences can be good indicators to differentiate the normal skin and hypertrophic scar tissue and demonstrate that non-linear spectral imaging microscopy has potential to noninvasively investigate the pathophysiology of human hypertrophic scar.

Dynamic changes of autophagy during hypertrophic scar formation and the role of autophagy intervention

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。

The expression of Cyclin A and p21^(cip1)in fibroblast of hypertrophic scar

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

Can we suppress excessive post-surgical scar formation:A case report

BACKGROUND Hypertrophic scars(HSs)formation is a complication that occurs after wounds heal with secondary intention and sometimes after clean surgical incisions.Many treatments are in vogue now with varying successes.Although the mechanism or mechanisms that cause a HS to form are not clearly understood,one thing that is clear is that once scar tissue matures,any intervention will not be successful.In this paper,we report on a case where a patient who was known to develop HS was treated with a new combination of ingredients(Phyto-chemicals+Silicone JUMI)to suppress HS formation.CASE SUMMARY A 68-year-old female of African descent presented a severe HS post total knee replacement(TKR),which the patient describes as itchy and painful.Due to complications caused by the scar,she was apprehensive about undergoing TKR on her other knee.However,after the TKR of the contralateral side post-removal of skin clips,JUMI anti-scar cream(JASC)was used to suppress excessive scar formation.CONCLUSION JASC appears potent and efficacious at suppressing excessive scar formation.We believe that this warrants further studies on larger patient groups and on different surgical sites.

Mechanical tension promotes skin nerve regeneration by upregulating nerve growth factor expression

This study aimed to explore the role of mechanical tension in hypertrophic scars and the change in nerve density using hematoxylin-eosin staining and S100 immunohistochemistry, and to observe the expression of nerve growth factor by western blot analysis. The results demonstrated that mechanical tension contributed to the formation of a hyperplastic scar in the back skin of rats, in conjunction with increases in both nerve density and nerve growth factor expression in the scar tissue. These experimental findings indicate that the cutaneous nervous system plays a role in hypertrophic scar formation caused by mechanical tension.

Technological Advances in Accelerated Wound Repair and Regeneration

We reviewed a number of wound repair, keloid and hypertrophic scar research methods that included lasers, microcurrent and ultra-low energy technologies. Laser research reports short-term improvement in wounds, keloid and hypertrophic scars, but without follow up to control for reoccurrence of keloids or diabetic lesions which generally reoccur following laser treatments. The microcurrent and ultra-low energy studies demonstrate significant healing where age is not a factor with no reoccurrence of diabetic wounds and other skin lesions. Our randomized, double-blind longitudinal research on eight wound repair clinical cases with an age range of 28 - 86, followed for one year, evidenced accelerated healing and no reoccurrence. The number of treatments required for substantial healing depended on the chronicity and severity of the lesion, with chronic severe lesions requiring more treatments, rather than age, a conclusion supported by ultra-low microcurrent research. These results on age-independent wound healing directly contradict a large body of literature postulating that healing is much slower with age due to immune insufficiency, age-accumulated oxidative stress, disrupted cell communications and sustained inflammation.

Comprehensive Strategy for Keloid Treatment:Experience at Shanghai Ninth People's Hospital

Keloids are a notorious fibroproliferative disorder that may cause cosmetic concerns and life inconvenience.Various methods such as surgery,injection,and laser have been used;however,single treatments are at risk of recurrence;therefore,comprehensive therapy is the better solution.Here,we focused on the management of different medical interventions according to subjective and objective conditions of keloid patients and summarized several clinical comprehensive strategies based on our clinical experience.One original concept of laser combined with radiotherapy was also introduced as a promising method,especially for wide-based pathological scars.

Evaluations of dielectric property and drug release profile of 5-FU patches based on plasma charged electrets

In the present study,the electret 5-fluorouracil patch was developed,the effective surface potential,piezoelectric coefficient d33,open-circuit thermally stimulated discharge（TSD） current spectra and shear adhesion of the patch were measured.The drug release profile of the patch was determined by using high performance liquid chromatography method.A stable potential difference which was positively dependent on the surface potential of the electret was generated on two sides of the patch.The measurements of d33 coefficient,TSD current spectra and adhesion performance showed that the electrostatic field of the electret could cause polarization and cohesive strength decreasing of the matrix molecules,change the distribution and interaction of the drug molecules in patch,therefore to increase the release of drug from the transdermal patch.

In-depth examination of hyperproliferative healing in two breeds of Sus scrofa domesticus commonly used for research

Background:Wound healing can result in various outcomes,including hypertrophic scar(HTS).Pigs serve as models to study wound healing as their skin shares physi-ologic similarity with humans.Yorkshire(Yk)and Duroc(Dc)pigs have been used to mimic normal and abnormal wound healing,respectively.The reason behind this differential healing phenotype was explored here.Methods:Excisional wounds were made on Dc and Yk pigs and were sampled and imaged for 98 days.PCR arrays were used to determine differential gene expression.Vancouver Scar Scale(VSS)scores were given.Re-epithelialization was analyzed.H&E,Mason's trichrome,and immunostains were used to determine cellularity,col-lagen content,and blood vessel density,respectively.Results:Yk wounds heal to a“port wine”HTS,resembling scarring in Fitzpatrick skin types(FST)I-III.Dc wounds heal to a dyspigmented,non-pliable HTS,resembling scarring in FST IV-VI.Gene expression during wound healing was differentially regulated versus uninjured skin in 40/80 genes,15 of which differed between breeds.Yk scars had a higher VSS score at all time points.Yk and Dc wounds had equivalent re-epithelialization,collagen disorganization,and blood vessel density.Conclusions:Our findings demonstrate that Dc and Yk pigs can produce HTS.Wound creation and healing were consistent among breeds,and differences in gene expression were not sufficient to explain differences in resulting scar phenotype.Both pig breeds should be used in animal models to investigate novel therapeutics to provide insight into a treatment's effectiveness on various skin types.

Botulinum Toxin Type A and Its Possible Mechanisms on Wound Healing

Botulinum toxin type-A (BTX-A), a subtype from known seven types of botulinum neurotoxin (serotype A-G), is produced by a gram-positive bacterium, Clostridium botulinum. The toxin is now widely and efficiently used in treating a plethora of diverse symptoms and conditions. Recent evidence in the literature also shows that BTX-A exhibits a wide range of effects on non-neuronal cells. Its potential has markedly expanded to clinical applications other than the treatment of neurological and muscular conditions that are characterized by neuronal hyperactivity. A number of studies have shown BTX-A to improve the quality of scar outcome and prevent the formation of keloids and HTS. Although the mechanism of action of BTX-A on wound healing is still not clearly understood, lately there has been extensive research to grasp the underlying mechanisms of this multifunctional toxin. BTX-A seems to affect wound healing by a number of mechanisms that include action on tensile forces, inhibition of fibroblasts differentiation, downregulation of TGF-β1 and collagen expression. This review will explore the responses of Botulinum toxin type-A on wound healing and preventing pathological scars like HTS and keloids, and comprehend the overall effect BTX-A has on wound healing.

Transdermal delivery of Chinese herbal medicine extract using dissolvable microneedles for hypertrophic scar treatment

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.

Diagnosis and Treatment of Keloids and Hypertrophic Scars—Japan Scar Workshop Consensus Document 2018

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.

Strategies to prevent hypertrophic scar formation:a review of therapeutic interventions based on molecular evidence

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.

Pressure therapy upregulates matrix metalloproteinase expression and downregulates collagen expression in hypertrophic scar tissue

Background Pressure therapy improves hypertrophic scar healing, but the mechanisms for this process are not well understood. We sought to investigate the differential expression of matrix metalloproteinases （Mmps） and collagen in post- traumatic hypertrophic scar tissue with mechanical pressure and delineate the molecular mechanisms of pressure therapy for hypertrophic scars. Methods Fibroblast lines of normal skin and scar tissue were established and a mechanical pressure system was devised to simulate pressure therapy. Reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting assays were used to compare differences in the mRNA and protein expression of Mmps and collagen in scar fibroblasts before and after pressure therapy. Results The expression differed between the hypertrophic scar cell line and the normal cell line. RT-PCR assays showed that Collagen I, highly expressed in the hypertrophic scar cell line, decreased significantly after pressure therapy. Mmp2, Mmp9, and Mmp12 expression in the hypertrophic scar tissue increased significantly after pressure therapy （P 〈0.05）. Western blotting assays further revealed that Mmp9 and Mmp12 expression increased significantly in the hypertrophic scar tissue after pressure therapy （P 〈0.05） but not Mmp2 expression （P 〉0.05）. Conclusion Mechanical pressure induces degradation of Collagen I in hypertrophic scar tissue by affecting the expression of Mmp9 and Mmp12.