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Skin 11β-hydroxysteroid dehydrogenase type 1 enzyme expression regulates burn wound healing and can be targeted to modify scar characteristics

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Burns & Trauma 2023年第1期11卷 32-45页

作者： kevin H.-Y.Tsai Huaikai Shi Roxanne J.Parungao Sina Naficy Xiaotong Ding Xiaofeng Ding Jonathan J.Hew Xiaosuo Wang Wojciech Chrzanowski Gareth G.Lavery Zhe Li Andrea C.Issler-Fisher Jun Chen Qian Tan peter k.maitz Mark S.Cooper Yiwei Wang Adrenal Steroid Group ANZAC Research InstituteConcord HospitalThe University of SydneySydneyNSW 2137Australia Burns and Reconstructive Surgery Research Group ANZAC Research InstituteConcord HospitalThe Uni-versity of SydneySydneyNSW 2137Australia School of Chemical and Biomolecular Engineering The University of SydneySydneyNSW 2006Australia Jiangsu Provincial Engineering Research Centre of TCM External Medication Development and Application Nanjing University of Chinese MedicineNanjingJiangsu210023China Department of Burns and Plastic Surgery Nanjing Drum Tower Hospital Clinical CollegeNanjing University of Chinese MedicineNanjingJiangsu210008China Heart Research Institute The University of SydneySydneyNSW 2006Australia Sydney Nano Institute Sydney Pharmacy SchoolFaculty of Medicine and HealthThe University of SydneySydneyNSW2006Australia Department of Biosciences Centre for Healthy Ageing and Understanding DiseaseNottingham Trent UniversityNG14BUUK Burns and Reconstructive Surgery Unit Concord Repatriation General HospitalSydneyNSW 2137Australia

Background:Excessive scarring and fibrosis are the most severe and common complications of burn *** exposure to high levels of glucocorticoids detrimentally impacts on skin,leading to skin thinning and impaired wound *** can generate active glucocorticoids locally through expression and activity of the 11β-hydroxysteroid dehydrogenase type 1 enzyme(11β-HSD1).We hypothesised that burn injury would induce 11β-HSD1 expression and local glucocorticoid metabolism,which would have important impacts on wound healing,fibrosis and *** additionally proposed that pharmacological manipulation of this system could improve aspects of post-burn ***:Skin 11β-HSD1 expression in burns patients and mice was *** impacts of 11β-HSD1 mediating glucocorticoid metabolism on burn wound healing,scar formation and scar elas-ticity and quality were additionally examined using a murine 11β-HSD1 genetic knockout ***-release scaffolds containing therapeutic agents,including active and inactive glucocorticoids,were developed and pre-clinically tested in mice with burn ***:We demonstrate that 11β-HSD1 expression levels increased substantially in both human and mouse skin after burn injury.11β-HSD1 knockout mice experienced faster wound healing than wild type mice but the healed wounds manifested significantly more collagen deposition,tensile strength and stiffness,features characteristic of excessive *** of slow-release prednisone,an inactive glucocorticoid,slowed the initial rate of wound closure but significantly reduced post-burn scarring via reductions in inflammation,myofibroblast generation,collagen production and scar ***:Skin 11β-HSD1 expression is a key regulator of wound healing and scarring after burn *** of an inactive glucocorticoid capable of activation by local 11β-HSD1 in skin slows the initial rate of wound closure but significantlyimproves scar characteristics po

关键词： Wound healing Burn injury Scarring Skin 11β-HSD1 11β-HSD1 knockout Glucocorticoid metabolism Polycaprolactone scaffold Drug delivery

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Challenges and innovations in treating chronic and acute wound infections:from basic science to clinical practice

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Burns & Trauma 2022年第1期10卷 513-528页

作者： Xiaotong Ding Qinghan Tang Zeyu Xu Ye Xu Hao Zhang Dongfeng Zheng Shuqin Wang Qian Tan Joanneke maitz peter k.maitz Shaoping Yin Yiwei Wang Jun Chen School of Pharmacy Jiangsu Provincial Engineering Research Center of Traditional Chinese Medicine External Medication Development and ApplicationNanjing University of Chinese MedicineNanjing 210023People’s Republic of China Department of Burns and Plastic Surgery The affiliated Drum TowHospital of Nanjing University of Chinese MedicineNanjing 210008People’s Republic of China Burns Injury and Reconstructive Surgery Research ANZAC Research InstituteUniversity of SydneySydneyAustralia2137 Burns Unit Concord Repatriation General HospitalConcordAustralia 2137

Acute and chronic wound infection has become a major worldwide healthcare burden leading to significantly high morbidity and *** underlying mechanism of infections has been widely investigated by scientist,while standard wound management is routinely been used in general ***,strategies for the diagnosis and treatment of wound infections remain a great challenge due to the occurrence of biofilm colonization,delayed healing and drug *** the present review,we summarize the common microorganisms found in acute and chronic wound infections and discuss the challenges from the aspects of clinical diagnosis,non-surgical methods and surgical ***,we highlight emerging innovations in the development of antimicrobial peptides,phages,controlled drug delivery,wound dressing materials and herbal medicine,and find that sensitive diagnostics,combined treatment and skin microbiome regulation could be future directions in the treatment of wound infection.

关键词： Wound infections Skin microbiome Diagnosis Antimicrobial wound dressings Herbal medicine Hydrogels Antimicrobial peptides Phages Drug delivery

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The contradictory role of androgens in cutaneous and major burn wound healing

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Burns & Trauma 2021年第1期9卷 545-557页

作者： Huaikai Shi kenny Cheer Ulla Simanainen Brian Lesmana Duncan Ma Jonathan J.Hew Roxanne J.Parungao Zhe Li Mark S.Cooper David J.Handelsman peter k.maitz Yiwei Wang Burns Research Group ANZAC Research InstituteUniversity of SydneyConcord HospitalGate3 Hospital roadConcordNSW 2139Australia Andrology ANZAC Research InstituteUniversity of SydneyConcord HospitalGate3 Hospital roadConcordNSW 2139Australia Adrenal Steroid Laboratory ANZAC Research InstituteUniversity of SydneyConcord HospitalGate3 Hospital roadConcordNSW 2139Australia Burns and Reconstructive Surgery Unit Concord HospitalGate3 Hospital roadConcordNSW 2139Australia

Wound healing is a complex process involving four overlapping phases:haemostasis,inflammation,cell recruitment and matrix *** mouse models,surgical,pharmacological and genetic approaches targeting androgen actions in skin have shown that androgens increase interleukin-6 and tumor necrosis factor-αproduction and reduce wound re-epithelization and matrix deposition,retarding cutaneous wound ***,clinical studies have shown that cutaneous wound healing is slower in men compared to ***,in major burn injury,which triggers not only local wound-healing processes but also systemic hypermetabolism,the role of androgens is poorly *** studies have claimed that a synthetic androgen,oxandrolone,increases protein synthesis,improves lean body mass and shortens length of hospital ***,the possible mechanisms by which oxandrolone regulates major burn injury have not been *** this review,we summarize the current findings on the roles of androgens in cutaneous and major burn wound healing,as well as androgens as a potential therapeutic treatment option for patients with major burn injuries.

关键词： Wound healing Androgen Mouse model Oxandrolone Cutaneous injury Major burn injury

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Low-protein diet accelerates wound healing in mice post-acute injury

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Burns & Trauma 2021年第1期9卷 339-350页

作者： Jonathan J.Hew Roxanne J.Parungao Craig P.Mooney Julian k.Smyth Sarah kim kevin H.-Y.Tsai Huaikai Shi Cassandra Chong Renee C.F.Chan Beba Attia Caroline Nicholls Zhe Li Samantha M.Solon-Biet David G.Le Couteur Stephen J.Simpson Marc G.Jeschke peter k.maitz Yiwei Wang Burns Research and Reconstructive Surgery ANZAC Research InstituteConcord HospitalUniversity of SydneySydneyAustralia 2139 Bone Biology Group ANZAC Research InstituteConcord HospitalUniversity of SydneySydneyAustralia 2139 Adrenal Steroids Laboratory ANZAC Research InstituteConcord HospitalUniversity of SydneySydneyAustralia 2139 Electron Microscopy Unit Anatomical PathologyConcord HospitalSydneyAustralia 2139 Burns Unit Concord Repatriation General HospitalConcordAustralia 2139 Ageing and Alzheimer Institute and ANZAC Research Institute Concord HospitalUniversity of SydneySydneyAustralia 2139 Charles Perkins Centre and School of Life and Environmental Sciences University of SydneyAustralia 2006 Sunnybrook Research Institute TorontoOntarioCanadaM4N 3M5 School of Pharmacy Nanjing University of Chinese MedicineNanjingPR China 210023

Background:Wound healing processes are influenced by macronutrient intake(protein,carbohydrate and fat).The most favourable diet for cutaneous wound healing is not known,although highprotein diets are currently favoured *** experimental study investigates the optimal macronutrient balance for cutaneous wound healing using a mouse model and the Geometric Framework,a nutrient modelling method,capable of analyzing the individual and interactive effects of a wide spectrum of macronutrient ***:Two adjacent and identical full-thickness skin excisions(1 cm^(2))were surgically created on the dorsal area of male C57BL/6 *** were then allocated to one of 12 high-energy diets that varied in protein,carbohydrate and fat *** select diets,wound healing processes,cytokine expression,energy expenditure,body composition,muscle and fat reserves were ***:Using the Geometric Framework,we show that a low-protein intake,coupled with a balanced intake of carbohydrate and fat is optimal for wound *** fed a low-protein diet progressed quickly through wound healing stages with favourable wound inflammatory cytokine expression and significantly accelerated collagen *** local processes were associated with an increased early systemic inflammatory response and a higher overall energy expenditure,related to metabolic changes occurring in key macronutrient reserves in lean body mass and fat ***:The results suggest that a low-protein diet may have a greater potential to accelerate wound healing than the current clinically used high-protein diets.

关键词： Wound healing Macronutrients Cutaneous Geometric Framework Mouse model Low-protein diet Nutrition

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Cell therapy for severe burn wound healing

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Burns & Trauma 2018年第2期6卷 72-81页

作者： Zhe Li peter maitz Burns Unit Concord HospitalConcordNew South Wales 2139Australia Skin Laboratory NSW Statewide Burns ServiceConcordNew South WalesAustralia Discipline of Surgery University of Sydney Medical SchoolCamperdownNew South WalesAustralia

Cell therapy has emerged as an important component of life-saving procedures in treating burns. Over past decades, advances in stem cells and regenerative medicine have offered exciting opportunities of developing cell-based alternatives and demonstrated the potential and feasibility of various stem cells for burn wound healing. However, there are still scientific and technical issues that should be resolved to facilitate the full potential of the cellular devices. More evidence from large, randomly controlled trials is also needed to understand the clinical impact of cell therapy in burns. This article aims to provide an up-to-date review of the research development and clinical applications of cell therapies in burn wound healing and skin regeneration.

关键词： Skin Burn injuries Stem cells Cell therapy Wound healing Skin regeneration

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An electrospun scaffold loaded with anti-androgen receptor compound for accelerating wound healing

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Burns & Trauma 2013年第2期1卷 95-101页

作者： Cassandra Chong Yiwei Wang peter k. M. maitz Ulla Simanainen Zhe Li Burns & Reconstructive Surgery Research Group Concord Repatriation General Hospital Concord New South Wales 2139 Australia Burns & Reconstructive Surgery Research Group Concord Repatriation General Hospital Concord New South Wales 2139 Australia Burns Unit Concord Repatriation General Hospital Concord New South Wales 2139 Australia Andrology Group of ANZAC Research Institute Concord Repatriation General Hospital Concord New South Wales 2139 Australia

Current dermal regenerative scaffolds provide wound coverage, and structural support and guidance for tissue repair, but usually lack enough bio-signals needed for speeding up skin cell growth, migration, wound closure, and skin regeneration. In this study, an androgen receptor (AR) inhibitor called ASC-J9 is used to demonstrate the concept and feasibility of fabricating drug-loaded scaffolds via electrospinning. Inhibition of androgen is known to promote skin wound healing. The novel ASC-J9 - loaded porous scaffold was fabricated for skin wound repair using electrospun fibers of collagen and polycaprolactone (PCL) blend. Our preliminary results indicated that ASC-J9 - loaded scaffolds facilitated more efficient attachment and ingrowth of dermal fibroblasts, compared to the control collagen-PCL scaffold. A significant increase of cell proliferation was observed with the drug-loaded scaffold over a 28-day period. The drug-loaded scaffold also accelerated keratinocyte migration and wound closure in a contraction-inhibited mouse wound model over 21 days. The data indicated a sustained release of ASC-J9 from the scaffold and its potential to accelerate wound healing by promoting cell proliferation and migration over an extended period of time. More importantly, our results proved the concept and feasibility of fabricating drug-releasing or bioactive dermal scaffolds for more effective wound healing.

关键词： Wound healing electrospun scaffold adrogen receptor inhibition ASC-J9

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An evaluation of Emergency Management of Severe Burn (EMSB) course in Bangladesh: a strategic direction

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Burns & Trauma 2017年第2期5卷 127-133页

作者： Animesh Biswas Fazlur Rahman peter maitz kamran Ul Baset Jahangir Hossain Saidur Rahman Mashreky Centre for Injury Prevention and Research Bangladesh (CIPRB) DhakaBangladesh Centre for Injury Prevention and Research Bangladesh (CIPRB) DhakaBangladesh Department of Epidemiology Bangladesh University of Health Sciences (BUHS) Dhaka Bangladesh The University of Sydney SydneyAustralia

Background: Burn is one of the major public health problems in Bangladesh. Specialized personnel and technologies are required, however, in many cases they are not readily available. Taking the situation into account,Interplast Australia and New Zealand, Australia & New Zealand Burn Association (ANZBA), and Centre for Injury Prevention and Research, Bangladesh (CIPRB) initiated Emergency Management of Severe Burn (EMSB) training programme for Bangladeshi physicians in 2008 to help improving their burn management skill. The study was designed to evaluate the effect of EMSB programme in ***: Both qualitative and quantitative methods were adopted. A cross-sectional survey was conducted to obtain quantitative information from 38 randomly selected EMSB-trained doctors among 380 trained physicians based on a five year database of EMSB (2008-2012). In-depth interviews (IDIs) and focus group discussion (FGD) were used as data collection techniques to get ***: A total of 32 participants completed the interview. It was found that 87.5% (n=28) doctors were using their skill in burn management that they learnt from the EMSB course. About 43.8% (n=14) doctors felt that the course largely helped improve their confidence. Majority (56.2%, n=18) of doctors stated EMSB is essential for the Bangladeshi doctors to learn better management of burns. Qualitative findings show that the courses were organized successfully with an excellent coordination, maintaining same quality and standard as running anywhere in the world. For its effectiveness, the course has been recommended to train graduate nurses and junior doctors from the periphery of the ***: EMSB has already created a large doctor community who are able to effectively manage burn patients. It also has proven its indispensability for learning burn management skill. The EMSB established a platform to serve the burn victims and reduce the burden of injuries in Bangladesh.

关键词： Burn EMSB Bangladesh Low-income countries

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