Role of wound microbiome, strategies of microbiota delivery system and clinical management

Qinghan Tang a,1 , Nannan Xue a,b,1 , Xiaofeng Ding c,d , Kevin H.-Y. Tsai e , Jonathan J. Hew f , Ruihan Jiang a ,

Rizhong Huang a , Xuxi Cheng a , Xiaotong Ding a , Yuen Yee Cheng g , Jun Chen a,b,⇑ , Yiwei Wang a,b,e,⇑

a Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing 210023, PR China

b Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China

c Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China

d Department of Plastic Surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, PR China

e Burns and Reconstructive Surgery Group, ANZAC Research Institute, Concord Hospital, The University of Sydney, Concord West, NSW 2137, Australia

f General Surgery, Lesimore Hospital, NSW 2480, Australia

g Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, University of Technology Sydney, NSW 2007 Australia

abstract

      Delayed wound healing is one of the most global public health threats affecting nearly 100 million people each year, particularly the chronic wounds. Many confounding factors such as aging, diabetic disease, medication, peripheral neuropathy, immunocompromises or arterial and venous insuffificiency hyperglycaemia are considered to inhibit wound healing. Therapeutic approaches for slow wound healing include anti-infection, debridement and the use of various wound dressings. However, the current clinical outcomes are still unsatisfified. In this review, we discuss the role of skin and wound commensal microbiota in the different healing stages, including inflflammation, cell proliferation, re-epithelialization and remodelling phase, followed by multiple immune cell responses to commensal microbiota. Current clinical management in treating surgical wounds and chronic wounds was also reviewed together with potential controlled delivery systems which may be utilized in the future for the topical administration of probiotics and microbiomes. This review aims to introduce advances, novel strategies, and pioneer ideas in regulating the wound microbiome and the design of controlled delivery systems.

article info

Article history:

Received 27 September 2022 Revised 23 November 2022 Accepted 14 December 2022 Available online 17 December 2022

Keywords:

Wound healing，Skin microbiome，Inflammation，Clinical wound care，Cell response to microbiome，Probiotic delivery

Abbreviations: 16S-rDNA, 16S ribosomal DNA identifification; b2-AR, b2-adrenergic receptor; ADAM10, A disintegrin and metalloprotease 10; AHR, aryl hydrocarbon receptor; AMP, adenosine monophosphate; B. subtilis, Bacillus subtilis; C. albicans, Candida albicans; CSF, colony-stimulating factor; CXCL2, chemokine (C-X-C motif) ligand 2; CXCL10, chemokine (C-X-C motif) ligand 10; CXCL12, chemokine (C-X-C motif) ligand 12; DFU, diabetic foot ulcer; ECM, extracellular matrix; E. coli, Escherichia coli; EPB, epidermal permeability barrier; EVs, extracellular vesicles; FDA, Food and Drug Administration; hBD, human b-defensin; HF, Hair follicle; HMP, Human Microbiome Project; IL-1, interleukin-1; IL-1R, interleukin-1R; IL-1b, interleukin-1b; IL-6, interleukin-6; IL-23, interleukin-23; K. pneumoniae, Klebsiella pneumoniae; L. acidophilus, Lactobacillus acidophilus; L. lactis, Lactococcus lactis; L. plantarum, Lactobacillus plantarum; L. reuteri, Lactobacillus reuteri; L. rhamnosus, Lactobacillus rhamnosus; M
CSF, macrophage colonystimulating factor; MHCII, major histocompatibility complex II; MMP-9, matrix metalloproteinase-9; MRSA, methicillin-resistant Staphylococcus aureus; MYD88, myeloid differentiation factor 88; NETs, neutrophil extracellular traps; NIH, National Institutes of Health; NPWT, negative pressure wound therapy; P. aeruginosa, Pseudomonas aeruginosa; pDCs, plasmacytoid dendritic cells; PEO, polyethylene oxide; PLA, polylactic acid; ROS, reactive oxygen species; PRP, Plat-rich plasma; PVA, polyvinyl alcohol; PVP, polyvinyl pyrrolidone; SadA, serum adenosine deaminase; S. aureus, Staphylococcus aureus; Sbi, staphylococcal immunoglobulin-binding protein; SCMC, sodium carboxymethylcellulose; S. epidermidis, Staphylococcus epidermidis; SLO, streptolysin O; SpA, Staphylococcal protein A; SPF, specifific pathogen-free; SSWI, surgical site wound infection; TAs, trace amines; Tc17, cytotoxic T cells 17; TGF-b1, transforming growth factor-b1; TNF-a, tumor necrosis factor-a; VEGF, vascular endothelial growth factor; WHO, World Health Organisation. ⇑ Corresponding authors at: Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, PR China. E-mail addresses: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。, 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J. Chen), 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (Y. Wang). 1 These authors contributed equally to these work.

https://doi.org/10.1016/j.addr.2022.114671 0169-409X/
2022 Published by Elsevier B.V.

Global mortality of diabetic foot ulcer: A systematic review and meta-analysis of observational studies

Lihong Chen MD1 | Shiyi Sun MD1 | Yunyi Gao MD2 | Xingwu Ran MD1

1 Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

2 Department of Medical Affairs, West China Hospital, Sichuan University, Chengdu, China

Correspondence

Xingwu Ran, MD, Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37 Guo Xue Lane, Chengdu 610041, China.

Email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Funding information

This study was partially supported by the Science and Technology Bureau of Sichuan Province (grant no. 2021JDKP004), West China Nursing Discipline Development Special Fund Project, Sichuan University (grant no. HXHL20005) and the 1.3.5 Project for disciplines of excellence, West China Hospital, Sichuan University (grant no. ZYGD18025).

Abstract

Aim: To estimate the long-term mortality and risk factors in patients with diabetic foot ulcer (DFU).

Methods: We systematically searched Medline (PubMed), Embase, Scopus, Web of Science, Cochrane Library, China Science and Technology Journal Database (CQVIP), China National Knowledge Infrastructure, the Chinese Biomedical Literature Database (SinoMed) and Wanfang Data from 1 January 2011 to 31 July 2022. All observational studies that reported long-term mortality of patients with DFU were included. Random effect models were used to pool the reconstructed participant data from Kaplan–Meier curves. The primary outcome was the long-term survival of patients with DFU. An aggregate data meta-analysis was also performed.

Results: We identified 34 studies, with 124 376 participants representing 16 countries, among whom there were 51 386 deaths. Of these, 27 studies with 21 171 patients were included in the Kaplan–Meier-based meta-analysis. The estimated Kaplan–Meier-based survival rates were 86.9% (95% confidence interval [CI] 82.6%- 91.5%) at 1 year, 66.9% (95% CI 59.3%-75.6%) at 3 years, 50.9% (95% CI 42.0%- 61.7%) at 5 years and 23.1% (95% CI 15.2%-34.9%) at 10 years. The results of the aggregate data-based meta-analysis were similar. Cardiovascular disease and infection were the most common causes of death, accounting for 46.6% (95% CI 33.5%-59.7%) and 24.8% (95% CI 16.0%-33.5%), respectively. Patients with older age (per1 year, hazard ratio [HR] 1.054, 95% CI 1.045-1.063), peripheral artery disease (HR 1.882, 95% CI 1.592-2.225), chronic kidney disease (HR 1.535, 95% CI 1.227-1.919), end-stage renal disease (HR 3.586, 95% CI 1.333-9.643), amputation (HR 2.415, 95% CI 1.323-4.408) and history of cardiovascular disease (HR 1.449, 95% CI 1.276-1.645) had higher mortality risk.

Conclusions: This meta-analysis found that the overall mortality of DFU was high, with nearly 50% mortality within 5 years. Cardiovascular disease and infection were the two leading causes of death.

KEYWORDS

cardiovascular disease, diabetic foot, mortality

Challenges faced in developing an ideal chronic wound model

Mandy Li Ling Tan, Jiah Shin Chin, Leigh Madden & David L. Becker

To cite this article: Mandy Li Ling Tan, Jiah Shin Chin, Leigh Madden & David L. Becker (2022): Challenges faced in developing an ideal chronic wound model, Expert Opinion on Drug Discovery,

DOI: 10.1080/17460441.2023.2158809

To link to this article: https://doi.org/10.1080/17460441.2023.2158809

© 2022 The Author(s). Published by Informa

UK Limited, trading as Taylor & Francis

Published online: 26 Dec 2022.

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Mandy Li Ling Tana,b# , Jiah Shin Chinb# , Leigh Maddenb and David L. Beckerb,c,d a Nanyang Institute of Health Technologies, Interdisciplinary Graduate School, Nanyang Technological University, 639798, Singapore; b Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore; c Skin Research Institute Singapore, Clinical Sciences Building, 11 Mandalay Road, 308232, Singapore; d National Skin Centre, Mandalay Road, Singapore

ABSTRACT

Introduction: Chronic wounds are a major drain on healthcare resources and can lead to substantial reductions in quality of life for those affected. Moreover, they often precede serious events such as limb amputations and premature death. In the long run, this burden is likely to escalate with an ageing population and lifestyle diseases such as obesity. Thus far, the identification of beneficial therapeutics against chronic wounds have been hindered by the lack of an ideal chronic wound animal model. Although animal models of delayed healing have been developed, none of these models fully recapitulate the complexity of the human chronic wound condition. Furthermore, most animals do not develop chronic wounds. Only the thoroughbred racehorse develops chronic ulcers.

Areas covered: In this review, the different characteristics of chronic wounds that highlight its complexity are described. In addition, currently available models reflecting different aspects of chronic wound pathology and their relevance to human chronic wounds are discussed. This article concludes by listing relevant features representative of an ideal chronic wound model. Additionally, alternative approaches for the development of chronic wound models are discussed.

Expert opinion: Delayed models of healing, including the streptozotocin diabetic model, skin flap model and magnet-induced IR models have emerged. While these models have been widely adopted for preclinical therapeutic testing, their relevance towards human chronic wounds remains debatable. In particular, current delayed healing models often fail to fully incorporate the key characteristics of chronic ulcers. Ultimately, more representative models are required to expedite the advancement of novel therapeutics to the clinic.

ARTICLE HISTORY

Received 5 October 2021 Accepted 12 December 2022

KEYWORDS

Animal models; biofilm infection; chronic wounds; delayed healing models; delayed wound closure; excessive extracellular matrix degradation; hyper thickened epidermis; increased senescent cells population; persistent inflammation

氦氖激光治疗喀什地区儿童弱视的随机对照研究

艾则孜●吾买尔，姜爱新，曹淑娟

(喀什地区第一人民医院眼科中心，新疆喀什844000)

[摘要] 目的:通过随机对照试验，观察氦氖激光在喀什地区弱视儿童中的治疗效果。方法:选取2016年2月至2018年11月期间就诊喀什地区第一人民医院符合纳排标准的弱视儿童，按随机数字表法，分为试验组(氦氖激光+弱视常规治疗组)与对照组(弱视常规治疗组)，比较两组的弱视治疗效果。
结果:本试验成功纳入弱视儿童111例(177眼),其中试验组61例(97眼)，对照组S0例(80眼)。与对照组相比，汉族试验组弱视儿童效果明显(P=0.023)，维吾尔族试验组弱视儿童未见明显疗效(P=0.481);试验组与对照组在喀什地区不同年龄、不同弱视程度、不同弱视类型及不同弱视眼数儿童中未见明显差异(P>0.05)。结论:氦氖激光治疗喀什地区弱视儿童作用有限，为避免过度医疗，不建议在南疆地区开展。
[关键词] 氦氖激光;弱视;随机对照研究

Efficacy of helium-neon laser in amblyopia of Kashgar children: A randomized controlled trial
AizeziWUMAIER, JIANG Aixin, CAO Shujuan
(Ophthalmological Center, First People's Hospital in Kashgar, Kashgar Xinjiang 844000, China)

Abstract Objective: To observe the therapeutic effect of helium-neon laser in amblyopia children in Kashgar by a randomized controlled trial. Methods: Amblyopia children who met eligibility criteria during February 2016 to November 2018 were selected and divided into two groups according to random number table: test group (helium neon laser + conventional treatment for amblyopia) and control group (conventional treatment for amblyopia). The effects of amblyopia treatment were compared between two groups. Results: One hundred and eleven amblyopic children (177 eyes), including 61 children (97 eyes) of the test group and 50 children (80 eyes) of the control group were included in this study. The efect of helium-neon laser was significant in Han children (P=0.023), but not in Uygur children (P=0.481) in the test group compared with the control group.

Condusion: Helium-neon laser has limited effect in treating children with amblyopia in K ashgar region. To avoid over-treatment, it is not recommended to perform it in southern Xinjiang.
Keywords：helium neon laser; amblyopia; randomized controlled trial

二氧化碳点阵激光美容技术应用于色素痣治疗中临床效果分析

陈敏，高春雪
(吉林国健美容医院，吉林长春，130013)
[摘要]目的探讨激光美容技术治疗色素性疾病色素痣的临床效果，为临床使用提供参考依据。方法选取我院2016年16月~ 2018年16月所收治色素痣色素性疾病患者78例，随机分为研究组和对照组。对照组39例，予以微创切除术;研究组39例，予以激光美容针。比较两组临床表现、疗效、不良反应差异。结果研究组患者中， 创面愈合时间为(8.19士 1.76)d、创面疼痛评分为(2.21+1.07) 分，均显著低于对照组，t分别为8.253、 4.761， 差异具有统计学意义(P< 0.05) 。研究组总有效率为97.44%，明显高于对照组的79 . 49%，(P< 0.05)。研究组患者中，色素沉着12例、红斑1例，不良反应发生率为33.35%，明显低于对照组的69.23%, X2为8.672，差异具有统计学意义(P< 0.05)。结论激激光 美容技术可明显提升色素痣临床疗效，缩短治疗周期，减轻患者痛苦，且不良反应更少，安全性高，更有利于改善患者外貌美观度， 值得临床推广应用。
[关键词]激光美容; 色素痣;不良反应 DOI; 10. 19593/j. issn. 2095-0721. 2019. 01. 016

Clinical effect analysis of carbon dioxide lattice laser cosmetic technique in the treatment of pigmented nevus CHEN Min, GAO Chun-xue (Jilin National Health and Beauty Hospital, Jilin Province, 130013,China)

[ABSTRACT] Objective To investigate the clinical effect of laser cosmetology in the treatment of pigmented nevus of pigmentary diseases, and to provide reference for clinical use. Methods 78 patients with pigmented nevus treated in our hospital from June 2016 to June 2018 were randomly divided into study group and control group. 39 cases in the control group were treated with minimally invasive resection and 39 cases in the study group were treated with laser cosmetic needle. The differences of clinical manifestations,curative effects and adverse reactions between the two groups were compared. Results In the study group, the wound healing time was (8.19+1.76) D and the wound pain score was (2.21+1 .07), which were significantly lower than those in the control group, t was 8.253 and 4.761, respectively, with statistical significance (P <0.05);The total effective rate was 97.44% in the study group, which was signifcantly higher than 79.49% in the control group (P <0.05); There were 12 cases of pigmentation and 1 case of erythema in the study group. The incidence of adverse reactions was 33.33%, which was significantly lower than 69.23% and 8.672 in the control group (P <0.05);. Conclusion Laser Laser Beauty Technology can significantly improve the clinical eficacy of pigmented nevus, shorten the treatment cycle, aleviate the pain of patients, and less adverse reactions, high safety, more conducive to improving the appearance and beauty of patients, worthy of clinical application.

[KEY WORDS] laser cosmetology; pigmented nevus; adverse reactions

阈下微脉冲激光在眼科疾病治疗中的应用

赵宏锟,邹悦,李云琴
引用:赵宏锟,邹悦,李云琴.阈下微脉冲激光在眼科疾病治疗中的应用.国际眼科杂志2020;20(1) :92-95
基金项目:云南省科技厅-昆明医科大学应用基础研究联合专项
资金项目[ No.2017FE467(- 146), 2018FE001(-077)];白求恩●朗沐中青年眼科科研基金( No. BJ-LM2018009J)
作者单位:(650021)中国云南省昆明市,云南省第二人民医院
昆明医科大学第四附属医院云南省眼科医院
作者简介:赵宏锟,硕士研究生,住院医师,研究方向:眼底病。
通讯作者:李云琴,博士,副主任医师，研究方向:眼底病.
liyunqin2004@ 126.com
收稿日期: 2019-06-21
修回日期: 2019-11-21

摘要
阈下微脉冲激光( SML)是-种短促重复的脉冲激光,与传统激光相比,SML不会破坏视网膜色素上皮(RPE)细胞，也不会留下激光斑,是一-种相对安全的治疗手段。SML可能的作用机制是通过重复的阈值下能量激活RPE细胞,促使热休克蛋白表达增加,从而启动RPE细胞的调节修复功能。目前SML的适应证主要有中心性浆液性脉络膜视网膜病变、糖尿病性黄斑水肿、视网膜静脉阻塞继发黄斑水肿、重度非增殖期糖尿病视网膜病变和增殖期糖尿病视网膜病变。本文旨在综述SML的作用机制及其在各适应证中的应用,以期为SML的临床应用提供参考。
关键词:阈下微脉冲激光;应用;机制;中心性浆液性脉络膜视网膜病变;糖尿病性黄斑水肿;糖尿病视网膜病变;视网膜静脉阻塞
DOI: 10.3980/j. issn.1672- 5123.2020.1.21

Process in application of subthreshold micropulse laser
Hong- -Kun Zhao, Yue Zou, Yun- Qin Li .
Foundation items: Yunnan Science and Technology Department -Kunming Medical University Joint Fund for Applied Basic Research [ No.2017FE467(-146); 2018FE001( -077)]; Bethune ●Lumitin Young Ophthalmology Research Fund ( No. BJ-LM2018009J)
The Second People's Hospital of Yunnan Province; the Fourth Affiliated Hospital of Kunming Medical University; Yunnan Eye Hospital , Kunming 650021, Yunnan Province , China
Correspondence to: Yun-Qin Li. The Second People's Hospital of
Yunnan Province ( The Fourth Affiliated Hospital of Kunming
Medical University; Yunnan Eye Hospital)， Kunming 650021 ,
Yunnan Province，China. liyunqin2004@ 126.com
Received :2019-06-21
Accepted:2019-11-21
Abstract
●Subthreshold micropulse laser ( SML) consists of shortrepetitive pulses of laser. This kind of treatment is safe and cheap, and contrary to conventional laser photocoagulation ( LPC )，SML doesn ’t involve destruction of retinal cells and leave no scars. The possible mechanism of SML is to stimulate retinal pigment epithelium ( RPE) cells for the production of heat shock proteins ( HSPs) and regulate its metabolism and improve its function. The clinical indication of SML includes central serous chorioretinopathy ( CSC)，diabetic retinopathy edema ( DME )， nonproliferative diabetic retinopathy ( NPDR) and proliferative diabetic retinopathy ( PDR) and macular edema ( ME) secondary to retinal vein occlusion ( RVO ). This article discussed the mechanism and safety of SML and reviewed the updates of its application.
KEYWORDS: subthreshold  micropulse laser; application; mechanism ; central serous chorioretinopathy; diabetic macular edema; diabetic retinopathy; retinal vein occlusion
Citation: Zhao HK, Zou Y, Li YQ. Process in application of subthreshold micropulse laser. Guoji Yanke Zazhi ( Int Eye Sci ) 2020;20(1) :92-95