细菌生物膜形成与慢性难愈性创面相关性的研究进展

感染是影响慢性难愈性创面愈合最常见的原因,由于多种细菌混合感染、耐药性产生、生物膜的形成使其治疗成为难题.其中,细菌生物膜形成是导致创面的难以愈合的重要因素之一.本文就慢性难愈合创面中细菌生物膜的形成机制、特征、生态学、对伤口愈合的影响以及可能的治疗对策等作一综述.     

基因治疗在慢性难愈创面的应用进展

众多疾病和创伤都会带来损伤创面的难愈问题,慢性难愈创面的长期存在不仅增加了局部感染的机会,而且大大影响了局部组织的结构和功能。基因治疗作为一种新的生物治疗方法,其相关理论和技术近来日臻完善,为慢性难愈创面的治疗提供了新的技术途径,有望带来突破性的治疗效果。     

VSD联合金因肽治疗手足外科难愈性伤口的临床研究

目的:观察封闭式负压引流技术(VSD)联合金因肽治疗手足外科难愈性伤口的临床疗效,为临床联合运用提供依据。方法:86例手足外科难愈性伤口患者随机分为治疗组和对照组各43例,治疗组采用VSD联合金因肽治疗,对照组采用常规换药治疗,观察两组临床疗效和上皮化时间、愈合时间、创面愈合率、换药次数、伤口疼痛评分、住院费用差异。结果:治疗组总有效率90.70%;对照组总有效率72.09%;两组比较,有显著性差异(P0.05);治疗组上皮化时间、愈合时间、创面愈合率、换药次数、伤口疼痛评分、住院费用较对照组相比明显缩短,差异有统计学意义(P0.05)。结论:VSD联合金因肽治疗手足外科难愈性伤口疗效确切,能更好促进损伤组织的修复,加速创面愈合,值得临床推广应用。     

蛆虫清创疗法在难愈性感染创面的临床应用

蛆虫治疗感染创面已有近千年的历史,始载于《本草纲目》,具有良好的疗效。20世纪40年代以后,随着抗生素的广泛使用,蛆虫治疗感染创面的方法逐渐被遗弃。但是随着抗生素的滥用,以及细菌严重耐药性的出现,使得人们开始重新审视这种古老而又充满生机的方法。在难愈性感染创面的治疗过程中,蛆虫通过多种作用机制能够促进创面的愈合,清除大量的坏死组织,促进肉芽组织生长,并有显著的抑菌作用。蛆虫通过多种作用机制协同作用能够促进难愈性感染伤口的愈合,值得进一步的临床研究及推广。本文广泛查阅近年国内外相关文献进行回顾与综合分析。对蛆虫清创疗法在难愈性感染创面的临床应用进行综述。     

负压封闭引流技术促进慢性复杂创面的愈合

目的:探讨负压封闭引流技术(VSD)对慢性复杂创面愈合的治疗效果。方法:选取各类慢性复杂性创面患者共65例,病程均超过3个月,将65例患者随机分为VSD组(35例)及对照组(30例)。VSD组定期更换VSD辅料;2周后视创面愈合情况,选择继续VSD治疗,或行II期修复治疗(直接拉拢缝合,皮片移植,或皮瓣移植修复)。对照组的治疗采用常规换药,即以凡士林油纱布及无菌纱布覆盖创面,内置引流条,每12 h换药一次。两组创面于治疗前及治疗后各个时间点分别对比创面愈合率及创面组织细菌计数。结果:VSD治疗组患者全部愈合,治愈率达100%,对照组30例患者中治愈率为86.7%。两组治愈率相比无明显统计学差异(P0.05)。VSD治疗组平均愈合时间为22±3.3天,对照组平均愈合时间为35±5.8天,两组愈合时间的差异具有统计学意义(P0.01)。治疗后相同检测时间点VSD组创面细菌含量显著低于对照组,两组创面细菌含量的差异具有统计学意义(P0.05)。结论:负压封闭引流技术(VSD)在提高慢性复杂创面的愈合率及清除创面细菌方面具有显著的效果。     

使用富血小板血浆对下肢慢性创面缺损的临床研究分析

目的:研究和探讨使用富血小板血浆(platelet-rich plasma, PRP)在人体下肢慢性创面缺损中的治疗作用,并试图寻找更佳的治疗皮肤慢性缺损的治疗方式。方法:对2016.03-2017.03一年以来在我科治疗,明确诊断为慢性创面缺损的,经纳入和排除标准筛选的共计16名患者进行分析。将其分为实验组(8人)与对照组(8人)。实验组通过对静脉血(肘部)进行抽取离心来制备富血小板血浆并加以覆盖。对照组则使用重组人表皮生长因子进行替代。两组患者均以7天为一疗程,进行换药和更换辅料。比较两组患者的创面愈合情况并比较其血液指标。结果:实验组患者在治疗后1周时观察创面,发现创面无明显渗出及感染征象,其面积缩小约1/4。对照组在1周后进行观察,发现1例有感染可能,给予再次清创并使用抗生素后辅料包扎。其余患者创面肉芽生长可,面积缩小约1/6。在治疗2周后再次进行观察,发现实验组患者创面面积缩小约2/3。而对照组患者面积缩小约1/4。在治疗后3周时,实验组所有患者创面已基本愈合85%以上。在延迟治疗1-2周后该组患者全部愈合。对照组患者在治疗3周后有两例患者愈合面积在50%以上。给予继续使用该治疗方法。剩余6例患者接受外科治疗(VSD+植皮/皮瓣)。实验组患者在各治疗观察点皮肤愈合情况较对照组均有显著改善(P0.05)。两组所有患者均未出现严重并发症。结论:对于下肢慢性创面,使用富血小板血浆进行治疗,能够有效的促进创面愈合,减少手术及外科治疗的风险,降低治疗费用,且相对安全,具有非常重要的临床推广价值。     

中药外治法应用于皮肤创面愈合中的研究进展

中药外治法是指将具有直接作用于创面后使之自然吸收,从而发挥其药物作用的方法,具有便宜快捷、副作用小、疗效显著等优势,但存在组成复杂、起效时间长、作用机制尚不清楚的问题。本文简述了中药外治法应用于急性创面和慢性创面两种不同愈合周期的创面,归纳了不同组方、不同中药制剂应用于不同类型的创面,得出了治疗手术创面主要采用熏洗法、油膏涂抹法和外敷法,常用的中药是苦参、大黄等;治疗急性褥疮创面主要采用外敷法、油膏涂抹法和中药外敷法联合护理法,常用的中药有黄芩、黄连;治疗溃疡性创面主要采用外敷法和泡洗法,常用的中药有三七、黄柏等;治疗烧伤主要采用油膏涂抹法或浸浴法,常用的中药有黄连、冰片、大黄;治疗感染的、难以愈合的创面一般采用中药浸泡法、外敷法,常用的中药有黄柏、金银花等,旨在为提高中药在创面愈合临床上的应用提供参考。     

负压创面治疗肝源性糖尿病并发糖尿病足的研究

目的:讨论创面负压治疗促进肝硬化合并糖尿病并发糖尿病足的临床疗效。方法:将30例慢性肝硬化合并糖尿病并发糖尿病足患者随机分为创面负压治疗组和敷料包扎组,观察两组创面细菌负荷及创面微循环血流量变化。结果:清创即刻,负压创面治疗组和敷料包扎组细菌负荷与创面微循环血流量无显著差异(P>0.01);创后3天、6天和9天时,负压创面组创面细菌负荷低于敷料包扎组(P<0.01),创面微循环血流量高于敷料包扎组(P<0.01)。负压创面组创面愈合时间少于敷料包扎组(P<0.01)。结论:负压创面治疗有助于慢性肝硬化并发糖尿病合并糖尿病足的创面愈合。     

负压封闭辅助闭合技术在难愈性伤口中的疗效观察

目的观察负压封闭辅助闭合（VAC）技术在难愈性伤口中的临床疗效。方法对我院2011年1月~2013年1月收治的19例难愈性伤口患者（为观察组）采用美国KCI公司VAC治疗系统进行负压封闭治疗,并随机选择2011年以前收治的难愈性伤口患者19例（为对照组）,采用常规换药治疗。观察比较两组患者伤口愈合率、愈合时间及换药次数。结果与对照组相比,观察组的伤口愈合率较高（P〈0.05）;伤口平均愈合时间缩短,平均换药次数明显减少（均P〈0.01）。结论 VAC技术治疗难愈性伤口的疗效明显,值得临床推广。     

老年难愈性创面患者临床特征及创面细菌学分析

目的分析老年难愈性创面患者的临床特征、创面细菌学及疗效,为临床治疗提供参考依据。方法回顾性分析我科2012年1月至2017年12月收治的114例老年难愈性创面患者的临床资料。对患者合并内科基础疾病、生理机能状况、创面病因和部位、创面分泌物细菌和多重耐药菌分布、创面治疗效果等进行分析。结果患者常见内科基础疾病有高血压(63例)、糖尿病(42例)、脑血管疾病(38例)和心脏病(31例),常见生理指标异常为白蛋白降低(89例)和贫血(70例)。本组共有186处创面(37例患者有1个以上创面),常见病因为烧伤(44.62%)、压迫(35.48%),常见病变部位为下肢(67.74%)。创面分离出病原菌113株,革兰阴性菌占71.68%。常见菌为铜绿假单胞菌(35.40%)、金黄色葡萄球菌(25.66%)、大肠埃希菌(12.39%)。多重耐药菌检出率为71.68%(81/113)。本组创面的治疗效果为:治愈94处、好转64处、未愈28处。38.17%创面进行了手术治疗。手术治疗的疗效为治愈58处、好转10处、未愈3处,明显优于非手术治疗(Z=-6.478,P=0.000)。结论老年难愈性创面患者合并内科基础病多、生理机能状况差,创面细菌以革兰阴性球菌为主、多重耐药菌比例高,创面治疗效果偏差,手术比例低,但手术治疗取得了较好疗效。     

Multipotent adult progenitor cells: their role in wound healing and the treatment of dermal wounds

The use of cellular therapy in the treatment of dermal wounds is currently an active area of investigation. Multipotent adult progenitor cells (MAPC) are an attractive choice for cytotherapy because they have a large proliferative potential, the ability to differentiate into different cell types and produce a variety of cytokines and growth factors important to wound healing. Whole bone marrow (BM) was one of the initial attempts to treat impaired wounds. While it has shown some promise, the low frequency of progenitor cell populations in BM and the large number of inflammatory cells make it less attractive. Multipotent mesenchymal stromal cells (MSC) and endothelial progenitor cells are populations of BM-derived progenitor cells that have been isolated and used to treat chronic wounds with some success. Skin-derived MAPC are another heterogeneous population of progenitor cells present in the skin with the potential to differentiate into skin elements and participate in wound healing. All of these progenitor cell populations are potential sources for cytotherapy of wounds. This review focused on the contribution of adult progenitor cell populations to dermal wound healing and their potential for use in cytotherapy.     

EGF and TGF-alpha in wound healing and repair

Wound healing is a localized process which involves inflammation, wound cell migration and mitosis, neovascularization, and regeneration of the extracellular matrix. Recent data suggest the actions of wound cells may be regulated by local production of peptide growth factors which influence wound cells through autocrine and paracrine mechanisms. Two peptide growth factors which may play important roles in normal wound healing in tissues such as skin, cornea, and gastrointestinal tract are the structurally related peptides epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). EGF/TGF-alpha receptors are expressed by many types of cells including skin keratinocytes, fibroblasts, vascular endothelial cells, and epithelial cells of the GI tract. In addition, EGF or TGF-alpha are synthesized by several cells involved in wound healing including platelets, keratinocytes, and activated macrophages. Healing of a variety of wounds in animals and patients was enhanced by treatment with EGF or TGF-alpha. Epidermal regeneration of partial thickness burns on pigs or dermatome wounds on patients was accelerated with topical application of EGF or TGF-alpha, and EGF treatment accelerated healing of gastroduodenal ulcers. EGF also increased tensile strength of skin incisions in rats and corneal incisions in rabbits, cats, and primates. Additional research is needed to better define the roles of EGF, TGF-alpha and their receptor in normal wound healing, to determine if alterations have occurred in the EGF/TGF-alpha system in chronic wounds, and optimize vehicles for effective delivery of peptide growth factors to wounds.     

Wound healing enhancement in leg ulcers: A case report

Wound healing in the skin is a complex biological process in which numerous types of cells, cytokines, growth factors, proteases and extracellular matrix components act in concert to restore the integrity of injured tissue. Cultivated allogenic human keratinocytes have been used for the treatment of various skin defects like burnwounds, surgical wounds, in exfoliative skin diseases and chronic wounds. A new method for wound healing enhancement in leg ulcers using cultured allogenic keratinocytes suspended in fibrin glue and used in spray technique is introduced. Allogenic keratinocytes are supposed to enhance granulation tissue production and to stimulate reepithelisation due to their release of growth factors and thus are able to recreate an active wound. This revised version was published online in July 2006 with corrections to the Cover Date.     

Leptin Promotes Wound Healing in the Skin

Introduction

Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties. Interestingly, skin wound healing was proven to delay in leptin-deficient ob/ob mice. However, little is known on the mechanisms of this phenomenon. In this study, we attempted to elucidate a role of leptin in wound healing of skin.

Methods

Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R) in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of wound repair was histologically observed and the area of ulceration was measured over time. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated.

Results

Ob-R was expressed in epidermal cells of human and mouse skin. Topical administration of leptin significantly promoted wound healing. Histological analysis showed more blood vessels in the dermal connective tissues in the leptin-treated group. The proliferation, differentiation/function and migration of human epidermal keratinocytes were enhanced by exogenous leptin.

Conclusion

Topically administered leptin was proven to promote wound healing in the skin by accelerating proliferation, differentiation/function and migration of epidermal keratinocytes and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the skin.     

The effect of induced biphasic pulsed currents on re-epithelialization of a novel wound healing model

The coordinated migration of keratinocytes is crucial to cutaneous wound healing; failure of keratinocytes to migrate into a wound can lead to chronic non-healing wounds. Keratinocyte migration can be influenced by applied electrical fields. Our aim was to investigate whether keratinocyte migration could be accelerated by applying an induced biphasic pulsed electrical field. We developed two in vitro biological systems models for this purpose: a keratinocyte colony-forming model and a reconstituted skin wound healing model with biphasic pulsed currents. Our in vitro skin models were capable of generating trans-epithelial potentials (TEP) similar to in vivo mammalian skin. Histological examination of the wound healing model also indicated that re-epithelialization occurred in a similar manner to that seen in vivo, although no evidence of a reconstitution of a basement membrane was seen during the 14 days in vitro experimental period. We found that growth of keratinocyte colonies and keratinocyte migration in an in vitro wound bed were not significantly affected by induced short duration biphasic pulsed currents at a frequency of 0.5 Hz of 100 and 200 mV/mm.     

Promotive effects of far-infrared ray on full-thickness skin wound healing in rats

The biological effects of far-infrared ray (FIR) on whole organisms remain poorly understood. The aim of our study was to investigate not only the hyperthermic effect of the FIR irradiation, but also the biological effects of FIR on wound healing. To evaluate the effect of FIR on a skin wound site, the speed of full-thickness skin wound healing was compared among groups with and without FIR using a rat model. We measured the skin wound area, skin blood flow, and skin temperature before and during FIR irradiation, and we performed histological inspection. Wound healing was significantly more rapid with than without FIR. Skin blood flow and skin temperature did not change significantly before or during FIR irradiation. Histological findings revealed greater collagen regeneration and infiltration of fibroblasts that expressed transforming growth factor-beta1 (TGF-beta1) in wounds in the FIR group than in the group without FIR. Stimulation of the secretion of TGF-beta1 or the activation of fibroblasts may be considered as a possible mechanisms for the promotive effect of FIR on wound healing independent of skin blood flow and skin temperature.     

微小RNA miR-21在皮肤创伤愈合中的研究进展

微小RNA是一类真核细胞中广泛存在的内源性转录后调控分子,其在细胞的增殖、分化、凋亡、迁移等过程中发挥了重要的调控作用。皮肤创伤修复涉及复杂的细胞与分子的相互作用网络。近年来研究表明micro RNAs在皮肤创伤修复中发挥调控作用,引人关注。miR-21作为重要的癌基因是目前研究的最多的miRNAs分子之一,其在皮肤创伤修复中的作用研究也越来越受到重视。研究表明miR-21参与了细胞增殖与迁移、炎症反应、血管生成和细胞外基质合成等重要修复相关事件的调控。因此,阐明miR-21分子在正常皮肤创伤愈合中的作用,厘清miR-21表达失调在修复不足和修复过度中的功能,将深化我们对于皮肤创伤愈合基本理论的认识,并为促进创面愈合与防治修复不足和过度提供潜在的治疗靶点。本文就miR-21分子在正常皮肤创伤修复、慢性难愈性创面和增生性瘢痕中作用的研究进展进行综述展望。     

A potential wound healing-promoting peptide from frog skin

Cutaneous wound healing is a dynamic, complex, and well-organized process that requires the orchestration of many different cell types and cellular processes. Transforming growth factor β1 is an important factor that plays a key role during wound healing. Amphibian skin has been proven to possess excellent wound healing ability, whilst no bioactive substrate related to it has ever been identified. Here, a potential wound healing-promoting peptide (AH90, ATAWDFGPHGLLPIRPIRIRPLCG) was identified from the frog skin of Odorrana grahami. It showed potential wound healing-promoting activity in a murine model with full thickness dermal wound. AH90 promoted release of transforming growth factor β1 through activation of nuclear factor-κB and c-Jun NH2-terminal kinase mitogen-activated protein kinases signaling pathways, while inhibitors of nuclear factor-κB and c-Jun NH2-terminal kinase inhibited the process. In addition, the effects of AH90 on Smads family proteins, key regulators in transforming growth factor β1 signaling pathways, could also be inhibited by transforming growth factor β1 antibody. Altogether, this indicated that AH90 promoted wound healing by inducing the release of transforming growth factor β1. This current study may facilitate the understanding of effective factors involved in the wound repair of amphibians and the underlying mechanisms as well. Considering its favorable traits as a small peptide that greatly promoting generation of endogenous wound healing agents (transforming growth factor β1) without mitogenic effects, AH90 might be an excellent template for the future development of novel wound-healing agents.     

Cytokines, growth factors, and plastic surgery.

Numerous inflammatory cytokines and growth factors have been identified and are known to be essential for normal wound healing and host defense, and many have been implicated in disease states treated by plastic surgeons. Cytokines and growth factors are members of a large functional group of polypeptide regulatory molecules secreted by different cell lines. These peptides exert their influence through autocrine and paracrine fashions within sites of injury and repair. Although cytokines and growth factors are crucial in initiating, sustaining, and regulating the postinjury response, these same molecules have been implicated in impaired wound healing, abnormal scarring, and chronic cutaneous diseases. Therapeutic manipulation of inflammatory mediators in normal and impaired wounds has been performed, with mixed clinical results, but evolving strategies such as gene therapy, as well as further characterization of the cellular-mechanism cytokines and growth-factor triggers, will further add to our therapeutic options. This article discusses the current understanding of important cytokines and growth factors involved in the normal injury response and then addresses pathological states associated with an inappropriate expression of these mediators. Finally, a summary of various cytokine and growth factor-directed strategies being used in impaired wound healing states is presented.