The influence of tissue oxygen and perfusion on wound healing

The availability of oxygen (O2) to cells in the wound area and the presence of adequate blood flow are important factors to the healing process. Oxygen plays a critical role in the formation of collagen, the growth of new capillaries, and the control of infection. Perfusion and delivery of O2 to tissue are closely related. Although an adequate blood flow does not guarantee a sufficient supply of O2, without it the provision of O2 to healing tissues will be impaired. Basic scientific studies have clarified how O2 and blood flow influence healing. Recent research has focused on clinical populations and begins to provide direction for additional clinical studies and interventions to support the healing process. Based on existing research, clinical interventions aimed to maintain perfusion and supply of O2 include fluid volume assessments, pulmonary hygiene regimens, postoperative position changes, and ambulation.     

Androgen receptor-mediated inhibition of cutaneous wound healing

Impaired wound healing states in the elderly lead to substantial morbidity, mortality, and a cost to the US Health Services of over $9 billion per annum. In addition to intrinsic aging per se causing delayed healing, studies have suggested marked sex-differences in wound repair. We report that castration of male mice results in a striking acceleration of local cutaneous wound healing, and is associated with a reduced inflammatory response and increased hair growth. Using a hairless mouse model, we have demonstrated that testosterone reduction stimulates the healing response not through hair follicle epithelial/mesenchymal cell proliferation, but directly via effects on wound cell populations. We suggest that endogenous testosterone inhibits the cutaneous wound healing response in males and is associated with an enhanced inflammatory response. The mechanisms underlying the observed effects involve a direct upregulation of proinflammatory cytokine expression by macrophages in response to testosterone. Blockade of androgen action systemically, via receptor antagonism, accelerates healing significantly, suggesting a specific target for future therapeutic intervention in impaired wound healing states in elderly males.     

基质细胞衍生因子1α促进皮肤创面的新血管形成

背景:基质细胞衍生因子1α是有促进血管生成作用的CXC类趋化因子,研究发现其在调节一些重要组织/器官的损伤修复过程中有重要作用,但对其在皮肤创伤愈合过程中的作用还不很清楚.目的:观察基质细胞衍生因子1α在创面新生血管形成过程中的作用.设计、时间及地点:随机对照动物实验,于2008-06/08在解放军第三军医大学大坪医院野战外科研究六室完成.材料:SPF级昆明小鼠60只,雌雄不拘,体质量25～30g;基质细胞衍生因子1α抗体为美国Santa Cruz Biotechnology 公司产品.方法:建立小鼠背部全层皮肤缺损伤模型,分为3组,即对照组,10mg/L基质细胞衍生因子1α抗体组和20 mg/L基质细胞衍生因子1α抗体组,每组20只.各组分别在创面及创周连续6d注射不同质量浓度的基质细胞衍生因子1α抗体(0,10,20mg/L).主要观察指标:创伤后3,4,5,6,7 d,以半定量反转录-聚合酶链反应检测创面CD146表达情况,并观察创面微血管密度及创面收缩率.结果:伤后各天,10 mg/L抗体组和20 mg/L抗体组CD146 mRNA表达和微血管密度均少于对照组(P<0.05),伤后5,6,7 d,抗体组CD146 mRNA表达和微血管密度多于3,4 d(P<0.05);伤后6,7 d,10 mg/L抗体组创面收缩率低于对照组(P<0.05),伤后5,6,7 d,20 mg/L抗体组创面收缩率低于对照组(P<0.05),抗体组间仅在伤后7d差异有显著性意义(P<0.05).结论:阻断创面基质细胞衍生因子1α作用,能够降低创面新血管化程度,从而可能影响创面愈合速度.     

Legal concerns in tissue viability and wound healing

In an age of increasing litigation, it is important for tissue viability practitioners to be aware of the legal issues surrounding their practice. Bridgit Dimond discusses some of the legal aspects that were raised as concerns by participants recently attending a post-graduate diploma course in tissue viability and wound healing. She clarifies the main legal requirements for healthcare professionals working in this field.     

组织纤维连接蛋白在软组织创伤修复中的作用

目的：探讨组织纤维连接蛋白在软组织创伤修复过程中的变化和意义。方法：采用大鼠腓肠肌钝击伤模型,分别于伤后８ｈ ,２４ｈ ,７２ｈ ,７ｄ 和１２ｄ 进行一般观察、组织切片、纤维连接蛋白免疫组化观察。结果： 创伤后组织纤维连接蛋白迅速增加,于伤后７２ｈ 达高峰,第７ｄ 开始消退,纤维连接蛋白阳性区主要分布于变性、坏死区域和小血管周围。７２ｈ 后成纤维细胞明显增多,细胞纤维连接蛋白阳性,但阳性程度不如前者。结论：软组织创伤修复过程中组织纤维连接蛋白主要来源于血浆纤维连接蛋白的沉积,而后期则有一部分来自成纤维细胞的合成     

Multimodal noninvasive monitoring of soft tissue wound healing

Here we report results of non-invasive measurements of indirect markers of soft tissue healing of traumatic wounds in an observational swine study and describe the quantification of analog physiological signals. The primary purpose of the study was to measure bone healing of fractures with four different wound treatments. A second purpose was to quantify soft tissue wound healing by measuring the following indirect markers: (1) tissue oxygenation, (2) fluid content, and (3) blood flow, which were all measured by non-invasive modalities, measured with available devices. Tissue oxygenation was measured by near infrared spectroscopy; fluid content was measured by bipolar bio-impedance; and blood flow was measured by Doppler ultrasound. Immediately after comminuted femur fractures were produced in the right hind legs of thirty anesthetized female Yorkshire swine, one of four wound treatments was instilled into each wound. The four wound treatments were as follows: salmon fibrinogen/thrombin—n = 8; commercial bone filler matrix—n = 7; bovine collagen—n = 8; porcine fibrinogen/thrombin—n = 7. Fractures were stabilized with an external fixation device. Immediately following wound treatments, measurements were made of tissue oxygenation, fluid content and blood flow; these measurements were repeated weekly for 3 weeks after surgery. Analog signals of each modality were recorded on both the wounded (right) hind leg and the healthy (left) hind leg, for comparison purposes. Data were processed off-line. The mean values of 10-s periods were calculated for right–left leg comparison. ANOVA was applied for statistical analysis. Results of the bone healing studies are published separately (Rothwell et al. in J Spec Oper Med 13:7–18, 2013). For soft tissue wounds, healing did not differ significantly among the four wound treatments; however, regional oxygenation of wounds treated with salmon fibrinogen/thrombin showed slightly different time trends. Further studies are needed to establish standards for healthy wound healing and for detection of pathological alterations such as infection. Non-invasive measurement and quantification of indirect markers of soft tissue wound healing support the goals and principles of evidence-based medicine and show potential as easy to administer tools for clinicians and battlefield medical personnel to apply when procedures such as the PET scan are not available or affordable. The method we developed for storing analog physiological signals could be used for maintaining electronic health records, by incorporating vital signs such as ECG and EEG, etc.     

脂肪组织促进创面愈合的机制

背景:随着对脂肪组织研究的不断深入,脂肪组织在创面愈合中的作用备受关注,脂肪组织促进创面愈合的机制以及应用方面的研究广泛开展.目的:文章从脂肪因子和脂肪干细胞两方面探讨脂肪组织促进创面愈合的机制,并就相关应用研究进行归纳分析,为临床创面治疗提供理论依据.方法:由第一作者用计算机检索中国期刊全文数据库(CNKI:2009/2010)和PubMed数据库(2009/2010),检索词分别为"脂肪组织,瘦素,抵抗素,脂肪干细胞,创面愈合"和"adipose tissue,leptin,resistin,adipose-derived stem cells,wound healing",语言分别设定为中文和英文.从脂肪因子和脂肪干细胞两方面入手,对脂肪组织促进创面愈合的机制及脂肪组织促进创面愈合的现有研究进行介绍.结果与结论:共检索到文献329篇,阅读标题和摘要后,按纳入标准,共纳入31篇.总结并分析文献内容后发现,血管再生、成纤维细胞及角朊细胞等的增殖是创面愈合的关键,而脂肪组织可通过脂肪干细胞及分泌脂肪因子促进血管内皮、成纤维、角朊等细胞增殖的方式,促进创面愈合,提高创面愈合质量.但有关创烧伤过程脂肪因子的调控机制,脂肪干细胞增殖、分化的机制,以及如何进而进一步提高创面愈合速率及质量等问题,仍需进一步研究.     

成骨细胞特异性因子2periostin及相关因子在大鼠全层缺损皮肤创面愈合过程中的表达

目的 观察大鼠皮肤缺损创面愈合过程中成骨细胞特异性因子2 periostin( PN)与血管生成素-1(Ang-1)、血管内皮生长因子(VEGF)及其受体2[VEGFR-2/胎肝激酶-1(FLK-1)]在创面及创缘周围皮肤的表达及对创面愈合的影响.方法 48只成年雄性SD大鼠按随机数字表法分成6组,每组8只.在大鼠背中部脊柱两侧各制作一个2cm×2cm全层皮肤缺损创面,分别于术后1、4、7、10、14、21d创面取材,行病理组织学检查及免疫组化染色检测创面PN、Ang-1、VEGF、FLK-1的表达;并以正常皮肤的表达量作为对照组.结果 创面局部组织中各因子的表达量在术后均迅速升高.与对照组比较,创面PN的表达量在术后1d即增加了234.4％,之后持续升高,至7d增加了597.9％并达到峰值,其后缓慢下降,21 d时增长率为280.9％,仍维持在较高水平(均P＜0.05);Ang-1的表达量在术后1d增加了128.1％,4d增加了327.5％并达到峰值,然后逐渐下降,14d的增长率仅为80.5％,之后轻度升高(均P＜0.05);VEGF的表达量在术后7d增加了165.8％并达到峰值,而后下降并伴有小幅波动(均P＜0.05):FLK-1术后1d增加了56.1％并维持这一水平,至7d增加了70.1％达峰值(均P＜0.05),10d后缓慢下降(均P＞0.05).结论 大鼠皮肤创面愈合过程中,PN、Ang-1、VEGF及其受体FLK-1蛋白均高表达,但各因子的表达高峰和持续时间有所不同.PN的表达量增幅最高且始终维持较高水平至创面表皮化后;说明PN、Ang-1、VEGF、FLK-1共同参与了大鼠皮肤创面的愈合,PN在创面愈合的整个过程巾发挥着重要作用.     

Therapeutic touch, nursing practice and contemporary cutaneous wound healing research

The nursing profession is and always has been at the cutting edge of research and development into innovative and effective methods to treat, manage and enhance wound regeneration. One such method which was developed specifically for nursing science is a non-invasive, easily administered technique known as therapeutic touch (TT). Although there have been numerous anecdotal reports over the last two decades attesting to the efficacy of TT for cutaneous wounds, there have been only five experimental studies to date which have examined the phenomena in a scientifically rigorous manner. These five studies utilized randomized, double-blind, placebo controlled protocols to analyse the effect of an experimental derivative of TT-non-contact therapeutic touch (NCIT)-on the healing rate of surgically administered full thickness human dermal wounds. The experiments introduced many original concepts and approaches to healing research and nursing practice. The data from the five studies indicated a statistically significant accelerated rate of wound healing for the treatment group in the initial two experiments, and nonsignificant and reverse significant effects for the remaining three studies. Although, experimentally, these results are far from impressive, clinically, the significant results of the first two experiments should be enough to encourage the nurse clinican to explore and utilize a similar non-invasive TT treatment method for patients with dermal lacerations. While the results of the studies were inconsistent overall, the series of experiments nonetheless significantly expanded the theorectical boundaries and understanding of the TT process and, due to the rigorous, double-blind methodological protocols used, have established the critical groundwork and guidelines for future nursing science research in the area.     

烧伤创面愈合过程中胶原代谢与针刺作用的影响

背景：针刺可促进烧伤创面愈合，但对创面组织胶原代谢的影响尚不清楚。目的：观察针刺对烧伤创面愈合过程中胶原代谢的影响。设计、时间及地点：随机对照动物实验，于1997—01／2005—12在广州市创伤外科研究所完成。材料：雌性新西兰大白兔27只，体质量2．0～2．5妇，用于制备深Ⅱ度烧伤模型。 方法：每个兔背部脊柱两旁造成10个创面。实验分为3组，正常组（n=3）：只背部剃毛备用；常规治疗组：伤后自由进食，创面外用25g／L的碘伏暴露：针刺组：在常规治疗的基础上，伤后24h内开始针刺治疗，取双侧“足三里（ST36）”穴，针刺后接电针仪，频率20Hz，时间30min，1次/d。伤后3，7，13，21d常规治疗组和针刺组各取3只动物处死，取组织待测。主要观察指标：各组动物不同时间点创面组织中羟脯氨酸水平。 结果：27只大白兔均进入结果分析。烧伤后13d常规治疗组和针刺组创面组织中羟脯氨酸水平均低于正常皮肤组织（P〈0．05）。伤后21d常规治疗组创面组织中羟脯氨酸达到正常皮肤组织水平，两组相比差异无显著性意义（P〉0．05）。而针刺组创面组织中羟脯氨酸水平高于常规治疗组和正常皮肤组织（P〈0．05）。结论：针刺可促进烧伤创面胶原的合成。     

Effects of high voltage stimulation on cutaneous wound healing in rabbits

The primary purpose of this study was to determine whether high voltage stimulation (HVS) enhances wound healing. Forty female rabbits were assigned to experimental or control groups and followed for four or seven days. We classified the groups as Exp4, Con4, Exp7, and Con7, respectively. Each animal was anesthetized, and a full-thickness incision, 3.5-cm long, was made on its back. After 24 hours, Exp4 and Exp7 rabbits received HVS with a negative polarity for two hours twice daily. Although tensile-strength values were 36% higher for Exp4 rabbits than for Con4 rabbits, no significant differences in tensile strength or percentage of wound closure existed between the two groups. After seven days, Con7 rabbits had a higher percentage of wound closure and significantly greater tensile-strength measures than Exp7 rabbits. Histologic examination of the wounds did not provide clear-cut evidence of differences between the experimental and control groups. Results suggest that 1) HVS did not significantly improve wound healing for Exp4 rabbits and 2) HVS as given, may have hampered the healing process for Exp7 rabbits.     

Tissue and wound healing effects of short duration postoperative oxygen therapy

The purpose of this study was to determine the effects of 28% oxygen given in the first 36 hours after surgery on tissue oxygen, collagen deposition, and clinical healing outcomes. Twenty-four subjects having cervical spine surgical procedures participated in a randomized, repeated-measures pilot study of tissue and healing effects of postoperative supplemental oxygen. The treatment group (n = 13) received 28% oxygen for the first 36 postoperative hours, whereas the control group (n = 11) was maintained on room air. Subcutaneous tissue oxygen and temperature were measured at intervals up to 36 hours postsurgery. Wound healing was evaluated by hydroxyproline content in a subcutaneous polytetrafluoroethylene tube removed on the 7th postoperative day. Clinical outcomes were evaluated for the 30 days post-hospital discharge. Subjects in the treatment group had significantly higher tissue oxygen tension overall, and at postoperative hours 1, 2, 18, and 36, with mean values 10 to 20 mm Hg higher than control subjects. Significant differences were not found in hydroxyproline levels or clinical wound outcome measures. Low level, short duration, supplemental oxygen increased and sustained wound tissue oxygen and was well tolerated by subjects. Larger studies of populations at risk for wound complications are needed to investigate variables of dose and duration of oxygen therapy in relation to clinical and cellular wound healing outcomes.     

脂联素在脂肪组织切口愈合中的作用及机制研究

目的 观察脂联素在脂肪组织切口愈合（ATWH）中的作用,探讨脂联素在ATWH中的作用机制.方法 制作猪ATWH模型;随机分为脂联素干预组和对照组（各组n=5）,观察ATWH等级,分析脂联素对ATWH的影响.应用免疫荧光标记技术和电镜观察脂肪细胞凋亡变化情况,分析脂联素水平对脂肪细胞凋亡的影响.结果 干预组切口愈合等级显著优于对照组（P〈0.05）;干预组脂肪细胞凋亡率明显少于对照组（P〈0.05）.结论 脂联素通过抑制脂肪细胞的凋亡促进ATWH.     

牛磺酸铜干预感染愈合创面血管内皮生长因子A的表达*☆

背景:铜具有广谱杀菌及耐药性强的特点,而且铜作为人体必需微量元素在创面愈合过程中发挥着重要作用.作者前期的实验得到了利于生物体吸收的牛磺酸铜有机化合物.目的:检测牛磺酸铜的抗菌活性及其对感染创面愈合过程中血管内皮生长因子A表达的影响.方法:①通过MTT比色法检测牛磺酸铜对金黄色葡萄球菌的最低抑菌浓度.②72只SD大鼠随机分为牛磺酸铜组与生理盐水组两组,于每只大鼠背部制作1个直径1.5 cm的圆形金黄色葡萄球菌感染创面.牛磺酸铜组创面应用最低抑菌浓度的牛磺酸铜溶液1 mL,生理盐水组创面应用生理盐水1 mL,隔日用药1次,直到创面完全愈合.结果与结论:①经测定牛磺酸铜对金黄色葡萄球菌的最低抗菌浓度为4 g/L.②用药后第7,10天,牛磺酸铜组创面愈合率明显高于生理盐水组(P <0.05);至第21天,两组创面都完全愈合.③组织学观察显示:用药后第7天,牛磺酸铜组肉芽组织更成熟;用药后第14天,牛磺酸铜组胶原纤维排列整齐,瘢痕窄,胶原内可见再生的毛囊和皮脂腺.④免疫组织化学检测创面血管内皮生长因子A的表达变化显示:牛磺酸铜组血管内皮生长因子A在用药后第3天表达明显高于生理盐水组(P <0.01),第7,10天,牛磺酸铜组血管内皮生长因子A表达量下降,但仍高于生理盐水组(P <0.05).其余时间点表达未见明显差异(P >0.05).证实感染创面外用牛磺酸铜药液可以发挥有效的杀菌作用,提高创面愈合率,促进大鼠感染创面血管内皮生长因子A的表达,从而提高创面的愈合质量.     

Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor

Characteristic of both chronic wounds and acute wounds that fail to heal are excessive leukocytosis and reduced matrix deposition. Estrogen is a major regulator of wound repair that can reverse age-related impaired wound healing in human and animal models, characterized by a dampened inflammatory response and increased matrix deposited at the wound site. Macrophage migration inhibitory factor (MIF) is a candidate proinflammatory cytokine involved in the hormonal regulation of inflammation. We demonstrate that MIF is upregulated in a distinct spatial and temporal pattern during wound healing and its expression is markedly elevated in wounds of estrogen-deficient mice as compared with intact animals. Wound-healing studies in mice rendered null for the MIF gene have demonstrated that in the absence of MIF, the excessive inflammation and delayed-healing phenotype associated with reduced estrogen is reversed. Moreover, in vitro assays have shown a striking estrogen-mediated decrease in MIF production by activated murine macrophages, a process involving the estrogen receptor. We suggest that estrogen inhibits the local inflammatory response by downregulating MIF, suggesting a specific target for future therapeutic intervention in impaired wound-healing states.     

糖尿病创面愈合过程的动态组织学特征

目的:动态观察糖尿病创面愈合过程及其组织学的特征,探讨糖尿病创面难愈可能的机制。方法:2001-06/2003-06广西医科大学第一附属医院烧伤整形康复中心采用15例糖尿病足部溃疡手术患者的供皮区共45个创面为实验组,以瘢痕整形手术患者供皮区为对照组,分别对术后第3,7,14天创面的上皮葡行情况、肉芽组织成熟程度、创面组织学特征进行动态观察,并取材。免疫组化方法检测皮肤创面局部糖基化终末产物(advancedglycationendproducts,AGEs)。结果:糖尿病创面上皮葡行以及肉芽成熟程度在早期与非糖尿病创面愈合过程无明显差异(P>0.05),但在愈合过程的中晚期明显滞后于非糖尿病创面愈合,术后14d时,术后创面残余面积实验组(0.92±0.09)cm2,对照组(0.78±0.10)cm2,肉芽组织成熟程度实验组“10例,“3例,对照组“3例,“5例,7“例(t=4.0303,P<0.05,或χ2=6.6516,6.7081,P<0.01)。组织学显示,糖尿病创面新生胶原稀疏、细小,极性差;新生的基底膜细小;已上皮化的创面仍可见较多的炎性细胞。糖尿病皮肤组织局部AGEs明显蓄积,而上皮化创面AGEs蓄积则不明显。结论:在糖尿病创面愈合过程中胶原形成不良、上皮迁移延迟以及炎症反应异常可能是糖尿病创面难愈的组织学基础,而糖尿病皮肤局部AGEs的过多蓄积可能是糖尿病创面组织学     

伤口愈合过程中的干细胞动态变化

组织修复对于动物的生存有着至关重要的作用.皮肤表皮特别容易受到伤害,因此需要快速修复.从各种皮肤区域募集的独特表皮干细胞与其他细胞类型的协同作用是确保有效和和谐的伤口愈合所必需的.细胞之间复杂的关联性可确保组织愈合时期细胞的活化,迁移和可塑性.大面积伤口或烧伤的伤口常常会导致伤口愈合时间过长,进而还可能会发生感染,最终...     

The reduction of itch during burn wound healing

The purpose of this study was to find a method to reduce the itch experienced by patients who have sustained burn injuries, by using and comparing the effectiveness of 2 shower and bath oils. One product contained liquid paraffin with 5% colloidal oatmeal and the other contained liquid paraffin. The study was carried out in the Adult Burns Unit, Royal Brisbane Hospital (RBH), Brisbane. It was conducted during a 10-month period from July 1998 until April 1999. Thirty-five acute burns patients participated in an assessor-blind clinical trial. Patients were asked twice daily to rate their discomfort from itch and pain. The amount of antihistamine requested by each patient was totalled daily. Analysis of data supplied by patients showed that the group using the product with colloidal oatmeal reported significantly less itch and requested significantly less antihistamine than those using the oil containing liquid paraffin.