Effect of silver on burn wound infection control and healing: review of the literature

Silver compounds have been exploited for their medicinal properties for centuries. At present, silver is reemerging as a viable treatment option for infections encountered in burns, open wounds, and chronic ulcers. The gold standard in topical burn treatment is silver sulfadiazine (Ag-SD), a useful antibacterial agent for burn wound treatment. Recent findings, however, indicate that the compound delays the wound-healing process and that silver may have serious cytotoxic activity on various host cells. The present review aims at examining all available evidence about effects, often contradictory, of silver on wound infection control and on wound healing trying to determine the practical therapeutic balance between antimicrobial activity and cellular toxicity. The ultimate goal remains the choice of a product with a superior profile of infection control over host cell cytotoxicity.     

影响碱性成纤维细胞生长因子促进烧伤创面愈合因素的探讨

采用大白鼠１５％Ⅲ度烧伤模型，探讨了影响碱性成纤维细胞生长因子（ｂＦＧＦ）促进烧伤创面愈合的因素。结果发现，烧伤创面早期切痂可保持ｂＦＧＦ的活性。４０天创面愈合率达８４．０％，而未切痂组愈合率仅９，Ｏ％。肝素可增强ｂＦＧＦ促进创面肉芽组织生长、毛细血管增生、纤维母细胞增殖及细胞ＤＮＡ合成。创面感染的控制有利于保护ｂＦＧＦ的活性。伤后１周开始使用ｂＦＧＦ为适宜时期。     

Relationship between healing time and mean perfusion units of laser Doppler imaging (LDI) in pediatric burns

Background

Laser Doppler imaging (LDI) is a noninvasive technique used to assess burn depth. However, there have been no studies regarding the use of LDI in predicting burn healing time.

Objectives

The aims of this study are to evaluate the relationship between healing time and the amount of perfusion seen on LDI and to determine a cut-off value for LDI that predicts if a burn will heal within 14 days.

Study design

Consecutive patients younger than 15 years old with partial-thickness burns were recruited from May to November 2006 for this prospective observational study. The mean number of perfusion units (PU) as determined by LDI (Periscan PIM 3 system) was obtained within 2–3 days following injury. Healing time was estimated clinically by two physicians and marked by the observation of reepithelization. The mean PU was compared between the early (healed with 14 days) and late healing groups (healed later than 14 days). The usefulness of the mean PU in predicting healing time within 14 days was estimated by receiver operating characteristic curve analysis.

Results

A total of 103 patients with 181 partial-thickness burn wounds were enrolled in this study. The mean PU from LDI was higher in the early healing group compared to the late healing group (380.2 ± 157.8 vs. 185.8 ± 115.8, p < 0.001). When using 250 PUs as a cut-off value to predict early healing, the sensitivity and specificity were 80.6% and 76.9%, respectively. The area under the ROC curve was 0.844 (p < 0.001, 95% CI = 0.780–0.908).

Conclusions

This study suggests the mean PU as determined by LDI can be used as a valuable tool in predicting the healing time of burn wounds.     

L-精氨酸对糖尿病烧伤创面促愈作用的研究

目的探讨精氨酸对糖尿病烧伤创面修复的影响及其可能的机制. 方法 SD大鼠随机分为正常对照组(A组)、糖尿病对照组(B组)、糖尿病精氨酸干预组(C组)和糖尿病甘氨酸对照组(D组).糖尿病模型通过腹腔注射STZ建立,然后喂养8周后给予深Ⅱ度烫伤,于伤后0、1、3、7、14、21 d时相点对创面愈合面积、组织形态学改变、创面组织糖含量、羟脯氨酸(OHP)含量及局部组织释放转化生长因子-β1(TGF-β1)含量进行检测. 结果应用精氨酸后,皮肤组织糖含量降低,创面局部炎症反应出现较早,坏死组织脱落及上皮匍行提前,OHP含量、组织释放TGF-β1能力均增加,创面愈合明显加快(P﹤0.05～0.01). 结论 L-精氨酸可通过降低皮肤组织糖含量及增加TGF-β1的合成和释放,促进糖尿病烧伤创面愈合.     

甲鱼油对大鼠浅Ⅱ度烫伤创面愈合过程中组织修复的影响

目的:探讨甲鱼油治疗大鼠浅Ⅱ度烫伤的效果及其对创面愈合过程中组织修复的影响。方法:108只Wistar大鼠随机分为单纯烫伤组、银锌霜治疗组和甲鱼油治疗组,每组36只。采用将脱毛区置于70℃恒温水浴中15s的方法制成10%体表面积浅Ⅱ度烫伤模型,伤情经病理切片证实。各组创面分别用生理盐水纱布(1ml/cm2)、银锌霜纱布(1ml/cm2)、甲鱼油(1ml/cm2)纱布覆盖包扎固定后放回笼中分笼饲养,换药1次/d。观察创面愈合率及愈合时间。各组动物分别于伤后1、3、5、10、14d取创面组织,常规苏木精-伊红染色,观察病理组织学变化;免疫组织化学链霉素-卵白素-生物素-过氧化物酶复合物法检测创面组织增殖细胞核抗原的表达。结果:①创面愈合时间:单纯烫伤组为(15.33±0.82)d、银锌霜治疗组(12.57±0.54)d,甲鱼油治疗组(11.33±0.67)d,甲鱼油治疗组比单纯烫伤组明显缩短(P<0.01)。②创面愈合率:3组大鼠伤后10和14d的创面愈合率与伤后7d相比差异均具有显著性(P<0.01),甲鱼油治疗组和银锌霜治疗组两组大鼠的创面愈合率比单纯烫伤组在伤后7、10及14d均明显升高(P<0.01)。③病理学观察:甲鱼油能减轻烫伤创面早期的炎症反应,组织学分析显示甲鱼油可促进创面的再上皮化和表皮各层的分化。④增殖细胞核抗原在创面组织标本中的表达量:甲鱼油治疗组比单纯烫伤组、银锌霜治疗组明显升高(P<0.01)。结论:甲鱼油能加速大鼠烫伤创面组织修复细胞的增殖,加快创面再上皮化,促进创面愈合。     

Nerve growth factor and burn wound healing: Update of molecular interactions with skin cells

Burn wound healing is a very intricate and complex process that conventionally includes three interrelated and overlapping stages of hemostasis/inflammation, proliferation and remodeling. This review aims to explore the molecular interactions of NGF with the most prominent cell types in the skin and their respective secretory products during wound healing, particularly burn wound healing. Different types of cells such as, nerve cells, endothelial cells, mast cells, macrophages, neutrophils, keratinocytes and fibroblasts all come into play through a plethora of cytokines and growth factors including nerve growth factor (NGF). NGF is a pleiotropic molecule that exerts its effects on all the aforementioned cells using two types of receptors (TrkA and p75) and affects wound healing by decreasing healing time and improving the quality of the scar. Both receptors mediate cellular proliferation, survival and apoptosis through complex signaling molecules. During the inflammatory phase, macrophages and mast cells secrete ample cytokines and growth factors, including NGF, which participate in the inflammatory reaction and induction of other cells targeting a homeostatic state. The proliferative phase follows, and NGF promotes angiogenesis through VEGF and FGF expression in endothelial cells. NGF also stimulates keratinocyte proliferation and neurite extension through the TrkA-PI3K/Akt pathway. Other molecules such as TGF-β1, IL-1β and TNF-α increase NGF expression in fibroblasts through dynamic interactions with Smads and MAPK molecules. Stimulated fibroblasts induce new collagen production to form the granulation tissue. In the remodeling phase, NGF regulates fibroblasts and induces their differentiation into myofibroblasts ultimately leading to wound contracture. In addition, NGF stimulates melanocytes and enhances hair growth and pigmentation. Such data depict the mechanisms of action of NGF implicated in the various stages of the healing process and support its applicability as a new targeted therapeutic molecule effective in burn wound healing but with some limitations.     

Burn healing is dependent on burn site: a quantitative analysis from a porcine burn model

This retrospective review examines healing in different sites on a porcine burn model; 24 pairs of burns on 18 pigs from other animal trials were selected for analysis. Each pair of burns was located on the either the cranial or the caudal part of the thoracic ribs region, on the same side of the animal. The burns were 40-50 cm(2) in size and of uniform deep-dermal partial thickness. Caudal burns healed significantly better than cranial burns, demonstrated by earlier closure of wounds, less scar formation and better cosmesis. To our knowledge, this is the first detailed study reporting that burn healing is affected by location on a porcine burn model. We recommend that similar symmetrical burns should be used for future comparative assessments of burn healing.     

An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor

Various studies have shown that chitosan is effective in promoting wound healing. In this study, we aimed to develop an effective chitosan gel formulation containing epidermal growth factor (EGF), and to determine the effect on healing of second-degree burn wounds in rats. Ten micrograms per millilitre EGF in 2% chitosan gel was prepared. In an in vitro study to investigate release of EGF from the formulations, the release rate was 97.3% after 24 h. In in vivo studies, animals were divided into six groups as follows: silver sulfadiazine [Silverdin cream (SIL)], chitosan gel with and without EGF (EJ, J), EGF solution (ES) and untreated control groups [unburned (S) and untreated (Y) rats] applied groups, respectively. A uniform deep second-degree burn of the backskin was performed with water heated to 94+/-1 degrees C during a 15-s exposure. The EGF formulations were repeatedly applied on the burned areas with a dose of 0.160 microg/cm2 for 14 days (one application per day). Healing of the wounds was evaluated immunohistochemically, histochemically and histologically on the tissue samples. When the results were evaluated immunohistochemically, there were significant increases in cell proliferation observed in the EGF containing gel applied group (p<0.001). The histochemical results showed that the epithelization rate in the EJ group was the highest compared to the ES group results (p<0.001). The histological results indicated and supported these findings. It can be concluded that a better and faster epithelization was observed in the EJ group compared to the other groups.     

Assessment of burn depth and burn wound healing potential

The depth of a burn wound and/or its healing potential are the most important determinants of the therapeutic management and of the residual morbidity or scarring. Traditionally, burn surgeons divide burns into superficial which heal by rapid re-epithelialization with minimal scarring and deep burns requiring surgical therapy. Clinical assessment remains the most frequent technique to measure the depth of a burn wound although this has been shown to be accurate in only 60-75% of the cases, even when carried out by an experienced burn surgeon. In this article we review all current modalities useful to provide an objective assessment of the burn wound depth, from simple clinical evaluation to biopsy and histology and to various perfusion measurement techniques such as thermography, vital dyes, video angiography, video microscopy, and laser Doppler techniques. The different needs according to the different diagnostic situations are considered. It is concluded that for the initial emergency assessment, the use of telemetry and simple burn photographs are the best option, that for research purposes a wide range of different techniques can be used but that, most importantly, for the actual treatment decisions, laser Doppler imaging is the only technique that has been shown to accurately predict wound outcome with a large weight of evidence. Moreover this technique has been approved for burn depth assessment by regulatory bodies including the FDA.     

Accuracy of early burn depth assessment by laser Doppler imaging on different days post burn

Background

Accurate diagnosis of burn depth is essential in selecting the most appropriate treatment. Early assessment of burn depth by clinical means only has been shown to be inaccurate, resulting in unnecessary operations or delay of grafting procedures. Laser Doppler imaging (LDI) was reported as an objective technique to determine the depth of a burn wound, but the accuracy on very early days post burn has never been investigated yet.

Methods

In 40 patients with intermediate depth burns, we prospectively evaluated and compared the accuracy of the LDI measurements with the clinical assessments on days 0, 1, 3, 5, 8. Clinical evaluation of the depth of the burn was performed by two observers blinded to the LDI images. Accuracies were assessed by comparison with outcome: healing times longer than 21 days were considered to be equivalent to a biopsy finding of a deep dermal wound. Obviously superficial and full thickness wounds were excluded. LDI flux level was used for LDI prediction of outcome: less than 220 PU to predict non-healing at day 21.

Results

The accuracies of burn depth assessments on the day of burn and post burn days 0, 1, 3, 5 and 8 using LDI were 54%, 79.5%, 95%, 97% and 100% compared with clinical assessment accuracies of 40.6%, 61.5%, 52.5%, 71.4% and 100%, respectively. LDI accuracy was significantly higher than clinical accuracy on day 3 (p < 0.001) and day 5 (p = 0.005). Burn depth conversion was also considered. This is the first study to quantify the advantage of LDI scanning over clinical assessments during these important early after burn days.     

Comparative study of conventional and topical heparin treatment in second degree burn patients for burn analgesia and wound healing

Objective

To compare clinical outcome of topical conventional with topical heparin treatment in 2nd degree or partial thickness (PTB) burn patients.

血浆冷沉淀物在深度烧伤创面应用的实验及临床研究

目的　观察血浆冷沉淀物应用烧伤创面的治疗效果。方法　通过对 4 0只豚鼠烧伤模型及 4 6例临床烧伤患者创面应用血浆冷沉淀物与创面应用磺胺嘧啶银对照观察伤后创面愈合率、愈合时间。结果　应用血浆冷沉淀实验组创面愈合率、愈合时间优于应用磺胺嘧啶银对照组 ,表明血浆冷沉淀具有促进烧伤创面愈合作用。结论　血浆冷沉淀中所含的主要成分纤维连接蛋白 ,具有很强的生物活性 ,它能促进上皮细胞生长     

The healing effect of pulsed magnetic field on burn wounds

A burn is one of the most difficult injuries people can face.The primary pathology is coagulation necrosis resulting from tissue damage.Many wound care products have been developed to be used in situations such as the poor general condition of the patient and lack of solid area to be grafted. However, the high costs of these products make their use complicated.In this study, the effect of PEMF on cutaneous wound healing in an animal burn model was evaluated and the dose and duration of the magnetic field should be discussed for this effect to occur. Animals were divided into five groups including eight each (n = 40) (Groups 1, 2, 3, 4, 5).Group 1 was the control group; received no treatment after second-degree burn wound. Group 2 received daily wound care with saline. Group 3 received daily wound care with pomade containing mupirocin. Group 4 received Pulsed Electromagnetic Field signal for 60 min (1.5 m T and 40 Hz for seven days and Group 5 also received PEMF signal for 60 min the same frequency and intensity for14 days. Microscopically, second-degree burn wounds were successfully detected in all rats. Histopathological examination results in no significant difference between groups in neutrophil infiltration. The difference between the groups in vascularization was statistically significant between Group II and Group V (p < 0.001) and between Group I and Group V (p = 0.005) Epithelialization was present in 75% of the rats in Group V, while no epithelialization was observed in any of the other groups. In conclusion, we observed a significant improvement in the stasis zone of the group receiving Pulsed Electromagnetic Field for two weeks.     

The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial

IntroductionBurn is among the most severe forms of critical illness, associated with extensive and prolonged physical, metabolic and mental disorders. The aim of this study was to assess the effect of an oral, low-cost, and accessible collagen-based supplement on wound healing in patients with burn.MethodsIn this randomized double-blind controlled pilot clinical trial, 31 men, 18–60 years, with 20–30% total body surface area burn were studied. Patients were randomly assigned to receive either a collagen-based supplement (1000 kcal) or an isocaloric placebo, for 4 weeks. Serum pre-albumin, rate of wound healing, length of hospital stay, and anthropometries were assessed at baseline, and the end of week 2 and 4.ResultsSerum pre-albumin was significantly higher at week 2 (29.7 ± 13.6 vs. 17.8 ± 7.5 mg/dL, P = 0.006) and week 4 (35.1 ± 7.6 vs. 28.3 ± 8.2 mg/dL, P = 0.023) in collagen than control group. Changes in pre-albumin concentration were also significantly higher in collagen group at week 2 (13.9 ± 9.8 vs. −1.9 ± 10.3 mg/dL, P < 0.001) and week 4 (19.2 ± 7.5 vs. 8.5 ± 10.1 mg/dL, P = 0.002). The Hazard ratio of wound healing was 3.7 times in collagen compared to control group (95% CI: 1.434–9.519, P = 0.007). Hospital stay was clinically, but not statistically, lower in collagen than control group (9.4 ± 4.6 vs. 13.5 ± 7 days, P = 0.063). There were no significant differences in weight, body mass index, dietary energy and protein intakes between the two groups.ConclusionThe findings showed that a hydrolyzed collagen-based supplement could significantly improve wound healing and circulating pre-albumin, and clinically reduce hospital stay in patients with 20–30% burn.     

烧伤创面愈合的理论探索与临床实践

The basic and clinical research in wound healing have made great progress in China in the past 50 years. The method of " intermingle skin transplantation" which was first advocated by surgeons of Ruijin Hospital in 1966 greatly reduced the amount of autologous donor skin, thus making the coverage of an extensive burn wound possible. This method is al so known as " Chinese therapy". In 1986,doctors of Jishuitan Hospital reported successful coverage of an extensive burn wound with mieroautografts and allogeneic skin. The basic research of wound healing has been carried out since 1992,a series of studies showed the characteristics of biological behaviours of cells in concern, extracellular matrix and growth factor, the mechanism underlying progressive injury in deep second burn wound, the effect of " skin island" and the local immune tolerance induced by it (which are the key factors of intermingle transplantation).The induction of local immune tolerance has now become the re search hot subject of skin transplantation immunology. Stem cell research in the field of wound healing has been extensively car ried out. The theory of " dermal template defection" has been proposed as one of the mechanisms of scar formation. On the other hand, great progress has been achieved in the treatment of bums on the basis of clinical researches. Doctors of PLA 304 hospital found that excision of eschar on patients with extensive deep burn injury at early shock stage greatly decreased the occurrence of complications and mortality. Doctors of Ruijin Hospital reported that healing of deep second burn wound could be improved by tangential excision of burn eschar within 24 hours after burn injury. Doctors of Xiang ya Hospital reported patients suffering from deep bums of the hands got satisfied functional restoration when treated with tangential excision of eschar while degraded dermal tissue could be retained with transplantation of autoskin grafts.     

烧伤创面愈合的信号转导机制

After 50 years of development in science of bums care in China, we have basically solved coverage of deep wounds of burn trauma, as well as role of multiple growth factors and stem cell in wound healing, making great contribution to improving the treatment of patients with large area of deep bums. Surgeons are paying close attention to problems of wound healing, especially in the fields of starless healing and rehabilitation. To solve these problems, we need to do further investigation on multiple growth factors as well as proliferation/differentiation of stem cells in regulation of cell growth and differentiation in wound healing. Therefore ,we are facing a even more serious challenge.     

重组人生长激素在严重烧伤病人中的应用研究

目的探讨生长激素对大面积烧伤病人蛋白质代谢、创面愈合能力、免疫功能及预后的作用。方法选择42例大面积烧伤病人,随机分为重组人生长激素(rhGH)治疗组和对照组,并分析比较两组一般状况、蛋白质代谢、创面愈合时间、免疫功能。结果 rhGH 组一般情况良好,体重增加,血浆蛋白质水平、供皮区愈合时间及体液和细胞免疫功能均比对照组好。结论 rhGH 能有效促进蛋白质合成,缩短创面愈合时间,增强机体免疫能力,从而提高大面积烧伤病人生存率。     

细胞免疫与烧伤创面愈合的实验研究

为探讨免疫低下对烧伤创面愈合的影响,设计了用低剂量钴源照射的方法建立的免疫抑制模型,并在该模型的基础上观察了免疫抑制大鼠Ⅱ度烧伤创面愈合的情况。结果表明:①大鼠接受2Gy~(60)Co 照射后20天内,Th/Ts 比值和 T 细胞肿瘤花环率持续下降。照射后皮肤组织 DNA 含量及细胞周期均无明显改变。②免疫抑制大鼠胶原修复能力下降,创面愈合百分率低于正常大鼠。由此证实了免疫功能低下对创面愈合的抑制作用。     

Prospective comparative evaluation study of Laser Doppler Imaging and thermal imaging in the assessment of burn depth

Introduction

The accurate assessment of burn depth is challenging but crucial for surgical excision and tissue preservation. Laser Doppler Imaging (LDI) has gained increasing acceptance as a tool to aid depth assessment but its adoption is hampered by high costs, long scan times and limited portability. Thermal imaging is touted as a suitable alternative however few comparison studies have been done.

烧伤后24 h内削痂防治深Ⅱ度创面进行性加深的组织学观察

目的　探讨烧伤后 2 4h内行削痂手术 ,对深Ⅱ度烧伤创面进行性加深的防治作用。方法　选择 12例深Ⅱ度烧伤患者 ,在伤后 2 4h内进行创面削痂手术。分别从手术前、手术后 (伤后 5～7d)和未手术创面 (伤后 5～ 7d)获取标本。采用HE染色、Masson′s染色和免疫组化技术标记Vi mentin抗原阳性细胞的方法 ,对创面组织标本进行组织学观察。　结果　随病程演进 ,未手术创面炎性反应程度明显加重 ,组织坏死范围扩大 ,原来残存的皮肤附件因炎症加重而消失 ;Masson′s染色棕红色范围扩大 ,亮绿色范围缩小 ;Vimentin抗原阳性细胞数量明显减少。伤后 2 4h内削痂创面局部炎症反应较未削痂创面明显减轻 ,可见新鲜肉芽形成和部分上皮修复 ,组织坏死范围未见进一步扩大 ,与未手术区比较差异有显著性意义 (P <0 .0 5 ) ;Masson′s染色亮绿色范围无明显缩小 ;Vimentin抗原阳性细胞数量明显多于未手术区 (P <0 .0 5 )。　结论　烧伤后 2 4h内削痂 ,能适时去除创面坏死组织、阻断组织变质性损害的加剧 ,从而有效改善深Ⅱ度创面的进行性加深现象 ,对创面愈合具有促进作用。