Sympathetic denervation impairs epidermal healing in cutaneous wounds

The involvement of peripheral nerves in dermal wound healing, particularly in the inflammatory response has not been extensively studied. Therefore, this study was performed to examine the role of peripheral nerves in the healing of rat skin linear incisions. We report that chemical sympathectomy with 6-hydroxydopamine significantly impaired wound healing as measured on days 7, 11, and 14 postsurgery (by day 14, 48% of the sympathectomized rats were healed in contrast with 84% of the controls; p = 0.0104). In contrast, neonatal capsaicin treatment, which predominantly destroys sensory afferents, had no effect on wound healing ( p > 0.05 on all days). These results support the hypothesis that sympathetic efferents are important for wound healing. Unlike previous research, which showed that peripheral nerves influence ischemic skin flaps, we are the first to demonstrate a role for peripheral nerves in the healing of skin incisions. Because inflammation is an important step in cutaneous wound healing, we propose that a reduction of neurogenic inflammation caused by sympathectomy may explain the impaired wound healing that we observed in our study.     

Wound healing in man: tensile strength of healing wounds in some patient groups.

The healing of test wounds was studied in 108 patients, in whom some impairment of wound healing was suspected. A 5 cm skin wound was performed in the forearm and the strength of the wound was tested after 5 days using the technique described by Sandblom and associates with two measurements in each wound. No differences in wound strength could be registered between the two wounds in each patient, between males and females nor in patients with malignant disease compared to other patients. Patients with low serum protein or serum albumin values had significantly weaker wounds than patients with normal protein values. Patients over 80 years of age had wounds somewhat weaker than those below 70, the difference having a statistical significance of 6%. The wound strength in patients was compared to values found elsewhere for wounds in rabbits, rats, and piglets. The pigs had much higher values than others, rabbits slightly stronger than and rats about equal to humans.     

基因治疗与皮肤创面愈合

皮肤创面愈合过程是一个多因素参与的复杂过程,慢性、难愈创面严重影响了人们的生活质量.重组生长因子已经在临床用于改善创面愈合,但由于半衰期短、生物利用度低等原因,使得其临床疗效欠佳.近年来,随着基因工程技术的不断发展,基因治疗已经成为改善创面愈合的一种新的治疗方法.本文就目前基因治疗方法的优缺点、治疗性基因选择和正在进行的临床试验等方面进行了综述.     

Wound healing potential of Cassia fistula on infected albino rat model

BACKGROUND: Infection is the major problem to treat the wound. Antibiotic resistance by the pathogenic microorganism renders drug ineffective and calls for improved designing and development of new drugs. New approach has been developed to isolate active components from botanicals. Our aim was to investigate the potential of Cassia fistula to treat the infected wound on albino rat model. MATERIAL AND METHODS: The alcohol extract of C. fistula leaves was analyzed for antibacterial effect against Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 27853. Formulated ointment was topically applied on the infected wound. Wound reduction rate, histological analysis, biochemical analysis, and gelatin zymography were obtained to assess the healing pattern. RESULTS: C. fistula treated rats showed, better wound closure, improved tissue regeneration at the wound site, and supporting histopathological parameters pertaining to wound healing. Biochemical analysis and matrix metalloproteinases expression correlated well with the results thus confirming efficacy of C. fistula in the treatment of the infected wound. CONCLUSION: Along with the other activities such as antitumor, antioxidant, hypoglycemic, hepatoprotective, antibacterial, hypocholesterolaemic, and antidiabetic activity, the healing potential of C. fistula provides a scientific rationale for the traditional use of this plant in the management of infected dermal wound and can be further investigated as a substitute to treat infected wounds without using synthetic antibiotics.     

TGF-beta1 alters the healing of cutaneous fetal excisional wounds.

BACKGROUND/PURPOSE: In a number of species, fetal wound healing differs from the adult in the absence of inflammation, fibrosis, scar formation, and excisional wound contraction. The lack of inflammation also may explain the relative absence of any cytokine levels at the wound site, such as transforming growth factor (TGF)-beta, and therefore the unique characteristics of fetal wound healing. The authors hypothesized that exogenous TGF-beta1 would induce contraction, inflammation, fibrosis, and scar formation in cutaneous excisional wounds in the fetal rabbit. METHODS: Cellulose discs (3 mm in diameter) were formulated with either 1.0 microg TGF-beta1 (n = 6) or bovine serum albumin (BSA; n = 7), as a control, for sustained-release over 3 days. Each disc was implanted into the subcutaneous tissue on the backs of fetal New Zealand White Rabbits in utero on day 24 of gestation (term, 31 days). A full-thickness, 3-mm excisional wound (7.4 mm2) was then made next to the implanted cellulose disc. All wounds were harvested 3 days later. RESULTS: At harvest, the excisional wounds in the TGF-beta1 group had contracted (5.6 +/- 2.0 mm2), whereas those in the control group had expanded (13.5 +/- 1.2 mm2, P< .01). The surrounding dermis in the TGF-beta1 group had 16.3 inflammatory cells per grid block compared with 12.4 cells in the control group (not significant). In addition, a greater amount of fibrosis was induced by the TGF-beta1 implant (1.7 +/- 0.3) than the control implant (0.4 +/- 0.2) on a scale of 0 to 3, P < .01. In situ hybridization analysis showed an increase in procollagen type 1alpha1 gene expression in the surrounding dermis of the TGF-beta1 group (36.7 +/- 3.6 grains per grid block) compared with the control group (7.1 +/- 0.9 grains per grid block, P < .001). CONCLUSIONS: These results demonstrate that the cytokine TGF-beta1 can induce fetal excisional wounds to contract, stimulate fibrosis, and increase procollagen type 1alpha1 gene expression. These findings further suggest that the absence of TGF-beta1 atthe wound site may be responsible in part for the lack of a postnatal healing response.     

Increased specific binding of insulin-like growth factor-I in healing cutaneous wounds

Insulin-like growth factor-I is a polypeptide hormone structurally related to insulin. It is a potent mitogen that promotes growth and differentiation in many tissues. A role for insulin-like growth factor-I in wound healing is suggested by its rapid rise in levels and increased insulin-like growth factor-I messenger RNA expression in tissue after wounding. We designed our study to characterize possible changes in insulin-like growth factor-I receptor binding during wound healing. Surgical wounds created on the abdominal skin of anesthetized New Zealand White rabbits were either left open or closed primarily. Size- and weight-matched specimens were harvested at wounding time (day 0), and at 1, 4, 7, 38, and 50 days after wounding. Preliminary experiments showed that the greatest difference in specific binding occurred between day 0 and day 7. (125)I-insulin-like growth factor-I binding studies were performed on frozen tissue specimens and autoradiography was performed and analyzed by computerized densitometry. Scatchard analysis of the binding data showed a single class of insulin-like growth factor-I binding sites whose affinity that is, binding constant (K(d) = 0.6 x 10(-9)) did not change significantly over time; in contrast there was a threefold increase in the number of receptors per milligram tissue in day 7 wound tissue versus normal skin harvested at day 0 (17.3 +/- 2.6 x 10(10) versus 4.7 +/- 2.5 x 10(10), respectively, p < 0.05). Binding inhibition experiments showed that (125)I-insulin-like growth factor-I binding was most specific to insulin-like growth factor-I with insulin-like growth factor-I > insulin-like growth factor-II > insulin. This increase in binding was due to upregulation of insulin-like growth factor-I receptors rather than increased levels of insulin-like growth factor-I binding protein as less than 20% of the threefold increase in binding at day 7 could be attributed to insulin-like growth factor-I binding protein in membrane-free extracts. The presence of specific, high-affinity insulin-like growth factor-I receptors in the skin and their upregulation at day 7 after wounding suggest that insulin-like growth factor-I plays an important role during wound healing.     

不同部位糖尿病足溃疡愈合情况分析

目的了解不同部位糖尿病足溃疡愈合情况。方法采用前瞻性研究方法,对142例Wagner分级2~4级的糖尿病足溃疡患者采取多学科协作的综合治疗方法,收集入院首次临床检查资料,留取入院每次清创后足溃疡照片,比较治疗30d内不同部位的足溃疡创面缩小率。结果发生在足背、足踝、足弓、足趾、足前掌及足跟的Wagner分级为2级的溃疡创面缩小率比较,差异有统计学意义(P0.01),发生在足趾的糖尿病足溃疡创面缩小率最小,足踝部及足背部溃疡创面缩小率较大。Wagner分级为2、3级的非受压组溃疡创面缩小率显著大于受压组(均P0.01)。结论不同部位糖尿病足溃疡愈合存在差异,治疗糖尿病足过程中采取适当的减压措施有利于糖尿病足溃疡的愈合。     

Lentiviral gene therapy with platelet-derived growth factor B sustains accelerated healing of diabetic wounds over time

The treatment of diabetic wounds is a formidable clinical challenge. In this study, lentiviral vectors carrying the human platelet-derived growth factor B (PDGF-B) gene were used to treated diabetic mouse wounds. Full-thickness 2.0-cm x 2.0-cm excisional wounds were created on the dorsa of genetically diabetic C57BL/KsJ-m+/+Lepr(db) mice. Lentiviral vectors containing the PDGF-B gene were injected into the wound margins and base. Mice were killed at 14-, 21-, and 35-day intervals. Measurement of the residual epithelial gap showed a trend towards increased healing in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at all time points. At 21 days, there was significantly increased healing in lentiviral PDGF-treated wounds (0.98+/-0.17 cm) compared with saline-treated wounds (1.22+/-0.30 cm; P<0.05). Immunohistochemistry for CD31 revealed significantly increased neovascularization in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at 14 and 21 days (P<0.01). Picrosirius red staining demonstrated thicker and more highly organized collagen fibers in treated wounds compared with untreated and saline-treated wounds. Quantitative analysis of collagen content showed a 3.5-fold and 2.3-fold increase in lentiviral PDGF-treated wounds versus untreated and saline-treated wounds, respectively (P<0.01). Lentiviral gene therapy with PDGF-B can sustain diabetic wound healing over time and may possess promising potential in the clinical setting.     

Influence of topical administration of n-3 and n-6 essential and n-9 nonessential fatty acids on the healing of cutaneous wounds.

Injury triggers a series of physiological events at the wound site. These include an inflammatory response that is established shortly after the injury, which is then followed by an intense formation of tissue over a period of days. Poly- and monounsaturated fatty acids exert major functions on the inflammatory responses, either in the form of phospholipids anchored in the cell membrane or as soluble lipoic mediators. We present evidence that linolenic (n-3), linoleic (n-6), and oleic (n-9) fatty acids can modulate the closure of surgically induced skin wounds. We found that n-9 fatty acids induced faster wound closure when compared to n-3, n-6, and control. In addition, n-9 fatty acids strongly inhibited the production of nitric oxide at the wound site. A mild improvement on wound closure was observed in the n-6 fatty acid-treated animals concurrent with a peak in nitric oxide production at 48 hours postsurgery. N-3 fatty acid treatment significantly delayed wound closure. Furthermore, we showed that n-3 fatty acid induced a peak in nitric oxide at 3 hours postsurgery and an intense deposition of extracellular matrix after 5 days of treatment. Thus, our results suggest a relevant role and potential therapeutic implication for fatty acids on skin wound healing.     

Lysophosphatidic acid enhances healing of acute cutaneous wounds in the mouse.

Lysophosphatidic acid is a phospholipid growth factor and intercellular signaling molecule released by activated platelets and injured fibroblasts that affects keratinocytes, fibroblasts, neutrophils,and monocytes. We therefore hypothesized that lysophosphatidic acid could influence the inflammation and reepithelialization phases of wound healing. Lysophosphatidic acid (100 microM) was applied daily for 5 days to 2 mm-diameter excisional mouse ear skin wounds and re-epithelialization was measured. We also evaluated whether the bioactivity of lysophosphatidic acid could be increased by zinc (Zn2+, 1 mM). Inflammatory cells were counted in wound sections after 1, 3, or 5 days of healing. Reepithelialization was accelerated significantly by either lysophosphatidic acid or lysophosphatidic acid + Zn2+ (p < 0.01 and p < 0.0001, respectively). Both lysophosphatidic acid solutions significantly increased the amount of new epithelium in the wounds on days 1, 2, and 3 (p < 0.05). Little wound area remained on day 4, and all wounds were fully reepithelialized by day 5. Lysophosphatidic acid did not affect the number of neutrophils or macrophages present in the wound area. Our findings show that lysophosphatidic acid increased the amount of reepithelialization in the early stages of cutaneous wound healing in excisional ear wounds, without affecting inflammatory function.     

Topical simvastatin promotes healing of Staphylococcus aureus‐contaminated cutaneous wounds

Cutaneous wounds are prompt to be contaminated by bacteria, but the clinical benefits of applying antibiotics and antiseptics in wound management have not been proven. Statins are 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors commonly used to lower cholesterol levels. Studies indicated that statins, especially simvastatin, promote wound healing in experimental models. As Staphylococcus aureus is one of the most important microorganism responsible for wound infections, the aims of this study were to characterise the anti‐staphylococcal activity of simvastatin and to evaluate the application of simvastatin as a topical therapy for S. aureus‐contaminated wounds. In the present study, simvastatin was bacteriostatic against S. aureus at sub‐inhibitory concentrations up to 8 hours after exposure. Further increased concentrations of simvastatin above the minimal inhibitory concentration (MIC) did not enhance the growth inhibitory effect. By contrast, the ability of simvastatin to inhibit S. aureus biofilm formation was concentration dependent. Topical application of simvastatin at its MIC against S. aureus accelerated the healing and bacterial clearance of S. aureus‐contaminated wounds in an excisional mice wound model. This effective concentration is well below the safe concentration for topical use. Collectively, topical application of simvastatin has the potential as a novel modality for managing wound infections and promoting wound healing.