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Background: Chronic wounds are one of the most important challenge for regenerative surgery. Plastic surgeon can use fat graft to increase wound healing because its growth factors can enhance tissue regeneration. In a recent study, the authors evaluated a reduction of pain in a cohort of patients submitted to breast reconstruction with breast implant and lipofilling, putting into evidence that growth factors in fat graft can reduce post‐surgical pain. The aim of this work is to evaluate ultra‐filtered fat graft potential in reducing pain in chronic wounds. Patients and Methods: Fifty new patients with chronic wounds of different etiology were recruited for this study and divided into two groups: A, treatment and B, control. Twenty‐five patients per group. Negative pressure therapy dressing was applied after surgical debridement. Three days later patients in group A received ultrafiltered fat graft. Pain was evaluated with preoperative Visual Analogic Scale, repeated twice a day for 14 days and finally 21 days from procedures. Results: In group A (treated patients), pain was lower. These data were confirmed even after 7 days. The overall statistical analysis of the average of all values (SD 1.72) confirmed that the differences were significant at the 95% with the Chi‐square test and analysis of variance (P value <.05). Conclusions: The ultra‐filtered fat graft placed on the wound bed and edges was effective in reducing pain in chronic wounds. The reduction of pain was statistically significant. [ABSTRACT FROM AUTHOR]

Keratin is an interesting protein needed for wound healing and tissue recovery. We have recently proposed a new, simple and inexpensive method to obtain fur and hair keratin-derived biomaterials suitable for medical application. The aim of the study was to evaluate the role of the fur keratin-derived protein (FKDP) dressing in the allogenic full-thickness surgical skin wound model. The data obtained using scanning electron microscopy showed that employed processed biomaterial had higher surface porosity compared with control raw material. From the MTS test, it was found keratin biomaterial is not only toxic to the NIH/3T3 cell line ( p < 0.05), but also enhances cell proliferation compared with the control. In vivo studies have shown keratin dressings are tissue biocompatible, accelerate wound closure and epithelialization to the statistically significant differences on day 5 ( p < 0.05) in comparison to control wounds. Histological examination revealed, that in FKDP-treated wounds the inflammatory response contained predominantly macrophages whilst their morphological untreated variants showed mixed cell infiltrates rich in neutrophils. Predominant macrophages based response creates more favorable environment for healing. In FKDP-dressed wounds the number of microhemorrhages was also significantly decreased ( p < 0.05) as compared with undressed wounds. Applied keratin dressing favors reconstruction of a more regular skin structure and assures better cosmetic effect in terms of scar formation and appearance. In conclusion, fur keratin-derived protein dressings significantly accelerated wound healing in the mouse model. Further studies are needed to determine the molecular mechanisms involved in the multilayer wound healing process and to assess the possible use of these dressings for medical purposes. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) is a fraction of blood with a platelet concentration above baseline. When platelets get activated, growth factors involved in wound healing are released. The application of PRP has shown good results in wound care, however, up to date no substantial research has been performed on the effect of PRP in burn treatment. This randomized double blind intra-patient controlled study investigates the effect of autologous PRP on wound healing in burns that require surgery with a meshed split skin graft (SSG). Fifty-two patients with various areas of deep dermal to full thickness burns, receiving surgery with a SSG were included after informed consent. Comparable study areas A and B (intra-patient) were appointed, randomized and either treated with a SSG and PRP or with a SSG alone. At day 5 to 7 postoperative, the epithelialization and graft take rate were assessed. Three, six, and twelve months postoperative, follow-up measurements were performed in the form of POSAS-questionnaires, DermoSpectroMeter, and Cutometer measurements. There was no statistically significant difference between the mean take rate nor the mean epithelialization rate at day 5-7 between the PRP-treated and control areas. However, PRP-treated wound areas showed more often better or equal epithelialization and take rates at day 5-7 than the standard treated areas. Minor effects were also seen in the reoperated and early operated subgroups. At 3, 6, and 12 months postoperative, POSAS scores from the patients and the observers, Dermaspectro-, and Cutometer measurements did not depict a significant difference between the PRP and standard treated areas. Concluding, the addition of PRP in the treatment of burn wounds did not result in improved graft take and epithelialization, nor could we demonstrate better scar quality. There was, however, a considerable variation in our clinical population. [ABSTRACT FROM AUTHOR]

Neutrophils infiltration/activation following wound induction marks the early inflammatory response in wound repair. However, the role of the infiltrated/activated neutrophils in tissue regeneration/proliferation during wound repair is not well understood. Here, we report that infiltrated/activated neutrophils at wound site release pyruvate kinase M2 (PKM2) by its secretive mechanisms during early stages of wound repair. The released extracellular PKM2 facilitates early wound healing by promoting angiogenesis at wound site. Our studies reveal a new and important molecular linker between the early inflammatory response and proliferation phase in tissue repair process. [ABSTRACT FROM AUTHOR]

Maggot debridement therapy (MDT) is the use of the larval stage of flies (i.e., Calliphoridae) to remove necrotic tissue and disinfect wounds. Effective MDT requires aseptic technique to prevent the unintentional introduction of pathogenic bacteria into a wound to be debrided; yet the external surface of Calliphoridae eggs is often heavily contaminated with bacteria. Studies of external disinfection of dipteran eggs have been reported, but neither their efficacy nor effect on egg viability has been adequately assessed. The present study evaluated the efficacy of ten disinfection techniques involving immersion, rinse, or a combination of both in formalin, Lysol, formaldehyde, bleach, ethanol, Sporgon, or benzalkonium chloride. All techniques resulted in significant decreases in culturable, aerobic bacterial load on Lucilia cuprina eggs. For L. cuprina, a 10 minute 3% Lysol immersion was the most efficacious, disinfecting 96.67% of egg samples, while resulting in 31.84% egg mortality. The 5% formalin immersion was least efficacious, disinfecting only 3.33% of L. cuprina egg samples, while resulting in 33.51% egg mortality. A formaldehyde immersion, one of the most commonly used disinfection techniques, was moderately effective, disinfecting 66.7% of egg samples, while resulting in 40.16% egg mortality. For Chrysomya rufifacies and Cochliomyia macellaria egg samples, the 10 minute 3% Lysol immersion disinfected 100% of the samples, and for Lucilia sericata, 80% of egg samples, while resulting in 33.97%, 7.34%, and 36.96% egg mortality, respectively. H2CO disinfected 16.67% of Ch. rufifacies, 26.67% of C. macellaria, and 56.67% of L. sericata egg samples, while resulting in 21.98%, 10.18%, and 32.19% egg mortality, respectively. Due to its high disinfection efficacy and relatively low egg mortality, a 10 minutes 3% Lysol immersion is recommended for sterilizing Calliphoridae eggs prior to rearing of larvae for use in MDT. [ABSTRACT FROM AUTHOR]

ABSTRACT Skin substitutes are heterogeneous biomaterials designed to accelerate wound healing through provision of replacement extracellular matrix. Despite growing evidence for their use in chronic wounds, the role of skin substitutes in acute wound management and their influence on fibrogenesis remains unclear. Skin substitute characteristics including biocompatibility, porosity, and elasticity strongly influence cellular behavior during wound healing. Thus, we hypothesize that structural and biomechanical variation between biomaterials may induce differential scar formation after cutaneous injury. The following human prospective cohort study was designed to investigate this premise. Four 5-mm full thickness punch biopsies were harvested from 50 volunteers. In all cases, site 1 healed by secondary intention, site 2 was treated with collagen-GAG scaffold (CG), and decellularised dermis (DCD) was applied to site 3 while tissue extracted from site 4 was replaced (autograft). Healing tissue was assessed weekly with optical coherence tomography (OCT), before being excised on days 7, 14, 21, or 28 depending on study group allocation for later histological and immunohistochemical evaluation. Extracted RNA was used in microarray analysis and polymerase chain reaction of highlighted genes. Autograft treatment resulted in minimal fibrosis confirmed immunohistochemically and with OCT through significantly lower collagen I levels ( p = 0.047 and 0.03) and reduced mean grayscale values ( p = 0.038 and 0.015), respectively. DCD developed intermediate scar formation with partial rete ridge reformation and reduced fasiculonodular fibrosis. It was uniquely associated with late up-regulation of matrix metalloproteinases 1 and 3, oncostatin M, and interleukin-10 ( p = 0.007, 0.04, 0.019, 0.019). Regenerated dermis was significantly thicker in DCD and autografts 28 days post-injury compared with control and CG samples ( p = 0.003 and <0.0001). In conclusion, variable fibrotic outcomes were observed in skin substitute-treated wounds with reduced scarring in autograft and DCD samples compared with controls. OCT enabled concurrent assessment of wound morphology and quantification of dermal fibrosis. [ABSTRACT FROM AUTHOR]

ABSTRACT The murine dorsum dermal excisional wound model has been widely utilized with or without splint application. However, variations in experimental methods create challenges for direct comparison of results provided in the literature and for design of new wound healing studies. Here, we investigated the effects of wound location and size, number of wounds, type of adhesive used for splint fixation on wound healing using splinted or unsplinted dorsum excisional full thickness wound models. One or two 6- or 8-mm full thickness wounds were made with or without splinting in genetically diabetic but heterozygous mice ( Dock7 m + / + Lepr db). Two different adhesives: tissue adhesive and an over the counter cyanoacrylate adhesive (OTCA) 'Krazy glue' were used to fix splints. Wound contraction, wound closure, and histopathological parameters including reepithelialization, collagen deposition and inflammation were compared between groups. No significant effect of wound number (1 vs. 2), side (left vs. right and cranial vs. caudal) or size on wound healing was observed. The OTCA group had a significantly higher splint success compared to the tissue adhesive group that resulted in significantly higher reepithelialization and collagen deposition in the OTCA group. Understanding the outcomes and effects of the variables will help investigators choose appropriate experimental conditions for the study purpose and interpret data. [ABSTRACT FROM AUTHOR]

ABSTRACT In the human body, vascular injuries that are caused by trauma, vessel lumen stenosis, and occlusions are often irreversible and can lead to sequelae formation as the vessels cannot reproduce fast enough. To solve this problem, the blood flow must be returned to the region as fast as possible. The adipose tissue contains progenitor cells with angiogenic potential and can be used to resolve the issue. In the present study, mesenchymal stem cells (MSCs) derived from rat adipose tissue, vascular endothelial growth factor (VEGF), and their mixture were applied on the dorsum of a rat, which was traumatized and its contribution to vascular regeneration was reviewed. No application was made to the control group. The results showed that the percentage of necrotic area was significantly lower in the MSC group than that of all the other groups. When the VEGF group was compared to the VEGF + MSCs, the percentage of necrotic area was observed to be similiar. However, VEGF showed effects only when a large quantites of VEGF was applied to the flap area. VEGF could not fully respond to the needs, whereas MSCs can produce VEGF according to the needs of tissue. This makes them superior to stem cells. [ABSTRACT FROM AUTHOR]

Growing evidence has shown the promise of mesenchymal stromal cells ( MSCs) for the treatment of cutaneous wound healing. We have previously demonstrated that MSCs seeded on an artificial dermal matrix, Integra (Integra Lifesciences Corp., Plainsboro, NJ) enriched with platelet-rich plasma ( Ematrix) have enhanced proliferative potential in vitro as compared with those cultured on the scaffold alone. In this study, we extended the experimentation by evaluating the efficacy of the MSCs seeded scaffolds in the healing of skin wounds in an animal model in vivo. It was found that the presence of MSCs within the scaffolds greatly ameliorated the quality of regenerated skin, reduced collagen deposition, enhanced reepithelization, increased neo-angiogenesis, and promoted a greater return of hair follicles and sebaceous glands. The mechanisms involved in these beneficial effects were likely related to the ability of MSCs to release paracrine factors modulating the wound healing response. MSC-seeded scaffolds, in fact, up-regulated matrix metalloproteinase 9 expression in the extracellular matrix and enhanced the recruitment of endogenous progenitors during tissue repair. In conclusion, the results of this study provide evidence that the treatment with MSC-seeded scaffolds of cutaneous wounds contributes to the recreation of a suitable microenvironment for promoting tissue repair/regeneration at the implantation sites. [ABSTRACT FROM AUTHOR]

The current work focuses on the in vivo performance of a newly developed injectable composite graft in infected full-thickness wounds. The composite graft was composed of bioactive porous Poly dl-lactide-co-glycolide scaffolds, antibiotic gentamicin, and crosslinked gelatin as carrier gel. Treated infected wounds exhibited a faster wound closure, rapid weight gain, lower neutrophil count, higher breaking strength, and 100 times lesser microbial count (102 colony forming units/g in infected treated vs. 104 colony forming units/g in infected control group) in comparison with infected control group 28 days post treatment. During healing, collagen production was more in the treated groups at day 7 than controls and thereafter gradually reduced to normal levels. Histology revealed a mature scar tissue formation, fibroblast proliferation, epidermal resurfacing, and collagen deposition in reticular alignment similar to normal healthy skin in treated wounds. Further, the plasma concentration of gentamicin was 35-45 μg/mL during the initial 12 hours and reduced to 1 μg/mL in 24 hours, which indicated safe levels of the antibiotic drug during healing. These results clearly indicate a faster, infection-free, and safe after treatment with the developed graft. [ABSTRACT FROM AUTHOR]

An interrupted stitch type with favorable tissue characteristics will reduce local wound complications. We describe a novel high-strength, low-tension repair for the interrupted closure of skin, cartilage, and muscle, the double loop mattress stitch, and compare it experimentally with other interrupted closure methods. The performance of the double loop mattress technique in porcine cartilage and skeletal muscle is compared with the simple, mattress, and loop mattress interrupted sutures in both a novel porcine loading chamber and mechanical model. Wound apposition is assessed by electron microscopy. The performance of the double loop mattress in vivo was confirmed using a series of 805 pediatric laparotomies/laparoscopies. The double loop mattress suture is 3.5 times stronger than the loop mattress in muscle and 1.6 times stronger in cartilage ( p ≤ 0.001). Additionally, the double loop mattress reduces tissue tension by 66% compared with just 53% for the loop mattress ( p ≤ 0.001). Wound gapping is equal, and wound eversion appears significantly improved ( p ≤ 0.001) compared with the loop mattress in vitro. In vivo, the double loop mattress performs as well as the loop mattress and significantly better than the mattress stitch in assessments of wound eversion and dehiscence. There were no episodes of stitch extrusion in our series of patients. The mechanical advantage of its intrinsic pulley arrangement gives the double loop mattress its favorable properties. Wound dehiscence is reduced because this stitch type is stronger and exerts less tension on the tissue than the mattress stitch. We advocate the use of this novel stitch wherever a high-strength, low-tension repair is required. These properties will enhance wound repair, and its application will be useful to surgeons of all disciplines. [ABSTRACT FROM AUTHOR]

The objectives of the study were (1) to look for any local, clinically apparent response, within and around a debrided wound, to a novel biocompatible polyurethane foam during repeated, short-term implantation, and (2) to assess the material's efficacy as a negative pressure wound therapy ( NPWT) interface compared with a widely used, commercially available foam. Twenty pressure ulcers in 18 patients underwent surgical debridement, then randomization to receive novel treatment or control foam as the wound interface for NPWT. Dressing changes every 2-3 days allowed qualitative wound assessment and quantitative measurement to compare outcomes. No adverse reaction was observed in any patient receiving the new foam. The new 'novel foam' performed as a NPWT interface as effectively as the control 'standard foam.' In deep wounds, the new foam was easier to remove, fragmented less, and showed less retention than the control foam. No marginal in-growth occurred, making removal less traumatic and reducing bleeding from cavity wall granulations. The results support previous large animal studies, and independent ISO10993 testing, that the new foam is safe and biocompatible. Its efficacy as an NPWT interface, nontraumatic removal with low fragmentation and retention rate, favors the new material, especially in deep cavity wounds. [ABSTRACT FROM AUTHOR]

Cross talk between fibroblasts and keratinocytes, which maintains skin homeostasis, is disrupted in chronic wounds. For venous leg ulcers and diabetic foot ulcers, a bilayered living cellular construct ( BLCC), containing both fibroblasts and keratinocytes that participate in cross talk, is a safe and effective product in healing chronic wounds. To show the importance of both cell types in BLCC, constructs were generated containing only fibroblasts or only keratinocytes and compared directly to BLCC via histology, mechanical testing, gene/protein analysis, and angiogenesis assays. BLCC contained a fully differentiated epithelium and showed greater tensile strength compared with one-cell-type constructs, most likely due to formation of intact basement membrane and well-established stratum corneum in BLCC. Furthermore, expression of important wound healing genes, cytokines, and growth factors was modulated by the cells in BLCC compared with constructs containing only one cell type. Finally, conditioned medium from BLCC promoted greater endothelial network formation compared with media from one-cell-type constructs. Overall, this study characterized a commercially available wound healing product and showed that the presence of both fibroblasts and keratinocytes in BLCC contributed to epithelial stratification, greater tensile strength, modulation of cytokine and growth factor expression, and increased angiogenic properties compared with constructs containing fibroblasts or keratinocytes alone. [ABSTRACT FROM AUTHOR]

The availability of fibroblasts that express green fluorescent protein ( GFP) would be of interest for the monitoring of cell growth, migration, contraction, and other processes within the fibroblast-populated collagen matrix and other culture systems. A plasmid lentiviral vector-GFP (pLV-GFP) was utilized for gene delivery to produce primary human foreskin fibroblasts ( HFFs) that stably express GFP. Cell morphology, cell migration, and collagen contraction were compared between nontransduced HFFs and transduced GFP- HFFs; no differences were observed. Immunocytochemical staining showed no differences in cell morphology between nontransduced and GFP- HFFs in both two-dimensional and three-dimensional culture systems. Furthermore, there was no significant difference in cellular population growth within the collagen matrix populated with nontransduced vs. GFP- HFFs. Within the limits of our assays, we conclude that transduction of GFP into HFFs did not alter the observed properties of HFFs compared with nontransduced fibroblasts. The GFP- HFFs may represent a new tool for the convenient monitoring of living primary fibroblast processes in two-dimensional or three-dimensional culture. [ABSTRACT FROM AUTHOR]

Sulfur mustard ( SM)-induced dermatotoxicity can be prevented by an immediate use of decontamination agents. However, practically due to the time lapse between decontamination and exposure, there is always a possibility of wound formation. In view of this, a hydrophilic decontamination formulation of CC-2 ( DRDE/ WH-03) was fortified with Aloe vera gel and betaine ( DRDE/ WH-01) for improving its wound healing ability. Swiss albino mice were exposed to SM percutaneously (5 mg/kg) once, and after 24 hours, DRDE/ WH-01, DRDE/ WH-03, framycetin, and aloe gel were applied topically, daily for 7 days. Skin sections were subjected to histopathology, histomorphologic grading, tissue leukocytosis, and immunohistochemistry of inflammatory-reparative biomarkers on 3 and 7 days, respectively. DRDE/ WH-01, framycetin, and aloe gel showed better reepithelialization, angiogenesis, and fibroplasia compared with DRDE/ WH-03 and SM control. On the basis of histomorphologic scale, DRDE/ WH-01, framycetin, and aloe gel were found to be equally efficacious. Up-regulation of interleukin-6 and infiltrating leukocytes, endothelial nitric oxide synthase and angiogenesis, fibroblast growth factor, and transforming growth factor-alpha with fibroplasia and reepithelialization were well correlated at various stages of the healing process. DRDE/ WH-01 was equally effective as framycetin and has shown improved wound healing efficacy compared with DRDE/ WH-03. Thus, DRDE/ WH-01 can be recommended as a universal decontaminant and wound healant against vesicant-induced skin injury. [ABSTRACT FROM AUTHOR]

Intensive insulin therapy during critical illness protects the endothelium and thereby prevents organ failure. This study tested the hypothesis that insulin directly affects the attenuation of burn injury-induced damage to pulmonary endothelial tight junction and investigated the underlying mechanisms. Sprague Dawley rats with severe burn injury were randomized to treatment with insulin dissolved in normal saline (maintenance of blood glucose at a level between 5.0 and 7.0 mmol/L) or normal saline alone (in vivo treatment). Pulmonary damage was evaluated. Rat pulmonary microvascular endothelial cells were treated with 20% burn serum or 20% burn serum + insulin (in vitro treatment). Selected cultures were pretreated with phosphatidylinositol 3-kinase/protein kinase B ( AKT) inhibitor ( LY294002). Permeability was assessed by migration of bovine serum albumin across cell monolayers. Cells were stained with rhodamine phalloidin and were examined. Cell extracts were obtained to assess zonula occludens-1, occludin, and phosphorylated AKT levels by immunoblotting. Treatment with insulin attenuated the pulmonary edema, hemorrhage, and inflammatory cell infiltration of rats with severe burn injury. Burn serum significantly enhanced monolayer permeability to albumin, whereas treatment with insulin (10−7 mol/L) limited this effect. Meanwhile, insulin (10−7 mol/L) reduced burn serum-induced F-actin stress fiber formation and decreased zonula occludens-1 expression. LY294002 decreased cytoplasmic AKT phosphorylation and inhibited the protection effects of insulin. Through the phosphatidylinositol 3-kinase/ AKT pathway, insulin independent of glucose toxicity can attenuate increased pulmonary endothelial permeability induced by burn injury. The effect is attributed to the attenuation of the architectural disruption of protein components of the endothelial tight junction. This result is useful in inhibiting multiple organ failure after burn injury. [ABSTRACT FROM AUTHOR]

We present results of an original clinical study investigating efficacy of a decellularized dermal skin substitute ( DCD) as part of a one-stage therapeutic strategy for recalcitrant leg ulcers. Twenty patients with treatment-resistant ulcers underwent hydrosurgical debridement, after which DCD was applied and covered with negative pressure dressings for 1 week. Participants were reviewed on seven occasions over 6 months. 3 D photography, full-field laser perfusion imaging, spectrophotometric intracutaneous analysis, and sequential biopsies were used to monitor healing. Mean ulcer duration and surface area prior to DCD placement were 4.76 years (range 0.25-40 years) and 13.11 cm2 (range 1.06-40.75 cm2), respectively. Seventy percent of ulcers were venous. Surface area decreased in all patients after treatment (range 23-100%). Mean reduction was 87% after 6 months, and 60% of patients healed completely. Wound bed hemoglobin flux increased significantly 6 weeks after treatment ( p = 0.005). Histological and immunohistochemical analysis confirmed progressive DCD integration with colonization by host fibroblasts, lymphocytes, and neutrophils, resulting in fibroplasia, reepithelialisation, and angiogenesis, with correlating raised CD31, collagen I, and collagen III levels. Subgroup analysis showed differing cellular behavior depending on wound duration, with delayed angiogenesis, reduced collagen deposition, and smaller reductions in surface area in ulcers present for over 1 year. The stain intensities of immunohistochemical markers including fibronectin, collagen, and CD31 differed depending on depth from the wound surface and presence of intact epithelium. DCD safely produced significant improvement in treatment-resistant leg ulcers. With no requirement for hospital admission, anesthetic, or autogenic skin grafting, this treatment could be administered in hospital and community settings. [ABSTRACT FROM AUTHOR]

Hyperbaric oxygen ( HBO) therapy is an effective treatment for diabetic chronic wounds. HBO reduces inflammation and accelerates wound healing, by mechanisms that remain unclear. Here we examined a mechanism by which HBO may reduce neutrophil recruitment, through changes in endothelial and neutrophil adhesion molecule expression and function. Human umbilical vein endothelial cells and neutrophils were exposed to selected chronic wound conditions, comprising hypoxia in the presence of lipopolysaccharide and tumor necrosis factor-alpha, and then treated with HBO. We observed neutrophil adhesion to endothelial cells following treatment with chronic wound conditions, which was reversed by HBO treatment. This was partly explained by reduced expression of endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by HBO. No changes in neutrophil adhesion molecule expression ( CD18, CD11b, CD62L, CD31) were observed following HBO treatment. However, HBO decreased hydrogen peroxide generation by neutrophils, and induced nitrous oxide-related protein modifications. The transnitrosating agent S-nitroso- L-cysteine ethyl ester (600 μM) also reduced neutrophil adhesion to human umbilical vein endothelial cell monolayers, and the iNOS inhibitor 1400 W (10 μM) and HgCl2, which promotes the decomposition of S-nitrosothiols (1 mM), reversed the effect of HBO, suggesting that S-nitrosation may inhibit neutrophil-endothelial cell adhesion. This study indicates that HBO could reduce inflammation in wounds through reduced neutrophil recruitment, mediated by S-nitrosation. [ABSTRACT FROM AUTHOR]

Venous ulcers are related to dysfunctions in extracellular matrix. Both matrix metalloproteinases ( MMP) and neutrophil gelatinase-associated lipocalin ( NGAL) could play a role in the healing process in patients with chronic venous ulcers. We evaluated the role of MMP-9 and NGAL in the healing process in venous ulceration. We performed an open-label, parallel groups, single clinical center study. Patients with chronic venous leg ulcers represented the test group (Group I), whereas patients without chronic ulcers represented the control group (Group II). In Group I plasma and wound fluid samples were collected at the time of admission, at the time of the surgery, and at the follow-up, while ulcer tissues were taken at the time of the surgery. In Group II, plasma and wound fluid were collected at admission and at the time of the surgery, whereas skin tissues were collected at the time of the surgery. Enzyme-linked immunosorbent assay test was used to evaluate the levels of MMP-9 and NGAL in plasma and wound fluid, whereas Western blot analysis was performed to estimate the expression of MMP-9 and NGAL in tissues. Enzyme-linked immunosorbent assay tests revealed significantly higher levels of MMP-9 and NGAL in both plasma and wound fluid of patients with ulcers compared to patients without ulcers ( p < 0.01). Moreover, Western blot analysis documented an increased expression of MMP-9 and NGAL in biopsy tissue of patients with ulcers compared to patients without ulcers ( p < 0.01). In conclusion MMP-9 and NGAL may correlate with the clinical course of venous ulcers. [ABSTRACT FROM AUTHOR]

Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa ( PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection model in C3 H/ He N and BALB/c mice. The chronic wound was established by an injection of seaweed alginate-embedded P. aeruginosa PAO1 beneath a third-degree thermal lesion providing full thickness skin necrosis, as in human chronic wounds. Cultures revealed growth of PA, and both alginate with or without PAO1 generated a polymorphonuclear-dominated inflammation early after infection. However, both at days 4 and 7, there were a more acute polymorphonuclear-dominated and higher degree of inflammation in the PAO1 containing group ( p < 0.05). Furthermore, PNA-FISH and supplemented DAPI staining showed bacteria organized in clusters, resembling biofilms, and inflammation located adjacent to the PA. The chronic wound infection showed a higher number of PAO1 in the BALB/c mice at day 4 after infection as compared to C3 H/ He N mice ( p < 0.006). In addition, a higher concentration of interleukin-1beta in the chronic wounds of BALB/c mice was observed at day 7 ( p < 0.02), despite a similar number of bacteria in the two mouse strains. The present study succeeded in establishing a chronic PA biofilm infection in mice. The results showed an aggravating impact of local inflammation induced by PA biofilms. In conclusion, our findings indicate that improved infection control of chronic wounds reduces the inflammatory response and may improve healing. [ABSTRACT FROM AUTHOR]

The contractile phenotype and function of myofibroblasts have been proposed to play a critical role in wound closure. It has been hypothesized that smooth muscle α-actin expressed in myofibroblasts is critical for its formation and function. We have used smooth muscle α-actin-null mice to test this hypothesis. Full-thickness excisional wounds closed at a similar rate in smooth muscle α-actin-null and wild-type mice. In addition, fibroblasts in smooth muscle α-actin-null granulation tissue when immunostained with a monoclonal antibody that recognizes all muscle actin isoforms exhibited a myofibroblast-like distribution and a stress fiber-like pattern, showing that these cells acquired the myofibroblast phenotype. Dermal fibroblasts from smooth muscle α-actin-null and wild-type mice formed stress fibers and supermature focal adhesions, and generated similar amounts of contractile force in response to transforming growth factor-β1. Smooth muscle γ-actin and skeletal muscle α-actin were expressed in smooth muscle α-actin-null myofibroblasts, as shown by immunostaining, real-time polymerase chain reaction, and mass spectrometry. These results show that smooth muscle α-actin is not necessary for myofibroblast formation and function and for wound closure, and that smooth muscle γ-actin and skeletal muscle α-actin may be able to functionally compensate for the lack of smooth muscle α-actin in myofibroblasts. [ABSTRACT FROM AUTHOR]

In this study, a multifunctional in situ-forming hydrogel ( MISG) was prepared as a wound dressing designed to stop bleeding, inhibit inflammation, relieve pain, and improve healing. A mixture of poloxamers 407 and 188 was used for the matrix of the MISG. Other ingredients include aminocaproic acid (to stop bleeding), povidone iodine (anti-infective), lidocaine (pain relief), and chitosan (to enhance wound healing and regeneration). The incipient gelation temperature of the MISG was modified by varying the poloxamer concentration. Poloxamer cytotoxicity was evaluated in addition to the effect of the MISG on hemostasis in rabbits, pain relief in mice, bacteriostasis in vitro, and wound healing. The optimal MISG matrix consisted of 30% (w/v) poloxamer (407/188, 1 : 1, w/w) solution and was able to change to a gel within 10 minutes at 37 °C. The poloxamer solution had no cytotoxicity in fibroblasts. Compared to sterile gauze alone, the MISG significantly shortened average hemostasis time and decreased bleeding. The hydrogel showed strong bacteriostatic action similar to povidone iodine solution. It markedly increased the pain threshold and accelerated wound healing compared to the gauze. The MISG is a promising formulation for wound healing in emergency situations. [ABSTRACT FROM AUTHOR]

Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measurements. Prostaglandin E2 content, matrix metalloproteinase-2 and 9 activity, and histopathology were conducted up to 4 weeks post-exposure. Sulfur mustard skin injury, including erythema and edema, impairment of skin barrier and wounds developed in a dose-dependent manner. Prostaglandin E2 content and matrix metalloproteinase-2 and 9 activities were elevated during the wound development and the healing process. Histological evaluation revealed severe damage to the epidermis and deep dermis and vesications. At 4 weeks postexposure, healing was not completed: significantly impaired stratum corneum, absence of hair follicles, and epidermal hyperplasia were observed. These results confirm the use of the superficial and deep dermal skin injuries in the hairless guinea pigs as suitable models that can be utilized for the investigation of the pathological processes of acute as well as long-term injuries. These models will be further used to develop treatments to improve the healing process and prevent skin damage and long-term effects. [ABSTRACT FROM AUTHOR]

Previous research has shown clinical effectiveness of dermal substitution; however, in burn wounds, only limited effect has been shown. A problem in burn wounds is the reduced take of the autograft, when the substitute and graft are applied in one procedure. Recently, application of topical negative pressure ( TNP) was shown to improve graft take. The aim of this study was to investigate if application of a dermal substitute in combination with TNP improves scar quality after burns. In a four-armed multicenter randomized controlled trial, a split-skin graft with or without a dermal substitute and with or without TNP was compared in patients with deep dermal or full-thickness burns requiring skin transplantation. Graft take and rate of wound epithelialization were evaluated. Three and 12 months postoperatively, scar parameters were measured. The results of 86 patients showed that graft take and epithelialization did not reveal significant differences. Significantly fewer wounds in the TNP group showed postoperative contamination, compared to other groups. Highest elasticity was measured in scars treated with the substitute and TNP, which was significantly better compared to scars treated with the substitute alone. Concluding, this randomized controlled trial shows the effectiveness of dermal substitution combined with TNP in burns, based on extensive wound and scar measurements. [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor ( MIF), a structurally and functionally unique pleiotropic mediator in inflammation and immune processes, was identified decades ago. There is now strong evidence that MIF promotes revascularization and is involved in wound healing processes. However, its exact role in wound healing is still a matter of debate. A cohort of 33 patients was recruited, including 14 patients with acute and 19 patients with chronic wounds. Both serum and wound fluid samples were collected from each patient, and MIF and cortisol concentrations were determined. To functionally underscore MIF's potential role in wound revascularization, a chemotaxis assay was adapted to test whether and to what extent serum samples and wound fluids of each group promote the chemotactic migration of endothelial progenitor cells ( EPCs). MIF serum levels were significantly higher in chronic wound patients than in acute wound patients. Wound exudates of chronic wounds, however, contained a significantly lower concentration of MIF. In chronic wound patients, EPC migration might be delayed, as suggested by in vitro chemotaxis experiments. Despite the overall descriptive nature of this study, we conclude that MIF is correlated with occurrence of chronic wound. The increased MIF levels in the serum of chronic wound patients might be due to MIF's systemic effect of its proinflammatory activities, while its locally decreased levels in chronic wound exudates might be responsible for impaired recruitment of EPCs. Additional prospective data and detailed in vivo models are needed for a more comprehensive understanding of the role of MIF in chronic wound healing. [ABSTRACT FROM AUTHOR]

This randomized, double-blind, placebo-controlled Phase 2 clinical trial explored NorLeu3- A(1-7) ( DSC127) safety and healing efficacy in diabetic foot ulcers. Patients with chronic, noninfected, neuropathic, or neuroischemic plantar Wagner Grade 1 or 2 foot ulcers ( n = 172) were screened for nonhealing. Subjects were randomized to receive 4 weeks' once-daily topical treatment with 0.03% DSC127 ( n = 26), 0.01% DSC127 ( n = 27), or Placebo ( n = 24), followed by 20 weeks' standard of care. DSC127 was assessed for safety (including laboratory values and adverse events), primary efficacy (% ulcers completely epithelialized at Week 12), and durability of effect. Baseline, demography, and safety parameters were compared between intent-to-treat groups and were comparable. Dose-response curves for DSC127 effect on % area reduction from baseline at Week 12 (40% placebo; 67% 0.01% DSC127; 80% 0.03% DSC127) and 24 (23% placebo; 53% 0.01% DSC127; 95% 0.03% DSC127) followed a log-linear pattern for both intent-to-treat and per-protocol populations. Covariate analysis compared reduction in ulcer area, depth, and volume from baseline; reductions in the 0.03% DSC127 group were greater at Weeks 12 and 24. Placebo-treated ulcers healed in a median 22 weeks vs. 8.5 weeks for 0.03% DSC127 ( p = 0.04). This study provides preliminary evidence that DSC127 is safe and effective in accelerating the healing of diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess healing after capsaicin-induced substance P ( SP) depletion during rat Achilles tendon repair by biomechanical testing. Capsaicin treatment reduced the concentrations of SP by ∼60% and calcitonin gene-related peptide by ∼40% as compared with the control group, as assessed by radioimmunoassay in the dorsal root ganglia, at 1 and 4 weeks post-tendon rupture. Also, the peripheral neuronal presence of SP and calcitonin gene-related peptide, as assessed by immunohistochemistry, was lower at both weeks 1 and 4. The decreased peripheral neuronal presence of SP at week 1 correlated with the corresponding levels in the dorsal root ganglia ( r = 0.54, p = 0.018). The reduced presence of SP/calcitonin gene-related peptide after capsaicin treatment was verified by a decreased sensitivity to painful mechanical and thermal stimuli ( p < 0.05). Correlation analyses between individual residual SP levels and biomechanical tissue properties were performed because of differences in failure mode between the groups and high individual variations in the SP levels after capsaicin treatment. Thus, the residual SP levels in the dorsal root ganglia correlated with transverse area, ultimate tensile strength, and stress at failure ( r = 0.39, p = 0.036; r = 0.53, p = 0.005; and r = 0.43, p = 0.023, respectively). Furthermore, individual pain sensitivity at week 2 correlated with peripheral occurrence of SP and was correlated with tensile strength and stress at failure ( r = 0.89, p = 0.006 and r = 0.78, p = 0.015) at week 4. In conclusion, rats with higher residual SP levels after capsaicin-induced neuropathy develop improved tensile strength and stress at failure in the healing of Achilles tendon. [ABSTRACT FROM AUTHOR]

Chronic non-healing wounds affect a significant number of patients worldwide. Although the etiologies of these wounds are varied, bacterial infection has been suggested as a major factor responsible for the perpetual inflammation and tissue destruction observed in such wounds. Recent evidence has emerged suggesting that bacterial biofilms in particular may have a significant role in this process. At the same time, topical negative pressure dressing is gaining acceptance as a therapy which promotes healing in recalcitrant wounds. In this study an in vitro Pseudomonas aeruginosa biofilm model was developed to mimic potential surface wound biofilms. Topical negative pressure dressing was applied to the model and the effects of topical negative pressure dressing on the in vitro wound biofilms were examined using both quantitative microbiological counting technique and imaging studies. The results demonstrated a small but statistically significant reduction in biofilm bacteria at 2 weeks when exposed to topical negative pressure. When this was combined with silver impregnated foam, the reduction was far more significant and was observable within 24 hours. Microscopically, it was also noted that topical negative pressure compressed the biofilm architecture with a reduction in thickness and diffusion distance. [ABSTRACT FROM AUTHOR]

Orchidectomy in rodents and lower testosterone levels in men are associated with improved cutaneous wound healing. However, due to the adverse effects on skeletal and sexual tissues, systemic androgen blockade is not a viable therapeutic intervention. Accordingly, we tested the hypothesis that topical application of an androgen antagonist would elicit accelerated wound healing without systemic androgen antagonism. Full-thickness cutaneous wounds were created on adult C57BL6/J mice. Daily topical application of androgen receptor antagonist, flutamide, resulted in improved gap closure similar to orchiectomized controls and faster than orchidectomized mice treated with topical testosterone. In vivo data showed that the effects of androgen antagonism on wound closure primarily accelerate keratinocytes migration without effecting wound contraction. Consequently, mechanisms of testosterone action on reepithelialization were investigated in vitro by scratch wounding assays in confluent keratinocytes. Testosterone inhibited keratinocyte migration and this effect was in part mediated through promotion of nuclear translocation of β-catenin and by attenuating transforming growth factor-β ( TGF-β) signaling through β-catenin. The link between Wnt and TGF beta signaling was confirmed by blocking β-catenin and by following TGF-β-induced transcription of a luciferase reporter gene. Together, these data show that blockade of β-catenin can, as a potential target for novel therapeutic interventions, accelerate cutaneous wound healing. [ABSTRACT FROM AUTHOR]

Transcutaneous oximetry ( PtcO2) has been proposed as a method to predict nonhealing of chronic wounds and the occurrence of healing complications. However, the validity of this method as an independent predictor and an optimal threshold value for this tool are poorly defined. We undertook a systematic review and meta-analysis to address these questions, searching five major medical databases, relevant review articles, and reference lists. We included all studies that used multivariable analysis to evaluate PtcO2 for its ability to predict chronic wound healing complications. Article selection and data abstraction were conducted independently and in duplicate. Four studies, enrolling 901 patients with 910 lower extremity chronic wounds, met our inclusion criteria. These studies showed that a peri-wound PtcO2 level below a cutoff of 20 mm Hg or 30 mm Hg was an independent predictor of chronic wound healing complications (odds ratio 3.21, 95% confidence interval 1.07-9.69, I2 = 77%). A threshold value of 20 mm Hg was used most frequently in the included studies and showed the strongest association. This review was limited by the small number of studies, a possible reporting bias, and heterogeneity. These results suggest that PtcO2 measurements have independent prognostic value in the assessment of chronic wounds, but further research is required to confirm these findings and define an optimal threshold value. [ABSTRACT FROM AUTHOR]

Malignant wounds ( MWs) occur in 5-10% of all cancer patients. Malodor and exudation are the most common side effects. The aim was to determine the influence of honey-coated compared with silver-coated bandages on treatment of MWs. Patients were randomly selected to enter either group A (honey-coated bandages) or group B (silver-coated bandages). Parameters were the following: wound size, cleanliness, malodor, exudation, and wound pain. Digital photographs, visual analog scales ( VAS), and wound morphology registration were used for measurement at baseline and following the 4-week intervention. Sixty-nine patients with MWs and advanced cancer, aged 47-90 (median 65.6), were included. No statistically significant difference was noted between the groups with respect to wound size, degree of cleanliness, exudation, malodor, and wound pain. There was a median decrease in wound size of 15 cm2 and 8 cm2 in group A and B, respectively ( p = 0.63). Based on post-intervention pooled data from the groups, improvement was seen in 62% of the participants with respect to wound size and in 58% ( n = 69) with respect to cleanliness. The VAS score for malodor ( p = 0.007) and exudation ( p < 0.0001) improved significantly post-intervention. Patients with reduced wound size had a median survival time of 387 days compared with 134 days in patients with no wound reduction ( p = 0.003). The use of honey-coated and silver-coated bandages improved the outcome of MWs. No differences were found between the two regimens. Both types of bandages are recommended for use by patients with MWs containing tumor debris and necrosis. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine the prevalence rate for inherited thrombophilia ( IT) in patients with chronic ( CVU) and recurrent venous leg ulceration. We also investigated and evaluated the severity of the clinical pattern of CVU in patients with and without IT. We examined 110 patients with CVU (the study group) and 110 healthy subjects (the control group). We prepared a questionnaire to be completed by each study participant. Ultrasound Doppler color imaging or/and duplex ultrasonography was performed to evaluate the efficiency of the venous system. The ankle-brachial index was calculated to determine the efficiency of the arterial system. We examined both groups for the presence of IT. IT was diagnosed in 30% of study group and in 1.8% of control group. Our diagnoses of deep vein thrombosis ( DVT) were based on medical interviews, physical examinations, and an ultrasonography of the venous system and concerned 64 study group patients (58.2%), 35 of whom (31.8%) experienced recurrent DVT. Proximal and/or distal DVT was determined in an interview and/or by an ultrasonography performed for all patients with CVU and IT. In 94% of these patients, DVT was recurrent, and in 88% of patients with CVU and IT, we observed recurrent DVT and CVU. It recurred more often and persisted longer when compared to patients with CVU and no IT, despite similar management. No differences were observed in ulcer size, localization, or pain level related to ulceration between patients with CVU and IT and those with CVU and no IT. [ABSTRACT FROM AUTHOR]

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A growing body of evidence suggests that in addition to hypoxia, ischemia-reperfusion injury, and intrinsic host factors, bacterial biofilms represent a fourth major pillar in chronic wound pathogenesis. Given that most studies to date rely on in vitro or observational clinical data, our aim was to develop a novel, quantitative animal model enabling further investigation of the biofilm hypothesis in vivo. Dermal punch wounds were created in New Zealand rabbit ears, and used as uninfected controls, or inoculated with green fluorescent protein-labeled Staphylococcus aureus to form wounds with bacteria predominantly in the planktonic or biofilm phase. Epifluorescence and scanning electron microscopy revealed that S. aureus rapidly forms mature biofilm in wounds within 24 hours of inoculation, with persistence of biofilm viability over time seen through serial bacterial count measurement and laser scanning confocal imaging at different time points postwounding and inoculation. Inflammatory markers confirmed that the biofilm phenotype creates a characteristic, sustained, low-grade inflammatory response, and that over time biofilm impairs epithelial migration and granulation tissue in-growth, as shown histologically. We have established and validated a highly quantitative, reproducible in vivo biofilm model, while providing evidence that the biofilm phenotype specifically contributes to profound cutaneous wound healing impairment. Our model highlights the importance of bacterial biofilms in chronic wound pathogenesis, providing an in vivo platform for further inquiry into the basic biology of bacterial biofilm-host interaction and high-throughput testing of antibiofilm therapeutics. [ABSTRACT FROM AUTHOR]

A novel noncontact optical coherence tomography based air-jet indentation system was developed for characterizing the biomechanical properties of soft tissue in a noncontact way. This study aimed to measure the stiffness of diabetic foot ulcer tissues by using this air-jet indentation system, and examining the test/retest reliability. Eight subjects with diabetes (seven males, one female), with a total of 10 foot ulcers between them, participated in the study. A total of 20 measuring sites located at the central wound bed ( n=10) or peri-ulcer areas ( n=10), respectively, were evaluated with the air-jet indentation system. Four cycles of loading and unloading, each with a duration of approximately 36 seconds at an indentation rate of 0.08 mm/s, were carried out for each indentation trial. The test/retest reliability was examined at all measuring points. The average stiffness coefficient of the peri-ulcer area (mean±SD: 0.47±0.15 N/mm) was significantly larger than that of the central wound bed area (mean±SD: 0.35±0.23 N/mm; p=0.042). A high value for test/retest reliability was shown (intraclass correlation coefficient: 0.986; Pearson's correlation: r=0.972, p<0.001). Our preliminary findings showed that the peri-ulcer area had greater stiffness than the central wound bed. This greater magnitude of hardness and inelasticity at the peri-ulcer region may scatter part of the contractile forces for wound contraction during the healing process. We found the novel air-jet system to be a reliable tool for characterizing the stiffness of soft tissues around the wound in a noncontact way. [ABSTRACT FROM AUTHOR]

The objective of these studies was to provide detailed analyses of the time course of sulfur mustard (SM) vapor-induced clinical, histological, and biochemical changes following cutaneous exposure in hairless guinea-pigs. Three 6 cm sites on the backs of each guinea-pig were exposed to SM vapor (314 mg) for 6 minutes (low dose) or 12 minutes (high dose). Animals were killed at 6, 24, and 48 hours, or 2 weeks postexposure. Erythema, edema, histopathology, and analysis of matrix metalloproteinase (MMP)-2 and -9 content were evaluated. Erythema was observed by 6 hours, and edema by 24 hours postexposure. Vapor exposure caused epidermal necrosis with varying degrees of dermatitis, ulceration, hemorrhage, and separation of the dermis from the epidermis. Later changes included epidermal regeneration with hyperplasia and formation of granulation tissue in the dermis with loss of hair follicles and glandular structures. Relative amounts of pro and active MMP-2 and MMP-9 were significantly increased in the high-dose SM group at 2 weeks. Erythema, edema, and histologic changes are consistent with findings among human victims of SM attack. This model, with observations to 2 weeks, will be useful in assessing the efficacy of countermeasures against SM. [ABSTRACT FROM AUTHOR]

The local pathogenesis of interstitial edema in burns is incompletely understood. This ex vivo study investigates the forces mediating water-transfer in and out of heat-denatured interstitial matrix. Experimentally, full-thickness dermal samples are heated progressively to disrupt glycosaminoglycans, kill cells, and denature collagen under conditions that prevent water loss/gain; subsequently, a battery of complementary techniques including among others, high-resolution magnetic resonance imaging, equilibrium vapor pressure and osmotic stress are used to compare water-potential parameters of nonheated and heated dermis. The hydration potential (HP) determined by osmotic stress is a measure of the total water-potential defined empirically as the pressure at which no net water influx/efflux into/from the dermis is detected. Results show that after heat denaturation, the HP, the intensity of T2-weighed magnetic resonance images, and the vapor pressure increase indicating higher water activity and necessarily, smaller contributions from colloidosmotic forces to fluid influx in burned relative to healthy dermis. Concomitant increases in HP and in water activity implicate local changes in interfacial and metabolic energy as the source of excess fluid-transfer potential. These ex vivo findings also show that these additional forces contributing to abnormal fluid-transfer in burned skin develop independently of inflammatory and systemic hydrodynamic responses. [ABSTRACT FROM AUTHOR]

Chronic venous leg ulcers are common and cause considerable burden of disease for affected patients with significant costs for health care systems worldwide. The complex pathophysiology of chronic venous leg ulcers is still not entirely understood. In addition, reliable pathogenic and/or prognostic parameters are not known. Published data suggest that patients with chronic venous leg ulcers reveal congenital or acquired thrombophilia. We examined the serum Lipoprotein (a) [Lp(a)] level, a proatherogenic and prothrombotic risk factor, in patients with chronic venous leg ulcers ( n=210, stratified into patients with postthrombotic syndrome or without) and in a healthy control group ( n=341). Forty-two percent of all patients, compared with 20% of healthy controls, revealed significantly increased Lp(a) serum concentrations above 0.3 g/L. Furthermore, 49% without postthrombotic syndrome but only 35% with postthrombotic syndrome showed increased Lp(a) levels. The increase of Lp(a) level was significantly different between all three groups ( p<0.001). There was no correlation of Lp(a) levels and CRP values in all groups. Based on these data, it is conceivable that Lp(a) plasma level is a novel pathogenic parameter for chronic venous leg ulcers. Elevated concentrations may contribute to the pathogenesis through induction of thrombogenic microcirculatory dysregulations, impaired extravascular fibrinolysis, or other mechanisms like proinflammatory effects. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop and validate a pressure ulcer risk assessment for acute hospitals. This tool was developed in a cohort of 342 patients with a mean age 63 years (SD 19.82) and validated in a second cohort of 165 patients with a mean age 68 years (SD 18.40). Risk factors for inclusion on The Northern Hospital Pressure Ulcer Prevention Plan (TNH-PUPP) were identified from the literature then examined and weighted using logistic regression. Risk factors included on the TNH-PUPP were requires assistance to move in bed (odds ratio [OR] 5.15; 95% confidence interval [CI]: 2.49-10.65), admission to intensive care during current admission (OR 2.98; 95% CI: 1.33-6.67), aged ≥65 years (OR 2.81; 95% CI: 1.24-6.36), reduced sensation (OR 2.29; 95% CI: 1.19-4.42), and cognitive impairment (OR 2.26; 95% CI: 1.09-4.67). The TNH-PUPP was validated in a prospective sample. The new tool had high diagnostic validity (area under the receiver operating curve=0.86), consistent in the validation sample (area under the receiver operating curve=0.90). The TNH-PUPP has a moderate positive predictive value (development=0.50; validation=0.13), and a high negative predictive value (development=0.94; validation=0.99) enabling low-risk patients to be screened out, as noncandidates for pressure ulcer prevention interventions. An accurate pressure ulcer risk assessment has been developed and validated, which identifies a high-risk group to whom limited pressure ulcer prevention resources should be directed. The TNH-PUPP facilitates effective resource allocation and is likely to reduce unnecessary patient harm and costs from pressure ulcers in acute hospitals. [ABSTRACT FROM AUTHOR]

Diabetes is characterized by several poorly understood phenomena including dysfunctional wound healing and impaired vasculogenesis. p53, a master cell cycle regulator, is upregulated in diabetic wounds and has recently been shown to play a regulatory roles in vasculogenic pathways. We have previously described a novel method to topically silence target genes in a wound bed with small interfering (si)RNA. We hypothesized that silencing p53 results in improved diabetic wound healing and augmentation of vasculogenic mediators. Paired 4-mm stented wounds were created on diabetic db/db mice. Topically applied p53 siRNA, evenly distributed in an agarose matrix, was applied to wounds at postwound day 1 and 7 (matrix alone and nonsense siRNA served as controls). Animals were sacrificed at postwound days 10 and 24. Wound time to closure was photometrically assessed, and wounds were harvested for histology, immunohistochemistry, and immunofluorescence. Vasculogenic cytokine expression was evaluated via Western blot, reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay. The ANOVA/ t-test was used to determine significance ( p≤ 0.05). Local p53 silencing resulted in faster wound healing with wound closure at 18±1.3 d in the treated group vs. 28±1.0 d in controls. The treated group demonstrated improved wound architecture at each time point while demonstrating near-complete local p53 knockdown. Moreover, treated wounds showed a 1.92-fold increase in CD31 endothelial cell staining over controls. Western blot analysis confirmed near-complete p53 knockdown in treated wounds. At day 10, VEGF secretion (enzyme-linked immunosorbent assay) was significantly increased in treated wounds (109.3±13.9 pg/mL) vs. controls (33.0±3.8 pg/mL) while reverse transcription-polymerase chain reaction demonstrated a 1.86-fold increase in SDF-1 expression in treated wounds vs. controls. This profile was reversed after the treated wounds healed and before closure of controls (day 24). Augmented vasculogenic cytokine profile and endothelial cell markers are associated with improved diabetic wound healing in topical gene therapy with p53 siRNA. [ABSTRACT FROM AUTHOR]

Venous ulcers are chronic wounds affecting up to 1% of adults in developed countries. Considering that noncontact normothermic therapy has been shown to modify the wound healing process, we conducted a prospective comparative clinical trial aimed at evaluating 980 nm diode laser in laser-assisted venous ulcer healing. Thirty-four Caucasian patients with venous leg ulcers were included in the study and separated into two homogenous groups based on age, sex ratio, size, and etiologies of the ulcers. In the laser group, 980 nm InGasAs diode laser (power 15 W, spot size 8 mm, time 3 seconds, fluence 90 J/cm) was applied weekly for 9 weeks to the ulcers in a homogenous standardized manner, resulting in a local temperature of 45-50 °C, which was controlled with a thermal infrared camera. Complete healing, reduction in size, and pain during and between each procedure were evaluated each time. Of the 18 patients in the laser group, three (16.7%) were completely healed during laser treatment. In the control group (16 patients), the healing was complete for four patients (25%). This difference was not significant ( p=0.62). At the ninth follow-up visit, in the control group, the ulcers had decreased on an average to 94.3% of the original area of the ulcers. In the laser group, the decrease was to 74.2% of the original area of the ulcers. Again, this difference was not significant ( p=0.60). The mean VAS score between each treatment was 2.7 (0.5-4.4) in the laser group compared with 3.8 (2.3-5.0) in the control group (0.13< p<0.86). During the treatment, the mean VAS score was 1.8 (0.2-3.8) in the laser group compared with 3.8 (2.1-6.0) in the control group (0.08< p<0.67). 980 nm diode laser-assisted venous ulcer healing was easy to perform and very well tolerated. However, there were no statistically significant differences in reduction of ulcer size between the two groups, suggesting that this particular laser regimen does not promote wound healing. Additional studies involving larger patient populations and an increased frequency of treatment should be performed to confirm our initial conclusions. [ABSTRACT FROM AUTHOR]

Liver regeneration is a complex process that is orchestrated by the precise interplay of cell proliferation, differentiation control, and molecular pathways, but this complicated molecular signaling network is not fully understood. In this study, we showed that N-Myc downstream-regulated gene 2 (NDRG2) is involved in this process. The mRNA and protein levels of NDRG2 were strongly reduced when liver regeneration reached a peak of activity. In addition, we found that rat NDRG2 expression and C-Myc expression were inversely correlated during this process. A low level of NDRG2 was observed as the C-Myc expression increased during regeneration. Moreover, a dramatic cell cycle arrest was found in normal rat liver-derived BRL cells 48 hours after being infected by adenoviral vectors expressing rat NDRG2. Meanwhile, the apoptotic rates were increased from 9.4% in control group to 64.7% in adenoviral vectors expressing rat NDRG2 group. These phenomena could also be observed in BRL 3A and L-02 cells. Further analysis revealed that NDRG2 overexpression may mediate the antiproliferative effect by inducing p53 and p21 regulated Bax/Bcl-2 increase and cyclin E-Cdk2 inhibition. In conclusion, our findings point to physiological roles for NDRG2 in liver regeneration. [ABSTRACT FROM AUTHOR]

Studies in the field of wound healing have utilized a variety of different housekeeping genes for reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. However, nearly all of these studies assume that the selected normalization gene is stably expressed throughout the course of the repair process. The purpose of our current investigation was to identify the most stable housekeeping genes for studying gene expression in mouse wound healing using RT-qPCR. To identify which housekeeping genes are optimal for studying gene expression in wound healing, we examined all articles published in Wound Repair and Regeneration that cited RT-qPCR during the period of January/February 2008 until July/August 2009. We determined that ACTβ, GAPDH, 18S, and β 2M were the most frequently used housekeeping genes in human, mouse, and pig studies. We also investigated nine commonly used housekeeping genes that are not generally used in wound healing models: GUS, TBP, RPLP2, ATP5B, SDHA, UBC, CANX, CYC1, and YWHAZ. We observed that wounded and unwounded tissues have contrasting housekeeping gene expression stability. The results demonstrate that commonly used housekeeping genes must be validated as accurate normalizing genes for each individual experimental condition. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study on high mortality rates in patients with chronic wounds in the U.S., which shows that 28% of wounded outpatients die within a two-year period as compared to 2.5% mortality among patients who are treated in hospitals.