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Immunofluorescence staining in the wound. Typical immunofluorescence staining for endothelial cells with CD31 expression (red) and pericytes with α-smooth muscle actin (α-SMA) expression (green) on days 7 and 10. Scale bar, 50 µm. Original magnification, x200.
Source publication
Negative pressure wound therapy (NPWT) has been demonstrated to accelerate wound healing by promoting angiogenesis. However, whether blood flow perfusion is regulated by microvessel maturation and pericytes following NPWT remains unclear, as well as the exact association between pericytes and collagen type IV. The aim of this study was to investiga...
Contexts in source publication
Context 1
... The double immunofluorescence marker, CD31, and α-SMA were combined to mark vascular endothelial cells and microvascular pericytes (Fig. 3). On the 1st day, a few CD31-positive cells were observed in the NPWT group, and a small amount of endothelial cells was detected with red marker CD31-positive cells in the NPWT group at day 3 (data not shown). On the 7th day, a large amount of endothelial cells was detected; in addition, a small number of endothelial cells was observed ...
Context 2
... detected on the 3rd day (data not shown). On the 7th day, a great number of pericytes was detected, and was distributed discontinuously around the endothelial cell lumen in the NPWT group. An abundance of pericytes was detected in the NPWT group on the 10th day, with the pericytes tightly encircling and covering the microvessel endothelial tubes (Fig. 3). Subsequently, a small number of pericytes was detected in the gauze group on the 3rd and 7th day, and a number of pericytes was detected on the 10th day in the gauze group; however, this number was significantly lower than that in the NPWT group at the same time points (P<0.05), and in the NPWT group it was significantly higher than ...
Citations
... NPWT suggests that negative pressure is responsible for the mechanism of action and thus its therapeutic success. However, its success is undisputedly the result of numerous different effects, including interstitial edema reduction, but above all improved blood circulation [11][12][13][14][15][16]. Over the last decade, this has 2 of 9 been cited many times, with the initial investigation being performed by Morykwas et al., which postulated an opening of the capillaries resulting in increased perfusion [17]. ...
Background: Negative pressure wound therapy (NPWT) is an intensely investigated topic, but its mechanism of action accounts for one of the least understood ones in the area of wound healing. Apart from a misleading nomenclature, by far the most used diagnostic tool to investigate NPWT, the laser Doppler, also has its weaknesses regarding the detection of changes in blood flow and velocity. The aim of the present study is to explain laser Doppler readings within the context of NPWT influence. Methods: The cutaneous microcirculation beneath an NPWT system of 10 healthy volunteers was assessed using two different laser Dopplers (O2C/Rad-97®). This was combined with an in vitro experiment simulating the compressing and displacing forces of NPWT on the arterial and venous system. Results: Using the O2C, a baseline value of 194 and 70 arbitrary units was measured for the flow and relative hemoglobin, respectively. There was an increase in flow to 230 arbitrary units (p = 0.09) when the NPWT device was switched on. No change was seen in the relative hemoglobin (p = 0.77). With the Rad-97®, a baseline of 92.91% and 0.17% was measured for the saturation and perfusion index, respectively. No significant change in saturation was noted during the NPWT treatment phase, but the perfusion index increased to 0.32% (p = 0.04). Applying NPWT compared to the arteriovenous-vessel model resulted in a 28 mm and 10 mm increase in the venous and arterial water column, respectively. Conclusions: We suspect the vacuum-mediated positive pressure of the NPWT results in a differential displacement of the venous and arterial blood column, with stronger displacement of the venous side. This ratio may explain the increased perfusion index of the laser Doppler. Our in vitro setup supports this finding as compressive forces on the bottom of two water columns within a manometer with different resistances results in unequal displacement.
... c conduit, m magnet, white box indicates the region of interest rats underwent either VAC or gauze treatment of a superficial leg wound. The results revealed that VAC therapy not only increased the blood flow perfusion in the wound area, but also promoted the overexpression of angiogenic factors and maturation of microvessels [44]. This would be interesting to also test in the animal model for gastric conduit with longer lasting experiments in a survival model in the future. ...
After esophagectomy, the postoperative rate of anastomotic leakage is up to 30% and is the main driver of postoperative morbidity. Contemporary management includes endoluminal vacuum sponge therapy (EndoVAC) with good success rates. Vacuum therapy improves tissue perfusion in superficial wounds, but this has not been shown for gastric conduits. This study aimed to assess gastric conduit perfusion with EndoVAC in a porcine model for esophagectomy.
A porcine model (n = 18) was used with gastric conduit formation and induction of ischemia at the cranial end of the gastric conduit with measurement of tissue perfusion over time. In three experimental groups EndoVAC therapy was then used in the gastric conduit (− 40, − 125, and − 200 mmHg). Changes in tissue perfusion and tissue edema were assessed using hyperspectral imaging. The study was approved by local authorities (Project License G-333/19, G-67/22).
Induction of ischemia led to significant reduction of tissue oxygenation from 65.1 ± 2.5% to 44.7 ± 5.5% (p < 0.01). After EndoVAC therapy with − 125 mmHg a significant increase in tissue oxygenation to 61.9 ± 5.5% was seen after 60 min and stayed stable after 120 min (62.9 ± 9.4%, p < 0.01 vs tissue ischemia). A similar improvement was seen with EndoVAC therapy at − 200 mmHg. A nonsignificant increase in oxygenation levels was also seen after therapy with − 40 mmHg, from 46.3 ± 3.4% to 52.5 ± 4.3% and 53.9 ± 8.1% after 60 and 120 min respectively (p > 0.05). An increase in tissue edema was observed after 60 and 120 min of EndoVAC therapy with − 200 mmHg but not with − 40 and − 125 mmHg.
EndoVAC therapy with a pressure of − 125 mmHg significantly increased tissue perfusion of ischemic gastric conduit. With better understanding of underlying physiology the optimal use of EndoVAC therapy can be determined including a possible preemptive use for gastric conduits with impaired arterial perfusion or venous congestion.
... NPWT is a device that optimises wound healing through various mechanisms including establishing a tissue pressure gradient [23], enhancing the wound bed environment, [24] micro-and macro deformations, encouraging cell mitosis [25] and promoting angiogenesis and lymphangiogenesis [26]. Our study team, led by Frear et al., completed a single-site randomised control trial (RCT) of 114 Australian children aged up to 16 years with small, superficial partial thickness paediatric burns and found that NWPT applied within the first 7 days, compared to standard dressings of Mepitel ® and ACTICOAT ™ , decreased the time to re-epithelialisation by 22% (95% CI 7 to 34%) [27]. ...
Introduction
The goal of paediatric hand and foot burn management is hypertrophic scar and/or contracture prevention. The risk of scar formation may be minimised by integrating negative pressure wound therapy (NPWT) as an acute care adjunct as it decreases the time to re-epithelialisation. NPWT has known associated therapeutic burden; however, this burden is hypothesised to be outweighed by an increased likelihood of hypertrophic scar prevention. This study will assess the feasibility, acceptability and safety of NPWT in paediatric hand and foot burns with secondary outcomes of time to re-epithelialisation, pain, itch, cost and scar formation.
Methods and analysis
This is a single-site, pilot randomised control trial. Participants must be aged ≤ 16 years, otherwise well and managed within 24 h of sustaining either a hand or foot burn. Thirty participants will be randomised to either standard care (Mepitel®—a silicone wound interface contact dressing—and ACTICOAT™—a nanocrystalline silver-impregnated dressing) or standard care plus NPWT. Patients will be reviewed until 3 months post-burn wound re-epithelialisation, with measurements taken at dressing changes to assess primary and secondary outcomes. Surveys, randomisation and data storage will be done via online platforms and physical data storage collated at the Centre for Children’s Health Research, Brisbane, Australia. Analysis will be performed using the Stata statistical software.
Ethics and dissemination
Queensland Health and Griffith University Human Research ethics approval including a site-specific assessment was obtained. The findings of this study will be disseminated through clinical meetings, conference presentations and peer reviewed journals.
Trial registration
Registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12622000044729, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381890&isReview=true, registered 17/01/2022).
... Open access macrodeformations promoting cell mitosis, angiogenesis and lymphangiogenesis. [7][8][9][10][11] In the context of burns, it is broadly thought to optimise the zone of stasis, preventing burn progression and ultimately decreasing the time to re-epithelialisation. 12 Despite the published benefits of NPWT in burn care, there has been a reluctance of uptake due to the perceived burden of treatment including the bulk of the device, mechanical issues and days off school. 6 In an attempt to reduce this burden, PICO; a small, ultraportable, single-use NPWT device, has been introduced as a substitute to the traditional larger NPWT devices. ...
Introduction
Negative pressure wound therapy (NPWT) in acute burn care may decrease the time to re-epithelialisation by more than 20%. Despite this, the perceived burden of use; including therapeutic, physical and financial, have limited the use of NPWT in acute burn care. This might be minimised by using the small, ultraportable, single-use NPWT device PICO as opposed to larger devices, which to date has never been studied in acute burn care. This research will; therefore, primarily assess the feasibility, acceptability and safety of PICO in paediatric burns. Secondary outcomes include time to re-epithelialisation, pain, itch, cost and scar formation.
Methods and analysis
This protocol details a clinical trial methodology and is pre-results. This single site, prospective, pilot randomised controlled trial will be conducted in an Australian quaternary paediatric burns centre. Participants must be aged ≤16 years, otherwise well and managed within 24 hours of sustaining a burn that fits beneath a PICO dressing. Thirty participants will be randomised to one of three groups: group A: Mepitel and ACTICOAT, group B: Mepitel, ACTICOAT and PICO and group C: Mepitel, ACTICOAT Flex and PICO. Patient outcomes will be recorded at each dressing change to assess efficacy and safety outcomes until 3 months postburn wound re-epithelialisation. Surveys, randomisation and data storage will be undertaken via online platforms and physical data storage collated at the Centre for Children’s Health Research, Brisbane, Australia. Analysis will be done by using StataSE 17.0 statistical software.
Ethics and dissemination
Ethics has been obtained from Queensland Health and Griffith Human Research Ethics committees including a site-specific approval. These data will be disseminated via clinical meetings, conference presentations and peer-reviewed journals.
Trial registration number
ACTRN12622000009718.
... The advantages of ciNPWT that might help to avoid adverse events were reducing shearing forces at approximated edges of the wound [23] and increasing blood flow and capillary venous oxygen saturation [24], in addition to reduction of tissue edema [25,26], through the creation of a negative pressure environment that inhibits seroma formation, thus decreasing bacterial infection and allowing wound contraction [27].Moreover, it creates a hypoxic environment and leads to an increase in circulating interleukin levels and expression of growth factors. This subsequently stimulates angiogenesis, granulation tissue formation and remodeling of the extracellular matrix [25,28]. ...
... The advantages of ciNPWT that might help to avoid adverse events were reducing shearing forces at approximated edges of the wound [23] and increasing blood flow and capillary venous oxygen saturation [24], in addition to reduction of tissue edema [25,26], through the creation of a negative pressure environment that inhibits seroma formation, thus decreasing bacterial infection and allowing wound contraction [27].Moreover, it creates a hypoxic environment and leads to an increase in circulating interleukin levels and expression of growth factors. This subsequently stimulates angiogenesis, granulation tissue formation and remodeling of the extracellular matrix [25,28]. ...
Background Surgical-site infections (SSIs) are found to occur after about 2-5% of all surgeries. SSIs have many drawbacks such as the need for readmission, revision operations, prolonged duration of hospital stay, increased financial burden on patients and increased risk of worsening outcome in cancer patients. Closed-incision negative-pressure therapy (CINPT) was studied as a method of preventing infections in wounds occurring after closed surgical incisions particularly during the covid-19 pandemic. There are many studies showed promising results of this procedure. Therefore, in this prospective clinical randomized study, we aimed to evaluate the benefit of performing prophylactic CINPT in controlling SSIs in open colorectal surgeries, hepatobiliary surgeries and gynecological cancer surgeries involving laparotomies, in comparison with the standard dressings. Patients and method We included 120 patients of SSIs with open colorectal surgeries, hepatobiliary surgeries and gynecological cancer surgeries involving laparotomies in the period between 2015 and 2020. We divided the patients randomly into two groups: the first group is the study group, which included 30 patients managed by CINPT, and the second group is the control group, which included 90 patients managed by standard non-CINPT management. We compared patients who underwent CINPT with the control group of high-risk patients undergoing routine management non-CINPT procedures. Results The median rate of occurrence of general adverse wound outcomes was 32.5% for all the included patients: 20% in the CINPT group and 36.7% in the control group (P =0.049). The median rate of occurrence of SSIs was 17.5% for all the included patients: 7% in the CINPT group and 15% in the control group (P=0.001). Time to diagnose SSIs in the CINPT group was longer than that in the control group (19 vs 13 days; P=0.03). The increased duration of operation and the presence of preoperative or postoperative stoma were associated with increased incidence of occurrence of SSI, while CINPT was associated with decreased incidence of occurrence of SSIs (P<0.001). Conclusion We observed a marked reduction in the rates of SSIs in closed laparotomy wounds in colorectal, hepato-pancreato-biliary and in gynecological oncology surgeries managed with prophylactic CINPT particularly during the Covid-19 pandemic.
... 3 The ultimate soft tissue covering should be applied as soon as possible, ideally during the first 72 h following trauma. 4 The therapy of tibia bone fractures with locking plates or intra-medullary inter-locking nails is well established in trauma orthopaedic surgery. However, it can be very difficult and expensive to cure soft tissue infections after surgery. ...
Background/Aim: Wound management of the compound open tibia (Gustilo-Anderson grade 2, 3a, 3b) is complicated by a higher infection and the problem of adequate soft tissue coverage is significant. Primary wound closure is not easily advisable in these types of compound open tibial fractures. Early tissue flap or graft procedure might increase the complication rate due to temporary graft rejection and wound infections. The aim of this study was to analyse the duration required for formation of healthy granulation tissue, duration required for making wound fit for skin cover procedure and duration of hospital stay in compound open tibia fracture treated with vacuum assisted closure (VAC). Methods: A prospective interventional study of 22 patients aged 18 to 60 years was done. After assessing the size of the wound, primary bone fixation and wound debridement were carried out as soon as possible and then VAC was applied. Assessment of VAC therapy was based on mean decreases in wound size and "modified Johner and Wruh's criteria", used for assessment of the functional outcome of tibial shaft fracture was recorded during each follow-up. Results: Twenty two patients suffered comminuted open fractures of tibia-fibula. Primary fixation of bone were done with vacuum dressing. During follow-up, the good decrease in wound size considering vacuum dressing remedy was once 18.75 ± 18.36 cm2 (p = 0.001). Six patients achieved excellent results according to "modified Johner and Wruh's criteria" of tibial shaft fracture. Conclusion: This technique effectively reduced wound size, accelerated the formation of healthy granulation tissue of wound with open fracture bone and provided a better functional outcome. The VAC treatment had suggestively increased wound closure rate, decreased morbidity and costs for patients.
... 52 Relevant studies have also proved the pathological and molecular mechanism of negative pressure technology in rapidly promoting wound healing, mainly involving inducing perfusion changes, micro deformation, bacterial inhibition, angiogenesis, and rapidly promoting the growth of fibrous granulation tissue. [54][55][56] At present, negative pressure therapy has become the most effective technical choice for wound treatment technology, which has acquired the consensus of international experts and manufacturers' guidelines, and has produced huge related commercial values. 57 Anastomotic leak is essentially a special kind of wound. ...
Anastomotic leak is still a severe complication in esophageal surgery due to high mortality. This article reviews the updates on the treatment of anastomotic leak after esophagectomy in order to provide reference for clinical treatment and research. The relevant studies published in the Chinese Zhiwang, Wanfang, and MEDLINE databases to December 21, 2021 were retrieved, and esophageal carcinoma, esophagectomy, anastomotic leakage, and fistula selected as the keywords. A total of 78 studies were finally included. The treatments include traditional surgical drainage, new reverse drainage trans‐fistula, stent plugging, endoscopic clamping, biological protein glue injection plugging, endoluminal vacuum therapy (EVT), and reoperation, etc. Early diagnosis, accurate classification and optimal treatment can promote the rapid healing of anastomotic leaks. EVT may be the most valuable approach, simultaneously with good commercial prospects. Reoperation should be considered in patients with complex fistula in which conservative treatment is insufficient or has failed. The aim of this review article is to discuss esophageal anastomotic leak, and describe modern treatment approaches. Endoluminal vacuum therapy (EVT, E‐VAT)may be the most promising therapeutic strategy for the most dreaded complication. EVT (E‐VAT) also has good commercial prospects.
... Various approaches to suppress SSI have been taken, including the use of a subcutaneous drain [3], delayed primary closure (DPC) [4], and SSI bundle [5]; however, these methods have not sufciently decreased the rate of SSI. Negative-pressure wound therapy (NPWT) has attracted attention recently; its use promotes wound healing by inducing angiogenesis, proliferating fbroblasts, and increasing granulation tissue [6,7]. NPWT was initially used to treat chronic wounds and tissue defects [8,9], but it is now used to prevent SSI even in abdominal surgical wounds. ...
... (3) Te costefectiveness of NPWT was not analyzed because of the study's single-arm, noncomparative design. (4) It was uncertain whether our 7-day protocol was optimal, although angiogenesis and the growth of granulation tissue during NPWT are reported to progress within 3-10 days [6]. Ma et al. also reported that NPWT signifcantly improved angiogenesis that preceded granulation in dermal regeneration from days 3 to 7 compared to gauze dressing [6]. ...
... (4) It was uncertain whether our 7-day protocol was optimal, although angiogenesis and the growth of granulation tissue during NPWT are reported to progress within 3-10 days [6]. Ma et al. also reported that NPWT signifcantly improved angiogenesis that preceded granulation in dermal regeneration from days 3 to 7 compared to gauze dressing [6]. Tese fndings were consistent with our clinical observations; it thus seemed rational to continue NPWT for at least 7 days. ...
Background:
Prophylactic negative-pressure wound therapy (NPWT) to prevent surgical site infection (SSI) may be effective for severely contaminated wounds. We investigated the safety and efficacy of NPWT with delayed primary closure (DPC) for preventing SSI.
Methods:
For patients with contaminated and dirty/infected surgical wounds after an emergency laparotomy, the abdominal fascia was closed with antibacterial absorbent threads and the skin was left open. Negative pressure (-80 mmHg) was applied through the polyurethane foam, which was replaced on postoperative days 3 and 7. DPC was performed when sufficient granulation was observed. The duration and adverse events of NPWT, the development of SSI, and the postoperative hospital stay were retrospectively reviewed.
Results:
We analyzed the cases of patients with contaminated (n = 15) and dirty/infected wounds (n = 7). The median duration of NPWT was 7 days (range 5-11 days). NPWT was discontinued in one (4.5%) patient due to wound traction pain. SSI developed in seven patients (31.8%), with incisional SSI in one (4.5%) and organ/space SSI in six (27.3%). The median postoperative hospital stay was 17 days (range 7-91 days). There was no significant relationship between postoperative hospital stay and wound classification (P=0.17) or type of SSI (P=0.07).
Conclusion:
Prophylactic NPWT with DPC was feasible and may be particularly suitable for severely contaminated wounds, with a low incidence of incisional SSI.
... Pericytes subjected to endothelial cell-derived factors, such as PDGF (DD and BB), endothelin-1, TGF-β, and HB-EGF, assemble around endothelial cells for tube formation [27]. Moreover, the association of pericytes and collagen type IV promotes the maturation of microvessels [28], and the promotion of endothelial cell junction and ECM deposition to the vascular basement membrane are vital to maintaining vascular stability and homeostasis [29]. ...
Wound healing is a highly regulated multi-step process that involves a plethora of signals. Blood perfusion is crucial in wound healing and abnormalities in the formation of new blood vessels define the outcome of the wound healing process. Thy-1 has been implicated in angiogenesis and silencing of the Thy-1 gene retards the wound healing process. However, the role of Thy-1 in blood perfusion during wound closure remains unclear. We proposed that Thy-1 regulates vascular perfusion, affecting the healing rate in mouse skin. We analyzed the time of recovery, blood perfusion using Laser Speckle Contrast Imaging, and tissue morphology from images acquired with a Nanozoomer tissue scanner. The latter was assessed in a tissue sample taken with a biopsy punch on several days during the wound healing process. Results obtained with the Thy-1 knockout
(Thy-1−/−) mice were compared with control mice. Thy-1−/− mice showed at day seven, a delayed re-epithelialization, increased micro- to macro-circulation ratio, and lower blood perfusion in the wound area. In addition, skin morphology displayed a flatter epidermis, fewer ridges, and almost no stratum granulosum or corneum, while the dermis was thicker, showing more fibroblasts and fewer lymphocytes. Our results suggest a critical role for Thy-1 in wound healing, particularly in vascular dynamics.
... In addition, this approach may provide more options for increased clinical efficacy either by using it individually or in combination with other conventional therapies, such as negative-pressure wound therapy, dressing, or scaffolds. [33][34][35][36] However, despite its advantages, the practical application of exogenous HGF is still limited because of its short half-life (approximately 2.4 minutes). 35 Our study showed that the cMet agonistic monoclonal antibody successfully activated the HGF/Met signaling pathway, including MAPK, mTOR, ROCK-1, and p-cMet expression (Fig. 6, below). ...
Background:
Diabetic wounds account for 25%-50% of total diabetic healthcare costs annually, and present overall healing rates of less than 50%. Since delayed diabetic wound healing is associated with impaired fibroblast function, we hypothesize that tyrosine kinase Met (cMet) agonistic monoclonal antibody (mAb) will promote diabetic wound healing via stable activation of HGF/cMet signaling.
Methods:
Two 6 mm dorsal wounds were created in each mice (6-week-old, male BKS.Cg-Dock7m+/+Leprdb/J, n=5). After subcutaneous injections of agonist (20 mg/kg) at 0 and 72h, the wound sizes were measured at days 0, 1, 3, 6, and 10. Histological and immunohistochemical analyses were performed at day 10 (cMet, α-SMA, CD68, and TGF-β). In vitro cytotoxicity and migration tests with diabetic fibroblasts were performed with/without agonist treatment (1 or 10 nM). cMet pathway activation of fibroblasts was confirmed through p-p44/42MAPK, p-mTOR, p-cMet, and ROCK-1 expression.
Results:
cMet agonistic mAb-treated group showed 1.60-fold lower wound area (p=0.027), 1.54-fold higher collagen synthesis (p=0.001), and 1.79-fold lower inflammatory cell infiltration (p=0.032) than the saline-treated control. The agonist increased cMet (1.86-fold, p=0.029), α-SMA (1.20-fold, p=0.018), and VEGF (1.68-fold, p=0.029) expression but suppressed CD68 (1.25-fold, p=0.043), TFG-β (1.25-fold, p=0.022), and MMP-2 (2.59-fold, p=0.029) expression. In vitro agonist treatment (10 nM) of diabetic fibroblasts increased their migration by 8.98-fold (p=0.029) and activated HGF/cMet pathway.
Conclusions:
cMet agonistic mAb treatment improved diabetic wound healing in mice and reduced wound-site inflammatory cell infiltration. These results need to be validated in large animals before piloting human trials.
