Inflammation and wound healing: a comprehensive overview of mechanisms, therapeutic strategies, and translational perspectives.

BackgroundChronic wounds present a significant challenge, resulting in prolonged care, extended hospital stays, and substantial financial and psychosocial burdens for patients and the healthcare system. Despite various techniques available to accelerate wound healing and reduce hospital stays, no standard approach for chronic wound care has been universally agreed upon. Negative pressure wound therapy (NPWT) is well-known, but its effectiveness as a primary treatment is uncertain. Hyperbaric oxygen therapy (HBOT) is another adjunctive technique that increases oxygen supply to wounds to promote healing, similar to NPWT. This study evaluates the effectiveness of combining HBOT with NPWT in treating chronic wounds.MethodsThis prospective multicenter randomized controlled trial involved patients with chronic wounds requiring NPWT. Participants were randomly assigned to receive either HBOT with NPWT or NPWT alone. The primary objective was to compare wound healing rates, with secondary outcomes including pain scores and bacterial contamination.ResultsEach study group included twenty-four patients. The analysis showed a significantly higher wound healing rate in the NPWT+HBOT group compared to the NPWT-only group (11.81 % vs. 8.54 % on day 3, 15.35 % vs. 11.17 % on day 6, 16.44 % vs. 12.14 % on day 9, 20.15 % vs. 14.9 % on day 12; P = 0.001). There were no significant differences in pain scores or bacterial contamination between the groups at any time point.ConclusionCombining NPWT and HBOT significantly improves the rate of wound healing compared to NPWT alone in chronic wounds, with no significant differences in pain or infection rates between the two treatment groups.

Angiogenesis and vasculogenesis: Inducing the growth of new blood vessels and wound healing by stimulation of bone marrow–derived progenitor cell mobilization and homing

Honoring the Past and Forging the Future

Wound healing is a fundamental process for survival. It makes an organism able to repair a damage and restore physiological condition. The whole process involves the coordinated interaction of many different cell populations and biochemical molecules, such as proteins, proteases, growth factors, and extracellular matrix (ECM) components. the possibility to carry out research in unloading conditions represents an unique tool to increase our knowledge on wound healing biomechanics and the role of gravity in the process. Moreover, in the perspective of longer-term space missions, with a growing number of astronauts involved, wound healing must be regarded as a serious problem, because the risk of injury due to traumatic events or unexpected emergency surgery will increase while medical evacuation times to Earth will become incompatible with the urgency of implementing assistance procedures. Therefore, it is crucial to understand the impact of microgravity (μg) on the mechanisms underlying wound healing. In the frame of these studies, we developed an in vivo model of wound healing based on leeches [Hirudo Medicinalis]. This invertebrate represents an interesting model, since the sequence of events occurring during the healing is similar as in vertebrates. Moreover, the leech is very resistant and, once nourished, can survive for some months without eating. For this reasons, it can be considered one the most suitable living beings to be used for experiments both in modeled and real μg, even during long-term space missions. The results of preliminary experiments about healing process are iullustrated and discussed

NPWT combined with porcine ADM dressing can effectively remove wound bacteria, reduce wound exudation, and promote wound healing in repairing deep partial-thickness burn wounds and full-thickness burn wounds. Its clinical effect is better than NPWT or porcine ADM dressing alone, and this method may be suitable for patients with non-surgical treatment.

Objective: Various treatment options exist for wound healing; however, clinical assessment of the patient and the wound environment must be considered before determining an optimal wound treatment plan. Negative pressure wound therapy alone and/or with an instilled topical solution can be effective in adjunctive management of acute and chronic wounds. Hyperbaric oxygen therapy has also been shown to contribute to the wound-healing process. A pilot evaluation using a multistep approach of adjunctive negative pressure wound therapy with instillation and a dwell time, standard negative pressure wound therapy, and hyperbaric oxygen therapy was explored to manage postsurgical, diabetic lower-extremity wounds with a significant bioburden. Methods: Three diabetic patients with lower-extremity ulcers were treated after surgical intervention. Multistep wound therapy consisted of (1) negative pressure wound therapy with instillation of normal saline with a 20-minute dwell time, followed by 2 hours of negative pressure at −150 mm Hg for 3 to 4 days; (2) 1 to 3 weeks of continuous negative pressure at −150 mm Hg; and (3) multiple treatments of hyperbaric oxygen therapy. Results: After surgery, wound closure was achieved within 4 weeks postinitiation of multistep wound therapy. All patients regained limb function and recovered with no long-term sequelae. Conclusions: In these 3 cases, a multistep wound therapy approach after surgery resulted in successful outcomes; however, larger prospective studies are needed to demonstrate the potential efficacy of this approach in the postsurgical management of complex, diabetic lower-extremity wounds.

The aim of this paper is to determine which therapy gives best results regarding process of healing of diabetic foot ulcers among three proposed: only negative pressure wound therapy, only hyperbaric oxygen therapy, and both when used in conjunction. This bicentric prospective study included 60 patients, and they were, consecutively, assigned to one of three groups. The first group consisted of 20 patients who were treated only by hyperbaric oxygen therapy, second group consisted of 20 patients treated with combined hyperbaric oxygen and negative pressure wound therapy, and third group consisted of 20 patients who were treated only by negative pressure wound therapy. In some cases, previous revascularization of lower limb was performed and patients with poor run-off, without possibility to perform revascularization, were excluded from the study. Patients were predominantly men (56.7%) and mean age was 60.57 years. Majority of patients had ulcers of ischemic origin (45%), in 30% of cases, the reason of foot ulceration was neuropathy, and in 25% of patients, the etiology was combined. During the study, in three patients (5%), minor amputations were observed. Regarding Wagner classification of foot ulcers, most dominant was stage II (χ = 12.618, df = 4, p < 0.05). Statistically significant reduction of wound area was achieved when hyperbaric oxygen and negative pressure wound therapy were used in conjunction comparing to isolated use either of these two modalities of treatment (χ = 116.000, df = 44, p < 0.01). Our data suggests simultaneous use of hyperbaric oxygen therapy and negative pressure wound therapy in diabetic foot ulcer treatment in order to achieve best results. Of great importance is previous wound debridement and successful limb revascularization.

To evaluate the effects of hyperbaric oxygen (HBO) therapy in the management of chronic wound and observe the correlation between wound healing and CD34+ endothelial progenitor cells (EPCs). A total of 119 patients with chronic wound in lower extremities lasting > 3 months were recruited for this randomized, single-center, placebo-controlled clinical trial. The changes of CD34+ average count before and after HBO therapy were detected by flow cytometry (FACS). There were 97 patients on long-term HBO therapy and in 22 patients on hyperbaric air therapy as control group. The CD34/Scal-1+ and CD34/CXCR4 dual-positive populations of gated cell were determined respectively by FACs. The outcomes of two groups were compared. Treatment was administered within a single-place hyperbaric chamber for 90-min daily (session duration 120 min) for 5 days a week for 4 weeks (20 treatment sessions). The wound size decreased at the 4-week end point (62.7% ± 22.3% in the HBO group vs 34.4% ± 20.6% in the control group, P < 0.05). After 10 episodes of HBO therapies for chronic non-healing wound, the peripheral CD34+ EPCs average count rose from 0.24% ± 0.03% at pre-treatment to 1.32% ± 0.05% while the number was 1.75% ± 0.17% after 20 episodes of HBO (P < 0.05). Both were significantly different from that of the patients at pre-treatment. However the overall circulating white cell count was not significantly elevated. The CD34/Scal-1+ and CD34/CXCR4 dual-positive populations of gated cell in HBO group were 5.8 and 5.2 folds than those at pre-treatment respectively. The number of EPCs was positively correlated with wound healing in lower extremities (correlation coefficient 0.84; P < 0.01). Adjunctive treatment of HBO facilitates the healing of chronic non-healing wound in selected patients through the mobilization of EPCs.

Comparison of the effect of negative pressure wound therapy with and without installation of polyhexanide on the bacterial kinetic in chronic wounds

Wound Healing Society 2014 update on guidelines for arterial ulcers.

In stalled, chronic wounds, more aggressive and proactive wound closure efforts are needed. We describe adjunctive use of epidermal grafting in patients with chronic wounds. Wound bed preparation consisted of surgical necrotectomy or sharp debridement, hyperbaric oxygen therapy, negative pressure wound therapy, compression therapy, platelet-rich plasma therapy and/or heparan sulphate agents. Epidermal grafts were harvested from the patient's thigh and applied to the wound. Wound and donor site healing was monitored. A total of 78 patients (average age = 64·1 ± 15·6 years) were included in the study. Common comorbidities included hypertension (47·4%), venous insufficiency (37·2%) and obesity (28·2%). Average wound duration was 13·2 months (range: 0·3-180 months). The most common wound types were dehiscence (29·5%), radiation ulcer (24·4%) and venous ulcer (17·9%). Total time from epidermal grafting to wound closure was 10·0 ± 7·3 weeks. Of the 78 wounds, 66 (84·6%) reached full wound closure (49 < 3 months, 16 > 3 months, 1 without time data). Of 78 wounds, 10 (12·8%) underwent partial wound healing, while 2 wounds (2/78; 2·6%) remained unhealed. These results suggest that wound surface reduction can be achieved by proactive early application of biological therapies and epidermal skin grafts, which may help decrease time to wound healing.

Objective To study on the changes of epidermal stem cells proliferation in the treatment of elderly diabetic ulcer wound by negative-pressure wound therapy (NPWT). Methods Elderly patients with diabetes mellitus complicated with chronic refractory wounds were selected from First Affiliated Hospital, Sun Yat-sen University and Shenzhen Longhua District Central Hospital from January 2011 to December 2015. NPWT was used to treat these wounds. Immunohistochemical method was used to detect the changes of integrin beta 1 in basal cells of wound healing process(respectively before treatment, 2 weeks after treatment, 4 weeks after treatment). The paired-samples t test was used. Results No integrin beta 1 positive cells were found in the basal cells of the limbus wound before the NPWT, the integrin beta 1 positive cells appeared at the periphery of the wound at 2 weeks after NPWT, the positive unit was 1.74±0.07. At 4 weeks after received NPWT, the positive unit (expression of integrin beta 1 positive cells) was 29.07±0.65. The expression of epidermal stem cells (integrin beta 1) at the 2 and 4 weeks after received NPWT was significantly different from that before received NPWT (t=75.29, 140.31, with P values below 0.05). There was significant difference in the expression of epidermal stem cells (integrin beta 1) at the 4 weeks after received NPWT and 2 weeks after received NPWT (t=134.25, P<0.05). Conclusion NPWT promotes the proliferation of epidermal stem cells in elderly diabetic ulcer wounds and promotes epithelial wound healing. Key words: Negative-pressure wound therapy; Diabetes mellitus; Ulcer; Aged; Cell proliferation; Epidermal stem cells

Non-healing wounds and associated health care cost is a global burden. This issue is a great challenge for developing countries. Negative pressure wound therapy (NPWT) is a popular treatment method currently being used for chronic wound healing worldwide. NPWT is a non-invasive closed system that creates a sub-atmospheric (negative) pressure environment. This therapy is mostly utilized in patients who have chronic wounds such as pressure ulcers and diabetic wounds. NPWT reduces debris, decreases swelling of the tissues and promotes rich blood flow to the wound site. The aim of the present study was to explore the progress of wound healing with the application of NPWT to a delayed-healing diabetic foot ulcer. The case study was conducted based on data gathered through direct patient observation during the application of NPWT. The study was about a 59-year-old male person who was diagnosed with diabetes mellitus and had delayed wound healing for more than 2 months on his left lower limb foot ulcer. After applying NPWT to the delayed healing wound for seven days, the medical team observed a rapid wound healing process including redness over the wound, less debris, less amount of slough, and closure of the wound from edges gave evidence of the effectiveness of the wound healing process.

Our aim was to examine histopathological changes in three chronic wounds, and to assess whether the application of negative pressure wound therapy (NPWT) changes the wound bed environment. - Results: We recruited three patients were recruited who had a non-healing wounds in excess of eight weeks. Histopathological changes in the wound bed supported the evidence that NPWT changes the wound bed environment by reducing inflammatory damage and facilitating wound bed perfusion with angiogenesis. We suggest that NPWT is a valuable adjunct to aid chronic wound healing. In this case series, we observed histopathological changes and improvement in the wounds, following one week's treatment with NPWT. Further analysis should be done to demonstrate any interaction between the cells involved in the wound healing process is enhanced, growth factor performance is optimised and cell migration is achieved following NPWT, in order to facilitate the healing process.

Negative pressure wound therapy (NPWT) is the treatment of choice for chronic wounds; yet, it is associated with considerable workload. Prompted by its nonadhesive and wound-healing properties, this study investigated the effect of an additional polymeric membrane interface dressing (PMD; PolyMem WIC) in NPWT. From October 2011 to April 2013, 60 consecutive patients with chronic leg wounds or surgical site infections after revascularization of lower extremities were randomly allocated to either treatment with conventional NPWT (control arm) or NPWT with an additional PMD (intervention arm). The primary outcome was wound healing achieved within 30 days, the secondary endpoints included: number of days between dressing changes, wound-related pain, cost efficiency, and occurrence of adverse events (ClinTrials.gov Identifier: NCT02399722). Forty-seven patients completed follow-up. No difference in wound healing was observed (p > 0.05) between both study arms. The additional PMD allowed significantly longer wearing times (days) between dressing changes (intervention: 8.8 ± 0.5, control: 4.8 ± 0.2; p < 0.001). Pain was slightly higher in patients randomized to NPWT alone (VAS score: 4.8 ± 2.9) compared to NPWT + PMD (VAS score: 3.0 ± 2.9, p = 0.063). No wound infections were observed. Costs were reduced by 34% per patient in the intervention arm. These results suggest that the combination of NPWT and an additional interface PMD is a safe and economic method for the treatment of chronic wounds, which requires significantly fewer dressing changes for a comparable wound healing.