Hypoxia, high ROS levels and chronic inflammation are the main factors that hinder the healing of diabetic wounds. Long-term exposed wounds are prone to bacterial infection, especially MRSA infection, which exacerbates the complex wound microenvironment of diabetes and threatens patients' lives. Here, we developed a ROS nanopurifier (CSVNP), which was prepared by loading superoxide dismutase (SOD), catalase (CAT) and vancomycin into nanogels through in-situ polymerization. CSVNP can effectively increase enzyme loading and stability, and improve cascade reaction efficiency between enzymes through nanosize effect, so that CSVNP can use a variety of ROS (H2O2 and ·O2-) as oxygen sources to generate much oxygen in situ, which can effectively alleviate the hypoxic environment and inflammatory response of diabetic tissues, theraby promoting cell migration and angiogenesis, and accelerating wound healing. In addition, the generated oxygen can further promote the transformation of pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages and reduce pro-inflammatory factors (TNF-α, IL-6, and IL-1β) release. CSVNP can also effectively eradicate MRSA by releasing vancomycin, preventing bacterial infection from exacerbating the deterioration of diabetic wounds. This multifunctional ROS nanopurifier with antiphlogosis, antibacterial and in-situ oxygen supply, provides a new strategy with universal and translational prospects for clinical diabetic tissue damage. STATEMENT OF SIGNIFICANCE: Methicillin-resistant staphylococcus aureus (MRSA)-infected diabetic wounds face significant challenges in clinical care, characterized by high ROS levels, acute inflammation, vascular lesions, and hypoxia, which impede healing and risk severe complications. Here, we originally developed a reactive oxygen species (ROS) nanopurifier prepared by in-situ polymerization of superoxide dismutase (SOD), catalase (CAT), and vancomycin. It uses SOD and CAT to continuously convert ROS (H2O2 and ·O2-) into O2 in diabetic tissues, effectively improving hypoxia and chronic inflammation, thereby promoting angiogenesis and cell proliferation and migration, and accelerating diabetic wound healing. Vancomycin can effectively kill MRSA bacteria, avoid bacterial infection spread, and reduce complications risk. This safe, efficient and easy-to-prepare ROS nanopurifier provides a general strategy for repairing MRSA-infected diabetic tissue damage.

Management of chronic diabetic wounds is challenging due to excess reactive oxygen species (ROS), hypoxia, persistent inflammation, and bacterial infection within the wound microenvironment. For addressing the aforementioned concern, we have developed a multifunctional hydrogel dressing (PMT-C@PhM) based on chitosan with self-healing, adhesive, antibacterial, and antioxidant capacities for therapeutic diabetic wounds. The hydrogel dressing consisted of quaternary ammonium salt- and catechol- modified chitosan (CQCS), thioctic acid-functionalized poly(ethylene glycol)s (PEGs), and polydopamine-coated honeycomb manganese dioxide nanoparticles (hMnO2@PDA NPs). The nanozyme-modified hydrogel exhibits superoxide dismutase (SOD) and catalase (CAT) activities to scavenge ROS while generating oxygen to alleviate oxidative stress and hypoxic environment in wounds, and to attenuate the inflammatory response through modulating macrophage polarization. The PMT-C@PhM hydrogel is effective in the treatment of diabetic wound infections caused by Staphylococcus aureus, and relieves oxidative stress, inhibits inflammation, and promotes neovascularization and dermal collagen synthesis thus providing favorable conditions for accelerated wound healing. In conclusion, the aforementioned approach offers a biosafe, straightforward, and efficient strategy for the management of diabetic wounds.

To assess the effects of several adjuvant therapies (AT) commonly used in the treatment of diabetic foot ulcers (DFU). The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome.

A Medline and Embase search were performed up to May 20th, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with DFU comparing AT with placebo/standard of care (SoC), with a duration of at least 12 weeks. Prespecified endpoints were: ulcer healing (principal), time-to-healing, major and minor amputation, serious adverse events (SAE), and all-cause mortality. AT assessed were: growth factors (GF), Platelet-rich plasma and fibrin (PRP/F), skin substitutes (SS), negative pressure wound therapy (NPWT), and hyperbaric oxygen therapy (HBOT). Mantel-Haenzel Odds ratios and 95% confidence intervals (MH-OR, 95% CIs) were either calculated or extracted directly from the publications. Weighted mean differences and 95% CIs were calculated for continuous variables.

Fifty-one studies fulfilled all inclusion criteria (3, 5, 27, 8, and 8 with GF, PRP/F, SS, NPWT, and HBOT, respectively). Participants treated with any of the explored AT had a significantly higher ulcer healing rate (MH-OR ranging from 2.17 to 4.18) and shorter time-to-healing in comparison with SoC/placebo. Only PRP/F and HBOT showed a significantly lower risk of major amputation (MH-OR: 0.32(0.11;0,93; p = 0.04 and 0.28(0.10;0,79; p = 0.02, respectively), despite a higher risk of SAE. No other significant effects on the above-reported prespecified endpoints were observed. For the primary endpoint, the quality of evidence was rated as "high" for all the AT, except for NPWT ("moderate").

In conclusion, AT can actively promote wound healing and shorten time-to-healing in patients with DFU. HBOT and PRP/F also showed a reduction of the risk of major amputation, despite a higher rate of SAE.

Background  Dermal substitutes offer a valuable tool in soft-tissue reconstruction, reducing the need for donor site tissue and its associated complications. However, conventional approaches often require multiple surgeries. This study aimed to compare the effectiveness of a single-stage procedure combining dermal substitute and skin grafting with hyperbaric oxygen (HBO) therapy to the standard multistage protocol. Materials and Methods  A comparative study was conducted from January 2022 to December 2023. The medical records of 24 patients who underwent soft-tissue reconstruction were reviewed. Patients were categorized into two groups based on whether they received HBO therapy (HBO group) or followed the standard multistage protocol (control group). Outcomes were compared between the groups. Results  The study included 18 males and 6 females with an average age of 43 years (range: 5-91 years). Underlying medical conditions included diabetes mellitus ( n  = 11) and peripheral vascular disease ( n  = 2). Wounds were due to various causes, including necrotizing fasciitis ( n  = 2), trauma ( n  = 10), diabetic ulcers ( n  = 6), postburn hypertrophic scars/contractures ( n  = 3), chronic ulcers ( n  = 1), and sternal wound dehiscence ( n  = 1). All the patients achieved successful wound closure with dermal substitute application, eliminating the need for additional surgery. Notably, the group receiving HBO therapy experienced a shorter overall hospital stay compared with the standard multistage group. Conclusion  This study demonstrates the effectiveness of dermal substitutes in soft-tissue reconstruction. Furthermore, the addition of HBO therapy in a single-stage procedure appears beneficial for successful outcomes, potentially reducing hospital stay compared with the traditional multistage approach.

Diabetes mellitus is an exponentially growing chronic metabolic disease identified by prolonged hyperglycemia that leads to a plethora of health problems. It is well established that the skin of diabetic patients is more prone to injury, and hence, wound healing is an utmost critical restorative process for injured skin and other tissues. Diabetes patients have problems with wound healing at all stages, which ultimately results in delays in the healing process. Therefore, it is vital to find new medications or techniques to hasten the healing of wounds. Metal-organic frameworks (MOFs), an assorted class of porous hybrid materials comprising metal ions coordinated to organic ligands, can display great potential in accelerating diabetic wound healing due to their good physicochemical properties. The release of metal ions during the degradation of MOFs can promote the differentiation of fibroblasts into myofibroblasts and subsequently angiogenesis. Secondly, similar to enzyme-like active substances, they can eliminate reactive oxygen species (ROS) overproduction (secondary to the bio-load of wound bacteria), which is conducive to accelerating diabetic wound healing. Subsequently, MOFs can support the slow release of drugs (molecular or gas therapeutics) in diabetic wounds and promote wound healing by regulating pathological signaling pathways in the wound microenvironment or inhibiting the expression of inflammatory factors. In addition, the combination of photodynamic and photothermal therapies using photo-stimulated porphyrin-based MOF nanosystems has brought up a new idea for treating complicated diabetic wound microenvironments. In this review, recent advances affecting diabetic wound healing, current means of rapid diabetic wound healing, and the limitations of traditional approaches are discussed. Further, the diabetic wound healing applications of MOFs have been discussed followed by the future challenges and directions of MOF materials in diabetic wound healing.

Diabetic foot ulcer (DFU) is one of the most costly and serious complications of diabetes. Treatment of DFU is usually challenging and new approaches are required to improve the therapeutic efficiencies. This review aims to update new and upcoming adjunctive therapies with noninvasive characterization for DFU, focusing on bioactive dressings, bioengineered tissues, mesenchymal stem cell (MSC) based therapy, platelet and cytokine-based therapy, topical oxygen therapy, and some repurposed drugs such as hypoglycemic agents, blood pressure medications, phenytoin, vitamins, and magnesium. Although the mentioned therapies may contribute to the improvement of DFU to a certain extent, most of the evidence come from clinical trials with small sample size and inconsistent selections of DFU patients. Further studies with high design quality and adequate sample sizes are necessitated. In addition, no single approach would completely correct the complex pathogenesis of DFU. Reasonable selection and combination of these techniques should be considered.

The increasing emergence of multidrug-resistant (MDR) pathogens causes difficult-to-treat infections with long-term hospitalizations and a high incidence of death, thus representing a global public health problem. To manage MDR bacteria bugs, new antimicrobial strategies are necessary, and their introduction in practice is a daily challenge for scientists in the field. An extensively studied approach to treating MDR infections consists of inducing high levels of reactive oxygen species (ROS) by several methods. Although further clinical investigations are mandatory on the possible toxic effects of ROS on mammalian cells, clinical evaluations are extremely promising, and their topical use to treat infected wounds and ulcers, also in presence of biofilm, is already clinically approved. Biochar (BC) is a carbonaceous material obtained by pyrolysis of different vegetable and animal biomass feedstocks at 200-1000 °C in the limited presence of O2. Recently, it has been demonstrated that BC's capability of removing organic and inorganic xenobiotics is mainly due to the presence of persistent free radicals (PFRs), which can activate oxygen, H2O2, or persulfate in the presence or absence of transition metals by electron transfer, thus generating ROS, which in turn degrade pollutants by advanced oxidation processes (AOPs). In this context, the antibacterial effects of BC-containing PFRs have been demonstrated by some authors against Escherichia coli and Staphylococcus aureus, thus giving birth to our idea of the possible use of BC-derived PFRs as a novel method capable of inducing ROS generation for antimicrobial oxidative therapy. Here, the general aspects concerning ROS physiological and pathological production and regulation and the mechanism by which they could exert antimicrobial effects have been reviewed. The methods currently adopted to induce ROS production for antimicrobial oxidative therapy have been discussed. Finally, for the first time, BC-related PFRs have been proposed as a new source of ROS for antimicrobial therapy via AOPs.

The hypoxic environment is among the most important factors that complicates the healing of chronic wounds, such as venous leg ulcers, pressure injuries and diabetic foot ulcers, which seriously affects the quality of life of patients. Various oxygen supply treatments are used in clinical practice to improve the hypoxic environment at the wound site. However, problems still occur, such as insufficient oxygen supply, short oxygen infusion time and potential biosafety risks. In recent years, artificial photosynthetic systems have become a research hotspot in the fields of materials and energy. Photosynthesis is expected to improve the oxygen level at wound sites and promote wound healing because the method provides a continuous oxygen supply and has good biosafety. In this paper, oxygen treatment methods for wounds are reviewed, and the oxygen supply principle and construction of artificial photosynthesis systems are described. Finally, research progress on the photosynthetic oxygen production system to promote wound healing is summarized.

Hyperbaric oxygen therapy (HBOT) has been used in patients with diabetic foot ulcers (DFU) for many years, but its clinical efficacy is still controversial. Therefore, this study explored the efficacy of HBOT applied to DFU by means of meta-analysis. PubMed, Cochrane Library, Embase, CNKI and Wanfang databases were searched, from database inception to October 2023, and published randomised controlled trials (RCTs) of HBOT in DFU were collected. Two investigators independently screened the collected literature, extracted relevant data and assessed the quality of the literature. Review Manager 5.4 software was applied for data analysis. Twenty-nine RCTs with 1764 patients were included. According to the combined results, when compared with conventional treatment, HBOT significantly increased the complete healing rate of DFUs (46.76% vs. 24.46%, odds ratio [OR]: 2.83, 95% CI: 2.29-3.51, p < 0.00001) and decreased the amputation rate (26.03% vs. 45.00%, OR: 0.41, 95% CI: 0.18-0.95, p = 0.04), but the incidence of adverse events was significantly higher in patients (17.37% vs. 8.27%, OR: 2.49, 95% CI: 1.35-4.57, p = 0.003), whereas there was no significant difference in the mortality (6.96% vs. 12.71%, OR: 0.52, 95% CI: 0.21-1.28, p = 0.16). Our results suggest that HBOT is effective in increasing the complete healing rate and decreasing the amputation rate in patients with DFUs, but increases the incidence of adverse events, while it has no significant effect on mortality.

It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design.

Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only.

For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality.

The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence.

Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.

Diabetic foot ulcers (DFUs) represent a major health concern for diabetic patients, often leading to debilitating complications. Hyperbaric oxygen therapy (HBOT) has been posited as an adjunctive therapeutic strategy to augment the healing rates of these ulcers. This systematic review and meta-analysis sought to critically evaluate the efficacy and safety of HBOT in the context of DFUs management. A rigorous search, adhering to PRISMA guidelines, was conducted across multiple electronic databases. Randomized controlled trials (RCTs) assessing the impact of HBOT on DFUs were included. Outcome measures were complete ulcer healing, major and minor amputation rates and adverse reactions. The analysis employed both fixed and random-effects models, contingent on the heterogeneity levels detected. Seven studies met the inclusion criteria. HBOT was found to significantly improve the complete healing rates of DFUs with a risk ratio (RR) of 3.59 (95% CI: 1.56-8.29, p < 0.001). However, HBOT's impact on both major and minor amputation rates did not yield statistically significant results. The sensitivity analysis underscored the robustness of the principal outcomes, and the publication bias assessment suggested the absence of any significant bias. Hyperbaric oxygen therapy stands out as a potent therapeutic tool in promoting the complete healing of diabetic foot ulcers, offering a promising adjunct to standard care protocols, while ensuring patient safety.

Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are of utmost importance when attempting to heal a chronic diabetes-related foot ulcer. However, the rising incidence and costs of diabetes-related foot ulcer management necessitate that interventions to enhance wound healing of chronic diabetes-related foot ulcers are supported by high-quality evidence of efficacy and cost effectiveness when used in conjunction with established aspects of gold-standard multidisciplinary care. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on wound healing interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline.

We followed the GRADE approach by devising clinical questions and important outcomes in the Patient-Intervention-Control-Outcome (PICO) format, undertaking a systematic review, developing summary of judgements tables, and writing recommendations and rationale for each question. Each recommendation is based on the evidence found in the systematic review and, using the GRADE summary of judgement items, including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability, we formulated recommendations that were agreed by the authors and reviewed by independent experts and stakeholders.

From the results of the systematic review and evidence-to-decision making process, we were able to make 29 separate recommendations. We made a number of conditional supportive recommendations for the use of interventions to improve healing of foot ulcers in people with diabetes. These include the use of sucrose octasulfate dressings, the use of negative pressure wound therapies for post-operative wounds, the use of placental-derived products, the use of the autologous leucocyte/platelet/fibrin patch, the use of topical oxygen therapy, and the use of hyperbaric oxygen. Although in all cases it was stressed that these should be used where best standard of care was not able to heal the wound alone and where resources were available for the interventions.

These wound healing recommendations should support improved outcomes for people with diabetes and ulcers of the foot, and we hope that widescale implementation will follow. However, although the certainty of much of the evidence on which to base the recommendations is improving, it remains poor overall. We encourage not more, but better quality trials including those with a health economic analysis, into this area.

Diabetic foot ulcers (DFUs) are common complications of uncontrolled diabetes mellitus that can result in infection and amputation of the lower extremities. This study compared the benefits and risks of hyperbaric oxygen therapy with those of other DFU treatments, based on the Wagner grading system.

Systematic searches for randomly controlled trials using hyperbaric oxygen therapy for DFUs were performed using PubMed, the Cochrane Library, and Embase. Data regarding demographics, wound healing, minor and major amputations, operative debridement, nonhealing wounds, and adverse effects were analyzed based on Wagner grades, using RevMan 5.4.1 and Microsoft Excel.

Hyperbaric oxygen therapy was significantly superior to other treatments for wound healing rates 8 or more weeks after the final treatment (RR = 2.39; 1.87-3.05; P < 0.00001) minor/distal amputations (RR = 0.58; 0.43-0.80; P < 0.007), and major/proximal amputations (RR = 0.31; 0.18-0.52; P < 0.00001) for the 14 studies analyzed. In addition, this therapy increased the rate of complete wound healing for Wagner grades II (RR = 21.11; 3.05-146.03; P = 0.002), III (RR = 19.58; 2.82-135.94, P = 0.003), and IV (RR = 17.53; 2.45-125.44; P = 0.004); decreased the minor/distal amputation rate for grade III (RR = 0.06; 0.01-0.29; P = 0.0004) and the major/proximal amputation rate on for grade IV (RR = 0.08; 0.03-0.25; P < 0.0001); and decreased the operative debridement rate for Wagner grade II (RR = 0.09; 0.01-0.60; P = 0.01).

Moderate-quality evidence revealed that adjunctive hyperbaric oxygen therapy improved DFU wound healing for Wagner grades II, III, and IV; prevented minor and major amputations for grades III and IV, respectively; and prevented operative debridement in grade II wounds.

Studies have revealed that both extracorporeal shock-wave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) can accelerate wound healing. This study aimed to compare the effectiveness of ESWT and HBOT in enhancing diabetic wound healing. A dorsal skin defect in a streptozotocin-induced diabetes rodent model was used. Postoperative wound healing was assessed once every 3 days. Histologic examination was performed with hematoxylin and eosin staining. Proliferation marker protein Ki-67 (Ki-67), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were evaluated with immunohistochemical (IHC) staining. The wound area was significantly reduced in the ESWT and HBOT groups compared to that in the diabetic controls. However, the wound healing time was significantly increased in the HBOT group compared to the ESWT group. Histological findings showed a statistical increase in neovascularization and suppression of the inflammatory response by both HBOT and ESWT compared to the controls. IHC staining revealed a significant increase in Ki-67, VEGF, and eNOS but suppressed 8-OHdG expression in the ESWT group compared to the HBOT group. ESWT facilitated diabetic wound healing more effectively than HBOT by suppressing the inflammatory response and enhancing cellular proliferation and neovascularization and tissue regeneration.

The meta-analysis aimed to assess the effect of hyperbaric oxygen treatment on diabetic foot ulcers. Using dichotomous or contentious random or fixed effect models, the outcomes of this meta-analysis were examined and the odds ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were computed. 17 examinations from 1992 to 2022 were enrolled for the present meta-analysis, including 7219 people with diabetic foot ulcers. Hyperbaric oxygen treatment had a significantly higher healed ulcer (OR, 14.39; 95% CI, 4.02-51.52, p < 0.001), higher adverse event (OR, 2.14; 95% CI, 1.11-4.11, p = 0.02), lower mortality (OR, 0.22; 95% CI, 0.07-0.71, p = 0.01) and higher ulcer area reduction (MD, 23.39; 95% CI, 11.79-34.99, p < 0.001) compared to standard treatment in patients with diabetic foot ulcers. However, hyperbaric oxygen treatment and standard treatment had no significant difference in amputation (OR, 0.62; 95% CI, 0.22-1.75, p = 0.37), major amputation (OR, 0.59; 95% CI, 0.18-1.92, p = 0.38), minor amputation (OR, 0.64; 95% CI, 0.15-2.66, p = 0.54) and healing time (MD, -0.001; 95% CI, -0.76 to 0.75, p = 0.99) in patients with diabetic foot ulcers. The examined data revealed that hyperbaric oxygen treatment had a significantly higher healed ulcer, adverse event, and ulcer area reduction and lower mortality, however, there was no significant difference in amputation and healing time compared to standard treatment in patients with diabetic foot ulcers. Yet, attention should be paid to its values since most of the selected examinations had a low sample size and some of the comparisons had a low number of selected studies.

Chronic wound unhealing is a common complication in diabetic patients, which is mainly caused by tissue hypoxia, slow vascular recovery, and a long period of inflammation. Here we present a sprayable alginate hydrogel (SA) dressing consisting of oxygen-productive (CP) microspheres and exosomes (EXO) to promote local oxygen generation, accelerate macrophage towards M2 polarization, and improve cell proliferation in diabetic wounds. Results show that the release of oxygen continues for up to 7 days, reducing the expression of hypoxic factors in fibroblasts. In vivo, the diabetic wounds experiment showed that the CP/EXO/SA dressing apparently accelerated full-thickness wound healing characteristics such as the promotion of wound healing efficiency, rapid re-epithelization, favorable collagen deposition, abundant angiogenesis at the wound beds, and shortened inflammation period. EXO synergistic oxygen (CP/EXO/SA) dressing suggests a promising treatment measure for diabetic wounds.

Hyperbaric oxygen therapy (HBOT) involves treating patients by providing 100% oxygen through inhalation while inside a treatment pressurized chamber. The oxygen acts as a drug and the hyperbaric chamber as the dosing device. The effect of hyperbaric hyperoxia is dose dependent and, therefore, treatment depth and duration are important when considering its use. HBOT can either be the primary method of treatment or used adjunctively to medications or surgical techniques. The underpinning physiology is to bring oxygen-rich plasma to hypoxic tissue, preventing reperfusion injury, strengthening immune responsiveness, and encouraging new collagen deposition as well as endothelial cell formation.

Diabetic foot ulcers (DFUs) are a major complication of diabetes mellitus and a leading cause of lower limb amputation. Interventions to reduce psychological stress may have the potential to improve self-care and greatly reduce the morbidity and mortality associated with DFU. This review is focused on the consequences of psychological stress in wound healing and reflects on the effects of currently used psychological stress-reducing interventions in patients with DFU, proposing new applications for currently used stress-reduction interventions.

Stress is a natural and fundamental survival mechanism that becomes harmful when chronic. DFU is associated with high levels of anxiety and chronic psychological stress. Chronic stressinduced cortisol and adrenaline release impair wound healing, independently of the stressor. Psychological stress-reducing interventions, such as relaxation with guided imagery, biofeedback-assisted relaxation, mindfulness-based strategies, and hypnosis, can lead to a reduction in perceived stress and improve wound healing by reducing wound inflammation and pain while improving glycemic control. All stress reduction interventions also lead to pain relief and improved patient's quality of life.

Psychological stress-reducing interventions are promising adjuvant therapies for DFU. Their clinical application can improve self-care by tackling patient's expectations, anxieties, and fears. They can also help patients manage stress and pain while reducing wound inflammation and improving wound healing.

The present systematic review and meta-analysis was performed to evaluate the efficacy of hyperbaric oxygen therapy (HBOT) in the treatment of diabetic foot ulcers (DFUs). Relevant articles were retrieved from PubMed, the Cochrane Library, EMBASE and other databases through November 2020. A total of 20 randomized clinical trials and 1263 trials were included in the meta-analysis. For each trial, the average difference, odds ratio and 95% confidence interval were calculated to evaluate the efficacy. Hyperbaric oxygen therapy increased the healing rate of diabetic foot ulcers (relative risk, 1.901; 95% CI = 1.484-2.435, p < 0.0001), shortened the healing time (MD = -19.360; 95% CI = -28.753~-9.966, p < 0.001), and reduced the incidence of major amputation (relative risk, 0.518, 95% CI = 0.323-0.830, P < 0.01). In summary, our meta-analysis confirmed that hyperbaric oxygen therapy offers great benefits in the treatment of DFU and the reduction of amputation. In addition, larger and well-designed randomized controlled trials need to be planned and conducted to verify this conclusion.

Ever-increasing demands on improving efficiencies of wound healing procedures are a strong driving force for the development of replacement approaches. This review focuses on wound healing management from the point of formation to the point of healing procedures. The most important usual healing modality with key characteristic is explained and their limitations are discussed. Novel interesting approaches are presented with a concentration of the unique features and action mechanisms. Special attention is paid to gas plasma and nanotechnology impact on wound healing management from fundamental processes to beneficial outcomes. Challenges and opportunities for the future trend that combined common protocols and emerging technologies are discussed.

Background and Objectives: Hyperbaric oxygen is a recognised treatment for a range of medical conditions, including treatment of diabetic foot disease. A number of studies have reported an impact of hyperbaric oxygen treatment on glycaemic control in patients undergoing treatment for diabetic foot disease. There has been no systematic review considering the impact of hyperbaric oxygen on glycaemia in people with diabetes. Materials and Methods: A prospectively PROSPERO-registered (PROSPERO registration: CRD42021255528) systematic review of eligible studies published in English in the PUBMED, MEDLINE, and EMBASE databases, based on the following search terms: hyperbaric oxygen therapy, HBO2, hyperbaric oxygenation, glycaemic control, diabetes, diabetes Mellitus, diabetic, HbA1c. Data extraction to pre-determined piloted data collection form, with individual assessment of bias. Results: In total, 10 eligible publications were identified after screening. Of these, six articles reported a statistically significant reduction in blood glucose from hyperbaric oxygen treatment, while two articles reported a statistically significant increase in peripheral insulin sensitivity. Two articles also identified a statistically significant reduction in HbA1c following hyperbaric oxygen treatment. Conclusions: There is emerging evidence suggesting a reduction in glycaemia following hyperbaric oxygen treatment in patients with diabetes mellitus, but the existing studies are in relatively small cohorts and potentially underpowered. Additional large prospective clinical trials are required to understand the precise impact of hyperbaric oxygen treatment on glycaemia for people with diabetes mellitus.

Nonhealing diabetic wounds are common complications for diabetic patients. Because chronic hypoxia prominently delays wound healing, sustained oxygenation to alleviate hypoxia is hypothesized to promote diabetic wound healing. However, sustained oxygenation cannot be achieved by current clinical approaches, including hyperbaric oxygen therapy. Here, we present a sustained oxygenation system consisting of oxygen-release microspheres and a reactive oxygen species (ROS)-scavenging hydrogel. The hydrogel captures the naturally elevated ROS in diabetic wounds, which may be further elevated by the oxygen released from the administered microspheres. The sustained release of oxygen augmented the survival and migration of keratinocytes and dermal fibroblasts, promoted angiogenic growth factor expression and angiogenesis in diabetic wounds, and decreased the proinflammatory cytokine expression. These effects significantly increased the wound closure rate. Our findings demonstrate that sustained oxygenation alone, without using drugs, can heal diabetic wounds.

Hyperbaric Oxygen Therapy (HBOT) is increasingly being used in the treatment of as diabetic foot ulcers (DFU). However, definitive evidence regarding its beneficial effects is still scarce. The present systematic review aims to analyse the role of HBOT in the prevention of limb amputation along with improvement of ulcer healing in patients with lower limbs DFU.

Three databases were searched: PubMed, Scopus, and ISI Web of Knowledge. The search was enrolled during October 2020. Both titles and abstracts were examined by two independent reviewers. Only randomized controlled trials (RCTs) reporting a comparison between standard DFU treatment and standard treatment associated with HBOT were included. In all studies eligibility was assessed and data regarding studies characteristics, methods and considered outcomes was obtained. Odds ratio (OR) was used to evaluate amputation and complete ulcer healing rates. Percentage of ulcer reduction at two weeks was evaluated using the inverse variance method, and the values were compared using mean difference values. Meta-analysis was done using a fixed-effect model if I2 values were under 50%, and a random-effects model if not.

Eleven RCTs were included, with a total of 668 patients studied. Patients undergoing HBOT had lower risk of amputation (OR 0.53 95% CI 0.32-0.90, I2=31%). No difference was found in minor amputations (OR 0.89 95% CI 0.35-2.24, I2=69%). Regarding, healing rates, HBOT patients had greater chances of ulcer healing (OR 4,00 95% CI 1.54-10.44, I2=70%). It has also shown higher percentage of ulcer area reduction after two weeks of treatment in the HBOT group (mean difference 23.19%; 95% CI 14.86-31.52; I2=0%).

The present review offers evidence that adjuvant HBOT decreases risk of major amputation while promoting wound healing when combined to standard treatment in the management of DFU. These findings may have clinical relevance in a selected group of patients, yet further larger studies are still needed.

The present article evaluates the results of the treatment with adjuvant hyperbaric oxygen therapy (HBOT) of patients with nonhealing, chronic wounds. In the period 2013 to 2016, 248 patients were referred from various hospitals because of chronic wounds that were recalcitrant in healing despite standard wound care as described in national and international guidelines. After inclusion, all patients were treated with HBOT and subjected to a weekly standard wound care treatment. During each HBOT session, 100% O2 was administered for 75 minutes under increased pressure of 2.4 ATA. Wounds and quality of life were assessed before and after the total treatment period. A total of 248 patients have been evaluated. Diabetic foot ulcers were present in 134 patients, the remainder (114 patients) showed a variety of wound locations and etiologies. The number of HBOT treatments amounted to an average of 48 (range 20-68) sessions. Before referral to our clinic, 31% of all wounds had existed for at least 18 months (72 patients). After HBOT, 81% of all wounds were near complete healing or completely healed, in 13% of the cases the wound was stable, and in 2% minor or major amputation had to be carried out. The mean treatment time for wounds pre-existing fewer than 6 weeks ("early referrals") was 67 days, and 119 days for wounds pre-existing more than 18 months ("late referrals"). A majority of the patients in our study referred with nonhealing wounds clinically improved when adjuvant HBOT was added to standard wound care protocols. No differences in success rate were seen between diabetic and nondiabetic wounds. It showed that HBOT is a well-tolerated treatment.

Historically, the field of regenerative medicine has aimed to heal damaged tissue through the use of biomaterials scaffolds or delivery of foreign progenitor cells. Despite 30 years of research, however, translation and commercialization of these techniques has been limited. To enable mammalian regeneration, a more practical approach may instead be to develop therapies that evoke endogenous processes reminiscent of those seen in innate regenerators. Recently, investigations into tadpole tail regrowth, zebrafish limb restoration, and the super-healing Murphy Roths Large (MRL) mouse strain, have identified ancient oxygen-sensing pathways as a possible target to achieve this goal. Specifically, upregulation of the transcription factor, hypoxia-inducible factor one alpha (HIF-1α) has been shown to modulate cell metabolism and plasticity, as well as inflammation and tissue remodeling, possibly priming injuries for regeneration. Since HIF-1α signaling is conserved across species, environmental or pharmacological manipulation of oxygen-dependent pathways may elicit a regenerative response in non-healing mammals. In this review, we will explore the emerging role of HIF-1α in mammalian healing and regeneration, as well as attempts to modulate protein stability through hyperbaric oxygen treatment, intermittent hypoxia therapy, and pharmacological targeting. We believe that these therapies could breathe new life into the field of regenerative medicine.

Studies have suggested that hyperbaric oxygen therapy (HBOT) is effective in the healing of diabetic foot ulcer (DFU); however, there is a lack of consensus. Therefore, to assess the efficacy of HBOT on diabetic foot ulcer among diabetic patients, controlled clinical trials were searched through PubMed, EMBASE, Clinical key, Ovid Discovery, ERMED, Clinical Trials.gov databases for randomized controlled trials (RCTs) and other sources until 15 September 2020. Studies that evaluated the effect of HBOT on diabetic foot ulcer, complete healing, amputation, adverse events, ulcer reduction area, and mortality rate were included. Of 1984 study records screened, 14 studies (768 participants) including twelve RCTs, and two CCTs were included as per inclusion criteria. The results with pooled analysis have shown that HBOT was significantly effective in complete healing of diabetic foot ulcer (OR = 0.29; 95% CI 0.14-0.61; I² = 62%) and reduction of major amputation (RR = 0.60; 95% CI 0.39-0.92; I² = 24%). Although, it was not effective for minor amputations (RR = 0.82; 95% CI 0.34-1.97; I² = 79%); however, less adverse events were reported in standard treatment group (RR = 1.68; 95% CI 1.07-2.65; I² = 0%). Nevertheless, reduction in mean percentage of ulcer area and mortality rate did not differ in HBOT and control groups. This review provides an evidence that hyperbaric oxygen therapy is effective as an adjunct treatment measure for the diabetes foot ulcers. These findings could be generalized cautiously by considering methodological flaws within all studies.

Photobiomodulation (PBM) by far-red (FR) to near-infrared (NIR) light has been demonstrated to accelerate diabetic wound healing in preclinical and clinical studies. Mitochondrial dysfunction and oxidative stress play key roles in impaired diabetic wound healing, and the effect of PBM on the metabolic state of diabetic wounds remains to be elucidated.

In this study, a custom-designed in vivo fluorescence imaging technique was used to quantitatively assess the effect of FR-PBM on the mitochondrial bioenergetics of diabetic wounds. The intrinsic fluorescence of two mitochondrial co-enzymes, nicotinamide adenine dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD), was monitored to quantify the redox ratio (RR) (NADH/FAD) of wounds over time.

Using an excisional model of wound healing, we demonstrated that 670 nm (FR) PBM improved mitochondrial bioenergetics and stimulated the rate of wound healing in diabetic db/db mice. Wound closure and the RR of diabetic wounds in response to 670 nm PBM (4.5 J/cm², 60 mW/cm² for 90 s per day, 5 days/week) were compared to the sham-treated group. At day 9 of post-wounding, we observed a 43% decrease in the wound area and a 75% increase in RR in FR-treated diabetic mice compared to sham-treated diabetic mice.

We conclude that the increase in mitochondrial RR and the related decrease in oxidative stress may be an important factor in FR-PBM mediated acceleration of wound healing in diabetic mice.

After reading this article, the participant should be able to: 1. Understand the basics of negative-pressure wound therapy and practical uses of various vacuum-assisted closure dressings. 2. Understand the mechanisms of action of negative-pressure therapies and other important adjuncts, such as perfusion imaging. 3. Discuss the evidence for hyperbaric oxygen therapy in wound care.

Wound healing requires creating an environment that supports the healing process while decreasing inflammation and infection. Negative-pressure wound therapy has changed the way physicians manage acute and chronic wounds for more than 20 years. It contracts wound edges, removes exudate, including inflammatory and infectious material, and promotes angiogenesis and granulation tissue formation. These effects have been consistently demonstrated in multiple animal and human randomized controlled trials. Recent innovations that include instillation therapy and closed incision have further increased our arsenal against difficult-to-treat wounds and incisions at high risk of complications. Instillation of topical wound solutions allows physicians to cleanse the wound without return to the operating room, resulting in fewer debridements, shorter hospital stays, and faster time to wound closure. Other concepts have yielded negative-pressure therapy on top of closed surgical incisions, which holds incision edges together, reduces edema, promotes angiogenesis, and creates a barrier to protect incisions during the critical healing period, thereby reducing surgical-site complications, especially infection. Other practical adjuncts to the modern-day treatment of acute and chronic wounds include indocyanine green angiography, which allows real-time assessment of perfusion, and hyperbaric oxygen treatment, which has been suggested to augment healing in acute, chronic, specifically diabetic foot ulcers and radiation-related wounds.

Hyperbaric oxygen therapy (HBOT) has been suggested to improve healing of lower limb ulcers, though the quality of available evidence is weak to moderate. This study assessed the opinions and use of HBOT by specialists treating lower limb ulcers.

Accredited vascular surgeons and podiatrists in Australia and New Zealand were sent an online survey via their professional organizations. The survey asked about their use and opinions of HBOT in treating lower limb ischemic, neuropathic and venous ulcers. Data were summarized with descriptive statistics. Non-parametric tests were used to compare survey results obtained from vascular surgeons and podiatrists.

61 vascular surgeons and 40 podiatrists completed the survey. Thirty-seven specialists used HBOT for treating lower limb ulcers, with the remainder indicating they did not feel there was a role for HBOT (n=25) or did not have access to HBOT (n=39). Less than 8% of specialists indicated that HBOT frequently or always had a role in treating ischemic, neuropathic or venous ulcers. Compared with podiatrists, vascular surgeons were significantly less likely to indicate HBOT had a treatment role for any ulcer type (p<0.001, p=0.004, and p<0.001, respectively), though significantly more likely to indicate they currently used HBOT for treating lower limb ulcers (p<0.001). Most specialists (n=76) believed that a large clinical trial is needed to determine the efficacy of HBOT in treating lower limb ulcers.

Vascular surgeons and podiatrists do not feel HBOT has a frequent role in treating lower limb ulcers, but do feel there needs to be a large clinical trial to test its value.

The management of diabetic foot ulcers (DFU) remains a challenge, and there is continuing uncertainty concerning optimal approaches to wound healing. The International Working Group of the Diabetic Foot (IWGDF) working group on wound healing has previously published systematic reviews of the evidence in 2008, 2012 and 2016 to inform protocols for routine care and to highlight areas which should be considered for further study. The working group has now updated this review by considering papers on the interventions to improve the healing of DFU's published between June 2014 and August 2018. Methodological quality of selected studies was independently assessed by a minimum of two reviewers using the recently published 21-point questionnaire as recommended by IWGDF/European Wound Management Association, as well as the previously incorporated Scottish Intercollegiate Guidelines Network criteria. Of the 2275 papers identified, 97 were finally selected for grading following full text review. Overall, there has been an improvement in study design and a significant rise in the number of published studies. While previous systematic reviews did not find any evidence to justify the use of newer therapies, except for negative pressure wound therapy in post-surgical wounds, in this review we found additional evidence to support some interventions including a sucrose-octasulfate dressing, the combined leucocyte, fibrin and platelet patch as well as topical application of some placental membrane products, all when used in addition to usual best care. Nonetheless, the assessment and comparison of published trials remains difficult with marked clinical heterogeneity between studies: in patient selection, study duration, standard of usual care provision and the timing and description of the clinical endpoints.

Diabetic foot ulcers are a common complication of diabetes, which affects 25% of patients and may ultimately lead to amputation of affected limbs. Research suggests hyperbaric oxygen therapy improves healing of these ulcers. However, this has not been reflected in previous reviews, possibly because they did not differentiate between patients with and without peripheral arterial occlusive disease. Therefore, we performed a systematic review of published literature in the MEDLINE, Embase, and Cochrane CENTRAL databases on nonischemic diabetic foot ulcers with outcome measures including complete ulcer healing, amputation rate (major and minor), and mortality. Seven studies were included, of which two were randomized clinical trials. Two studies found no difference in major amputation rate, whereas one large retrospective study found 2% more major amputations in the hyperbaric oxygen group. However, this study did not correct for baseline differences. Two studies showed no significant difference in minor amputation rate. Five studies reporting on complete wound healing showed no significant differences. In conclusion, the current evidence suggests that hyperbaric oxygen therapy does not accelerate wound healing and does not prevent major or minor amputations in patients with a diabetic foot ulcer without peripheral arterial occlusive disease. Based on the available evidence, routine clinical use of this therapy cannot be recommended. However, the available research for this specific subgroup of patients is scarce, and physicians should counsel patients on expected risks and benefits. Additional research, focusing especially on patient selection criteria, is needed to better identify patients that might profit from this therapy modality.

Modic changes (MCs) have attracted great interest in recent years. The complex process of MC development and progression seems to involve interplay between mechanical, infective, inflammatory, and degenerative processes that cannot be clearly differentiated. Based on signal intensity on T1- and T2-weighted MRI scans, MCs can be divided three types: Type 1, Type 2, and Type 3. Predominantly Type 1 MCs are commonly associated with chronic low back pain that is unresponsive to classic treatment options. Infection with low-virulent anaerobic microorganisms, most commonly Propionibacterium acnes, has been implicated in MC development following a disc herniation when a tear enables bacteria to enter the disc. Recent studies in patients with chronic low back pain following a lumbar disc herniation associated with Type 1 MCs have reported promising results following prolonged systemic antibiotic treatment with amoxicillin-clavulanate. Hyperbaric oxygen therapy, as primary or adjuvant treatment in association combination with systemic antibiotics or anti-inflammatory therapy, could offer important advantages in treating patients with suspected low-virulent disc infections due to anaerobic microorganisms associated with Type 1 MCs. We believe that hyperbaric oxygenation could contribute to faster resolution of Type 1 MCs and associated pain through multiple effects-including direct antimicrobial effects through formation of reactive oxygen species (ROS), altering the favorable low oxygen tension milieu such that it becomes unfavorable for bacterial growth and survival, and anti-biofilm effects. Additionally, hyperbaric oxygenation could contribute to faster pain resolution via direct and indirect anti-inflammatory effects. As an adjuvant treatment administered in combination with systemic antibiotics, HBOT could increase the sensitivity of Propionibacterium acnes to antimicrobial drugs under hyperoxic conditions, resulting in faster MC resolution. Overall, the faster infection resolution, diminished bacterial load, and anti-inflammatory effects due to reduced cytokine expression and levels of infectious by-products could lead to faster pain resolution following HBOT, and a significant improvement of quality of life in these patients.

Patients with severe diabetic foot ulcerations that fail to heal with standard conventional therapies may be candidates for hyperbaric oxygen therapy; these patients also should be evaluated for atypical wound etiologies. Medical evaluation includes thorough history, physical examination, screening laboratory tests, and ulcer biopsy. During hyperbaric oxygen therapy, patients breathe 100% oxygen at 2 times to 3 times atmospheric pressure while enclosed in a hyperbaric chamber. Over time, administration of hyperbaric oxygen therapy can result in wound neovascularization and enhanced limb salvage. In patients with suspected atypical ulceration, referral to a multidisciplinary wound healing center is considered standard of care.

To examine the efficacy of hyperbaric oxygen therapy in healing diabetes-related lower limb ulcers through a meta-analysis of randomized clinical trials.

A literature search was conducted to identify appropriate clinical trials. Inclusion required randomized study design and reporting of the proportion of diabetes-related lower limb ulcers that healed. A meta-analysis was performed to examine the effect of hyperbaric oxygen therapy on ulcer healing. The secondary outcomes were minor and major amputations.

Nine randomized trials involving 585 participants were included. People allocated to hyperbaric oxygen therapy were more likely to have complete ulcer healing (relative risk 1.95, 95% CI 1.51-2.52; P<0.001), and less likely to require major (relative risk 0.54, 95% CI 0.36-0.81; P=0.003) or minor (relative risk 0.68, 95% CI 0.48-0.98; P=0.040) amputations than control groups. Sensitivity analyses suggested the findings were dependent on the inclusion of one trial. Adverse events included ear barotrauma and a seizure. Many of the trials were noted to have methodological weaknesses including absence of blinding of outcome assessors, lack of a justifiable sample size calculation and limited follow-up.

This meta-analysis suggests hyperbaric oxygen therapy improves the healing of diabetes-related lower limb ulcers and reduces the requirement for amputation. Confidence in these results is limited by significant design weaknesses of previous trials and inconsistent findings. A more rigorous assessment of the efficacy of hyperbaric the efficacy of hyperbaric oxygen therapy is needed.

Diabetic foot ulcer is a common chronic complication of diabetes mellitus. In addition to conventional primary therapy, there are adjuvant therapy methods such as hyperbaric oxygen therapy for the healing of diabetic foot ulcer wounds. The present study aimed to determine the efficacy of hyperbaric oxygen therapy in diabetic foot ulcers based on Wagner classification. It was performed retrospectively from prospectively collected data. One hundred thirty patients with diabetic foot ulcers were assessed in 2 groups: 1 group received hyperbaric oxygen therapy; the other group did not. Patients were examined according to age, sex, ulcer grade based on Wagner classification; ulcer healing status; whether hyperbaric oxygen therapy was received; duration of diabetes in years; HbA1C, sedimentation, C-reactive protein levels; and presence of accompanying diseases, including peripheral arterial disease, chronic obstructive pulmonary disease, hypertension, chronic kidney disease, neuropathy, and retinopathy. The mean follow-up period was 19.5 ± 4.45 months (range 12 to 28 months). Seventy-one (54.6%) patients received hyperbaric oxygen therapy, and 59 (45.4%) patients did not. All patients in Wagner grade 2 healed in both groups. In the group that received hyperbaric oxygen therapy for grade 3 and 4 patients, 35 (87.5%) and 11 (84.6%) healed, respectively. In total, 60 (84.5%) patients in the group that received hyperbaric oxygen therapy healed. The subgroup comparison conducted according to Wagner classification revealed no differences between the 2 groups of grades 2 and 5 patients. It also revealed that treatment had higher levels of efficacy in the healing of ulcers in grade 3 and 4 patients.

Diabetic foot ulceration remains a major challenge and is one of the most expensive and leading causes of major and minor amputations among patients with diabetic foot ulcer. Hence the purpose of this review is to emphasize on potential molecular markers involved in diabetic foot ulcer physiology, the efficacy of different types of dressing materials, adjunct therapy and newer therapeutic approach like nanoparticles for the treatment of diabetic foot ulcer.

We conducted a systematic literature review search by using Pubmed and other web searches. The quality evidence of diabetic foot ulcer biomolecules and treatments was collected, summarized and compared with other studies.

The present investigation suggested that impaired wound healing in diabetic patients is an influence of several factors. All the advanced therapies and foot ulcer dressing materials are not suitable for all types of diabetic foot ulcers, however more prospective follow ups and in vivo and in vitro studies are needed to draw certain conclusion. Several critical wound biomolecules have been identified and are in need to be investigated in diabetic foot ulcers. The application of biocompatible nanoparticles holds a promising approach for designing dressing materials for the treatment of diabetic foot ulcer.

Understanding the cellular and molecular events and identifying the appropriate treatment strategies for different foot ulcer grades will reduce recurrence of foot ulcer and lower limb amputation.

Objective: The goal of this research was to identify a population of diabetic foot ulcer patients who demonstrate a significant response to hyperbaric oxygen therapy (HBOT) using a large sample size to provide guidance for clinicians when treating these complicated patients. Approach: The effect of HBOT on diabetic foot ulcers, Wagner grades 3 and 4, was evaluated using a retrospective observational real-world data set. The study reported on the overall healing rate, (74.2%) at the population level, for >2 million wounds. Results: When a subgroup of patients of only foot ulcers with a Wagner grade 3 or 4 were considered, the healing rate was only 56.04%. The use of HBOT, without filtering for the number of treatments received, improved the healing rate to 60.01% overall. Healing rates for this same subgroup, however, were improved to 75.24% for patients who completed the prescribed number of hyperbaric treatments. Innovation: This observational study discusses the importance of reporting at the population level, specific wound etiology level, a risk-stratified level, and to then overlay the effect of treatment adherence on those outcomes to provide clinicians with a comprehensive understanding of when to prescribe an advanced modality such as hyperbaric oxygen. Conclusion: The authors provide healing outcomes data from several prior HBOT studies as well as other advanced modalities that have been used in diabetic foot ulcer care for comparison and context.

Hyperbaric oxygen therapy (HBOT) is a treatment procedure that involves breathing 100% O₂ for a certain time and under a certain pressure. HBOT is commonly administrated as a primary or alternative therapy for different diseases such as infections. In this paper, we reviewed the general aspect of HBOT procedures, the mechanisms of antimicrobial effects and the application in the treatment of infections. Parts of the antimicrobial effects of HBOT are believed to result of reactive from the formation of reactive oxygen species (ROS). It is also said that HBOT enhances the antimicrobial effects of the immune system and has an additive or synergistic effect with certain antimicrobial agents. HBOT has been described as a useful procedure for different infections, particularly in deep and chronic infections such as necrotizing fasciitis, osteomyelitis, chronic soft tissue infections, and infective endocarditis. The anti-inflammation property of HBOT has demonstrated that it may play a significant role in decreasing tissue damage and infection expansion. Patients treated by HBOT need carful pre-examination and monitoring. If safety standards are strictly tracked, HBOT can be considered a suitable procedure with an apt rate of complication.

To evaluate the role of platelet-rich plasma (PRP) in healing diabetic fool ulcers (DFUs), and to compare the rate of healing and final outcome with conventional therapy.

A prospective study conducted between October 2013 and July 2015. Participants were divided in to two groups: a study group in which PRP was used and a control group receiving standard therapy. Wound assessment was carried out according to the Bates-Jensen Wound Assessment Tool at 0, 7, 14, 21 and 28 days.

A total of 55 patients were recruited to the study. There were 29 patients in the study group and 26 patients in the control group. After application of PRP, there was significant improvement in mean wound score and significant percent improvement in wound score in the study group (p<0.0001). Complete healing occurred in all patients in the study group in (mean score and standard deviation) 36.7±3 days compared with 60.6±3.7 days in the control group (p<0.0001). There were no unwanted side effects in patients using the PRP in this study.

PRP appears to be a promising agent in the management of DFUs. In this study, DFUs healed more quickly in the study group than in the control group. There was also significant percent improvement in wound score as compared with debridement and dressing only. If proper selection criteria are applied, PRP could be a useful aid to wound healing in people with DFUs.

Hyperbaric oxygen therapy (HBOT) is effective for the medical treatment of diverse diseases, infections, and tissue injury. In fact, in recent years there is growing evidence on the beneficial effect of HBOT on non-healing ischemic wounds. However, there is still yet discussion on how this treatment could benefit from combination with regenerative medicine strategies. Here we analyzed the effects of HBOT on three specific aspects of tissue growth, maintenance, and regeneration: (i) modulation of adult rodent (Mus musculus) intestinal stem cell turnover rates; (ii) angiogenesis dynamics during the development of the chorio-allantoic membrane (CAM) in Gallus gallus embryos; (iii) and wound-healing in a spontaneous type II diabetic mouse model with a low capacity to regenerate skin. To analyze these aspects of tissue growth, maintenance, and regeneration, we used HBOT alone or in combination with cellular therapy. Specifically, Wharton Jelly Mesenchymal Stem cells (WJ-MSC) were embedded in a commercial collagen-scaffold. HBOT did not affect the metabolic rate of adult mice nor of chicken embryos. Notwithstanding, HBOT modified the proliferation rate of stem cells in the mice small intestinal crypts, increased angiogenesis in the CAM, and improved wound-healing and tissue repair in diabetic mice. Moreover, our study demonstrates that combining stem cell therapy and HBOT has a collaborative effect on wound-healing. In summary, our data underscore the importance of oxygen tension as a regulator of stem cell biology and support the potential use of oxygenation in clinical treatments.