Stimulate Wound Healing Research Articles

Biomedical materials for wound dressing: recent advances and applications.

Wound healing is vital to maintain the physiological functions of the skin. The most common treatment is the use of a dressing to cover the wound and reduce infection risk and the rate of secondary injuries. Modern wound dressings have been the top priority choice for healing various types of wounds owing to their outstanding biocompatibility and biodegradability. In addition, they also maintain temperature and a moist environment, aid in pain relief, and improve hypoxic environments to stimulate wound healing. Due to the different types of wounds, as well as the variety of advanced wound dressing products, this review will provide information on the clinical characteristics of the wound, the properties of common modern dressings, and the in vitro, in vivo as well as the clinical trials on their effectiveness. The most popular types commonly used in producing modern dressings are hydrogels, hydrocolloids, alginates, foams, and films. In addition, the review also presents the polymer materials for dressing applications as well as the trend of developing these current modern dressings to maximize their function and create ideal dressings. The last is the discussion about dressing selection in wound treatment and an estimate of the current development tendency of new materials for wound healing dressings.

Is there an effective way to control pain perception after free gingival graft removal? A systematic review and meta-analysis.

The literature describes multiple ways to stimulate wound healing to reduce the patient's perception of pain. This systematic review aimed to evaluate if methods that enhance wound healing can reduce the patient's perception of pain after free gingival graft removal from the palate region compared to natural healing. A systematic review protocol was written following the PRISMA checklist. Electronic searches of five databases were performed to identify randomized clinical trials (RCTs) that assessed the patient's perception of pain after the removal of a free gingival graft from the palate. The primary outcome was the visual analog scale (VAS) score assessing the patient's perception of pain 7 days after the free gingival graft removal from the palate region. Of the 1,622 potentially relevant articles retrieved from the electronic databases, 16 RCTs were selected for qualitative analysis, and of these, 6 RCTs were included in the meta-analysis. RCTs showed a significant VAS reduction associated with the use of methods to enhance wound healing. The pooled estimates revealed a significant overall VAS reduction of 2.20 (95% CI 2.32, 2.07) 7 days after surgery. The methods that presented the greatest reduction in the perception of pain were platelet-rich fibrin, hyaluronic acid, and autologous fibrin glue. Methods that enhance wound healing, including platelet-rich fibrin, hyaluronic acid, and autologous fibrin glue, can reduce pain perception after free gingival graft removal in the palate region. However, only 1 RCT investigated each approach, which hinders the conclusion regarding the best procedure to reduce the perception of pain.

The role of activated androgen receptor in cofilin phospho-regulation depends on the molecular subtype of TNBC cell line and actin assembly dynamics.

Triple negative breast cancer (TNBC) is highly metastatic and of poor prognosis. Metastasis involves coordinated actin filament dynamics mediated by cofilin and associated proteins. Activated androgen receptor (AR) is believed to contribute to TNBC tumorigenesis. Our current work studied roles of activated AR and cofilin phospho-regulation during migration of three AR+ TNBC cell lines to determine if altered cofilin regulation can explain their migratory differences. Untreated or AR agonist-treated BT549, MDA-MB-453, and SUM159PT cells were compared to cells silenced for cofilin (KD) or AR expression/function (bicalutamide). Cofilin-1 was found to be the only ADF/cofilin isoform expressed in each TNBC line. Despite a significant increase in cofilin kinase caused by androgens, the ratio of cofilin:p-cofilin (1:1) did not change in SUM159PT cells. BT549 and MDA-MB-453 cells contain high p-cofilin levels which underwent androgen-induced dephosphorylation through increased cofilin phosphatase expression, but surprisingly maintain a leading-edge with high p-cofilin/total cofilin not found in SUM159PT cells. Androgens enhanced cell polarization in all lines, stimulated wound healing and transwell migration rates and increased N/E-cadherin mRNA ratios while reducing cell adhesion in BT549 and MDA-MB-453 cells. Cofilin KD negated androgen effects in MDA-MB-453 except for cell adhesion, while in BT549 cells it abrogated androgen-reduced cell adhesion. In SUM159PT cells, cofilin KD with and without androgens had similar effects in almost all processes studied. AR dependency of the processes were confirmed. In conclusion, cofilin regulation downstream of active AR is dependent on which actin-mediated process is being examined in addition to being cell line-specific. Although MDA-MB-453 cells demonstrated some control of cofilin through an AR-dependent mechanism, other AR-dependent pathways need to be further studied. Non-cofilin-dependent mechanisms that modulate migration of SUM159PT cells need to be investigated. Categorizing TNBC behavior as AR responsive and/or cofilin dependent can inform on decisions for therapeutic treatment.

ANTI-MICROBIAL ACTIVITY AND DIABETIC WOUND HEALING EFFECTS OF PSIDIUM GUAVA AND MELASTOMA MALABATHRICUM LINN LEAVES GEL IN RATS (SPRAGUE DAWLEY)

The purpose of this study was to determine the potential of guava and melastoma malabathricum linn leaves mixed gel activity as anti-microbial and wound healing in experimental rats (Sprague dawley). The thick extracts of melastoma malabathricum linn and guava leaves were made in a gel dosage form with a concentration of 4% and 6% and clindamycin as a positive control. This study used experimental laboratory methods, and the population in this study were white male rats and was carried out in the Pharmacology and Pharmaceutical Laboratory, National Institute of Science and Technology. The pharmacological activity was tested in the form of a gel dosage formula, and the rats were made diabetic through an inducing agent, namely alloxan, then the potential of the extract was seen in repairing diabetic wounds in male rats. Melastoma malabathricum Linn and guava Leaves extract gels have an effect in healing diabetic-induced rat wounds using alloxan. This can be seen from the change in the diameter of wound healing. Secondary metabolites of both plant materials are thought to provide anti-microbial activity and stimulate wound healing which helps epithelial cells and tissues so that they regenerate. The chemical content in the extracts of the test preparation has different mechanisms in helping the healing process.
 

The Effect of Aloe Vera Topical Gel Extraction on Tgf-Β1 Expression in Thermal Burn Eyelid Grade II Rats Model

Grade II eyelid burns are burns that reach the epidermis and part of the dermis of the palpebrae and can have impaired wound healing. TGF β1 has the broadest spectrum of action, affecting all cell types involved in all stages of wound healing. TGF β1 increases rapidly after injury and reaches peak levels three days after injury, which coincides with the peak of the inflammatory phase of wound healing. Decreased expression of TGF β1 is associated with impaired wound healing. Aloe Vera has long been known in Indonesia as a healing plant. Aloe Vera extract contains a variety of bioactive compounds that play a role in stimulating wound healing. The administration of Aloe Vera extract on thermal burns aims to reduce inflammation, increase collagen content, and increase the rate of re-epithelization. The administration of Aloe Vera gel extract allows faster healing of thermal burns and rebuilds the vascularity of the wound tissue. Objective of this study is to determine the difference between the expression of Transforming Growth Factor Beta 1 (TGF β1) in a rat model of thermal burn injury grade II of the eyelids treated with topical Aloe Vera gel extract with the concentrations of 20%, 40%, Balanced Salt Sodium (BSS) and a control group that was not given burn intervention. An experimental study with the post-test-only approach with a control group design. 24 Rats have induced grade II eyelid thermal burns, divided into four groups: Normal (without treatment), negative control (BSS), given Aloe vera 20%, 40%. Then TGF β1expression was quantified using the Image J application. The Topical application of Aloe vera gel can increase the expression of TGF along with the increase in dose. The highest rise in TGF expression was found in the group with 40% Aloe vera gel, followed by 20% Aloe vera gel compared to the negative control (BSS Balanced Salt Solution). Aloe Vera can increase TGF expression in a rat model of grade II palpebral burn injury and is dose-dependent.

PHOTOBIOMODULATION IN DENTAL IMPLANT THERAPY: A REVIEW

Photobiomodulation (PBM) or formerly known as low-level laser therapy (LLLT) is nothing but low-dosage biophotonics for therapy which presents an advancing new era of regenerative modalities in dental implantology. It utilizes light emitting diodes (LEDs), broad light sources and lasers for this purpose. Photobiomodulation is intended for relieving pain and inammation, regulating immune responses as well as stimulating wound healing and tissue regeneration. This helps in combatting the main pathological causes of implant failures that are, peri-implant mucositis and peri-implantitis as well as helps promote osseointegration and improve stability of implants. While the scope of photobiomodulation has been thoroughly investigated in in-vitro and animal studies, human clinical trials are still scarce which makes appropriate protocol formation with respect to dosage and mode of delivery among other parameters difcult. A recently introduced and potential application of photobiomodulation in the eld of implantology aims to deliver the positive effects of biophotonics through in-situ ambulatory PBM therapy called the smart dental implant (SDI) system. This comprehensive review presents the current and future trends in the application of photobiomodulation in the eld of dental implantology.

Smoking habits do not affect biological responses induced by leucocyte and platelet-rich fibrin in periodontal ligament cells.

Leucocyte- and platelet-rich fibrin has been developed to stimulate wound healing response. However, it is currently unknown whether smoking affects the biological responses elicited by leucocyte- and platelet-rich fibrin on periodontal ligament-derived mesenchymal stromal cells. This study analyzes the kinetics of biomolecule release from leucocyte- and platelet-rich fibrin derived from smokers and nonsmokers and their effect on periodontal ligament cell proliferation and migration as essential biological activities during wound healing. Biomolecules present in leucocyte- and platelet-rich fibrin exudates and conditioned media collected from smokers and nonsmokers were analyzed by Luminex arrays. Periodontal ligament-derived mesenchymal stromal cell obtained from one nonsmoker were treated with leucocyte- and platelet-rich fibrin exudates or leucocyte- and platelet-rich fibrin conditioned media derived from both smokers and nonsmokers. The parameters evaluated included cell proliferation, determined by Ki67 immunostaining and migration assessed using transwell assays. Also, cells were treated with nicotine in the presence of fetal bovine serum 10% or leucocyte- and platelet-rich fibrin conditioned media. A similar biomolecular profile was detected in leucocyte- and platelet-rich fibrin exudates and leucocyte- and platelet-rich fibrin conditioned media from smokers and nonsmokers, stimulating (periodontal ligament-derived mesenchymal stromal cell) proliferation, and migration to a comparable degree. Nicotine reduced cell proliferation and migration of periodontal cells; however, this effect was recovered in the presence of leucocyte- and platelet-rich fibrin conditioned media. Leucocyte- and platelet-rich fibrin derived from smokers could be an autologous source of biomolecules to stimulate cell biological activities involved in wound healing in smokers who have difficulties in ceasing this habit. Clinical trials are required to evaluate the impact of leucocyte- and platelet-rich fibrin on healing responses in smokers.

Collagen as a Biomaterial for Skin and Corneal Wound Healing.

The cornea and the skin are two organs that form the outer barrier of the human body. When either is injured (e.g., from surgery, physical trauma, or chemical burns), wound healing is initiated to restore integrity. Many cells are activated during wound healing. In particular, fibroblasts that are stimulated often transition into repair fibroblasts or myofibroblasts that synthesize extracellular matrix (ECM) components into the wound area. Control of wound ECM deposition is critical, as a disorganized ECM can block restoration of function. One of the most abundant structural proteins in the mammalian ECM is collagen. Collagen type I is the main component in connective tissues. It can be readily obtained and purified, and short analogs have also been developed for tissue engineering applications, including modulating the wound healing response. This review discusses the effect of several current collagen implants on the stimulation of corneal and skin wound healing. These range from collagen sponges and hydrogels to films and membranes.

Euodia daniellii Hemsl. Extract and Its Active Component Hesperidin Accelerate Cutaneous Wound Healing via Activation of Wnt/β-Catenin Signaling Pathway

The activation of the Wnt/β-catenin signaling pathway plays a key role in the wound-healing process through tissue regeneration. The extract of Euodia daniellii Hemsl. (E. daniellii), a member of the Rutaceae family, activates the Wnt/β-catenin signaling pathway. However, the function of E. daniellii in wound healing has not yet been elucidated. We performed a migration assay to determine the wound-healing effect of E. daniellii extract in vitro using human keratinocytes and dermal fibroblast. In addition, a mouse acute wound model was used to investigate the cutaneous wound-healing effect of E. daniellii extract in vivo and confirm the potential mechanism. E. daniellii extract enhanced the migration of human keratinocytes and dermal fibroblasts via the activation of the Wnt/β-catenin pathway. Moreover, the E. daniellii extract increased the levels of keratin 14, PCNA, collagen I, and α-SMA, with nuclei accumulation of β-catenin in vitro. E. daniellii extract also efficiently accelerated re-epithelialization and stimulated wound healing in vivo. Furthermore, we confirmed that hesperidin, one of the components of E. daniellii, efficiently accelerated the migration of human keratinocytes and dermal fibroblasts, as well as wound healing in vivo via the activation of the Wnt/β-catenin pathway. Overall, E. daniellii extract and its active component, hesperidin, have potential to be used as therapeutic agents for wound healing.

Soluble CD83 improves and accelerates wound healing by the induction of pro-resolving macrophages.

To facilitate the recovery process of chronic and hard-to-heal wounds novel pro-resolving treatment options are urgently needed. We investigated the pro-regenerative properties of soluble CD83 (sCD83) on cutaneous wound healing, where sCD83 accelerated wound healing not only after systemic but also after topical application, which is of high therapeutic interest. Cytokine profile analyses revealed an initial upregulation of inflammatory mediators such as TNFα and IL-1β, followed by a switch towards pro-resolving factors, including YM-1 and IL-10, both expressed by tissue repair macrophages. These cells are known to mediate resolution of inflammation and stimulate wound healing processes by secretion of growth factors such as epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), which promote vascularization as well as fibroblast and keratinocyte differentiation. In conclusion, we have found strong wound healing capacities of sCD83 beyond the previously described role in transplantation and autoimmunity. This makes sCD83 a promising candidate for the treatment of chronic- and hard-to-heal wounds.

LL37 and collagen-binding domain-mediated LL37 binding with type I collagen: Quantification via QCM-D

Antimicrobial peptide (AMP)-loaded biomaterials may represent a viable alternative for stimulating wound healing while protecting against infections. Previously, to develop an efficient delivery system for the cathelicidin antimicrobial peptide, LL37, our lab modified LL37 with a collagen-binding domain derived from collagenase (cCBD) as an anchoring unit to collagen-based wound dressings. However, a direct quantification of unmodified LL37 and cCBD-LL37 binding with collagen has not been performed. In this study, we used quartz crystal microbalance with dissipation monitoring (QCM-D), immunohistochemistry (IHC), and atomic force microscopy (AFM) to establish and characterize an adsorbed layer of type I collagen on the QCM-D sensor and quantify peptide-collagen binding. A collagen deposition protocol was successfully established by measuring concentration-dependent deposition of collagen in QCM-D, and collagen self-assembly was observed by IHC and AFM. Hydrophobicity is known to affect the behavior of collagen adsorption. Therefore, we compared the deposition of collagen on hydrophilic SiO2-coated sensors vs. hydrophobic polystyrene (PS)-coated sensors via QCM-D, and found that the hydrophobic surface yielded more collagen adsorption, which suggested that hydrophobic surfaces are preferable for collagen layer establishment. There was no significant difference between LL37 and cCBD-LL37 binding with collagen, but the cCBD-LL37 showed better retention on the collagen after washing with PBS, indicating that there is an advantage to using cCBD as an anchoring unit to collagen. Collectively, these results provide important information on cCBD-mediated AMP-binding mechanisms and establish an effective method for quantifying peptide-collagen binding.

Pulsed low-intensity laser treatment stimulates wound healing without enhancing biofilm development in vitro.

Treating infected or chronic wounds burdened with biofilms still is a major challenge in medical care. Healing-stimulating factors lose their efficacy due to bacterial degradation, and antimicrobial substances negatively affect dermal cells. Therefore, alternative treatment approaches like the pulsed low intensity laser therapy (LILT) require consideration. The effect of pulsed LILT (904nm, in three frequencies) on relevant human cells of the wound healing process (fibroblasts (BJ), keratinocytes (HaCaT), endothelial cells (HMEC), monocytes (THP-1)) were investigated in in-vitro and ex-vivo wound models with respect to viability, proliferation and migration. Antimicrobial efficacy of the most efficient frequency in cell biological analyses of LILT (3200Hz) was determined in a human biofilm model (lhBIOM). Quantification of bacterial load was evaluated by suspension method and qualitative visualization was performed by scanning electron microscopy (SEM). Pulsed LILT at 904nm at 3200Hz±50% showed the most positive effects on metabolic activity and proliferation of human wound cells in vitro (after 72h - BJ: BPT 0.97±0.05 vs. 0.75±0.04 (p=0.0283); HaCaT: BPT 0.79±0.04 vs. 0.59±0.02 (p=0.0106); HMEC: 0.74±0.02 vs. 0.52±0.04 (p=0.009); THP-1: 0.58±0.01 vs. 0.64±0.01 (p>0.05) and ex vivo. Interestingly, re-epithelialization was stimulated in a frequency-independent manner. The inhibition of metabolic activity after TNF-α application was abolished after laser treatment. No impact of LILT on monocytes was detected. Likewise, the tested LILT regimens showed no growth rate reducing effects on three bacterial strains (after 72h - PA: -1.03%; SA: -0.02%; EF: -1,89%) and one fungal (-2.06%) biofilm producing species compared to the respective untreated control. Accordingly, no significant morphological changes of the biofilms were observed after LILT treatment in the SEM. Frequent application of LILT (904nm, 3200Hz) seems to be beneficial for the metabolism of human dermal cells during wound healing. Considering this, the lack of disturbance of the behavior of the immune cells and no growth-inducing effect on bacteria and fungi in the biofilm can be assigned as rather positive. Based on this combined mode of action, LILT may be an option for hard to heal wounds infected with persistent biofilms.

3D Living Dressing Improves Healing and Modulates Immune Response in a Thermal Injury Model.

Thermal injury trauma can induce a state of immunosuppression, causing wounds to become chronic in nature. Stem cell-based therapies represent a promising new approach to treat such wounds due to their capacity to self-renew and their multi-lineage potential. Mesenchymal stem cells (MSCs) are known to secrete endogenous factors that stimulate wound healing by promoting angiogenesis, extracellular matrix remodeling, skin regeneration, and by dampening down inflammation. MSC delivery in a biomaterial construct can augment their wound-healing capacity by concentrating cells at the burn site and upregulating trophic factor secretion. The work presented is the first to evaluate repair in an in vitro raft thermal injury model using a regenerative, dual cell delivery three-dimensional (3D) core/shell (c/s) "living dressing" construct. This previously characterized 3D c/s bioprinted construct, which delivers both MSCs and endothelial cells, was used to treat an in vitro 3D raft skin thermal injury wound model. The mesenchymal stromal cell line (T0523) was encapsulated within a gelatin-based shell bioink, and human umbilical vein endothelial cells within a chitosan-based core bioink to biofabricate a living dressing for enhanced thermal injury repair and regeneration. We hypothesized that the cell-laden c/s tissue engineered construct (TEC) would strengthen the wound's proangiogenic, anti-inflammatory, and skin regeneration potential. An in vitro thermal injury in a 3D raft skin model showed a slight delay in wound closure in the presence of the c/s TEC but was augmented by corresponding increases in the release of wound-healing factors, epidermal growth factor, matrix metalloproteinases-9, transforming growth factor-α, platelet-derived growth factor; a decrease in pro-inflammatory factor interleukin-6, and evidence of neovascularization.

Polarized Light Therapy in the Treatment of Wounds: A Review.

The most prevalent type of photo therapies are low-level laser therapy (LLLT) and ultraviolet (UV) treatments, which are distinguished by the physical properties of the light employed. However, in latest years, it has been suggested that polarization and an extensive light band including all light spectra are essential aspects in light treatment. Light waves are filtered to align and vibrate in a single plane, resulting in polarized light (PL). Light that has been polarized can penetrate tissues more deeply than light that has not been polarized. The visible light spectrum is very broad. PL varies from other types of light therapy in that it uses a considerably wider spectrum of wavelengths than LLLT or UV. As a result, PLT devices are often less expensive and simple to operate. Since the late 1960s, light therapy has been used to treat anything from neonatal jaundice to psoriasis and vitiligo. Fenyö created a PL source and found that it can stimulate wound healing in a similar way to the low-energy laser. In comparison to the laser, this source of light had numerous gains: lesser prices, fewer hazards, a greater area to be treated, and no sophisticated user expertise. Despite several findings from fundamental research (in vitro, in vivo, and animal trials), practitioners continue to have reservations regarding PL's potency and utility in treating musculoskeletal problems. It is even largely believed that the commercial use of these therapies is validated by a sufficient amount of scientific evidence based on reliable clinical papers. The major goal of this study is to gather information on the use of PL for treatment of various wound types in animal and human investigations.

An injectable, self-healing carboxymethylated chitosan hydrogel with mild photothermal stimulation for wound healing

Hydrogels can mimic extracellular matrix and provide a suitable microenvironment for accelerating wound healing. Nevertheless, the complicated wound condition, the disturbance of external forces, and the manufacturing process of the dressing were still difficult problems. An injectable self-healing hydrogel with mild photothermal therapy (MPTT) was developed for wound healing via dynamic Schiff bonds. After covalently incorporating GO-BPEI (branched polyethyleneimine grafting graphene oxide), an observable mechanical strength improvement and photothermal conversion property of GO-BPEI/carboxymethylated chitosan (CMCS) /aldehyde terminated polyethylene glycol (PEG-CHO) (GCP) hydrogel has been witnessed. MPTT induced by near-infrared (NIR) irradiation could accelerate NIH-3 T3 cells proliferation in vitro. Moreover, in vivo wound defect healing and histological analysis suggested that GCP hydrogels incorporated with MPTT significantly accelerated wound healing by improving collagen fibers deposition, enhancing re-epithelialization, and promoting granulation tissue neogenesis. The GCP hydrogels provide a unique route for wound dressing and present new inspirations for complicated wound management.

Therapeutic Potential of Exosomes Derived from Diabetic Adipose Stem Cells in Cutaneous Wound Healing of db/db Mice.

(1) Background: Diabetes impairs angiogenesis and wound healing. Paracrine secretion from adipose stem cells (ASCs) contains membrane-bound nano-vesicles called exosomes (ASC-Exo) but the functional role and therapeutic potential of diabetic ASC-Exo in wound healing are unknown. This study aims to investigate the in vivo mechanistic basis by which diabetic ASC-Exo enhance cutaneous wound healing in a diabetic mouse model. (2) Methods: Topically applied exosomes could efficiently target and preferentially accumulate in wound tissue, and the cellular origin, ASC or dermal fibroblast (DFb), has no influence on the biodistribution pattern of exosomes. In vivo, full-thickness wounds in diabetic mice were treated either with ASC-Exo, DFb-Exo, or phosphate-buffered saline (PBS) topically. ASC-Exo stimulated wound healing by dermal cell proliferation, keratinocyte proliferation, and angiogenesis compared with DFb-Exo and PBS-treated wounds. (3) Results: Diabetic ASC-Exo stimulated resident monocytes/macrophages to secrete more TGF-β1 and activate the TGF-β/Smad3 signaling pathway. Fibroblasts activated by TGF-β1containing exosomes from ASCs initiate the production of TGF-β1 protein in an autocrine fashion, which leads to more proliferation and activation of fibroblasts. TGF-β1 is centrally involved in diabetic ASC-Exo mediated cellular crosstalk as an important early response to initiating wound regeneration. (4) Conclusions: The application of diabetic ASC-Exo informs the potential utility of a cell-free therapy in diabetic wound healing.

EFFECTS OF HYPERBARIC OXYGEN THERAPY IN PATIENT WITH ACUTE UPPER LIMB FINGER GANGRENE WITH COVID-19

The COVID-19 pandemic (Corona Virus Diseas) was caused by a new beta coronavirus in early 2020, also called Severe Acute Respiratory Syndrome (SARS-CoV-2). Predilection sites of virus entry are the lungs, intestines, blood vessels, kidney, and adipose tissue cells are the virus reservoir. The virus causes a violent reaction of inammatory cytokines - cytokine storm, activation of coagulation and formation of thrombin. The initial coagulopathy of COVID-19 is manifested by a pronounced disorder of D-dimer and brin/brinogen degradation products, while abnormalities in prothrombin time, partial thromboplastin time and platelet count are relatively rare at the onset of the disease. Later, the phenomenon of thrombotic microangiopathy occurs, which is a consequence of inammation of the blood vessels endothelium. In severe cases of infection, thromboembolism or acute thrombosis of peripheral blood vessels may occur. The paper presents a case of a patient with COVID-19 infection in whom, in addition to the usual clinical picture of the disease with changes in lung parenchyma (bilateral pneumonia), thrombosis of the a. radialis and a. ulnaris of the left hand developed, and fteen days after the infection development, the development of gangrene of the distal articles II, III and IV of the nger occurs. In addition to therapy used according to the national guide to COVID-19, hyperbaric oxygen therapy (HBOT) was used. The effect of this therapy was used to increase vascular permeability and create factors that affect angiogenesis and improve blood ow in the ischemic region. HBOT also affected the demarcation of necrotic from healthy tissue, and stimulated wound healing. After two sessions of HBOT treatment, there was a complete restitution of blood ow with full function of the left hand and all its ngers.

Artificial Nonenzymatic Antioxidant MXene Nanosheet-Anchored Injectable Hydrogel as a Mild Photothermal-Controlled Oxygen Release Platform for Diabetic Wound Healing.

Hypoxia, excessive reactive oxygen species (ROS), impaired angiogenesis, lasting inflammation, and bacterial infection, are key problems impeding diabetic wound healing. Particularly, controllable oxygen release and ROS scavenging capacities are critical during the wound healing process. Here, an injectable hydrogel based on hyaluronic acid-graft-dopamine (HA-DA) and polydopamine (PDA) coated Ti3C2 MXene nanosheets is developed catalytically cross-linked by an oxyhemoglobin/hydrogen (HbO2/H2O2) system combined with mild photothermal stimulation for diabetic wound healing. HbO2 not only acts as a horseradish peroxidase-like to catalyze the hydrogel formation but also as an oxygen carrier to controllably release oxygen when activated by the mild heat produced from near-infrared (NIR) irradiation. Specifically, HbO2 can provide oxygen repeatedly by binding oxygen in the air when the NIR is off. The stable photoresponsive heating behavior of MXene ensures the repeatable oxygen release. Additionally, artificial nonenzymatic antioxidant MXene nanosheets are proposed to scavenge excessive reactive nitrogen species and ROS including H2O2, O2•-, and •OH, keeping the intracellular redox homeostasis and alleviating oxidative stress, and eradicate bacteria to avoid infection. The antioxidant and antibacterial abilities of MXene are further improved by PDA coating, which also promotes the MXene nanosheets cross-linking into the network of the hydrogel. HA-DA molecules endow the hydrogel with the capacity to regulate macrophage polarization from M1 to M2 to achieve anti-inflammation. More importantly, the MXene-anchored hydrogel with multifunctions including tissue adhesion, self-healing, injectability, and hemostasis, combined with mild photothermal stimulation, greatly promotes human umbilical vein endothelial cell proliferation and migration and notably facilitates infected diabetic wound healing.

Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability.

The prevalent use of electronic cigarettes (e-cigarettes) has increased exponentially in recent years, especially in youth who are attracted to flavored e-cigarettes. Indeed, e-cigarette or vaping product use-associated lung injury (EVALI) cases started to emerge in the United States in August 2019, resulting in 2807 hospitalized cases and 68 deaths as of 18 February 2020. In the present study, we investigated, for the first time, whether flavored and nicotine containing e-cigarettes induce endothelial dysfunction to result in impaired angiogenesis and wound healing particularly under diabetic condition. Nicotine containing e-cigarettes with various contents of nicotine (0, 1.2%, 2.4%), and flavored e-cigarettes of classic tobacco, mint, menthol, and vanilla or fruit from BLU (nicotine 2.4%) or JUUL (nicotine 3%), were used to treat endothelial cells in vitro and streptozotocin-induced diabetic mice in vivo. Endothelial cell superoxide production, determined by dihydroethidium (DHE) fluorescent imaging and electron spin resonance (ESR), was markedly increased by exposure to e-cigarette extract (e-CSE) in a nicotine-content dependent manner, while nitric oxide (NO) bioavailability detected by DAF-FM fluorescent imaging was substantially decreased. All of the different flavored e-cigarettes examined also showed significant effects in increasing superoxide production while diminishing NO bioavailability. Endothelial cell apoptosis evaluated by caspase 3 activity was markedly increased by exposure to e-CSE prepared from flavored and nicotine containing e-cigarettes. Endothelial monolayer wound assays revealed that nicotine-containing and flavored e-cigarettes induced impaired angiogenic wound repair of endothelial cell monolayers. Furthermore, vascular endothelial growth factor (VEGF) stimulated wound healing in diabetic mice was impaired by exposure to e-CSEs prepared from nicotine-containing and flavored e-cigarettes. Taken together, our data demonstrate for the first time that flavored and nicotine-containing e-cigarettes induce endothelial dysfunction through excessive ROS production, resulting in decreased NO bioavailability, increased endothelial cell apoptosis, and impairment in angiogenesis and wound healing, especially under diabetic condition. These responses of endothelial dysfunction likely underlie harmful effects of e-cigarettes in endothelial-rich organs, such as heart and lungs. These data also indicate that rigorous regulation on e-cigarette use should be enforced in diabetic and/or surgical patients to avoid severe consequences from impaired angiogenesis/wound healing.

The use of Indonesian randu honey for chronic wounds in a patient with uncontrolled type 2 diabetes mellitus: A case report.

Introduction and importanceHoney has been recorded as having healing properties at a low cost. Many studies have been conducted related to Manuka honey, but studies about Indonesian randu honey are still limited. We report the use of Indonesian randu honey as a wound dressing on non-pressure chronic skin ulcers in uncontrolled T2DM patient.Case presentationA 54-year-old man with uncontrolled T2DM came with an unrecovered wound. A thorough inspection revealed several exposed bones, tendons, muscles, and meniscus in the left lower leg region. It was supposed to be amputated, but he declined. He received insulin, debridement, STSG, and a combination of Indonesian randu honey dressing and VAC on the exposed wound before and after the debridement and STSG. There was skin graft lysis, and we intended to do another surgery, but he preferred to be an outpatient. As an outpatient, he received honey wound dressing and insulin. After 1.5 years, the wound was fully closed, and he could walk with the help of a walking stick.Clinical discussionTreatment for multiple exposed bones, tendons, and muscles in uncontrolled T2DM patient are complex. Studies reported that Indonesian honey could provide an antibacterial effect, cost-efficiency, speed up wound healing with no side effects, and no physical-chemical properties differences compared to Manuka honey.ConclusionUsing Indonesian randu honey as wound dressing could stimulate wound healing with no side effects in chronic wounds with uncontrolled T2DM that were supposed to be amputated. However, it took several months for the wound to fully close.