scholarly journals Sustained Oxygenation Accelerates Diabetic Wound Healing by Simultaneously Promoting Epithelialization and Angiogenesis, and Decreasing Tissue Inflammation

2021 ◽  
Author(s):  
Ya Guan ◽  
Hong Niu ◽  
Zhongting Liu ◽  
Yu Dang ◽  
Jie Shen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Dermal Fibroblasts ◽  
Diabetic Patients ◽  
Diabetic Wound ◽  
Oxygen Release ◽  
Ros Scavenging ◽  
M1 Macrophage ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Non-healing diabetic wound is one of the most common complications for diabetic patients. Chronic hypoxia is among the prominent factors that delay the wound healing process. Therefore, sustained oxygenation to alleviate hypoxia is hypothesized to promote diabetic wound healing. Yet it cannot be achieved by current clinical approaches including hyperbaric oxygen therapy. Herein, we developed a sustained oxygenation system consisting of oxygen-release microspheres and a reactive oxygen species (ROS)-scavenging hydrogel. The hydrogel was used to capture the ROS that is elevated in the diabetic wounds, and that may be generated due to oxygen release. The sustainedly released oxygen augmented survival and migration of keratinocytes and dermal fibroblasts; promoted angiogenic growth factor expression, and angiogenesis in the diabetic wounds; and decreased M1 macrophage density. These effects led to a significant increase of wound closure rate. These findings reveal that sustained oxygenation alone without using drugs is capable of healing diabetic wounds.

Updates in Diabetic Wound Healing, Inflammation, and Scarring

2021 ◽  
Author(s):  
Nina Dasari ◽  
Austin Jiang ◽  
Anna Skochdopole ◽  
Jayer Chung ◽  
Edward Reece ◽  
...  
Keyword(s):  
Wound Healing ◽  
Disease Process ◽  
Wound Dehiscence ◽  
Diabetic Patients ◽  
Wound Infections ◽  
Diabetic Wound ◽  
Complex Process ◽  
Diabetic Wound Healing ◽  
Almost All ◽  
Diabetic Wounds

AbstractDiabetic patients can sustain wounds either as a sequelae of their disease process or postoperatively. Wound healing is a complex process that proceeds through phases of inflammation, proliferation, and remodeling. Diabetes results in several pathological changes that impair almost all of these healing processes. Diabetic wounds are often characterized by excessive inflammation and reduced angiogenesis. Due to these changes, diabetic patients are at a higher risk for postoperative wound healing complications. There is significant evidence in the literature that diabetic patients are at a higher risk for increased wound infections, wound dehiscence, and pathological scarring. Factors such as nutritional status and glycemic control also significantly influence diabetic wound outcomes. There are a variety of treatments available for addressing diabetic wounds.

Angiogenic Nanoscaffold Accelerates Diabetic Wound Healing and Improves Wound Tissue Strength in db/db Mice

2009 ◽  
Author(s):  
Swathi Balaji ◽  
Abdul Q. Sheikh ◽  
Lee Morris ◽  
Foong Y. Lim ◽  
Timothy M. Crombleholme ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wound Healing Process ◽  
Diabetic Patients ◽  
Diabetic Wound ◽  
Normal Wound Healing ◽  
Inflammatory Phase ◽  
Diabetic Wound Healing ◽  
Ecm Degradation ◽  
Chronic Ulcers

Chronic ulcers are a leading cause of morbidity in diabetic patients. Diabetes is associated with major changes in the wound microenvironment and disruption of normal wound healing process, characterized by a prolonged inflammatory phase with elevated levels of wound proteases and increased degradation of extracellular matrix (ECM) components [1]. This impedes wound healing due to a lack of provisional matrix, impaired recruitment and survival of endothelial (EC) and endothelial precursor (EPC) cells, and insufficient neovascularization, resulting in delayed healing. Therefore, strategies focused on restoring the diabetic wound microenvironment by decreasing ECM degradation and promoting neovascularization are promising for development of new therapies to treat chronic diabetic ulcers.

A dual functional collagen scaffold coordinates angiogenesis and inflammation for diabetic wound healing

2020 ◽  
Vol 8 (22) ◽  
pp. 6337-6349
Author(s):  
Ge Long ◽  
Dingyang Liu ◽  
Xi He ◽  
Yeyu Shen ◽  
Yannan Zhao ◽  
...  
Keyword(s):  
Wound Healing ◽  
Collagen Scaffold ◽  
Diabetic Patients ◽  
Diabetic Wound ◽  
Dual Functional ◽  
Persistent Inflammation ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds ◽  
Impaired Angiogenesis

Chronic diabetic wounds, which are associated with persistent inflammation and impaired angiogenesis, occur frequently in diabetic patients.

scholarly journals Molecular Changes in Diabetic Wound Healing following Administration of Vitamin D and Ginger Supplements: Biochemical and Molecular Experimental Study

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Hadeel A. Al-Rawaf ◽  
Sami A. Gabr ◽  
Ahmad H. Alghadir
Keyword(s):  
Vitamin D ◽  
Wound Healing ◽  
Wound Closure ◽  
Healing Process ◽  
Molecular Targets ◽  
Wound Healing Process ◽  
Diabetic Wound ◽  
Fibrin Deposition ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Background. Circulating micro-RNAs are differentially expressed in various tissues and could be considered as potential regulatory biomarkers for T2DM and related complications, such as chronic wounds. Aim. In the current study, we investigated whether ginger extract enriched with [6]-gingerol-fractions either alone or in combination with vitamin D accelerates diabetic wound healing and explores underlying molecular changes in the expression of miRNA and their predicted role in diabetic wound healing. Methods. Diabetic wounded mice were treated with [6]-gingerol-fractions (GF) (25 mg/kg of body weight) either alone or in combination with vitamin D (100 ng/kg per day) for two weeks. Circulating miRNA profile, fibrogenesis markers, hydroxyproline (HPX), fibronectin (FN), and collagen deposition, diabetic control variables, FBS, HbA1c, C-peptide, and insulin, and wound closure rate and histomorphometric analyses were, respectively, measured at days 3, 6, 9, and 15 by RT–PCR and immunoassay analysis. Results. Treatment of diabetic wounds with GF and vitamin D showed significant improvement in wound healing as measured by higher expression levels of HPX, FN, collagen, accelerated wound closure, complete epithelialization, and scar formation in short periods (11-13 days, (P<0.01). On a molecular level, three circulating miRNAs, miR-155, miR-146a, and miR-15a, were identified in diabetic and nondiabetic skin wounds by PCR analysis. Lower expression in miR-155 levels and higher expression of miR-146a and miR-15a levels were observed in diabetic skin wounds following treatment with gingerols fractions and vitamin D for 15 days. The data showed that miRNAs, miR-146a, miR-155, and miR-15a, correlated positively with the expression levels of HPX, FN, and collagen and negatively with FBS, HbA1c, C-peptide, and insulin in diabetic wounds following treatment with GF and /or vitamin D, respectively. Conclusion. Treatment with gingerols fractions (GF) and vitamin D for two weeks significantly improves delayed diabetic wound healing. The data showed that vitamin D and gingerol activate vascularization, fibrin deposition (HPX, FN, and collagen), and myofibroblasts in such manner to synthesize new tissues and help in the scar formation. Accordingly, three miRNAs, miR-155, miR-146a, and miR-15, as molecular targets, were identified and significantly evaluated in wound healing process. It showed significant association with fibrin deposition, vascularization, and reepithelialization process following treatment with GF and vitamin D. It proposed having anti-inflammatory action and promoting new tissue formation via vascularization process during the wound healing. Therefore, it is very interesting to consider miRNAs as molecular targets for evaluating the efficiency of nondrug therapy in the regulation of wound healing process.

scholarly journals Mathematical Model Predicts that Acceleration of Diabetic Wound Healing is Dependent on Spatial Distribution of VEGF-A mRNA (AZD8601)

2021 ◽  
Author(s):  
S. Michaela Rikard ◽  
Paul J. Myers ◽  
Joachim Almquist ◽  
Peter Gennemark ◽  
Anthony C. Bruce ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Wound Healing ◽  
Spatial Distribution ◽  
Surrounding Tissue ◽  
Diabetic Patients ◽  
Model Parameters ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds ◽  
The Impact

Abstract Introduction Pharmacologic approaches for promoting angiogenesis have been utilized to accelerate healing of chronic wounds in diabetic patients with varying degrees of success. We hypothesize that the distribution of proangiogenic drugs in the wound area critically impacts the rate of closure of diabetic wounds. To evaluate this hypothesis, we developed a mathematical model that predicts how spatial distribution of VEGF-A produced by delivery of a modified mRNA (AZD8601) accelerates diabetic wound healing. Methods We modified a previously published model of cutaneous wound healing based on coupled partial differential equations that describe the density of sprouting capillary tips, chemoattractant concentration, and density of blood vessels in a circular wound. Key model parameters identified by a sensitivity analysis were fit to data obtained from an in vivo wound healing study performed in the dorsum of diabetic mice, and a pharmacokinetic model was used to simulate mRNA and VEGF-A distribution following injections with AZD8601. Due to the limited availability of data regarding the spatial distribution of AZD8601 in the wound bed, we performed simulations with perturbations to the location of injections and diffusion coefficient of mRNA to understand the impact of these spatial parameters on wound healing. Results When simulating injections delivered at the wound border, the model predicted that injections delivered on day 0 were more effective in accelerating wound healing than injections delivered at later time points. When the location of the injection was varied throughout the wound space, the model predicted that healing could be accelerated by delivering injections a distance of 1–2 mm inside the wound bed when compared to injections delivered on the same day at the wound border. Perturbations to the diffusivity of mRNA predicted that restricting diffusion of mRNA delayed wound healing by creating an accumulation of VEGF-A at the wound border. Alternatively, a high mRNA diffusivity had no effect on wound healing compared to a simulation with vehicle injection due to the rapid loss of mRNA at the wound border to surrounding tissue. Conclusions These findings highlight the critical need to consider the location of drug delivery and diffusivity of the drug, parameters not typically explored in pre-clinical experiments, when designing and testing drugs for treating diabetic wounds.

scholarly journals Healing Effects of Photobiomodulation on Diabetic Wounds

2019 ◽  
Vol 9 (23) ◽  
pp. 5114
Author(s):  
Nicolette Houreld
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Diabetic Patients ◽  
Diabetic Wound ◽  
Recurrence Rates ◽  
Speed Up ◽  
Diabetic Wound Healing ◽  
Underlying Mechanisms ◽  
Diabetic Wounds

Diabetic patients frequently develop chronic ulcers of the lower extremities, which are a frequent cause for hospitalization and amputation, placing strain on patients, their families, and healthcare systems. Present therapies remain a challenge, with high recurrence rates. Photobiomodulation (PBM), which is the non-invasive application of light at specific wavelengths, has been shown to speed up healing of chronic wounds, including diabetic foot ulcers (DFUs). PBM produces photophysical and photochemical changes within cells without eliciting thermal damage. It has been shown to promote tissue regeneration and speed up wound repair by reducing inflammation and oxidative stress, accelerating cell migration and proliferation, and promoting extracellular matrix production and release of essential growth factors. The shortage of rigorous, well-designed clinical trials makes it challenging to assess the scientific impact of PBM on DFUs, and lack of understanding of the underlying mechanisms also hinders the conventional use of this therapy. This review gives a glimpse into diabetic wound healing and PBM, and the effects of PBM on diabetic wound healing.

scholarly journals Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization

2020 ◽  
Vol 133 (19) ◽  
pp. jcs235838
Author(s):  
Peilang Yang ◽  
Xiqiao Wang ◽  
Di Wang ◽  
Yan Shi ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Macrophage Polarization ◽  
Healing Process ◽  
Polarization State ◽  
Wound Healing Process ◽  
Diabetic Wound ◽  
Insulin Degrading Enzyme ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

ABSTRACTBesides regulating glucose levels, insulin has been reported to participate actively in many other functions, including modulating inflammatory reactions. In this study we investigated how topical insulin application would affect the diabetic wound healing process. We found that the excessive expression of insulin-degrading enzyme led to insufficient insulin levels in diabetic skin during wound healing, which ultimately reduced the recovery rate of diabetic wounds. We confirmed that topical insulin application could reverse the impaired inflammation reaction in the diabetic wound environment and promote healing of diabetic wounds. Our study revealed that insulin promoted apoptosis of neutrophils and subsequently triggered polarization of macrophages. Both in vivo and in vitro studies verified that insulin re-established phagocytosis function and promoted the process of phagocytosis-induced apoptosis in neutrophils. Furthermore, we found that insulin treatment also promoted efferocytosis of the apoptosed neutrophils by macrophages, and thus induced macrophages to change their polarization state from M1 to M2. In conclusion, our studies proved that the exogenous application of insulin could improve diabetic wound healing via the restoration of the inflammatory response.

A Novel Functionalization of Bioactive Antimicrobial Peptide onto the Nano-CeO2/Reduced Graphene Oxide Cluster Type Biocomposite Wound Dressings for Diabetic Wound Care Management: In Vitro and In Vivo Evaluations

2020 ◽  
Vol 10 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Ran Wei ◽  
Shijun Nie ◽  
Jing Ma ◽  
Changmei Feng ◽  
Hongyu Kuang
Keyword(s):  
Wound Healing ◽  
Graphene Oxide ◽  
Reduced Graphene Oxide ◽  
Healing Process ◽  
Wound Healing Process ◽  
Diabetic Patients ◽  
Diabetic Wound ◽  
Reduced Graphene ◽  
Diabetic Wound Healing

Diabetic wound ulcers and unhealed ulcerations have caused in severe difficulties of diabetic patients all around the world. The anti-microbial peptides (AMP) and nanomaterials have been demonstrated beneficial in diabetic wound healing studies. Diabetic wound healing process can be delayed significantly due to the infection issues. Hence in this report, biologically synthesized cerium oxide (CeO2) nanoparticles incorporated with reduced graphene oxide (RGO) and AMP for effective and rapid diabetic wound healing have been reported. At first, reduced graphene oxide was prepared from graphene oxide to prepare CeO2/RGO nanocomposites. Biocompatible AMP (IP-1) functionalized CeO2/RGO nanocomposites were accordingly prepared to study the diabetic wound healing process. Rats, the wound healing models with the wound size of about 1.5 cm2 were tested with the as-prepared samples. Further, the prepared samples were tested in a wound healing model of rate with the wound of size 1.5 cm2. Almost complete recovery of wounds i.e., 100% closure of wound area was observed after 2 weeks of treatment by the prepared samples. Biocompatible AMP (IP-1) functionalized CeO2/RGO nanocomposites enhances rapid keratinocytes proliferation by short time thereby it proves the enhanced ability of the prepared samples to act as a wound healing in-vivo drugs. HE and MTC staining protocols to illustrate histological observations elucidates the keratinocytes creation by biocompatible AMP (IP-1) functionalized CeO2/RGO nanocomposites.

Diabetic wound healing approaches: an update

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Raghuvir Keni ◽  
Farmiza Begum ◽  
Karthik Gourishetti ◽  
Gollapalle Lakshminarayanashastry Viswanatha ◽  
Pawan Ganesh Nayak ◽  
...  
Keyword(s):  
Wound Healing ◽  
Diabetic Foot ◽  
Healing Process ◽  
Clinical Importance ◽  
Diagnostic Tools ◽  
Wound Infections ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Abstract Diabetic wounds are of profound clinical importance. Despite immense efforts directed towards its management, it results in the development of amputations, following a diagnosis of diabetic foot. With a better understanding of the complexities of the microbalance involved in the healing process, researchers have developed advanced methods for the management of wounds as well as diagnostic tools (especially, for wound infections) to be delivered to clinics sooner. In this review, we address the newer developments that hope to drive the transition from bench to bedside in the coming decade.

scholarly journals Recovery of Altered Diabetic Myofibroblast Heterogeneity and Gene Expression Associated with CD301b+ Macrophages

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1752
Author(s):  
MaryEllen R. Haas ◽  
Darlene V. Nguyen ◽  
Brett A. Shook
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Healing Process ◽  
Mouse Skin ◽  
Tissue Analysis ◽  
Diabetic Wound ◽  
Phenotypic Switch ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds ◽  
And Control

Diabetic wound healing is associated with impaired function and reduced numbers of myofibroblasts, a heterogeneous cell population with varying capacities to promote repair. To determine how diabetes alters myofibroblast composition, we performed flow cytometry and spatial tissue analysis of myofibroblast subsets throughout the healing process in diabetic (db/db) and control (db/+) mouse skin. We observed reduced numbers of profibrotic SCA1+; CD34+; CD26+ myofibroblasts in diabetic wounds five days after injury, with decreased expression of fibrosis-associated genes compared to myofibroblasts from db/+ mouse wounds. While the abundance of myofibroblasts remained reduced in db/db mouse wounds compared to controls, the altered myofibroblast heterogeneity and gene expression in diabetic mice was improved seven days after injury. The natural correction of myofibroblast composition and gene expression in db/db wound beds temporally corresponds with a macrophage phenotypic switch. Correlation analysis from individual wound beds revealed that wound healing in control mice is associated with CD206+ macrophages, while the rescued myofibroblast phenotypes in diabetic wounds are correlated with increased CD301b+ macrophage numbers. These data demonstrate how diabetes impacts specific subsets of myofibroblasts and indicate that signaling capable of rescuing impaired diabetic wound healing could be different from signals that regulate wound healing under nonpathological conditions.

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