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.

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.

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 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 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.

A bioglass sustained-release scaffold with ECM-like structure for enhanced diabetic wound healing

Nanomedicine ◽  
2020 ◽  
Vol 15 (23) ◽  
pp. 2241-2253
Author(s):  
Pengju Zhang ◽  
Yuqi Jiang ◽  
Dan Liu ◽  
Yan Liu ◽  
Qinfei Ke ◽  
...  
Keyword(s):  
Wound Healing ◽  
Therapeutic Option ◽  
Effective Strategy ◽  
Diabetic Wound ◽  
Nano Structure ◽  
Wound Site ◽  
Diabetic Wound Healing ◽  
Coaxial Fibers ◽  
Diabetic Wounds ◽  
Endothelial Cell Adhesion

Aim: To develop an effective strategy for increasing angiogenesis at diabetic wound sites and thereby accelerating wound healing. Materials & methods: A micropatterned nanofibrous scaffold with bioglass nanoparticles encapsulated inside coaxial fibers was prepared by electrospinning. Results: Si ions could be released in a sustained manner from the scaffolds. The hierarchical micro-/nano-structure of the scaffold was found to act as a temporary extracellular matrix to promote endothelial cell adhesion and growth. The scaffold greatly improved angiogenesis and collagen deposition at the wound site, which shortened the healing period of diabetic wounds. Conclusion: This study provides a promising therapeutic option for chronic diabetic wounds with improved angiogenesis.

Extracellular vesicles derived from adipose-derived stem cells accelerate diabetic wound healing by suppressing the expression of matrix metalloproteinase-9

2021 ◽  
Vol 22 ◽  
Author(s):  
Jiang-wen Wang ◽  
Yuan-zheng Zhu ◽  
Xuan Hu ◽  
Jia-ying Nie ◽  
Zhao-hui Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mouse Model ◽  
Adipose Derived Stem Cells ◽  
Collagen Deposition ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds ◽  
Metalloproteinase 9

Background: The healing of diabetic wounds is poor due to a collagen deposition disorder. Matrix metalloproteinase-9 (MMP-9) is closely related to collagen deposition in the process of tissue repair. Many studies have demonstrated that extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) promote diabetic wound healing by enhancing collagen deposition. Objective: In this study, we explored if ADSC-EVs could downregulate the expression of MMP-9 in diabetic wounds and promote wound healing by improving collagen deposition. The potential effects of ADSC-EVs on MMP-9 and diabetic wound healing were tested both in vitro and in vivo. Methods: We first evaluated the effect of ADSC-EVs on the proliferation and MMP-9 secretion of HaCaT cells treated with advanced glycation end product-bovine serum albumin (AGE-BSA), using CCK-8 western blot and MMP-9 enzyme-linked immunosorbent assay(ELISA). Next, the effect of ADSC-EVs on the healing, re-epithelialisation, collagen deposition, and MMP-9 concentration in diabetic wound fluids was evaluated in an immunodeficient mouse model via MMP-9 ELISA and haematoxylin and eosin, Masson’s trichrome, and immunofluorescence staining for MMP-9. Results: In vitro, ADSC-EVs promoted the proliferation and MMP-9 secretion of HaCaT cells.In vivo, ADSC-EVs accelerated diabetic wound healing by improving re-epithelialisation and collagen deposition and by inhibiting the expression of MMP-9. Conclusion: ADSC-EVs possessed the healing of diabetic wounds in a mouse model by inhibiting downregulating MMP-9 and improving collagen deposition.Thus ,ADSC-EVs are a promising candidate for the treatment of diabetic wounds .

scholarly journals Platelet-Rich Plasma with Endothelial Progenitor Cells Accelerates Diabetic Wound Healing in Rats by Upregulating the Notch1 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Cheng Zhang ◽  
Yu Zhu ◽  
Shengdi Lu ◽  
Wanrun Zhong ◽  
Yanmao Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Signaling Pathway ◽  
Platelet Rich Plasma ◽  
Diabetic Wound ◽  
Endothelial Progenitor ◽  
Notch1 Signaling ◽  
Diabetic Wound Healing ◽  
Notch1 Signaling Pathway ◽  
Diabetic Wounds

Diabetic wounds, as a kind of refractory wound, are very difficult to heal. Both endothelial progenitor cell (EPC) transplantation and platelet-rich plasma (PRP) can improve diabetic wound healing to some extent. However, PRP application cannot provide reparative cells, while EPC transplantation cannot replenish the required growth factors for wound healing. Thus, when applied alone, neither of these factors is sufficient for effective wound healing. Furthermore, the proliferation, differentiation, and fate of the transplanted EPCs are not well known. Therefore, in this study, we examined the efficacy of combined PRP application with EPC transplantation in diabetic wound healing. Our results indicated that PRP application improved EPC proliferation and migration. The Notch signaling pathway plays a key role in the regulation of the proliferation and differentiation of stem cells and angiogenesis in wound healing. The application of PRP upregulated the Notch pathway-related gene and protein expression in EPCs. Furthermore, experiments with shNotch1-transfected EPCs indicated that PRP enhanced the function of EPCs by upregulating the Notch1 signaling pathway. In vivo studies further indicated that the combination of PRP and EPC transplantation increased neovascularization, reduced wound size, and improved healing in rat wound models. Thus, PRP application can provide the necessary growth factors for wound healing, while EPC transplantation offers the required cells, indicating that the combination of both is a potent novel approach for treating diabetic wounds.

γ-PGA hydrogel loaded with cell-free fat extract promotes the healing of diabetic wounds

2020 ◽  
Vol 8 (36) ◽  
pp. 8395-8404
Author(s):  
Mengting Yin ◽  
Xiangsheng Wang ◽  
Ziyou Yu ◽  
Yun Wang ◽  
Xiansong Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Schematic of Ceffe–γ-PGA hydrogel treatment for diabetic wound healing.

scholarly journals Enhanced Healing of Diabetic Wounds by Subcutaneous Administration of Human Umbilical Cord Derived Stem Cells and Their Conditioned Media

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Chandrama Shrestha ◽  
Liling Zhao ◽  
Ke Chen ◽  
Honghui He ◽  
Zhaohui Mo
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Umbilical Cord ◽  
Subcutaneous Administration ◽  
Conditioned Media ◽  
Human Umbilical Cord ◽  
Diabetic Wound ◽  
Significant Difference ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Objective. Mesenchymal stem cells (MSCs) isolated from the umbilical cord and their conditioned media (CM) can be easily obtained and refined compared with stem cells from other sources. Here, we explore the possibility of the benefits of these cells in healing diabetic wounds.Methodology and Results. Delayed wound healing animal models were established by making a standard wound on the dorsum of eighteen db/db mice, which were divided into three groups with six mice in each: groups I, II, and III received PBS, UC-MSC, and CM, respectively. UC-MSC and their CM significantly accelerated wound closure compared to PBS-treated wounds, and it was most rapid in CM-injected wounds. In day-14 wounds, significant difference in capillary densities among the three groups was noted (n=6;P<0.05), and higher levels of VEGF, PDGF, and KGF expression in the CM- and UC-MSC-injected wounds compared to the PBS-treated wounds were seen. The expression levels of PDGF-βand KGF were higher in CM-treated wounds than those in UC-MSC-treated wounds.Conclusion. Both the transplantation of UC-MSC and their CM are beneficial to diabetic wound healing, and CM has been shown to be therapeutically better than UC-MSC, at least in the context of diabetic wound healing.

scholarly journals The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Sandra Matabi Ayuk ◽  
Heidi Abrahamse ◽  
Nicolette Nadene Houreld
Keyword(s):  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Main Function ◽  
Diabetic Wound ◽  
Impaired Wound Healing ◽  
Inflammatory Phase ◽  
Diabetic Wound Healing

The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI) or photobiomodulation (PBM) is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.

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