ArticleCellular and molecular bioengineering2021
Mathematical Model Predicts that Acceleration of Diabetic Wound Healing is Dependent on Spatial Distribution of VEGF-A mRNA (AZD8601).
Article in Cellular and molecular bioengineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Therapeutic strategies to enhance proliferation in diabetic wound contraction: a comprehensive review from 1991-2025.Acta diabetologica · 2026Review
- Transcriptional analyses identify pericyte-centered signaling programs altered by sex and brain region in Alzheimer's Disease.Communications biology · 2026Article
- mRNA vaccines in disease prevention and treatment.Signal transduction and targeted therapy · 2023Review
- In silico optimization of heparin microislands in microporous annealed particle hydrogel for endothelial cell migration.Acta biomaterialia · 2022Article
- Photoacoustic microscopy of vascular adaptation and tissue oxygen metabolism during cutaneous wound healing.Biomedical optics express · 2022Article
- 4-Hexylresorcinol: pharmacologic chaperone and its application for wound healing.Maxillofacial plastic and reconstructive surgery · 2022Review
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionPharmacologic 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.
methodsWe 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
resultsWhen 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.
conclusionsThese 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00678-9.
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