ArticleFrontiers in physiology2019
Predictive Approach Identifies Molecular Targets and Interventions to Restore Angiogenesis in Wounds With Delayed Healing.
Article in Frontiers in physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Cellular gatekeepers of infected wounds: the dual role of adipocytes in coordinating immunity and regeneration.Frontiers in immunology · 2026Review
- Comparative Study of Placental Allografts with Distinct Layer Composition.International journal of molecular sciences · 2025Article
- LncRNA NEAT1/miR-146a-5p Axis Restores Normal Angiogenesis in Diabetic Foot Ulcers by Targeting mafG.Cells · 2024Article
- A review of the evidence to support electrical stimulationRegenerative therapy · 2023Review
- Immune cells and associated molecular markers in dermal fibrosis with focus on raised cutaneous scars.Experimental dermatology · 2023Review
- Cellular and Molecular Events of Wound Healing and the Potential of Silver Based Nanoformulations as Wound Healing Agents.Bioengineering (Basel, Switzerland) · 2022Review
- In silico optimization of heparin microislands in microporous annealed particle hydrogel for endothelial cell migration.Acta biomaterialia · 2022Article
- Systems biology of angiogenesis signaling: Computational models and omics.WIREs mechanisms of disease · 2022Review
- Molecular Mechanism of Traditional Chinese Ointment of Xuzhou Qufu Shengji in Infected Wounds.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Regenerative Potential of DPSCs and Revascularization: Direct, Paracrine or Autocrine Effect?Stem cell reviews and reports · 2021Review
- Mathematical Model Predicts that Acceleration of Diabetic Wound Healing is Dependent on Spatial Distribution of VEGF-A mRNA (AZD8601).Cellular and molecular bioengineering · 2021Article
- Review
- Visualisation of HMikrochimica acta · 2020Article
- Stromal vascular fraction promotes migration of fibroblasts and angiogenesis through regulation of extracellular matrix in the skin wound healing process.Stem cell research & therapy · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impaired angiogenesis is a hallmark of wounds with delayed healing, and currently used therapies to restore angiogenesis have limited efficacy. Here, we employ a computational simulation-based approach to identify influential molecular and cellular processes, as well as protein targets, whose modulation may stimulate angiogenesis in wounds. We developed a mathematical model that captures the time courses for platelets, 9 cell types, 29 proteins, and oxygen, which are involved in inflammation, proliferation, and angiogenesis during wound healing. We validated our model using previously published experimental data. By performing global sensitivity analysis on thousands of simulated wound-healing scenarios, we identified six processes (among the 133 modeled in total) whose modulation may improve angiogenesis in wounds. By simulating knockouts of 25 modeled proteins and by simulating different wound-oxygenation levels, we identified four proteins [namely, transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and angiopoietin-2 (ANG-2)], as well as oxygen, as therapeutic targets for stimulating angiogenesis in wounds. Our modeling results indicated that simultaneous inhibition of TGF-β and supplementation of either FGF-2 or ANG-2 could be more effective in stimulating wound angiogenesis than the modulation of either protein alone. Our findings suggest experimentally testable intervention strategies to restore angiogenesis in wounds with delayed healing.
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