Mechanism of sustained release of vascular endothelial growth factor in accelerating experimental diabetic healing
Open accessAbstract
In this study, we hypothesize that local sustained release of vascular endothelial growth factor (VEGF), using adenovirus vector (ADV)-mediated gene transfer, accelerates experimental wound healing. This hypothesis was tested by determining the specific effects of VEGF(165) application on multiple aspects of the wound healing process, that is, time to complete wound closure and skin biomechanical properties. After showing accelerated wound healing in vivo, we studied the mechanism to explain the findings on multiple aspects of the wound healing cascade, including epithelialization, collagen deposition, and cell migration. Intradermal treatment of wounds in non-obese diabetic and db/db mice with ADV/VEGF(165) improves healing by enhancing tensile stiffness and/or increasing epithelialization and collagen deposition, as well as by decreasing time to wound closure. VEGF(165), in vitro, stimulates the migration of cultured human keratinocytes and fibroblasts, thus revealing a non-angiogenic effect of VEGF on wound closure. In conclusion, ADV/VEGF is effective in accelerating wound closure by stimulating angiogenesis, epithelialization, and collagen deposition. In the future, local administration and sustained, controlled release of VEGF(165) may decrease amputations in patients with diabetic foot ulcers and possibly accelerate closure of venous ulcers and pressure ulcers.
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Previous studies have demonstrated that platelet-derived growth factor, fibroblast growth factor, vascular endothelial growth factor, or erythropoietin can improve healing in diabetic mice.
“Although previous studies have demonstrated that platelet-derived growth factor, fibroblast growth factor, vascular endothelial growth factor (VEGF), or erythropoietin can improve healing in diabetic mice (13,36,37)”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [36]
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Mirza, R. E., Fang, M. M., Weinheimer-Haus, E. M., Ennis, W. J., & Koh, T. J. (2014) · Diabetes · doi:10.2337/db13-0927 · Cited by 319 · see citing works
- Authors
- Brem, H., Kodra, A., Golinko, M. S., Entero, H., Stojadinovic, O., Wang, V. M., Sheahan, C. M., Weinberg, A. D., Woo, S. L. C., Paul Ehrlich, H., & Tomic-Canic, M.
- Affiliations
- NYU Langone Health (US)
- Rush University Medical Center (US)
- Louisiana State University Health Sciences Center New Orleans (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Brem, Harold
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 129
- Issue
- 9
- Pages
- 2275-2287
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W1970179942
- Cited by
- 182
- References
- 63
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 8 · 2023: 4 · 2022: 13 · 2021: 16 · 2020: 13 · 2019: 12 · 2018: 8 · 2017: 14 · 2016: 14 · 2015: 9 · 2014: 13 · 2013: 12 · 2012: 13
- FWCI
- 11.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- National Institutes of Health (5r21dk060214-02)
- National Institute of Nursing Research (NR08029, R01NR008029)
- National Institute of General Medical Sciences (GM56851, R01GM056851)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK59424, K08DK059424, DK060214)
- U.S. National Library of Medicine (R01LM008443, LM08443)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- vascular endothelial growth factor, VEGF165, sustained drug release, adenoviral vector, gene therapy, diabetic wound healing, diabetic foot ulcer, re-epithelialization, collagen deposition, keratinocyte migration, fibroblast migration, skin biomechanics, tensile stiffness, angiogenesis, db/db mice
- MeSH terms
- Adenoviridae, Animals, Collagen, Diabetes Mellitus, Epithelium, Female, Granulation Tissue, Humans, Regeneration, Tensile Strength, Wound Healing, Genetic Therapy, Mice, Inbred NOD, Vascular Endothelial Growth Factor A, Mice
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