Chitosan Particles Complexed with CA5-HIF-1α Plasmids Increase Angiogenesis and Improve Wound Healing

Author:

Born Louis J.12,Bengali Sameer2,Hsu Angela Ting Wei2,Abadchi Sanaz Nourmohammadi2,Chang Kai-Hua2,Lay Frank2,Matsangos Aerielle2,Johnson Christopher2,Jay Steven M.13ORCID,Harmon John W.2

Affiliation:

1. Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA

2. Hendrix Burn and Wound Healing Laboratory, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

3. Program in Molecular and Cell Biology, University of Maryland, College Park, MD 20742, USA

Abstract

Wound therapies involving gene delivery to the skin have significant potential due to the advantage and ease of local treatment. However, choosing the appropriate vector to enable successful gene expression while also ensuring that the treatment’s immediate material components are conducive to healing itself is critical. In this study, we utilized a particulate formulation of the polymer chitosan (chitosan particles, CPs) as a non-viral vector for the delivery of a plasmid encoding human CA5-HIF-1α, a degradation resistant form of HIF-1α, to enhance wound healing. We also compared the angiogenic potential of our treatment (HIF/CPs) to that of chitosan particles containing only the plasmid backbone (bb/CPs) and the chitosan particle vector alone (CPs). Our results indicate that chitosan particles exert angiogenic effects that are enhanced with the human CA5-HIF-1α-encoded plasmid. Moreover, HIF/CPs enhanced wound healing in diabetic db/db mice (p < 0.01), and healed tissue was found to contain a significantly increased number of blood vessels compared to bb/CPs (p < 0.01), CPs (p < 0.05) and no-treatment groups (p < 0.01). Thus, this study represents a method of gene delivery to the skin that utilizes an inherently pro-wound-healing polymer as a vector for plasmid DNA that has broad application for the expression of other therapeutic genes.

Funder

National Institutes of Health

National Science Foundation

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference57 articles.

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3. ADA (2020, November 24). Statistics About Diabetes. Available online: https://www.diabetes.org/resources/statistics/statistics-about-diabetes.

4. Chronic Wound Healing: A Review of Current Management and Treatments;Han;Adv. Ther.,2017

5. An In Vivo Comparison of Commonly Used Topical Antimicrobials on Skin Graft Healing After Full-Thickness Burn Injury;Abbas;J. Burn. Care Res.,2015

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