Electrostatically assembled wound dressings deliver pro-angiogenic anti-miRs preferentially to endothelial cells
Name
nihms-1918363.pdf
Description
Accepted version
Size
1.76 MB
Format
Adobe PDF
Checksum (MD5)
bc3a4d385d1f91d657197a8158661b31
Author(s)
Berger, Adam G
Deiss-Yehiely, Elad
Vo, Chau
McCoy, Michael G
Almofty, Sarah
Feinberg, Mark W
Hammond, Paula T
Date Issued
September 2023
Journal
Biomaterials
Publisher
Elsevier BV
Citation
Berger, Adam G, Deiss-Yehiely, Elad, Vo, Chau, McCoy, Michael G, Almofty, Sarah et al. 2023. "Electrostatically assembled wound dressings deliver pro-angiogenic anti-miRs preferentially to endothelial cells." Biomaterials, 300.
Version
Author's final manuscript
Abstract
Chronic non-healing wounds occur frequently in individuals affected by diabetes, yet standard-of-care treatment leaves many patients inadequately treated or with recurring wounds. MicroRNA (miR) expression is dysregulated in diabetic wounds and drives an anti-angiogenic phenotype, but miRs can be inhibited with short, chemically-modified RNA oligonucleotides (anti-miRs). Clinical translation of anti-miRs is hindered by delivery challenges such as rapid clearance and uptake by off-target cells, requiring repeated injections, excessively large doses, and bolus dosing mismatched to the dynamics of the wound healing process. To address these limitations, we engineered electrostatically assembled wound dressings that locally release anti-miR-92a, as miR-92a is implicated in angiogenesis and wound repair. In vitro, anti-miR-92a released from these dressings was taken up by cells and inhibited its target. An in vivo cellular biodistribution study in murine diabetic wounds revealed that endothelial cells, which play a critical role in angiogenesis, exhibit higher uptake of anti-miR eluted from coated dressings than other cell types involved in the wound healing process. In a proof-of-concept efficacy study in the same wound model, anti-miR targeting anti-angiogenic miR-92a de-repressed target genes, increased gross wound closure, and induced a sex-dependent increase in vascularization. Overall, this proof-of-concept study demonstrates a facile, translational materials approach for modulating gene expression in ulcer endothelial cells to promote angiogenesis and wound healing. Furthermore, we highlight the importance of probing cellular interactions between the drug delivery system and the target cells to drive therapeutic efficacy.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
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Creative Commons Attribution-Noncommercial-ShareAlike
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DOI of Published Version
https://doi.org/10.1016/j.biomaterials.2023.122188
