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A collagen-based scaffold delivering exogenous microrna-29b to modulate extracellular matrix remodeling

Monaghan, Michael
; 
Browne, Shane
; 
Schenke-Layland, Katja
; 
Pandit, Abhay
Identifiers
http://hdl.handle.net/10379/12945
 https://doi.org/10.13025/28752
Publication Date
2014-04-01
Keywords
myocardial-infarction, stem-cells, in-vivo, rna, expression, tissue, apoptosis, fibrosis, mir-29, metalloproteinases
Type
Article
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Citation
Monaghan, Michael; Browne, Shane; Schenke-Layland, Katja; Pandit, Abhay (2014). A collagen-based scaffold delivering exogenous microrna-29b to modulate extracellular matrix remodeling. Molecular Therapy 22 (4), 786-796
Abstract
Directing appropriate extracellular matrix remodeling is a key aim of regenerative medicine strategies. Thus, antifibrotic interfering RNA (RNAi) therapy with exogenous microRNA (miR)-29B was proposed as a method to modulate extracellular matrix remodeling following cutaneous injury. It was hypothesized that delivery of miR-29B from a collagen scaffold will efficiently modulate the extracellular matrix remodeling response and reduce maladaptive remodeling such as aggressive deposition of collagen type I after injury. The release of RNA from the scaffold was assessed and its ability to silence collagen type I and collagen type III expression was evaluated in vitro. When primary fibroblasts were cultured with scaffolds doped with miR-29B, reduced levels of collagen type I and collagen type III mRNA expression were observed for up to 2 weeks of culture. When the scaffolds were applied to full thickness wounds in vivo, reduced wound contraction, improved collagen type III/I ratios and a significantly higher matrix metalloproteinase (MMP)-8: tissue inhibitor of metalloproteinase (TIMP)-1 ratio were detected when the scaffolds were functionalized with miR-29B. Furthermore, these effects were significantly influenced by the dose of miR-29B in the collagen scaffold (0.5 versus 5 mu g). This study shows a potential of combining exogenous miRs with collagen scaffolds to improve extracellular matrix remodeling following injury.
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Publisher
Elsevier BV
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)