Publication

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

Monaghan, Michael
Browne, Shane
Schenke-Layland, Katja
Pandit, Abhay
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.
Funder
Publisher
Elsevier BV
Publisher DOI
10.1038/mt.2013.288
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland