title: A collagen-based scaffold delivering exogenous microrna-29B to modulate extracellular matrix remodeling.
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 μg). This study shows a potential of combining exogenous miRs with collagen scaffolds to improve extracellular matrix remodeling following injury.
authors.affiliation: 1] Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland [2] Department of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany [3] University Women's Hospital, Eberhard Karls University, Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Monaghan
authors.affiliation: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
authors.forename: Shane
authors.initials: S
authors.lastname: Browne
authors.affiliation: 1] Department of Cell and Tissue Engineering, Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany [2] University Women's Hospital, Eberhard Karls University, Tübingen, Germany [3] Department of Medicine/Cardiology, Cardiovascular Research Laboratories, University of California, Los Angeles, CA, USA.
authors.forename: Katja
authors.initials: K
authors.lastname: Schenke-Layland
authors.affiliation: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
authors.forename: Abhay
authors.initials: A
authors.lastname: Pandit
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics* / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D044968:Regenerative Medicine; D054457:Tissue Scaffolds
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D020784:Matrix Metalloproteinase 8