Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGFβ Signaling
| Autor: | Julia R. Greer, Alessandro Maggi, Jubin Ryu, Jessica L. Allen, Bianca Flores, Tejal A. Desai |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
business.product_category Biocompatibility Cellular differentiation Biomedical Engineering Bioengineering Biochemistry 3T3 cells Transforming Growth Factor beta1 Biomaterials Mice 03 medical and health sciences In vivo Microfiber medicine Animals Myofibroblasts Receptor Chemistry Cell Differentiation Membranes Artificial 3T3 Cells Original Articles Antigens Differentiation Fibrosis Cell biology 030104 developmental biology medicine.anatomical_structure Signal transduction business Myofibroblast Signal Transduction Biomedical engineering |
| Zdroj: | Tissue Engineering Part A. 22:142-150 |
| ISSN: | 1937-335X 1937-3341 |
| DOI: | 10.1089/ten.tea.2015.0087 |
| Popis: | Fibrotic encapsulation limits the efficacy and lifetime of implantable biomedical devices. Microtopography has shown promise in the regulation of myofibroblast differentiation, a key driver of fibrotic encapsulation. However, existing studies have not systematically isolated the requisite geometric parameters for suppression of myofibroblast differentiation via microtopography, and there has not been in vivo validation of this technology to date. To address these issues, a novel lamination method was developed to afford more control over topography dimensions. Specifically, in this study we focus on fiber length and its effect on myofibroblast differentiation. Fibroblasts cultured on films with microfibers exceeding 16 μm in length lost the characteristic morphology associated with myofibroblast differentiation, while shorter microfibers of 6 μm length failed to produce this phenotype. This increase in length corresponded to a 50% decrease in fiber stiffness, which acts as a mechanical cue to influence myofibroblast differentiation. Longer microfiber films suppressed expression of myofibroblast specific genes (αSMA, Col1α2, and Col3α1) and TGFβ signaling components (TGFβ1 ligand, TGFβ receptor II, and Smad3). 16 μm long microfiber films implanted subcutaneously in a mouse wound-healing model generated a substantially thinner fibrotic capsule and less deposition of collagen in the wound bed. Together, these results identify a critical feature length threshold for microscale topography-mediated repression of fibrotic encapsulation. This study also demonstrates a simple and powerful strategy to improve surface biocompatibility and reduce fibrotic encapsulation around implanted materials. |
| Databáze: | OpenAIRE |
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