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Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGF? Signaling.

ABSTRACT: 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 ?m in length lost the characteristic morphology associated with myofibroblast differentiation, while shorter microfibers of 6 ?m 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 (?SMA, Col1?2, and Col3?1) and TGF? signaling components (TGF?1, T?R2, and Smad3). About 16 ?m long microfiber films subcutaneously implanted 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.

SUBMITTER: Allen J

PROVIDER: S-EPMC5802271 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGFβ Signaling.

Allen Jessica J Ryu Jubin J Maggi Alessandro A Flores Bianca B Greer Julia R JR Desai Tejal T

Tissue engineering. Part A 20151218 1-2

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 metho ...[more]

PMID: 26507808

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Dataset Information

Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGF? Signaling.

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Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGFβ Signaling.

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