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Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGFβ Signaling

Allen, Jessica and Ryu, Jubin and Maggi, Alessandro and Flores, Bianca and Greer, Julia and Desai, Tejal (2016) Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGFβ Signaling. Tissue Engineering Part A, 22 (1-2). pp. 142-150. ISSN 1937-3341. PMCID PMC5802271. https://resolver.caltech.edu/CaltechAUTHORS:20151103-104811137

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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 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1089/ten.TEA.2015.0087DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802271/PubMed CentralArticle
ORCID:
AuthorORCID
Greer, Julia0000-0002-9675-1508
Desai, Tejal0000-0003-3409-9208
Additional Information:© 2015 Mary Ann Liebert. Published in Volume: 22 Issue 1-2: January 15, 2016; Online Ahead of Print: December 18, 2015; Online Ahead of Editing: October 28, 2015. The authors would like to thank R. Fearing and A. Gillies at the Berkeley Biomimetic Millisystems Lab for sharing their expertise in microscale topography and granting us access to their lamination equipment. We gratefully acknowledge use of the Carl Zeiss Ultra 55 FE-SEM and supporting equipment at SF State. The FE-SEM and supporting facilities were obtained under NSF-MRI award #0821619 and NSF-EAR award #0949176, respectively. We would also like to acknowledge B. Hann and D. Wang for their aid in development and execution of the in vivo studies. This work was funded by the National Science Foundation (NSEC). J. R. Greer and A. Maggi gratefully acknowledge the financial support of Caltech's EAS Discovery Funds.
Funders:
Funding AgencyGrant Number
NSFMRI-0821619
NSFEAR-0949176
Caltech Engineering and Applied Science Discovery FundUNSPECIFIED
Subject Keywords:microtopography, myofibroblast, TGFβ, fibrotic encapsulation
Issue or Number:1-2
PubMed Central ID:PMC5802271
Record Number:CaltechAUTHORS:20151103-104811137
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20151103-104811137
Official Citation:Allen Jessica, Ryu Jubin, Maggi Alessandro, Flores Bianca, Greer Julia R., and Desai Tejal. Tissue Engineering Part A. January 2016, 22(1-2): 142-150. doi:10.1089/ten.tea.2015.0087
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:61795
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Nov 2015 19:02
Last Modified:04 Mar 2020 23:42

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