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Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts

Biomaterial augmentation of surgically repaired rotator cuff tendon tears aims to improve the high failure rates (∼40%) of traditional repairs. Biomaterials that can alter cellular phenotypes through the provision of microscale topographical cues are now under development. We aimed to systematically...

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Autores principales: Baldwin, Mathew J., Mimpen, Jolet Y., Cribbs, Adam P., Stace, Edward, Philpott, Martin, Dakin, Stephanie G., Carr, Andrew J., Snelling, Sarah JB.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790033/
https://www.ncbi.nlm.nih.gov/pubmed/35096791
http://dx.doi.org/10.3389/fbioe.2021.795748
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author Baldwin, Mathew J.
Mimpen, Jolet Y.
Cribbs, Adam P.
Stace, Edward
Philpott, Martin
Dakin, Stephanie G.
Carr, Andrew J.
Snelling, Sarah JB.
author_facet Baldwin, Mathew J.
Mimpen, Jolet Y.
Cribbs, Adam P.
Stace, Edward
Philpott, Martin
Dakin, Stephanie G.
Carr, Andrew J.
Snelling, Sarah JB.
author_sort Baldwin, Mathew J.
collection PubMed
description Biomaterial augmentation of surgically repaired rotator cuff tendon tears aims to improve the high failure rates (∼40%) of traditional repairs. Biomaterials that can alter cellular phenotypes through the provision of microscale topographical cues are now under development. We aimed to systematically evaluate the effect of topographic architecture on the cellular phenotype of fibroblasts from healthy and diseased tendons. Electrospun polydioxanone scaffolds with fiber diameters ranging from 300 to 4000 nm, in either a highly aligned or random configuration, were produced. Healthy tendon fibroblasts cultured for 7 days on scaffolds with highly aligned fibers demonstrated a distinctive elongated morphology, whilst those cultured on randomly configured fibers demonstrated a flattened and spread morphology. The effect of scaffold micro-architecture on the transcriptome of both healthy and diseased tendon fibroblasts was assessed with bulk RNA-seq. Both healthy (n = 3) and diseased tendon cells (n = 3) demonstrated a similar transcriptional response to architectural variants. Gene set enrichment analysis revealed that large diameter (≥2000 nm) aligned scaffolds induced an upregulation of genes involved in cellular replication and a downregulation of genes defining inflammatory responses and cell adhesion. Similarly, PDPN and CD248, markers of inflammatory or “activated” fibroblasts, were downregulated during culture of both healthy and diseased fibroblasts on aligned scaffolds with large (≥2000 nm) fiber diameters. In conclusion scaffold architectures resembling that of disordered type III collagen, typically present during the earlier phases of wound healing, resulted in tendon fibroblast activation. Conversely, scaffolds mimicking aligned diameter collagen I fibrils, present during tissue remodelling, did not activate tendon derived fibroblasts. This has implications for the design of scaffolds used during rotator cuff repair augmentation.
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spelling pubmed-87900332022-01-27 Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts Baldwin, Mathew J. Mimpen, Jolet Y. Cribbs, Adam P. Stace, Edward Philpott, Martin Dakin, Stephanie G. Carr, Andrew J. Snelling, Sarah JB. Front Bioeng Biotechnol Bioengineering and Biotechnology Biomaterial augmentation of surgically repaired rotator cuff tendon tears aims to improve the high failure rates (∼40%) of traditional repairs. Biomaterials that can alter cellular phenotypes through the provision of microscale topographical cues are now under development. We aimed to systematically evaluate the effect of topographic architecture on the cellular phenotype of fibroblasts from healthy and diseased tendons. Electrospun polydioxanone scaffolds with fiber diameters ranging from 300 to 4000 nm, in either a highly aligned or random configuration, were produced. Healthy tendon fibroblasts cultured for 7 days on scaffolds with highly aligned fibers demonstrated a distinctive elongated morphology, whilst those cultured on randomly configured fibers demonstrated a flattened and spread morphology. The effect of scaffold micro-architecture on the transcriptome of both healthy and diseased tendon fibroblasts was assessed with bulk RNA-seq. Both healthy (n = 3) and diseased tendon cells (n = 3) demonstrated a similar transcriptional response to architectural variants. Gene set enrichment analysis revealed that large diameter (≥2000 nm) aligned scaffolds induced an upregulation of genes involved in cellular replication and a downregulation of genes defining inflammatory responses and cell adhesion. Similarly, PDPN and CD248, markers of inflammatory or “activated” fibroblasts, were downregulated during culture of both healthy and diseased fibroblasts on aligned scaffolds with large (≥2000 nm) fiber diameters. In conclusion scaffold architectures resembling that of disordered type III collagen, typically present during the earlier phases of wound healing, resulted in tendon fibroblast activation. Conversely, scaffolds mimicking aligned diameter collagen I fibrils, present during tissue remodelling, did not activate tendon derived fibroblasts. This has implications for the design of scaffolds used during rotator cuff repair augmentation. Frontiers Media S.A. 2022-01-12 /pmc/articles/PMC8790033/ /pubmed/35096791 http://dx.doi.org/10.3389/fbioe.2021.795748 Text en Copyright © 2022 Baldwin, Mimpen, Cribbs, Stace, Philpott, Dakin, Carr and Snelling. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Baldwin, Mathew J.
Mimpen, Jolet Y.
Cribbs, Adam P.
Stace, Edward
Philpott, Martin
Dakin, Stephanie G.
Carr, Andrew J.
Snelling, Sarah JB.
Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts
title Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts
title_full Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts
title_fullStr Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts
title_full_unstemmed Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts
title_short Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts
title_sort electrospun scaffold micro-architecture induces an activated transcriptional phenotype within tendon fibroblasts
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790033/
https://www.ncbi.nlm.nih.gov/pubmed/35096791
http://dx.doi.org/10.3389/fbioe.2021.795748
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