Fibronectin matrix assembly and TGFβ1 presentation for chondrogenesis of patient derived pericytes for microtia repair

Donnelly, H., Kurjan, A., Yong, L. Y., Xiao, Y., Lemgruber, L. , West, C., Salmeron-Sanchez, M. and Dalby, M. J. (2023) Fibronectin matrix assembly and TGFβ1 presentation for chondrogenesis of patient derived pericytes for microtia repair. Biomaterials Advances, 148, 213370. (doi: 10.1016/j.bioadv.2023.213370) (PMID:36931082)

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Abstract

Tissue engineered cartilage for external ear reconstruction of congenital deformities, such as microtia or resulting from trauma, remains a significant challenge for plastic and reconstructive surgeons. Current strategies involve harvesting autologous costal cartilage or expanding autologous chondrocytes ex vivo. However, these procedures often lead to donor site morbidity and a cell source with limited expansion capacity. Stromal stem cells such as perivascular stem cells (pericytes) offer an attractive alternative cell source, as they can be isolated from many human tissues, readily expanded in vitro and possess chondrogenic differentiation potential. Here, we successfully isolate CD146+ pericytes from the microtia remnant from patients undergoing reconstructive surgery (Microtia pericytes; MPs). Then we investigate their chondrogenic potential using the polymer poly(ethyl acrylate) (PEA) to unfold the extracellular matrix protein fibronectin (FN). FN unfolding exposes key growth factor (GF) and integrin binding sites on the molecule, allowing tethering of the chondrogenic GF transforming growth factor beta 1 (TGFβ1). This system leads to solid-phase, matrix-bound, GF presentation in a more physiological-like manner than that of typical chondrogenic induction media (CM) formulations that tend to lead to off-target effects. This simple and controlled material-based approach demonstrates similar chondrogenic potential to CM, while minimising proclivity toward hypertrophy, without the need for complex induction media formulations.

Item Type:Articles
Additional Information:This work was supposed by EPSRC grant (EP/P001114/1). LYY and CWW was supported by a Royal College of Surgeons Edinburgh pump priming grant (SPPG/17/112) and a grant from the William Rooney Plastic Surgery and Burns Research Trust.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Donnelly, Dr Hannah and Dalby, Professor Matthew and Lemgruber Soares, Dr Leandro and Xiao, Yinbo
Authors: Donnelly, H., Kurjan, A., Yong, L. Y., Xiao, Y., Lemgruber, L., West, C., Salmeron-Sanchez, M., and Dalby, M. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Biomaterials Advances
Publisher:Elsevier
ISSN:2772-9516
ISSN (Online):2772-9508
Published Online:08 March 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Biomaterials Advances 148: 213370
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173192Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - Biomedical Engineering