Migliorini, E, Horn, P, Haraszti, T et al. (5 more authors) (2017) Enhanced Biological Activity of BMP‐2 Bound to Surface‐Grafted Heparan Sulfate. Advanced Biosystems, 1 (4). ARTN 1600041. ISSN 2366-7478
Abstract
Over the last decade, there has been a growing interest in the development of new materials to improve bone morphogenetic protein‐2 (BMP‐2) delivery for tissue regeneration. This study reports the development and application of model surfaces that present BMP‐2 via heparan sulfate (HS), a ubiquitous component of the extracellular matrix (ECM). On these surfaces, HS is grafted by its reducing end, to mimic the natural arrangement of HS proteoglycans in the ECM. The binding of each component on these biomimetic surfaces is highly controlled, in terms of stoichiometry of molecules and BMP‐2/grafted‐HS affinity, as determined by surface‐sensitive techniques. For comparison, this study also uses surfaces presenting immobilized BMP‐2 alone. Functional validations of the surfaces are performed using a murine myoblast cell line (C2C12) and primary human mesenchymal stromal cells. In both cell types, HS‐bound BMP‐2 and surface‐immobilized BMP‐2 significantly prolong SMAD 1/5 phosphorylation, compared to BMP‐2 added to the culture media. Moreover, HS‐bound BMP‐2 enhances p‐SMAD 1/5 levels in C2C12 cells and reduces noggin antagonistic activity. Thus, grafted HS positively affects BMP‐2 cellular activity. This innovative surface design, which mimics natural interactions of growth factors with ECM components, constitutes a promising candidate for future regenerative medicine applications.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article: Enhanced Biological Activity of BMP‐2 Bound to Surface‐Grafted Heparan Sulfate, which has been published in final form at https://doi.org/10.1002/adbi.201600041. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. |
Keywords: | biomimetic platforms; BMP‐2; extracellular matrix; heparan sulfate; noggin |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Nov 2018 13:13 |
Last Modified: | 16 Nov 2018 13:47 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/adbi.201600041 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:138657 |