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  Enhanced biological activity of BMP-2 bound to surface-grafted heparan sulfate

Migliorini, E., Horn, P., Haraszti, T., Wegner, S., Hiepen, C., Knaus, P., et al. (2017). Enhanced biological activity of BMP-2 bound to surface-grafted heparan sulfate. Advanced Biosystems, 4(1): 1600041, pp. 1-7. doi:10.1002/adbi.201600041.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-DFA7-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-5E50-4
Genre: Journal Article

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 Creators:
Migliorini, Elisa1, 2, Author              
Horn, Patrick, Author
Haraszti, Tamas1, 2, Author              
Wegner, S.1, 2, Author              
Hiepen, Christian, Author
Knaus, Petra, Author
Richter, Ralf P., Author
Cavalcanti-Adam, Elisabetta Ada1, 2, Author              
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              
2Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany, ou_persistent22              

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Free keywords: biomimetic platforms; BMP-2; extracellular matrix; heparan sulfate; noggin
 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.

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Language(s): eng - English
 Dates: 2016-12-132017-03-272017-04-19
 Publication Status: Published online
 Pages: 7
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1002/adbi.201600041
 Degree: -

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Title: Advanced Biosystems
Source Genre: Journal
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Publ. Info: Weinheim : Wiley-VCH Verlag GmbH & Co. KGaA
Pages: - Volume / Issue: 4 (1) Sequence Number: 1600041 Start / End Page: 1 - 7 Identifier: ISSN: 2366-7478