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Cell-Mediated Proteolytic Release of Growth Factors from Poly(Ethylene Glycol) Matrices


Metzger, Stéphanie; Blache, Ulrich; Lienemann, Philipp S; Karlsson, Maria; Weber, Franz E; Weber, Wilfried; Ehrbar, Martin (2016). Cell-Mediated Proteolytic Release of Growth Factors from Poly(Ethylene Glycol) Matrices. Macromolecular Bioscience, 16(11):1703-1713.

Abstract

Engineering in vitro tissue mimetics that resemble the corresponding living tissues requires the 3D arrangement of tissue progenitor cells and their differentiation by localized growth factor (GF) signaling cues. Recent technological advances open a large field of possibilities for the creation of complex GF arrangements. Additionally, cell-instructive biomaterials, which bind GFs by various mechanisms and release them with different kinetics depending on binding affinity, have become available. This paper describes the development of a matrix metalloproteinase (MMP)-degradable streptavidin-based linker module, which allows the release of immobilized GFs from synthetic biomimetic poly(ethylene glycol) hydrogels independently of the hydrogel degradation. The MMP-sensitive streptavidin linker is shown to efficiently bind biotinylated molecules, and as proof of concept, bone morphogenetic protein-2 (BMP-2) delivery via the MMP-degradable linker is used to induce osteogenic differentiation in C2C12 cells and mesenchymal stem cells. The results show a significantly increased net effect of proteolytically releasable BMP-2 in comparison to stably immobilized and soluble BMP-2. This study indicates that a GF delivery system directly responsive to cellular activity can have important implications for the synthesis of tissue mimetics and regenerative medicine, as it can influence the availability, the localization of effects, as well as efficacy of employed GFs.

Abstract

Engineering in vitro tissue mimetics that resemble the corresponding living tissues requires the 3D arrangement of tissue progenitor cells and their differentiation by localized growth factor (GF) signaling cues. Recent technological advances open a large field of possibilities for the creation of complex GF arrangements. Additionally, cell-instructive biomaterials, which bind GFs by various mechanisms and release them with different kinetics depending on binding affinity, have become available. This paper describes the development of a matrix metalloproteinase (MMP)-degradable streptavidin-based linker module, which allows the release of immobilized GFs from synthetic biomimetic poly(ethylene glycol) hydrogels independently of the hydrogel degradation. The MMP-sensitive streptavidin linker is shown to efficiently bind biotinylated molecules, and as proof of concept, bone morphogenetic protein-2 (BMP-2) delivery via the MMP-degradable linker is used to induce osteogenic differentiation in C2C12 cells and mesenchymal stem cells. The results show a significantly increased net effect of proteolytically releasable BMP-2 in comparison to stably immobilized and soluble BMP-2. This study indicates that a GF delivery system directly responsive to cellular activity can have important implications for the synthesis of tissue mimetics and regenerative medicine, as it can influence the availability, the localization of effects, as well as efficacy of employed GFs.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Obstetrics
04 Faculty of Medicine > Center for Dental Medicine > Clinic for Cranio-Maxillofacial Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:22 August 2016
Deposited On:20 Oct 2016 10:59
Last Modified:06 Oct 2017 03:59
Publisher:Wiley-VCH Verlag
ISSN:1616-5187
Publisher DOI:https://doi.org/10.1002/mabi.201600223
PubMed ID:27548907

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