@article {19174,
	title = {Design of protein delivery systems by mimicking extracellular mechanisms for protection of growth factors},
	journal = {Acta Biomaterialia},
	year = {2017},
	month = {2017-08-30 00:00:00},
	pages = {in press},
	publisher = {Elsevier},
	abstract = {

Heparin sulfate proteoglycans (HSPGs) are responsible for the storage and stabilization of numerous growth factors in the extracellular matrix. In this complex native environment, the efficient binding of the growth factors is determined by multivalent, specific and reversible electrostatic interactions between the sulfate groups of HSPGs and the positively charged amino acids of the growth factor. Inspired by this naturally occurring stabilization process, we propose the use of diblock copolymers of heparin and polyethylene glycol (Hep-b-PEG) for protection and delivery of FGF-2. We describe the encapsulation of FGF-2 into spontaneously assembling polyelectrolyte complexes (PECs) with Hep-b-PEG in which the Hep block ensures the formation of the PECs, while the PEG moiety confers stability of the generated complex by a stealth corona. Our results demonstrate that by this method we can generate homogeneous complexes (ca. 400 nm diameter, PDI 0.29{\textpm}0.07) with a very high encapsulation efficiency (about 99\% encapsulated FGF-2). The release of the growth factor in response to different stimuli such as pH, ionic strength or presence of heparinase was also studied. We report a sustained release of up to 80 \% during 28 days which is not influenced by the presence of heparinase {\textendash} a result that clearly demonstrates the protective effect of the stealth corona. We also show that FGF-2 remains bioactive as it influences the morphology of bone marrow mesenchymal stem cells.

}, keywords = {Delivery system, FGF-2, heparin, Oxime click reaction, Polyelectrolyte complexation}, issn = {1878-7568}, doi = {10.1016/j.actbio.2017.08.042}, url = {http://www.sciencedirect.com/science/article/pii/S1742706117305561}, author = {Silva, C. and Carretero, A. C. and Soares da Costa, D. and Reis, R. L. and Novoa-Carballal, R. and Pashkuleva, I.} }

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