Enzymatic, physicochemical and biological properties of MMP-sensitive alginate hydrogels

last updated: 2014-11-11
TitleEnzymatic, physicochemical and biological properties of MMP-sensitive alginate hydrogels
Publication TypePapers in Scientific Journals
Year of Publication2013
AuthorsFonseca K. B., Maia F. R., Cruz F. A., Andrade D., Juliano M. A., Granja P. L., and Barrias C. C.

Protease-sensitive hydrogels that recapitulate the mechanisms of cell-driven enzymatic remodelling of the natural extracellular matrix (ECM) have been gaining popularity as artificial 3D cell-microenvironments. Here, the matrix metalloproteinase (MMP)-sensitive peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG) was double-end grafted to alginate forming water-soluble PVGLIG–alginate conjugates. The PVGLIG peptide was synthesized as a Fluorescence Resonance Energy Transfer (FRET) sensor and showed to be a good substrate for MMP-2, MMP-9, MMP-13 and MMP-14. After demonstrating that human MSC (hMSC) expressed both MMP-2 and MMP-14 under basal and osteogenic in vitro conditions, the effect of 3D-culture within MMP-sensitive alginate hydrogels on hMSC behaviour was addressed. In situ-forming alginate hydrogels containing only cell-adhesive RGD peptides (RGD–alginate, MMP-insensitive) or both peptides (PVGLIG/RGD–alginate, MMP-sensitive) were used. Cell–matrix and cell–cell interactions were enhanced in hMSC-laden MMP-sensitive alginate hydrogels, as compared to MMP-insensitive hydrogels with identical viscoelastic and microstructural properties. hMSC underwent osteogenic differentiation in both types of matrices. However, the presence of PVGLIG stimulated the secretion of proteases (most likely MMP-2) by hMSC, in both undifferentiated and differentiated cultures. By using the FRET sensor, it was possible to demonstrate that the cocktail of hMSC-secreted MMPs was effectively active in cleaving the PVGLIG motif. Protease-sensitive alginates can be used to create cell-responsive 3D microenvironments and offer promise as injectable carriers for therapeutic hMSC-delivery.

JournalSoft Matter
Date Published2013-01-25
DOI 10.1039/C3SM27560D
Keywordsmesenchymal stem cells, Protease-sensitive hydrogels
Peer reviewedyes

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