@article {18181, title = {Enzymatic, physicochemical and biological properties of MMP-sensitive alginate hydrogels}, journal = {Soft Matter }, volume = {9}, year = {2013}, month = {2013-01-25 00:00:00}, pages = {3283-3292}, abstract = {

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{\textendash}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{\textendash}alginate, MMP-insensitive) or both peptides (PVGLIG/RGD{\textendash}alginate, MMP-sensitive) were used. Cell{\textendash}matrix and cell{\textendash}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.

}, keywords = {mesenchymal stem cells, Protease-sensitive hydrogels}, doi = { 10.1039/C3SM27560D }, url = {http://pubs.rsc.org/en/content/articlelanding/2013/SM/c3sm27560d$\#$!divAbstract}, author = {Fonseca, K. B. and Maia, F. R. and Cruz, F. A. and Andrade, D. and Juliano, M. A. and Granja, P. L. and Barrias, C. C.} }