Biomaterials, Biodegradables and Biomimetics Research Group

Papers in Scientific Journals

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

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–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.

Journal
Soft Matter
Volume
9
Pagination
3283-3292
URL
http://pubs.rsc.org/en/content/articlelanding/2013/SM/c3sm27560d#!divAbstract
Keywords
mesenchymal stem cells, Protease-sensitive hydrogels
Rights
Open Access
Peer Reviewed
Yes
Status
published
This website uses cookies. By using this website you consent to our use of these cookies. For more information visit our Policy Page.