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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Keila B. Fonseca (Author) Other; F. Raquel Maia (Author) Other; Filipe A. Cruz (Author) FEUP; Douglas Andrade (Author) Other; Maria A. Juliano (Author) Other; Pedro L. Granja (Author) FEUP; Cristina C. Barrias (Author) Other

Journal

Title: Soft Matter

Vol. 9 No. 12

Pages: 3283-3292

ISSN: 1744-683X

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 12 Citations

Scientific classification

CORDIS: Technological sciences > Engineering > Biomedical enginnering

FOS: Engineering and technology > Materials engineering

Other information

Authenticus ID: P-002-1G8

DOI: 10.1039/c3sm27560d

Abstract (EN): 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 creat(e) cell-responsive 3D microenvironments and offer promise as injectable carriers for therapeutic hMSC-delivery.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10