Molecularly designed alginate hydrogels susceptible to local proteolysis as three-dimensional cellular microenvironments

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Keila B Fonseca (Author) Other; Silvia J Bidarra (Author) Other; Maria J Oliveira (Author) FEUP; Pedro L Granja (Author) FEUP; Cristina C Barrias (Author) Other

Journal

Title: Acta Biomaterialia

Vol. 7

Pages: 1674-1682

ISSN: 1742-7061

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 84 Citations

Scopus - 43 Citations

Scientific classification

FOS: Engineering and technology > Environmental biotechnology

Other information

Authenticus ID: P-002-STQ

DOI: 10.1016/j.actbio.2010.12.029

Abstract (EN): The development of sophisticated three-dimensional (3-D) cell culture microenvironments that recreate some of the complexity of the natural extracellular matrix (ECM) remains a challenging task. Here, the modification of alginate through partial crosslinking with a matrix metalloproteinase (MMP) cleavable peptide (proline-valine-glycine-leucine-isoleucine-glycine, PVGLIG) is described, and its use in the preparation of injectable, in situ crosslinkable hydrogel-like matrices is proposed. PVGLIG-grafted alginates were synthesized by carbodiimide chemistry and characterized. Their biological performance was evaluated by comparing the response of 3-D cultured mesenchymal stem cells (MSCs) to alginate hydrogels containing only cell-adhesion peptides (RGD-alginate) or both peptides (PVGLIG/RGD-alginate). After 1 week, cells remained essentially round within RGD-alginate, while they exhibited an elongated morphology within PVGLIG/RGD-alginate hydrogels, forming cellular networks. This suggests that cells were able to structurally reorganize the matrix, through enzymatic hydrolysis of PVGLIG residues, overcoming biophysical hydrogel resistance. As shown by gelatine-zymography, MSC presented higher activity of MMP-2 when cultured within alginate functionalized with MMP-sensitive peptide, suggesting that the cell's proteolytic phenotype was modulated by the matrix composition. Additionally, PVGLIG/RGD-alginate hydrogels were clearly degraded in cell culture. Taken together, the results demonstrate that the co-incorporation of MMP-labile peptides in cell-adhesive RGD-alginate hydrogels improved their performance as ECM analogues, providing a more dynamic and physiological 3-D cellular microenvironment.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9