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Unformatted text preview: onal derivatives, namely through the
incorporation of cell-signalling moieties.
INEB – Instituto de Engenharia Biom´dica, Universidade do Porto, Rua do Campo
Alegre 823, 4150-180 Porto, Portugal. E-mail: firstname.lastname@example.org; Fax: +351226094567; Tel: +351-226074982 a b
Departamento de Engenharia Metalurgica e Materiais, Faculdade de Engenharia da
Universidade do Porto (FEUP), Porto, Portugal
Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de Sao
Paulo, Rua Trˆs de Maio 100, 04044-020 Sao Paulo, Brazil
Instituto de Ciˆncias Biom´dicas Abel Salazar (ICBAS), Universidade do Porto, Porto,
Portugal This journal is ª The Royal Society of Chemistry 2013 3D The incorporation of ECM-like peptides on the polymer
backbone is among the strategies most used to promote cell
interactions with hydrogels.10,11 Since the rst modication of
alginate with tethered motifs containing the cell-adhesive
peptide sequence Arg-Gly-Asp (RGD),12 several authors explored
the behaviour of various cell types cultured on or within RGDalginate hydrogels, in vitro and in vivo.5,13–15 The co-incorporation of proteolytically cleavable peptides into hydrogels to
promote cell-mediated degradation, a strategy originally
proposed for the modication of PEG,16 may empower the
future applications of alginate matrices as biomaterials.
Recently, we reported the functionalization of alginate with the
peptide sequence GGYGPVGYLIGGK, which contains a matrix
metalloproteinase (MMP)-sensitive substrate (underlined; the
arrow represents the cleavage site).17 The designed sequence
bears a free amine at each end, the terminal a-amino and Lys 3amino groups, providing two reactive sites for the carbodiimide
peptide graing into alginate carboxyl groups.17 This doubleend graing strategy was intended to aﬀord a low degree of
PVGLIG-mediated crosslinking of the polymer chains, which
thus remained water-soluble and could still be converted into
hydrogels using an in situ ionic crosslinking approach as
envisaged. This crosslinking process is reversible upon addition
of a chelating agent, allowing cell recovery without the need for Soft Matter, 2013, 9, 3283–3292 | 3283 View Article Online Downloaded by State University of New York at Buffalo on 16/04/2013 03:56:51.
Published on 08 February 2013 on http://pubs.rsc.org | doi:10.1039/C3SM27560D Soft Matter
any mechanical or enzymatic treatments, which represents an
additional advantage of these hydrogels as 3D culture matrices.
The PVGLIG motif, originally deduced from a combinatorial
peptide library of MMP–substrates,18 was rst proposed by Chau
et al. as a labile linker for MMP-activated delivery of chemotherapeutics,19 and later on used to functionalize self-assembling peptide hydrogels.20 It was shown to be cleavable by
MMP-2 and MMP-9, but no other MMPs were tested.19 Since
MMPs generally share many common features in their
consensus cleavage motifs,18 a more detailed analysis of
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- Spring '13