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Biomaterials. 2014 May;35(15):4525-4535. doi: 10.1016/j.biomaterials.2014.02.008. Epub 2014 Mar 5.

The effect of delivering the chemokine SDF-1α in a matrix-bound manner on myogenesis.

Author information

1
CNRS UMR 5628 (LMGP), 3 parvis Louis Néel, 38016 Grenoble, France.
2
Université Grenoble Alpes, LMGP, 3 parvis Louis Néel, 38016 Grenoble, France.
3
FONDATION ARC, 9 rue Guy Môquet 94803 Villejuif, France.
4
Univ. Grenoble Alpes, Institut de Biologie Structurale (IBS), F-38027 Grenoble, France.
5
CNRS, IBS, F-38027 Grenoble, France.
6
CEA, DSV, IBS, F-38027 Grenoble, France.
7
Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052 - CNRS 5286, 28, rue Laennec, 69373 LYON cedex 08, France.
8
Inserm U823, ERL CNRS5284, Université Joseph Fourier, Institut Albert Bonniot, Site Santé, BP170, 38042 Grenoble cedex 9, France.
#
Contributed equally

Abstract

Several chemokines are important in muscle myogenesis and in the recruitment of muscle precursors during muscle regeneration. Among these, the SDF-1α chemokine (CXCL12) is a potent chemoattractant known to be involved in muscle repair. SDF-1α was loaded in polyelectrolyte multilayer films made of poly(L-lysine) and hyaluronan to be delivered locally to myoblast cells in a matrix-bound manner. The adsorbed amounts of SDF-1α were tuned over a large range from 100 ng/cm(2) to 5 μg/cm(2), depending on the initial concentration of SDF-1α in solution, its pH, and on the film crosslinking extent. Matrix-bound SDF-1α induced a striking increase in myoblast spreading, which was revealed when it was delivered from weakly crosslinked films. It also significantly enhanced cell migration in a dose-dependent manner, which again depended on its presentation by the biopolymeric film. The low-crosslinked film was the most efficient in boosting cell migration. Furthermore, matrix-bound SDF-1α also increased the expression of myogenic markers but the fusion index decreased in a dose-dependent manner with the adsorbed amount of SDF-1α. At high adsorbed amounts of SDF-1α, a large number of Troponin T-positive cells had only one nucleus. Overall, this work reveals the importance of the presentation mode of SDF-1α to emphasize its effect on myogenic processes. These films may be further used to provide insight into the role of SDF-1α presented by a biomaterial in physiological or pathological processes.

KEYWORDS:

CXCR4; Drug delivery; Migration; Myoblast; Polyelectrolyte multilayer film; SDF-1α/CXCL12

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