rhBMP-2 = recombinant human bone morphogenetic protein 2.
Layer-By-Layer Films as a Biomimetic Reservoir for rhBMP-2 Delivery: Controlled Differentiation of Myoblasts to Osteoblasts†
Article first published online: 13 FEB 2009
Copyright © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Volume 5, Issue 5, pages 598–608, March 6, 2009
How to Cite
Crouzier, T., Ren, K., Nicolas, C., Roy, C. and Picart, C. (2009), Layer-By-Layer Films as a Biomimetic Reservoir for rhBMP-2 Delivery: Controlled Differentiation of Myoblasts to Osteoblasts. Small, 5: 598–608. doi: 10.1002/smll.200800804
- Issue published online: 12 MAR 2009
- Article first published online: 13 FEB 2009
- Manuscript Revised: 28 JUL 2008
- Manuscript Received: 6 JUN 2008
- Association Française contre les Myopathies (AFM). Grant Number: 12671
- Association pour la Recherche sur la Cancer. Grant Number: 7918
- Fondation Recherche Médicale. Grant Number: INE20061108297
- Agence Nationale pour la Recherche. Grant Number: ANR-06-NANO-006
Efficient delivery of growth or survival factors to cells is one of the most important long-term challenges of current cell-based tissue engineering strategies. The extracellular matrix acts as a reservoir for a number of growth factors through interactions with its components. In the matrix, growth factors are protected against circulating proteases and locally concentrated. Thus, the localized and long-lasting delivery of a matrix-bound recombinant human bone morphogenetic protein 2 (rhBMP-2) from a biomaterial surface would mimic in vivo conditions and increase BMP-2 efficiency by limiting its degradation. Herein, it is shown that crosslinked poly(L-lysine)/hyaluronan (HA) layer-by-layer films can serve as a reservoir for rhBMP-2 delivery to myoblasts and induce their differentiation into osteoblasts in a dose-dependent manner. The amount of rhBMP-2 loaded in the films is controlled by varying the deposition conditions and the film thickness. Its local concentration in the film is increased up to ≈500-fold when compared to its initial solution concentration. Its adsorption on the films, as well as its diffusion within the films, is evidenced by microfluorimetry and confocal microscopy observations. A direct interaction of rhBMP-2 with HA is demonstrated by size-exclusion chromatography, which could be at the origin of the rhBMP-2 “trapping” in the film and of its low release from the films. The bioactivity of rhBMP-2-loaded films is due neither to film degradation nor to rhBMP-2 release. The rhBMP-2-containing films are extremely resistant and could sustain three successive culture sequences while remaining bioactive, thus confirming the important and protective effect of rhBMP-2 immobilization. These films may find applications in the local delivery of immobilized growth factors for tissue-engineered constructs and for metallic biomaterial surfaces, as they can be deposited on a wide range of substrates with different shapes, sizes, and composition.