@article {17703, title = {Extrapolation of hybrid polysaccharide and recombinant polypeptide multilayer films towards three-dimensional compartmentalization}, booktitle = {Term Stem 2013}, volume = {7}, year = {2013}, month = {2013-09-30 00:00:00}, pages = {16}, publisher = {John Wiley \& Sons, Ltd.}, organization = {John Wiley \& Sons, Ltd.}, address = {Porto, Portugal}, abstract = {

Layer-by-layer (LbL) is a mild and versatile surface modification technique that allows producing robust coatings even in substrates with complex geometries. Taking advantage of the 3D possibilities opened by LbL, we present customized compartmentalized capsules inspired by the complex structure of cells, with temperature and magnetic-based responsiveness, and hierarchical organization from the nano- to the visible scales. These capsules consisted in liquefied alginate macroscopic beads coated with a chitosan/alginate shell confining molecular compounds and microcapsules, with the latter encapsulating further either more molecular compounds or magnetic nanoparticles (MNPs).

The microcapsules were constructed resorting to LbL, assembling chitosan and temperature-responsive elastin-like recombinamers (ELR) around calcium carbonate particles. The appropriate LbL assembly conditions of these ingredients were screened resorting to quartz-crystal microbalance. The multilayer build-up of chitosan and one of nine ELRs differing in aminoacid content, length and biofunctionality was followed in situ at pH 4.0 and 5.5, accounting for 18 combinatorial conditions. Their thicknesses were estimated using the Voigt model, revealing that thicker films were obtained in the presence of hydrophobic interactions between ELRs and partially neutralized chitosan[1]. From these results, the microcapsules were constructed with chitosan and a RGD-containing ELR at pH 5.5. Release studies at 25 and 37 {\textdegree}C with BSA demonstrated that the microcapsules are less permeable at physiological temperature, providing a sustained release over 14 days. The microcapsules were also noncytotoxic towards L929 cells[2]. The microcapsules could also be loaded with MNPs, which react towards external magnetic fields.

Finally, the compartmentalized liquefied macrocapsule was constructed bearing the microcapsules and rhodamine for quick assessment of the multilayer coatings{\textquoteright} permeability. For 25 {\textordmasculine}C and 37 {\textordmasculine}C, rhodamine encapsulated within the inner microcapsules showed sustained release, with the diffusion kinetics being even lower at physiological temperature. Rhodamine encapsulated in the outer alginate compartment did not show significant difference between each temperature. The devices were robust and could withstand handling and centrifugal stress. MNPs loaded within the microcapsules were able to render the whole compartmentalized device magnetic responsive[3]. Such customizable system can be envisaged to transport bioactive agents and cells in tissue engineering applications and construct disease and microtissue production models.

[1] Costa RR, Testera AM, Arias FJ, Rodr{\'\i}guez-Cabello JC, Mano JF, J Phys Chem B 2013, 117, 6839.

[2] Costa RR, Cust{\'o}dio CA, Arias FJ, Rodr{\'\i}guez-Cabello JC, Mano JF, Nanomedicine: NBM, in press.

[3] Costa RR, Castro E, Arias FJ, Rodr{\'\i}guez-Cabello JC, Mano JF, Biomacromolecules 2013, 14, 2403.

}, keywords = {Compartments, Hierarchical organization, magnetic properties, Multilayers, Polymers}, doi = {10.1002/term.1822}, url = {http://onlinelibrary.wiley.com/doi/10.1002/term.2013.7.issue-s1/issuetoc}, author = {Costa, R. R. and Castro-Otero, E. and Cust{\'o}dio, C. A. and Testera, A. M. and Arias, F. J. and Rodr{\'\i}guez-Cabello, J. C. and Mano, J. F.} }