Self-Assembled Microcapsules with Tunable and Sustained Release of Macromolecules for Tissue Engineering

Layer-by-layer (LbL) has been presented as a tool capable of constructing tunable and sustained release reservoirs for therapeutic and proliferation/differentiation agents. We report the conception of biocompatible stimuli-responsive microcapsules fabricated using LbL containing BSA as model protein. The capsules were constructed by the sequential adsorption of chitosan and a temperature-responsive elastin-like recombinamer (ELR) containing RGD into self-assembled layers and onto inorganic CaCO₃ microparticle templates. By increasing the temperature (25–37 ºC), a considerable shrinking was observed (5.5–3.2 micrometers) as well as higher retention of the encapsulated BSA. Such variations were observed for the first time at a relevant physiological temperature, contrary to similar LbL systems requiring temperatures ranging 50–70 ºC. Different number of bilayers allowed tuning further the permeability: more layers resulted in a more effective barrier to the protein diffusion. Cell viability tests using L929 cells also demonstrated the non-cytotoxicity of these structures. The developed nanostructured reservoirs exhibited tunable and sustained permeability by simply varying the temperature and the number of layers. Exploiting both permeability mechanisms, it would be possible to control the release not only of a pharmaceutical in traditional drug delivery applications but also of agents in tissue engineering that influence the proliferation and differentiation of cells.