Supercritical CO2 generating chitosan devices with controlled morphology. Potential application for drug delivery and mesenchymal stem cell culture

In this work, a novel approach involving supercritical carbon dioxide (scCO(2)) induced phase inversion technique was developed to produce chitosan devices using moderate temperatures and three very environmentally acceptable solvents (water, ethanol and CO2). The morphology and three-dimensional (3D) structure were controlled by altering the co-solvent (ethanol) composition in the carbon dioxide non-solvent stream during the demixing induced process. Microarchitectural analysis by scanning electron microscopy identified the production of particulate agglomerates when 10% of ethanol in the scCO(2) stream was used and the ability to make porous membranes with different morphologies and mechanical properties depending on the programmed gradient mode and the entrainer percentage (2.5-5%) added to the scCO2 stream. These structures were characterized in terms of pure water flux, porosity, mechanical properties and biodegradability. These chitosan matrices exhibited low solubility at neutral pH conditions, with no further modifications. We also demonstrated that the current method allows for a single-step preparation of an implantable antibiotic release system by co-dissolving gentamicin with chitosan and the solvent. Finally, the cytotoxicity, as well as the ability of these structures to support the adhesion and proliferation of human mesenchymal stem cells (MSC) in vitro were also addressed. The studies described may provide a starting point for the "green" design and production of chitosan-based materials with potential applications in tissue engineering and regenerative medicine, as well as drug delivery. (C) 2008 Elsevier B.V. All rights reserved.