RESUMO
Chitosan is widely used in the preparation of organic-inorganic composite materials, such as n-HAp/CS composites, which find application for bone regeneration. The methods for their preparation are various, and usually based on the preparation of intermediate n-HAp/CS dispersions, which can greatly influence the final properties of the resulting composites since it is expected that homogenous and stable dispersions lead to composite materials with improved final properties. This work hypothesizes that, additionally to process parameters such as pH, n-HAp/CS weight ratio, mixing conditions and the presence of salts, chitosan itself has a high impact on dispersions stability. Thus, the importance of properly control the preparation of the n-HAp/CS intermediate dispersions is highlighted by doing a systematic study where relevant processing parameters were studied at lab scale using ultrasonication, alone or in the presence of chitosan, namely on particle size and zeta potential. Furthermore, and based on the best laboratorial conditions, the production of n-HAp/CS nanocomposite dispersions in continuous mode was attempted through NETmix® technology, an innovative static mixer and reactor developed at the Associate Laboratory LSRE-LCM of the Faculty of Engineering of the University of Porto (FEUP).
RESUMO
Hybrid scaffolds composed of hydroxyapatite (HAp), in particular in its nanometric form (n-HAp), and chitosan (CS) are promising materials for non-load-bearing bone graft applications. The main constraints of their production concern the successful implementation of the final purification/neutralization and sterilization steps. Often, the used purification strategies can compromise scaffold structural features, and conventional sterilization techniques can result in material's thermal degradation and/or contamination with toxic residues. In this context, this work presents a process to produce n-HAp/CS scaffolds mimicking bone composition and structure, where an innovative single step based on supercritical CO2 extraction was used for both purification and sterilization. A removal of 80% of the residual acetic acid was obtained (T = 75°C, p = 8.0 MPa, 2 extraction cycles of 2 h) giving rise to scaffolds exhibiting adequate interconnected porous structure, fast swelling and storage modulus compatible with non-load-bearing applications. Moreover, the obtained scaffolds showed cytocompatibility and osteoconductivity without further need of disinfection/sterilization procedures. Among the main advantages, the proposed process comprises only three steps (n-HAp/CS dispersion preparation; freeze-drying; and supercritical CO2 extraction), and the supercritical CO2 extraction show clear advantages over currently used procedures based on neutralization steps. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 965-975, 2018.
