Preparation of nano-hydroxyapatite/chitosan aqueous dispersions: From lab scale to continuous production using an innovative static mixer.

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).

Supercritical CO2 assisted process for the production of high-purity and sterile nano-hydroxyapatite/chitosan hybrid scaffolds.

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.

Prophylaxis of acute renal failure in patients with rhabdomyolysis.

Patients that develop rhabdomyolysis of different causes are at high risk of acute renal failure. Efforts to minimize this risk include volume repletion, treatment with mannitol, and urinary alkalinization as soon as possible after muscle injury. This is a retrospective analysis (from January 1, 1992, to December 31, 1995) of therapeutic response to prophylactic treatment in patients with rhabdomyolysis admitted to an intensive care unit (ICU). The diagnosis of rhabdomyolysis was based on creatinine kinase (CK) level (> 500 Ui/L) and the criteria for prophylaxis were: time elapsed between muscle injury to ICU admission < 48 h and serum creatinine < 3 mg/dL. Fifteen patients were treated with the association of saline, mannitol, and sodium bicarbonate (S + M + B group) and 9 patients received only saline (S group). Serum creatinine at admission was similar in both groups: 1.6 +/- 0.6 mg/dL in the S + M + B group and 1.5 +/- 0.6 mg/dL in the S group (p > 0.05). Maximum serum CK measured was 3351 +/- 1693 IU/L in the S + M + B group and 1747 +/- 2345 IU/L in the S group (p < 0.05). However the measurement of CK was earlier in S + M + B patients (1.7 vs 2.7 days after rhabdomyolysis). APACHE II scores were 16.9 +/- 7.4 and 13.4 +/- 4.9 in the S + M + MB and S groups, respectively (p > 0.05). Despite the treatment protocol the serum levels of creatinine had similar behavior and reached normal levels in all patients in 2 or 3 days. The saline infusion during the first 60 h on the ICU was 206 mL/h in the S group and 204 mL/h in S + M + B (p > 0.05). Mannitol dose was 56 g/day, and bicarbonate 225 mEq/day during 4.7 days. Our data show that progression to established renal failure can be totally avoided with prophylactic treatment, and that once appropriate saline expansion is provided, the association of mannitol and bicarbonate seems to be unnecessary.