Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system

AIM： To establish a highly reproducible animal model of acute liver failure （ALF）, for assessing the effect of bioartificial liver support system （BALSS）. METHODS： A two-phase complete liver devascularization procedure was performed in eight Ioco-hybrid pigs. Blood biochemical index and liver biopsy were studied every 2 h after surgery, and survival time was recorded. The BALSS constructed with high volume recirculating technique was a hollow fiber circulating system consisting of a hepatocyte reactor-hollow fiber module inoculated with microcarrieradhering hepatocytes, and a double pump, heparinized, thermostabilized, micro-capsulized activated carbonadsorbing plasmapheresis system. Twelve pigs undergoing two-phase surgery were randomized into： control group （perfused without hepatocytes, n = 6） and treatment group （perfused with hepatocytes, n = 6）. Intergroup liver biochemical indexes, survival time, and liver pathological changes were analyzed at regular intervals. RESULTS： Two-phase surgery was performed in all the experimental pigs, and there was no obvious difference between their biochemical indexes. After 3 h of phase II surgery, ammonia （Amm） increased to （269＋37）μmol/L. After 5 h of the surgery, fibrinogen （Fib） decreased to （1.5±0.2） g/L. After 7 h of the surgery, ALT, AST, Tbil and PT were （7.6±1.8） nka/L, （40±5） nka/L, （55±8）μmol/L and （17.5±1.7） nka/L respectively. After 9 h of surgery, ALB and Cr were （27±4） g/L and （87±9）μmol/L. After 13 h of surgery, BUN was （3.5±0.9） μmol/L. All the above values were different from those determined before surgery. Survival time of pigs averaged 13.5±1.4 h. ALF pigs in the other group were treated with BALSS. The comparison analysis between the treated and control animals showed the changes of Tbil, PT, AIb, BUN, Cr, Fib, and Amm （P〈0.01）, but there was no change of ALT and AST. The survival time was statistically different （P〈0.01）, and there was no significant difference in histological changes.CONCLUSION： The porcine ALF model established by two-phase devascularized surgery is valid and reproducible. The hollow fiber BALSS can meet the needs of life support and is effective in treating ALF.

Synthesis of crystals and particles by crystallization and polymerization in droplet-based microfluidic devices

The recent advances in crystallization and polymerization assisted by droplet-based microfluidics to synthesize micro-particles and micro-crystals are reviewed in this paper.Droplet-based microfluidic devices are powerful tools to execute some precise controls and operations on the flow inside microchannels by adjusting fluid dynamics parameters to produce monodisperse emulsions or multiple-emulsions of various materials.Major features of this technique are producing particles of monodispersity to control the shape of particles in a new level,and to generate droplets of diverse materials including aqueous solutions,gels and polymers.Numerous microfluidic devices have been employed to generate monodisperse droplets of range from nm toμm,such as T junctions,flow-focusing devices and co-flow or cross-flow capillaries.These discrete,independently controllable droplets are ideal microreactors to be manipulated in the channels to synthesize the nanocrystals,protein crystals,polymer particles and microcapsules.The generated monodisperse particles or crystals are to meet different technical demands in many fields,such as crystal engineering,encapsulation and drug delivery systems.Microfluidic devices are promising tools in the synthesis of micron polymer particles that have diverse applications such as the photonic materials,ion-exchange and chromatography columns,and field-responsive rheological fluids.Processes assisted by microfluidic devices are able to produce the polymer particles(including Janus particles)with precise control over their sizes,size distribution,morphology and compositions.The technology of microfluidics has also been employed to generate core-shell microcapsules and solid microgels with precise controlled sizes and inner structures.The chosen“smart”materials are sensitive to an external stimulus such as the change of the pH,electric field and temperature.These complex particles are also able to be functionalized by encapsulating nanoparticles of special functions and by attaching some special groups like targeting ligands.The nucleation kinetics of some crystals like KNO_(3)was investigated in different microfluidic devices.Because of the elimination of the interactions among crystallites in bulk systems,using independent droplets may help to measure the nucleation rate more accurately.In structural biology,the droplets produced in microfluidic devices provide ideal platforms for protein crystallization on the nanoliter scale.Therefore,they become one of the promising tools to screen the optimal conditions of protein crystallization.