Fabrication Of Functional Liver-on-a-chip As Drug Evaluation Systerm

Organ-on-a-chip systerm is a kind of new biomedical research methods using for drug evaluation and disease model which have been proposed in recent years.It can be used to simulate the microstructure,microenvironment,and functional features of human organ,and potential to apply in drug screening and clinical diagnosis and treatment.What is more,it is also need to establish a safe and effective drug intervention and evaluation measures to timely carry out the on-orbit disease treatment and ensure the successful completion of space mission for astronaut in manned space mission.Therefore,it is of great scientific significance to do research on drug metabolism in space flight.The liver is the most important detoxification organs,and one of the main organs of drug conversion and metabolism,building physiological and pathological liver on a chip with the simulation of organ structure and function will provide a good platform for biomedical research.The research content of this paper is concentred on developing liver on a chip for physiological and pathological models.Specific work is as follows:(1)Microvessel liver on a chip which is effectively simulating the complex physiological microstructure and microenvironment of hepatic lobule based on cellular aggregates is succesfully designed and constructed.It contains an inverse opal porous membrane mimicing vascular endothelial barrier properties,which divides the chip into the upper chamber as bionic microvessel area and lower chamber as hepatocytes aggregates and multicellular partition co-culture area.Liver on a chip contains delicate microstructures for capturing and localized culturing primary hepatocytes aggregates and maintains their functional activity such as albumin secretion and urea synthesis,and online evaluates the toxic effects of model drugs such as exposed to acetaminophen.(2)Space-orientated drawer-type three-dimensional(3D)vascularized tissue culture chip is succesfully designed and constructed.It is also benefiting the succesfully fabrication of 3D vascularized liver tissue culture chip and development of online drug evaluation method.The prepared hollow fibers and formed 3D vascularized tissue through coaxial needle are orderly arranged on the arm-type cantilever and promote the maintenance of activity and function of primary hepatocytes.The novel design of drawer-type chip can achieve the easily and successfully fixed and assembly between 3D vascularized liver tissue and chip,and be used for on-line assessment of drug toxicity to liver,it can also meet the special requirements in complex environment to reduce and avoid manual manipulationn in space.(3)3D vascularied liver tumor invasion model chip is succesfully designed and constructed,the spherical or ellipsoidal aggregates formed in 3D vascularied tissue gradually grow and form invasion site,and penetrate the binding of gel matrix,and eventually rlease circulating hepatocellular carcinoma cells.Preparing 3D tissue built-in hollow channels is firstly carried out by 3D printing scaffold for arranging glass tube as a sacrificial template;another merhod is handwriting with hollow fiber laden with cells fabricated by microfluidic technology to construct 3D scaffold and vascularied tissue.Spherical or ellipsoidal cell aggregates and their invasion sites are formed in 3D vascularied tissue,hepatoma carcinoma cell break through the matrix and escape from loose tumor tissue and form metastases in circulating tumor cells into vascular channels,and expected to capture in the microcarriers detection pool.At the same time,the antitumor activity of doxorubicin hydrochloride was also evaluated,which proved that the chip can simulate the tumor invasion model in 3D tissue and be used for drug evaluation.(4)Intergrating photonic crystal encoded microspheres within the organ-on-a-chip systerm can simultaneously capture,detect,and release multiple types of circulating tumor cells and be expected to applicate for multiple bioassay and detection.The surface of the barcode particles with their physical structure color was slightly etched to form a patterned surface topography,and decorated with highly branched dendrimer-amplified aptamer probes.Specific combining ability between different DNA aptamers and releated cell surface receptors are benefiting the actived capture,release and separation of circulating tumor cells.