Preparation And Properties Of Polyhydroxyethylmethacrylate Cryogel For Hemoperfusion

Blood purification technique is to reduce some symptoms,treatment of a disease or by reducing the harmful to the body in the blood concentration of substances,thus reducing the harmful material for the purpose of the body damage degree,among them,the blood perfusion technique is an important part of blood purification technology,because its can remove,macromolecule toxins and gradually become a mainstream in clinical treatment.The core of hemoperfusion technology is hemoperfusion materials.Currently,common hemoperfusion materials include activated carbon materials,polysaccharide materials and resin materials,among which activated carbon materials are easy to fall off and have poor selective adsorption,while polysaccharide materials have poor mechanical strength and certain toxicity after modification.Resin materials are widely used in clinical treatment because of their good stability and easy modification.Common resin hemoperfusion devices include HA280 resin perfusion device,HA230 resin perfusion device and HA130 resin perfusion device.However,resin materials are adsorbent by molecular sieve action or charge attraction between molecular groups.There are some problems such as poor adsorption specificity and low mass transfer rate.In view of the above problems,based on the concept and ideas of precise blood purification,this paper prepared polyhydroxyethyl methacrylate(PHEMA)cryogel by freezing polymerization using hydroxyethyl methacrylate as the polymerization monomer.By accurately regulating the macroporous structure and other physical parameters of cryogel,blood compatibility and surface active group density were improved.cryogel substrate was designed and prepared,and the longitudinal flow was changed to tangential flow to solve the mechanical performance problem under high flow rate,and at the same time,the contact area between blood and perfusion material was increased,and the adsorption efficiency was improved.The recombinant protein A was immobilized on the surface of cryogel by epoxy activation to simulate its adsorption effect on human immunoglobulin and improve the adsorption specificity.The details are as follows:(1)Preparation,characterization and pore size control of PHEMA cryogel.Using hydroxyethyl methacrylate as polymeric monomer and N,N’-methylene bisacrylamide as crosslinking agent,PHEMA cryogel was prepared,the influence of concentration of polymeric monomer and crosslinking agent on pore size distribution,porosity and swelling ratio of PHEMA cryogel was studied.The results showed that the concentration of polymeric monomer was negatively correlated with the porosity and swelling ratio of PHEMA cryogel.The concentration of crosslinker was positively correlated with the porosity and swelling ratio of PHEMA cryogel at first and then negatively correlated.The pore sizes of cryogels with 7%,9%and 11%monomer concentration are 80-180μm,50-130μm and 40-120μm.Accurate control of pore size distribution of PHEMA cryogel is of great significance to control the stability of pore structure and avoid hemolysis.(2)Preparation and performance optimization of PHEMA cryogel substrate.With polydimethylsiloxane(PDMS)as the substrate material,it is modified by plasma oxidation,silane coupling agent and surfactant.PHEMA hydrogel adhesive layer was prepared by means of photoinitiation,and PHEMA cryogel functional layer was prepared according to the principle of polymer molecular chain interpenetration.The adhesion force between layers and tangential mechanical properties were optimized,and the swelling characteristics,water loss characteristics and stability of the optimized target were evaluated.The results showed that the surface adhesion between the silanized PDMS was the strongest with the surface bonding energy of 40.56J/m~2and the maximum unit load of 64.21 N/m after the pretreatment of dibenzophenone and the application of 25%PHEMA hydrogel as the adhesive layer.The elastic limit of 25%PHEMA hydrogel adhesive layer is 45.16kpa,the maximum elastic shape variable is 7.55%,and young’s modulus is 0.598Mpa.The elastic limit of the functional layer of 9%HEMA-2%MBAAm cryogel is 15.16kpa and Young’s modulus is 0.204Mpa.Good mechanical properties ensure the stable use of PHEMA cryogel substrate.(3)Construction and simulated adsorption of hemoperfusion cryogel device.The recombinant protein A was immobilized on the surface of cryogel by epoxy activation to simulate its adsorption effect on human immunoglobulin,and the relationship between fluid flow rate and tube pressure was analyzed.The results showed that the protein A load of epoxy activated cryogel was 6.41mg/g±0.09mg cryogel,the flow rate of tangential flow cryogel was127.4 m L/min,and the pressure in the channel was lower than 6.5kpa.The Ig G adsorption capacity of recombinant protein A substrate was 1.37mg/g,and the adsorption efficiency was21.40%.Subsequently,the adsorption capacity can be increased by enlarging production,and the adsorption efficiency can also be improved by optimizing adsorption conditions.