Development And Study Of Hemoadsorbents Based On Novel Porous Materials

Currently,hemoperfusion based on adsorption is an important therapy for the treatment of hepatic diseases.However,the adsorption-based removal performance of traditional activated carbon and resin-based hemoadsorbents towards toxins is still un-satisfactory.Herein,based on metal-organic frameworks（MOFs）,porous organic pol-ymers（POPs）,and covalent organic frameworks（COFs）materials,a series of novel hemoadsorbents with high efficiency were developed and studied.The potential of MIL-101（Cr）applied in hemoperfusion to remove bilirubin（a represent toxin of hepatic diseases）was firstly studied.The results showed that MIL-101（Cr）could efficiently adsorb and remove bilirubin,however,its hemocompatibility was poor.Therefore,MIL-101（Cr）protected by zwitterionic poly-carboxybetaine（PCB）hydrogel coating,namely PCB-MIL101,was developed,and its hemocompatibility was significantly improved.Bilirubin uptake of PCB-MIL101 was～30 times and～5 times that of activated carbon(adsorption capacity of～0.76 mg g^-1)and resin(adsorption capacity of～4.59 mg g^-1),respectively.In addition,the potential of PCN-333 and MOF-808 applied in hemoperfusion was also studied,and the results showed that they possessed excellent hemocompatibility and highly efficient adsorption performance to-wards bilirubin.Especially,PCN-333 performed a fast adsorption（saturation within 5mins）and an ultra-high maximum adsorption capacity(～1004 mg g^-1).In 100%fetal bovine serum（FBS）,bilirubin uptake（or adsorption speed）of PCN-333 was～69 times and～11 times（or～4 times and～2 times）that of activated carbon and resin,respec-tively.The reusability of adsorbents can save the cost.However,the strong alkali envi-ronment that bilirubin desorption required can destroy the coordination structures of MIL-101（Cr）,PCN-333 and MOF-808.Therefore,based on“monomer copolymeriza-tion”strategy,strong covalent bond-linked zwitterionic POPs were prepared through ono-step reaction of free radical polymerization and solvothermal method.The results showed that POP-CB-40%exhibited excellent hemocompatibility and reusability.Bilirubin uptake of POP-CB-40%in 100%FBS was～37 times and～6 times that of activated carbon and resin,respectively.Next,to further improve adsorption perfor-mance,the potential of crystalline COFs with internal ordering applied in hemoperfu-sion was studied,and the results showed that all of 2D and 3D COFs owned good he-mocompatibility and most of them exhibited highly efficient adsorption performance towards bilirubin.Among these COFs,bilirubin uptake of 3D COF_TFPA-ETTA in 100%FBS was～107 times and～18 times that of activated carbon and resin,respectively.Also,3D COF_TFPA-ETTA showed a decent reusability.Most importantly,the clinically simulated hemoperfusion experiment indicated that 3D COF_TFPA-ETTA adsorption col-umn could achieve a very high bilirubin removal efficiency up to～98%.These studies provided some new strategies for the development of novel hemoadsorbents with high efficiency,and bridged the gaps between novel porous materials and hemoperfusion therapy.