Synthesis And Modification Of Biodegradable Polyurethane Elastomer And Their Application In Vascular Tissue Regeneration

Coronary arteriosclerotic heart disease and peripheral vascular disease have become the serious burdens of human.According to the statistics,there are more than ten million blood vessel transplants in the world every year.Autologous and allogeneic vascular grafts cannot meet so many vascular substitute requirements.On other hand,several large-diameter vascular grafts such as polyester?PET?and expanded polytetrafluoroethylene?ePTFE?have been have been used in clinical surgery successfully.However,the transplantation of PET and ePTFE artificial blood vessels with a diameter of 6 mm are always failing.The main reasons are the poor hemocompatibility and biocompatibility of the material,the change of fluid mechanics at the implant site,the change of the local microenvironment after the blood vessel transplantation,and other procoagulant factors may the main reasons of transplantation failure.In order to solve the above problems,the method of preparing biologically active small-dimater scaffolds via tissue engineering came into being.a series of tissue engineering vascular scaffolds?TEVS?have been developed and mainly focused on small-diameter vascular reconstruction,including cell-sheet,decellularized-matrix and biodegradable natural or synthetic-guided?cell seeded or recruited in-situ?grafts.Among them,biodegradable synthetic polymers scaffolds with a wide range of raw material sources,available off-the-shelf,and possess broad affordability and availability are attractive for the future clinic-scale applications.Elastic biodegradable polyurethanes?EBPUs?are considered as promising base materials for the fabrication of vascular.However,thrombosis and intimal hyperplasia also are the major reasons,which leading to the failures of EBPUs vascular scaffolds in surgical implantation.Thus,the reliable anticoagulant surface surface treatment before surgical implantation are crucial.Based on the above,the purpose of our research is to develop a new biodegradable polyurethane elastomer.A three-dimensional structure-controlled tubular scaffold were designed and modified via electrospinning and thermal induced phase seperation?TIPS?to improve the blood compatibility,biocompatibility and mechanical matching.After then,the functionalized scaffolds were implanted into the carotid artery defect site of rabbits.The main work and conclusions were listed as following:1.C-PEUU?HDI?,C-PEUU?LDI?,C-PEEUU?HDI?and C-PEEUU?LDI?polymer elastomers were synthesized and processed with electrospinning.The results show that the biodegradable polyurethane based on the synthetic monomer of HDI,LDI or PEG600 exhibited different crystallization properties,thermal properties,mechanical and degradation properties.The presence of PEG600 in the soft segment of EBPUs reduce the values of stress and strain significantly.And it is still meet the requirements of blood vessel transplantation.On the other hand,PEG600 in of C-PEUU nanofibrous membranes improved the degradation rate from 18%to 70%at 24 weeks.2.C-PEUU-NH₂ polymer elastomer were synthesized via the two-stage solution polymerization.Ac-GRGD was successfully grafted C-PEUU-NH₂ nanofibers.The hydrophilicity of C-PEUU-RGD nanofibrous membranes have no significantly improving compared with C-PEUU nanofibrous membrane.From the results of compatibility with endothelial cells and in vitro platelet adhesion experiments,the grafted RGD on the surfaces of C-PEUU nanofibrous membranes have promoted the expression of HUVECs cells and improved the blood compatibility of C-PEUU nanofibers.The morphology of C-PEUU-RGD nanofibers haven't significantly change compared with C-PEUU nanofibesa during the chemical grafting process.The mechanical resistance of C-PEUU-RGD nanofibrous membranes did not change significantly compared with C-PEUU nanofibrous membranes.The biological experiments in vitro revealed that the C-PEUU-RGD nanofiber membrane is the propential intima of small-diameter artificial blood vessels,which will improve rapid endothelialization and promote long-term patency of vascular scaffolds.3.The prepared nanofibrous tubular scaffolds were subjected to amine hydrolysis and hydrolytic attack on the surface of the fiber through 1,6-hexamethylenediamine aqueous solution and NaOH aqueous solution,respectively.The active amino and carboxyl groups were successfully introduced onto the surfaces of C-PEUU nanofiber.The quantitative calculation and analysis of the active amine and carboxyl groups on the surface of C-PEUU nanofibers after amine hydrolysis and hydrolysis were via chemical adsorption with acid orange II and toluidine blue.1,6-hexamethylenediamine were dissolved in water and then carried out aminolysis on a nanofibrous tubular scaffolds.The degree of amine hydrolysis can be controlled during aminolysis reaction.However,the degree of hydrolysis of the surface of the nanofibrous scaffold through the NaOH aqueous solution are hard work.After these,heparin and PEG_2k molecules were grafted onto C-PEUU-NH₂ nanofibrous tubular scaffolds via amidation.The prepared C-PEUU-PEG_2k-Hep nanofibrous tubuar scaffold not only possesses suitable mechanical properties,but also improves greatly the ability of scaffold to resist platelet adhesion.4.The C-PEEUU three-dimensional porous scaffolds were prepared via TIPS technology.C-PEEUU?50:50?dissolved in DMSO with the rate of 4%exhibit a good gel state.After solvent exchange-freeze-drying process,the pore structure can be obtained and the pore size about 200²50?m.And the prepared scaffolds are suitable for the regeneration of soft tissue.The hybrid bilayered scaffold with with 2 mm inner diameter and 0.4 mm wall thickness was constructed and implant in the artery of the small animal.Compared and analyzed the compatibility of tisue between the C-PEUU-PEG_2k-Hep/RGD nanofibrous tubular scaffold and the C-PEEUU?50:50?TIPS tubular scaffold during tissue transplantation in animal experiments.The results shown that the prepared hybrid bilayered scaffold possessed a good material-tissue compatibility and mechanical compatibility and its patency rate after 4 weeks of transplantation was 50%.