Preparation And Functional Studies Of Degradable Polyurethane For Biomedical Application

Polyurethane(PU)is widely used as medical materials due to its excellent mechanical properties and certain biocompatibility.However,when PU is used as an implant material or blood contact material,the adverse reactions were still occured such as decreased mechanical properties,inflammation,and even thrombosis.Therefore,improving the biocompatibility and preparing multifunctional medical biodegradable of PU which can resist bacteria and repair itself has become a research difficulty and hotspot in this field.In this thesis,with polyester/polyether glycol as a soft segment and annular aliphatic diisocyanate as a hard segment,two novel multifunctional biodegradable medical PU materials with high biocompatibility,antibacterial and self-healing properties were prepared by introducing biomimetic phosphorylcholine compounds,natural antibacterial substances and disulfide-containing compounds.The functionality of these two PU materials have been studied to verify application in the field of long-term implant materials,providing ideas and research basis for the design and preparation of such materials.The main research content is divided into the following two parts:Ⅰ.Preparation and functional study of medical polyurethane modified by phosphorylcholine and quercetin:First,2-methacryloyloxyethyl phosphorylcholine glycol(MPC-diol)was synthesized by“click”reaction.Then,gather(ε-Polycondensation of caprolactone)-diol,MPC-diol and excessive isophorone diisocyanate(IPDI)were prepared prepolymer with-NCO terminated.A series of QR modified polyurethanes(PEU-MQ)which containing phosphorylcholine(PC)in the side chain were prepared by extending the chain of natural flavonoid compound-quercetin(QR).Finally,the corresponding membrane materials were obtained by solvent casting.The structures of MPC-diol and PEU-MQ membrane material were characterized by NMR,FT-IR,XPS,etc.The effects of the content of MPC-diol and QR on the thermal properties,mechanical properties,surface hydrophilicity,swelling,degradation,and water vapor permeability of PEU-MQ membranes were studied in detail.PEU-MQ membrane material has low glass transition temperature(T_g),crystallinity and high thermal decomposition temperature.The hydrophilicity and swelling ratio of the surface increased with the increase of MPC-diol content in the material,and the water contact angle of the surface decreased rapidly with the increase of time,indicating that the hydrophilic group PC at the end of the side chain would enrich to the surface in the water environment,with a high utilization rate;The introduction of QR increased the density of hydrogen bonds,endowed the materials with a compact three-dimensional network structure.PEU-MQ showed excellent mechanical properties(Breaking strength: 11.6~61.2 MPa;Elongation at break: 815.3~539.3%;Segment fracture toughness: 37.5~118.9 MJ/m3)and slow degradation rate(60 days in vitro simulation,degradation weight loss < 5%).The antibacterial ability of PEU-MQ was tested by the inhibition zone method,the results showed the diameter of the inhibition zone against E.coil and S.aureus reached 16.0 mm and 18.0 mm,respectively,indicating that the membrane material exhibited good broad-spectrum antibacterial activity.The result of anti-protein adsorption and platelet adhesion tests showed that this material had high anti-protein adsorption and platelet adhesion capabilities,which mean excellent blood compatibility;The result of MTT assay showed that the cell survival rate of this material was higher than 75%,which proved thst it had good cell compatibility.Overall,PEU-MQ material had outstanding mechanical properties,slow degradation rate,good antibacterial activity,excellent blood compatibility and cell compatibility,and showed potential applications in long-term implantation materials or blood contact materials in vivo.Ⅱ.Preparation and functional study of tannic acid modified medical degradable polyurethane containing disulfide bond: The-NCO terminated prepolymer was prepared by condensation polymerization of excess dicyclohexylmethane diisocyanate(HMDI),polytetramethylene glycol(PTMG)and bis(4-hydroxyphenyl)disulfide(BHD),and then a series of tannic acid(TA)modified polyether polyurethanes(PU-TS)containing disulfide bonds were obtained by crosslinking with TA.The chemical structure of PU-TS was characterized by FT-IR and XPS,and the effect of disulfide bond/TA content(or crosslinking degree)on the physical and chemical properties of the membrane was studied.With the increase of TA content(the increase of crosslinking degree),the Tg and thermal stability of PU-TS increased gradually,but the crystallization capacity decreased;The three-dimensional network structure formed by covalent bonds and multiple hydrogen bonds which provided excellent mechanical properties.The breaking strength,elongation at break and fracture toughness of PU-TS-V with the highest TA content were 51.45 MPa,636.9% and 128.7 MJ/m3,respectively;The unreacted hydroxyl group on the TA chain segment improved the surface hydrophilicity,swelling property and hydrolysis degradation rate of the material,but the weight loss of degradation in vitro for 30 days was still lower 5%,indicating this material had good biological stability.The introduction of TA endowed the material with good broad-spectrum antibacterial property,and the diameter of PU-TS-V inhibition zone on E.coil and S.aureus reached 10.5 mm and 20.1 mm,respectively;The disulfide bond and phenol carbamate bond endowed the material with excellent room temperature self-healing property.The self-healing efficiency of PU-TS-III in 24 h was 90.8% at room temperature,and the self-healing efficiency was 74.4% after 10 repetitions;Multiple hydrogen bonds endowed the material with excellent shape memory properties,and the shape recovery rate(Rr)of PU-TS-V was 99.8% after recovering 5 s at body temperature.Finally,the biocompatibility of the material was preliminarily evaluated by protein adsorption and cytotoxicity tests.The results showed that the introduction of TA could improve the anti protein adsorption capacity and cellular compatibility of PU-TS membranes,among which the anti-protein adsorption of PU-TS-V was 1.3 μg/cm2 and the cell activity was higher than 75%.PU-TS material not only has excellent mechanical properties,degradability and biocompatibility,but also has antibacterial activity,shape memory,self-healing properties and other properties,which provided a design idea for the research and preparation of multi-functional medical polyurethane materials,and also offered a foundation for expanding the application of polyurethane in the medical field.