Ring Opening Polymerization Of D,L-Lactide Catalyzed By BAIP-Ti(â…£) Complex And Electrospun Study Of PDLLA

Polylactide (PLA) is one kind of thermoplastic polyester materials with good biocompatibility and biodegradability and widely used in the fields of biologic medicine and tissue engineering. Recently, people play more attentions to the synthesis and applications of PLA. Thereofore, it has drawn more attentions for ring-opening polymerization (ROP) of the lactide and its applications in medicine and tissue engineering. The tin(â…¡) bis(2-ethylhexanoate)(Sn(Oct)2) was widely employed as the initiator for ROP of lactide to produce PLA. However, it is important to note that Sn(Oct)2could be decomposed over100℃and hydrolyzed in presence of a little water. Subsequently, some side reactions would be take place during ROP of lactide. The results were that the (Sn(Oct)2) as initiator was inactivation for ROP of lactide and its catalytical activation was decreased. Therefore, it made molecular weight distributions of PLA broaden and the mechanics strength of PLA material was also decreased. So it was needed to develop new thermal stabilitable metal catalyst with insensitive property in presence of water to produce PLA by the method of ROP of lactide.In the thesis, a thernmal stabilitable and higher reactive catalyst, bis(alkoxy-imine-phenoxy) titanium (â…£)[BAIP-Ti(â…£)] complex, was synthesed and characterizaed by all kinds of methods to ROP for D,L-lactide. Experimental results revealed that the BAIP-Ti(â…£) complex could efficiently catalyze the ROP of D,L-lactide, and the kinetic and mechanism of ROP reactions were studied. The mechanical test and biocompatibility of the obtained poly(D,L-lactide)(PDLLA) were assyed and preliminary estimated, repectively. In the electraspun experiments of the PDLLA, we studied the influencing factors of variations in diameter distribution and morphology of the PDLLA fibers, such as concentration and feed rate of PDLLA solution, and the duration of the vacuum freeze-drying. As well, the cultivation and growth of the MC3T3-E1cells on the of macro-and nanao-structure PDLLA fiber as scaffold materials was studied. The main works and results were included as follows:1. BAIP-Ti(â…£) complex was synthesized with the3,5-di-tert-butylsalicylaldehyde, ethanolamine and tetraethyl titanate as react reagents, and its structure was characterizaed.â‘ Preparation of BAIP-Ti(IV) complex:the Schiff base was synthezed through the condensation reaction between3,5-di-tert-butylsalicylaldehyde and ethanolamine. Then the Schiff base reacted with tetraethyl titanate following the alcohol exchange protocol, and the BAIP-Ti(IV) complex was obtained by the method of recrystallization.â‘¡The BAIP-Ti(IV) complex was structurally characterized by element analysis(EA), fourier transform infrared spectrometry (FTIR), nuclear magnetic resonance spectrometer(NMR), X-ray fluorescence spectroscopy(XRF) and thermal gravity analysis/differential scanning calorimeter (TG/DSC) methods. The X-ray diffraction results showed that the titanium ion was bonded with two3,5-di-tert-butylsalicylaldehyde-co-ethanolamine ligands in O,N,O-tridentate mode, and there were four O-Ti covalent bonds and two Nâ†'Ti coordiantion bonds. It indicated that the center of titanium ion in the complex was closed by double ligands.2. The poly(D,L-lactide)(PDLLA) was produced by ROP of D,L-lactide in bulk phase with the BAIP-Ti(IV) complex as catalyst. We studied the molecular weights and polydispersity index (PDI) under different experimental factors, and the kinetic and mechanisim of ROP for D,L-lactide were also studied.â‘ The ROP of D,L-lactide could affected by the molar ratio of D,L-lactide to complex ([M]0/[Ti]0, M=D,L-lactide monomer,[Ti]=titanium (IV) complex), polymerization temperature and duration time. In our study, we had gained the polylactide with maximum number average molecular weight (Mn=8.80×104g/mol) at [M]0/[Ti]0molar ratio of2000/1for a16h duration at160℃②The kinetic studies showed that the ROP of D,L-lactide could be performed over130℃and the polymerization reaction was the second-order on D,L-lactide monomer concentration and the first-order on catalyst concentration, and the values of apparent activation energy (â–³Ea=76.63kJ/mol) and frequency factor (A=2.9×1011) were obtained according to the Arrhenius equation. And the values of apparent activation energy (â–³Ea=76.63kJ/mol) was closed to the that (â–³Ea=70.9kJ/mol) of ROP of L-LA with Sn(Oct)2as catalyst. The results showed that the the ROP of D,L-lactide catalyzed by the BAIP-Ti(IV) complex was a facile reaction and the BAIP-Ti(IV) complex had the higher catalytical activation with the Sn(Oct)2as catalyst.â‘¢The mechanism study by1H NMR spectrum of poly(D,L-lactide) with terminal benzyl ester group and the BAIP-Ti(IV) complex revealed that the polymerization proceeded through the traditional activated monomer mechanism and the acyl-oxygen bond cleavage mode of monomer.â‘£The D,L-lactide polymerization results at different temperature showed that a linear relationship between Mn and rac-lactide monomer conversion and the narrow molecular distributionlow (MW/Mn=1.10-1.25) of the PDLLA at160℃implied the highly controlled and "living" character of the polymerization process.3. The PDLLA was chanracterizaed by fourier transform infrared spectrometry (FTIR), nuclear magnetic resonance spectrometer (1H NMR and13C NMR), and thermal gravity analysis/differential scanning calorimeter (TG/DSC) methods. The mechanical property of PDLLA was perfomed from the tension and compression experiments, and the tension fracture face morphology of PDLLA was chanracterizaed by the scanning electron microscopy (SEM).â‘ The results from1H NMR and13C NMR of PDLLA showed that that the PDLLA (Ti-P) was essential atactic polymer. There was the methine protons resonance absorption peak in iss stereosequence at69.4ppm, and it indicatd that no intermolecular transesterification took place in ROP of lactide with BAIP-Ti(IV) complex as catalyst. And the proportionality (Pr) of intensities of isi (δ=5.16ppm) and sis (δ=5.23ppm) steresquences to the intensities of other steresquences was0.64, the results showed the complex showed a hetereotactic and well-controlled selectional manner for ROP of D,L-lactide.â‘¡From the study of the intensities of methenyl carbon with tetrad stereosequences and carbonyl carbon with hexad stereosequences in the13C NMR of PDLLA and the probability(P1=0.58) of isotactic addition reaction, it revealed that there was moderate stereoselectivity of isotactic addition reactions with BAIP-Ti(IV) complex as catalyst for ROP of D,L-lactide.â‘¢In contrast to the Sn-P (the PDLLA with Sn(Oct)2as catalyst), the Ti-P (the PDLLA with BAIP-Ti(IV) complex as catalyst), in spite of similar Ma and different PDI and the TG/DSC analysis showed that the Ti-P polymer was more thermal stable and higer glass transition temperature (Tg) than Sn-P polymer, which indicated that there was few branched polylactide and thermally unstable groups.â‘£The results of tension and compression experiments showed that the properties of tension and compression of Ti-P polymer was stronger than that of Sn-P polymer.and the SEM of Ti-P fracture face morphology showed that fracture face was smooth, and no apparente gab and claw could be observed. As well, there was no the distinct silkiness and fracture deck in the SEM. Therefore, it revealed that the Ti-P material showed the chanracter of brittleness fracture.4. In contrast to the Sn-P material, the surface hydrophilicity/hydrophobicity and degradation of Ti-P materoal were investigated The evaluating indicators of surface wettability were mainly static water contact angle and water absorption ratio, while the evaluating indicators of degradation behavior were pH value changes and the weight loss ratio.â‘ The results showed that static water contact angle of Ti-P materoal was higher than that of Sn-P material, while the water absorption ratio was smaller than that of Sn-P material. So hydrophilicity of Ti-P material was lower than that of Sn-P materal due to the lower number of carboxyl and hydroxyl on the surface of Ti-P materoal.â‘¡The dgradable experimental results of Ti-P and Sn-P materials in vitro revealed that the interval time of quickly grew weight loss and sudden depressed degradable pH value of Ti-P was longer than that of Sn-P, and there was obvious acid catalyzed auto-accelerating degradation. The PDI value of Ti-P material was lower than that of Sn-P material and the fewer number of hydrophilicity group on the surface of Ti-P material decrease the concentration of carboxyls, which made the lower auto-accelerating degradation of Ti-P material than that of Sn-P material.5. The biocompatibility of MC3T3-E1cell on the surface of glass, Ti-Pmaterial and Sn-P material were investigated, respectively. The MC3T3-E1cell was estimated by means of morphology, the distribution of F-actin, proliferation. The results revealed:â‘ All MC3T3-E1cells had spread on three materials, such as glass, Ti-Pand Sn-P material after48h cultivation.â‘¡The F-actin morphology of MC3T3-E1cells spread on glass, Ti-Pand Sn-P material was observed by the method of laser confocal microscopy. The results showed that MC3T3-E1cells had adhered and apread the three materials well after48h cultivation.â‘¢The proliferation vigor and speed of MC3T3-E1cells on the surface of glass, Ti-P and Sn-P material were assayed. The result proved that proliferation tendency of MC3T3-E1cells on Ti-P material was similar to that of Sn-P material, however, the proliferation vigor of MC3T3-E1cells on the two materials was notable higer than that of glass, and there wasn’t significant difference between Ti-P and Sn-P material.6. The electraspun of PDLLA (Ti-P) with8.8×104g/mol molecular weight and low PDI (1.17) was studied. In the study, we investigated that the experimental factors could affect on fiber diameter distribution and morphology. As the studied model, the biocompatibility of MC3T3-E1cell on the Ti-P fibers was investigated. The results revealed:â‘ The miacrofibers could obtained at0.8kv/cm electric field strength,0.20g/ml concentration of Ti-P solution and0.8ml/h feed rate, the diameter distribution of these fibers was range from1.1to1.7μmâ‘¡The nanofibers could obtained under cryodesiccate at vaccum for8h, and their diameter distribution was range from500to900nm and these fiber was about74%in total diameter distribution.â‘¢The MC3T3-E1cells were found that they could adhere to the surface of the Ti-P fibers when MC3T3-E1cells were cultured on the surface of the Ti-P fibers. However, there was visible extracellular matrix (ECM) on the surface of MC3T3-E1cell after5days cultivation. It revealed that the Ti-P fibers after cryodesiccate at vaccum were good biocompatibility to MC3T3-E1cells and these MC3T3-E1cells had showed important biologic feature.In conclusion, the BAIP-Ti(IV) complex had showed that controlled manner for ROP of D,L-Lactide. The physical and chemical properties of Ti-P polymer were gooder than that of Sn-P polymer and the Ti-P polymer was biocompatibility for the adhesion and proliferation of osteoblast.