| Aiming to develop a biomaterial with excellent biocompability and biospecificy and physiological functions, in this thesis, D,L-lactide was prepared from D,L-lactic acid by adopting a new lanthanum-titanium composite oxides as the catalyst. First, poly(D,L-lactic acid) (PLA) was prepared from D,L-lactide with the use of Sn(Oct)2, and then, with a series of chemical reactions in the bulk, it was modified by introducingβ-cyclodextrin(β-CD) oligosaccharide into PDLLA backbone, at last, a novel PLA was acquired, which was based on fully biodegradable matrix materials modified by polysaccharides. To explore the structures and properties of the obtained polymers, characterizations included multi-angle laser light scattering (MALLS), fourier transform infrared spectrometry (FTIR), nuclear magnetic resonance spectrometer (NMR), differential scanning calorimeter (DSC) and some classical chemical analysis methods, and then, surface wettability, biodegradation and biocompatibility of the synthetic materials were investigated, too. The main works and conclusions are listed as below:⑴Synthesis of reactable poly(D,L-lactic acid).①With D,L-lactic acid as raw material and lanthanum-titanium composite oxides as catalyst, the D,L-lactide was synthesized. The catalyst of lanthanum-titanium composite oxides is high efficient in decreasing the dehydrate temperature, pyrolysis temperature and viscosity of the reacting system, consequently the oligomer of lactic acid was kept in the reactor instead of escaping with lactide, which prevents the contamination of lactide by oligomer. Glass transition temperature of the D,L-lactide tested by DSC was 126.4℃, and analysis of X-ray photoelectron spectroscopy (XPS) indicated that the lactide was found to be hardly contaminated by La-radioactivity.②Poly(D,L-lactic acid) was synthesized by melt ring-opening polymerization of D,L-lactide with Sn(Oct)2 as catalyst. Molecular weight (Mw=22480, Mn=19548), and polydispersity (PD=1.15) of PLA were detected by MALLS.③To introduce highly reactive anhydride into backbone of PLA lacking of reaction group, free radical copolymerization happened between PLA and maleic anhydride(MAH) with the help of benzoyl peroxide (BPO) as an initiator. It is demonstrated by FTIR and 1HNMR that the MAH had been imported in PLA backbone successfully, and the relative optimum reactive conditions of MPLA were obtained: weight ratio of PLA to MAH was 10:1, weight ratio of BPO to MAH was 0.04, and reaction time was 10h, reaction temperature was 95℃. The results of rhodamine-carboxyl interaction method showed that under such conditions, the MAH grafting ratio in MPLA was 2.45%. Molecular weight and polydispersity of MPLA were detected by MALLS about Mw=20473, Mn=16510 and PD=1.24, respectively.⑵Preparation of mono(6-(2-aminoethyl)-amino-6-deoxy)-β-cyclodextrin。①It was indicated by FTIR, 1HNMR and DSC-TGA analysis that mono-6-O-6- tosyl-β-cyclo-dextrin(β-CD-6-OTs) had been successfully prepared by dropping p-TsCl acetonitrile solution intoβ-CD NaOH solution under 10℃, and then the reaction mixture was heated up to 25°C and lasted for 2h. Decomposition temperature ofβ-CD-6-OTs determined by DSC-TGA was 181.7℃and a strong decomposition peak was 187℃. The effect of reaction conditions on the yield ratio ofβ-CD-6-OTs was investigated, and the optimum conditions were: molar ratio of p–TsCl toβ-CD was 1.5, reaction time was 2h, reaction temperature was 23~25℃, the mixture was adjusted with 20%-hydrochloric acid solution to ca. pH7~8, theβ-CD-6-OTs yield could reach to 14%.②It was shown by FTIR, 1HNMR and EA analysis thatβ-CD-6-E had been successfully prepared by the reaction ofβ-CD-6-OTs and excess ethylenediamine at 75℃for 4h.⑶It was exhibited by FTIR, 1H NMR and DSC analysis that, by N-acylation reaction,β-CD was able to be introduced into the backbone of MPLA(maleic anhydride modified poly(d,l-lactic acid)) and the main chain structure of MPLA was maintained. And the glass transition temperature of PLA-β-CD acquired was 59.8℃by DSC analysis, the unique Tg of PLA-β-CD indicated that the purification method was efficient enough to produce pure PLA-β-CD. The optimum conditions were: molar ratio ofβ-CD-6-E to MPLA was 1.2, reaction temperature was 35~40℃, reaction time was 2h, the yield of PLA-β-CD was found to be 55%. It was indicated by Phenol-sulfuric Acid method that the content ofβ-CD was 12.7% under the above conditions.⑷The properties of various poly(D,L-lactic acid) based substrate films were investigated, including surface wettability and biodegradation. The surface wettability evaluation was based on static water contact angle and water adsorption ratio, while the degradation experimentation in vitro was used to estimate the bio degradation behavior.①The tests indicated that the static water contact angle of copolymer PLA-β-CD was decreased appreciably from 76.7o to 72.1o comparing with PLA, while the water absorption ratio was increased from 18.3% to 23.9%. The results revealed that hydrophilicity of PLA-β-CD was better than PLA.②In the whole degradation period of PLA-β-CD materials in distilled water, the change rule of the pH value was: At first, the pH value of PLA-β-CD is slightly higher than that of PLA within the first 5 weeks, and then, the former is a little lower than the latter in all other degradation period after that time, and the rapid drop time of PLA-β-CD advanced 1 week comparing with PLA.③Tests indicated that: the degradation stages of material PLA-β-CD in medium PBS tended to be accordance with the weight loss change trend of PLA, but the degradation rate improved to some extent. It demonstrated that the hydrophilicity of PLA-β-CD acquired by this research was improved, while the acidity of PLA had not enhanced by the introduction of MAH.⑸Biocompatibility of PLA-β-CD and PLA with osteoblasts obtained from newborn Wistar calvaria was preliminarily investigated by means of cell morphology and cell proliferation. The morphology of the cells was observed by phase contrast microscope and cell proliferation determined by MTT assay. The morphology observations revealed that the osteoblasts cultured on PLA-β-CD spread was wider than PLA and the cell density on PLA-β-CD was higher than PLA. Cell proliferation was determined by MTT assay at 2,4,6,8d, The results showed that proliferation power of osteoblasts cultured on PLA-β-CD notablely stronger than PLA. The results revealed the much better biocompatibility of PLA-β-CD with osteoblasts than that of PLA. Carbohydrate-protein interactions are the fundamentals of many cellular processes, such as signal ransduction, cell adhesion, proliferation, differentiation and immune response. Saccharide show an affinity for peptide and protein, while show an affinity for cells. Therefore, PLA-β-CD was a promising biomedical material and hopeful to gain potentially wide application in biomedical fields, especially in tissue engineering and drug delivery system.
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