基于新型PEG衍生物共聚改性聚乳酸的骨再生材料的研究
[Abstract]:Bone tissue engineering provides a new way and hope for the patients with bone disease. The design of tissue regeneration scaffold is the key to the success of bone tissue engineering. It is usually required to meet certain mechanical strength, controllable degradation performance and reasonable surface induction of cell proliferation and differentiation and tissue regeneration. However, few materials can be used at the same time at the same time. The purpose of this study is to design a new type of bone tissue engineering material to make it capable of controlling degradation properties, certain mechanical strength, appropriate hydrophilic properties and functional surfaces. Based on the PEG derivative poly (ethylene glycol -co- benzoate anhydride) imide (PAPI), copolymerization of D, L- C (D, L-LA) ester, and copolymerization of PAPI) A series of new PAPI-PDLLA copolymers with adjustable performance are prepared. Using nuclear magnetic resonance (NMR), Fu Liye transform infrared spectrometer (FTIR), gel chromatography - eighteen angle laser scatterometer (GPC-MALLS), ultraviolet visible spectrometer (UV), differential scanning calorimeter (DSC), X photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), atomic force microscopy (AFM) and other copolymers The properties of chemical and physical properties were characterized. The affinity / hydrophobicity of PAPI-PDLLA copolymer, in vitro biodegradability, mechanical properties (tensile properties and compression properties), and the changes of mechanical properties during the degradation process were investigated. The amino and hydroxyl groups of the PAPI-PDLLA copolymers were studied. Finally, the PAPI-PDLLA was evaluated. Biocompatibility of copolymers and surface functionalized materials in vitro. The main contents and conclusions are as follows:
1. a new PEG derivative P (ATPGE-co-PMDA) (PAPI) was synthesized by the high temperature condensation reaction of PEG (ATPEG, Mr:900) and benzyldianhydride (PMDA) at low molecular weight, and the influence of monomer ratio, temperature and reaction time on the molecular weight of the polymer and the process of imimide during the reaction process were investigated. The derivate was connected by the benzimide ring and the introduction of the imide ring provided the conditions for the opening ring function grafting. The ability of Ding Eran, ethanolamine to react with the imide ring in PAPI was studied, and the structure of all the synthesized materials was characterized.
(1) FTIR, 1H NMR, 13C NMR, GPC-MALLA and UV detection results show that ATPEG and PMDA are successfully polymerized, and the micro excess of ATPEG makes the PAPI end have amino. When the molar ratio of the two is more than ATPEG/PMDA=1.05, after the reaction is completed at a set temperature, the imide base is complete, and the molecular weight of the polymer is larger and the polymer fraction is obtained. Thermogravimetric analysis showed that the thermal stability of PAPI relative to PEG was enhanced.
(2) FTIR showed that the imide ring in PAPI successfully reacted with butyl two amine and ethanolamine at room temperature without catalyst, which might provide a reaction site for graft functional groups.
(3) the gel was produced by crosslinking with butyl two amine, which has a certain mechanical strength and porosity, which is expected to be used in the field of drug release or tissue engineering.
The co initiation system of 2.PAPI and stannous octanate initiated a series of D, L- lactide ring opening and a series of PAPI-PDLLA copolymers. The effects of PAPI/D, L- lactide, reaction temperature and reaction time on the molecular weight of PAPI-PDLLA copolymers were investigated, and the chemical structure and thermal properties of the copolymers were characterized.
(1) the results of FTIR, 1H NMR, 13C NMR and GPC-MALLS showed that the co initiation system of PAPI and stannous octanate initiated the opening ring of lactide, and the PAPI-PDLLA copolymer was prepared. The optimum reaction time was 36 hours and the reaction temperature was 150.
(2) a series of copolymers with different molecular weights and properties can be prepared by adjusting the material ratio of PAPI and D, L- lactide. The amount of polylactic acid graft is calculated by 1H NMR. With the increase of PAPI/D, the proportion of L- lactide is increased, and the molecular weight of the grafted polylactic acid decreases.
(3) DSC results show that the PAPI-PDLLA copolymer has only one glass transition temperature, which indicates that the thermal compatibility of the two phases is good and the glass transition temperature decreases with the increase of the proportion of PAPI. The results of thermogravimetric analysis show that the PAPI-PDLLA has two obvious decomposition temperatures, first of which is PDLLA block decomposition, then the decomposition of PAPI, by thermogravimetric analysis. The mass ratio of the two block is obtained.
3. the Pro / hydrophobicity and degradation properties of PAPI-PDLLA copolymer were studied. The hydrophobicity and hydrophobicity of the copolymer were evaluated by two methods of static water contact angle and total water absorption on the surface of the material, and the degradation properties of the materials were evaluated by the weight loss rate, the change of molecular weight, the change of the pH value and the change of the surface morphology after the degradation.
The results of Pro / hydrophobicity test showed that the static water contact angle of PAPI-PDLLA copolymer was less than PDLLA, and the water absorption rate was greater than that of PDLLA, and the hydrophilic property increased with the increase of the hydrophilic block PAPI in the copolymer.
The in vitro degradation experiment of PAPI-PDLLA copolymer showed that the weight loss of PAPI-PDLLA Series in the five weeks before degradation, the decrease of molecular weight and the change of pH value were faster than that of the PDLLA control group. But in the whole degradation process, it was found that PDLLA caused a steep drop due to the autocatalytic effect of acid accumulation during the degradation process, and in PAPI-PDLLA. In the series of materials, the degradation rate is more controllable and the natural logarithm and time of the degradation weight loss are fitted. It is found that the pseudo first order dynamic model Mnmolecular has no steep drop. This is due to the introduction of the hydrophilic block PAPI, which accelerates the dispersing of the degraded acid small molecules, and does not lead to the apparent autocatalytic degradation of the material. The scanning electron microscopy (SEM) after degradation showed that PDLLA could produce local heterogeneous degradation, while the degradation surface of PAPI-PDLLA copolymer was more uniform. Therefore, the degradation control performance of the material was higher than that of PDLLA.
4. the tensile and compression tests were used to investigate the mechanical properties of the material. The results showed that the copolymer had certain tensile strength and compressive strength, and the strength increased with the reduction of the material ratio of PAPI/D, L- lactide, and the elongation at break increased significantly with the increase of the material ratio of PAPI/D and L- lactide. The compression modulus is between 48-280MPa. The compression modulus is between 108-780MPa and the compression modulus of the cancellous bone. With the degradation of the material, the mechanical strength of the material gradually loses, and with the increase of the proportion of PAPI in the copolymer, the mechanical loss accelerates, and the tensile properties are almost all after the degradation of PAPD4/15 (PAPI-PDLLA PAPI/D, L-LA=4/15) for four weeks. The loss, and PAPD4/25 only lost about 20%.
5. the amino and hydroxyl groups were introduced on the surface of PAPI-PDLLA copolymer membrane by wet chemical method. The amino and hydroxyl groups grafted on the surface of the material were qualitatively and quantitatively characterized by XPS, colorimetric method, AFM and other methods. The amino and hydroxyl groups were easily introduced on the surface of the material without catalyst and at normal temperature. The amino density of the surface grafting of the base.PAPD4/15-BDA material is 3.41 * 10~ (-6) mol/cm~2. when the grafting of the amino group and the hydroxyl group, the surface of the material becomes coarser compared with the reaction before the reaction.
6. the cytotoxicity of PAPI and PAPI-PDLLA was evaluated by rat osteoblasts of rat milk. The cytocompatibility of PAPI-PDLLA and functional surface with PDLLA was systematically compared from the aspects of osteoblast morphology, adhesion, spreading, proliferation, differentiation and mineralization.
(1) the maximum amount of PMDA immersion solution, which could be produced by PAPI immersion and PAPI and PAPI-PDLLA degradation, was used to culture osteoblasts. It was found that osteoblasts were cultured in the above culture medium, and PAPI and PMA culture medium did not affect the morphology and proliferation of the cells, which showed that there was no obvious cytotoxicity of PAPI and PAPI-PDLLA.
Compared with PDLLA, proper introduction of PAPI promotes the adhesion and spreading of osteoblasts, while excessive PAPI is not conducive to cell adhesion, and the functional PAPI-PDLLA membrane surface is also beneficial to cell adhesion and spreading, and the adhesion of amino functional surface cells is most obvious.
(3) relative to PDLLA, the PAPI-PDLLA membrane with proper PAPI content is beneficial to cell proliferation, while the functionalized surface of amino and hydroxyl groups makes cell proliferation more significant.
The differentiation and mineralization of osteoblasts on the surface of the material were measured by alkaline phosphatase, inorganic calcium secretion and collagen secretion. The results showed that the differentiation and mineralization ability of the cells on the surface of the amino functional PAPI-PDLLA membrane was slightly better than that of PAPI-PDLLA, while the mineralization ability on the PAPI-PDLLA membrane was better than that of PDLLA..
【学位授予单位】:重庆大学
【学位级别】:博士
【学位授予年份】:2012
【分类号】:R318.08
【参考文献】
相关期刊论文 前10条
1 糜丽;潘君;赵明媚;刘颖;王彬;王远亮;;一种可促进成骨细胞黏附和生长的聚乙二醇接枝聚乳酸材料[J];材料导报;2008年08期
2 宋谋道,朱吉亮,张邦华,郝广杰,周庆业,张莹,赵芬芝,赵英奇,杨世强,范玉玲;聚乙二醇改性聚乳酸的研究[J];高分子学报;1998年04期
3 张国栋,冯新德,顾忠伟;端基含葡氨糖衍生物的聚乳酸的合成与表征[J];高分子学报;1998年04期
4 卢红斌,何天白;聚酰亚胺反应动力学研究进展[J];高分子材料科学与工程;2000年05期
5 赵明媚;潘君;李永刚;刘颖;王远亮;牛旭峰;;一种可阻止非特异性蛋白质吸附的新型聚乳酸材料——聚乙二醇接枝聚乳酸[J];高分子材料科学与工程;2007年03期
6 罗彦凤;王素军;牛旭锋;王远亮;付春华;黄美娜;;RGDS和胶原改性聚(DL-乳酸)的合成与表征[J];高分子材料科学与工程;2008年05期
7 蔡开勇,林松柏,姚康德;组织工程相关生物材料表面工程的研究进展[J];化学进展;2001年01期
8 贺亚敏,黄培林,吕晓迎;几种医用材料的细胞生物相容性评价的实验研究[J];东南大学学报(医学版);2003年02期
9 路庆华,王宗光,孙立民,刘勇;聚酰亚胺的热亚胺化动力学研究[J];上海交通大学学报;1997年07期
10 杨晓芳,奚廷斐;生物材料生物相容性评价研究进展[J];生物医学工程学杂志;2001年01期
相关博士学位论文 前4条
1 阮长顺;新型骨修复材料可降解哌嗪基聚氨酯脲的研究[D];重庆大学;2011年
2 罗彦凤;聚(DL—乳酸)的改性及体外降解和细胞相容性研究[D];重庆大学;2003年
3 杨媛;交联型生物可控降解骨组织修复材料的制备及应用[D];暨南大学;2007年
4 黄美娜;可预防骨不连的骨修复用新型形状记忆聚氨酯-脲的研究[D];重庆大学;2010年
相关硕士学位论文 前1条
1 林福春;力生长因子E肽(MGF-Ct24E)与应力作用对成骨细胞基因表达影响的基因芯片分析[D];重庆大学;2011年
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