基于聚羟基脂肪酸酯双亲嵌段共聚物的合成、表征、自组装及生物相容性研究
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摘要
聚羟基脂肪酸酯(Polyhydroxyalkanoates或PHAs)是一类微生物发酵、可生物降解的高分子聚酯,因其具有卓越的生物相容性和生物降解性而受到越来越多的关注。聚乙二醇(Polyethylene glycol或PEG)是一类水溶性和生物性相容的物质,可安全存在于人体的血液中。本文选用了PHAs家族中聚三羟基丁酸酯(PHB)、三羟基丁酸和四羟基丁酸共聚酯(P3/4HB)和三羟基丁酸三羟基己酸共聚酯(PHBHHx)分别为硬段、疏水段和软段、亲水段的PEG通过化学共聚的方式合成三个系列的多嵌段双亲性共聚物。
所聚合的产物通过核磁(NMR)和红外(IR)对其结构进行分析,结合凝胶渗透色普(GPC)测试结果,验证了产物的嵌段结构。示差扫描量热测试结果(DSC)显示所有的产物只有一个内移的玻璃化转变温度(Tg),表现出PHA相和PEG相有一定的相容性,且由于彼此链段的影响使两相都处于半结晶状态。而通过调节不同的组分组成,产物在久置后能达到相分离的状态。热稳定分析(TGA)结果表明多嵌段共聚物中由于PEG和亚氨酯基团的引入,增加了PHA的热加工区间。三个系列的多嵌段共聚物中由于PHA链段不同的结晶性,形成了材料不同的表面形态和特殊的生物学意义。当PHA是高结晶的PHB片段时,共聚物表面形态时多孔网状结构;当PHA时完全无定形态的P3/4HB时,共聚物表面形态是连续的平滑结构;当PHA是半结晶状态的PHBHHx时,共聚物表面形态是介于多孔和平滑之间。实现了选用不同结晶态的PHA的方法来调控共聚物的表面形态的设想。共聚物的这种特性也使他们在不同方面表现出了新的性能和应用。随着PEG的引入,PHB-b-PEG系列多嵌段共聚物的血液相容性得到很大程度的提高。主要体现在凝血时间的增加和共聚物表面血小板贴附数目的减少。完全无定形态的P3/4HB使得P3/4HB-b-PEG系列多嵌段共聚能够溶于水,且在水包油的乳液中根据组分的不同自组装成为不同的形状(树叶状和三角形状)。半结晶态的PHBHHx使PHBHHx-b-PEG系列多嵌段共聚物有着更强的机械强度和断裂伸长率,动物实验表明PHBHHx-b-PEG系列多嵌段共聚物有着比纯PHBHHx更好的组织重建和组织相容性。这将会使PHBHHx-b-PEG系列多嵌段共聚物在术后抗粘连和伤口的修复方面有潜在的生物医学应用。
本文成功的改善了PHA作为生物材料疏水的特点,并研究了改性后的多嵌段共聚物相比于纯的PHA的独特性能和生物医学应用。这将为拓展PHA应用领域,尤其在高级自组装功能材料和开发新型生物医学材料方面有着独特的贡献。
Polyhydroxyalkanoates (PHAs) are a class of biodegradable polyesters produced by microorganisms. Due to their biodegradability and biocompatibility, PHAs have received much attention as a friendly material recently. Polyethylene glycol (PEG) is a water-soluble substrate as its popular hydrophilicity. Particularly, it can be found in human blood for its good biocompatibility. In this essay, three series of poly(ester-urethane)s (PUs) were synthesized from copolymerization of different PHA members (PHB, P3/4HB and PHBHHx) which behave as a hard and hydrophobic portion and PEG functions as soft and hydrophilic moieties.
The resultant products were characterized by NMR and Fourier transform infrared spectroscopy (IR), as well as gel permeation chromatography (GPC), which indicated the block copolymer architecture. Differential scanning calorimetry (DSC) revealed that PUs multiblock copolymers possess a semi-crystalline morphology with a single inner Tg due to the segments interaction. Whilst, a two phase separation was observed after placed for crystallinity equilibrium depending on its chemical composition. Thermogravimetric analysis (TGA) showed that the PUs multiblock copolymers had better thermal processability than their precursors. The morphologies of the three types PUs were controlled by the crystallinity of the PHA segments which would be potential in biomedical area. It is porous and net-like surface of crystal PHB based PUs copolymers while continuous and smooth when amorphous P3/4HB was employed. For semi-crystal block PHBHHx, the morphology changes between the two mentioned above due to the very low crystallinity rate. The differences of the aforesaid morphologies behaved novel properties and applications of the PUs. The blood compatibility of PHB-b-PEG series multiblock copolymers revealed an increasing blood clot formation time and reduced blood adhesion with increasing PEG content in the multiblock copolymers compared with the PHB only polymers. The P3/4HB and PEG block copolymers showed water dispersion behavior and the changes on hydrophilic/hydrophobic ratios led to the formation of different polymer shapes in Oil-in-Water emulsion (leaf-like and triangle). The mechanical properties assessment of the PUs based PHBHHx and PEG recorded an improved and adjustable ductility and toughness than pure PHBHHx with changing segment composition. Implantation of PU in mouse abdominal cavity indicated that tissue regeneration and tissue compatibility of PUs film was better than that of PHBHHx film. This kind of multiblock copolymer has great potential to be developed as a suitable candidate biomaterial for anti-adhesion and wound healing.
To sum up, the hydrophobicity of PHA was modified successfully by copolymerization with hydrophilic PEG segments and made comparison in terms of novel properties and biomedical application between the synthesized PUs and neat PHA only materials. This would make great contributions to broaden PHA application area, especially in advanced self-assembly and biomedical materials aspects.
所聚合的产物通过核磁(NMR)和红外(IR)对其结构进行分析,结合凝胶渗透色普(GPC)测试结果,验证了产物的嵌段结构。示差扫描量热测试结果(DSC)显示所有的产物只有一个内移的玻璃化转变温度(Tg),表现出PHA相和PEG相有一定的相容性,且由于彼此链段的影响使两相都处于半结晶状态。而通过调节不同的组分组成,产物在久置后能达到相分离的状态。热稳定分析(TGA)结果表明多嵌段共聚物中由于PEG和亚氨酯基团的引入,增加了PHA的热加工区间。三个系列的多嵌段共聚物中由于PHA链段不同的结晶性,形成了材料不同的表面形态和特殊的生物学意义。当PHA是高结晶的PHB片段时,共聚物表面形态时多孔网状结构;当PHA时完全无定形态的P3/4HB时,共聚物表面形态是连续的平滑结构;当PHA是半结晶状态的PHBHHx时,共聚物表面形态是介于多孔和平滑之间。实现了选用不同结晶态的PHA的方法来调控共聚物的表面形态的设想。共聚物的这种特性也使他们在不同方面表现出了新的性能和应用。随着PEG的引入,PHB-b-PEG系列多嵌段共聚物的血液相容性得到很大程度的提高。主要体现在凝血时间的增加和共聚物表面血小板贴附数目的减少。完全无定形态的P3/4HB使得P3/4HB-b-PEG系列多嵌段共聚能够溶于水,且在水包油的乳液中根据组分的不同自组装成为不同的形状(树叶状和三角形状)。半结晶态的PHBHHx使PHBHHx-b-PEG系列多嵌段共聚物有着更强的机械强度和断裂伸长率,动物实验表明PHBHHx-b-PEG系列多嵌段共聚物有着比纯PHBHHx更好的组织重建和组织相容性。这将会使PHBHHx-b-PEG系列多嵌段共聚物在术后抗粘连和伤口的修复方面有潜在的生物医学应用。
本文成功的改善了PHA作为生物材料疏水的特点,并研究了改性后的多嵌段共聚物相比于纯的PHA的独特性能和生物医学应用。这将为拓展PHA应用领域,尤其在高级自组装功能材料和开发新型生物医学材料方面有着独特的贡献。
Polyhydroxyalkanoates (PHAs) are a class of biodegradable polyesters produced by microorganisms. Due to their biodegradability and biocompatibility, PHAs have received much attention as a friendly material recently. Polyethylene glycol (PEG) is a water-soluble substrate as its popular hydrophilicity. Particularly, it can be found in human blood for its good biocompatibility. In this essay, three series of poly(ester-urethane)s (PUs) were synthesized from copolymerization of different PHA members (PHB, P3/4HB and PHBHHx) which behave as a hard and hydrophobic portion and PEG functions as soft and hydrophilic moieties.
The resultant products were characterized by NMR and Fourier transform infrared spectroscopy (IR), as well as gel permeation chromatography (GPC), which indicated the block copolymer architecture. Differential scanning calorimetry (DSC) revealed that PUs multiblock copolymers possess a semi-crystalline morphology with a single inner Tg due to the segments interaction. Whilst, a two phase separation was observed after placed for crystallinity equilibrium depending on its chemical composition. Thermogravimetric analysis (TGA) showed that the PUs multiblock copolymers had better thermal processability than their precursors. The morphologies of the three types PUs were controlled by the crystallinity of the PHA segments which would be potential in biomedical area. It is porous and net-like surface of crystal PHB based PUs copolymers while continuous and smooth when amorphous P3/4HB was employed. For semi-crystal block PHBHHx, the morphology changes between the two mentioned above due to the very low crystallinity rate. The differences of the aforesaid morphologies behaved novel properties and applications of the PUs. The blood compatibility of PHB-b-PEG series multiblock copolymers revealed an increasing blood clot formation time and reduced blood adhesion with increasing PEG content in the multiblock copolymers compared with the PHB only polymers. The P3/4HB and PEG block copolymers showed water dispersion behavior and the changes on hydrophilic/hydrophobic ratios led to the formation of different polymer shapes in Oil-in-Water emulsion (leaf-like and triangle). The mechanical properties assessment of the PUs based PHBHHx and PEG recorded an improved and adjustable ductility and toughness than pure PHBHHx with changing segment composition. Implantation of PU in mouse abdominal cavity indicated that tissue regeneration and tissue compatibility of PUs film was better than that of PHBHHx film. This kind of multiblock copolymer has great potential to be developed as a suitable candidate biomaterial for anti-adhesion and wound healing.
To sum up, the hydrophobicity of PHA was modified successfully by copolymerization with hydrophilic PEG segments and made comparison in terms of novel properties and biomedical application between the synthesized PUs and neat PHA only materials. This would make great contributions to broaden PHA application area, especially in advanced self-assembly and biomedical materials aspects.
引文
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