首页> 外文学位 >Vascular endothelial growth factor-loaded polyphosphazene nanohydroxyapatite composite scaffords: Promoting neovascularization.
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Vascular endothelial growth factor-loaded polyphosphazene nanohydroxyapatite composite scaffords: Promoting neovascularization.

机译:加载有血管内皮生长因子的聚磷腈纳米羟基磷灰石复合材料:促进新血管形成。

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摘要

The purpose of this work is to develop, characterize and evaluate the ability of novel vascular endothelial growth factor (VEGF)-loaded three dimensional (3-D) composite poly(ethyl phenylalanato-glycinato)phosphazene-hydroxyapatite (PNPhGly-HAp) microsphere scaffolds to promote neovascularization and perform superiorly to bone treatment systems lacking a vascular network. PNPhGly was synthesized via a thermal ring opening polymerization method and the degradation profile of this polymer revealed minimal fluctuation in pH compared to the conventionally employed biodegradable poly(lactide-co-glycolide) (PLGA), which erodes to harmful acidic byproducts. Once PNPhGly microspheres were formed using emulsion-solvent evaporation, microsphere scaffolds were optimized for bone repair in terms of morphology, pore architecture, and mechanical strength. A 25%THF, 75% hexanes sintering solution generated scaffolds with a porosity measured by mercury intrusion porosimetry to be suitable for replacing trabecular bone tissue; and the addition of HAp improved the scaffold compressive modulus (37.24 +/- 11.99 MPa). Evaluation of protein release patterns from four sintering/VEGF loading solutions revealed that less VEGF was loaded and released from composite PNPhGly-HAp scaffolds compared to noncomposite PNPhGly matrices due to inherent properties of the protein and release media (i.e., isoelectric point and pH). A series of protein elution and extraction procedures also revealed that using this loading method, three physiologically relevant fractions of VEGF exist on the scaffolds - freely diffusible, adsorbed, and physically entrapped. Next, human umbilical vein endothelial cell (HUVEC) tubule formation assays proved that the 'free' fraction of VEGF released from the loaded PNPhGly scaffolds maintains bioactivity when compared to the 50ng/mL VEGF positive control. Though, in vivo, the low concentration of VEGF released from the scaffolds exhibited an angiogenic inhibitory behavior, using a conventional biocompatibility grading system that takes into the number and types of inflammatory cells, the PNPhGly polymer was determined to be suitable for drug delivery and bone tissue repair.
机译:这项工作的目的是开发,表征和评估新型血管内皮生长因子(VEGF)负载的三维(3-D)复合聚(乙基苯基丙氨酸-甘氨酸)磷腈-羟基磷灰石(PNPhGly-HAp)微球支架的能力促进新血管形成,并优于缺乏血管网络的骨治疗系统。 PNPhGly是通过热开环聚合方法合成的,与常规使用的可生物降解的聚(丙交酯-乙交酯-乙交酯)(PLGA)相比,该聚合物的降解曲线显示pH值波动最小,后者会侵蚀有害的酸性副产物。一旦使用乳液-溶剂蒸发形成PNPhGly微球,就可以在形态,孔结构和机械强度方面优化微球支架以进行骨修复。 25%THF,75%己烷烧结溶液产生的支架具有通过水银压入孔隙率法测得的孔隙度,适合替换小梁骨组织。 HAp的添加改善了支架的压缩模量(37.24 +/- 11.99 MPa)。对四种烧结/ VEGF负载溶液中蛋白质释放模式的评估显示,由于蛋白质和释放介质的固有特性(即等电点和pH),与非复合PNPhGly基质相比,从复合PNPhGly-HAp支架中负载和释放的VEGF更少。一系列蛋白质洗脱和提取程序还显示,使用这种加载方法,在支架上存在VEGF的三个生理相关部分-可自由扩散,吸附和物理截留。接下来,人脐静脉内皮细胞(HUVEC)小管形成试验证明,与50ng / mL VEGF阳性对照相比,从负载的PNPhGly支架释放的VEGF的“游离”部分具有生物活性。尽管在体内从支架释放的低浓度VEGF表现出了血管生成抑制行为,但使用常规的生物相容性分级系统(考虑了炎症细胞的数量和类型),PNPhGly聚合物被确定为适合药物输送和骨骼的组织修复。

著录项

  • 作者单位

    University of Virginia.;

  • 授予单位 University of Virginia.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 333 p.
  • 总页数 333
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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