利用静电纺丝技术构建双组份药物缓释纳米组织工程支架
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摘要
组织工程是一门将材料科学和细胞生物学相结合的新兴交叉学科。通过将种子细胞种植在仿生支架后在体外培养增殖而形成新组织取代原受损组织,达到修复和重建原组织结构和功能的目的。而在其中,制备具有一定生物学相容性的组织工程支架是组织工程中一个重要的研究方向。
静电纺丝是一种借助于静电场作用对聚合物溶液或熔体进行纺丝,是一种制备超细纤维的方法,成本低廉、简单易行。近十几年来,电纺丝技术在理论研究和实验参数研究等方面取得了不小的进展。尤其在生物医药领域,电纺丝超细纤维可广泛用作组织工程支架、药物传输与控制释放的载体等,这也是国际上的一个研究热点。
本实验利用静电纺丝技术,将传统意义上的两种载体结合在一起,构建了能够同时负载两种药物并分别缓释的双组份复合载体。通过多种实验技术检测双组份载体的物理化学性质。并通过负载两种模式药物的双组份载体的缓释曲线,研究双组份载体放入药物缓释机理。最后利用双组份载体与细胞的粘附增殖实验检测载体的细胞亲和性和组织相容性,以探讨该类型放入药物释放体系在临床上的潜在应用。
实验结果表明:制得的双组份缓释载体表面和内壁负载纳米粒,造成表面有突起和凹凸不平的结构。在内部化学结构上,没有观察到两种载体的化学键结合和特殊晶体结构的形成。亲水性良好,极大的增强了细胞的粘附效果和亲和性。缓释实验证明双组份载体系统中的两种载体各自释放,有效的促进了缓释效果。尤其对于纳米粒释放的效果改进最为明显,延长了释放时间,减小了突释效应。对于实验中用到的三种细胞,双组份载体系统都表现出优良的粘附效应和亲和性,甚至对于特定种类细胞有诱导细胞径向生长的效果,因此在临床上具有潜在应用前景。
可以预见,随着研究的进一步深入,这样的双组份缓释载体系统凭借其能够同时缓释多种药物的优点和良好的细胞相容性,必然在今后的组织工程支架的研究和临床应用中具有巨大的价值。
Tissue engineering (TE) is one of the new interdisciplinary fields which combined biology and material science. The aim is to reestablish human tissue and its function by planting scaffolds with functional cells incorporated into the damaged position. Among which, fabricating tissue engineering scaffolds with great biocompatibility become an important research direction.
Electrospinning is a process that produces polymer fibers under the action of an external electric field imposed on a polymer solution or melt. Electrospinning technology is a simple and cost-effective method to prepare ultrafine fibers. In the past decades, significant progresses were achieved on theoretical and experimental studies. Especially, in biomedical fields, ultrafine fibers prepared by elelctrospinning have been widely used in tissue engineering scaffolds, drug delivery system, which has attracted more and more attentions in the world.
Two traditional drug carriers were combined by electrospinning to form a dual-drug composite carrier system which carries two different drugs at one time and release them separately. The physicochemical characteristics of the dual-drug system were assessed by using different methods, the release profiles were then studied and the release mechanism was analyzed after loading and releasing two modal drugs in each carrier of the system.In addition , the adhesion and proliferation of resulting releasing system on different cells were investigated by detecting the biocompatibility and cytocompatibility of the system. Their potential clinical applications were discussed.
The results showed that the nanoparticles were distributed on the surface and internal wall of the nanofibers, which lead the rough fiber surface with sags and crests. No new chemical bond and special crystal structures were observed according to their chemical structures.These resulting releasing system exhibited improved cell adhesion and proliferation due to their good hydrophilcity. The releasing experiments demonstrated the drugs released from each control-release carrier in the dual-drug system separately, which tremendously improved the release efficiency of different drugs. Especially for nanopaticles releasing, release duration was enlarged in a wide range, and the burst releasing or another word-dumping was restrained effectively. Furthermore, three kinds of cells adhered and proliferated very well in the dual-drug releasing mats, the mats have also a capability to induce cells grow in a radial direction, which make it possible to develop thus dual-drug system for clinical application.
Predictably, as the studies goes on, such dual-drug controlled releasing system will be playing a significant role in future scientific researches and clinical applications, thanks to its characteristic in releasing several drugs separately at one time and great biocompatibility.
静电纺丝是一种借助于静电场作用对聚合物溶液或熔体进行纺丝,是一种制备超细纤维的方法,成本低廉、简单易行。近十几年来,电纺丝技术在理论研究和实验参数研究等方面取得了不小的进展。尤其在生物医药领域,电纺丝超细纤维可广泛用作组织工程支架、药物传输与控制释放的载体等,这也是国际上的一个研究热点。
本实验利用静电纺丝技术,将传统意义上的两种载体结合在一起,构建了能够同时负载两种药物并分别缓释的双组份复合载体。通过多种实验技术检测双组份载体的物理化学性质。并通过负载两种模式药物的双组份载体的缓释曲线,研究双组份载体放入药物缓释机理。最后利用双组份载体与细胞的粘附增殖实验检测载体的细胞亲和性和组织相容性,以探讨该类型放入药物释放体系在临床上的潜在应用。
实验结果表明:制得的双组份缓释载体表面和内壁负载纳米粒,造成表面有突起和凹凸不平的结构。在内部化学结构上,没有观察到两种载体的化学键结合和特殊晶体结构的形成。亲水性良好,极大的增强了细胞的粘附效果和亲和性。缓释实验证明双组份载体系统中的两种载体各自释放,有效的促进了缓释效果。尤其对于纳米粒释放的效果改进最为明显,延长了释放时间,减小了突释效应。对于实验中用到的三种细胞,双组份载体系统都表现出优良的粘附效应和亲和性,甚至对于特定种类细胞有诱导细胞径向生长的效果,因此在临床上具有潜在应用前景。
可以预见,随着研究的进一步深入,这样的双组份缓释载体系统凭借其能够同时缓释多种药物的优点和良好的细胞相容性,必然在今后的组织工程支架的研究和临床应用中具有巨大的价值。
Tissue engineering (TE) is one of the new interdisciplinary fields which combined biology and material science. The aim is to reestablish human tissue and its function by planting scaffolds with functional cells incorporated into the damaged position. Among which, fabricating tissue engineering scaffolds with great biocompatibility become an important research direction.
Electrospinning is a process that produces polymer fibers under the action of an external electric field imposed on a polymer solution or melt. Electrospinning technology is a simple and cost-effective method to prepare ultrafine fibers. In the past decades, significant progresses were achieved on theoretical and experimental studies. Especially, in biomedical fields, ultrafine fibers prepared by elelctrospinning have been widely used in tissue engineering scaffolds, drug delivery system, which has attracted more and more attentions in the world.
Two traditional drug carriers were combined by electrospinning to form a dual-drug composite carrier system which carries two different drugs at one time and release them separately. The physicochemical characteristics of the dual-drug system were assessed by using different methods, the release profiles were then studied and the release mechanism was analyzed after loading and releasing two modal drugs in each carrier of the system.In addition , the adhesion and proliferation of resulting releasing system on different cells were investigated by detecting the biocompatibility and cytocompatibility of the system. Their potential clinical applications were discussed.
The results showed that the nanoparticles were distributed on the surface and internal wall of the nanofibers, which lead the rough fiber surface with sags and crests. No new chemical bond and special crystal structures were observed according to their chemical structures.These resulting releasing system exhibited improved cell adhesion and proliferation due to their good hydrophilcity. The releasing experiments demonstrated the drugs released from each control-release carrier in the dual-drug system separately, which tremendously improved the release efficiency of different drugs. Especially for nanopaticles releasing, release duration was enlarged in a wide range, and the burst releasing or another word-dumping was restrained effectively. Furthermore, three kinds of cells adhered and proliferated very well in the dual-drug releasing mats, the mats have also a capability to induce cells grow in a radial direction, which make it possible to develop thus dual-drug system for clinical application.
Predictably, as the studies goes on, such dual-drug controlled releasing system will be playing a significant role in future scientific researches and clinical applications, thanks to its characteristic in releasing several drugs separately at one time and great biocompatibility.
引文
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