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Functionally graded scaffolds for the engineering of interface tissues using hybrid twin screw extrusion/electrospinning technology.

机译:使用混合双螺杆挤出/静电纺丝技术对界面组织进行工程改造的功能分级支架。

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Tissue engineering is the application of the principles of engineering and life sciences for the development of biological alternatives for improvement or regeneration of native tissues. Native tissues are complex structures with functions and properties changing spatially and temporally, and engineering of such structures requires functionally graded scaffolds with composition and properties changing systematically along various directions. Utilization of a new hybrid technology integrating the controlled feeding, compounding, dispersion, deaeration, and pressurization capabilities of extrusion process with electrospinning allows incorporation of liquids and solid particles/nanoparticles into polymeric fibers/nanofibers for fabrication of functionally graded non-woven meshes to be used as scaffolds in engineering of tissues. The capabilities of the hybrid technology were demonstrated with a series of scaffold fabrication and cell culturing studies along with characterization of biomechanical properties. In the first study, the hybrid technology was employed to generate concentration gradations of beta-tricalcium phosphate (beta-TCP) nanoparticles in a polycaprolactone (PCL) binder, between two surfaces of nanofibrous scaffolds. These scaffolds were seeded with pre-osteoblastic cell line (MC3T3-E1) to attempt to engineer cartilage-bone interface, and after four weeks, the tissue constructs revealed formation of continuous gradations in extracellular matrix akin to cartilage-bone interface in terms of distributions of mineral concentrations and biomechanical properties. In a second demonstration of the hybrid technology, graded differentiation of stem cells was attempted by using insulin, a known stimulator of chondrogenic differentiation, and beta-glycerol phosphate (beta-GP), for mineralization. Concentrations of insulin and beta-GP in PCL were controlled to monotonically increase and decrease, respectively, along the length of scaffolds, which were then seeded with adipose derived stromal cells (h-ADSCs). Analysis of resulting tissue constructs revealed chondrocytic differentiation of h-ADSCs, with both the chondrocytic cell concentration and mineralization varying as a function of distributions of concentrations of insulin and beta-GP, respectively. The investigation also covered characterization of biomechanical properties of native bovine osteochondral tissue samples, which were then compared with biomechanical properties of tissue constructs at different stages of development. The hybrid technology developed in this thesis should provide another enabling platform for the fabrication of functionally graded scaffolds that aim to mimic the elegant gradations found in myriad native tissues.
机译:组织工程学是工程学和生命科学原理在开发生物替代品以改善或再生天然组织方面的应用。天然组织是复杂的结构,其功能和特性会在空间和时间上发生变化,而此类结构的工程设计需要功能分级的支架,其组成和特性会沿各个方向系统地变化。利用一种新的混合技​​术,将挤压过程的受控进料,混料,分散,除气和加压功能与静电纺丝相结合,可将液体和固体颗粒/纳米颗粒掺入聚合物纤维/纳米纤维中,以制造功能梯度的非织造网。在组织工程中用作支架。通过一系列支架制造和细胞培养研究以及生物力学特性表征,证明了混合技术的功能。在第一个研究中,采用混合技术在纳米纤维支架的两个表面之间的聚己内酯(PCL)粘合剂中生成β-磷酸三钙(β-TCP)纳米颗粒的浓度梯度。这些支架上植入了成骨细胞前体细胞系(MC3T3-E1),以试图工程化软骨-骨界面,并在四周后,组织构建体显示出在细胞外基质中就软骨-骨界面而言连续渐变的形成矿物质浓度和生物力学特性。在杂交技术的第二次演示中,试图通过使用已知的软骨形成分化刺激剂胰岛素和β-甘油磷酸酯(β-GP)来实现干细胞的分级分化。控制PCL中胰岛素和β-GP的浓度分别沿支架的长度单调增加和减少,然后将其接种到脂肪来源的基质细胞(h-ADSCs)中。所得组织构建物的分析揭示了h-ADSC的软骨细胞分化,软骨细胞浓度和矿化度分别随胰岛素和β-GP的浓度分布而变化。该研究还涵盖了天然牛骨软骨组织样品生物力学特性的表征,然后将其与处于不同发育阶段的组织构建体的生物力学特性进行了比较。本文开发的混合技术应该为功能梯度支架的制造提供另一个平台,该支架旨在模仿无数天然组织中发现的优雅梯度。

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