Development of Vascular Inspired Electrospun Hollow Fibre Membranes for use in 3D Tissue Culture

开发用于 3D 组织培养的受血管启发的静电纺丝中空纤维膜

• 批准号: 2116587
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2116587
• 关键词: Development; Vascular; Inspired; Electrospun; Hollow

The indispensability of two-dimensional (2D) tissue culture techniques is marred by its insufficient mimicry of cell-cell and cell-extracellular matrix (ECM) interactions. In static three-dimensional (3D) tissue culture scaffolds more than 200 m thick, the short effective range of diffusive mass transfer results in ischemic tissue damage and necrotic regions1-4.In vivo, vasculature transports nutrients and oxygen to tissues through arteries and removes waste metabolites in veins. In leu of a native vascular network in tissue engineered constructs, hollow fibre membranes (HFMs) have been utilised to facilitate convective mass transport5-7. The rigidity and monolithic surface of existing HFMs, however, disrupts passive mechanical cues while inhibiting multimodal mechanical stimulation. Electrospinning, a versatile technique enabling the drawing of nano-fibres from polymer solutions or melts, has enabled the development of bioactive materials which mimic the fibrous structure of the ECM8. Through the utilisation of this technique, electrospun vascular scaffolds (EVSs) have been developed to exhaustively mimic the morphology and mechanical properties of native vasculature. The methods used to produce EVSs have, however, limited their length to short sections. Recently electrospinning has also been implemented in the production of long flexible filaments with similar mechanical properties to that of tendon9. The combination of these techniques may thereby facilitate the novel production of long sections of vascular mimetic HFMs. These in turn may be used to facilitate nutrient and gas transfer while maintaining physiological mechanical cues10,11.While trial and error fabrication has predominantly driven EVS development to date, several complications are still associated with their use. Recent developments in vascular growth and regeneration modelling techniques hold promise towards their use to expedite the identification of optimal scaffold characteristics12. Concurrently, in view of the complex interconnected nature of biological systems, mathematical modelling techniques have been used to decipher the underlying mechanisms determining; culture outcomes, optimising culture conditions and improving culture yields of several cell types13-16. By combining lessons learnt from each of these model development techniques it may thereby be possible to develop a novel model to enable the identification of optimal culture conditions within an electrospun HFM bioreactor. Considering this current state of affairs, my research aims to answer the questions: 1) Can HF membranes be fabricated continuously by electrospinning in a reproducible way to mimic the morphological and mechanical properties of native vasculature and facilitate nutrient exchange to a tertiary scaffold in static and dynamic culture conditions?2) Can such HFs be used as a substrate for biomedical research, potentially for the production of biomaterials intended for therapeutic application?To answer these questions, my specific objectives are therefore:I. Produce novel electrospun HFs which mimic the morphology and mechanical properties of native vasculature through a novel continuous process in a reproducible controllable manner.II. Characterise the transport properties of the membranes and how they may change under mechanical loadingIII. Develop a novel mathematical model to describe the transport across the electrospun HFMsIV. Develop a static and mechanically dynamic HF bioreactor, geometrically informed from the electrospun HFM transport modelV. Evaluate the use of the electrospun HFs for tissue culture in (a) static and (b) mechanically dynamic HF bioreactor configurationsThis project falls within the EPSRC Health Care Technologies research area, specifically towards the development of biomaterials and tissue engineering.

二维（2D）组织培养技术的不可或缺的性能因其细胞细胞和细胞 - 细胞细胞基质（ECM）相互作用的模仿不足而破坏。在超过200 m厚的静态三维（3D）组织培养支架中，扩散质量转移的短有效范围会导致缺血性组织损伤和坏死区域1-4.在体内，脉管系统将养分和氧气传递到通过动脉和静脉中的废物代谢物中的动脉转移到组织中。在组织工程结构中的天然血管网络的LEU中，空心纤维膜（HFM）已被用来促进对流质量传输5-7。然而，现有HFM的刚性和整体表面会破坏被动的机械提示，同时抑制多模式的机械刺激。静电纺丝是一种多功能技术，可以从聚合物溶液或熔体中绘制纳米纤维，从而使生物活性材料的发展能够模仿ECM8的纤维结构。通过这种技术的利用，已经开发出电纺血管支架（EVS），以详尽地模仿天然脉管系统的形态和机械性能。但是，用于生产电动汽车的方法将其长度限制在短部分。最近，静电纺丝在生产具有与肌腱9相似的机械性能的长柔性丝中实施。这些技术的结合可能会促进血管模拟HFM的长期生产。这些反过来又可以用来促进营养和气体转移，同时保持生理机械的CUES10,11111111111.迄今为止，试验和错误制造主要是驱动EVS的开发，但仍有几种并发症与它们的使用有关。血管生长和再生建模技术的最新发展对加快最佳脚手架特征鉴定的使用有望有望。12。同时，鉴于生物系统的复杂相互联系的性质，数学建模技术已被用来破译确定的基本机制。培养结果，优化培养条件并改善几种细胞类型的培养产量13-16。通过结合从每种模型开发技术中学到的经验教训，可以开发出一种新型模型，以鉴定电纺HFM生物反应器中的最佳培养条件。考虑到当前的事务状况，我的研究旨在回答以下问题：1）可以通过可重复的方式通过静电纺丝连续制作HF膜，以模仿天然脉管系统的形态和机械性能，并促进营养交换以在静态和动态培养的情况下进行三位型的研究吗？旨在用于治疗应用的生物材料？回答这些问题，我的具体目标是：i。通过以可重复的可控方式通过新型的连续过程来模仿天然脉管系统的形态和机械性能。II。表征膜的传输特性及其在机械载荷下如何变化。开发一种新型的数学模型来描述跨电纺HFMSIV的运输。开发一种静态和机械动态的HF生物反应器，从电纺HFM传输模型中告知几何学。评估（a）和（b）机械动态的HF生物反应器构型在（a）和（b）在EPSRC卫生保健技术研究领域中的使用，特别是在生物材料和组织工程的开发中，评估了电纺HFS在（a）和（b）机械动态HF生物反应器构型中的使用。