Microfabrication approaches to understanding fibroblast roles in tissue regeneration

通过创建限制性和限制性3D微环境在体外模型中引入复杂性是一种新兴的、以地形为导向的方法，它最近为生物材料和细胞生物学研究团体提供了关于细胞迁移和细胞分化机制的复杂方面的关键数据[1，2]。目的：本项目的目标是开发一系列使用添加剂制造和静电纺丝来研究成纤维细胞表型的微支架。根据我们的试验数据，我们假设微制膜将为成纤维细胞提供一个正常的生理学样环境，在这个环境中，它们将保持静止。通过该项目获得的数据将是为复杂的体外组织再生和癌症进展模型的未来发展奠定基础的关键，其中成纤维细胞已被证明是必不可少的。这项研究符合EPSRC投资组合，涵盖了EPSRC战略中突出的广泛主题。将在该博士项目期间开发的研究将支持以下主题中的研究：1)医疗保健技术主题，在该主题中，该研究将支持包括生物材料、组织工程和聚合物材料在内的关键领域：该项目旨在使用聚合物基质(特别是聚己内酯和聚乳酸)来开发用作体外模型的创新膜，并最终为创建可能的组织工程结构做出贡献。2)制造未来主题，在该主题中，该博士项目将支持制造技术、工程设计、材料工程和生物材料：该项目将包括普通纤维膜的制造以及微细加工电纺膜的制造，这些膜将结合添加制造技术(包括显微立体光刻和选择性激光熔化)和传统技术(电纺)进行开发。3)工程主题，在该主题中，本提案将发展生物材料、材料工程和临床技术等战略领域的研究：在该项目中，我们计划开发一系列将使用CAD/CAM和电纺方法制造的微结构生物材料设备。

Introducing complexity within in vitro models via the creation of restrictive and confined 3D microenvironments is an emerging and topographically-orientated approach which has recently provided the biomaterials and cell biology research communities with key data regarding intricate aspects of cell migration as well as cell differentiation mechanisms [1, 2].Aim: The aim of this project is to develop a range of microfabricated scaffolds using additive manufacturing and electrospinning to study fibroblast phenotype. Based on our pilot data, we hypothesise the microfabricated membranes will provide fibroblasts with a normal physiology-like environment in which they will stay quiescent. The data obtained through this project will be key in setting the bases for the future development of complex in vitro tissue regeneration and cancer progression models, in which fibroblasts have shown to be essential.This research fits within the EPSRC portfolio covering a broad range of the themes highlighted in the EPSRC strategy. The research that will be developed during this PhD project will support research included in the following themes:1) Healthcare Technologies Theme in which this research will support key areas including Biomaterials and Tissue Engineering and Polymer Materials: this project aims to use polymeric substrates (polycaprolactone and polylactic acid specifically) for developing innovative membranes to be used as in vitro models and, ultimately, to contribute to the creation of possible tissue engineering constructs.2) Manufacturing the Future Theme in which this PhD project will support research in the areas of Manufacturing Technologies, Engineering Design, Materials Engineering and Biomaterials: this project will include the manufacturing of plain fibrous membranes as well as the fabrication of microfabricated electrospun membranes which will be developed using a combination of additive manufacturing techniques (including microstereolithography and selective laser melting) and conventional techniques (electrospinning).3) Engineering Theme in which this proposal will develop research in the strategic areas of Biomaterials, Materials Engineering and Clinical Technology: in this project we plan to develop a series of microstructured biomaterial devices which will be manufactured using CAD/CAM and electrospinning approaches.