Scaff-Net: 3 Dimensional multiphoton polymerisation printed scaffolds for medium throughput recording from stem cell derived human cortical networks.

Scaff-Net：3 维多光子聚合打印支架，用于从干细胞衍生的人类皮质网络进行中等通量记录。

• 批准号: EP/X018385/1
• 负责人: Harri Parri
• 金额: $ 25.63万
• 依托单位: Aston University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX018385%2F1
• 关键词: Scaff; Net; Dimensional; multiphoton; polymerisation

A major growing threat to human health, quality of life and society is that of neurological and neurodegenerative diseases. The annual cost of treating brain conditions in the EU is estimated at ~798 billion Euros, with brain disorders such as depression, bipolar disorder, epilepsy and dementia affecting about 165 million Europeans or 1 in 3 people (European Commission).There is a need for drug treatments and therapies for such conditions, however, advance is hampered by the lack of suitable methods to test and screen potentially useful molecules. One major problem is that most research traditionally has been conducted using animal tissues such as rat or mouse brains or cultured neurons from these animals. However, it seems that human brain cells responses and their connections in many ways may be different to mouse neurons. Another problem is that although cells can be cultured and investigated over a period of weeks or months they are usually grown on flat surfaces for testing by scientists and the pharmaceutical industry, which is totally different to the way that they grow in the brain. The human brain consists of networks of neurons communicating with each through connections that radiate in all directions in 3 dimensions. The pattern of connections and its complexity is one of the fundamental features that enables human brains to function as they do. Cultures of neuronal networks grown on flat 2D surfaces cannot make the same connections as they would in the living brain, and therefore the activity that they produce will also be different. To be able to develop drugs and therapies for human conditions, the ideal cell system would be 3 dimensional cultures of human neuronal networks that we could record activity from and test drugs. It would also be ideal if many recordings could be done at the same time from different networks so that many drugs could be tested in a shorter time. This is what we will achieve with Scaff-Net. Using laser-based technology we will "print" small scaffolds that will support neuronal networks. To obtain human neuronal networks we will use human derived stem cells that come from skin samples. We will grow neurons from the stem cells and culture these on the scaffolds where they will form connected networks. Many of the 2D flat cultures grown today are grown on grids of many small electrodes to record activity. In Scaff-Net we will print a single scaffold and neuronal network on each single electrode of these grids of multi electrode arrays. This will mean that these electrode arrays will be transformed from being able to record at many sites on a single flat 2D culture to be able to record activity from many 3D networks on scaffolds (about 60!) at the same time. This will mean that the testing of drugs can be made quicker, and so therapeutic discoveries will be made quicker. In the future we would expect Scaff-Net devices to have a major impact on the way that drug discovery is conducted and transform the field.

神经疾病和神经退行性疾病是对人类健康、生活质量和社会的一个日益严重的威胁。据估计，欧盟每年治疗脑部疾病的费用约为7980亿欧元，抑郁症、躁郁症、癫痫和痴呆症等脑部疾病影响到约1.65亿欧洲人，即三分之一的人(欧盟委员会)。这些疾病需要药物治疗和治疗，但由于缺乏合适的方法来测试和筛选潜在有用的分子，这一进展受到阻碍。一个主要问题是，大多数研究传统上都是使用动物组织，如大鼠或小鼠的大脑或培养的这些动物的神经元进行的。然而，似乎人类脑细胞的反应和它们在许多方面的联系可能与小鼠的神经元不同。另一个问题是，尽管细胞可以在几周或几个月的时间里培养和研究，但它们通常生长在平坦的表面上，供科学家和制药行业测试，这与它们在大脑中的生长方式完全不同。人脑由神经元网络组成，每个神经元通过连接在3个维度向各个方向辐射。连接的模式及其复杂性是使人类大脑能够正常运作的基本特征之一。生长在平面2D表面上的神经元网络的培养不能像在活的大脑中那样建立同样的连接，因此它们产生的活动也将不同。为了能够开发针对人类状况的药物和疗法，理想的细胞系统将是人类神经网络的三维培养，我们可以从中记录活动并测试药物。如果可以从不同的网络同时进行许多录音，这样就可以在更短的时间内对许多药物进行测试，这也是理想的。这就是我们将通过Scaff-Net实现的。利用基于激光的技术，我们将“打印”支持神经元网络的小型支架。为了获得人类神经元网络，我们将使用来自皮肤样本的人类干细胞。我们将从干细胞中培养神经元，并将其培养在支架上，在那里它们将形成相互连接的网络。今天种植的许多2D平板培养物是在许多小电极的栅格上生长的，以记录活动。在SCAFF-Net中，我们将在这些多电极阵列的网格的每个单一电极上打印单个支架和神经元网络。这将意味着这些电极阵列将从能够在单个平面2D培养上记录多个地点的电极阵列转变为能够记录支架上多个3D网络的活动(约60！)在同一时间。这将意味着可以更快地进行药物测试，从而更快地发现治疗方法。在未来，我们预计Scaff-Net设备将对药物发现的进行方式产生重大影响，并改变该领域。