Nanovibrational control of chondrogenic differentiation

软骨形成分化的纳米振动控制

• 批准号: 2795762
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2795762
• 关键词: Nanovibrational; control; chondrogenic; differentiation

Studentship strategic priority area: Healthcare TechnologiesKeywords: Osteoarthritis (OA), Tissue Engineering (TE) Nanovibration, Chondrogenesis, PEG-hydrogelsCartilage is an avascular and aneural tissue and so suffers poor healing and unattended cartilage damage leads to osteoarthritis (OA), a degenerative joint disease. At present, the World Health Organization (WHO) has ranked OA as the second greatest cause of disability and the primary health disease with the fastest rate of growth. As a result, tissue engineering (TE) is an emerging technique for cartilage regeneration. In this new project, we will use a novel bioreactor that delivers tiny, nanoscale (30 nm, 1000 Hz) vibrations to MSCs to expand and differentiate them into chondrocytes that produce the correct hyaline cartilage phenotype. This nanovibrational control of cells has as a result to form the smooth, articulating cartilage of the joint and prevents fibrocartilage formation. Interferometry and accelerometry measurements will be done to characterize the nano-mechanical cues that force the cells into differentiation in the bioreactor. Following these steps, we are going to characterize and identify the cells' phenotype in response to nanovibrations by using super-resolution confocal microscopy, qPCR, western analysis, RNA seq, and metabolomics. Then we are going to move to the encapsulation of the nanovibrated-chondrocytes into our novel hydrogel family. These synthetic, bioengineered, viscoelastic hydrogels belong to a family of polyethylene glycol (PEG)-based hydrogels where we will seek to manipulate the biophysical properties to match the stiffness of native cartilage. These hydrogels will be made of interpenetrated polymer networks (IPNS) that contain an elastic first network and the second network of a high molecular weight polymer that provides the viscous component. The second network will present peptide motifs (such as HAVDI) that are cadherin mimics; important for cartilage formation. Rheological measurements will be carried out to determine the elastic (G') and loss (G'') shear modulus of the material. The project aims to build a 3D delivery platform (tailored hydrogels) to support the nanovibrated-chondrocytes culture and prevent fibrocartilage formation as is the case with current carriers such as alginate gels or collagen membranes. Here we are presenting a highly interdisciplinary project that promises to manufacture a new technology system that focuses on bioengineered cell therapy. These biomaterials are promising as they are helping us to explore new methods to replace animal experimentation, and most importantly, create a deliverable injectable system that can be tuned to maximally support chondrogenesis and maintain mobility for people in need.

学生战略优先领域：医疗保健技术关键词：骨关节炎(OA)，组织工程(TE)纳米振动，软骨生成，聚乙二醇水凝胶软骨是一种无血管和神经组织，因此愈合不良，无人看管的软骨损伤会导致骨关节炎(OA)，一种退行性关节疾病。目前，世界卫生组织(WHO)已将骨性关节炎列为第二大致残原因和增长速度最快的主要健康疾病。因此，组织工程是一种新兴的软骨再生技术。在这个新的项目中，我们将使用一种新型的生物反应器，将微小的纳米级(30 nm，1000赫兹)的振动传递给MSCs，使其扩张并分化为软骨细胞，从而产生正确的透明软骨表型。这种对细胞的纳米振动控制结果是形成了关节的光滑关节软骨，并防止了纤维软骨的形成。将进行干涉测量和加速测量，以表征迫使细胞在生物反应器中分化的纳米机械信号。在这些步骤之后，我们将使用超分辨率共聚焦显微镜、qPCR、蛋白质分析、RNA序列和代谢组学来表征和鉴定细胞对纳米振动的响应表型。然后，我们将转向将纳米振动软骨细胞封装到我们的新型水凝胶家族中。这些合成的、生物工程的粘弹性水凝胶属于聚乙二醇基水凝胶家族，我们将寻求操纵生物物理特性以匹配天然软骨的硬度。这些水凝胶将由互穿聚合物网络(IPN)制成，该网络包含弹性的第一网络和提供粘性成分的第二网络的高分子量聚合物。第二个网络将呈现多肽基序(如HAVDI)，它们是钙粘附素的模拟物；对软骨形成很重要。将进行流变学测量，以确定材料的弹性(G‘)和损失(G’)剪切模数。该项目旨在建立一个3D传递平台(定制水凝胶)，以支持纳米振动软骨细胞的培养，并防止纤维软骨的形成，就像目前的载体如海藻酸凝胶或胶原膜一样。在这里，我们提出了一个高度跨学科的项目，承诺制造一种专注于生物工程细胞疗法的新技术系统。这些生物材料前景看好，因为它们正在帮助我们探索新的方法来取代动物实验，最重要的是，它们创建了一个可交付的可注射系统，可以进行调整，以最大限度地支持软骨生成并保持有需要的人的流动性。