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.

学生验证战略优先领域：医疗保健技术关键单词：骨关节炎（OA），组织工程（TE）纳米振动，软骨发生，Peg-Hydregelscartilage是一种管脉和脑膜组织，因此会遭受较差的愈合和无关紧要的软骨损害，导致了稳定的软骨疾病（osteoarity）（osteoartheris）（o.Aa）（OAA）。目前，世界卫生组织（WHO）将OA列为残疾第二大原因和原发性疾病，其增长率最快。结果，组织工程（TE）是一种新兴的软骨再生技术。在这个新项目中，我们将使用一种新型的生物反应器，该生物反应器可将微小的纳米级（30 nm，1000 Hz）振动提供给MSCS，以扩展并区分它们为产生正确的透明软骨表型的软骨细胞。这种细胞的纳米振动控制具有形成平滑，明确的软骨的关节的软骨，并防止纤维球杆菌的形成。将进行干涉测量和加速度测量值，以表征纳米机械线索，这些线索迫使细胞在生物反应器中分化。遵循这些步骤，我们将通过使用超分辨率共聚焦显微镜，QPCR，Western Analysis，RNA SEQ和代谢组学来表征和识别细胞表型，以应对纳米振荡。然后，我们将转移到纳米校准的软骨细胞中，以纳入我们的新型水凝胶家族。这些合成的，生物工程的粘弹性水凝胶属于基于聚乙烯乙二醇（PEG）的水凝胶家族，我们将寻求操纵生物物理特性以匹配天然软骨的刚度。这些水凝胶将由包含弹性第一网络的互穿聚合物网络（IPN）制成，以及提供粘性成分的高分子重量聚合物的第二个网络。第二个网络将呈现肽蛋白模仿的肽基序（例如HAVDI）；对于软骨形成很重要。将进行流变学测量，以确定材料的弹性（g'）和损失（G''）剪切模量。该项目旨在建立一个3D递送平台（量身定制的水凝胶），以支持纳米型的 - 软骨细胞培养物，并防止纤维电纤维形成，就像当前载体（如藻酸盐凝胶或胶原蛋白膜）一样。在这里，我们提出了一个高度的跨学科项目，该项目有望制造一种专注于生物工程细胞疗法的新技术系统。这些生物材料很有希望，因为它们正在帮助我们探索替代动物实验的新方法，最重要的是，创建了可交付的可注射系统，该系统可以调整以最大程度地支持软骨生成并维持有需要的人的流动性。