Nanovibrational control of chondrogenic differentiation

软骨形成分化的纳米振动控制

• 批准号: EP/X013057/1
• 负责人: Matthew Dalby
• 金额: $ 110.75万
• 依托单位: University of Glasgow
• 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%2FX013057%2F1
• 关键词: Nanovibrational; control; chondrogenic; differentiation

Cartilage has very low self-healing capacity as it has no blood supply. This means that damage is not repaired and gets worse with time. Arthritis arising from cartilage damage, osteoarthritis (OA), is a massive healthcare burden costing the UK £13B pa when considering healthcare and days lost from work. It can affect reasonably young people with one-third of 50-64-year-olds presenting with OA. Surgeons are very limited in the interventions they can use. They can clean up cartilage defects using keyhole surgery and this can provide some temporary pain relief. They can bring blood from the bone using drilling to encourage the cartilage cells (chondrocytes) to grow, but this results in poor quality cartilage with poor mechanical characteristics (fibrocartilage) and again is a temporary fix. They also have the option of using autologous chondrocyte implantation (ACI) or matrix-assisted ACI, MACI. Here lab-grown chondrocytes are implanted, engraft and form new cartilage. However, lab-grown chondrocytes are not the same as the chondrocytes that allow joint movement and the procedure is thus expensive with limited success. Typically, surgeons will just keep an eye on degeneration and patient pain until joint replacement becomes inevitable. This is a concern as we are an ageing population and increasingly outlive joint replacement lifetime resulting in replacement surgery with much worse outcomes. This leaves older people with pain and limited mobility resulting in physical and mental co-morbidities and reduced lifespan.We have developed a novel bioreactor that can manufacture lab-grown chondrocytes with the correct phenotype. The bioreactor uses tiny vibrations (30 nm applied 1000 times a second) to tell the patients' bone marrow stem cells to turn into the type of chondrocytes found at the articulating surface of joints. We have previously applied the bioreactor to bone cell therapies where we are preparing for a first human trial. Further, cell engraftment is much more successful if the cells are delivered with a supporting scaffold (i.e. in a material). We have developed injectable gels where we can control mechanical properties, degradability and add in little bits of signalling molecules that the chondrocytes like.Together, the technologies can provide an attractive route towards injectable cell therapies delivered via keyhole surgery that can facilitate cartilage regeneration. To address the massive problem of OA, we need to be able to intervene and regenerate and the optimal chondrocyte phenotype is hard to establish; our technologies will enable this.

软骨的自我修复能力很低，因为它没有血液供应。这意味着损坏没有得到修复，并且随着时间的流逝而变得更糟。因软骨损伤，骨关节炎（OA）引起的关节炎是一种大规模的医疗保健伯恩，在考虑医疗保健和工作中损失的天数时，英国造成了英国的耗资13B PA。它可能会影响有合理的年轻人，其中三分之一的50-64岁年轻人出现了OA。外科医生在可以使用的干预措施方面非常有限。他们可以使用钥匙孔手术清理软骨缺陷，这可以减轻一些暂时的疼痛。它们可以使用钻孔从骨骼中带来血液，以鼓励软骨细胞（软骨细胞）生长，但这导致质量较差，机械特征（纤维球杆底）较差，并且再次是临时固定。他们还可以选择使用自体软骨细胞植入（ACI）或基质辅助ACI，MACI。在这里，实验室种植的软骨细胞被植入，植入并形成新软骨。然而，实验室生长的软骨细胞与允许关节运动的软骨细胞不同，因此该过程的成功率很高。通常，外科医生只会关注变性和患者疼痛，直到不可避免地进行关节置换为止。这是一个问题，因为我们是人口老龄化，并且越来越多的关节替代寿命，导致替代手术的结果差得多。这会使老年人患有疼痛和有限的活动能力，导致身体和精神合并症，并降低了寿命。我们开发了一种新型的生物反应器，可以用正确的表型生产实验室生长的软骨细胞。生物反应器使用微小的振动（每秒施加1000倍的30 nm）来告诉患者的骨髓干细胞，将其变成在关节表面表面上发现的软骨细胞的类型。我们以前已经将生物反应器应用于骨细胞疗法中，我们正在为第一次人类试验做准备。此外，如果细胞用支撑支架传递（即在材料中），则细胞植入更加成功。我们已经开发了可注射的凝胶，可以控制机械性能，降解性并增加一些信号分子，而这些软骨细胞像类似的软骨细胞。为了解决OA的巨大问题，我们需要能够干预和再生，并且很难确定最佳的软骨细胞表型。我们的技术将实现这一目标。