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.

软骨的自愈能力很低，因为它没有血液供应。这意味着损坏无法修复，并且随着时间的推移而变得更糟。由软骨损伤引起的关节炎，骨关节炎（OA），是一个巨大的医疗保健负担，在考虑医疗保健和工作日损失时，每年花费英国130亿英镑。它可以影响相当年轻的人，三分之一的50-64岁的人患有OA。外科医生可以使用的干预措施非常有限。他们可以清理软骨缺损使用锁孔手术，这可以提供一些暂时的疼痛缓解。他们可以使用钻孔从骨骼中获取血液以促进软骨细胞（软骨细胞）生长，但这会导致具有较差机械特性的劣质软骨（纤维软骨），并且再次是临时修复。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，实验室培养的软骨细胞被植入，移植并形成新的软骨。然而，实验室培养的软骨细胞与允许关节运动的软骨细胞不同，因此该过程昂贵且成功率有限。通常情况下，外科医生只会密切关注退化和病人的疼痛，直到关节置换成为不可避免的。这是一个值得关注的问题，因为我们是一个老龄化的人口，越来越多的寿命超过关节置换术的寿命，导致置换手术的结果更差。这给老年人带来了疼痛和行动不便，导致身体和精神共病和寿命缩短。我们开发了一种新型生物反应器，可以制造具有正确表型的实验室培养软骨细胞。生物反应器使用微小的振动（每秒施加1000次30 nm）来告诉患者的骨髓干细胞转化为关节关节表面发现的软骨细胞类型。我们之前已经将生物反应器应用于骨细胞疗法，我们正在准备进行首次人体试验。此外，如果细胞与支撑支架一起递送（即在材料中），则细胞移植更加成功。我们已经开发出可注射的凝胶，我们可以控制机械性能，降解性，并添加软骨细胞喜欢的信号分子。这些技术可以共同提供一种有吸引力的途径，通过锁孔手术提供可注射的细胞疗法，可以促进软骨再生。为了解决OA的巨大问题，我们需要能够进行干预和再生，而最佳的软骨细胞表型很难建立;我们的技术将实现这一点。