Developing the NanoKick bioreactor to enable tissue engineered bone graft and use of metabolomics to identify bone specific drug candidates.

开发 NanoKick 生物反应器以实现组织工程骨移植，并利用代谢组学来识别骨特异性候选药物。

• 批准号: EP/N013905/1
• 负责人: Matthew Dalby
• 金额: $ 52.09万
• 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: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN013905%2F1
• 关键词: Developing; NanoKick; bioreactor; enable; tissue

Bone graft is regularly used in surgery (plastics, maxillofacial surgery and orthopaedics); bone is actually the second most grafted tissue after blood. Ideally the surgeon wishes to take bone from one area (donor site) to another area (recipient site) to support the operation they are performing. However, a patient's own donor bone is in short supply and its removal can lead to complications in the donor site. This means the surgeon will often recourse to allograft - decellularised (and thus biologically inferior) - bone from other people. A third, and growing, option is synthetic graft. Synthetic graft can be made from biologically active materials, but is not viable and thus not yet as good as living bone. Our bioreactor, that supplies nanoscale 'kicks' to cells in culture can be used to convert mesenchymal stem cells (the stem cells of the bone, simple to isolate from a patient's iliac crest or fat tissue) to bone forming osteoblasts. It can achieve this with cells seeded into 3D environments such as gels or potentially synthetic graft materials. This thus allows us to envisage supply of living bone graft derived from a patient's own cells. The ability to supply such materials would provide a new gold standard for bone grafting.In this project we will thus develop our bioreactor into a flexible platform for study of bone regeneration (which will also be of significant interest to many academic labs in the field) and provision of bone graft. Further to this vision of tissue engineered bone supply, there is also a big need in Pharma for relevant bone models to reduce use of both standard lab models that are very dissimilar to the in-body environment and animal testing which has large cost and ethical consideration. Our ability to produce 3D bone in the lab simply, reproducibly, at low cost and without need for chemical control of cell phenotype (we will just use the nanokicks) will provide an excellent model for testing of drugs for e.g. osteoporosis, osteogenesis imperfecta and other bone conditions. In this project, we will use our technique to study 3D bone formation in the lab and look at what metabolites, the basic building blocks of life, the cell use as they form bone. We will then identify bioactive metabolites and validate them in our bone mimics.Finally, we will test to see feasibility of applying nanokicks to humans to help treat e.g. spinal injury, slow bone repair and osteoporosis etc. We will move from mechanical nanokicks to acoustic nanokicks to achieve this.

骨移植通常用于外科手术（整形外科、颌面外科和整形外科）;骨实际上是仅次于血液的第二大移植组织。理想情况下，外科医生希望将骨从一个区域（供体部位）带到另一个区域（受体部位），以支持他们正在执行的手术。然而，患者自身的供体骨供应短缺，并且其移除可能导致供体部位的并发症。这意味着外科医生经常求助于异体移植-脱细胞（因此生物学上较低）-来自其他人的骨。第三种选择是合成移植，这种选择正在增加。合成移植物可以由生物活性材料制成，但不能存活，因此不如活骨好。我们的生物反应器可以为培养中的细胞提供纳米级的“刺激”，可以用于将间充质干细胞（骨的干细胞，简单地从患者的髂嵴或脂肪组织中分离出来）转化为骨形成成骨细胞。它可以通过将细胞接种到3D环境中来实现这一目标，例如凝胶或潜在的合成移植材料。因此，这使我们能够设想来自患者自身细胞的活骨移植物的供应。在这个项目中，我们将把我们的生物反应器开发成一个灵活的平台，用于研究骨再生（这也将是该领域许多学术实验室的重要兴趣）和提供骨移植物。除了组织工程化骨供应的这一愿景之外，制药公司还非常需要相关的骨模型，以减少使用与体内环境非常不同的标准实验室模型和具有大量成本和伦理考虑的动物试验。我们在实验室中简单、可重复、低成本、不需要化学控制细胞表型（我们将只使用nanokicks）生产3D骨骼的能力将为测试骨质疏松症、骨生成障碍和其他骨骼疾病的药物提供一个很好的模型。在这个项目中，我们将使用我们的技术在实验室中研究3D骨形成，并观察细胞在形成骨时使用的代谢物，生命的基本组成部分。最后，我们将测试将纳米颗粒应用于人类的可行性，以帮助治疗例如脊柱损伤，骨修复缓慢和骨质疏松症等。我们将从机械纳米颗粒转移到声学纳米颗粒来实现这一目标。

项目成果

Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis

用于成骨的新型纳米振动生物反应器和培养器皿的设计、构建和表征

• DOI: 10.1101/543660
• 发表时间: 2019
• 作者: Campsie P

The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells.

• DOI: 10.1126/sciadv.abb7921
• 发表时间: 2021-03
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Hodgkinson T;Tsimbouri PM;Llopis-Hernandez V;Campsie P;Scurr D;Childs PG;Phillips D;Donnelly S;Wells JA;O'Brien FJ;Salmeron-Sanchez M;Burgess K;Alexander M;Vassalli M;Oreffo ROC;Reid S;France DJ;Dalby MJ
• 通讯作者: Dalby MJ

Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products.

• DOI: 10.1042/bcj20190382
• 发表时间: 2020-09-18
• 期刊: The Biochemical journal
• 作者: Childs PG;Reid S;Salmeron-Sanchez M;Dalby MJ
• 通讯作者: Dalby MJ

The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells

• DOI: 10.1101/2020.02.07.938811
• 发表时间: 2020-02
• 期刊: Science Advances
• 影响因子: 13.6
• 作者: T. Hodgkinson;P. Tsimbouri;V. Llopis-Hernandez;P. Campsie;D. Scurr;Peter G. Childs;David Phillips;S. Donnelly;J. Wells;F. O'Brien;M. Salmerón-Sánchez;Karl E. V. Burgess;M. Alexander;M. Vassalli;R. Oreffo;S. Reid;David J. France;M. Dalby

Designing stem cell niches for differentiation and self-renewal.

设计用于分化和自我更新的干细胞生态位。

• DOI: 10.1098/rsif.2018.0388
• 发表时间: 2018-08
• 期刊: Journal of the Royal Society, Interface
• 作者: Donnelly H;Salmeron-Sanchez M;Dalby MJ
• 通讯作者: Dalby MJ