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.

骨移植物经常用于手术（塑料，颌面外科和骨科）；骨骼实际上是仅次于血液的第二大植物组织。理想情况下，外科医生希望将骨头从一个区域（供体部位）带到另一个区域（接收者部位），以支持他们执行的操作。但是，患者自己的供体骨骼缺乏供应，其去除可能会导致供体部位并发症。这意味着外科医生通常会从其他人那里求助于同种异体移植物 - 脱细胞（因此生物学上的）骨头。三分之一且生长的选择是合成移植物。合成移植物可以由生物活性材料制成，但不可行，因此尚不像活骨一样好。我们的生物反应器，将纳米级“踢”向培养细胞提供的纳米级“踢”可用于转化间充质干细胞（骨骼的干细胞，易于分离从患者的伊利亚克rest或脂肪组织）变成成骨细胞的骨骼。它可以通过播种成3D环境（例如凝胶或潜在合成移植物材料）的细胞来实现这一目标。因此，这使我们能够设想源自患者自身细胞的活骨移植物的供应。提供此类材料的能力将为骨移植提供新的黄金标准。在该项目中，我们将将生物反应器开发为一个灵活的骨骼再生平台（这对现场的许多学术实验室也将引起骨移植的重要兴趣）和骨移植。除了对组织工程的骨骼供应的愿景之外，药物对相关骨模型的使用也很需要减少两种标准实验室模型的使用，这些模型与内部内部环境和动物测试非常不同，这些模型和动物测试具有很大的成本和道德考虑。我们在实验室中简单地（可重复地）以低成本而无需对细胞表型的化学控制（我们将仅使用纳米克人）生产3D骨的能力将为测试药物的出色模型，例如骨质疏松症，骨生成不完美和其他骨条件。在这个项目中，我们将使用我们的技术研究实验室中的3D骨形成，并研究哪些代谢物，生命的基本构建基础，细胞形成骨骼的使用。然后，我们将识别生物活性代谢产物并在骨模拟物中验证它们。在本文中，我们将测试以发现将纳米棒应用于人类以帮助治疗的可行性，例如脊柱损伤，缓慢的骨骼修复和骨质疏松症等。我们将从机械纳米基转移到声学纳米基，以实现这一目标。

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.

• 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