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

骨移植经常用于外科手术(整形外科、颌面部外科和矫形外科)；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(供区)移至另一个区域(受区)，以支持他们正在进行的手术。然而，患者自己的供骨供应不足，摘除供骨可能会导致供骨部位的并发症。这意味着外科医生通常会求助于同种异体骨移植--脱细胞的(因此生物学上劣质的)--来自其他人的骨。第三种选择是合成嫁接，而且这种选择还在不断增加。合成移植物可以由生物活性材料制成，但不可行，因此还没有活骨那么好。我们的生物反应器为培养中的细胞提供纳米级的“踢”，可以用来将间充质干细胞(骨的干细胞，很容易从患者的髂骨或脂肪组织中分离出来)转化为成骨细胞。它可以通过将细胞种植到3D环境中来实现这一点，例如凝胶或潜在的合成移植材料。因此，我们可以设想从患者自己的细胞中获得活的骨移植的供应。这种材料的供应能力将为骨移植提供一个新的黄金标准。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(这也将引起该领域许多学术实验室的极大兴趣)和提供骨移植。除了这种组织工程化骨骼供应的愿景外，制药公司还非常需要相关的骨骼模型，以减少使用与体内环境非常不同的标准实验室模型，以及具有高昂成本和伦理考虑的动物试验。我们能够在实验室中简单、可重复、低成本地生产3D骨，并且不需要对细胞表型进行化学控制(我们将只使用纳米棒)，这将为测试治疗骨质疏松症、成骨不全和其他骨骼疾病的药物提供一个极好的模型。在这个项目中，我们将使用我们的技术来研究实验室中的3D骨骼形成，并查看哪些代谢物，生命的基本组成部分，细胞在形成骨骼时使用。然后，我们将识别生物活性代谢物，并在我们的骨骼模拟物中验证它们。最后，我们将测试将纳米棒应用于人类以帮助治疗脊髓损伤、缓慢的骨骼修复和骨质疏松症等的可行性。我们将从机械纳米棒转向声学纳米棒来实现这一目标。

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.