Rapid Bone Graft Synthesis Through Dual Piezoelectric/Nanomechaniocal Stimulation

通过压电/纳米机械双刺激快速骨移植合成

• 批准号: BB/P00220X/1
• 负责人: Matthew Dalby
• 金额: $ 51.93万
• 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: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP00220X%2F1
• 关键词: Rapid; Bone; Graft; Synthesis; Through

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 or to replace damaged, infected or cancerous tissue . However, a patient's own donor bone is in short supply and its removal can lead to complications at the donor site. This means the surgeon will often recourse to allograft - decellularised (and thus biologically inferior) - bone from cadavers or other people. A third, and growing, option is synthetic graft. Synthetic graft can be made from biologically active materials, but is not viable at the time of implantation and thus not yet as good as living bone, as cells must be made to infiltrate the material prior to regeneration. It has been known for many decades that bone tissue responds to mechanical loading and commonly, mechanical loading via a bioreactor device is employed to enhanced bone formation in vitro. Recently, it has been also discovered that cells respond to nanoscale mechanical stimulation, and in particular, that nanoscale vibrations induce rapid bone formation from cells cultured in vitro. Interestingly, bone tissue produces minute electrical fields when loaded, a phenomenon which is hypothesised to help with the bone remodelling process during regeneration. However, if this electrical stimulation is important for the rapid generation of bone graft is not yet known and is a focus of this project. 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. We will optimise this by designing new 3D architectures for the cells to grow in that work in synergy with the bioreactor. The scaffolds will emit physiological electrical signals that the body uses as cues to heal bone. Further, we will look at the biological building blocks, metabolites, that the cells use to form bone and incorporate these into delivery systems that also work with the bioreactor. The electricity produced by the scaffolds will trigger release of the metabolites, further driving bone formation.This will ultimately allow us to improve the quality of living bone graft derived from a patient's own cells while reducing the lab time we need to make it.

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或替换受损，感染或癌组织。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。这意味着外科医生将经常求助于同种异体移植-脱细胞（因此生物学上较低）-来自尸体或其他人的骨。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，但在植入时不能存活，因此还不如活骨，因为细胞必须在再生之前渗透材料。几十年来，已知骨组织对机械负荷有反应，并且通常，通过生物反应器装置的机械负荷用于增强体外骨形成。最近，还发现细胞响应于纳米级机械刺激，特别是纳米级振动诱导体外培养的细胞快速形成骨。有趣的是，骨组织在加载时产生微小的电场，这种现象被假设有助于再生过程中的骨重塑过程。然而，这种电刺激是否对骨移植物的快速生成很重要尚不清楚，这是该项目的重点。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。我们将通过设计新的3D结构来优化这一点，使细胞在与生物反应器协同工作的环境中生长。这些支架会发出生理电信号，身体会利用这些信号来修复骨骼。此外，我们将研究细胞用于形成骨骼的生物构建块，代谢物，并将其纳入与生物反应器一起工作的输送系统。支架产生的电流将触发代谢物的释放，进一步推动骨形成。这将最终使我们能够提高从患者自身细胞中提取的活骨移植物的质量，同时减少我们所需的实验室时间。

项目成果

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

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

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