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（受体部位），以支持他们执行或替代受损，感染或癌组织的操作。但是，患者自己的供体骨骼供应不足，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尸体或其他人那里求助于同种异体移植 - 脱细胞（因此生物学上的较低）。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，但在植入时不可生存，因此不如生物骨骼那样好，因为必须在再生之前制作细胞才能渗入材料。几十年来，骨组织对机械负荷有反应，通常使用生物反应器装置进行机械载荷来增强体外骨形成。最近，还发现细胞对纳米级的机械刺激有反应，尤其是纳米级振动会诱导体外培养的细胞的快速骨形成。有趣的是，骨组织在加载时会产生微小的电场，这是一种现象，该现象可以假设在再生过程中有助于骨骼重塑过程。但是，如果这种电刺激对于尚不知道骨移植的快速产生很重要，并且是该项目的重点。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。我们将通过设计新的3D体系结构，以使细胞与生物反应器的协同作用中生长，从而优化这一点。脚手架将发出人体用作治愈骨骼的线索的生理电信号。此外，我们将研究细胞用来形成骨骼的生物构建块，代谢产物，并将其结合到也与生物反应器一起使用的递送系统中。脚手架产生的电力将触发代谢产物的释放，进一步驱动骨形成。这最终将使我们能够提高源自患者自身细胞的活骨移植质量，同时减少我们需要制作的实验室时间。

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

Receptor control in mesenchymal stem cell engineering

• DOI: 10.1038/natrevmats.2017.91
• 发表时间: 2018-03-01
• 期刊: NATURE REVIEWS MATERIALS
• 影响因子: 83.5
• 作者: Dalby, Matthew J.;Garcia, Andres J.;Salmeron-Sanchez, Manuel
• 通讯作者: Salmeron-Sanchez, Manuel

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