Rapid Bone Graft Synthesis Through Dual Piezoelectric/Nanomechaniocal Stimulation

骨移植常用于外科手术（整形外科、颌面外科和骨科）；骨实际上是仅次于血液的第二大移植组织。理想情况下，外科医生希望将骨头从一个部位（供体部位）移到另一个部位（受体部位），以支持他们正在进行的手术，或替换受损、感染或癌变的组织。然而，患者自己的供体骨供应不足，切除供体骨会导致供体部位的并发症。这意味着外科医生通常会求助于同种异体移植——去细胞（因此生物学上是劣等的）——来自尸体或其他人的骨头。第三种选择是人工移植物，这种选择正在不断发展。人造骨可以由生物活性材料制成，但在植入时不可行，因此还不如活骨好，因为在再生之前必须让细胞渗入材料。几十年来，人们已经知道骨组织对机械负荷有反应，通常，通过生物反应器装置进行机械负荷来增强体外骨形成。最近，人们还发现细胞对纳米级机械刺激有反应，特别是纳米级振动诱导体外培养的细胞快速成骨。有趣的是，骨组织在加载时会产生微小的电场，这种现象被假设有助于再生过程中的骨重塑过程。然而，这种电刺激对骨移植物的快速生成是否重要尚不清楚，是本项目的重点。我们的生物反应器为培养的细胞提供纳米级的“踢”，可用于将间充质干细胞（骨的干细胞，很容易从患者的髂嵴或脂肪组织中分离出来）转化为成骨细胞。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情况下生长。这些支架会发出生理电信号，身体以此作为线索来愈合骨骼。此外，我们将研究细胞用来形成骨骼的生物构件，代谢物，并将它们整合到与生物反应器一起工作的输送系统中。支架产生的电将触发代谢产物的释放，进一步推动骨的形成。这将最终使我们能够提高来自患者自身细胞的活骨移植物的质量，同时减少我们制作它所需的实验室时间。

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.