The Henry Royce Institute, Royce Hub Building, The University of Manchester, Manchester M13 9PL, UK.
Civil Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Acta Biomater. 2022 Feb;139:204-217. doi: 10.1016/j.actbio.2021.08.010. Epub 2021 Aug 11.
Electrical stimulation of cells allows exogenous electric signals as stimuli to manipulate cell growth, preferential orientation and bone remodelling. In this study, commercially pure titanium discs were utilised in combination with a custom-built bioreactor to investigate the cellular responses of human mesenchymal stem cells via in-vitro functional assays. Finite element analysis revealed the homogeneous delivery of electric field in the bioreactor chamber with no detection of current density fluctuation in the proposed model. The custom-built bioreactor with capacitive stimulation delivery system features long-term stimulation with homogeneous electric field, biocompatible, sterilisable, scalable design and cost-effective in the manufacturing process. Using a continuous stimulation regime of 100 and 200 mV/mm on cp Ti discs, viability tests revealed up to an approximately 5-fold increase of cell proliferation rate as compared to non-stimulated controls. The human mesenchymal stem cells showed more elongated and differentiated morphology under this regime, with evidence of nuclear elongation and cytoskeletal orientation perpendicular to the direction of electric field. The continuous stimulation did not cause pH fluctuations and hydrogen peroxide production caused by Faradic reactions, signifying the suitability for long-term toxic free stimulation as opposed to the commonly used direct stimulation regime. An approximate of 4-fold increase in alkaline phosphatase production and approximately 9-fold increase of calcium deposition were observed on 200 mV/mm exposed samples relative to non-stimulated controls. It is worth noting that early stem cell differentiation and matrix production were observed under the said electric field even without the presence of chemical inductive growth factors. STATEMENT OF SIGNIFICANCE: This manuscript presents a study on combining pure titanium (primarily preferred as medical implant materials) and electrical stimulation in a purpose-built bioreactor with capacitive stimulation delivery system. A continuous capacitive stimulation regime on titanium disc has resulted in enhanced stem cell orientation, nuclei elongation, proliferation and differentiation as compared to non-stimulated controls. We believe that this manuscript creates a paradigm for future studies on the evolution of healthcare treatments in the area of targeted therapy on implantable and wearable medical devices through tailored innovative electrical stimulation approach, thereby influencing therapeutic conductive and electroactive biomaterials research prospects and development.
电刺激细胞可以将外部电信号作为刺激物来操纵细胞生长、优先取向和骨骼重塑。在这项研究中，商用纯钛盘与定制的生物反应器结合使用，通过体外功能测定来研究人骨髓间充质干细胞的细胞反应。有限元分析显示，生物反应器腔室内均匀地传递电场，在所提出的模型中没有检测到电流密度波动。具有电容刺激传递系统的定制生物反应器具有长期的均匀电场刺激、生物相容性、可灭菌性、可扩展性设计和制造过程中的成本效益。在 100 和 200 mV/mm 的 cp Ti 盘连续刺激下，与非刺激对照组相比，细胞增殖率提高了约 5 倍。在这种条件下，人骨髓间充质干细胞表现出更细长和分化的形态，核伸长和细胞骨架取向垂直于电场方向的证据。连续刺激不会引起 Faradic 反应引起的 pH 波动和过氧化氢产生，这表明与常用的直接刺激相比，它适合长期无毒性刺激。与非刺激对照组相比，在 200 mV/mm 暴露的样品中观察到碱性磷酸酶产量增加约 4 倍，钙沉积增加约 9 倍。值得注意的是，即使不存在化学诱导生长因子，也观察到了在所述电场下的早期干细胞分化和基质产生。 意义声明：本文介绍了一项将纯钛（主要作为医用植入材料首选）与带有电容刺激传递系统的定制生物反应器相结合的研究。与非刺激对照组相比，钛盘上的连续电容刺激可增强干细胞的定向、核伸长、增殖和分化。我们相信，本文为未来在植入式和可穿戴医疗设备领域的靶向治疗中通过定制创新的电刺激方法对医疗保健治疗的发展演变的研究创建了一个范例，从而影响治疗性导电和电活性生物材料的研究前景和发展。
