The Molecular Mechanism of the Surface Charge of Piezoelectric Materials for Bone Regenerative Engineering

骨再生工程压电材料表面电荷的分子机制

基本信息

  • 批准号:
    9890521
  • 负责人:
  • 金额:
    $ 19.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-01-01 至 2021-12-31
  • 项目状态:
    已结题

项目摘要

Abstract Each year in the United States, over 1 million bone reconstruction procedures are performed. Electrical stimulation (ES) has been shown to exhibit profound effects on bone repair and regeneration in clinical applications. However, current ES devices present many drawbacks including the inefficiency of generated electrical fields (for external ES devices), the bulky size and toxic materials used in electrical stimulators, and the non-degradability of implanted ES devices. Piezoelectric materials, which can generate electric charge during deformation and vice versa, can be employed to create self-powered electrical stimulators that can effectively to stimulate bone repair and regeneration. Specifically, piezoelectric charges generated on the surface of the piezoelectric materials have proven to effectively stimulate stem cell proliferation, migration, osteogenic differentiation and remodeling both in vitro and in vivo. However, the underlying molecular mechanism responsible for these observations is still unclear. The preliminary results demonstrated that surface charge on a biomaterial could alter the calcium signaling pathways, which could possess intrinsic osteoinductivity by stimulating the production and secretion of cell-based osteoinductive protein growth factor (BMP-2). The hypothesis of this grant application is that surface charge generated on piezoelectric materials will induce enhanced Ca2+ oscillation and/or ECM protein adsorption, and such a change may trigger the stem cell osteo-differentiation and/or cytokine-based inductive autocrine and paracrine loops. The main goal of this application is to investigate the fundamental molecular mechanism of how the surface charge of piezoelectric materials can positively influence the degree of healing and promote bone tissue regeneration. Three specific aims are proposed to test the hypothesis of our proposal. In Aim 1, we will design, fabricate, and characterize piezoelectric materials for the study of osteogenic signal mechanisms. In Aim 2, we will study how Ca2+ signaling mechanisms and/or ECM deposition in respond to the piezoelectric charges generated on the piezoelectric materials. In Aim 3, using microarrays, we will examine the expression profile of a variety of genes during osteogenic differentiation of the seeded mesenchymal stem cells (MSC) on the piezoelectric materials. The data from this project will provide the necessary information to explore further the nature of piezoelectric surface charge for bone repair and regeneration applications. The first milestone achievable through this proposal is the development of a piezoelectric scaffold and the setup for studying the osteogenic signaling mechanisms and the related characterizations of the scaffold itself. The second achievable milestone is the evaluation of the role of Ca2+ signaling mechanisms as well as ECM adsorption in response to the surface charges generated on the piezoelectric materials. The third milestone is the assessment of the expression profiles of a variety of genes during osteogenic differentiation of MSCs on the piezoelectric scaffold.
摘要 在美国,每年进行超过100万例骨重建手术。电 刺激(ES)已被证明在临床上对骨修复和再生具有深远的影响, 应用.然而,当前的ES设备存在许多缺点,包括生成的能量的低效率。 电场(用于外部ES器械),电刺激器中使用的体积庞大和有毒材料,以及 植入ES器械的不可降解性。压电材料,可以产生电荷 在变形过程中以及在变形过程中可以用来产生自供电电刺激器 有效地刺激骨修复和再生。具体地,在压电晶体上产生的压电电荷 压电材料的表面已被证明可以有效地刺激干细胞增殖,迁移, 成骨分化和重塑的体外和体内研究。然而, 造成这些现象的机制尚不清楚。初步结果表明, 生物材料上的表面电荷可以改变钙信号通路,这可能具有内在的 通过刺激基于细胞的骨诱导蛋白生长因子的产生和分泌的骨诱导性 (BMP-2)。这项资助申请的假设是压电材料表面产生的电荷 将诱导增强的Ca 2+振荡和/或ECM蛋白吸附,并且这样的变化可能触发干细胞的凋亡。 细胞骨分化和/或基于精氨酸的诱导性自分泌和旁分泌环。这个的主要目标 应用是研究压电材料表面电荷的基本分子机制, 材料可以积极影响愈合程度并促进骨组织再生。三个具体 提出了目标来检验我们提案的假设。在目标1中,我们将设计、制造和表征 压电材料用于成骨信号机制的研究。在目标2中,我们将研究Ca 2 + 信号传导机制和/或ECM沉积响应于在膜上产生的压电电荷, 压电材料在目标3中,使用微阵列,我们将检查各种表达谱, 基因在成骨分化过程中的种子间充质干细胞(MSC)的压电 材料.该项目的数据将提供必要的信息,以进一步探讨 用于骨修复和再生应用的压电表面电荷。第一个里程碑 通过这一建议,压电支架的发展和研究成骨细胞的设置, 信号传导机制和支架本身的相关表征。第二个可实现的里程碑 是对Ca 2+信号传导机制的作用以及ECM吸附的评估, 压电材料上产生的表面电荷。第三个里程碑是评估 在压电支架上MSC的成骨分化过程中各种基因的表达谱。

项目成果

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Wai Hong Lo其他文献

Wai Hong Lo的其他文献

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{{ truncateString('Wai Hong Lo', 18)}}的其他基金

Novel Injectable Analgesic Delivery System for Chronic Musculoskeletal Pain Manag
用于治疗慢性肌肉骨骼疼痛的新型注射镇痛输送系统
  • 批准号:
    9097142
  • 财政年份:
    2016
  • 资助金额:
    $ 19.34万
  • 项目类别:
Novel Injectable Analgesic Delivery System for Chronic Musculoskeletal Pain Manag
用于治疗慢性肌肉骨骼疼痛的新型注射镇痛输送系统
  • 批准号:
    8916551
  • 财政年份:
    2014
  • 资助金额:
    $ 19.34万
  • 项目类别:
Novel Injectable Analgesic Delivery System for Chronic Musculoskeletal Pain Manag
用于治疗慢性肌肉骨骼疼痛的新型注射镇痛输送系统
  • 批准号:
    8683507
  • 财政年份:
    2014
  • 资助金额:
    $ 19.34万
  • 项目类别:

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