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

• 批准号: 9890521
• 负责人: Wai Hong Lo
• 金额: $ 19.34万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/9890521
• 关键词: Adsorption; Age; Aging; Applications Grants; Biochemistry; Biocompatible Materials; Biological Assay; Biomedical Engineering; Bone Regeneration; Bone Tissue; Calcium; Calcium Binding; Calcium Signaling; Calcium ion; Calcium-Binding Proteins; Cell secretion; Cell-Matrix Junction; Cells; Cellular Morphology; Cellular biology; Charge; Data; Deposition; Development; Devices; Drug Delivery Systems; EF Hand Motifs; Electric Stimulation; Engineering; Enzyme-Linked Immunosorbent Assay; Evaluation; Exhibits; Expression Profiling; Extracellular Matrix; Fracture; Genes; Goals; Growth Factor; Human; Implant; In Vitro; Intracellular Membranes; Ions; Lead; Light; Measures; Mediating; Membrane Potentials; Mesenchymal Differentiation; Mesenchymal Stem Cells; Molecular; Monitor; Musculoskeletal; Musculoskeletal Diseases; Natural regeneration; Nature; Osteoblasts; Osteogenesis; Pathway interactions; Population; Procedures; Process; Production; Proteins; Research; Research Personnel; Role; Signal Pathway; Signal Transduction; Surface; Testing; Tissue Engineering; United States; autocrine; base; bone; bone morphogenetic protein 2; clinical application; cytokine; design; electric field; experience; healing; in vivo; materials science; migration; osteogenic; paracrine; reconstruction; regenerative; repaired; response; scaffold; skeletal tissue; stem cell proliferation; stem cells; tissue regeneration

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.

抽象的 美国每年进行超过 100 万例骨重建手术。电气 刺激（ES）已被证明对临床骨修复和再生具有深远的影响 应用程序。然而，当前的 ES 设备存在许多缺点，包括生成的效率低下。 电场（对于外部 ES 设备）、电刺激器中使用的体积大和有毒材料，以及 植入 ES 装置的不可降解性。压电材料，可以产生电荷 在变形期间，反之亦然，可用于创建自供电电刺激器，该刺激器可以 有效刺激骨骼修复和再生。具体来说，在 压电材料表面已被证明能有效刺激干细胞增殖、迁移、 体外和体内的成骨分化和重塑。然而，底层分子 负责这些观察的机制仍不清楚。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，该通路可能具有内在的 通过刺激细胞骨诱导蛋白生长因子的产生和分泌来实现骨诱导性 （BMP-2）。该资助申请的假设是压电材料上产生的表面电荷 将诱导Ca2+振荡和/或ECM蛋白吸附增强，这种变化可能会触发茎 细胞骨分化和/或基于细胞因子的诱导自分泌和旁分泌环。此次活动的主要目标 应用是研究压电材料表面电荷如何产生的基本分子机制 材料可以积极影响愈合程度并促进骨组织再生。三具体 提出的目标是检验我们提案的假设。在目标 1 中，我们将设计、制造和表征 用于研究成骨信号机制的压电材料。在目标 2 中，我们将研究 Ca2+ 如何 信号机制和/或 ECM 沉积响应压电电荷产生 压电材料。在目标 3 中，我们将使用微阵列检查多种 压电陶瓷上接种的间充质干细胞（MSC）成骨分化过程中的基因 材料。该项目的数据将为进一步探索其本质提供必要的信息 用于骨修复和再生应用的压电表面电荷。可实现的第一个里程碑 通过该提案开发了压电支架和研究成骨的装置 信号机制和支架本身的相关特征。第二个可实现的里程碑 是对 Ca2+ 信号传导机制以及 ECM 吸附响应的作用的评估 压电材料上产生的表面电荷。第三个里程碑是评估 压电支架上间充质干细胞成骨分化过程中多种基因的表达谱。