Multiscale structural and functional biomechanics of contracting platelet-fibrin based biomaterials and blood clots in oral microenvironment

口腔微环境中收缩血小板纤维蛋白基生物材料和血凝块的多尺度结构和功能生物力学

基本信息

  • 批准号:
    10303258
  • 负责人:
  • 金额:
    $ 24.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-21 至 2023-09-21
  • 项目状态:
    已结题

项目摘要

Project Summary Platelet-rich plasma clots are a unique biomaterial used for oral and dental surgical procedures to promote wound healing and tissue regeneration in the oral cavity. While aspects of platelet biochemical regenerative potential have been previously studied, the biomechanical function of platelets resulting in contraction of fibrin matrix and blood clots at injury sites in the oral environment has not been addressed. Blood clot contraction is a result of the biomechanical interactions between activated platelets and polymerized fibrin, the two major components of hemostatic clots at oral injury sites, other than red blood cells and fewer leukocytes. The biomedical importance of clot contraction in vivo is evident from promoting wound healing around teeth and implants by approximating the edges of the wound and formation of impermeable physical barriers against bacterial invasion and toxin propagation in oral wounds. Despite the importance of the platelet contractile function for remodeling of blood clots at oral injury sites and clots comprising platelet-rich fibrin surgical hemostatic sealants, the relation between clot contraction dynamics and metabolic and structural changes in activated platelets in oral wounds remains largely unknown. Thus, the main objective of the proposed research is to discover multiscale and time-dependent biomechanical and structural mechanisms of platelet-induced clot contraction in the oral microenvironment and its functional consequences, including modulations of clot mechanical properties and stability. We will focus on the following Aims: Aim 1. Determine structural mechanisms of platelet-induced clot contraction studied at the cellular and subcellular levels. Aim 2. Define the impact of salivary extracellular vesicles on structural properties and viscoelasticity of contracting platelet-rich plasma clots. Aim 3. Identify late-stage structural, metabolic, and functional consequences of platelet activation and contraction in the oral microenvironment. To reach our goals, we will apply state-of-the-art biophysical and biochemical methods with quantitative characterization and structural details from the molecular and cellular levels up to the scale of the entire clot. By applying a combination of different techniques, including high- resolution light microscopy, rheometry, and biochemical assays, our project will bridge the gap between different spatial scales and will establish relations between the molecular, single-cell and single-fiber levels to global structural and mechanical modulations of the entire blood clot. The proposed study will establish a mechanistic basis for platelet-driven clot contraction in the presence of salivary extracellular vesicles, which will yield insights into the structure and function of activated platelets as well as variations of viscoelastic properties and architecture of platelet-fibrin scaffolds at oral injury sites. The acquired knowledge will improve our understanding of hemostasis in the oral microenvironment, inform design of new treatment modalities and assist in development of platelet-fibrin-based biomaterials for oral cavities with modulated mechanical properties to improve patient recovery and oral health.
项目摘要 富血小板血浆凝块是一种独特的生物材料,用于口腔和牙科手术, 促进口腔伤口愈合和组织再生。虽然血小板生化方面 再生潜力以前已经研究过,血小板的生物力学功能导致 在口腔环境中损伤部位的纤维蛋白基质和血凝块的收缩还没有得到解决。血液 凝块收缩是活化的血小板和聚合的纤维蛋白之间的生物力学相互作用的结果, 口腔损伤部位止血凝块的两种主要成分,除了红细胞和较少的白细胞。 体内凝块收缩的生物医学重要性从促进牙齿周围的伤口愈合和 通过缝合伤口边缘和形成不可渗透的物理屏障, 口腔伤口中的细菌侵入和毒素繁殖。尽管血小板收缩功能的重要性 用于口腔损伤部位的血凝块的重塑和包含富含血小板的纤维蛋白的凝块的外科止血剂 封闭剂,血凝块收缩动力学与代谢和结构变化之间的关系, 口腔伤口中的血小板仍然是未知的。因此,拟议研究的主要目标是 发现血小板诱导凝块的多尺度和时间依赖性生物力学和结构机制 口腔微环境的收缩及其功能后果,包括凝块的调节 机械性能和稳定性。我们将专注于以下目标:目标1。确定结构 在细胞和亚细胞水平研究血小板诱导的血凝块收缩的机制。目标二。定义 唾液细胞外囊泡对收缩中富含血小板血管结构特性和粘弹性的影响 血浆凝块目标3。确定血小板活化的晚期结构、代谢和功能后果 和口腔微环境的收缩。为了实现我们的目标,我们将应用最先进的生物物理和 生物化学方法与定量表征和结构细节的分子和细胞 达到整个血块的水平。通过采用不同技术的组合,包括高- 分辨率光学显微镜,流变仪和生化分析,我们的项目将弥合不同之间的差距 空间尺度,并将建立分子,单细胞和单纤维水平之间的关系,以全球 整个血凝块的结构和机械调节。这项研究将建立一个机制, 在唾液细胞外囊泡存在下血小板驱动凝块收缩的基础,这将产生见解 活化血小板的结构和功能以及粘弹性的变化, 血小板-纤维蛋白支架在口腔损伤部位的结构。获得的知识将提高我们的理解力 止血在口腔微环境,通知新的治疗方式的设计,并协助开发 用于口腔的基于血小板-纤维蛋白的生物材料,具有调节的机械性能, 恢复和口腔健康。

项目成果

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