ERI: Biological Effects of Low-Frequency, Low-Intensity Ultrasound on Endothelial Cell and Macrophage Co-Culture

ERI：低频、低强度超声对内皮细胞和巨噬细胞共培养的生物学效应

• 批准号: 2347558
• 负责人: Olivia Boerman
• 金额: $ 19.99万
• 依托单位: Bucknell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2347558&HistoricalAwards=false
• 关键词: ERI; Biological; Effects; Low; Frequency

This Engineering Research Initiation (ERI) award will support research to investigate the effects of ultrasound on endothelial cells (blood vessel cells) and macrophages (immune cells). Endothelial cells and macrophages work together in many biological processes, one of which is angiogenesis, the creation of blood vessels. Angiogenesis is critical for the healing of damaged tissues as in the case of chronic wounds. Chronic wounds last on average twelve months and may lead to amputation of lower limbs or possibly even death. Human clinical trials have shown that low-frequency, low-intensity ultrasound advances chronic wound healing. However, the biological mechanisms are still not understood. The knowledge gained from understanding how ultrasound affects endothelial cells and macrophages individually and together may enhance ultrasound therapies for advanced healing and ultimately increase the quality of life for patients. This award will also promote undergraduate and high school student exposure and training in tissue engineering, particularly for underrepresented students and women in engineering through hands-on laboratory experiences. Formal course offerings in tissue engineering will also be developed for both engineering and non-engineering majors with a focus on minoritized students and women in engineering. The research goal is to evaluate the promotion of angiogenesis as a possible biological mechanism of therapeutic ultrasound. This will be achieved through two objectives: (1) characterize uni- and bi-directional effects of low-frequency, low-intensity ultrasound on macrophage and endothelial cell pro-angiogenic factors via macrophage and endothelial direct co-culture, indirect co-culture (transwell), and individually (endothelial alone and macrophage alone) and (2) analyze gene expression changes using bulk RNAseq and global bioinformation methods. These objectives will be conducted in vitro using 3D collagen scaffolds to more closely mimic physiological conditions. Understanding the effects of therapeutic ultrasound on angiogenesis will provide insight to the possible biological mechanisms of ultrasound. Preliminary data and published literature strongly suggest that stimulation of angiogenesis may be the mechanism through which ultrasound mediates healing. If this is confirmed by the data collected, this may indicate that ultrasound could be an effective therapy to recover functional endothelial behavior where pathological angiogenesis is a hallmark of diseases including atherosclerosis, rheumatoid arthritis, and autoimmune diseases. These data would provide insights into novel therapeutic applications of ultrasound.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该工程研究启动 (ERI) 奖将支持研究超声波对内皮细胞（血管细胞）和巨噬细胞（免疫细胞）的影响。内皮细胞和巨噬细胞在许多生物过程中协同工作，其中之一是血管生成，即血管的形成。血管生成对于受损组织的愈合至关重要，就像慢性伤口的情况一样。慢性伤口平均持续十二个月，可能导致下肢截肢甚至死亡。人体临床试验表明，低频、低强度超声波可促进慢性伤口愈合。然而，其生物学机制仍不清楚。通过了解超声如何单独和共同影响内皮细胞和巨噬细胞而获得的知识可以增强超声治疗以实现高级愈合，并最终提高患者的生活质量。该奖项还将促进本科生和高中生在组织工程领域的接触和培训，特别是通过实验室实践经验，帮助工程领域代表性不足的学生和女性。还将为工程和非工程专业开发组织工程的正式课程，重点关注工程领域的少数族裔学生和女性。研究目标是评估促进血管生成作为超声治疗的可能生物学机制。这将通过两个目标来实现：（1）通过巨噬细胞和内皮细胞直接共培养、间接共培养，表征低频、低强度超声对巨噬细胞和内皮细胞促血管生成因子的单向和双向影响（transwell）和单独（单独的内皮细胞和单独的巨噬细胞）和（2）使用批量 RNAseq 和全局生物信息方法分析基因表达变化。这些目标将使用 3D 胶原支架在体外进行，以更接近地模拟生理条件。了解治疗性超声对血管生成的影响将为了解超声可能的生物学机制提供见解。初步数据和已发表的文献强烈表明，刺激血管生成可能是超声介导愈合的机制。如果收集的数据证实了这一点，则可能表明超声波可能是恢复功能性内皮行为的有效疗法，其中病理性血管生成是动脉粥样硬化、类风湿性关节炎和自身免疫性疾病等疾病的标志。这些数据将为超声波的新颖治疗应用提供见解。该奖项反映了 NSF 的法定使命，并且通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。