CAREER: Self-Assembled, H2S-Releasing Gels for Promoting Angiogenesis

职业：自组装、释放 H2S 的凝胶，用于促进血管生成

• 批准号: 1454754
• 负责人: John Matson
• 金额: $ 53万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1454754&HistoricalAwards=false
• 关键词: CAREER; Self; Assembled; H2S; Releasing

Non-technical summaryDespite its reputation as a foul-smelling, toxic gas, hydrogen sulfide gas (H2S) is a vital biological signaling molecule that is constantly produced and consumed in the human body. Over the past decade and a half, researchers have discovered that H2S carries out biological functions in the human brain, heart, liver, kidneys, and other organs. In all of these studies, however, none have examined the effects of H2S delivered from implantable materials. This CAREER award explores the synthesis and construction of the first-ever H2S-releasing gels and their effect on H2S signaling. Graduate students contributing to this project will use advanced techniques in organic chemistry, materials science, and cell biology to synthesize and fully characterize these novel materials. First-generation college students will be recruited to join the project as undergraduate researchers, exposing them to the field of biomaterials in a highly interdisciplinary laboratory environment. The gels that will be made over the course of this award will provide new tools for biologists studying the physiological roles of H2S, and results generated from this award will provide a basis for examining these materials as stimulators of angiogenesis, the process through which the body makes new blood vessels.Technical SummaryHydrogen sulfide (H2S) is the most recently discovered addition to a critical class of gaseous biological signaling molecules called gasotransmitters. While the signaling capacity of H2S has been known for nearly two decades, no materials currently exist to deliver H2S in a controllable manner. As a result, how the signaling capacity of H2S is affected by localized (vs. systemic) release is unknown, as is the broader question of how matrix mechanical properties affect H2S signaling. This CAREER award focuses on the synthesis and characterization of novel peptide-based H2S-releasing gels and their effects on angiogenesis, the process through which the body makes new blood vessels from existing ones. The central hypothesis is that both the rate of H2S delivery and the mechanical properties of the matrix will influence pro-angiogenic H2S signaling. Graduate students involved in this project will use the tools of organic chemistry to develop the gels and characterize them using analytical techniques common in materials science, including electron microscopy, rheology, and other advanced analytical techniques. Through these efforts, the first family of H2S-releasing biomaterials will be designed, and these materials will provide a new understanding of how biochemical and biophysical cues can combine to promote angiogenesis.

尽管硫化氢气体（H2S）被认为是恶臭的有毒气体，但它是人体中不断产生和消耗的重要生物信号分子。在过去的15年里，研究人员发现H2S在人类的大脑、心脏、肝脏、肾脏和其他器官中发挥着生物学功能。然而，在所有这些研究中，没有一项研究检查了植入材料输送的H2S的影响。这个职业奖探索了有史以来第一个H2S释放凝胶的合成和构建及其对H2S信号传导的影响。对该项目做出贡献的研究生将使用有机化学，材料科学和细胞生物学的先进技术来合成和充分表征这些新材料。第一代大学生将被招募加入该项目作为本科研究人员，使他们在高度跨学科的实验室环境中接触生物材料领域。将在本奖项过程中制造的凝胶将为研究H2S生理作用的生物学家提供新的工具，本奖项产生的结果将为检查这些材料作为血管生成刺激剂提供基础。身体制造新血管的过程。技术摘要硫化氢（H2S）是最近发现的一个关键类别的气体生物信号分子称为gasotransmitters。虽然人们已经知道H2S的信号能力近二十年了，但目前还没有材料可以以可控的方式输送H2S。因此，H2S的信号传导能力如何受到局部（与全身）释放的影响是未知的，基质机械性能如何影响H2S信号传导的更广泛的问题也是未知的。该职业奖的重点是新型肽基H2S释放凝胶的合成和表征及其对血管生成的影响，血管生成是身体从现有血管生成新血管的过程。 中心假设是H2S递送速率和基质的机械性质将影响促血管生成H2S信号传导。参与该项目的研究生将使用有机化学工具开发凝胶，并使用材料科学中常见的分析技术对其进行表征，包括电子显微镜，流变学和其他先进的分析技术。通过这些努力，第一个家庭的硫化氢释放生物材料将被设计，这些材料将提供一个新的理解，如何生物化学和生物物理线索可以联合收割机，以促进血管生成。