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

尽管硫化氢气体(H2S)被认为是一种臭气熏天的有毒气体，但它是一种重要的生物信号分子，在人体内不断产生和消耗。在过去的15年里，研究人员发现硫化氢在人类的大脑、心脏、肝脏、肾脏和其他器官中具有生物功能。然而，在所有这些研究中，没有一项检查从植入性材料中释放的硫化氢的影响。这一职业奖探索了有史以来第一个硫化氢释放凝胶的合成和建造及其对硫化氢信号的影响。为这个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，作为本科生研究人员，让他们在高度跨学科的实验室环境中接触到生物材料领域。在该奖项的过程中将制造的凝胶将为生物学家研究硫化氢的生理作用提供新的工具，而该奖项产生的结果将为研究这些材料作为血管生成刺激物提供基础，血管生成是人体通过其制造新血管的过程。技术概述硫化氢(H2S)是最近发现的一种被称为气体传递器的关键类别的气体生物信号分子的补充。虽然硫化氢的信号传递能力早在近二十年前就已为人所知，但目前还没有能够以可控的方式传递硫化氢的材料。因此，局部性(相对于全身性)释放如何影响硫化氢的信号传递能力是未知的，还有一个更广泛的问题，即基质机械性质如何影响硫化氢信号传递。这一职业奖的重点是基于多肽的新型硫化氢释放凝胶的合成和表征及其对血管生成的影响，血管生成是人体从现有血管生成新血管的过程。中心假设是硫化氢的输送速度和基质的机械性能都会影响促血管生成的硫化氢信号。参与这个项目的研究生将使用有机化学的工具来开发凝胶，并使用材料科学中常见的分析技术来表征它们，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，将设计出第一族释放硫化氢的生物材料，这些材料将提供一个新的理解，即生化和生物物理线索如何结合起来促进血管生成。

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.