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

Virginia Polytechnic Institute And State University, Blacksburg VA

Investigators

Abstract

Non-technical summary Despite 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 Summary Hydrogen 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.