The PI will program two "smart" functions (i.e., oxidative stress-responsive and shape memory functions) into biomaterials by employing shape memory polymers crosslinked with peptide sequences that degrade in response to injury-mediated overproduction of reactive oxygen species. The "smart" functions of these biomaterials will be evaluated as a form of an injectable vascular patch whose shape, size, and thickness can be tuned to custom-fit even small blood vessels. Stimuli-sensitive materials change their structure and shape in response to changes in environment, such as heat, light, moisture or magnetic field. In the proposed project, oxidative stress is selected as an external stimulus because overproduction of reactive oxygen species is a universal mark of damaged organs, tissues, and cells. Reactive oxygen species-degradable peptides that can crosslink polymers when making patch scaffolds will be used to generate the oxidative stress-responsive function. Shape memory polymers in a combinatorial format, x% crosslinkable unit -co-y%non-crosslinkable unit, where x and y% indicate the molar ratio, will be used to tune the ability to memorize temporary shapes and regain their original shape after exposure to body temperature (37 °C). The basic polymer type proposed for this study has shown excellent vascular compatibility in previous studies. Furthermore, the polymer-peptide complex will be fabricated asvascular patch scaffolds aimed at repairing small blood vessels (e.g., cerebral hemorrhage and stroke). The patch scaffold surface will be coated with antibodies against vascular cell adhesion molecule-1 to generate a "suture-free sealing effect" by mimicking inflammatory cell adhesion onto injured endothelium. The "smart" functions and their subsequent effects on vascular healing will be evaluated in a bioreactor system that mimics the vascular environment. This is a very challenging research task due to the interdisciplinary nature of the conceptual and technical approaches.
Intellectual Merit: The proposed research will advance the state of the art in methods and techniques for applications of "smart" biomaterials to develop therapeutic inventions. Some of the innovative expected results include: 1) providing a stepping stone to develop the next generation of biomaterials that enable artificial intelligence-like work flow (i.e., navigating, sensing, and fixing); 2) incorporating biological molecules into a shape memory material function; 3) advancing "smart" material functions to cope with complex biological signaling; 4) a new therapeutic approach to regeneration of injured small blood vessels and a therapy of further pathogenesis, such as cerebral hemorrhage and stroke; and 5) generating a new tool box for minimally-invasive surgery and for design of scaffolds with customizable size, shape, and thickness. The proposed research will have a far reaching impact in terms of real applications of the research developed, as well as the broad spectrum of research areas. Achieving the goals of this project requires a deep understanding of material design and fabrication, as well as biomedical applications.
Broader Impact: Direct outcomes of this research will influence a large cross-section of the engineering and biomedical community and will stimulate education towards multidisciplinary subjects. Successful translation of the research to real world applications has the potential to revolutionize biomaterials and the regenerative medicine industry. Broader impacts also result from a range of education and dissemination activities, including 1) integrating research projects with coursework, outreach, and training through the existing courses and programs; 2) teaching abroad to expand outreach; and 3) creating a web-based vibrant youth community comprised of students in the US and S. Korea. Though the focus is biomaterials and tissue engineering, the basic elements will appeal to students from all areas of science and engineering. The PI will use established assessment tools to evaluate and adjust his pedagogical methods in these various integrative learning environments. He will also disseminate his new pedagogical methods for use by other instructors.
