This Career award by the Biomaterials program in the Division of Materials Research to Johns Hopkins University is to explore new collagen modification technique and develop spatially functionalized collagen scaffolds for controlled microvasculature formation and artificial cornea fabrication. The modification technique is based on collagen's native ability to associate into triple-helical molecular architecture similar to DNA strand invasion and exchange. Using synthetic collagen mimetic peptide (CMP) as a collagen-specific "hitch-hiker," Dr. Michael Yu will synthesize 3D collagen-based tissue scaffolds with exogenous bioactive components (growth factors, cell adhesion peptides, and antimicrobial peptides) in defined locations within the scaffolds and investigate their effectiveness for controlled tissue generation. Specific goals of the project are: a) design of collagen mimetic peptide analogues with enhanced collagen binding properties and perform fundamental study of CMP-collagen interactions; b) investigation in the use of CMPs in fabricating collagen surfaces and gels with controlled bioactivity; and c) testing the performance as tissue scaffolds for ordered microvasculature and functional artificial cornea. In addition to tissue engineering application, the modification technique may also lead to technological innovation in detection and treatment of diseases related to pathologic scar tissue and other abnormal extra cellular matrices.
In collaboration with National Federation of the Blind Jernigan Institute, based in Baltimore, the PI will develop a biomaterials laboratory session for blind high school students as part of the Blind Youth STEM Academy. Goals of this outreach program are: a) expose blind youth to STEM through hands-on programs that powerfully demonstrate that they can play a major role in such fields; b) stimulate graduate students to pursue research projects, technology development and educational activities that address problems of full inclusion of persons with disabilities in STEM careers; and c) educate parents, teachers, and general public that STEM fields are open to blind youth. Within the Johns Hopkins community, the project will develop innovative materials biology curriculum to create new breed of material researchers who can work across traditional materials and biology disciplines.
Collagen, the most abundant protein in mammals, plays a crucial role in tissue development and regeneration, and its structural and metabolic abnormalities are associated with debilitating genetic diseases and numerous pathologic conditions. The ability to target collagens in diseased tissue could lead to new diagnostics and therapeutics, as well as applications in regenerative medicine. In this project, we developed a new collagen targeting strategy that is based on triple helical hybridization between collagen (and gelatin) and synthetic collagen mimetic peptide. This hybridization resulted in robust collagen specific binding both in vitro and in vivo which allowed fabrication new tissue engineering scaffolds, as well as detection of degraded collagens present in normal tissues undergoing fast remodeling (e.g. bones and cartilage) and those in diseased tissues with persistent wound healing activity (e.g. tumor, fibrosis). In particular, we were able to produce collagen scaffolds that are encoded with angiogenic signals and demonstrate that blood vessel-like structure can be induced locally in artificial system. We also conducted various experiments designed to elucidate the mechanism of the hybridization as well as those verifying the CMP’s collagen binding capacity both in vitro and in vivo. Finally, we succeeded in detecting and imaging diseased tissues (e.g. cancer and fibrosis) in mouse disease model by systemic delivery of collagen mimetic peptide conjugated to imaging moiety. This is an entirely new way to target the microenvironment of malignant tissues and could lead to new opportunity for management of numerous pathologic conditions associated with high collagen degradation and remodeling activity. Broader Impact: During the grant period, I have been involved in helping blind people learn science by developing innovative hands-on laboratory sessions as part of Blind Youth STEM program and participated in National Federation of Blind Youth Slam for 2007 (hosted by Johns Hopkins) and 2009 (hosted by University of Maryland, College Park). In addition, I was an active participant of NSF/NIH workshop on chemists, chemical engineers, and materials scientists with disabilities (2009).
