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SPAAC 3D Hydrogels for Neural Tissue Engineering

Presenters Name: 
Anne Katherine Brooks
Co Presenters Name: 
Primary Research Mentor: 
Kyle Lampe
Secondary Research Mentor: 
Session: 
3
Location: 
Newcomb Hall Ballroom
Grant Program Recipient: 
Harrison Undergraduate Research Grant
Abstract: 

The central nervous system (CNS) cannot fully repair native tissue in the cases of traumatic brain injury or neurodegenerative disease, which may be remedied by hydrogel systems conducive to neural tissue regeneration. Native tissue ECM properties vary at the microscale level, and introducing micro-architecture into biomaterial scaffold design has been shown to influence stem cell proliferation and differentiation. In this project, elastin-like protein (ELP) and poly(ethylene glycol) (PEG) hydrogels were crosslinked using strain-promoted azide-alykne cycloaddition (SPAAC), a click chemistry reaction that completes in minutes without interfering with native cell processes. ELP is a recombinant engineered protein that exhibits a unique lower critical solution temperature (LCST) transition. Crosslinking with bio-inert PEG macromer above and below the LCST can create hydrogels with and without protein rich regions within the bulk hydrogel. ELP also includes RGD ligands, which promote cell adhesion to the gel. It was found that by crosslinking the materials below the ELP LCST resulted in homogenous architecture, while crosslinking above the ELP LCST resulted in heterogeneous architecture characterized by ELP-rich conglomerates. This is relevant for tissue repair because biomaterials characterized by heterogeneous architecture can promote stem cell proliferation and differentiation at an injury site. Rheology revealed that the stiffness of the gels was within the range of native CNS tissue, around 100-1000 Pa, while the time to gelation was 20 minutes. These findings suggest that PEG-ELP hydrogels are ideal for eventual medical applications, paving the way for more effective therapies in CNS injury repair.