Catch and Release: Biomolecular Ligation and Cleavage Strategies for Generating Instructive and Dynamically Responsive 3D Biomaterials

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

This award by the Biomaterials program in the Division of Materials Research to University of Illinois at Urbana-Champaign is to create a robust system based on collagen-glycosaminoglycan biomaterials, benzophenone photoimmobilization, and stimuli-responsive release chemistries that enables both spatial and temporal control over the presentation of a wide range of adhesive and proliferative cues (growth factors, ligands, proteins, carbohydrates, genetic sequences, etc.). The systematic approach used here to integrate collagen biomaterials with photochemically controlled immobilization techniques will enable design of new classes of biomaterials for complex tissue engineering applications that recapitulate much of the biomolecular complexity found in native tissues and tissue interfaces. Simple, yet generic tethering chemistries that allow spatial localization of a wide range of biomolecules as well as exogenously or endogenously cued release of the same biomolecules will be invaluable for generating novel classes of instructive biomaterials. Such materials would offer the ability to mimic the dynamic and spatial heterogeneities of the natural extracellular matrix. Apart from basic insights into developing molecularly general methods for creating spatially and temporally patterned instructive cues within 3D biomaterials, this work will enable fabrication of new classes of biomaterials for both translational regenerative medicine as well as mechanistic investigations of cell behavior. Broader impacts of this work are both to re-imagine how biomaterials can be used to control cell behaviors as well as to provide a valuable multidisciplinary training experience that affords significant research projects for undergraduates from multiple departments and colleges across campus. In doing this, this project will create a highly interdisciplinary environment that exposes, educates, and empowers the next generation of undergraduate and graduate engineers and chemists to address critical challenges at the intersection of biological, physical, and engineering sciences. Tissues are complex, three-dimensional environments that present multiple types of cues which regulate cell fate. The ability to spatially control the display of biomolecules within three-dimensional biomaterials does not currently exist, but this is a fundamental technological gap that must be bridged to develop next generation biomaterials for use both in the body, to regenerate tissues, and outside of the body, to study how cells sense and respond to their microenvironment. Materials created using the patterning tools developed here will be both instructive and responsive to surrounding cells and tissues, and will provide mechanistic insights into cell-matrix interactions as well advanced bioactive materials for more complex regenerative medicine applications. Through a coordinated research and educational plan, the project will directly support a number of critical outreach programs on campus. The tools developed during this project will serve as the foundation for ongoing and future novel research projects at the confluence of chemistry-biology-engineering disciplines for under-represented undergraduate students in science and engineering, and will form the basis for a new teaching module in an ongoing Tissue Engineering course on campus.