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.

Project Report

Overview. Advances in the field of tissue engineering are increasingly reliant on biomaterials that instruct, rather than simply permit, a desired cellular response. Growth factors are commonly used to instruct cell behaviors such as proliferation, however in three-dimensional biomaterials growth factors can rapidly diffuse away. Moreover, current techniques to create patterns of growth factors within biomaterials are limited. The scientific object of this project was to develop photolithography (light-based patterning) methods to create pattern of growth factors on and within collagen biomaterials that are being developed for a range of tissue engineering applications. Intellectual Merit. In this project we developed new fundamental science regarding patterning growth factors within three-dimensional collagen biomaterials. We identified bioactive ranges of growth factors that when patterned were able to direct cell behaviors such as proliferation and differentiation. We developed metrics to assess non-specific fouling, determined the maximum depth to which patterns could be generated within three-dimensional biomaterials, and showed that spatial-patterns of covalently-attached growth factors could be used to locally control cell behavior. Moreover, we refined a concept using non-covalent interactions to control growth factor bioactivity over time. Importantly, the fundamental developments have led to a wide variety of new project using these methods for new applications in tissue engineering, particularly in the design of biomaterials to repair damaged orthopedic structures. Broader Impacts. This work has also supported significant training and outreach efforts. This project supported an interdisciplinary environment to educate and empowers a next generation of engineers and chemists to address challenges at the intersection of biological, physical, and quantitative sciences. Project trainees gained critical research, scientific communication, and mentoring skills that benefitted not only the four primary graduate trainees, but also additional undergraduate research volunteers that participated in our laboratory studies. These students (graduate and undergraduate) are carefully mentored in technical scientific accomplishments (research planning, execution, and analysis), but also in professional development and career path decisions. The PIs and trainees also took part in annual outreach efforts targeting the general public regarding the application of academic research towards human health, but also programs explicitly targeting underrepresented student groups in science, technology, engineering, and mathematics (STEM). Notably, we developed educational modules for middle through high school aged girls interested in scientific careers. These efforts use examples form laboratory research performed during this project along with concepts from biomimicry and composite materials in nature to engage high school girls in hand-on scientific and engineering exploration. Together, these represent significant impacts to the community in training and mentoring future scientists.

National Science Foundation (NSF)
Division of Materials Research (DMR)
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Joseph A. Akkara
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University of Illinois Urbana-Champaign
United States
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