Christine Schmidt, University of Texas at Austin
The goal of this project is to develop novel techniques for controlling sub-cellular level biological cues in 3D. Other studies in this area have been unable to create such intricate architecture, at the submicron scale, and within 3D hydrogel systems. This project is truly unique and will provide an important platform for developing scaffolds for regenerative medicine and for more physiological, 3D in vitro culture systems. In addition, this research is particularly targeted for guiding axonal growth, which has potential implications for promoting regeneration in both the peripheral and central nervous systems.
This interdisciplinary research is at the intersection of chemical and biomedical engineering, materials science, chemistry, optics/physics, and biology. Two graduate students and several undergraduate students will conduct the proposed research. The PI and Co-PI will work one-on-one with all students and each undergraduate student will also be paired with a graduate student mentor who will help guide research and oversee training. Furthermore, the PI and Co-PI's research groups are active in K-12 outreach programs (e.g., women and minority-based programs) as a means to educate young students about bioengineering, in addition to other scientific mentoring programs such as the Beckman Scholars Program and the Welch Summer Scholar Program.
The objective of the proposed research was to develop methods to direct-write three-dimensional (3D), bioactive microstructures within hydrogel materials that mimic the composition and size scale of the native extracellular environment. Precise control over material properties such as modulus (i.e., stiffness), surface chemistry, and topography can be achieved on a sub-micron scale using multiphoton-excited photopolymerization (MPP). We have been interested in hyaluronic acid (HA)-based biomaterials because HA is native in tissues in the body and HA plays a normal role in wound healing. The long-term goal of our research is to engineer improved biomaterial scaffolds for wound healing, regenerative medicine, and in vitro 3D culture applications. We have made substantial progress patterning complex 3D geometries of protein microstructures in HA hydrogels. HA-based hydrogels patterned with bovine serum albumin protein structures in 3D can spatially direct primary neuronal cell attachment, migration, and differentiation in vitro (Figure 1). We have also been able to refine the MPP fabrication methods to achieve precise control over the biochemical and mechanical properties of 3D microstructures fabricated from biological materials. We have made substantial progress towards creating tunable gradients of both mechanical and biochemical signals using MPP technology. In the nervous system, neurite outgrowth and glial migration are particularly influenced by spatial organization of biomolecular cues into concentration gradients. The mechanical environment resulting from the physical structure and composition of the extracellular environment has also been shown to influence cell phenotype, and gradients of these physical cues can guide cell migration. Techniques to fabricate microstructures (such as microtubes, which mimic many tissue architectures such as nerve and muscle) which present definable biomolecular and mechanical gradients will greatly facilitate research to elucidate mechanisms of cell-ECM interactions and exploit those mechanisms to control cell-biomaterial interactions. Figure 2 shows an array of microtubes created using MPP. Structures such as this could be useful in applications where uninterrupted, micron-scale features are needed for cell guidance over millimeters or centimeters, as in peripheral nerve guides. As part of this NSF project, the PI and her research team contributed significantly to community outreach. The PI gave many talks on research or other topics to various student organizations, K-12 outreach programs, and retired citizen groups every semester. In particular, her focus has been on community service to educate young students and the average citizen about engineering, science, and technology. She and her group are actively involved with bringing students into the labs for hands-on tours and demos, to encourage students to consider careers in science and engineering. Intellectual Merit: The goal of this research was to develop novel techniques for controlling sub-cellular level biological cues in 3D. Other studies in this area have been unable to create such intricate architecture, at the submicron scale, and within 3D hydrogel systems. Thus, this research is truly unique and has provided an important platform for developing scaffolds for regenerative medicine and for more physiological, 3D in vitro culture systems. Broader Impact: This project was a collaborative effort that was initiated as part of an NSF IGERT student training fellowship program here at UT-Austin (in which students are required to be co-advised by faculty mentors in different departments). This interdisciplinary research has been at the intersection of chemical and biomedical engineering, materials science, chemistry, optics/physics, and biology. The PI and Co-PI have worked one-on-one with all students on this project. Furthermore, as mentioned above, the PI and Co-PI's research groups have been active in K-12 outreach programs (e.g., women and minority-based programs) as a means to educate young students about bioengineering, in addition to other scientific mentoring programs such as the Beckman Scholars Program and the Welch Summer Scholar Program.