This Materials World Network award by the Biomaterials program and the Office of Special Program in the Division of Materials Research to Georgia Institute of Technology supports an international collaboration for research and education between Georgia Tech (USA) and the Max-Planck Institut fur Polymerforschung (Germany). The objective of this project is to engineer phototriggerable materials to dynamically present and/or release bioadhesive motifs via the use of UV-labile caged bioadhesive ligands, which are expected to provide precise control over cell-material interactions both in vitro and in vivo. The project is to develop two biomaterial platforms (surfaces, hydrogels) with triggerable adhesive arginine-glycine-aspartic acid (RGD) tripeptide ligands in order to investigate the effects of spatiotemporal adhesion in cell processes. A major and unique strength of the proposed work is the ongoing international collaboration integrating photocaged chemistry and biomaterials engineering. The overall objective will be accomplished by completing the following specific aims: a) synthesize surfaces presenting caged RGD peptides that are activated or inactivated via exposure to UV light to spatiotemporally modulate cell adhesion; b) analyze the role of temporal ligand presentation on cell proliferation and differentiation on bioadhesive surfaces; c) engineer hydrogels presenting caged RGD peptides that exhibit spatiotemporal control of in vivo cell adhesion. These phototriggerable materials are expected to have wide-spread applications in basic-science studies of cell function as well as dynamic, tunable implants for tissue repair and regeneration.
The proposed research will generate a general biomaterial strategy for precise spatiotemporal control of biological functionalities. These innovative biomaterials will then be used to provide new insights on cell-biomaterial interactions in vitro and in vivo. Furthermore, the focus on engineering triggerable hydrogels provides a pathway for translation into many biotechnological and biomedical applications. Because of these strengths, the proposed research will be highly transformative. Finally, this project will also strengthen the ongoing collaboration by enabling significant interactions and expanding research activities. The research will result in the advanced training of undergraduate and graduate researchers, including an underrepresented minority student from Georgia Tech, with unique analytical skills based on a multi-disciplinary, integrative perspective.
Intellectual Merit. Materials engineered to elicit targeted cellular responses in regenerative medicine must display biomolecules with precise spatiotemporal control. Although materials with temporally regulated presentation of molecules that promote cell adhesion using external triggers, such as light and electric fields, have been recently realized for cells in culture, the impact of in vivo temporal molecule presentation on cell-material responses is unknown. In this project, we established a general strategy to temporally control the in vivo presentation of cell-adhesive molecules using cell adhesive peptides with a protecting group that can be easily removed via light exposure through the skin to render the cell-adhesive molecule fully active. We demonstrate that temporal activation of cell-adhesive peptide on implanted biomaterials regulates in vivo cell recruitment, inflammation, fibrous encapsulation, and vascularization of the material. This work shows that triggered in vivo presentation of bioactive molecules can be harnessed to direct tissue reparative responses associated with implanted biomaterials. Broader Impact. This research established a general biomaterial strategy for precise spatiotemporal control of biological functionalities. These innovative biomaterials provided new insights on cell-biomaterial interactions in vitro and in vivo. Finally, this project will strengthened the ongoing collaboration with the Max Plack Institute in Germany by enabling significant interactions and expanding research activities. The research resulted in the advanced training of undergraduate and graduate researchers.
