| dc.description.abstract | Protein-based materials have exceptional biological and mechanical properties, making these materials useful for many biomedical applications, including tissue engineering, drug delivery, enzyme immobilization, and biosensing. Bioactive materials can be created by genetically fusing a self-assembling protein to a functional protein. Key advantages of the protein fusion approach include elimination of a separate functionalization step during materials synthesis, uniform coverage of the material by the functional protein, and stabilization of the functional protein. The benefits of fusion protein materials offer opportunities to further develop this useful technique.
Previously, our lab has generated novel protein-based materials from the Drosophila Hox protein Ultrabithorax (Ubx), which self-assembles in vitro. Ubx materials are cytocompatible, biocompatible, biodegradable, and have tunable mechanical properties. Functionalization of Ubx materials can be accomplished via protein fusion, in which functional proteins are stabilized and retain their function while incorporated into materials. The unique properties of Ubx materials make them useful for a diverse range of applications.
In this work, we focused on developing Ubx-based materials to promote neovascularization. Stimulating neovascularization to support cell survival is critical for a variety of applications, including tissue engineering and wound healing. Neovascularization is a multi-step, complex process that is promoted by several growth factors (GFs). Herein, we have genetically fused vascular endothelial growth factor (VEGF), stromal cell-derived factor 1 (SDF-1), and basic fibroblast growth factor (bFGF) to Ubx in order to generate materials displaying pro-angiogenic GFs.
We confirmed that GFs remain active and stable when covalently incorporated into Ubx materials by the ability of fibers composed of GFs alone or in combination to induce endothelial cell (EC) migration and survival. We further demonstrated that Ubx materials displaying a combination of multiple GFs promote and guide neovascularization in vivo within 2 weeks in a mouse model. In addition, long-term studies suggested that GFs immobilized by Ubx materials induced vessel patency after 7 weeks.
Collectively, our data indicate that Ubx materials incorporating a combination of VEGF, bFGF, and SDF-1 promote the formation and stabilization of functional blood vessels. These materials have potential for use in tissue engineering and regenerative medicine, among other applications. | |
