Molecular Regulation of Sprouting Angiogenesis.

The term angiogenesis arose in the 18th century. Several studies over the next 100 years laid the groundwork for initial studies performed by the Folkman laboratory, which were at first met with some opposition. Once overcome, the angiogenesis field has flourished due to studies on tumor angiogenesis and various developmental models that can be genetically manipulated, including mice and zebrafish.

Functionalization of Ultrabithorax Materials with Vascular Endothelial Growth Factor Enhances Angiogenic Activity.

Successful design of tissue engineering scaffolds must include the ability to stimulate vascular development by incorporating angiogenic growth factors. Current approaches can allow diffusion of growth factors, incorporate active factors randomly, or can leave residual toxins. We addressed these problems by genetically fusing the gene encoding Vascular Endothelial Growth Factor (VEGF) with the Ultrabithorax (Ubx) gene to produce fusion proteins capable of self-assembly into materials.

Identification of multiple dityrosine bonds in materials composed of the protein Ultrabithorax.

The recombinant protein Ultrabithorax (Ubx), a Hox transcription factor, self-assembles into biocompatible materials that are remarkably extensible and strong. Here, we demonstrate that the strength of Ubx materials is due to intermolecular dityrosine bonds. Ubx materials auto-fluoresce blue, a characteristic of dityrosine, and bind dityrosine-specific antibodies.

Regional changes in elastic fiber organization and transforming growth factor β signaling in aortas from a mouse model of marfan syndrome.

In Marfan Syndrome (MFS), development of thoracic aortic aneurysms (TAAs) is characterized by degeneration of the medial layer of the aorta, including fragmentation and loss of elastic fibers, phenotypic changes in the smooth muscle cells, and an increase in the active form of transforming growth factor-β (TGFβ), which is thought to play a major role in development and progression of the aneurysm. We hypothesized that regional difference in elastic fiber fragmentation contributes to TGFβ activation and hence the localization of aneurysm formation. The fibrillin-1-deficient mgR/mgR mouse model of MFS was used to investigate regional changes in elastin fiber fragmentation, TGFβ activation and changes in gene expression as compared to wild-type littermates.

Materials composed of the Drosophila Hox protein Ultrabithorax are biocompatible and nonimmunogenic.

Although the in vivo function of the Drosophila melanogaster Hox protein Ultrabithorax (Ubx) is to regulate transcription, in vitro Ubx hierarchically self-assembles to form nanoscale to macroscale materials. The morphology, mechanical properties, and functionality (via protein chimeras) of Ubx materials are all easily engineered. Ubx materials are also compatible with cells in culture.