A challenge for scientists and engineers, however, has been getting FGF-2 to bind with cell receptors — the very molecules often found on the surface of the cell that receive chemical signals and direct activity in the cell from outside sources.
To overcome this, Baker’s method embeds the growth factors in synthetic lipid-based nanoparticles containing a coreceptor known as syndecan-4. The nanoparticles containing co-receptors that, when delivered with the growth factor, enable improved cell binding so that the growth factor can direct the targeted cell to divide, proliferate and form new cells for tissue regrowth.
The incased substance was injected into rats with hindlimb ischemia and stimulated a complete recovery from the ischemia in just seven days.
Samuel Stupp and his colleagues developed a liquid that, when injected into patients, forms a matrix of loosely tangled nanofibers. Each of these fibers is covered in microscopic protuberances that mimic vascular endothelial growth factor, or VEGF - a protein that occurs naturally in the body and causes chemical reactions that result in the growth of new blood vessels. By mimicking VEGF, the nanofiber has the same biological effect.
Jeff Karp, director of the Laboratory for Advanced Biomaterials and Stem-Cell-Based Therapeutics at Brigham & Women’s Hospital, says, “this is an elegant approach to rationally design engineered materials to stimulate specific biological pathways.” Karp was not involved with the project.
Ali Khademhosseini, an associate professor at the Harvard-MIT Division of Health Sciences and Technology, adds that “the ability to induce blood vessel formation is one of the major problems in tissue engineering.”
Tissue engineers have tried using VEGF itself to stimulate the growth of blood vessels, but clinical trials with the protein were unsuccessful, says Stupp, director of the Institute for BioNanotechnology in Medicine at Northwestern. This is because VEGF tends to diffuse out of the target tissue before it can do its job. Maintaining a therapeutic concentration in the target tissue would require a series of expensive, invasive injections.
The new nanomaterial has a similar effect, but it lasts much longer, and is completely biodegradable once its job is finished. Stem cells could be used to regenerate blood vessels, but their use is expensive and controversial.
“We hope this research will increase our understanding of how tissues become resistant to revascularization therapies and may lead to more effective treatments for this widespread and debilitating disease,” said Baker, who was recognized last year with the National Institutes of Health Director’s New Innovator Award.
Designed to support unusually creative new investigators with highly innovative research ideas at an early stage of their career, the award provides Baker with $1.5 million over five years to study and develop ways to regrow small blood vessels. With it, Baker is studying why previous attempts to restore blood flow to the heart have not been effective. His research aims to design new molecular tools and drug delivery methods to enable blood vessel growth in patients with diseases such as diabetes.
University of Texas at Austin
E. Jang, H. Albadawi, M. T. Watkins, E. R. Edelman, A. B. Baker. Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle. Proceedings of the National Academy of Sciences, 2012; 109 (5): 1679 DOI: 10.1073/pnas.1117885109