What’s on the horizon for regenerative medicine?

Organo-electric nanowires.  (Tovar Lab/JHU)

Organo-electric nanowires. (Tovar Lab/JHU)

Editor’s Note: The following is a summary of one of the talks from the 2013 Nano-bio Symposium hosted by Johns Hopkins Institute for NanoBioTechnology held May 17. This summary was written by Christian Pick, a doctoral candidate in the chemical and biomolecular engineering laboratory of Joelle Frechette. Look for other symposium summaries on the INBT blog.

The fundamental goal of regenerative medicine is to allow the body to restore normal function to damaged or diseased tissues. Tissue scaffolds provide a structure for cells to grow on to accomplish this task. The pinnacle of scaffold function would be for the tissue grown from a scaffold to be completely indistinguishable from natural, undamaged tissue.

In order to improve scaffolds, researchers need to better understand how scaffolds interact with the body. Peter Gabriele, Director of Emerging Technology at Secant Medical, discussed FT-IR microscopy,  which is a unique tool that can help researchers with this very task.

Fourier transform infrared (FTIR) spectroscopy is a powerful technique for analyzing the chemical identity of materials. FTIR spectroscopy has been used for years in forensic analysis for identifying unknown samples. FTIR microscopy combines the functionality of FTIR spectroscopy with optical microscopy.

For the field of regenerative medicine, this means that the surface functionality of a scaffold can be mapped and studied throughout its entire lifetime: from production through degradation in-vivo. For instance, FTIR microscopy can be used to analyze surface modifications made to a scaffold during fabrication.

Additionally, it can be used to track tissue formation in implanted scaffolds. As an example, Mr. Gabriele described studies on “biorubber” or poly(glycerol sebacate) (PGS). FTIR microscopy has been used to identify collagen integration within the polymer during implantation as well as map the erosion of the material once implanted. Through the use of tools such as FT-IR microscopy, researchers can continue to expand the functionality of tissue scaffolds.

Secant Medical

Watch a video about INBT’s current research efforts in the realm of regenerative medicine here.

DNA folded into shapes offers alternative gene delivery vehicle

DNA molecules (light green) packaged into nanoparticles of different shapes using a polymer with two different segments. Cartoon illustrations created by Wei Qu, Northwestern University and Martin Rietveld, Johns Hopkins /INBT. Microscopic images created by Xuan Jiang, Johns Hopkins University.

Using snippets of DNA as building blocks to create nanoscale rods, worms and spheres, researchers at Johns Hopkins and Northwestern universities have devised a means of delivering gene therapy that avoids some of the undesirable aspects of using viruses to deliver genes to treat disease. The shape and size of the DNA-based nanoparticle also affected how well the genes were delivered.

Worm shapes, for example, were particularly effective.

“The worm-shaped particles resulted in 1,600 times more gene expression in the liver cells than the other shapes,” said Hai-Quan Mao, an associate professor ofmaterials science and engineering in Johns Hopkins’ Whiting School of Engineering. “This means that producing nanoparticles in this particular shape could be the more efficient way to deliver gene therapy to these cells.”

This study was published in the Oct. 12 online edition of Advanced Materials.

Initial funding for the research came from a seed grant provided by the Johns Hopkins Institute for NanoBioTechnology, of which Mao is an affiliate. The Johns Hopkins-Northwestern partnership research was supported by a National Institutes of Health grant.

Read the entire Johns Hopkins press release by Phil Sneiderman (JHU) and Megan Fellman (Northwestern) here.

 

 

Shaping up nanoparticles for DNA delivery to cancer cells

Hai-Quan Mao, 2012 Johns Hopkins Nano-Bio Symposium. Photo by Mary Spiro

To treat cancer, scientists and clinicians have to kill cancer cells while minimally harming the healthy tissues surrounding them. However, because cancer cells are derived from healthy cells, targeting only the cancer cells is exceedingly difficult. According to Dr. Hai-Quan Mao of the Johns Hopkins University Department of Materials Science and Engineering, the “key challenge is between point of delivery and point of target tissue” when it comes to delivering cancer therapeutics. Dr. Mao spoke about the difficulties of specifically delivering drugs or genetic material to cancer cells at the 2012 Johns Hopkins University Nano-Bio Symposium. Scientists had originally thought they could create a “magic bullet” to patrol for cancer cells in the body. However, this has not been feasible; only 5 percent of injected nanoparticles reach the targeted tumor using current delivery techniques. Simply put, scientists need to figure out how to inject a treatment into the body and then selectively direct that treatment to cancer cells if the treatments are to work to their full potential.

With this in mind, Dr. Mao and his research team aim to optimize nanoparticle design to improve delivery to tumor cells by making the nanoparticles more stable in the body’s circulatory system. Mao’s group uses custom polymers and DNA scaffolds to create nanoparticles. The DNA serves dual purposes, as a building block for the particles and as a signal for cancer cells to express certain genes (for example, cell suicide genes). By tuning the polarity of the solvent used to fabricate the nanoparticles, the group can control nanoparticle shape, forming spheres, ellipsoids, or long “worms” while leaving everything else about the nanoparticles constant. This allows them to test the effects of nanoparticle size on gene delivery. Interestingly, “worms” appear more stable in the blood stream of mice and are therefore better able to deliver targeted DNA. Studies of this type will allow intelligent nanoparticle design by illuminating the key aspects for efficient tumor targeting.

Currently, Dr. Mao’s group is extending their fabrication methods to deliver other payloads to cancer cells. Small interfering ribonucleic acid (siRNA), which can suppress expression of certain genes, can also be incorporated into nanoparticles. Finally, Mao noted that the “worm”-shaped nanoparticles created by the group look like naturally occurring virus particles, including the Ebola and Marburg viruses. In the future, the group hopes to use their novel polymers and fabrication techniques to see if shape controls virus targeting to specific tissues in the body. This work could have important applications in virus treatment.

Story by Colin Paul, a Ph.D. student in the Department of Chemical and Biomolecular Engineering at Johns Hopkins with interests in microfabrication and cancer metastasis.