Giuseppe Battaglia (GB), Professor at The Krebs Institute, The Centre for Membrane Interactions and Dynamics & Department of Biomedical Science, University of Sheffield and Adam J. Engler (AJE) Professor of Bioengineering Sanford Consortium for Regenerative Medicine, University of California talk to Kal Kaur at AZoNano about Nano-Scopic Foam Biomaterial.
KK - What are the current issues with stem cell growth and how has this encouraged the development of nano-scopic foam biomaterial?
GB & AJE - Stem cell engineering is the paradise for material scientists as most of the structure/function relationship has not been disclosed. Clearly these need to be assessed by taking inspiration from Nature extracting the most appropriate cues that some how have to be convolved into some sort of device. However, this is not an easy task as Nature is complex and still very much undisclosed. This concept makes this area of research extremely exciting as not only can we produce more effective devices but we can stumble across new biological discoveries. Most synthetic scaffolds used in the lab to test cells prior to their use in animals and humans do not adequately reflect all of the properties of a given tissue in the body.
One classic example is stiffness: most labs still grow cells on plastic dishes but most of the body is not hard like plastic. Similarly tissues are composed of extracellular matrix, a scaffold to which cells attach, but this matrix is sticky only in discrete areas. Most synthetic materials in the lab are adhesive all over rather than in small spots. The nano-scopic foam mixes stick and non-sticky materials together in ratios that result in these small sticky spots.
KK - How is the nano-scopic foam biomaterial made?
GB & AJE - We take our sticky and non-sticky materials and put them into a mixture of oil and water. These materials are such to sit at the interface between the oil and water (just like soap). Just like a salad dressing, we then shake up the oil and water, making tiny droplets of water in an oily matrix, and while they are still small, we lock the materials into place by crosslinking the matrix. We can then remove the water, leaving only the consequent porous material behind.
The sticky and non-sticky patches that develop at the oil/water interface are the result of the two materials naturally wanting to associate with themselves and not mix with the other. So, when you have mostly non-sticky materials with a small amount of sticky material present, you end up with small patches of stickiness in an otherwise non-sticky foam. We call this interface engineering.
KK - What advantages does the structure of the nano-scopic foam have for its function in helping stem cell growth?
GB & AJE - Aside from the benefits of having sticky patches, we made materials reassembling closely the natural 3D environment and changing the surface of the scaffold throughout the material giving more space to the cell to function.
KK - What challenges were involved in designing this nano-scopic foam?
GB & AJE - Making this type of porous material is not new and it’s been around for a while; however, they were the perfect scaffolds to prove our interface engineering approach. We faced significant problems characterizing the sticky patches on the foam at the nano-meter length scale. While making the material at the appropriate composition was challenging, we had to develop the imaging method at that small length scale to be able to observe the patches.
Detection was performed using atomic force microscopy (AFM) with special functionalized tips which were scanned across the material at 20nm resolution (much better than conventional light microscopy). Also AFM is a functional assay where we could assess not just the presence of adhesion but also the strength of adhesion (in nanoNewtons of force) at a given spot.
KK - How will this technology allow researchers across the world to make biomaterials better suited for stem cells to grow?
GB & AJE - Our approach is very simple and can be replicated relatively easily by any scientists across the world. We would like to propose that with a more biomimetic environment, researchers should be better able to direct differentiation of their stem cells or regulate the behavior of normal adult cells. While this material addresses adhesion, there are certainly many other parameters that must be optimized (stiffness, topography, porosity, ligand composition), and so this is the next step in making adhesion more mimetic. Ultimately however, these properties must be integrated together to improve mimicry.
Scanning electron microscope image of newly developed foam biomaterial with just the right amount of random stickiness so that stem cells can adhere and grow into mature tissue cells.
KK - Are there any design and development challenges that still require further research attention for such technology?
GB & AJE - As mentioned above, the integration of multiple material technologies into a dynamic but controllable material that displays defined matrix properties is still a long way from being a reality and will require many more years of work to develop.
KK - How well can this technology mimic the natural processes in the human body?
GB & AJE - We showed that there is the same degree of heterogeneity within the material as exists in the body, so I believe that it does a very nice job of mimicking the natural adhesion of matrix in tissues.
KK - What does this technology mean for stem cell research on degenerative conditions such as Diabetes, Multiple Sclerosis, and Parkinson’s Disease?
GB & AJE - With these foams, you can more completely mimic the environment in which cells should grow. Thus we can create more completely differentiated cells outside the body for use inside the body once injected. Engler’s lab is interested in using the scaffolds to better differentiate stem cells into muscle, and these muscle cells could then be injected into patients with Duchenne Muscular Dystrophy (DMD). These cells could then fuse with existing muscle and deliver appropriate copies of the gene that is mutated in DMD. Battaglia’s lab has similarly engaged with more translational approaches and using similar scaffolds to control neuronal differentiation for Deafness or other neurodegenerative diseases.
KK - How do you plan on developing your recent research efforts on nano-scopic foam biomaterial?
GB & AJE - We have begun to tackle the issue of improving the porosity and topology of the foam by using the same materials but fashioning them into interwoven fibers rather than using the materials in a foam structure.
About Giuseppe Battaglia
Giuseppe Battaglia is a professor of Synthetic Biology in the Department of Biomedical Science at the University of Sheffield. Giuseppe Battaglia is interested in research problems that require a considerable understanding of biology to tackle clinical challenges via the development of new physical tools. His research tackle this by studying the specific design rules behind inter/intra molecular interactions and self-assembly of soft matter systems, often taking inspiration from biological systems such as cells and viruses. Giuseppe Battaglia’s research team subsequently translate these rules into the engineering of nanostructured biomaterials. This involves the detailed biological and pharmacological evaluation of these novel functional polymers for applications that range from drug and gene delivery, diagnostic, to cell and tissue engineering.
About Adam Engler
Adam J. Engler is a professor of Bioengineering at University of California, San Diego and is affiliated with Material Science and Biomedical Sciences Programs. He is also a resident scientist at the Sanford Consortium for Regenerative Medicine. His research focuses on how physical properties of the niche influence stem cell function, misregulated muscle function and heart performance during disease and aging. Dr. Engler earned his B.S.E. degree in bioengineering and a Ph.D. in mechanical engineering and applied mechanics at the University of Pennsylvania whilst working in Dr. Dennis Discher’s lab.
Dr. Engler then moved to Princeton University's Department of Molecular Biology as a Postdoctoral Research Fellow working in Dr. Jean Schwarzbauer’s lab where his work was funded by the National Cancer Institute. Dr. Engler is the 2008 recipient of the Rupert Timpl and Rita Schaffer Young Investigator Awards from the International Society for Matrix Biology and the Biomedical Engineering Society, respectively. He is also a 2009 NIH Innovator Award recipient and a 2010 Young Investigator Awardee from the Human Frontier Science Program.