In this short interview, the main topic of discussion is the use of nanoscale scaffolding materials in tissue engineering. They act as a temporary substitute for the extracellular matrix that normally supports cells, allowing cells to survive and move in order to form new tissue. Ultimately the cells replace the scaffold with new extracellular matrix structures, and the end result is regrowth of tissue where that regeneration would not normally have occurred.

For tissue engineering and repair, we've been focusing lately on skeletal muscle. There's really a medical need for platforms or scaffolds for muscle fiber regeneration, since after injury the body's abilities to repair skeletal muscle are really quite limited. Skeletal muscle makes up a large part of the human body - 40 to 50 percent by weight. And when damage occurs to skeletal muscle on a small scale, we've seen that skeletal muscle possesses innate repair mechanisms. Through these mechanisms, a new fiber can grow, for example, essentially repairing or replacing the damaged one. But above a critical threshold of damage to skeletal muscle, our bodies no longer employ those effective repair mechanisms. Instead, the body forms scar tissue at the wound site - and then you've essentially lost control of that muscle function. You can't get it back. Surgically, you could graft in skeletal muscle. But that depends on the availability of donor tissue. So we know that the body can repair skeletal muscle. It just doesn't do so beyond a certain threshold of damage.

Natural skeletal muscle is surrounded by a complex extracellular matrix that supports muscle fibers as they form and grow in the body. What we would like to do in this field, which many researchers are working on, is to create an artificial extracellular matrix into which we could introduce a progenitor type of cell - like stem cells or muscle progenitor cells - and then provide them with the proper signals to differentiate into muscle fibers. We believe that scaffold and signals are what is needed to grow new muscle fibers, which you could then transplant to the site of damage. In general, with designing scaffolds for cell growth, the material we work with really depends on the type of cell we'd like to introduce into the scaffold to proliferate. For bone tissue regeneration, which we've worked on in the past, we created a scaffold made of chitosan - a complex polysaccharide, essentially long chains of sugar-like molecules - combined with other materials to create a calcified scaffold. For skeletal muscle, we and other researchers work with a variety of anisotropic materials.

Anisotropic materials have physical properties that differ based on direction or orientation. They form the basis of the scaffolds and are usually complex polymer materials. The innate "directionality" of anisotropic materials helps the progenitor cells grow into three-dimensional forms like a myotube, which is a precursor to a muscle fiber. But there are structural challenges to overcome. The scaffold must be micropatterned to promote cell migration, growth and proliferation in the right direction. This involves nanoscale design details, and some polymers are better for this than others. The production of highly aligned nanofibers in a large area remains a great challenge. We have developed several methods to produce nanofibers made of natural polymers with a high degree of alignment and uniformity over large areas. In addition, we often coat the scaffold with biomolecules that help the cells stick to the scaffold and provide them with the right signals to grow and differentiate: adhesion proteins, growth factors and transcription factors that deliver specific messages to cells depending on their structure and location in the scaffold. By changing what we make the scaffolds out of, the protein messages we coat them with or the nanopore structures within the scaffolds, we can reveal many different properties of cells. We can also test the types of external signals, be it a structural feature of the scaffold or a protein message, that can promote or inhibit cell growth.