ARLINGTON, Va., April 19, 2005 -- Imitation may be the sincerest flattery, but in tissue regeneration it is essential.

“What we want to do is make a scaffold that can truly mimic nature at the nanoscale,” says Peter Ma, Ph.D, associate professor of biomedical engineering at the University of Michigan. “That might give us the optimal scaffold for tissue regeneration.”

Ma creates synthetic scaffolds from biodegradable polymers in a process that closely mimics the nanometer-scale structure of living tissue.

“We thought that such scaffolds were ideal for tissue regeneration because they mimic the natural extracellular matrix, which is mostly collagen, so those scaffolds would support cell growth and regeneration but not have most of the problems with natural collagen scaffolds.”

Collagen is a fibrous protein and key ingredient in the extracellular matrix, the body’s structural framework for cells and tissues. Tissue engineers often create scaffolds using collagen from cadavers or animals. Those sources risk disease transmission or immune rejection because they are foreign materials and they could potentially bring a pathogen into the body.

Synthetic polymers can provide the three-dimensional structure necessary for an effective scaffold but without the risk of disease. They eventually degrade, leaving no long-term effect on the body.

Several years ago, Ma thought synthetic scaffolds could be improved by making their nanometer-scale structure resemble more closely that of collagen. The resulting scaffold would be more attractive to cells, encouraging them to grow and differentiate in abundance.

To achieve the desired structure, Ma begins by dissolving a polymer and then freezing the solution. He drops the temperature of the mixture to a certain point, causing the dispersed polymer molecules to come together and the solvent molecules to do the same.

If the temperature is right, the polymer molecules cling together to form nanofibers. The solvent molecules clump together in a way that spreads the polymer molecules apart, pushing them into a structure that resembles a fine sponge.

When the two materials have completely frozen, the solid is placed in a vacuum and the solvent is evaporated away in a process called sublimation. This leaves behind a polymer structure that is highly porous—98 percent air by volume.

The polymer structure closely resembles that of the body’s extracellular matrix. The high porosity allows cells to grow into the structure while also permitting the easy penetration of nutrients and disposal of metabolic waste, all of which are critical to tissue growth.

“It’s pretty similar to natural collagen,” Ma says. Because he begins with a liquid, Ma can easily mold his polymer into any shape: “All you need to do is pour the polymer solution into the mold. If you want an ear, you can make a mold of an ear. If you want to make a nose, you can make a mold of a nose. If you want to make a finger, you can make a mold of a finger.”

By using different polymers and temperatures, Ma can control the size of the pores (the air space) in the polymer structure to match the pore size of specific tissues.

“If you want to generate nerve, you want those channels to allow nerve cells and tissue to align in those directions,” Ma says. “If you want to generate a blood vessel, you want certain aspects to allow the cells to form a vessel structure, or, in the case of tendons, a parallel tubular structure or other specially oriented pores.”

Tissues that do not have aligned structures might require a spherical shape to give them a lot of space to grow. This is true for such tissues as skin and cartilage. For bone, Ma has embedded within the scaffold a substance that signals immature bone cells, directing them where to attach and how to grow and differentiate.

Ma is working to understand the mechanism of nanometer-scale fiber formation during phase separation. He hopes to apply this technology to other polymers. He is also modifying the surface chemistry of the fibers so they interact better with cells:

“In our body we have all kinds of tissue with all kinds of structures, so we need to be able to create structures to satisfy the body’s requirements.” Ma received a Whitaker Biomedical Engineering Research Grant in 1999 for work on tissue-engineered cartilage.

Contact:
Peter Ma, University of Michigan
Mark Bowman, The Whitaker Foundation