Replacing and repairing human tissue is becoming feasible largely due to advances in the use of stem cells.
“Cells do not simply reside within a material, they actively re-engineer it,” says Kelly Schultz, P.C. Rossin assistant professor of chemical and biomolecular engineering at Lehigh University’s P.C. Rossin College of Engineering and Applied Science.
“Characterizing how cells behave in 3-Dimensional synthetic material is critical to advancing biomaterial design used in wound healing, tissue engineering, and stem cell expansion.” Schultz recently received a three-year grant from National Institutes of Health grant to study how cells remodel their microenvironment-a crucial step toward engineering cells to move through synthetic material and tissue more quickly for faster wound healing and tissue regeneration.
Schultz will build on previous work in which she and her colleagues revealed that during attachment, spreading and motility, cells degrade material in the pericellular region the region directly around the cell- in an entirely different manner than researchers had previously believed.
Prior to Schultz’s earlier study, scientists believed cells moved through the material while simultaneously degrading it – like a Pac-Man gobbling up dots while making its way through a video game maze.
After encapsulating mesenchymal stem cells in a hydrogel, the team measured dynamic interactions between the cells as they moved through the material.
Once identified, the researchers hope to “Tune” the inhibitor to shut off during secretion so that the cell will move through and degrade the material faster.
Engineering the cell to move faster is important for wound healing, Schultz says, since the sooner the cells arrive at the wound site, the sooner they can start to regenerate the tissue.
“Our goal is to prevent the cell from stalling, encouraging it to become active right away and arrive at the wound site at twice the speed,” said Schultz.
A scaffold to mimic bone With broad implications for biomaterial design, Schultz’s project will focus on a broad range of tissues, from adipose to bone, to measure how changing the physical environment might change the strategies cells use to degrade the material.
She works with mesenchymal stem cells-a type of adult stem cells that that have the ability to differentiate into a variety of cell types.
First, it mimics tissue well, providing an ideal physical environment to characterize cell behavior in 3D. Hydrogels are greater than 90% water, very porous and can be “Tuned” to change properties to mimic anything from bone to fat Second, once the hydrogel is implanted in a human, it can be used as a scaffold to re-structure a critical size wound that the body would not be able to heal.
If a patient is missing a piece of bone that is too large to heal or regenerate-on its own, a hydrogel structure can be implanted. Inside the structure are stem cells that have been given an environment that would push them down a lineage into bone cells,” said Schultz.
“Once implanted the stem cells reproduce themselves, ‘filling in’ the part of the bone that is missing. While the bone is growing outside the implant, new tissue is growing on the inside-speeding healing. As the bone regenerates, the implant disintegrates.” To make the hydrogel structures, Schultz mixes polymers, peptides, stem cells, and microparticles.
The techniques and strategies she and her team develop are expected to contribute to the understanding of cell-material interactions and identify how these interactions can be exploited to manipulate cellular behavior for 3D cell culture platforms and tissue regeneration applications.