For a salamander or a starfish, a severely damaged (or even amputated) limb is no big deal. But for humans – whose ability to regenerate tissue does not match that of Urodela and echinoderms – significant bone loss from trauma, osteoporosis or cancer can be debilitating.
According to Amy Yousefi, associate professor in the department of chemical, paper and biomedical engineering, a human bone defect of a certain critical size (about one inch in the radius or ulna or two inches in the femur or tibia) will not heal completely without a graft. Traditionally, grafts are taken from elsewhere in the patient’s body or from a human donor. However, there are a number of complications associated with this approach, so synthetic bone graft substitutes, or bone scaffolds, are increasingly used in place of natural human bone.
Ideally, a synthetic bone scaffold will foster biological regeneration processes while also assuming the load-bearing function of healthy bone. “The scaffold should be receptive to cells; cells should like it in terms of structure and chemistry,” Yousefi says. At the same time, the scaffold’s mechanical properties should enable the patient to exercise almost immediately following surgery because, as Yousefi points out, “Exercise is stimulation that promotes bone growth and prevents bone resorption.”
But it turns out that these criteria compete with one another. “It’s difficult to get everything working at the same time,” Yousefi says. “There are other research teams working on the same kind of design. Some of them have constructs that are load-bearing, but they’re not necessarily porous enough, or if they’re porous enough, they don’t have the required mechanical properties, or if they have both, they won’t have the right chemistry and cells won’t necessarily like the structures.”
Yousefi saw an opportunity to assemble an interdisciplinary team at Miami with the potential to resolve the tensions between the competing criteria. Yousefi; Paul James, associate professor of biology; Shouzong Zou, associate professor of chemistry; Jing Zhang, assistant professor of statistics; and Jens Mueller, senior research computing specialist, each contribute a key piece to the complex puzzle.
“Amy’s part of the project is to develop the materials that we’re going to grow these cells on that are going to mimic the properties of bone. My part of the project is to actually grow the cells and seed them into these scaffolds,” James says. “We know what goes into the material,” he continues, “but in the final product, we don’t know exactly where it is and that’s what Zou will be doing – looking at where the specific materials that we put into the scaffold end up in the final product.”
With chemical, biological and engineering variables all at play, designing experiments that will ultimately yield the optimal solution is a daunting prospect. “A high number of variables gives you a high number of experiments and structures to build,” explains Yousefi. So Zhang and Mueller are applying their respective statistical and computing expertise to more efficiently account for and manage the copious parameters. “We want to develop a strategy for designing these scaffolds that is easier for the researchers to use,” Yousefi says, “so the experimental design itself is something we want to come up with, to offer to the research community.”
Once enough pieces of the puzzle are in place to allow an appreciation of the overall picture, Yousefi and her team hope to advance their project with funding from the National Institutes of Health or the National Science Foundation. “Miami’s office for the advancement of research and scholarship has provided seed funding that will enable us to generate some preliminary data and increase the chance of outside funding,” Yousefi says. While that may not be the final piece in the puzzle, it will be an important step in getting this biomedical technology into the hands – and arms and legs – of patients.
Written by Heather Beattey Johnston, OARS assistant director and information coordinator
. Image provided by Amy Yousefi.