The biomimetic fix
Because the grading between tendon and bone occurs at both microscopic and nanoscopic levels, Thomopoulos teamed up with Xia, an expert in nanotechnology, to find a solution to this problem.
In 2009, Xia and Thomopoulos proposed a simple solution: a temporary scaffold that will guide the healing process along the path it follows during development.
"A few scaffolds have been attempted in rotator cuff repair in humans," says Thomopoulos, "with only limited success. These patches are fairly compliant materials, even compared to tendon. The hope is that they'll stimulate a better healing response, but it hasn't happened yet. Our scaffold approach is to mimic the natural tissue by stepping up gradually in stiffness from tendon to bone."
The WUSTL scaffold consists of a mat of nanoscopic fibers electrospun in Xia's lab that mimics the structure of the collagen fibers in a tendon. The mat is then coated with a continuous gradient of hydroxyapatite, a mineral containing calcium and phosphorus that gives strength to bone, so that it is stiff and bone-like toward one end and compliant and tendon-like toward the other.
Finally the scaffold is seeded with adult mesenchymal stem cells, a type of stem cell that can mature into osteoblasts (bone-forming cells) or fibroblasts (cells common in tendon).
The idea is that as the fibers disintegrate over the course of a few months, the mineral gradient will promote the graduated differentiation of the stem cells. Stem cells toward the bone end will be coaxed by the presence of mineral to differentiate into osteoclasts while the stem cells at the tendon end, surrounded by aligned, unmineralized fibers, will form fibroblasts.
"The tendon side is a little bit easier because stem cells tend to go toward the fibroblast-like lineage if you don't do much to them," says Thomopoulos.
The presence of either type of ce
|Contact: Diana Lutz|
Washington University in St. Louis