Tissue engineers have designed scaffolds for stem cells made from nanotubes that induce them to form cartilage. These nanofibers are tiny, artificial fiber scaffolds that are thousands of times smaller than a human hair. Cartilage formation has succeeded in laboratory and animal model systems.
Much more work is necessary before these scaffolds can be used inside a human body; the results of this present study hold promise for designing new techniques to help millions who endure joint pain.
Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology and director of the Translational Tissue Engineering Center at the Johns Hopkins University School of Medicine, said: “Joint pain affects the quality of life of millions of people. Rather than just patching the problem with short-term fixes, like surgical procedures such as microfracture, we’re building a temporary template that mimics the cartilage cell’s natural environment, and taking advantage of nature’s signals to biologically repair cartilage damage,”
Unfortunately, cartilage does not repair itself when damaged. For the last decade, Elisseeff’s research team has been trying to better understand the development and growth of cartilage cells (chondrocytes). Part of these studies has involved building scaffolds that mimics the environment inside the body that produces new cartilage tissue. The cartilage-making environment consists of a three-dimensional mix of protein fibers and gel. This matrix provides support to connective tissue throughout the body, and physical and biological cues for cells to grow and differentiate.
In the laboratory, the Elisseeff team created a nanofiber-based network that utilized a process called electrospinning. Electrospinning shoots a polymer stream onto a charged platform, to which a compound called chondroitin sulfate is added. Chondroitin sulfate is commonly found in many joint supplements. After characterizing the manufactured fibers, they made several different scaffolds from spun polymer or spun polymer plus chondroitin sulfate. Elisseeff and her colleagues then seeded the scaffolds with bone marrow stem cells from goats in order to test how well the scaffolds supported the growth of the stem cells.
The results showed that the scaffold-supported stem cells formed more voluminous, cartilage-like tissues that those grown without the manufactured scaffolds.
“The nanofibers provided a platform where a larger volume of tissue could be produced,” said Elisseeff, adding that 3-dimensional nanofiber scaffolds were more useful than the more common nanofiber sheets for studying cartilage defects in humans.
Next, Elisseeff and her group tested the ability of these nanotube scaffolds and the cartilage they produce in an animal model. They implanted the nanofiber scaffolds into damaged cartilage in the knees of rats. They compared the quality of the knee repair to damaged cartilage in knees that were not treated with any stem cells. The nanofiber scaffolds improved tissue development and repair. The nanofiber-implanted knees produced far more cartilage as measured by the production of collagen, which is a component of cartilage. The nanofiber scaffolds induced the production of larger quantities of a more durable type of collagen, which is typically absent in surgically repaired cartilage tissue. In rats, the limbs with damaged cartilage treated with nanofiber scaffolds generated a higher percentage of the more durable collagen (type 2) than those damaged areas that were left untreated.
“Whereas scaffolds are generally pretty good at regenerating cartilage protein components in cartilage repair, there is often a lot of scar tissue-related type 1 collagen produced, which isn’t as strong,” said Elisseeff. “We found that our system generated more type 2 collagen, which ensures that cartilage lasts longer. Creating a nanofiber network that enables us to more equally distribute cells and more closely mirror the actual cartilage extracellular environment are important advances in our work and in the field. These results are very promising.”