Weaving a New Knee
Although cartilage is a relatively simple tissue – bearing no blood vessels or nerves and only three main constituents (water, collagen and proteoglycans) – scientists still face challenges in engineering and growing replacement material that behaves like natural tissue. Biomedical engineers have been able to create rudimentary cartilage to replace that damaged by arthritis, but they are still working to develop cartilage with the same mechanical and biophysical properties as natural cartilage.
Challenges of Engineering Cartilage
Cartilage possesses complex mechanical properties that allow for its crucial load-supporting and low-friction assets, properties that have proven difficult to simulate. Once chondrocytes (cartilage cells) are transplanted into a joint, they can synthesize proteoglycans fairly quickly, giving the tissue compressive strength. However, collagen synthesis is much slower, and collagen gives the tissue its tensile strength (the resistance of a material from being torn apart). It is the combination of compressive strength and tensile strength that allows joints to withstand the loads transmitted across them.
It takes longer for the body to grow transplanted cartilage at maximum strength than people are willing to stay off of the joint. So, scientists must develop a framework upon which the chondrocytes grow that possesses enough strength and lubrication to allow the joint to function while the chondrocytes synthesize proteoglycans and collagen.
Obtaining cells to regrow cartilage has been another hurdle for scientists. Chondrocytes can be removed from the patient, grown in the lab, and then put back into the patient. However, this process requires two invasive procedures. Stem cells (cells that can differentiate into any of several different types of mature cells) can be grown with certain chemicals to encourage them to differentiate into chondrocytes for implantation. Stem cells from human embryos are not abundantly available and their use can be controversial.
Furthermore, natural cartilage is organized into three distinct layers, each of which contain slightly different types of chondrocytes. To date, most attempts to grow cartilage have involved seeding a uniform framework with identical chondrocytes, creating a structurally consistent tissue. Jennifer Elisseeff, PhD, has been working to solve this particular challenge. See the May/June issue of Research Update for a summary of her Arthritis Foundation-funded work.
Meeting the Challenges
Farshid Guilak, PhD, of Duke University Medical Center, and colleagues at Duke and at the Massachusetts Institute of Technology in Cambridge have created a novel framework upon which cartilage tissue can be grown. They developed a microscopic weaving technology to generate structures with fibers woven in three orientations. This three-dimensional scaffold is porous and has different mechanical properties along each plane of symmetry. The team is able to seed the fabric with cells suspended in a gel and to transplant the seeded fabric into the damaged joint. This scaffold shows better mechanical properties than the previously used matrices, allowing the chondrocytes the time they need to synthesize proteoglycans and collagen. The plan is that the gel and fabric will eventually degrade and be absorbed by the body, leaving only healthy, strong cartilage.
Along with creating this new woven scaffold, Guilak’s team has taken advantage of another source of cells to be used for cartilage growth. They have found that a large number of stem cells can be extracted from liposuctioned fat. These cells can be induced to differentiate into chondrocytes by exposing them to certain chemicals in the laboratory. Guilak is optimistic that this process has little potential for rejection or other health risks. “The cells we are using can be implanted in the patient because they come from the patient. The stem cells will probably be extracted with a needle from adipose [fat] tissue located in the stomach or the buttock of the patient."
Future Plans
Beginning this month, Guilak can add the Arthritis Foundation to his list of funding sources. Along with several National Institutes of Health grants, he has been awarded an Innovative Research Grant, supported by Gordon and Carole Segal, founders of the national home furnishings retailer Crate & Barrel and major contributors to the Arthritis Foundation’s research program. Through the Arthritis Foundation, the Segals fund an initiative targeted to find better treatments, earlier diagnosis, and eventual cures for osteoarthritis.
Guilak and team plan to continue suspending stem cells derived from adipose tissue in their specially woven fabric. The next step is to test the engineered tissue on mice to ensure the cartilage will function properly. If everything progresses according to plan, a new form of engineered cartilage will be available to treat joints damaged by osteoarthritis or other cartilage injuries.
