StemCell Therapy

San Diego researchers have reported a medical milestone: Theyve grown a whole meniscus, the slippery crescent of cartilage that cushions the knee joint.

Animal testing will be needed before the replacement meniscus can be used in people, said Darryl DLima, a Scripps Health physician-scientist who led the study.

Clinical trials will show whether the lab-cultivated meniscus can prevent or delay development of arthritis which commonly occurs when people lose their original meniscus and the accompanying pain and limitations in movement.

If such trials are established, signs of potential effectiveness could emerge as soon as two years into the testing, said DLima, who works at Scripps Clinics Shiley Center for Orthopaedic Research and Education. But it may take up to a decade to be sure.

The lab-grown meniscus contains all the major components of the natural one, DLima said. Made by a printer-like device using high-voltage technology borrowed from textile manufacturing, the meniscus has living cartilage cells embedded in fibers of bovine collagen, a structural protein.

The structure is as necessary as the ingredients to keep the shape of the meniscus amid the stresses it encounters in the knee, DLima said. Merely grinding up the components and molding them into the shape of a meniscus would produce something like cake batter, he said.

We call it the micro-architecture, he added. The Holy Grail has been to replicate the micro-architecture at the macroscopic level.

A physician who holds a doctorate in bioengineering from UC San Diego, DLima is skilled at synthesizing engineering and biology. Colleagues have described him as proficient at looking outside of biology for technologies that can be adapted for biomedical purposes.

DLima and fellow researchers have been pursuing their meniscus work for several years, thanks to various grants.

The details of their milestone achievement were presented last week at the Orthopaedic Research Societys annual meeting in San Diego. There, DLima discussed the types of cells needed for regenerative medicine while the meniscus study itself was discussed by colleague Jihye Baek of The Scripps Research Institute in La Jolla.

The meniscus has a limited ability to recover from injuries because its poorly supplied with blood vessels. Minor damage can be repaired, but extensive injury will destroy it.

In some cases, a cadaver meniscus is used to replace the destroyed one. But the cadaver tissue must be tested to see if it contains dangerous pathogens, and it must be of the right size and shape for the patient. And cadaver meniscus transplants have a 50 percent failure rate.

DLima and his team said growing a replacement could be a better option. The meniscus could be custom-made and grown under sterile conditions to ensure its disease-free.

Experiments using artificial meniscus replacements are being tested, but those products will degrade over time, DLima said. In my opinion, theyre the strongest the day you put them in, because artificial materials can only get weaker, he said.

The theory is that a living replacement will maintain itself, making it more durable in the long run.

In any testing, an artificial material will actually beat a biological material, DLima said. Theres no way a bone can stand up to a steel beam. But a steel beam will eventually break, whereas your bone is constantly repairing itself. And thats whats happening in the meniscus.

If his teams research succeeds, it would represent a major triumph in the emerging field of bioprinting, in which individual cells are placed into a specific pattern that resembles natural tissue.

Companies such as San Diegos Organovo have tapped such technology to produce liver and other kinds of tissue for research. The liver tissue can be treated with various experimental drugs to see whether theyre likely to cause liver toxicity in patients. Organovo is also developing bioprinted tissue for future therapeutic uses.

The meniscus is hard to replicate, with cartilage cells woven in with collagen fibers at a microscopic level. This means both elements must be supplied the cartilage cells alone wont suffice. And arraying the cells and fibers in the proper pattern requires great precision.

DLimas team accomplished that feat by borrowing technology used to make textiles and air filters for vehicles. One, called electrospinning, uses high voltages to array fibers into precise positions. Another, known as electrospraying, deposits the cells inside the woven fibers as they are being spun into position.

The electrospinning process required 20,000 volts, but the cells survived because the current is low. Static electricity produce by shuffling across a carpet in cold, dry weather provides a familiar example of this effect the shock can be strongly felt because of the high voltage, but is harmless because of the low current.

The process is not quite the same as traditional bioprinting, DLima said, but the concept is similar.

The new study was funded by Donald & Darlene Shiley and the California Institute of Regenerative Medicine. Scripps Health initiated the study, provided most of the staffing and collaborated with The Scripps Research Institute.

bradley.fikes@sduniontribune.com

(619) 293-1020

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Lab-grown meniscus could one day prevent arthritis in knees - The San Diego Union-Tribune

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