In the operating room, orthopaedic surgeon Stephen B. Trippel replaces knees and performs other surgeries to reconstruct joints that have been damaged by arthritis. In his research laboratory, he is working on ways to make such surgeries unnecessary, by convincing cartilage to repair itself.

Articular cartilage is the thin layer of tissue covering the bones in joints, allowing them to move smoothly. When the cartilage deteriorates, as in arthritis, painful scraping results. Using genetic engineering techniques, Trippel has successfully inserted a particular gene into cartilage cells. In the laboratory, those cells have begun creating new cartilage tissue, raising the possibility that cartilage damage could be prevented, or repaired, without resorting to the surgical knife.

“Arthritis is a biological problem, and what we’re seeking is a biological solution,” says Trippel.

A professor of orthopaedic surgery at IU School of Medicine, Trippel has teamed up with researchers at Zimmer Inc. and Purdue University to turn his laboratory progress into products that can treat patients by restoring cartilage damaged by arthritis, sports injuries, and other causes. The collaboration is supported by a $2 million grant from the Indiana 21st Century Research and Development Fund.

The gene of interest in Trippel’s work is responsible for a protein called insulin-like growth factor-1, or IGF-1. It came to Trippel’s attention as he looked at how cells are regulated by growth factors—proteins that are part of the mechanism that tells cells when to divide and make new tissue.

The IGF-1 gene is most active very early in life, during the growth and development of the skeleton. After that, levels of IGF-1 decline, though it may still play a role in maintaining the health of bone and cartilage tissue.

Given IGF-1’s role in skeletal growth and development—which occurs through division and differentiation of cartilage tissue—Trippel thought the growth factor might be used to encourage cartilage cells to begin repair efforts. IGF-1 is present in the cells naturally, but at low levels. “The cells don’t make enough of it on their own to make adequate repairs,” Trippel says.

To get the cartilage cells to produce IGF-1, the gene is inserted along with a “promoter” gene that works like a switch to turn on the IGF-1 gene.

But why pursue this approach when joint replacement surgery has a successful track record? Why not develop better surgical techniques and materials?

Surgery is successful, agrees Trippel, but it’s not a cure—it doesn’t make the joint normal. Surgeons have artificial surfaces that can eliminate the pain, but they also can fail. And while developing new techniques and materials is important, research revealing the biological causes and mechanisms of cartilage damage suggests new treatments.

“As we understand the mechanisms that cause the disease, my sense is that the need for joint replacement is going to diminish,” Trippel says, “because we will be able to prevent or cure the disease rather than have to go in and replace a joint after the disease has destroyed it.”