Collagen matrices may play a larger role in treating soft tissue injuries

Early research indicates they aid healing of ACL and cartilage injuries, but more study is needed before they become the gold standard.

Issue: October 2005

IN SUMMARY

Some researchers believe that a collagen matrix helps “organize the quality” of what happens during treatment by offering structural benefits.
Collagen can be immunogenic.
The FDA has not approved any collagen grafts for soft tissue treatments in the knee.

If some orthopedists have their way, patients around the globe may one day receive a collagen matrix as part of a routine treatment for a torn meniscus, ACL or PCL.

But until then, researchers must continue studying the safety and effectiveness of these matrices to ensure the benefits far outweigh patients’ risk for developing an autoimmune response, said Cyril B. Frank, MD, chair of orthopedic surgery at the University of Calgary in Alberta, Canada, and scientific director of the Canadian Musculoskeletal Health and Arthritis Institute.

Frank and his colleagues are overseeing creation of a national database to track surgeons’ success in treating various orthopedic problems, including injuries to soft tissues like the meniscus, cartilage, ligaments and tendons. He hopes the database will eventually shed light on how biologic agents, like collagen matrices, fit into the picture.

“We’re trying to develop strategies to treat these [soft tissue] problems better,” he told Orthopedics Today. “My own interest has been in ligaments, and my clinical practice is focused on arthroscopic knee surgery and soft tissue reconstructions of knee joints. I’m looking at the role collagen [and other] biologics can play in these cases, and it seems as though they can be an important part in this process.”

The FDA has not approved any collagen grafts as treatments for soft tissues in the knee.

Improving scar healing

In recent research, Frank and his colleagues altered proteoglycan and collagen composition to optimize the properties of scars in various animals.

“We’ve done some gene therapy to manipulate properties of scars in rabbit models over the years, and now we’re working on a sheep model of osteoarthritis (OA) to see if we can prevent OA in these unstable knees,” he said.

Frank typically uses autografts in his patients and affirmed that they are best for soft tissue repair. However, many allografts and, in some cases, xenografts are also effective and have the potential to heal a torn ACL or similar soft tissue injury, he said.

A mix of agents

Cyril B. Frank, MD [photo]
Cyril B. Frank

Collagen — the natural protein-based tissue compound found in the body — combined with some bone morphogenetic proteins (BMPs) like BMP-2 or BMP-7 and “an ex vivo bioreactor-type enhancement prior to implantation,” might be the ideal biologic approach, said Frank, who will chair a Gordon research conference in Andover, N.H., next August to address vital musculoskeletal issues such as the use of collagen.

“I hope the [collagen] matrices help stimulate the repair of joint surfaces and torn ligaments and tendons, and I think we’ll see this more in shoulder cuff repair, where the endogenous repair responses are too limited or are in the wrong place to produce optimal repair,” he said. “A lot of people are also looking into how well [collagen and other biologics] can do in disc repair. I think we’ll see a lot more about that in the next few years.”

What role will collagen play?

Frank said orthopedic researchers must ask themselves how important scaffolds are in the final equation. “Also, how important is the choice of cells that we use in these cases? Should we use embryonic stem cells or adult stem cells?”

He added: “I think all of the evidence supports the notion that a collagen matrix helps organize the quality of what happens during treatment. A matrix offers structural benefits by providing tensile strength and stiffness to whatever tissue or implant is being implanted. Without it, the cellular material is like jelly.”

Not home-free yet

Still, Frank admitted that many orthopedic surgeons and regulatory agencies in North America resist the idea of using collagen matrices to heal an ACL or troublesome disc, although some surgeons have readily accepted their use in rotator cuff tears [see Focus on Biologics insert, August issue, Orthopedics Today].

“I don’t think that the collagen matrix is ready for prime time use yet in many soft tissue cases,” he said. “There is nothing as good as autografts now, which are the gold standard for soft tissue reconstructions both nationally and internationally, and allografts are almost equal in most people’s minds. I use both autografts and allografts in my own cases.

“Therefore, the tissue engineering approaches we are developing, including using collagen matrices, have to be compared to the gold standard,” he said. “Most of the matrices are too weak, frail and slow in recovery when compared to the strength and stiffness that autografts and allografts offer at the time of implantation.”

The collagen can also be immunogenic.

“There can be immune responses if it isn’t host collagen, and if it isn’t treated properly, there can be problems with xenograft collagen,” he said. Xenogeneic collagen can cause an immune response in patients, which occurred in cases in the 1970s and 1980s when patients developed a reaction after receiving bovine collagen grafts. Surgeons eventually stopped using those grafts.

“Everyone is vigilant now at making sure there is compatibility [between] the patient and the graft,” he said. “Those [bad incidents] scared a lot of people, so the last thing we want is an adverse reaction to the graft.”