By: Kevin R. Stone
In 2010, I was honored to give a TED talk on the future of biologic joint replacements. A biologic joint replacement essentially means rebuilding or regenerating a damaged joint naturally, rather than replacing it with metal and plastic.
Part of my talk mentioned the possibility of one day being able to humanize animal tissue to create a biologic replacement device to repair joints. At that time, a company that I had founded, Aperion Biologics Inc., was working on developing a bioengineered porcine ligament device, called a Z-Lig, to reconstruct a torn human anterior cruciate ligament in the knee.
Currently, ruptured ACLs are reconstructed using a patient’s own tissue, such as part of the hamstring (autograft) or using human donor tissue (allograft). While an allograft is preferable, since it does not involve further damage to the patient, widespread use is limited for a number of reasons: donor tissue shortfall (there are 1 million soft-tissue repair surgeries in the U.S. but only around 15,000 to 20,000 orthopedic tissue donors) age of donor tissue (tissue from older donors is less robust) and concerns about sterility.
This past month, the future that I talked about at TED four years ago became a reality, when Aperion secured approval to sell the Z-Lig in Europe and other CE (European Conformity) mark countries. It means that surgeons can now use animal tissue (xenograft) to reconstruct or revise a ruptured ACL.
The successful clinical trial proves that it is possible to substitute animal tissue for human tissue in ligament reconstruction surgery. Up until now, animal tissue, when transplanted into humans, has been plagued with problems such as rejection and inferior performance in demanding applications such as knee reconstruction procedures.
Attempts in the past to cross-link animal tissue in a chemical solution have failed. The cross-linked tendons worked for a limited time and then failed due to their mechanical properties, inability to remodel and the patient’s reaction due to the chemicals leaching from the tissue graft into the knee joint.
Early-stage development and pilot trials of the Z-Lig were conducted by The Stone Clinic, together with Uri Galili and Tom Turek. What we developed was a Z-Process technique, which is able to strip the animal tissue of the key rejection antigen (a specific carbohydrate on the cells and extracellular matrix called the alpha-galactosyl epitope) without damaging the tissue’s biological or mechanical characteristics, creating a scaffold that remodels over time into the patient’s own human ligament.
We now have patients with Z-Lig devices 10 years after implantation. More recently, Aperion conducted a prospective, randomized controlled clinical trial in Europe and South Africa to compare the Z-Lig to donor tissue. The clinical results demonstrated biological acceptance of the device, immediate and continued re-establishment of function and stability in the knee, and gradual remodeling of the device into human tissue over time.
For now, the device is permitted in Europe and South Africa. U.S. clinical trials are being planned to obtain FDA approval for the device allowing it to be sold in the USA. Meanwhile, we are investigating the very real possibility that the Z-Process of reducing the antigenicity of animal tissues may be applied to a variety of tissues and indications, from orthopedic ligaments, bone and meniscus to cardiovascular heart valves and vessels to soft-tissue grafts for general surgical augmentation and repair. We see this as the beginning of a new era in biologic surgical solutions.
Dr. Kevin R. Stone is an orthopedic surgeon at The Stone Clinic and chairman of the Stone Research Foundation in San Francisco. He pioneers advanced orthopedic surgical and rehabilitation techniques to repair, regenerate and replace damaged cartilage and ligaments. For more info, visit www.stoneclinic.com.