Stopping Osteoarthritis Before It Starts with a Novel Bio-Implant
More than 1 million Americans undergo knee and hip arthroplasty annually, a last-resort treatment to address pain and mobility issues associated with osteoarthritis (OA).
What if physicians could intervene and repair damaged cartilage before surgery is needed?
According to a study from the Keck School of Medicine of USC published in npj Regenerative Medicine, the technology to do so may be available in the not-too-distant future – provided the positive results observed in a large animal model can be duplicated in humans.
That research used a stem cell-based bio-implant to repair cartilage and delay joint degeneration, demonstrating long-term functional repair of porcine full-thickness articular cartilage defects. The work will now advance into humans with support from a $6 million grant from the California Institute of Regenerative Medicine (CIRM).
Intervening Early in OA
To prevent the development of OA and alleviate the need for invasive joint replacement surgeries, the USC researchers propose intervening earlier in the disease.
“In some patients, joint degeneration starts with post-traumatic focal lesions, which are lesions in the articular cartilage ranging from 1 cm2 to 8 cm2 in diameter,” said Denis Evseenko, MD, PhD, Associate Professor of Orthopaedic Surgery, Director of the Skeletal Regeneration Program, and Vice Chair for Research of Orthopaedic Surgery at the Keck School of Medicine of USC.
“Since these can be detected by imaging techniques such as MRI, this opens up the possibility of early intervention therapies that limit the progression of these lesions so we can avoid the need for total joint replacement.”
Full Integration into Damaged Cartilage
That joint preservation technology developed at USC is a therapeutic bio-implant, called Plurocart, composed of a scaffold membrane seeded with stem cell-derived chondrocytes, the cells responsible for producing and maintaining healthy articular cartilage tissue.
Building on previous research to develop and characterize the implant, the current study involved implantation of the Plurocart membrane into a porcine model of OA. The study resulted in the long-term repair of articular cartilage defects.
“This is the first time an orthopaedic implant composed of a living cell type was able to fully integrate in the damaged articular cartilage tissue and survive in vivo for up to 6 months,” Dr. Evseenko said. “Previous studies have not been able to show survival of an implant for such a long time.”
Dr. Evseenko said molecular characterization studies showed the bio-implant mimicked natural articular cartilage, with more than 95% of implanted cells being identified as articular chondrocytes. The cartilage tissue generated was also biomechanically functional, both strong enough to withstand compression and elastic enough to accommodate movement without breaking.
Preparing Implants for Humans
With support from the $6 million translational grant from CIRM, the researchers are using this technology to manufacture the first 64 Plurocart implants to be tested in humans.
“Many of the current options for cartilage injury are expensive, involve complex logistical planning, and often result in incomplete regeneration,” said Frank Petrigliano, MD, Associate Professor of Clinical Orthopaedic Surgery and Chief of the USC Epstein Family Center for Sports Medicine at the Keck School of Medicine of USC.
“Plurocart represents a practical, inexpensive, 1-stage therapy that may be more effective in restoring damaged cartilage and improve the outcome of such procedures.”
Petrigliano FA, Liu NQ, Lee S, et al. Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes. NPJ Regen. 2021 Nov 23;6(1):77. doi: 10.1038/s41536-021-00187-3