Intervertebral discs are successfully transplanted to the goat.

For the first time, bioengineering intervertebral disks were successfully implanted and provided a long-term function in the largest animal model ever used in this direction.

A new study by Penn Medicine, published in Science Translational Medicine, shows convincing evidence that the cells of patients suffering from neck and back pain can be used in the engineering of a new intervertebral disk in the laboratory to replace the damaged one. The goat study was conducted by an interdisciplinary team of the Faculty of Medicine, the School of Engineering and Applied Sciences and the School of Veterinary Medicine at the University of Pennsylvania.

Soft tissues in the spine, intervertebral discs, are needed in movements such as turning the head or tying shoelaces. But about half of the adult population in the United States suffers from back or neck pain, and treating and caring for them puts a serious economic burden on society — about $ 195 billion a year. While the destruction of the intervertebral disc is often associated with this pain, the main causes of its destruction remain less clear. Modern approaches, including spinal surgery and mechanical replacement implants, provide symptomatic treatment, but they do not restore the structure, function, and range of movement of the native disk, and they often have limited effectiveness. Thus, there is a request for new treatments.

Tissue engineering has great promise. It involves combining the patient’s own stem cells or animals with biomaterial scaffolds in the laboratory to construct a complex structure that is then implanted in the spine as a replacement disk. For the past 15 years, the Penn research team has been developing a bioengineering disk using tissue engineering, moving from basic in vitro research to models with small animals and models with larger animals, focusing on human testing.

“This is an important step: to grow such a large disk in a laboratory, place it in disk space, and then force it to integrate with the surrounding native tissue. This is very promising, ”said Robert L. Mock, a professor of education and research in orthopedic surgery at the Perelman School of Medicine in Penne, as well as a researcher at the Corporal Michael Crescenz VA Medical Center (CMC VAMC) in Philadelphia and the main author of the publication. "The current therapies do not really restore the disc, so we hope that with this implant we will replace it with a biological, functional way and restore the full range of motion."

Past research conducted by the team successfully showed the integration of their bioengineering disks, known as disc-like angle ply structures (DAPS), into the tails of rats for five weeks. This latest study extended this period on the rat to 20 weeks - but with updated disks, known as endplate-modified DAPS or eDAPS, to mimic the structure of the native spinal segment. The addition of end plates helped to preserve the engineering structure and promote its integration into the native tissue.

MRI, along with histological, mechanical and biochemical analysis, showed that eDAPS restored the structure of the native disk, biology and mechanical function in a rat model. Building on this success, the researchers then implanted eDAPS into the cervical spine of the goats. They chose a goat because the dimensions of its cervical-spinal disc are human-like, and the goats have a semi-permanent figure.

Researchers have shown a successful complete disc replacement in the goat's cervical region. One month later, the matrix distribution was either preserved or improved within the framework of eDAPS. The MRI results also suggest that the composition of the disc was maintained or improved after eight weeks, and that the mechanical properties were either consistent or superior to those of the native goat disc.

“I think it's great that we have gone from rat tails to human-sized implants,” said Harvey E. Smith, MD, associate professor at the Department of Orthopedic Surgery and Neurosurgery at Perelman Medical School. and a full-time surgeon at CMC VAMC, as well as a senior researcher and clinical research manager. "When you look at the success in the literature on mechanical devices, I believe that there is a very good reason for optimism that we can achieve the same success if we do not surpass it using bioengineering disks."

The research team links the success of this work with the interdisciplinary and translational approach that they used from the very beginning in Penn, where many experts from various faculties and schools that were involved in this project live.

“We used all the different directions Penn has under his roof, from basic research to clinicians. We have an incredible network that can be used for this and other research, ”said study author Thomas P. Schaer, director of VMD, director of translational orthopedic research and preclinical research at the School of Veterinary Medicine, University of Pennsylvania New Bolton Center. "Not every academic institution has such a collaborative ecosystem that was a huge advantage for us when we started this study and then supported it in time."

The team also includes first author Sarah Gulbrend, research assistant at the Department of Orthopedic Surgery at Penn Medicine and the Translational Musculoskeletal Research Center at the Corporal Michael Crescenz VA Medical Center, Lachlan Smith, and a staff member at the Department of Neurosurgery and Orthopedic Surgery at Penne and Dawn M. Elliott, former researcher Penna, currently head of the Department of Biomedical Engineering at the University of Delaware.

The next step is to conduct more long-term eDAPS function tests in the goat model, the authors said, as well as to simulate the destruction of intervertebral discs in humans and to test how their bioengineering disks work in this context.

“It is advisable to implant biological tissues made up of your own cells,” said Smith. “The use of a real tissue replacement implant in arthroplasty is something we have not done in orthopedics. I believe that this will be a paradigm shift in how we treat spinal diseases and how we reconstruct joints. ”