Medical Device Daily National Editor

Collaboration between physician-scientists at Weill Cornell Medical College (New York) and researchers working on biological regeneration systems at Cornell University (Ithaca, New York) has led to the creation of bioengineered intervertebral (IVD) discs, in the laboratory, for transplantation into the spines of rats.

Such a development could lead to a bioengineered disc in human use, or, failing that, it will provide insights into advanced approaches and techniques for the treatment of disc problems in humans.

Leading the research are Roger Härtl, MD, chief of spinal surgery at New York-Presbyterian Hospital/Weill Cornell Medical Center and Lawrence Bonassar, MD, an associate professor in the departments of biomedical engineering and mechanical and aerospace engineering at Cornell.

Härtl's expertise is in complex surgical procedures on the cervical, thoracic and lumbar spine and the use of minimally invasive spine surgery techniques, and thus he is focused on the surgical factors involved in the study.

Bonassar's research has included development of microfluidic scaffolds used to control cellular development in vitro, and he is responsible for creation of the biologically manufactured discs used in the study.

Härtl initially was responsible for supplying Bonassar and his group with human tissue from the discs of patients he had worked on surgically. But he told Medical Device Daily that the team has more recently begun to use disc tissue from sheep, simply as a matter of being easier to obtain and offering a larger supply to work with.

From this tissue Bonassar isolates the cells and grows them in an incubator that simulates the environment in the body. Once more fully developed, they are placed on a bioengineered scaffold, enabling the assembly of the cells and scaffold into an IVD-shaped implant, consisting of an outer collagen envelope and inner spinal tissue material - paralleling the outside annulus and central nucleus of the typical discs of the vertebrate spinal column.

Bonassar's research group specializes in the regeneration and analysis of bone and cartilage. His laboratory has developed techniques called tissue injection molding and cell-mediated sintering, which induce cultured cells to produce complex tissue structures such that of an IVD disc. He and his team previously reported growing discs from bovine cells and implanting them in nude mice.

Bonassar returns these biologically created discs to Härtl, who inserts them into the spinal vertebrae of the rats to see how they develop and how they will react to the resultant mechanical and biological demands of the rat's body.

So far, Härtl described the results as "promising" at the six-week follow-up to implantation and that a key follow-up assessment will come six months post-implantation, in terms of the animal's behavior but also using MRI to examine the disc's histology.

He said that his primary contribution to this research is in addressing the surgical issues involved for implanting a bioengineered disc – such as choosing the best approach to insert the disc between the vertebrae, and how to minimize the trauma of the procedure, if it were to move to human use.

Other issues involve methods of stabilizing the disc. And because the disc is avascular, how will it obtain the necessary nutrients from the bloodstream? Will simple diffusion be sufficient?

These, he said, are some of the questions being explored in the rat models.

The next step in the research will be to insert the bioengineered discs into a larger animal, probably sheep, with a spinal architecture more closely resembling that of humans.

Further out, of course, are hoped-for clinical studies leading to general use of discs such as these in humans, to aid some of the 20 million in the U.S. alone who suffer the pain caused by injured or degenerated discs.

Härtl acknowledged that the study, to date, is only at the proof-of-concept stage and that the ultimate goal of replacing the original human disc with the bioengineered type – as, for instance, an alternative to disc fusion or use of mechanical discs – is in the much longer-term future.

Failing achievement of this goal, Härtl said that the research still will be valuable, especially in the possibility for developing improved pathways to treat a variety of human spinal problems, particularly in his area of surgical interest.

In the current study, for instance, he said that a variety of technical developments were necessary in order to create the rat model for this study, such as methods for removal of the discs in these much smaller animals (sheep are likely to offer fewer difficulties) and then inserting and holding in place the artificial disc material.

Bonasssar's work in creating the basic elements of an intervertebral disc could lead to new insights into new methods for repair the annulus of a real disc, Härtl said. Most importantly, the repair of holes which allow the inner disc material to poke through onto a spinal nerve, creating the pain of what is generally called a "slipped disc."

The work by Härtl and Bonassar is one of a small number of approaches looking to develop a biological disc for humans.

Last year, Chinese researchers had promising results in transplanting IVDs from human cadavers into patients with degenerative disc disease and herniated discs. This method, however, shares that of all transplant strategies: a limited number of donors.

Another approach is the injection of cartilage cells, called chondrocytes, directly into a damaged disc, hoping that these cells will serve to repair the disc. This approach, however, has been considered insufficient for repairing tissues in conjunction with the bony structures of the vertebrae.

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