Michael Gordon, MD, a spine surgeon with Hoag Orthopedic Institute in Irvine, Calif., weighs in on trends he sees with regard to the use of spinal biologics.
Question: What are some key trends in biologics use for spine surgery over the next five years?
Dr. Michael Gordon: The use of biologics in spine surgery seeks to provide tissue growth without consuming autogenous structures and thus creating patient morbidity. This is a huge subject, and my comments are basic and are intended only as a brief over view. Two basic questions are: How to induce the growth of tissue to solve a surgical problem, such as need fusion or enhanced stability? In other words, how can I avoid taking a painful iliac bone graft and still get a fusion? The second question is how to induce the growth of tissue to repair a pathologic condition? In other words, is there a product I can use that will regenerate this disc so pain will go away without the need for fusion surgery?
For both questions certain issues remain: what is the cost, how easy are the products to use, how long do they last and is their effectiveness worth the price? A product that is five times more expensive than what I'm using today and only 20 percent more effective will not cut it. At the present, FDA-approved technologies exist only as an answer to the first question — creating a fusion in the spine. Available today are various demineralized bone matrix products, allograft and a variety of crystalline hydroxyapatite agents.
As familiar as the tenets of bone-grafting are — structural load bearing, osteoconductive, and osteoinductive as well as osteogenic — all too often products available today that are only modestly effective in this regard. As an example, many DBM products on the market are soft and putty-like with little structural effectiveness, have variable effectiveness in promoting the formation of new cells and are modestly osteoinductive. A piece of dead femoral allograft, although structurally sound may only provide scaffolding for ingrowth over a small surface, and has no inherent live cells. The bone morphogenic proteins, although extremely effective in inducing bone growth, are also extremely expensive, have no structural load-bearing capabilities and require cages and supplemental fixation systems. Although BMP has been shown "superior" to DBM in many fusion models, DBM is much cheaper and in its concentrated form will produce a cervical fusion at one or two levels as well or almost as well as autograft.
Basic science studies comparing the effectiveness of these allograft substitutes are lacking. Very few of the DBM bone graft substitutes on the market today have undergone rigorous primate studies and precious few longitudinal human studies or head-to-head trials are available to determine the effectiveness or even the dose-response curve of effectiveness-for-fusion.
A new push by industry has been autogenous bone-forming infused DBM products promising a cellular regenerative product to grow bone. They are actually allografts that have been selectively depleted of non-bone forming cells, leaving osteoprogenitor cells behind. Their effectiveness remains to be seen.
I anticipate that very soon prices on bone substitutes will decline, particularly as BMP comes off patent. It has become common knowledge that highly hyped first generation hydroxyapatite products, such as coral and "bioactive glass" are next to worthless in the spine, even in the intervertebral space. The industry would be well advised to temper its' enthusiasm and economic incentives around products with poor track records or minimal basic science investigations. A new push into microfibrillar nano-crystalline polysilicate glass may get around the disappointing results of prior hydroxyapatite agents.
Porous 3-D printed titanium has quickly jumped into mainstream use with the promise of lessened need for any biologic to promote fusion, but long-term studies are lacking now — look to the next five years for more science on cell ingrowth into pores. A better understanding of the surface properties of bone growth enhancers at the nano particle level can be anticipated, especially towards directed cell-integration by stimulation of cell surface cytokines. Look to most implants to be either 3-D printed or created as a 100 percent-connected porous structure to stimulate biointegration of bone.
Inducing growth of new tissue to repair damaged cells is the holy grail of regenerative medicine. Tissue regeneration requires either cell therapy (the injection of existing stem cells either autogenous or allogenic), use of growth factors applied exogenously or gene therapy applied to mature cells. The earliest trials are occurring with cell therapy, but there is intense interest in growth factors. Gene therapy, also the subject of great interest, will likely remain out of reach over the next five years unless something startling happens.
With regard to the repair and regeneration of damaged tissue, as in reversing early stages of disc degeneration, there has been intense study of mesenchymal stem cells in the last five years. Several human clinical trials have been in the works in the last five years. NuQu, a study of human chondrocyte implantation in degenerative discs, will not proceed to stage II clinical trials due to non-superiority to saline placebo. Mesoblast, a study of allogenic stem cells, has shown promise in pain relief and will proceed to stage II clinical trials.
The promise of a single injection into painful degenerative discs that will result in its regeneration and return to normal hydrated appearance, although produced with some success in lower animals, remains elusive in humans.
As with all new technologies for use in medicine, hope springs eternal but aging remains a certainty.