MATERIAL MATTERS COLUMN
The herniated disc
I have written about the spine in this column before,1 but while attending the Biospine 2 Conference in September 2007 in Leipzig, Germany,2 it was obvious that therapies for the various conditions of the spine are changing fast, including the role of biomaterials. A reappraisal is therefore appropriate, especially as I read the headline in a British newspaper on my way back from the conference: “Cell transplant can ease slipped disc pain,”3 which was a journalistic representation of one of the industry-based papers at the conference.4
It is not necessary to repeat here the reasons for surgical interventions in the spine. They arise from trauma or degeneration and affect the spinal cord itself or the structural components of the spinal column, that is, the vertebra, the intervertebral discs and the ligaments. With regard to injuries to the spinal cord, we have come a long way in understanding the mechanisms of nerve repair and new knowledge suggests developments are leading to effective strategies for spinal cord injury repair. One of the important lessons, for example, is that some neurons in the central nervous system can regenerate their axons, in a directed way and over long distances, just as they can in many situations in the peripheral nerve system. However, they are normally prevented from doing so by the cascade of events that occurs immediately after injury. Even neurons that are unaffected by the direct injury become damaged by the deleterious effects of the immune and cellular response and lose the beneficial effect of neurotrophic and other growth promoting factors. The strategy that many workers are concentrating on involves a combination of immediate neuroprotection to support neuron survival and the provision of the appropriate molecular environment to facilitate regeneration, including the delivery of neurotrophic factors, cell therapy and gene therapy. There is obviously some way to go here, but the signs are positive at this stage.
Professor David Williams DSc, FREng
is Professor of Tissue Engineering at the University of Liverpool and Director of the UK Centre for Tissue Engineering located in the Universities of Liverpool and Manchester. He is Editor-in-Chief of Biomaterials, the leading journal in the biomaterials field. He is Scientific Director of STEPS, the European Commission Framework VI Programme on a Systems Approach to Tissue Engineering Products and Processes. Professor Williams is also a Managing Partner of Morgan & Masterson LLC, a consulting partnership that focusses on global health-care issues.
Turning to the problems of degeneration, these are now within the domain of reasonably effective clinical procedures. The major issue here is the degeneration of the disc. This is a two-component structure with an inner high water content cartilaginous nucleus, the nucleus pulposus, which is surrounded by a tough fibrous ring, the annulus fibrosus. This combined structure allows transmission of forces from one vertebra to the next and also movement between adjacent vertebra. With age, the nucleus pulposus may gradually lose water, leading to increased pressure on the annulus fibrosus and possibly herniation and the prolapsed tissue presses onto adjacent nerve tissue. This, in turn, leads to pain, paresthesia and possibly paralysis of some muscles. Although conservative treatments with rest and analgesic/anti-inflammatory drugs may provide palliation, in many cases the only way to resolve chronic symptoms is to remove the herniated disc material. This can be done successfully by a variety of techniques, including minimally invasive endoscopic surgery. This may relieve the symptoms, but it does not leave the intervertebral joint as a normally functioning unit, and over time the prolapse may recur as the remaining disc degenerates further.
Interbody spinal fusion
There are two approaches to this problem. The first is to remove the disc and encourage bony fusion, which eliminates movement at the vertebral joint, but also eliminates the associated pain. The second is to try to replace the disc itself. Spinal interbody fusion, as it is called, has been performed for a number of years. This may be achieved with autografts, the autologous bone derived from another part of the patient’s body. There is no doubt that bone grafting works, but for a clinically successful outcome it may need some help, especially with respect to restoring a normal intervertebral spacing. That help can come in different forms, including synthetic cages that are placed between the vertebrae and contain the bone graft and supplements to the graft material.
Interbody fusions cages were first made of titanium and have proved successful. Titanium is, however, rigid compared with bone and its radio-opaqueness makes radiographic determination of fusion difficult. For these reasons there have been attempts to use more flexible radiolucent polymers and opinion seems divided on the specific choice. There are those who believe that a polymer as inert or even more inert than titanium is required, with a much lower elastic modulus. The material that appears as a strong candidate in this respect is polyetheretherketone (PEEK).5 I will be discussing the properties of PEEK in a future column and will not describe it in detail here. However, it should be noted that it is a thermoplastic material of high chemical inertness and apparently good general biocompatibility, and it is used in several high performance engineering applications.
Then there are those who believe that a better approach would be to use a biodegradable polymer, which would resorb as new bone grows. This is obviously not a new concept, but one that is attractive in the facilitation of spinal fusion and to avoid the chronic presence of a foreign body within the spinal column. It is not surprising that it is the ubiquitous polyesters such as polylactic acid, polyglycolic acid and their copolymers that have received most attention for this application. However, as discussed by Wuisman and Smit,6 there is some way to go before their properties are optimised, especially with respect to degradation rates and the minimisation of the inflammatory response to degradation.
With regard to supplements to bone grafts, there are two choices. First, we can use autograft extenders to achieve a greater volume of bone for the spinal fusion. This could be done with allograft materials derived from another human via a bone bank. These usually take the form of demineralised bone matrix or mineralised allograft, both of which must be treated carefully to avoid disease transmission. Second, and perhaps of more relevance here are the synthetic extenders: primarily, the calcium phosphates such as hydroxyapatite, tricalcium phosphate and mixtures referred to as biphasic calcium phosphates, which are appearing to be highly effective. There have been significant developments with injectable calcium phosphates. These can be used as alternatives to preprepared granules and are being employed to support the bone within the vertebrae, for example in severe cases of spinal osteoporosis. The alternative to using this type of extender involves the use of biomolecules that enhance the osteogenic performance of the bone graft. This may be achieved with a concentrate of the patient’s own blood, for example as in platelet rich plasma, or through the use of a bone morphogenetic protein. Animal trials have shown these molecules to be effective and clinical trials appear to confirm safety7 with, for example, recombinant human bone morphogenetic proteins rhBMP-2 and rhBMP-7.
Disc replacement and regeneration
In recent years, a series of complete intervertebral joint replacement prostheses has been introduced, although long term success has not yet been demonstrated.8 Of equal interest, but also equal uncertainty because of the lack of long term follow-up available as yet, has been the development of nucleus replacements, for example with hyaluronic acid derivatives and cross-linked albumin, both of which may be injected into the pulposus.
Then there is the newspaper report of tissue engineered disc regeneration. This is a version of the autologous chondrocyte therapy used to treat articular cartilage in knee joints. Here, chondrocytes are derived from the herniated disc following removal of the prolapsed part of the disc. These chondrocytes are purified and multiplied ex vivo and then the expanded colony of chondrocytes is transplanted into the affected nucleus approximately three months later. This technique is the subject of an ongoing clinical trial. This is not the only attempt at tissue engineering or cell therapy approaches to the intervertebral disc; other groups are exploring the use of stem cells and support matrices.
The disc is such an important structure, yet so vulnerable, that all avenues to relieve pain and improve the quality of life must be explored. Let the best technique win.
1. D.F. Williams, “The Back of the Problem,” Medical Device Technology, 15,11 , 9–13 (2004).
2. Biospine 2, 2nd International Congress, Biotechnologies for Spinal Surgery, 20–22 September 2007, Leipzig, Germany, www.biospine.org
3. Daily Telegraph, 22 September 2007.
4. co.don AG, www.co.don.de
5. J.M. Toth et al., “Polyetheretherketone as a Biomaterial For Spinal Applications,” Biomaterials, 27, 3, 324–34 (2006).
6. P.I.J. Wuisman and T.H. Smit, “Bioresorbable Polymers: Heading For a New Generation of Spinal Cages,” European Spine J., 15, 2, 133–48 (2006,).
7. E. Carlisle and J.S. Fischgrund, “Bone Morphogenetic Proteins for Spinal Fusion,” Spine J., 5, 6, p. 2405–95 (2005).
8. B. J. Freeman and J. Davenport, “Total Disc Replacement in the Lumbar Spine: A Systematic Review of the Literature,” European Spine J., 15 (Suppl. 3) S439–47 (2006).
David Williams, Clinical Engineering Department, Royal Liverpool University Hospital, Liverpool L69 3BX, UK, tel. +44 151 706 5606, fax +44 151 706 5803, e-mail: email@example.com.