Slipped disc gel: microbial remedy

Replacing nuclear pulp

Viable nucleus pulposus (NP) implant materials for repairing damaged intervertebral discs, comprising novel hydrogels, have been developed and studied using the techniques of Fourier-transform infrared and nuclear magnetic resonance spectroscopy.

Anyone who has suffered damage to an intervertebral disc in their spine or has a degenerative of the discs will know only too well how debilitating can be the attendant inflammation and pain caused by such damage and pressure on the sciatic, and other, nerves. Alleviating the pain to an extent is sometimes possible through spinal manipulation, physiotherapy, anti-inflammatory agents or surgery. However, there is a pressing need to develop artificial implants that can remedy the loss of the gelatinous filling to intervertebral discs as an alternative to simply removing damaged or diseased discs and fusing the vertebrae.

As well as being a problem for sufferers, economically, lower back pain, sciatica and associated problems, are also a major burden on employers and healthcare systems around the world. Now, Joana Silva-Correia, Joaquim Oliveira, Sofia Caridade, Joao Oliveira, Rui Sousa, Joao Mano and Rui Reis of both the 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, at the University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, and also the the ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, Portugal, believe they have taken us a step closer to a solution.

Pulp fact

"The IVD is a specialized cartilaginous structure that provides ?exibility to the spine and allows limited movements while supporting compressive loads arising from body weight and muscle tension," the team explains. Unfortunately, these discs have very little associated blood supply and only a limited number of cells and so the potential for self-repair that is so obvious in other body tissues does not necessarily occur once a disc is damaged or degraded. As mentioned above, there are several approaches to treating disc problems some more invasive than others, but in general, even surgical intervention does not necessarily provide an entirely successful outcome for patients many of whom will require extensive physiotherapy before they even begin to approach relative normal levels of mobility. Moreover, surgical intervention involving removal of a disc and the fusing of adjacent vertebrae can lead to complications and degradation of discs at other points along the length of the spine. It would be much more beneficial to the patient if, instead of simply addressing symptoms or the source of the pain, a degenerative disc might be repaired.

"The regeneration of the damaged IVD using tissue-engineering strategies, i.e. combining cells and scaffolds, appears to be a particularly promising alternative to the current ineffective treatments," the team says. "We now face other challenges, particularly the selection of an optimal scaffold material that enables an efficient regeneration of degenerated IVD," they add.

The researchers point out that IVDs have two distinct compartments, the nucleus pulposus (NP) and the annulus fibrosus (AF). The NP is the "gel-like" substance in the core of the spinal disc. The AF is the fibrous tissue that surrounds the gel. Silva-Correia and colleagues explain that each compartment would require different scaffolds for tissue engineering repairs. To replace the NP, a hydrogel derived from natural sources, such as chitosan, hyaluronic acid, alginate and carboxymethylcellulose, which can be injected, might be useful. However, mechanical properties and degradation remain problematic in their use. As such, Silva-Correia and co-workers have turned to a gellan gum-based hydrogel system that might be injected into the NP space. Gellan gum is an anionic, and so water soluble, heteropolysaccharide made by the bacterium Pseudomonas elodea. It consists of repeating units of "glucose-glucuronic acid-glucose-rhamnose" and undergoes a transition to a gel state in the presence of metal ions.

Gummy bare no longer

Previously, the team demonstrated that gellan gum can support the growth of cells in vitro and in vivo. There is a drawback with the material though in that at body temperature structural integrity can be lost as ionic cross-links fail and the gel dissolves. The team has now developed a workaround that could lead to a much more stable gel for use in IVD repair. By adding a methacrylate group to the gum, and photo-polymerising with ultraviolet light, the team was able to modify the physicochemical properties appropriately. They used Fourier-transform infrared, FTIR, spectroscopy and proton nuclear magnetic resonance, NMR, spectroscopy to follow the reaction. They used scanning electron microscopy to assess the morphology of the gels and tested them in vitro and in vivo to ensure they were not cytotoxic. They also demonstrated that gelation time was merely minutes, a prerequisite for the surgical procedure.

"The proposed gellan gum-based hydrogels may be useful in intervertebral disc regeneration as acellular or cellular substitutes of the nucleus pulposus," the team concludes. They are now focusing on how the materials might be tested for particular applications.

"We are very optimistic and do hope to reach clinical application," Oliveira told SpectroscopyNOW. "Certainly, we hope to help improve the quality of life for millions of people worldwide, in the near future." He adds that, "Biomechanical analysis is ongoing to evaluate the range of motion and the preliminary data is very promising as the proposed gels can mimic human native NP. The next step is to investigate the biological performance of the developed NP substitutes in the lumbar spine of a sheep model."

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.