Intervertebral disc (IVD) degeneration is inadequately understood due to the lack of in vitro systems that fully mimic the mechanical and biological complexity of this organ. We have recently made an advancement by developing a bioreactor able to simulate physiological, multiaxial IVD loading and maintain the biological environment in ex vivo IVD models [1].

To validate this new bioreactor system, we simulated natural spine movement by loading 12 bovine IVDs under a combination of static compression (0.1 MPa), cyclic flexion/extension (±3˚, ±6˚ or 0-6˚) and cyclic torsion (±2˚, ±4˚ or 0-4˚) for more than 10’000 (0.2 Hz) or 100’000 (1 Hz) cycles over 14 days. A higher number of cycles increased the release of glycosaminoglycans and nitric oxide, as an inflammation marker, whereas fewer cycles maintained these two factors at physiological levels. All applied protocols upregulated the expression of MMP13 in the outermost annulus fibrosus (AF), indicating a collagen degradation response. This was supported by fissures observed in the AF after a longer loading duration. Increasing loading cycles induced high cell death in the nucleus pulposus and inner AF, while with fewer cycles, high cell viability was maintained in all IVD regions, irrespective of the magnitude of rotation.

Less frequent multiaxial loading maintains IVD homeostasis while more frequent loading initiates an IVD degenerative profile. Specifically, the morphological and molecular changes were localized in the AF, which can be associated with combined flexion/extension and torsion. More loading cycles induced region-specific cell death and a higher release of extracellular matrix molecules from the innermost IVD regions, likely associated with longer exposure to static compression. Altogether, we demonstrated the advantages of the multiaxial bioreactor to study region-specific response in the IVD, which will allow a more profound investigation of IVD degeneration under different combinations of motions.

The fatigue failure of bone cement, leading to loosening of the stem, is likely to be one mode of failure of cemented total hip replacements. There is strong evidence that cracks in the cement are initiated at voids which act as stress risers, particularly at the cement-stem interface. The preferential formation of voids at this site results from shrinkage during polymerisation and the initiation of this process at the warmer cement-bone interface, which causes bone cement to shrink away from the stem. A reversal of the direction of polymerisation would shrink the cement on to the stem and reduce or eliminate the formation of voids at this interface.

We have investigated this by implanting hip prostheses, at room temperature or preheated to 44°C, into human cadaver femora kept at 37°C. Two types of bone cement were either hand-mixed or vacuum-mixed before implantation. We found that the area of porosity at the cement-stem interface was dramatically reduced by preheating the stem and that the preheating temperature of 44°C determined by computer analysis of transient heat transfer was the minimum required to induce initial polymerisation at the cement-stem interface. Temperature measurements taken during these experiments in vitro showed that preheating of the stem caused a negligible increase in the temperature of the bone. Reduction of porosity at the cement-stem interface could significantly increase the life of hip arthroplasties.