Viscoelastic heating of insulated bovine intervertebral disc.

Back pain is the leading cause of disability globally and the second most common cause of doctors' visits. Despite extensive research efforts, the underlying mechanism of back pain has not been fully elucidated. The intervertebral disc (IVD) is a viscoelastic tissue that provides flexibility to the spinal column and acts as a shock absorber in the spine. When viscoelastic materials like the IVD are cyclically loaded, they dissipate energy as heat. Thus, diurnal, regular movements of the vertebral column that deform the IVD could increase disc temperature through viscoelastic heating. This temperature rise has the potential to influence cell function, drive cell death and induce nociception in innervating nociceptive neurons within the IVD. The present study was conducted to investigate the capacity of IVD to increase in temperature due to viscoelastic heating. Insulated caudal bovine IVD were subjected to physiological cyclic uniaxial compression over a range of frequencies (0.1-15 Hz) and loading durations (1-10 min) ex vivo, and the temperature rise in the tissue was recorded. According to our findings, the IVD can experience a temperature rise of up to 2.5°C under cyclic loading. Furthermore, under similar conditions, the inner nucleus pulposus exhibits more viscoelastic heating than the outer annulus fibrosis, likely due to its more viscous composition. The measured temperature rise of the disc has physiological relevance as degenerative IVD tissue has been shown to produce a sensitization of nociceptive neurons that spontaneously fire at 37°C, with a T50 response at 37.3°C and a maximum response at 38°C. Our results suggest that viscoelastic heating of IVD could interact with sensitized nociceptive neurons in the degenerative IVD to play a role in back pain.

Fabrication of dense anisotropic collagen scaffolds using biaxial compression.

We developed a new method to manufacture dense, aligned, and porous collagen scaffolds using biaxial plastic compression of type I collagen gels. Using a novel compression apparatus that constricts like an iris diaphragm, low density collagen gels were compressed to yield a permanently densified, highly aligned collagen material. Micro-porosity scaffolds were created using hydrophilic elastomer porogens that can be selectively removed following biaxial compression, with porosity modulated by using different porogen concentrations. The resulting scaffolds exhibit collagen densities that are similar to native connective tissues (∼10% collagen by weight), pronounced collagen alignment across multiple length scales, and an interconnected network of pores, making them highly relevant for use in tissue culture, the study of physiologically relevant cell-matrix interactions, and tissue engineering applications. The scaffolds exhibited highly anisotropic material behavior, with the modulus of the scaffolds in the fiber direction over 100 times greater than the modulus in the transverse direction. Adipose-derived mesenchymal stem cells were seeded onto the biaxially compressed scaffolds with minimal cell death over seven days of culture, along with cell proliferation and migration into the pore spaces. This fabrication method provides new capabilities to manufacture structurally and mechanically relevant cytocompatible scaffolds that will enable more physiologically relevant cell culture studies. Further improvement of manufacturing techniques has the potential to produce engineered scaffolds for direct replacement of dense connective tissues such as meniscus and annulus fibrosus. STATEMENT OF SIGNIFICANCE: In vitro studies of cell-matrix interactions and the engineering of replacement materials for collagenous connective tissues require biocompatible scaffolds that replicate the high collagen density (15-25%/wt), aligned fibrillar organization, and anisotropic mechanical properties of native tissues. However, methods for creating scaffolds with these characteristics are currently lacking. We developed a new apparatus and method to create high density, aligned, and porous collagen scaffolds using a biaxial compression with porogens technique. These scaffolds have a highly directional structure and mechanical properties, with the tensile strength and modulus up to 100 times greater in the direction of alignment. We also demonstrated that the scaffolds are a suitable material for cell culture, promoting cell adhesion, viability, and an aligned cell morphology comparable to the cell morphology observed in native aligned tissues.

Biomaterials for intervertebral disc regeneration and repair.

The intervertebral disc contributes to motion, weight bearing, and flexibility of the spine, but is susceptible to damage and morphological changes that contribute to pathology with age and injury. Engineering strategies that rely upon synthetic materials or composite implants that do not interface with the biological components of the disc have not met with widespread use or desirable outcomes in the treatment of intervertebral disc pathology. Here we review bioengineering advances to treat disc disorders, using cell-supplemented materials, or acellular, biologically based materials, that provide opportunity for cell-material interactions and remodeling in the treatment of intervertebral disc disorders. While a field still in early development, bioengineering-based strategies employing novel biomaterials are emerging as promising alternatives for clinical treatment of intervertebral disc disorders.