Composite Hydrogels for the Replacement of the Nucleus Pulposus

The intervertebral disc (IVD), which provides flexibility to the spine and facilitates damping and motion, is composed of two distinct structures: the annulus fibrosus (AF) and the nucleus pulposus (NP). The AF, which is fibrous and elastic, confines the NP, a gel-like material, containing 65 to 90% of water. The NP mediates load bearing in the spine by maintaining a suitable disc height and adequate loading of the AF. The effectiveness of this mechanism depends on the swelling capacity of the NP and the intra-discal pressure, and it becomes severely limited once the NP has degenerated. Up to now, the main strategy for relieving back pain has been vertebral fusion or total disc replacement. However, there is currently a shift in emphasis towards preservation techniques. NP replacement in particular has attracted considerable interest and various types of synthetic NP have been investigated as a means to restore IVD functions. The present study has focused on injectable, UV curing composite hydrogels for NP replacement. The objectives have been to: (a) synthesize methacrylated monomers based on Tween 20 surfactant precursors, and to use these as a crosslinker in combination with linear hydrophilic molecules in order to obtain hydrogels, (b) investigate the UV curing kinetics, swelling and mechanical properties of the hydrogels and their variation with crosslinker and photoinitiator concentration, (c) evaluate their biocompatibility and (d) study the influence of the filler on the performance of composite hydrogels based on these materials, and hence assess their potential as NP implants. The synthesis of new methacrylated monomers based on Tween 20, yielded reproducible conversions between 75 to 85 %. Tween 20 trimethacrylate (T3), a branched molecule, was then used as a crosslinker in hydrogel systems derived from either N-vinyl-2-pyrrolidone (NVP) or 2-hydroxyethyl methacrylate (HEMA). The study of the curing kinetics by photorheology and photo differential scanning calorimetry of both systems showed that the concentration of T3 controled the crosslinking density whereas the amount of initiator and of UV intensity controled the time of curing and the formation of dangling chains and cyclization. The build-up of the network prior to gelation of the two blends was analyzed using existing growth models and particularly complex patterns of growth were identified for T3/NVP. From the study of the curing kinetics, optimum conditions for processing could be determined. The mechanical behavior of T3/NVP hydrogels was strongly dependent on the concentration of T3 and on the water content of the network. Swelling ratios varied from 1.6 to 5.8 with decreasing T3 content, which is comparable with the behaviour of the human NP, which shows swelling ratios from 1.8 to 9. The elastic modulus varied from about 4400 to 3 kPa for dried and fully hydrated samples, respectively, which is close to the modulus of 3 to 6 kPa observed in the native NP at swelling equilibrium. Preliminary biocompatibility studies showed cell viability and the hydrogels exhibited a highly interconnected porous structure at swelling equilibrium. They could also be further reinforced with nano-fibrillated cellulose (NFC), a hydrophilic material, with a 3 to 8-fold increase in elastic modulus being observed with respect to the neat hydrogel depending on the NFC content, i.e. greater stiffness than the native NP, as required. However, the swelling ratio was decreased compared to that of the neat hydrogel. To overcome this without compromising the mechanical properties, the NFC fibres were chemically modified to increase their hydrophilicity. The swelling ratio of these new composite hydrogels was increased by 1 to 20 % depending on the NFC content. The possibility of tailoring both the swelling behaviour and mechanical performance suggests these materials to be ideal for NP replacement.


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