Nanofibrillated cellulose composite hydrogel for the replacement of the nucleus pulposus

The swelling and compressive mechanical behavior as well as the morphology and biocompatibility of composite hydrogels based on Tween® 20 trimethacrylate (T3), N-vinyl-2-pyrrolidone (NVP) and nanofibrillated cellulose (NFC) were assessed in the present study. The chemical structure of T3 was verified by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance, and the degree of substitution was found to be around 3. Swelling ratios of neat hydrogels composed of different concentrations of T3 and NVP were found to range from 1.5 to 5.7 with decreasing concentration of T3. Various concentrations of cellulose nanofibrils (0.2-1.6wt.%) were then used to produce composite hydrogels that showed lower swelling ratios than neat ones for a given T3 concentration. Neat and composite hydrogels exhibited a typical nonlinear response under compression. All composite hydrogels showed an increase in elastic modulus compared to neat hydrogel of about 3- to 8-fold, reaching 18kPa at 0% strain and 62kPa at 20% strain for the hydrogel with the highest NFC content. All hydrogels presented a porous and homogeneous structure, with interconnected pore cells of around 100nm in diameter. The hydrogels are biocompatible. The results of this study demonstrate that composite hydrogels reinforced with NFC may be viable as nucleus pulposus implants due to their adequate swelling ratio, which may restore the annulus fibrosus loading, and their increased mechanical properties, which could possibly restore the height of the intervertebral discs.

Curing Kinetics and Mechanical Properties of a Composite Hydrogel for the Replacement of the Nucleus Pulposus

Ana Borges de Couraça, Pierre-Etienne Bourban, Jan-Anders Månson, Dominique Pioletti

A polymer material system has been developed to propose an injectable, UV and in situ curable hydrogel with properties similar to the native nucleus pulposus of intervertebral disc. Neat hydrogels based on Tween® 20 trimethacrylates (T3) and N-vinyl-2-pyrrolidone (NVP) and composite hydrogels of same composition reinforced by nano-fibrillated cellulose were synthesized with different T3 concentrations and their curing kinetics was investigated by photorheology using UV light. The T3 concentration has an influence on the time of curing and final shear stiffness of the material. NFC does not alter the time of curing but increases the final mechanical performance of the hydrogels for a same chemical composition. Hydrogel samples, neat and composite, were then tested in unconfined compression at different hydration stages and in confined compression and their elastic modulus was determined. The amount of fluid present in the network is mostly responsible for the mechanical properties and NFC fibres proved to be an efficient reinforcement. The elastic modulus ranged from 0.02 to 8 MPa. Biocompatibility studies showed that cells are confluent at 90% and do not show any morphology change when in contact with the hydrogel. The present hydrogel can therefore be considered for NP replacement.

Elsevier2010

Composite Hydrogels for the Replacement of the Nucleus Pulposus

Ana Borges de Couraça

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.

EPFL2010

Biocomposite Hydrogels with Carboxymethylated, Nanofibrillated Cellulose Powder for Replacement of the Nucleus Pulposus

Ana Borges de Couraça, Pierre-Etienne Bourban, Fabien Duc, Jan-Anders Månson

Biocomposite hydrogels with carboxymethylated, nanofibrillated cellulose (c-NFC) powder were prepared by UV polymerization of N-vinyl-2-pyrrolidone with Tween 20 trimethacrylate as a cross-linking agent for replacement of the native, human nucleus pulposus (NP) in intervertebral disks. The swelling ratios and the moduli of elasticity in compression of neat and biocomposite hydrogels were evaluated in dependence of c-NFC concentration (ranging from 0 to 1.6% v/v) and degree of substitution (DS, ranging from 0 to 023). The viscoelastic properties in shear and the material relaxation behavior in compression were measured for neat and biocomposite hydrogels containing 0.4% v/v of fibrils (DS ranging from 0 to 0.23), and their morphologies were characterized by cryo-scanning electron microscopy (cryo-SEM). The obtained results show that the biocomposite hydrogels can successfully mimic the mechanical and swelling behavior of the NP. In addition, the presence of the c-NFC shows lower strain values after cyclic compression tests and consequently creates improved material relaxation properties compared with neat hydrogels. Among the tested samples, the biocomposite hydrogel containing 0.4% v/v of c-NFC with a DS of 0.17 shows the closest behavior to native NP. Further investigation should focus on evaluation and improvement of the long-term relaxation behavior.

2011

Composite Hydrogels for the Replacement of the Nucleus Pulposus

Ana Borges de Couraça

EPFL2010