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

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.

Nanofibrillated cellulose composite hydrogel for the replacement of the nucleus pulposus

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

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.

2011

Nano Fibrillated Cellulose Based Composite Hydrogels for an Injectable Intervertebral Disc Implant

Azadeh Khoushabi

Replacing the gel-like central part of the intervertebral disc (IVD), so-called nucleus pulposus (NP), via a minimally invasive surgery is one of the most recent approaches in the lower back pain treatments. An appropriate biomaterial for NP replacement (NPR) preferably possesses the mechanical and swelling properties similar to those of the native tissue. Furthermore, it should be injectable, biocompatible and stable in the IVD environment. From the surgical point of view, employing a photopolymerizable hydrogel for NPR is beneficial as it can be injected in the liquid form to the IVD and subsequently cured in situ. Such an approach provides a better control for the surgeon over the operation and minimizes the invasion of the surrounding tissue. The application of hydrogels as load-bearing biomedical components is, however, limited by their mechanical properties. Conventional approaches to address such an issue often favors one mechanical property while compromising the others. The present study aims to develop a novel injectable, photopolymerizable hydrogel for NPR with concurrently enhanced mechanical properties and optimal processability. Hydrogels based on photopolymerization of a monomer, i.e. N-vinyl-2-pyrrolidone (NVP), and cross-linking of a preformed functionalized polymer, i.e. poly(ethylene glycol)dimethacrylate (PEGDM), are synthesized. The hydrogels are thoroughly characterized as a function of cross-link density and initial water content in order to examine their applicability for NPR. While a wide range of properties is obtained by variation of the aforementioned parameters, an enhancement of stiffness is associated with brittleness or loss of water content. In addition, homogenous volumetric photopolymerization of such hydrogels is found to be limited especially in case of local illumination. To resolve such issues, a composite material design approach is adopted and the abovementioned polymer networks of hydrogels are combined with nano fibrillated cellulose (NFC). It is demonstrated that the NFC significantly increases the hydrogelsâ stiffness (up to 275%) without compromising the failure strength or reducing the water content. Moreover, the NFC fibers effectively prevent formation of the swelling induced cracks in the NVP based hydrogels. The results of rheology experiments indicate that the dispersed NFC fibers form a network-like structure in the hydrogels precursor solution. Such a structure, as confirmed through the photorheology tests, serves as a light-scattering source when the solution is illuminated by UV light. The latter accelerates the kinetics of photopolymerization and consequently allows reducing the required concentration of photoinitiator. The enhanced and tunable properties of the PEGDM-NFC composite hydrogel, developed in this work, make it a promising implant material for NPR. The applicability and reliability of such a material design approach for NPR is examined using a bovine organ model. In order to meet the properties of the native tissue, the mechanical properties of the composite hydrogel are tuned. The performance of the optimized composite hydrogel versus the native NP tissue is evaluated in several functional tests such as extrusion, confined compression and swelling pressure...

EPFL2016

Nano Fibrillated Cellulose Based Composite Hydrogels for an Injectable Intervertebral Disc Implant

Azadeh Khoushabi

EPFL2016