Tailoring swelling to control softening mechanisms during cyclic loading of PEG/cellulose hydrogel composites

One of the novel approaches for discogenic lower back pain treatment is to permanently replace the core of the intervertebral disc, so-called Nucleus Pulposus, through minimally invasive surgery. Recently, we have proposed Poly(Ethylene Glycol) Dimethacrylate (PEGDM) hydrogel reinforced with Nano-Fibrillated Cellulose (NFC) fibers as an appropriate replacement material. In addition to the tuneable properties, that mimic those of the native tissue, the surgeon can directly inject it into the degenerated disc and cure it in situ via UV-light irradiation. However, in view of clinical applications, the reliability of the proposed material has to be tested under long-term fatigue loading. To that end, the present study focused on the characterization of the fatigue behavior of the composite hydrogel and investigated the governing physical phenomena behind it. The results show that composite PEGDM-NFC hydrogel withstands the 10 million compression cycles at physiological condition. However, its modulus decreases by almost 10% in the first cycle and then remains constant, while cyclic loading does not affect the neat PEGDM hydrogel. The observed softening behavior has similar characteristics of the Mullins effect. It is shown that the reduction of modulus is due to the gradual change of NFC network, which is highly stretched in the swollen state. Moreover, the swelling degree of the matrix is correlated to the extent of softening during cyclic loading. Consequently, softening can be minimized by lowering the swelling of the composite hydrogel

Miniature probe for the delivery and monitoring of a photopolymerizable material

Photopolymerization is a common method to cure materials initially in a liquid state, such as dental implants or bone or tissue fillers. Recent advances in the development of biocompatible gel- and cement-systems open up an avenue for in situ photopolymerization. For minimally invasive surgery, such procedures require miniaturized surgical endoscopic probes to activate and control photopolymerization in situ. We present a miniaturized light probe in which a photoactive material can be (1) mixed, pressurized, and injected, (2) photopolymerized/photoactivated, and (3) monitored during the chemical reaction. The device is used to implant and cure poly(ethylene glycol) dimethacrylate-hydrogel-precursor in situ with ultraviolet A (UVA) light (365 nm) while the polymerization reaction is monitored in real time by collecting the fluorescence and Raman signals generated by the 532 nm excitation light source. Hydrogels could be delivered, photopolymerized, and monitored by the probe up to a curing depth of 4 cm. The size of the photopolymerized samples could be correlated to the fluorescent signal collected by the probe, and the reproducibility of the procedure could be demonstrated. The position of the probe tip inside a bovine caudal intervertebral disc could be estimated in vitro based on the collected fluores- cence and Raman signal

Photo-polymerization, swelling and mechanical properties of cellulose fibre reinforced poly(ethylene glycol) hydrogels

The application of hydrogels as load-bearing biomedical components is often limited by their mechanical properties. Often an attempt to improve a hydrogel's stiffness is accompanied by a loss of toughness and swelling properties. In this work, we show that the addition of nanofibrillated cellulose (NFC) provides a mean to tailor both the swelling and the mechanical properties of the hydrogel. Various volume fractions of NFC were added to poly(ethylene glycol) dimethacrylate (PEGDM) precursors with two different molecular weights (6 and 20 kDa). The viscosity measurements of the precursor solutions indicated that the dispersed NFCs form a network-like structure in the hydrogel precursor. Such a structure, as observed in the photo-rheology experiments, serves as a light-scattering source when the solution is illuminated by UV light, which provides a uniform polymerization of the hydrogel in three-dimension and reduces the curing time. Mechanical properties of the neat and composite hydrogels were characterized using monotonic and cyclic compression tests. NFC reinforcement increases the hydrogel's stiffness by a factor 2 and 3.5 for the PEGDM matrixes with molecular weights of 6 and 20 kDa respectively without compromising their toughness. Moreover, the desired stiffness and swelling properties can be simultaneously achieved by adapting the reinforcement concentration and the hydrogel cross-link density. The obtained composite hydrogels offer enhanced and tuneable properties and are proposed for injectable and photo-curable load-bearing implants

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

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..

The Report on 2 Cases of Fragile X Syndrome Comorbid with Attention Deficit/Hyperactivity Disorder

The term “fragile X syndrome” is named after a constriction recognizable on chromosome (at Xq 27.3) cultured at chromosome media without folic acid. The unstable part includes repetition of 3 nucleotides which is intensified at subsequent generation (DNA amplification) and gives rise to a more severe phenotype in the individual. About 20% of males have normal fragile X syndrome. The daughters of these individuals have abnormal chromosomes (carrier) and their grandchildren will be marked. In typical syndrome, the boys will suffer from mental retardation, macrocephalia, large or protruding ears, elongated face, and macroorchidism. In terms of behavioral comorbidity, symptoms are similar to pervasive developmental disorder such as autism and attention deficit/hyperactivity disorder. The impairments in cognitive abilities are manifested as learning difficulties to severe problems. Our patients were 2 boys (6 and 7 years old) referred due to their hyperactivity. In physical examination, attention deficit/hyperactivity disorder as well as fragile X syndrome were confirmed. In chromosome culture test, the constriction at Xq 27.3 was specified