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

Photopolymerizable hydrogels for implants: Monte-Carlo modeling and experimental in vitro validation.

Photopolymerization is commonly used in a broad range of bioapplications, such as drug delivery, tissue engineering, and surgical implants, where liquid materials are injected and then hardened by means of illumination to create a solid polymer network. However, photopolymerization using a probe, e.g., needle guiding both the liquid and the curing illumination, has not been thoroughly investigated. We present a Monte Carlo model that takes into account the dynamic absorption and scattering parameters as well as solid-liquid boundaries of the photopolymer to yield the shape and volume of minimally invasively injected, photopolymerized hydrogels. In the first part of the article, our model is validated using a set of well-known poly(ethylene glycol) dimethacrylate hydrogels showing an excellent agreement between simulated and experimental volume-growth-rates. In the second part, in situ experimental results and simulations for photopolymerization in tissue cavities are presented. It was found that a cavity with a volume of 152  mm3 can be photopolymerized from the output of a 0.28-mm2 fiber by adding scattering lipid particles while only a volume of 38  mm3 (25%) was achieved without particles. The proposed model provides a simple and robust method to solve complex photopolymerization problems, where the dimension of the light source is much smaller than the volume of the photopolymerizable hydrogel

Mechanical Properties of a Photopolymerizable Hydrogel for Intervertebral Disc Replacement.

We report on the modelling and experimental validation of a photopolymerizable hydrogel for a Nucleus Pulposus replacement

A photopolymerized composite hydrogel and surgical implanting tool for a nucleus pulposus replacement.

Nucleus pulposus replacements have been subjected to highly controversial discussions over the last 40 years. Their use has not yet resulted in a positive outcome to treat herniated disc or degenerated disc disease. The main reason is that not a single implant or tissue replacement was able to withstand the loads within an intervertebral disc. Here, we report on the development of a photo-polymerizable poly(ethylene glycol)dimethacrylate nano-fibrillated cellulose composite hydrogel which was tuned according to native tissue properties. Using a customized minimally-invasive medical device to inject and photopolymerize the hydrogel insitu, samples were implanted through an incision of 1 mm into an intervertebral disc of a bovine organ model to evaluate their long-term performance. When implanted into the bovine disc model, the composite hydrogel implant was able to significantly re-establish disc height after surgery (p < 0.0025). The height was maintained after 0.5 million loading cycles (p < 0.025). The mechanical resistance of the novel composite hydrogel material combined with the minimally invasive implantation procedure into a bovine disc resulted in a promising functional orthopedic implant for the replacement of the nucleus pulposus

Composite Double-Network Hydrogels To Improve Adhesion on Biological Surfaces.

Despite the development of hydrogels with high mechanical properties, insufficient adhesion between these materials and biological surfaces significantly limits their use in the biomedical field. By controlling toughening processes, we designed a composite double-network hydrogel with ∼90% water content, which creates a dissipative interface and robustly adheres to soft tissues such as cartilage and meniscus. A double-network matrix composed of covalently cross-linked poly(ethylene glycol) dimethacrylate and ionically cross-linked alginate was reinforced with nanofibrillated cellulose. No tissue surface modification was needed to obtain high adhesion properties of the developed hydrogel. Instead, mechanistic principles were used to control interfacial crack propagation. Comparing to commercial tissue adhesives, the integration of the dissipative polymeric network on the soft tissue surfaces allowed a significant increase in the adhesion strength, such as ∼130 kPa for articular cartilage. Our findings highlight the significant role of controlling hydrogel structure and dissipation processes for toughening the interface. This research provides a promising path to the development of highly adhesive hydrogels for tissues repair

Multi-Scale Modeling Of Photopolymerization For Medical Hydrogel-Implant Design

We report on the modeling of a photopolymerizable hydrogel and its application as a replacement of the interior of the intervertebral disc (so called Nucleus Pulposus). The hydrogel is initially injected in its liquid form and then photopolymerized via a small catheter. Therefore, also the light necessary for the photopolymerization is constrained to a small light guide to keep the surgical procedure as minimally invasive as possible. Hence, the hydrogel is photopolymerized inside. For applications with restricted physical access and illumination time, such as an Nucleus Pulposus replacement, photopolymerization of volumes with a large volume/illumination-area ratio becomes highly challenging. During polymerization, the material's absorption and scattering coefficients change and directly influence local polymerization rates. By understanding and controlling such polymerization patterns, local material properties can be engineered (e. g. elastic modulus, swelling ratio), to match the set of mechanical requirements for the implant. Thus, it is essential to better understand and model photopolymerization reactions. Experiments were conducted by polymerizing a hydrogel in a column-like volume using an optical fiber for light delivery. Quantitative scattering and absorption values as well as monomer conversion rates of the hydrogel sample were validated using a newly established Monte Carlo model for photopolymerization. The results were used to study and predict 3D polymerization patterns for different illumination configurations. In particular, we show an example of a lumbar intervertebral disc replacement where the jelly core of the intervertebral disc (Nucleus Pulposus) is replaced by an in situ photopolymerized hydrogel. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels