Hybrid granular hydrogels: combining composites and microgels for extended ranges of material properties

Developing hydrogels with optimal properties for specific applications is challenging as most of these properties, such as toughness, stiffness, swelling or deformability, are interrelated. The improvement of one property usually comes at the cost of another. In order to decouple the interdependence between these properties and to extend the range of material properties for hydrogels, we propose a strategy that combines composite and microgel approaches. The study focuses first on tailoring the swelling performance of hydrogels while minimally affecting other properties. The underlying principle is to partially substitute some of the hydrogels with pre-swollen microgels composed of the same materials. Swelling reductions up to 45% were obtained. Those granular hydrogels were then reinforced with nano-fibrillated cellulose fibres obtaining hybrid granular materials to improve their toughness and to further reduce their initial swelling. Four different structures of neat, granular and composite hydrogels including 63 different hydrogel compositions based on 20 kDa poly(ethylene glycol)dimethacrylate showed that the swelling ratio could be tailored without significantly affecting elastic modulus and deformation performance. The results explain the role of the PEGDM precursors on the swelling of the microgels as well as the influence of the microgel and fibre contents on the final properties. Moreover, the precursors of hydrogels with similar mechanical or swelling performance were injectable with a wide range of complex viscosities from 0.1 Pa s to over 1000 Pa s offering new opportunities for applications in confined as well as in unconfined environments.

Hybrid hydrogels for load-bearing implants

Céline Samira Wyss

Load-bearing tissues such as articular cartilage or meniscus are not infallible. They might fail due to trauma, over-solicitations, or diseases, which could subsequently alter the mobility of the patient. Repairing these damaged tissues in a minimally invasive way is nowadays widely studied. Hydrogels are promising for repairing soft tissues. However, trying to reproduce the highly hierarchical microstructures of load-bearing tissues is extremely complicated. In fact, conceiving hydrogels with optimal properties for specific applications is challenging as most of the hydrogel's properties are interrelated, such as toughness, stiffness, swelling, or deformability. The improvement of one property usually comes at the cost of another. This thesis aims to develop different hydrogel microstructures and evaluate their potential for load-bearing implants. In particular, the study focuses on (i) designing tough and fatigue resistant hydrogels, (ii) establishing a methodology to control the stiffness and the swelling of hydrogels independently, and (iii) considering processing ease by tailoring each hydrogel precursor viscosity. An extensive parametric study on hydrogels' structure and composition allowed establishing complete property charts for mechanical, swelling, and rheological properties. Seven different hydrogel structures based on poly(ethylene glycol) dimethacrylate were developed: neat, double network, composite, double network composite, granular, hybrid granular, and silk granular hydrogels. The precursors of neat hydrogels had the lowest viscosity. Microgels of similar composition were added to the precursor to adapt and increase its viscosity for unconfined applications. In parallel, adding nano-fibrillated cellulose fibers was effective for increasing toughness. This method was more efficient than creating a double network with alginate. Moreover, fatigue tests revealed that hydrogel composites successfully survive 10 million loading cycles at 20% applied strain. However, it became softer after the first loading cycles and behaved similarly to the Mullins effect. Subsequently, we assessed how cyclic loading affects fracture behavior, distribution of strain fields, and microstructure. The study demonstrated that cyclic loading on hydrogel composites re-arrange the fiber network without seriously deteriorating the mechanical properties. Additionally, we demonstrated that combining composite and microgel approaches, i.e. hybrid granular hydrogels, effectively tailored hydrogels' swelling and viscosity without significantly affecting stiffness, toughness, and deformability. Finally, the microgels were swollen in silk fibroin solution for forming self-reinforced silk granular hydrogels. Those hydrogels exhibited considerably higher stiffness and lower swelling but also reduced elongation performances. We demonstrated that hydrogels' mechanical and physical properties could be effectively controlled with the microstructures and compositions of well-known biomaterials. Subsequently, a hydrogel composite and a silk granular hydrogel, based this time on gelatin hydrogels, were synthesized, validating the potential of studied structures with other hydrogels and microgels. Finally, the analyzed material systems can be combined through a sequential layering, forming hybrid hydrogels, to obtain local or gradient properties addressing specific biomedical applications, soft robotics, sensing applications, or even food packaging.

EPFL2021

Silk granular hydrogels self-reinforced with regenerated silk fibroin fibers

Pierre-Etienne Bourban, Adrien Julien Demongeot, Peyman Karami, Dominique Pioletti, Céline Samira Wyss

Granular hydrogels with high stability, strength, and toughness are laborious to develop. Post-curing is often employed to bind microgels chemically and enhance mechanical properties. Here a unique strategy was investigated to maintain microgels together with a novel self-reinforced silk granular hydrogel composed of 10 wt% 20 kDa poly(ethylene glycol) dimethacrylate microgels and regenerated silk fibroin fibers. The principle is to use the swelling of microgels to concentrate the surrounding solution and regenerate silk fibroin in situ. Self-reinforcement is subsequently one of the added functions. We showed that silk fibroin in most compositions was homogeneously distributed and had successfully regenerated in situ around microgels, holding them together in a network-like structure. FTIR analysis revealed the presence of amorphous and crystalline silk fibroin, where 50% of the secondary structures could be assigned to strong β-sheets. Swelling ratios, i.e. 10–45 vol%, increased proportionally with the microgel content, suggesting that mainly microgels governed swelling. In contrast, the elastic modulus, i.e. 58–296 kPa, increased almost linearly with silk fibroin content. Moreover, we showed that the precursor could be injected and cast into a given shape. Viscous precursors of various compositions were also placed side by side to create mechanical gradients. Finally, it was demonstrated that silk granular hydrogel could successfully be synthesized with other microgels like gelatin methacryloyl. Silk granular hydrogels represent, therefore, a novel class of self-reinforced hydrogel structures with tunable swelling and elastic properties.

2021

Hybrid hydrogels for load-bearing implants

Céline Samira Wyss

EPFL2021