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 crosslinked poly(ethylene glycol) dimethacrylate and ionically crosslinked alginate was reinforced with nano-fibrillated cellulose. No tissue surface modification was needed to obtain high adhesion properties of the developed hydrogel. Instead, mechanistic principles were used to control interfacial cracks propagation. Comparing to commercial tissue adhesives, the integration of the dissipative polymeric network on the soft tissue surfaces allowed increasing significantly 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.

Intrinsically adhesive hydrogels have various functions in biomedical areas particularly in minimally-invasive surgical treatments. [1,2] In these medical situations, bioadhesives have to present not only strong adhesion to wet tissues but specific ranges of injectability, degradability, swelling, biocompatibility, and mechanical match. [3,4] This is particularly challenging as the adhesive mechanism of the hydrogel should also allow proper material functionality in its bulk. The adhesion of hydrogels could be enhanced by strong bonds with the tissue as well as the material's capacity to dissipate energy. [5,6] Dissipative double-network hydrogels show high adhesion when either the tissue or the hydrogel substrate is chemically treated, so that the interfacial bonds can be created. However, it is difficult to use these adhesive systems in minimally-invasive biomedical situations, in which hydrogel must be injected and formed in situ and tissue treatment would impose serious limitations. In Attaching hydrogels to soft internal tissues is crucial for the development of various biomedical devices. Tough sticky hydrogel patches present high adhesion, yet with lack of injectability and the need for treatment of contacting surface. On the contrary, injectable and photo-curable hydrogels are highly attractive owing to their ease of use, flexibility of filling any shape, and their minimally invasive character, compared to their conventional preformed counterparts. Despite recent advances in material developments, a hydrogel that exhibits both proper injectability and sufficient intrinsic adhesion is yet to be demonstrated. Herein, a paradigm shift is proposed toward the design of intrinsically adhesive networks for injectable and photo-curable hydrogels. The bioinspired design strategy not only provides strong adhesive contact, but also results in a wide window of physicochemical properties. The adhesive networks are based on a family of polymeric backbones where chains are modified to be intrinsically adhesive to host tissue and simultaneously form a hydrogel network via a hybrid cross-linking mechanism. With this strategy, adhesion is achieved through a controlled synergy between the interfacial chemistry and bulk mechanical properties. The functionalities of the bioadhesives are demonstrated for various applications, such as tissue adhesives, surgical sealants, or injectable scaffolds.

The fracture properties of hydrogels which present similar characteristics to the Mullins effect is expected to decrease under repeated cyclic loading. Therefore, we assessed how cyclic loading affects the fracture behavior, the distribution of strain fields and the microstructure of hydrogel composites reinforced with nano-fibrillated cellulose fibers. Surprisingly, we observed that preloading before the creation of a crack in the hydrogel composite increased the fracture strength of pre-notched samples, while the corresponding fracture energy decreased. To understand this behavior, a digital image correlation analysis at the macro-and microscopic scale was performed to obtain local information on the strain field. In addition, the morphology of cellulose fibers was directly observed through fluorescence confocal microscopy before and after cyclic loading at different maximal applied strains. Microscopy results show that cyclic loading rearrange the fiber network and relax local residual stresses in the hydrogel composite. The rearrangement of the fiber network decreases the overall elastic modulus and correspondingly the fracture energy. However, this phenomenon helps the hydrogel composite to accommodate larger strains before the crack starts to propagate, which subsequently improves the fracture strength of pre-notched samples.

A B S T R A C TOne 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.

This work presents a novel strategy that combines microgel and composite approaches in order to enhance some hydrogel's properties such as swelling, elastic modulus and processing ease as well as to decouple their interdependence.