Given the importance of the extracellular medium during tissue formation, it was wise to develop an artificial structure that mimics the extracellular matrix while having improved physico-chemical properties. That is why the choice was focused on gelatin methacryloyl (GelMA), an inexpensive biocompatible hydrogel. Physicochemical and mechanical properties were improved by the incorporation of nanoparticles developed from two innovative fabrication processes: High shear fluid and low frequencies/high frequencies ultrasounds. Both rapeseed nanoliposomes and nanodroplets were successfully incorporated in the GelMA networks during the photo polymerization process. The impact on polymer microstructure was investigated by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and enzymatic degradation investigations. Mechanical stability and viscoelastic tests were conducted to demonstrate the beneficial effect of the functionalization on GelMA hydrogels. Adding nanoparticles to GelMA improved the surface properties (porosity), tuned swelling, and degradability properties. In addition, we observed that nanoemulsion didn’t change significantly the mechanical properties to shear and compression solicitations, whereas nanoliposome addition decreased Young’s modulus under compression solicitations. Thus, these ways of functionalization allow controlling the design of the material by choosing the type of nanoparticle (nanoliposome or nanoemulsion) in function of the application.

The development of nanocomposite hydrogels that take advantage of hierarchic building blocks is gaining increased attention due to their added functionality and numerous biomedical applications. Gathering on the unique properties of these platforms, herein we report the synthesis of bioactive nanocomposite hydrogels comprising naringin-loaded salmon-derived lecithin nanosized liposomal building blocks and gelatin methacryloyl (GelMA) macro-sized hydrogels for their embedding. This platform takes advantage of liposomes’ significant drug loading capacity and their role in hydrogel network reinforcement, as well as of the injectability and light-mediated crosslinking of bioderived gelatin-based biomaterials. First, the physicochemical properties, as well as the encapsulation efficiency, release profile, and cytotoxicity of naringin-loaded nanoliposomes (LipoN) were characterized. Then, the effect of embedding LipoN in the GelMA matrix were characterized by studying the release behavior, swelling ratio, and hydrophilic character, as well as the rheological and mechanical properties of GelMA and GelMA-LipoN functionalized hydrogels. Finally, the dispersion of nanoliposomes encapsulating a model fluorescent probe in the GelMA matrix was visualized. The formulation of naringin-loaded liposomes via an optimized procedure yielded nanosized (114 nm) negatively charged particles with a high encapsulation efficiency (~99%). Naringin-loaded nanoliposomes administration to human adipose-derived stem cells confirmed their suitable cytocompatibility. Moreover, in addition to significantly extending the release of naringin from the hydrogel, the nanoliposomes inclusion in the GelMA matrix significantly increased its elastic and compressive moduli and decreased its swelling ratio, while showing an excellent dispersion in the hydrogel network. Overall, salmon-derived nanoliposomes enabled the inclusion and controlled release of pro-osteogenic bioactive molecules, as well as improved the hydrogel matrix properties, which suggests that these soft nanoparticles can play an important role in bioengineering bioactive nanocomposites for bone tissue engineering in the foreseeable future.