Interaction of graphene and WS2 with neutrophils and mesenchymal stem cells: implications for peripheral nerve regeneration.

Graphene and bidimensional (2D) materials have been widely used in nerve conduits to boost peripheral nerve regeneration. Nevertheless, the experimental and commercial variability in graphene-based materials generates graphene forms with different structures and properties that can trigger entirely diverse biological responses from all the players involved in nerve repair. Herein, we focus on the graphene and tungsten disulfide (WS2) interaction with non-neuronal cell types involved in nerve tissue regeneration. We synthesize highly crystalline graphene and WS2 with scalable techniques such as thermal decomposition and chemical vapor deposition. The materials were able to trigger the activation of a neutrophil human model promoting Neutrophil Extracellular Traps (NETs) production, particularly under basal conditions, although neutrophils were not able to degrade graphene. Of note is that pristine graphene acts as a repellent for the NET adhesion, a beneficial property for nerve conduit long-term applications. Mesenchymal stem cells (MSCs) have been proposed as a promising strategy for nerve regeneration in combination with a conduit. Thus, the interaction of graphene with MSCs was also investigated, and reduced viability was observed only on specific graphene substrates. Overall, the results confirm the possibility of regulating the cell response by varying graphene properties and selecting the most suitable graphene forms.

Multimaterial and multiscale scaffold for engineering enthesis organ.

Tendon and ligament injuries are relevant clinical problems in modern society, and the current medical approaches do not guarantee complete recovery of the physiological functionalities. Moreover, they present a non-negligible failure rate after surgery. Failures often occur at the enthesis, which is the area of tendons and ligaments insertion to bones. This area is highly anisotropic and composed of four distinct zones: tendon or ligament, non-mineralized fibrocartilage, mineralized fibrocartilage, and bone. The organization of these regions provides a gradient in mechanical properties, biochemical composition, cellular phenotype, and extracellular matrix organization. Tissue engineering represents an alternative to traditional medical approaches. This work presents a novel biofabrication approach for engineering the enthesis. Gradient-based scaffolds were fabricated by exploiting the combination of electrospinning and three-dimensional (3D) bioprinting technologies. Studies were conducted to evaluate scaffold biocompatibility by seeding bone marrow-derived mesenchymal stem cells (BM-MSCs). Then, the scaffold's ability to promote cellular adhesion, growth, proliferation, and differentiation in both tenogenic and osteogenic phenotypes was evaluated. Fabricated scaffolds were also morphologically and mechanically characterized, showing optimal properties comparable to literature data. The versatility and potentiality of this novel biofabrication approach were demonstrated by fabricating clinical-size 3D enthesis scaffolds. The mechanical characterization highlighted their behavior during a tensile test was comparable to tendons and ligaments in vivo.