Gelatin/nanoceria nanocomposite fibers as antioxidant scaffolds for neuronal regeneration.

BACKGROUND: The design of efficient nerve conduits able to sustain the axonal outgrowth and its guidance towards appropriate targets is of paramount importance in nerve tissue engineering. METHODS: In this work, we propose the preparation of highly aligned nanocomposite fibers of gelatin/cerium oxide nanoparticles (nanoceria), prepared by electrospinning. Nanoceria are powerful self-regenerative antioxidant nanomaterials, that behave as strong reactive oxygen species scavengers, and among various beneficial effects, they have been proven to inhibit the cell senescence and to promote the neurite sprouting. RESULTS: After a detailed characterization of the developed substrates, they have been tested on neuron-like SH-SY5Y cells, demonstrating strong antioxidant properties and beneficial multi-cue effects in terms of neurite development and alignment. CONCLUSIONS: Obtained findings suggest efficiency of the proposed substrates in providing combined topographical stimuli and antioxidant effects to cultured cells. GENERAL SIGNIFICANCE: Proposed nanocomposite scaffolds represent a promising approach for nerve tissue engineering and regenerative medicine.

Polydopamine Nanoparticle-Based Combined Chemotherapy and Photothermal Therapy for the Treatment of Liver Cancer.

Polydopamine nanoparticles (PDA NPs) are proposed as an anti-cancer tool against hepatocellular carcinoma through the combination of near-infrared (NIR)-mediated hyperthermia and loading with a chemotherapeutic drug, sorafenib (SRF). Cell membranes isolated from a liver cancer cell line (HepG2) have been exploited for the coating of the nanoparticles (thus obtaining CM-SRF-PDA NPs), to promote homotypic targeting toward cancer cells. The selective targeting ability and the combined photothermal and chemotherapeutic activity of the CM-SRF-PDA NPs following NIR irradiation have been evaluated on cell cultures in static and dynamic conditions, besides three-dimensional culture models. Eventually, the therapeutic effectiveness of the proposed approach has also been tested ex ovo on HepG2 spheroid-grafted quail embryos. This comprehensive investigation, supported by proteomic analysis, showed the effectiveness of the proposed nanoplatform and strongly suggests further pre-clinical testing in the treatment of liver cancer.

Engineering and Development of a Tissue Model for the Evaluation of Microneedle Penetration Ability, Drug Diffusion, Photothermal Activity, and Ultrasound Imaging: A Promising Surrogate to Ex Vivo and In Vivo Tissues.

Driven by regulatory authorities and the ever-growing demands from industry, various artificial tissue models have been developed. Nevertheless, there is no model to date that is capable of mimicking the biomechanical properties of the skin whilst exhibiting the hydrophilicity/hydrophobicity properties of the skin layers. As a proof-of-concept study, tissue surrogates based on gel and silicone are fabricated for the evaluation of microneedle penetration, drug diffusion, photothermal activity, and ultrasound bioimaging. The silicone layer aims to imitate the stratum corneum while the gel layer aims to mimic the water-rich viable epidermis and dermis present in in vivo tissues. The diffusion of drugs across the tissue model is assessed, and the results reveal that the proposed tissue model shows similar behavior to a cancerous kidney. In place of typical in vitro aqueous solutions, this model can also be employed for evaluating the photoactivity of photothermal agents since the tissue model shows a similar heating profile to skin of mice when irradiated with near-infrared laser. In addition, the designed tissue model exhibits promising results for biomedical applications in optical coherence tomography and ultrasound imaging. Such a tissue model paves the way to reduce the use of animals testing in research whilst obviating ethical concerns.