Bioinspired In Vitro Brain Vasculature Model for Nanomedicine Testing Based on Decellularized Spinach Leaves.

Animal testing is often criticized due to ethical issues and complicated translation of the results obtained to the clinical stage of drug development. Existing alternative models for nanopharmaceutical testing still have many limitations and do not significantly decrease the number of animals used. We propose a simple, bioinspired in vitro model for nanopharmaceutical drug testing based on the decellularized spinach leaf's vasculature. This system is similar to human arterioles and capillaries in terms of diameter (300-10 µm) and branching. The model has proven its suitability to access the maneuverability of magnetic nanoparticles, particularly those composed of Fe3O4. Moreover, the thrombosis has been recreated in the model's vasculature. We have tested and compared the effects of both a single-chain urokinase plasminogen activator (scuPA) and a magnetically controlled nanocomposite prepared by heparin-mediated cross-linking of scuPA with Fe3O4 nanoparticles. Compositions were tested both in static and flow conditions.

Bioreactivity of decellularized animal, plant, and fungal scaffolds: perspectives for medical applications.

Numerous biomedical applications imply supportive materials to improve protective, antibacterial, and regenerative abilities upon surgical interventions, oncotherapy, regenerative medicine, and others. With the increasing variability of the possible sources, the materials of natural origin are among the safest and most accessible biomedical tools. Animal, plant, and fungal tissues can further undergo decellularization to improve their biocompatibility. Decellularized scaffolds lack the most reactive cellular material, nuclear and cytoplasmic components, that predominantly trigger immune responses. At the same time, the outstanding initial three-dimensional microarchitecture, biomechanical properties, and general composition of the scaffolds are preserved. These unique features make the scaffolds perfect ready-to-use platforms for various biomedical applications, implying cell growth and functionalization. Decellularized materials can be repopulated with various cells upon request, including epithelial, endothelial, muscle and neuronal cells, and applied for structural and functional biorepair within diverse biological sites, including the skin and musculoskeletal, cardiovascular, and central nervous systems. However, the molecular and cellular mechanisms behind scaffold and host tissue interactions remain not fully understood, which significantly restricts their integration into clinical practice. In this review, we address the essential aspects of decellularization, scaffold preparation techniques, and its biochemical composition and properties, which determine the biocompatibility and immunogenicity of the materials. With the integrated evaluation of the scaffold profile in living systems, decellularized animal, plant, and fungal scaffolds have the potential to become essential instruments for safe and controllable biomedical applications.