3D Bioprinting of Miniaturized Tissues Embedded in Self‐Assembled Nanoparticle‐Based Fibrillar Platforms

Abstract

The creation of microphysiological systems like tissue and organ-on-chip for in vitro modeling of human physiology and diseases is gathering increasing interest. However, the platforms used to build these systems have limitations concerning implementation, automation, and cost-effectiveness. Moreover, their typical plastic-based housing materials are poor recreations of native tissue extracellular matrix (ECM) and barriers. Here, the controlled selfassembly of plant-derived cellulose nanocrystals (CNC) is combined with the concept of 3D bioprinting in suspension baths for the direct biofabrication of microphysiological systems embedded within an ECM mimetic fibrillar support material. The developed support CNC fluid gel allows exceptionally highresolution bioprinting of 3D constructs with arbitrary geometries and low restrictions of bioink choice. The further induction of CNC self-assembly with biocompatible calcium ions results in a transparent biomimetic nanoscaled fibrillar matrix that allows hosting different compartmentalized cell types and perfusable channels, has tailored permeability for biomacromolecules diffusion and cellular crosstalk, and holds structural stability to support long-term in vitro cell maturation. In summary, this xeno-free nanoscale CNC fibrillar matrix allows the biofabrication of hierarchical living constructs, opening new opportunities not only for developing physiologically relevant 3D in vitro models but also for a wide range of applications in regenerative medicine.

Modulation of bioactive calcium phosphate micro/nanoparticle size and shape during in situ synthesis of photo-crosslinkable gelatin methacryloyl based nanocomposite hydrogels for 3D bioprinting and tissue engineering

“…The in-situ nanoparticle formation may induce more space in the gel structure leading to slightly higher swelling compared to separately mixed one. The self-standing height crosses 2 cm in the case of CNP GelMA which is significantly better height than the 3D bioprinted samples with various multi-component advanced gels reported by other researchers [ 34 – 42 ]. It can be concluded from the Figs.…”

Boosting the Clinical Translation of Organ-on-a-Chip Technology

“…Overall, the synergistic combination of microfluidics and biosensors can revolutionize data collection for pharmaceutical and biotechnological industries by providing real-time data about the efficacy and side-effects of drugs in a rapid and throughput manner, thus optimizing the pipeline of drug discovery and screening. To achieve this, the typical microfabrication techniques used by academic labs are not appropriate; they have been replaced by the industry with more efficient manufacturing processes, such as injection molding or additive manufacturing tools for the rapid and large-scale production of OoC [ 46 , 47 ]. Similarly, chip designs and operating methods have been standardized to decrease manufacturing costs and, importantly, to permit the direct comparison of the obtained results between different laboratories, including clinical pharmacological analysis at hospitals, aiming to decrease the traditional variability reported in OoC assays in academic research.…”

Regulable Supporting Baths for Embedded Printing of Soft Biomaterials with Variable Stiffness

“…As an example, adamantane and β-cyclodextrin were used to modify pure hyaluronic acid (HA), which induced the formation of a supramolecular hydrogel with mechanical strength-enhanced gel networks. , Also, bisphosphonate groups were conjugated to HA due to the complexing capacity, which could rapidly form a hydrogel after adding CaCl 2 . Besides, microcrystalline cellulose was hydrolyzed by sulfuric acid, leading to negatively charged nanoparticles grafted with sulfate groups, whose rheological properties could also be tuned with the addition of Ca 2+ Despite the excellent rheological properties provided by these bulk gel baths, the complex physical and chemical modification steps challenge the bath production and regulation …”

“…Besides, microcrystalline cellulose was hydrolyzed by sulfuric acid, leading to negatively charged nanoparticles grafted with sulfate groups, whose rheological properties could also be tuned with the addition of Ca 2+ Despite the excellent rheological properties provided by these bulk gel baths, the complex physical and chemical modification steps challenge the bath production and regulation …”