Current Advances in 3D Tissue and Organ Reconstruction

Abstract

Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. Here, we describe the mechanisms used by cells to perceive and respond to biomechanical cues and the main signaling pathways involved. We provide an overall perspective of the most recent 3D technologies. Given the breadth of the subject, we concentrate on the use of hydrogels, bioreactors, 3D printing and bioprinting, nanofiber-based scaffolds, and preparation of a decellularized bio-matrix. In addition, we report the possibility to combine the use of 3D cultures with functionalized nanoparticles to obtain highly predictive in vitro models for use in the nanomedicine field.

Keywords: 3D matrices; 3D printing and bioprinting; biomechanical cues; decellularization; hydrogel; micro-bioreactor; microenvironment remodeling; nanofiber-based scaffolds; nanomedicine; tissue engineering.

Figure 1

The sensors (integrins) and effectors (Rho and Hippo pathways) driving mechano-transduction processes, regulating YAP/TAZ localization and the subsequent cell behavior. Signaling pathways are described in detail in the text. Black arrow: activation, red T bar: inhibition of phosphorylation and molecule activation.

Figure 2

Schematic representation of the protocol used to produce micro-bioreactors and obtain spheroid organoids. 2D cultured cells are detached for the dish and centrifuged. Droplets of medium containing cells are dispensed onto the hydrophobic powder bed. The powder covers the drop, leading to the creation of the liquid marble that allows cell aggregation and organoid formation.

Figure 3

The main fundamental steps needed to construct an artificial organ in vitro. The 3D scaffold shape is modeled using computer-aided design (CAD) software (design). The support is 3D printed after an accurate selection of the most adequate method (manufacturing). Lastly, it is repopulated with the specific cell type/types (regeneration).

Figure 4

The two main ways and essential key aspects to successfully recreate in vitro a fully functional bio-artificial organ.

Figure 5

Nanomedicine approaches are improved through a combined use of NP-based techniques and 3D culture systems.