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.

In Vitro Characterization of Poly(Lactic Acid)/ Poly(Hydroxybutyrate)/ Thermoplastic Starch Blends for Tissue Engineering Application

“…Bioreactors play a crucial role in this process and also promote tissue maturation. Moreover, this system enables the application of the physical stimuli which is crucial for the TE of the elastic and complex tissues such as blood vessels or the urethra 2 , 31 . The disadvantage of the bioreactor system is its cost extensiveness.…”

“…They provide mechanical support for the proliferating cells and enable them to create newly formed 3D tissue by directing cell growth. For in vivo application, the material used for the scaffolding has to meet several requirements, most importantly biocompatibility and biodegradability 1 – 3 . The importance of biodegradation is underlined with the fact that this process enables tissue remodeling.…”

3D Bioprinting of Vascularized Tissues for in vitro and in vivo Applications

“…With the current advances in the incorporation of vasculature into 3D bioprinted tissue and organs, bioprinting remains one of the most promising methods to construct vascularized tissue for implantation that mimics the native tissue that it will replace or support. However, research still needs to be done before 3D printed vascularized tissue constructs can be widely used in human patients ( Dimitrievska and Niklason, 2018 ; Pennarossa et al, 2021 ). Meanwhile, the use of fabricated vascularized tissue for in vitro applications such as drug screening and high throughput assays in clinical trials is feasible and would most likely be employed in the near future, thereby reducing the costs for drug development while providing important preclinical information that could be used for both toxicity and efficacy of targeted action of the agent.…”

“…Presently, many in vitro developed models have been employed to screen medications and to examine healthy and diseased states in a controlled environment that attempts to mimic the normal physiology of the tissue or organ ( Pennarossa et al, 2021 ). The ability to test agents in both normal and diseased cells can lead to improved screening of agents and discoveries for improved long term outcomes for the patient.…”

A Novel 3D Culture Model of Human ASCs Reduces Cell Death in Spheroid Cores and Maintains Inner Cell Proliferation Compared With a Nonadherent 3D Culture

“…At present, 3D cell culture technologies mainly have two types of methods: scaffold and scaffold-free techniques ( De Pieri et al, 2021 ). Scaffold-based techniques such as hydrogel scaffolds, paper-based culture, fiber scaffolds, and other synthetic biological materials are employed, each of which has its advantages and applications ( Pennarossa et al, 2021 ). Another method is scaffold-free techniques, such as the hanging drop method, magnetic levitation, and the ultra-low attachment (ULA) surface of culture vessels ( Shen and Horbett, 2001 ; Ovsianikov et al, 2018 ).…”