Vascularization Strategies in 3D Cell Culture Models: From Scaffold-Free Models to 3D Bioprinting

Abstract

The discrepancies between the findings in preclinical studies, and in vivo testing and clinical trials have resulted in the gradual decline in drug approval rates over the past decades. Conventional in vitro drug screening platforms employ two-dimensional (2D) cell culture models, which demonstrate inaccurate drug responses by failing to capture the three-dimensional (3D) tissue microenvironment in vivo. Recent advancements in the field of tissue engineering have made possible the creation of 3D cell culture systems that can accurately recapitulate the cell–cell and cell–extracellular matrix interactions, as well as replicate the intricate microarchitectures observed in native tissues. However, the lack of a perfusion system in 3D cell cultures hinders the establishment of the models as potential drug screening platforms. Over the years, multiple techniques have successfully demonstrated vascularization in 3D cell cultures, simulating in vivo-like drug interactions, proposing the use of 3D systems as drug screening platforms to eliminate the deviations between preclinical and in vivo testing. In this review, the basic principles of 3D cell culture systems are briefly introduced, and current research demonstrating the development of vascularization in 3D cell cultures is discussed, with a particular focus on the potential of these models as the future of drug screening platforms.

Global hotspots and emerging trends in 3D bioprinting research

“…“Vasculogenesis” is a new research direction in the field of 3D bioprinting in recent years. Due to the dependency of cells on oxygen and nutrients, vascularization during the 3D bioprinting process is a key focus for constructing engineered tissues and organs ( Anthon and Valente, 2022 ). Moreover, the top 20 author keywords with the strongest citation bursts are shown in Figure 10 .…”

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells

“…The major ones include forced floating, hanging drop, magnetic levitation and stirring spinner flask culture. The forced floating method primarily uses ultra-low attachment plates, which are usually treated with hydrophilic or hydrophobic coatings, or agarose, to prevent cell adhesion to the substrate, promoting spheroid formation [ 90 , 91 ]. Although this method is simple and easy to execute, it cannot control the number of cells per spheroid and is not easy to repeat [ 89 ].…”

Cancer Models on Chip: Paving the Way to Large‐Scale Trial Applications

“…In addition, the ability to integrate perfusable vascular networks and the highthroughput fabrication of tumor models make bioprinting an attractive choice. [110] Using multiple materials in one bioprint can produce multiple patient-specific models. In a study by Yi et al, three different inks were used to print multiple models on a glass substrate.…”