3D bioprinting complex models of cancer.

Cancer is characterized by the uncontrolled division of cells, resulting in the formation of tumors. The tumor microenvironment (TME) consists of a variety of cell types present within a heterogeneous extracellular matrix (ECM). Current 2D culture methods for mimicking this microenvironment remain limited due to spatial constraints. Many different types of 3D cancer models have been developed in recent years using spheroids/organoids, biomaterial scaffolds, and cancer-on-chip systems. However, these models cannot precisely control the organization of multiple cell types inside of complex architectures. Bioprinted cancer models can incorporate both stromal and cancer cells inside of 3D constructs to generate custom models of this complex disease. 3D bioprinting can generate complex, multicellular, and reproducible constructs where the matrix composition and rigidity are tailored locally to the tumor. These capabilities make 3D bioprinting an attractive method for reproducing the tumor TME found in vivo. Recent advancements in biomaterial-based bioinks enable the generation of 3D bioprinted cancer models that accurately mimic the TM. Here we discuss recent examples of such 3D-bioprinted cancer models, including those of the lungs, prostate, skin, brain, and colon. We then highlight the advantages of using 3D bioprinting compared to other in vitro modeling techniques and detail its limitations.

3D-bioprinted cardiac tissues and their potential for disease modeling.

Heart diseases cause over 17.9 million total deaths globally, making them the leading source of mortality. The aim of this review is to describe the characteristic mechanical, chemical and cellular properties of human cardiac tissue and how these properties can be mimicked in 3D bioprinted tissues. Furthermore, the authors review how current healthy cardiac models are being 3D bioprinted using extrusion-, laser- and inkjet-based printers. The review then discusses the pathologies of cardiac diseases and how bioprinting could be used to fabricate models to study these diseases and potentially find new drug targets for such diseases. Finally, the challenges and future directions of cardiac disease modeling using 3D bioprinting techniques are explored.

3D Bioprinting Mesenchymal Stem Cell-Derived Neural Tissues Using a Fibrin-Based Bioink.

Current treatments for neurodegenerative diseases aim to alleviate the symptoms experienced by patients; however, these treatments do not cure the disease nor prevent further degeneration. Improvements in current disease-modeling and drug-development practices could accelerate effective treatments for neurological diseases. To that end, 3D bioprinting has gained significant attention for engineering tissues in a rapid and reproducible fashion. Additionally, using patient-derived stem cells, which can be reprogrammed to neural-like cells, could generate personalized neural tissues. Here, adipose tissue-derived mesenchymal stem cells (MSCs) were bioprinted using a fibrin-based bioink and the microfluidic RX1 bioprinter. These tissues were cultured for 12 days in the presence of SB431542 (SB), LDN-193189 (LDN), purmorphamine (puro), fibroblast growth factor 8 (FGF8), fibroblast growth factor-basic (bFGF), and brain-derived neurotrophic factor (BDNF) to induce differentiation to dopaminergic neurons (DN). The constructs were analyzed for expression of neural markers, dopamine release, and electrophysiological activity. The cells expressed DN-specific and early neuronal markers (tyrosine hydroxylase (TH) and class III beta-tubulin (TUJ1), respectively) after 12 days of differentiation. Additionally, the tissues exhibited immature electrical signaling after treatment with potassium chloride (KCl). Overall, this work shows the potential of bioprinting engineered neural tissues from patient-derived MSCs, which could serve as an important tool for personalized disease models and drug-screening.