Microfluidic bioprinting of tough hydrogel-based vascular conduits for functional blood vessels.

Three-dimensional (3D) bioprinting of vascular tissues that are mechanically and functionally comparable to their native counterparts is an unmet challenge. Here, we developed a tough double-network hydrogel (bio)ink for microfluidic (bio)printing of mono- and dual-layered hollow conduits to recreate vein- and artery-like tissues, respectively. The tough hydrogel consisted of energy-dissipative ionically cross-linked alginate and elastic enzyme-cross-linked gelatin. The 3D bioprinted venous and arterial conduits exhibited key functionalities of respective vessels including relevant mechanical properties, perfusability, barrier performance, expressions of specific markers, and susceptibility to severe acute respiratory syndrome coronavirus 2 pseudo-viral infection. Notably, the arterial conduits revealed physiological vasoconstriction and vasodilatation responses. We further explored the feasibility of these conduits for vascular anastomosis. Together, our study presents biofabrication of mechanically and functionally relevant vascular conduits, showcasing their potentials as vascular models for disease studies in vitro and as grafts for vascular surgeries in vivo, possibly serving broad biomedical applications in the future.

Accelerating cardiovascular research: recent advances in translational 2D and 3D heart models.

In vitro modelling the complex (patho-) physiological conditions of the heart is a major challenge in cardiovascular research. In recent years, methods based on three-dimensional (3D) cultivation approaches have steadily evolved to overcome the major limitations of conventional adherent two-dimensional (2D) monolayer cultivation. These 3D approaches aim to study, reproduce or modify fundamental native features of the heart such as tissue organization and cardiovascular microenvironment. Therefore, these systems have great potential for (patient-specific) disease research, for the development of new drug screening platforms, and for the use in regenerative and replacement therapy applications. Consequently, continuous improvement and adaptation is required with respect to fundamental limitations such as cardiomyocyte maturation, scalability, heterogeneity, vascularization, and reproduction of native properties. In this review, 2D monolayer culturing and the 3D in vitro systems of cardiac spheroids, organoids, engineered cardiac microtissue and bioprinting as well as the ex vivo technique of myocardial slicing are introduced with their basic concepts, advantages, and limitations. Furthermore, recent advances of various new approaches aiming to extend as well as to optimize these in vitro and ex vivo systems are presented.

Additive manufacturing in respiratory sciences - Current applications and future prospects.

Additive Manufacturing (AM) comprises a variety of techniques that enable fabrication of customised objects with specific attributes. The versatility of AM procedures and constant technological improvements allow for their application in the development of medicinal products and medical devices. This review provides an overview of AM applications related to respiratory sciences. For this purpose, both fields of research are briefly introduced and the potential benefits of integrating AM to respiratory sciences at different levels of pharmaceutical development are highlighted. Tailored manufacturing of microstructures as a particle design approach in respiratory drug delivery will be discussed. At the dosage form level, we exemplify AM as an important link in the iterative loop of data driven inhaler design, rapid prototyping and in vitro testing. This review also presents the application of bioprinting in the respiratory field for design of biorelevant in vitro cellular models, followed by an overview of AM-related processes in preventive and therapeutic care. Finally, this review discusses future prospects of AM as a component in a digital health environment.

Current Advances in 3D Bioprinting for Cancer Modeling and Personalized Medicine.

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.