Three-Dimensional Bioprinting of an In Vitro Lung Model.

In December 2019, COVID-19 emerged in China, and in January 2020, the World Health Organization declared a state of international emergency. Within this context, there is a significant search for new drugs to fight the disease and a need for in vitro models for preclinical drug tests. This study aims to develop a 3D lung model. For the execution, Wharton's jelly mesenchymal stem cells (WJ-MSC) were isolated and characterized through flow cytometry and trilineage differentiation. For pulmonary differentiation, the cells were seeded in plates coated with natural functional biopolymer matrix as membrane until spheroid formation, and then the spheroids were cultured with differentiation inductors. The differentiated cells were characterized using immunocytochemistry and RT-PCR, confirming the presence of alveolar type I and II, ciliated, and goblet cells. Then, 3D bioprinting was performed with a sodium alginate and gelatin bioink in an extrusion-based 3D printer. The 3D structure was analyzed, confirming cell viability with a live/dead assay and the expression of lung markers with immunocytochemistry. The results showed that the differentiation of WJ-MSC into lung cells was successful, as well as the bioprinting of these cells in a 3D structure, a promising alternative for in vitro drug testing.

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.

Effect of Hydrogel Contact Angle on Wall Thickness of Artificial Blood Vessel.

Vascular replacement is one of the most effective tools to solve cardiovascular diseases, but due to the limitations of autologous transplantation, size mismatch, etc., the blood vessels for replacement are often in short supply. The emergence of artificial blood vessels with 3D bioprinting has been expected to solve this problem. Blood vessel prosthesis plays an important role in the field of cardiovascular medical materials. However, a small-diameter blood vessel prosthesis (diameter < 6 mm) is still unable to achieve wide clinical application. In this paper, a response surface analysis was firstly utilized to obtain the relationship between the contact angle and the gelatin/sodium alginate mixed hydrogel solution at different temperatures and mass percentages. Then, the self-developed 3D bioprinter was used to obtain the optimal printing spacing under different conditions through row spacing, printing, and verifying the relationship between the contact angle and the printing thickness. Finally, the relationship between the blood vessel wall thickness and the contact angle was obtained by biofabrication with 3D bioprinting, which can also confirm the controllability of the vascular membrane thickness molding. It lays a foundation for the following study of the small caliber blood vessel printing molding experiment.

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.

Application of 3D bioprinting in the prevention and the therapy for human diseases.

Rapid development of vaccines and therapeutics is necessary to tackle the emergence of new pathogens and infectious diseases. To speed up the drug discovery process, the conventional development pipeline can be retooled by introducing advanced in vitro models as alternatives to conventional infectious disease models and by employing advanced technology for the production of medicine and cell/drug delivery systems. In this regard, layer-by-layer construction with a 3D bioprinting system or other technologies provides a beneficial method for developing highly biomimetic and reliable in vitro models for infectious disease research. In addition, the high flexibility and versatility of 3D bioprinting offer advantages in the effective production of vaccines, therapeutics, and relevant delivery systems. Herein, we discuss the potential of 3D bioprinting technologies for the control of infectious diseases. We also suggest that 3D bioprinting in infectious disease research and drug development could be a significant platform technology for the rapid and automated production of tissue/organ models and medicines in the near future.

3D Bioprinting for fabrication of tissue models of COVID-19 infection.

Over the last few decades, the world has witnessed multiple viral pandemics, the current severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic being the worst and most devastating one, claiming millions of lives worldwide. Physicians, scientists, and engineers worldwide have joined hands in dealing with the current situation at an impressive speed and efficiency. One of the major reasons for the delay in response is our limited understanding of the mechanism of action and individual effects of the virus on different tissues and organs. Advances in 3D bioprinting have opened up a whole new area to explore and utilize the technology in fabricating models of these tissues and organs, recapitulating in vivo environment. These biomimetic models can not only be utilized in learning the infection pathways and drug toxicology studies but also minimize the need for animal models and shorten the time span for human clinical trials. The current review aims to integrate the existing developments in bioprinting techniques, and their implementation to develop tissue models, which has implications for SARS-CoV-2 infection. Future translation of these models has also been discussed with respect to the pandemic.

Level up for culture models - How 3D cell culture models benefit SARS-CoV-2 research.

Welcome to a new decade and a new issue of the Biomedical Journal - casting a sorrowful look onto a year that will go down in history as a tombstone etched by the COVID-19 pandemic, but also a hopeful glance into the future, now that multiple vaccination programs against the SARS-CoV-2 virus have started. This issue is dedicated to the continuous effort by researchers all around the globe to understand and counter the pathogen, as well as to be better prepared for future threats. Therefore, we learn about the advantages of complex 3D cell culture models for studying host-virus interactions, and the disease course of COVID-19 in children. Moreover, we discover how neutralising monoclonal antibodies and peptide-based vaccines against SARS-CoV-2 are developed, and the therapeutic potentials of lopinavir/ritonavir, mesenchymal stem cells, as well as plant and algae extracts. Finally, we ponder over the lessons to be learnt from SARS-CoV and MERS, and hear about differences between nucleotide-based SARS-CoV-2 detection methods.