A handheld bioprinter for multi-material printing of complex constructs.

In situbioprinting-the process of depositing bioinks at a defected area, has recently emerged as a versatile technology for tissue repair and restorationviasite-specific delivery of pro-healing constructs. The ability to print multiple materialsin situis an exciting approach that allows simultaneous or sequential dispensing of different materials and cells to achieve tissue biomimicry. Herein, we report a modular handheld bioprinter that deposits a variety of bioinksin situwith exquisite control over their physical and chemical properties. Combined stereolithography 3D printing and microfluidic technologies allowed us to develop a novel low-priced handheld bioprinter. The ergonomic design of the handheld bioprinter facilitate the shape-controlled biofabrication of multi-component fibers with different cross-sectional shapes and material compositions. Furthermore, the capabilities of the produced fibers in the local delivery of therapeutic agents was demonstrated by incorporating drug-loaded microcarriers, extending the application of the printed fibers to on-demand, temporal, and dosage-control drug delivery platforms. Also, the versatility of this platform to produce biosensors and wearable electronics was demonstrated via incorporating conductive materials and integrating pH-responsive dyes. The handheld printer's efficacy in generating cell-laden fibers with high cell viability for site-specific cell delivery was shown by producing single-component and multi-component cell-laden fibers. In particular, the multi-component fibers were able to model the invasion of cancer cells into the adjacent tissue.

Tissue-engineered heart chambers as a platform technology for drug discovery and disease modeling.

Current drug screening approaches are incapable of fully detecting and characterizing drug effectiveness and toxicity of human cardiomyocytes. The pharmaceutical industry uses mathematical models, cell lines, and in vivo models. Many promising drugs are abandoned early in development, and some cardiotoxic drugs reach humans leading to drug recalls. Therefore, there is an unmet need to have more reliable and predictive tools for drug discovery and screening applications. Biofabrication of functional cardiac tissues holds great promise for developing a faithful 3D in vitro disease model, optimizing drug screening efficiencies enabling precision medicine. Different fabrication techniques including molding, pull spinning and 3D bioprinting were used to develop tissue-engineered heart chambers. The big challenge is to effectively organize cells into tissue with structural and physiological features resembling native tissues. Some advancements have been made in engineering miniaturized heart chambers that resemble a living pump for drug screening and disease modeling applications. Here, we review the currently developed tissue-engineered heart chambers and discuss challenges and prospects.

Latest Advances in 3D Bioprinting of Cardiac Tissues.

Cardiovascular diseases (CVDs) are known as the major cause of death worldwide. In spite of tremendous advancements in medical therapy, the gold standard for CVD treatment is still transplantation. Tissue engineering, on the other hand, has emerged as a pioneering field of study with promising results in tissue regeneration using cells, biological cues, and scaffolds. Three-dimensional (3D) bioprinting is a rapidly growing technique in tissue engineering because of its ability to create complex scaffold structures, encapsulate cells, and perform these tasks with precision. More recently, 3D bioprinting has made its debut in cardiac tissue engineering, and scientists are investigating this technique for development of new strategies for cardiac tissue regeneration. In this review, the fundamentals of cardiac tissue biology, available 3D bioprinting techniques and bioinks, and cells implemented for cardiac regeneration are briefly summarized and presented. Afterwards, the pioneering and state-of-the-art works that have utilized 3D bioprinting for cardiac tissue engineering are thoroughly reviewed. Finally, regulatory pathways and their contemporary limitations and challenges for clinical translation are discussed.