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Vascularization is essential for realizing thick and functional tissue constructs that can be utilized for in vitro study platforms and in vivo grafts. The vasculature enables the transport of nutrients, oxygen, and wastes and is also indispensable to organ functional units such as the nephron filtration unit, the blood–air barrier, and the blood–brain barrier. This review aims to discuss the latest progress of organ-like vascularized constructs with specific functionalities and realizations even though they are not yet ready to be used as organ substitutes. First, the human vascular system is briefly introduced and related design considerations for engineering vascularized tissues are discussed. Second, up-to-date creation technologies for vascularized tissues are summarized and classified into the engineering and cellular self-assembly approaches. Third, recent applications ranging from in vitro tissue models, including generic vessel models, tumor models, and different human organ models such as heart, kidneys, liver, lungs, and brain, to prevascularized in vivo grafts for implantation and anastomosis are discussed in detail. The specific design considerations for the aforementioned applications are summarized and future perspectives regarding future clinical applications and commercialization are provided. 

Abstract Three-dimensional (3D) bioprinting has emerged as a powerful engineering approach for various tissue engineering applications, particularly for the development of 3D cellular structures with unique mechanical and/or biological properties. For the jammed gelatin microgel-gelatin solution composite bioink, comprising a discrete phase of microgels (enzymatically gelled gelatin microgels) and a cross-linkable continuous gelatin precursor solution-based phase containing transglutaminase (TG), its rheological properties and printability change gradually due to the TG enzyme-induced cross-linking process. The objective of this study is to establish a direct mapping between the printability of the gelatin microgel-gelatin solution based cross-linkable composite bioink and the TG concentration and cross-linking time, respectively. Due to the inclusion of TG in the composite bioink, the bioink starts cross-linking once prepared and is usually prepared right before a printing process. Herein, the bioink printability is evaluated based on the three metrics: injectability, feature formability, and process-induced cell injury. In this study, the rheological properties such as the storage modulus and viscosity have been first systematically investigated and predicted at different TG concentrations and times during the cross-linking process using the first-order cross-linking kinetics model. The storage modulus and viscosity have been satisfactorily modeled as exponential functions of the TG concentration and time with an experimentally calibrated cross-linking kinetic rate constant. Furthermore, the injectability, feature formability, and process-induced cell injury have been successfully correlated to the TG concentration and cross-linking time via the storage modulus, viscosity, and/or process-induced shear stress. By combing the good injectability, good feature formability, and satisfactory cell viability zones, a good printability zone (1.65, 0.61, and 0.31 h for the composite bioinks with 1.00, 2.00, and 4.00% w/v TG, respectively) has been established during the printing of mouse fibroblast-based 2% gelatin B microgel-3% gelatin B solution composite bioink. This printability zone approach can be extended to the use of other cross-linkable bioinks for bioprinting applications. 

Abstract Three-dimensional (3D) extrusion printing of cellular/acellular structures with biocompatible materials has been widely investigated in recent years. However, the requirement of a suitable solidification rate of printable ink materials constrains the utilization of extrusion-based 3D printing techniques. In this study, the nanoclay yield-stress suspension-enabled extrusion-based 3D printing system has been investigated and demonstrated to overcome solidification rate constraints during printing. Utilizing the liquid–solid transition property of nanoclay suspension, two fabrication approaches, including nanoclay support bath-enabled printing and nanoclay-enabled direct printing, have been proposed. For the former approach, nanoclay (Laponite® EP) has been used as a support bath material to fabricate alginate-based tympanic membrane patches. The constituents of alginate-based ink have been investigated to have the desired mechanical property of alginate-based tympanic membrane patches and facilitate the printing process. For the latter approach, nanoclay (Laponite® XLG) has been used as an internal scaffold material to help print poly (ethylene glycol) diacrylate (PEGDA)-based neural chambers, which can be further cross-linked in air. Mechanical stress analysis has been performed to explore the geometric limitation of printable Laponite® XLG-PEGDA neural chambers. 

Three-dimensional (3D) extrusion printing of cellular/acellular structures with biocompatible materials has been widely investigated in recent years. However, the requirement of suitable solidification rate of printable ink materials constrains the utilization of extrusion-based 3D printing technique. In this study, the yield-stress nanoclay suspension-enabled extrusion-based 3D printing system has been investigated and demonstrated to overcome solidification rate constraints during printing. Utilizing the liquid-solid transition property of nanoclay suspension, two fabrication approaches, including nanoclay support bath-enabled printing and nanoclay-enabled direct printing, have been proposed. For the former approach, nanoclay (Laponite EP) has been used as a support bath material to fabricate alginate-based tympanic membrane patches. The constituents of alginate-based ink have been investigated to have the desired mechanical property of alginate-based tympanic membrane patches and facilitate the printing process. For the latter approach, nanoclay (Laponite XLG) has been used as an internal scaffold material to help print poly (ethylene glycol) diacrylate (PEGDA)-based neural chambers, which can be further cross-linked in air. Mechanical stress analysis has been performed to explore the geometric limitation of printable Laponite XLG-PEGDA neural chambers.