Dragging 3D printing technique controls pore sizes of tissue engineered blood vessels to induce spontaneous cellular assembly.

To date, several off-the-shelf products such as artificial blood vessel grafts have been reported and clinically tested for small diameter vessel (SDV) replacement. However, conventional artificial blood vessel grafts lack endothelium and, thus, are not ideal for SDV transplantation as they can cause thrombosis. In addition, a successful artificial blood vessel graft for SDV must have sufficient mechanical properties to withstand various external stresses. Here, we developed a spontaneous cellular assembly SDV (S-SDV) that develops without additional intervention. By improving the dragging 3D printing technique, SDV constructs with free-form, multilayers and controllable pore size can be fabricated at once. Then, The S-SDV filled in the natural polymer bioink containing human umbilical vein endothelial cells (HUVECs) and human aorta smooth muscle cells (HAoSMCs). The endothelium can be induced by migration and self-assembly of endothelial cells through pores of the SDV construct. The antiplatelet adhesion of the formed endothelium on the luminal surface was also confirmed. In addition, this S-SDV had sufficient mechanical properties (burst pressure, suture retention, leakage test) for transplantation. We believe that the S-SDV could address the challenges of conventional SDVs: notably, endothelial formation and mechanical properties. In particular, the S-SDV can be designed simply as a free-form structure with a desired pore size. Since endothelial formation through the pore is easy even in free-form constructs, it is expected to be useful for endothelial formation in vascular structures with branch or curve shapes, and in other tubular tissues such as the esophagus.

Biohybrid 3D Printing of a Tissue-Sensor Platform for Wireless, Real-Time, and Continuous Monitoring of Drug-Induced Cardiotoxicity.

Drug-induced cardiotoxicity is regarded as a major hurdle in the early stages of drug development. Although there are various methods for preclinical cardiotoxicity tests, they cannot completely predict the cardiotoxic potential of a compound due to the lack of physiological relevance. Recently, 3D engineered heart tissue (EHT) has been used to investigate cardiac muscle functions as well as pharmacological effects by exhibiting physiological auxotonic contractions. However, there is still no adequate platform for continuous monitoring to test acute and chronic pharmacological effects in vitro. Here, a biohybrid 3D printing method for fabricating a tissue-sensor platform, composed of a bipillar-grafted strain gauge sensor and EHT, is first introduced. Two pillars are three-dimensionally printed as grafts onto a strain gauge-embedded substrate to promote the EHT contractility and guide the self-assembly of the EHTs along with the strain gauge. In addition, the integration of a wireless multi-channel electronic system allows for continuous monitoring of the EHT contractile force by the tissue-sensor platform and, ultimately, for the observation of the acute and chronic drug effects of cardiotoxicants. In summary, biohybrid 3D printing technology is expected to be a potential fabrication method to provide a next-generation tissue-sensor platform for an effective drug development process.

Modular assembly of bioprinted perfusable blood vessel and tracheal epithelium for studying inflammatory respiratory diseases.

In vitroorgan models allow for the creation of precise preclinical models that mimic organ physiology. During a pandemic of a life-threatening acute respiratory disease, an improved trachea model (TM) is required. We fabricated a modular assembly of the blood vessel and TMs using 3D bioprinting technology. First, decellularized extracellular matrix (dECM) were prepared using the porcine trachea and blood vessels. A trachea module was fabricated based on the tracheal mucosa-derived dECM and microporous membrane. Further, a blood vessel module was manufactured using the prepared vascular-tissue-derived dECM. By assembling each manufactured module, a perfusable vascularized TM simulating the interface between the tracheal epithelium and blood vessels was fabricated. This assembled model was manufactured with efficient performance, and it offered respiratory symptoms, such as inflammatory response and allergen-induced asthma exacerbation. These characteristics indicate the possibility of manufacturing a highly functional organ model that mimics a complex organ environment in the future.