No abstract

Tissue engineering has emerged as a promising approach to viable small-diameter vascular grafts that may be used to treat cardiovascular diseases. One challenge in constructing such blood vessels is proper localization of endothelial cells and smooth muscle cells, as well as promotion of their cellular functions to generate functional tissues. Thus far, construction of small-diameter vascular substitutes with both endothelial and muscular tissues, which is essential for the grafts to acquire antithrombosis function and sufficient strength to avoid thrombus formation as well as to withstand blood pressure, has not yet been demonstrated. In this study, we engineer small-diameter blood vessel grafts containing both functional endothelial and muscular cell layers, which has been demonstrated in vivo in a living rat model. Our construction of the blood vessel grafts uses vascular-tissue-derived extracellular matrix bioinks and a reservoir-assisted triple-coaxial cell printing technique. The prematured vessel was implanted for three weeks as a graft of rat abdominal aorta in a proof-of-concept study where all implants showed great patency, intact endothelium, remodeled smooth muscle, and integration with host tissues at the end of the study. These outcomes suggest that our approach to tissue-engineered biomimetic blood vessels provides a promising route for the construction of durable small-diameter vascular grafts that may be used in future treatments of cardiovascular diseases.

A new concept, assembling cell‐laden tissue modules, is for the first time proposed for soft tissue engineering. Adipose‐vascular tissue modules composed of a synthetic polymer‐based substructure and customized bioinks using planar 3D cell printing are engineered. Such tissue modules are systematically assembled into a synthetic polymer‐based module holder fabricated with rotational 3D printing, resulting in the development of a flexible and volumetric tissue assembly. Whereas most of the previous studies about the construction of adipose tissue are limited to hypoxia, poor vascularization, rapid resorption, and mismatch in mechanical properties, it is aimed to realize the construction of nonhypoxic, flexible, and volume‐stable tissue assembly in this study. The significance of engineered tissue assembly is proven through various in vitro and in vivo evaluations. In particular, stable volume and remarkable neovascularization/adipogenesis are observed in the implanted assembly over four weeks. Interestingly, the size of newly formed lipid droplets and the remodeled morphology in the assembly are comparable to those in native adipose tissue. As far as it is known, this work is a first report suggesting a cell printing‐based tissue assembly for functional reconstruction of soft tissue.

Retinal pigment epithelium (RPE) is a monolayer of the pigmented cells that lies on the thin extracellular matrix called Bruch’s membrane. This monolayer is the main component of the outer blood–retinal barrier (BRB), which plays a multifunctional role. Due to their crucial roles, the damage of this epithelium causes a wide range of diseases related to retinal degeneration including age-related macular degeneration, retinitis pigmentosa, and Stargardt disease. Unfortunately, there is presently no cure for these diseases. Clinically implantable RPE for humans is under development, and there is no practical examination platform for drug development. Here, we developed porcine Bruch’s membrane-derived bioink (BM-ECM). Compared to conventional laminin, the RPE cells on BM-ECM showed enhanced functionality of RPE. Furthermore, we developed the Bruch’s membrane-mimetic substrate (BMS) via the integration of BM-ECM and 3D printing technology, which revealed structure and extracellular matrix components similar to those of natural Bruch’s membrane. The developed BMS facilitated the appropriate functions of RPE, including barrier and clearance functions, the secretion of anti-angiogenic growth factors, and enzyme formation for phototransduction. Moreover, it could be used as a basement frame for RPE transplantation. We established BMS using 3D printing technology to grow RPE cells with functions that could be used for an in vitro model and RPE transplantation.

The development of artificial tissue/organs with the functional maturity of their native equivalents is one of the long-awaited panaceas for the medical and pharmaceutical industries. Advanced 3D cell-printing technology and various functional bioinks are promising technologies in the field of tissue engineering that have enabled the fabrication of complex 3D living tissue/organs. Various requirements for these tissues, including a complex and large-volume structure, tissue-specific microenvironments, and functional vasculatures, have been addressed to develop engineered tissue/organs with native relevance. Functional tissue/organ constructs have been developed that satisfy such criteria and may facilitate both in vivo replenishment of damaged tissue and the development of reliable in vitro testing platforms for drug development. This review describes key developments in technologies and materials for engineering 3D cell-printed constructs for therapeutic and drug testing applications.