Application of stem cells in engineered vascular graft and vascularized organs.

Recent studies report that stem cell therapies have been applied successfully to patients, This has increased anticipations that this regeneration strategy could be a potential method to treat a wide range of intractable diseases some day. Stem cells offer new prospects for the treatment of incurable diseases and for tissue regeneration and repairation because of their unique biological properties. Angiogenesis a key process in tissue regeneration and repairation. Vascularization of organs is one of the main challenges hindering the clinical application of engineered tissues. Efficient production of engineered vascular grafts and vascularized organs is of critical importance for regenerative medicine. In this review, we focus on the types of stem cells that are widely used in tissue engineering and regeneration, as well as their application of these stem cells in the construction of tissue-engineered vascular grafts and vascularization of tissue-engineered organs.

Liver bioprinting within a novel support medium with functionalized spheroids, hepatic vein structures, and enhanced post-transplantation vascularization.

Cell-laden bioprinting is a promising biofabrication strategy for regenerating bioactive transplants to address organ donor shortages. However, there has been little success in reproducing transplantable artificial organs with multiple distinctive cell types and physiologically relevant architecture. In this study, an omnidirectional printing embedded network (OPEN) is presented as a support medium for embedded 3D printing. The medium is state-of-the-art due to its one-step preparation, fast removal, and versatile ink compatibility. To test the feasibility of OPEN, exceptional primary mouse hepatocytes (PMHs) and endothelial cell line-C166, were used to print hepatospheroid-encapsulated-artificial livers (HEALs) with vein structures following predesigned anatomy-based printing paths in OPEN. PMHs self-organized into hepatocyte spheroids within the ink matrix, whereas the entire cross-linked structure remained intact for a minimum of ten days of cultivation. Cultivated HEALs maintained mature hepatic functions and marker gene expression at a higher level than conventional 2D and 3D conditions in vitro. HEALs with C166-laden vein structures promoted endogenous neovascularization in vivo compared with hepatospheroid-only liver prints within two weeks of transplantation. Collectively, the proposed platform enables the manufacture of bioactive tissues or organs resembling anatomical architecture, and has broad implications for liver function replacement in clinical applications.

Advances of 3D Printing in Vascularized Organ Construction.

In the past several decades, three-dimensional (3D) printing has provided some viable tissues and organs for repairing or replacing damaged tissues and organs. However, the construction of sufficient vascular networks in a bioartificial organ has proven to be challenging. To make a fully functional bioartificial organ with a branched vascular network that can substitute its natural counterparts, various studies have been performed to surmount the limitations. Significant progress has been achieved in 3D printing of vascularized liver, heart, bone, and pancreas. It is expected that this technology can be used more widely in other bioartificial organ manufacturing. In this review, we summarize the specific applications of 3D printing vascularized organs through several rapid prototyping technologies. The limitations and future directions are also discussed.

Engineering tissue-specific blood vessels.

Vascular diversity among organs has recently become widely recognized. Several studies using mouse and human fetal tissues revealed distinct characteristics of organ-specific vasculature in molecular and functional levels. Thorough understanding of vascular heterogeneities in human adult tissues is significant for developing novel strategies for targeted drug delivery and tissue regeneration. Recent advancements in microfabrication techniques, biomaterials, and differentiation protocols allowed for incorporation of microvasculature into engineered organs. Such vascularized organ models represent physiologically relevant platforms that may offer innovative tools for dissecting the effects of the organ microenvironment on vascular development and expand our present knowledge on organ-specific human vasculature. In this article, we provide an overview of the current structural and molecular evidence on microvascular diversity, bioengineering methods used to recapitulate the microenvironmental cues, and recent vascularized three-dimensional organ models from the perspective of tissue-specific vasculature.