Although there are various pre‐existing technologies for engineering vasculatures, multiscale modeling of the architecture of human vasculature at a capillary scale remains a challenge. In this study, a novel technology is developed for the production of a functional, multiscale microvasculature comprising of endothelialized channels and tissue‐specific capillary networks. Perfusable, endothelialized channels are bioprinted, after which angiogenic sprouts are grown into user‐designed capillary networks. The induction of branched and liver‐lobule‐like capillary networks confirm that the technology can produce various types of tissue‐specific multiscale microvasculatures. Further, the channels and capillaries are deemed to be functional when evaluated in vitro. An ex vivo assay demonstrates that the microvasculature can induce neovessel ingrowth, integrate with host vessels, and facilitate blood flow. Remarkably, blood flows through the implanted capillary network without any change in its morphology. Finally, the technology is applied to produce a vascularized liver tissue; it significantly improves its hepatic function. It is believed that this new technology will create new possibilities in the development of highly vascularized and functional tissues/organs on a clinically relevant scale.

3D printed biomaterials have been extensively investigated and developed in the field of bone regeneration related to clinical issues. However, specific applications of 3D printed biomaterials in different dental areas have seldom been reported. In this study, we aimed to and successfully fabricated 3D poly (lactic-co-glycolic acid)/β-tricalcium phosphate (3D-PLGA/TCP) and 3D β-tricalcium phosphate (3D-TCP) scaffolds using two relatively distinct 3D printing (3DP) technologies. Conjunctively, we compared and investigated mechanical and biological responses on human dental pulp stem cells (hDPSCs). Physicochemical properties of the scaffolds, including pore structure, chemical elements, and compression modulus, were characterized. hDPSCs were cultured on scaffolds for subsequent investigations of biocompatibility and osteoconductivity. Our findings indicate that 3D printed PLGA/TCP and β-tricalcium phosphate (β-TCP) scaffolds possessed a highly interconnected and porous structure. 3D-TCP scaffolds exhibited better compressive strength than 3D-PLGA/TCP scaffolds, while the 3D-PLGA/TCP scaffolds revealed a flexible mechanical performance. The introduction of 3D structure and β-TCP components increased the adhesion and proliferation of hDPSCs and promoted osteogenic differentiation. In conclusion, 3D-PLGA/TCP and 3D-TCP scaffolds, with the incorporation of hDPSCs as a personalized restoration approach, has a prospective potential to repair minor and critical bone defects in oral and maxillofacial surgery, respectively.

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Müller cells are the principal glial cells for the maintenance of structural stability and metabolic homeostasis in the human retina. Although various in vitro experiments using two-dimensional monolayer cell (2D) cultures have been performed, the results provided only limited results because of the lack of 3D structural environment and different cellular morphology. We studied a Müller cell-based 3D biomimetic model for use in experiments on the in vivo-like functions of Müller cells within the sensory retina. Isolated primary Müller cells were bioprinted and a 3D-aligned architecture was induced, which aligned Müller cell structure in retinal tissue. The stereographic and functional characteristics of the biomimetic model were investigated and compared to those of the conventional 2D cultured group. The results showed the potential to generate Müller cell-based biomimetic models with characteristic morphological features such as endfeet, soma, and microvilli. Especially, the 3D Müller cell model under hyperglycemic conditions showed similar responses as observed in the in vivo diabetic model with retinal changes, whereas the conventional 2D cultured group showed different cytokine and growth factor secretions. These results show that our study is a first step toward providing advanced tools to investigate the in vivo function of Müller cells and to develop complete 3D models of the vertebrate retina.

Pre-vascularization has been receiving significant attention for developing implantable engineered 3D tissues. While various pre-vascularization techniques have been developed to improve graft vascularization, the effect of pre-vascularized patterns on in vivo neo-vessel formation has not been studied. In this study, we developed a functional pre-vascularized construct that significantly promotes graft vascularization and conducted in vivo evaluations of the micro-vascular patterns (µVP) in various printed designs. µVP formation, composed of high-density capillaries, was induced by the co-printing of endothelial cells (EC) and adipose-derived stem cells (ADSC). We implanted the printed constructs with various µVP designs into a murine femoral arteriovenous bundle model and evaluated graft vascularization via 3D visualization and immune-histological analysis of the neo-vessels. The µVP-distal group (µVP located away from the host vessel) showed approximately 2-fold improved neo-vascularization compared to the µVP-proximal group (µVP located near the host vessel). Additionally, we confirmed that the µVP-distal group can generate the angiogenic factor gradient spatial environment for graft vascularization via computational simulations. Based on these results, the ADSC mono pattern (AMP), which secretes four times higher angiogenic factors than µVP, was added to the µVP + AMP group design. The µVP + AMP group showed approximately 1.5- and 1.9-fold higher total sprouted neo-vessel volume than the µVP only and AMP only groups, respectively. In immunohistochemical staining analysis, the µVP + AMP group showed 2-fold improved density and diameter of the matured neo-vessels. To summarize, these findings demonstrate graft vascularization accelerated due to design optimization of our pre-vascularized constructs. We believe that the developed pre-vascularization printing technique will facilitate new possibilities for the upscaling of implantable engineered tissues/organs.