3D Bioplotter Research Papers

Biofabrication is crucial in contemporary tissue engineering. The primary challenge in biofabrication lies in achieving simultaneous replication of both external organ geometries and internal structures. Particularly for organs with high oxygen demand, the incorporation of a vascular network, which is usually intricate, is crucial to enhance tissue viability, which is still a difficulty in current biofabrication technology. In this study, we address this problem by introducing an innovative three-dimensional (3D) printing strategy using a thermo-reversible supporting bath which can be easily removed by decreasing the temperature. This technology is capable of printing hydrated materials with diverse crosslinked mechanisms, encompassing gelatin,…

In recent years, extrusion-based three-dimensional (3D) bioprinting is employed for engineering cardiac patches (CP) due to its ability to assemble complex structures from hydrogel-based bioinks. However, the cell viability in such CPs is low due to shear forces applied on the cells in the bioink, inducing cellular apoptosis. Herein, we investigated whether the incorporation of extracellular vesicles (EVs) in the bioink, engineered to continually deliver the cell survival factor miR-199a-3p would increase the viability within the CP. EVs from THP-1-derived activated macrophages (MΦ) were isolated and characterized by nanoparticle tracking analysis (NTA), cryogenic electron microscopy (cryo-TEM), and Western blot analysis.…

In vitro models of soft tissues, such as neural, vitreous, or hematopoietic human tissues, require three-dimensional (3D), soft, and functionalized constructs that mimic the complex extracellular microenvironment and support tissue growth and differentiation. While bioprinting has gained significant interest in bioengineering, there is limited research on process control for the biomanufacturing of soft tissues, which is still in its early stages. Material extrusion of suspended hydrogels has shown promise in processing low-viscosity inks, but challenges in developing bioinks that maintain good shape fidelity, repeatability, and long-term stability in culture media have slowly progressed. In this study, we optimize the bioprinting…

Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth…

In recent years, a new additive manufacturing (AM) method for three-dimensional (3D) syringe-extrusion (bio)printing of soft hydrogels has been introduced under the name of Freeform Reversible Embedding of Suspended Hydrogels (FRESH). The most common FRESH bath contains gelatin as the main compound and low concentrations of crosslinker(s) (whose nature depends on the hydrogel) for the initiation of an in-situ pre-crosslinking process during printing. In the case of sodium alginate (SA)-based hydrogels ionically crosslinked via calcium chloride (CaCl2), the crosslinker percentage in the gelatin bath is equal to ~10 mM, usually combined with a post-crosslinking at higher concentrations. However, according to the…

The emergence and innovation of three-dimensional (3D) bioprinting provide new development opportunities for tissue engineering and regenerative medicine. However, how to obtain bioinks with both biomimicry and manufacturability remains a great issue in 3D bioprinting. Developing intelligent responsive biomaterials is conducive to break through the current dilemma. Herein, a stepwise multi-cross-linking strategy concerning thermosensitive thiolated Pluronic F127 (PF127-SH) and hyaluronic acid methacrylate (HAMA) is proposed to achieve temperature-controlled 3D embedded bioprinting, specifically pre-cross-linking (Michael addition reaction) at low temperatures (4–20 °C) and subsequently self-assembly (hydrophobic interaction) in a high-temperature (30–37 °C) suspension bath as well as final photo-cross-linking (mainly thiol-ene…

Background There is a great clinical need and it remains a challenge to develop artificial soft tissue constructs that can mimic the biomechanical properties and bioactivity of natural tissue. This is partly due to the lack of suitable biomaterials. Hydrogels made from human placenta offer high bioactivity and represent a potential solution to create animal-free 3D bioprinting systems that are both sustainable and acceptable, as placenta is widely considered medical waste. A combination with silk and gelatin polymers can bridge the biomechanical limitations of human placenta chorion extracellular matrix hydrogels (hpcECM) while maintaining their excellent bioactivity.   Method In this…

Cardiac tissue engineering has emerged as a promising strategy to treat infarcted cardiac tissues by replacing the injured region with an ex vivo fabricated functional cardiac patch. Nevertheless, integration of the transplanted patch with the host tissue is still a burden, limiting its clinical application. Here, a bi-functional, 3D bio-printed cardiac patch (CP) design is proposed, composed of a cell-laden compartment at its core and an extracellular vesicle (EV)-laden compartment at its shell for better integration of the CP with the host tissue. Alginate-based bioink solutions were developed for each compartment and characterized rheologically, examined for printability and their effect…

Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel-like scaffolds and endothelial cells seeded in their lumen form native-like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites…