International Journal of Bioprinting最新文献

In situ bioprinting is one of the most clinically relevant techniques in the emerging bioprinting technology because it could be performed directly on the human body in the operating room and it does not require bioreactors for post-printing tissue maturation. However, commercial in situ bioprinters are still not available on the market. In this study, we demonstrated the benefit of the originally developed first commercial articulated collaborative in situ bioprinter for the treatment of full-thickness wounds in rat and porcine models. We used an articulated and collaborative robotic arm from company KUKA and developed original printhead and correspondence software enabling in situ bioprinting on curve and moving surfaces. The results of in vitro and in vivo experiments show that in situ bioprinting of bioink induces a strong hydrogel adhesion and enables printing on curved surfaces of wet tissues with a high level of fidelity. The in situ bioprinter was convenient to use in the operating room. Additional in vitro experiments (in vitro collagen contraction assay and in vitro 3D angiogenesis assay) and histological analyses demonstrated that in situ bioprinting improves the quality of wound healing in rat and porcine skin wounds. The absence of interference with the normal process of wound healing and even certain improvement in the dynamics of this process strongly suggests that in situ bioprinting could be used as a novel therapeutic modality in wound healing.

299Bioprinting offers a new approach to addressing the organ shortage crisis. Despite recent technological advances, insufficient printing resolution continues to be one of the reasons that impede the development of bioprinting. Normally, machine axes movement cannot be reliably used to predict material placement, and the printing path tends to deviate from the predetermined designed reference trajectory in varying degrees. Therefore, a computer vision-based method was proposed in this study to correct trajectory deviation and improve printing accuracy. The image algorithm calculated the deviation between the printed trajectory and the reference trajectory to generate an error vector. Furthermore, the axes trajectory was modified according to the normal vector approach in the second printing to compensate for the deviation error. The highest correction efficiency that could be achieved was 91%. More significantly, we discovered that the correction results, for the first time, were in a normal distribution instead of a random distribution.

The importance of three-dimensional (3D) models in pharmacological tests and personalized therapies is significant. These models allow us to gain insight into the cell response during drug absorption, distribution, metabolism, and elimination in an organ-like system and are suitable for toxicological testing. In personalized and regenerative medicine, the precise characterization of artificial tissues or drug metabolism processes is more than crucial to gain the safest and the most effective treatment for the patients. Using these 3D cell cultures derived directly from patient, such as spheroids, organoids, and bioprinted structures, allows for testing drugs before administration to the patient. These methods allow us to select the most appropriate drug for the patient. Moreover, they provide chance for better recovery of patients, since time is not wasted during therapy switching. These models could be used in applied and basic research as well, because their response to treatments is quite similar to that of the native tissue. Furthermore, they may replace animal models in the future because these methods are cheaper and can avoid interspecies differences. This review puts a spotlight on this dynamically evolving area and its application in toxicological testing.

Benzyl isothiocyanate (BITC) is an isothiocyanate of plant origin, especially the mustard family, which has good antibacterial properties. However, its applications are challenging due to its poor water solubility and chemical instability. We used food hydrocolloids, including xanthan gum, locust bean gum, konjac glucomannan, and carrageenan as three-dimensional (3D)-printing food ink base and successfully prepared 3D-printed BITC antibacterial hydrogel (BITC-XLKC-Gel). The characterization and fabrication procedure of BITC-XLKC-Gel was studied. The results show that BITC-XLKC-Gel hydrogel has better mechanical properties by low-field nuclear magnetic resonance (LF-NMR), mechanical properties, and rheometer analysis. The strain rate of BITC-XLKC-Gel hydrogel is 76.5%, which is better than that of human skin. Scanning electron microscope (SEM) analysis showed that BITC-XLKC-Gel has uniform pore size and provides a good carrier environment for BITC carriers. In addition, BITC-XLKC-Gel has good 3D-printing performance, and 3D printing can be used for customizing patterns. Finally, inhibition zone analysis showed that the BITC-XLKC-Gel added with 0.6% BITC had strong antibacterial activity against Staphylococcus aureus and the BITC-XLKC-Gel added with 0.4% BITC had strong antibacterial activity against Escherichia coli. Antibacterial wound dressing has always been considered essential in burn wound healing. In experiments that simulated burn infection, BITC-XLKC-Gel showed good antimicrobial activity against methicillin-resistant S. aureus. BITC-XLKC-Gel is a good 3D-printing food ink attributed to strong plasticity, high safety profile, and good antibacterial performance and has great application prospects.

Spinal cord injury (SCI) causes severe neural tissue damage and motor/sensory dysfunction. Since the injured spinal cord tissue has limited self-regeneration ability, several strategies, including cell therapy, drug delivery, and tissue engineering scaffold implantation, have been employed to treat SCI. However, each of these strategies fails to obtain desirable outcomes due to their respective limitations. In comparison, advanced tissue engineering scaffolds with appropriate topographical features, favorable composition, and sustained drug delivery capability can be employed to recruit endogenous neural stem cells (NSCs), induce neuronal differentiation, and facilitate neuron maturation. This can lead to the regeneration of injured spinal cord tissue and the recovery of motor function. In this study, fiber bundle-reinforced spinal cord extracellular matrix hydrogel scaffolds loaded with oxymatrine (OMT) were produced through nearfield direct write electrospinning. The spinal cord extracellular matrix-based hydrogel was then coated with OMT. The physical/chemical properties and in vitro degradation behavior of the composite scaffolds were investigated. The in vitro cell culture results showed that composite scaffolds loaded with OMT promoted the differentiation of NSCs into neurons and inhibited differentiation into astrocytes. The in vivo results showed that the composite scaffolds loaded with OMT recruited NSCs from the host tissue, promoted neuronal differentiation and axon extension at the lesion site, inhibited glial scar formation at/around the lesion site, and improved the recovery of motor function in rats with SCI. To sum up, 3D-printed microfiber-reinforced spinal cord extracellular matrix hydrogel scaffolds loaded with OMT are promising biomaterials for the treatment of SCI.

The major apparatuses used for three-dimensional (3D) bioprinting include extrusion-based, droplet-based, and laser-based bioprinting. Numerous studies have been proposed to fabricate bioactive 3D bone tissues using different bioprinting techniques. In addition to the development of bioinks and assessment of their printability for corresponding bioprinting processes, in vitro and in vivo success of the bioprinted constructs, such as their mechanical properties, cell viability, differentiation capability, immune responses, and osseointegration, have been explored. In this review, several major considerations, challenges, and potential strategies for bone bioprinting have been deliberated, including bioprinting apparatus, biomaterials, structure design of vascularized bone constructs, cell source, differentiation factors, mechanical properties and reinforcement, hypoxic environment, and dynamic culture. In addition, up-to-date progress in bone bioprinting is summarized in detail, which uncovers the immense potential of bioprinting in re-establishing the 3D dynamic microenvironment of the native bone. This review aims to assist the researchers to gain insights into the reconstruction of clinically relevant bone tissues with appropriate mechanical properties and precisely regulated biological behaviors.

Scaffold-based approach is a developed strategy in biomanufacturing, which is based on the use of temporary scaffold that performs as a house of implanted cells for their attachment, proliferation, and differentiation. This strategy strongly depends on both materials and manufacturing processes. However, it is very difficult to meet all the requirements, such as biocompatibility, biodegradability, mechanical strength, and promotion of cell-adhesion, using only single material. At present, no single bioprinting technique can meet the requirements for tissue regeneration of all scales. Thus, multi-material and mixing-material scaffolds have been widely investigated. Challenges in terms of resolution, uniform cell distribution, and tissue formation are still the obstacles in the development of bioprinting technique. Hybrid bioprinting techniques have been developed to print scaffolds with improved properties in both mechanical and biological aspects for broad biomedical engineering applications. In this review, we introduce the basic multi-head bioprinters, semi-hybrid and fully-hybrid biomanufacturing systems, highlighting the modifications, the improved properties and the effect on the complex tissue regeneration applications.

1The necessity to preserve meniscal function prompts the research and development of novel treatment options, like three-dimensional (3D) bioprinting. However, bioinks for meniscal 3D bioprinting have not been extensively explored. Therefore, in this study, a bioink composed of alginate, gelatin, and carboxymethylated cellulose nanocrystal (CCNC) was formulated and evaluated. Firstly, bioinks with varying concentrations of the aforementioned components were subjected to rheological analysis (amplitude sweep test, temperature sweep test, and rotation). The optimal bioink formulation of 4.0% gelatin, 0.75% alginate, and 1.4% CCNC dissolved in 4.6% D-mannitol was further used for printing accuracy analysis, followed by 3D bioprinting with normal human knee articular chondrocytes (NHAC-kn). The encapsulated cells' viability was > 98%, and collagen II expression was stimulated by the bioink. The formulated bioink is printable, stable under cell culture conditions, biocompatible, and able to maintain the native phenotype of chondrocytes. Aside from meniscal tissue bioprinting, it is believed that this bioink could serve as a basis for the development of bioinks for various tissues.

Three-dimensional (3D) extrusion-based bioprinting is the most widely used bioprinting technology to fabricate bionic tissue or organ constructs by combining biomaterial ink and living cells for tissue engineering and regenerative medicine. One critical issue of this technique is the selection of suitable biomaterial ink to simulate extracellular matrix (ECM) that provides mechanical support for cells and regulates their physiological activities. Previous studies have demonstrated that it is an enormous challenge to form and maintain reproducible 3D constructs and eventually achieve the balance among biocompatibility, mechanical properties, and printability. This review highlights the properties of extrusion-based biomaterial inks and recent developments as well as details various biomaterial inks classified by their function. Key approaches related to their modification methods according to the functional requirements are also discussed, along with the selection strategies by varying extrusion paths and methods in extrusion-based bioprinting. This systematical review will assist researchers in identifying the most suitable extrusion-based biomaterial inks based on their requirements, as well as in elaborating current challenges and prospects of extrudable biomaterial inks in the field of bioprinting of in vitro tissue models.

Complex curved structures of tissues have been recognized to influence the behavior and function of cells. Tissue curvatures sensed by cells are approximately on the millimeter scale. However, previous research mainly focused on the effect of micro- and nano-scale spatial curved structures, underestimating the significance of milli-scale curvature. Here, we employed fused deposition modeling (FDM) with two-stage temperature control, superfine cone-shaped needle, stable air pressure, and precise motion platform for the customized production of homogeneous, precise, and curved fibers; the responses of M-22 cells to FDM-printed curved channels with radii of 1.5 to 3 mm were systematically investigated. The cells aligned with these curved channels and exhibited various aspect ratios in the channels with different curvatures. Cell proliferation, migration speed of single cells, and front-end speed of collective cells were tightly regulated by these curved structures. Also, a computational model based on force equilibrium was proposed to explore the essential factors and mechanisms of curvature affecting cell behavior. Our simulation results demonstrated that the curvature and width of channels, along with the relative size of cells, can significantly impact the cell-boundary interaction force and the number of valid pseudopodia generated by cells in the process of cell migration. These results provide a comprehensive understanding of the effect of milli-scale curvature on the cells and underpin the design of scaffolds that can be produced easily with sophisticated micro- and nano-scale curved features to regulate cell behavior in tissue engineering.