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Abstract Three-dimensional bioprinting is a promising field in regenerating patient-specific tissues and organs due to its inherent capability of releasing biocompatible materials encapsulating living cells in a predefined location. Due to the diverse characteristics of tissues and organs in terms of microstructures and cell types, a multinozzle extrusion-based 3D bioprinting system has gained popularity. The investigations on interactions between various biomaterials and cell-to-material can provide relevant information about the scaffold geometry, cell viability, and proliferation. Natural hydrogels are frequently used in bioprinting materials because of their high-water content and biocompatibility. However, the dominancy of liquid characteristics of only-hydrogel materials makes the printing process challenging. Polycaprolactone (PCL) is the most frequently used synthetic biopolymer. It can provide mechanical integrity to achieve dimensionally accurate fabricated scaffolds, especially for hard tissues such as bone and cartilage scaffolds. In this paper, we explored various multimaterial bioprinting strategies with our recently proposed bio-inks and PCL intending to achieve dimensional accuracy and mechanical aspects. Various strategies were followed to coprint natural and synthetic biopolymers and interactions were analyzed between them. Printability of pure PCL with various molecular weights was optimized with respect to different process parameters such as nozzle temperature, printing pressure, printing speed, porosity, and bed temperature to coprint with natural hydrogels. The relationship between the rheological properties and shape fidelity of natural polymers was investigated with a set of printing strategies during coprinting with PCL. The successful application of this research can help achieve dimensionally accurate scaffolds.more » « less
Granular, microgel‐based materials have garnered interest as promising tissue engineering scaffolds due to their inherent porosity, which can promote cell infiltration. Adapting these materials for 3D bioprinting, while maintaining sufficient void space to enable cell migration, can be challenging, since the rheological properties that determine printability are strongly influenced by microgel packing and void fraction. In this work, a strategy is proposed to decouple printability and void fraction by blending UV‐crosslinkable gelatin methacryloyl (GelMA) microgels with sacrificial gelatin microgels to form composite inks. It is observed that inks with an apparent viscosity greater than ≈100 Pa s (corresponding to microgel concentrations ≥5 wt%) have rheological properties that enable extrusion‐based printing of multilayered structures in air. By altering the ratio of GelMA to sacrificial gelatin microgels, while holding total concentration constant at 6 wt%, a family of GelMA:gelatin microgel inks is created that allows for tuning of void fraction from 0.20 to 0.57. Furthermore, human umbilical vein endothelial cells (HUVEC) seeded onto printed constructs are observed to migrate into granular inks in a void fraction‐dependent manner. Thus, the family of microgel inks holds promise for use in 3D printing and tissue engineering applications that rely upon cell infiltration.
Bioprinting has emerged as an advanced method for fabricating complex 3D tissues. Despite the tremendous potential of 3D bioprinting, there are several drawbacks of current bioinks and printing methodologies that limit the ability to print elastic and highly vascularized tissues. In particular, fabrication of complex biomimetic structure that are entirely based on 3D bioprinting is still challenging primarily due to the lack of suitable bioinks with high printability, biocompatibility, biomimicry, and proper mechanical properties. To address these shortcomings, in this work the use of recombinant human tropoelastin as a highly biocompatible and elastic bioink for 3D printing of complex soft tissues is demonstrated. As proof of the concept, vascularized cardiac constructs are bioprinted and their functions are assessed in vitro and in vivo. The printed constructs demonstrate endothelium barrier function and spontaneous beating of cardiac muscle cells, which are important functions of cardiac tissue in vivo. Furthermore, the printed construct elicits minimal inflammatory responses, and is shown to be efficiently biodegraded in vivo when implanted subcutaneously in rats. Taken together, these results demonstrate the potential of the elastic bioink for printing 3D functional cardiac tissues, which can eventually be used for cardiac tissue replacement.
Three‐dimensional (3D) bioprinting is a promising technology to produce tissue‐like structures, but a lack of diversity in bioinks is a major limitation. Ideally each cell type would be printed in its own customizable bioink. To fulfill this need for a universally applicable bioink strategy, a versatile bioorthogonal bioink crosslinking mechanism that is cell compatible and works with a range of polymers is developed. This family of materials is termed UNIversal, Orthogonal Network (UNION) bioinks. As demonstration of UNION bioink versatility, gelatin, hyaluronic acid (HA), recombinant elastin‐like protein (ELP), and polyethylene glycol (PEG) are each used as backbone polymers to create inks with storage moduli spanning from 200 to 10 000 Pa. Because UNION bioinks are crosslinked by a common chemistry, multiple materials can be printed together to form a unified, cohesive structure. This approach is compatible with any support bath that enables diffusion of UNION crosslinkers. Both matrix‐adherent human corneal mesenchymal stromal cells and non‐matrix‐adherent human induced pluripotent stem cell‐derived neural progenitor spheroids are printed with UNION bioinks. The cells retained high viability and expressed characteristic phenotypic markers after printing. Thus, UNION bioinks are a versatile strategy to expand the toolkit of customizable materials available for 3D bioprinting.
Jang, Jinah (Ed.)Abstract 3D printing, or additive manufacturing, is a process for patterning functional materials based on the digital 3D model. A bioink that contains cells, growth factors, and biomaterials are utilized for assisting cells to develop into tissues and organs. As a promising technique in regenerative medicine, many kinds of bioprinting platforms have been utilized, including extrusion-based bioprinting, inkjet bioprinting, and laser-based bioprinting. Laser-based bioprinting, a kind of bioprinting technology using the laser as the energy source, has advantages over other methods. Compared with inkjet bioprinting and extrusion-based bioprinting, laser-based bioprinting is nozzle-free, which makes it a valid tool that can adapt to the viscosity of the bioink; the cell viability is also improved because of elimination of nozzle, which could cause cell damage when the bioinks flow through a nozzle. Accurate tuning of the laser source and bioink may provide a higher resolution for reconstruction of tissue that may be transplanted used as an in vitro disease model. Here, we introduce the mechanism of this technology and the essential factors in the process of laser-based bioprinting. Then, the most potential applications are listed, including tissue engineering and cancer models. Finally, we present the challenges and opportunities faced by laser-based bioprinting.more » « less