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.
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Engineered assistive materials for 3D bioprinting: support baths and sacrificial inks
Abstract Three-dimensional (3D) bioprinting is a promising technique for spatially patterning cells and materials into constructs that mimic native tissues and organs. However, a trade-off exists between printability and biological function, where weak materials are typically more suited for 3D cell culture but exhibit poor shape fidelity when printed in air. Recently, a new class of assistive materials has emerged to overcome this limitation and enable fabrication of more complex, biologically relevant geometries, even when using soft materials as bioinks. These materials include support baths, which bioinks are printed into, and sacrificial inks, which are printed themselves and then later removed. Support baths are commonly yield-stress materials that provide physical confinement during the printing process to improve resolution and shape fidelity. Sacrificial inks have primarily been used to create void spaces and pattern perfusable networks, but they can also be combined directly with the bioink to change its mechanical properties for improved printability or increased porosity. Here, we outline the advantages of using such assistive materials in 3D bioprinting, define their material property requirements, and offer case study examples of how these materials are used in practice. Finally, we discuss the remaining challenges and future opportunities in the development of assistive materials that will propel the bioprinting field forward toward creating full-scale, biomimetic tissues and organs.
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- NSF-PAR ID:
- 10388736
- Date Published:
- Journal Name:
- Biofabrication
- Volume:
- 14
- Issue:
- 3
- ISSN:
- 1758-5082
- Page Range / eLocation ID:
- 032001
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Microextrusion‐based 3D bioprinting into support baths has emerged as a promising technique to pattern soft biomaterials into complex, macroscopic structures. It is hypothesized that interactions between inks and support baths, which are often composed of granular microgels, can be modulated to control the microscopic structure within these macroscopic‐printed constructs. Using printed collagen bioinks crosslinked either through physical self‐assembly or bioorthogonal covalent chemistry, it is demonstrated that microscopic porosity is introduced into collagen inks printed into microgel support baths but not bulk gel support baths. The overall porosity is governed by the ratio between the ink's shear viscosity and the microgel support bath's zero‐shear viscosity. By adjusting the flow rate during extrusion, the ink's shear viscosity is modulated, thus controlling the extent of microscopic porosity independent of the ink composition. For covalently crosslinked collagen, printing into support baths comprised of gelatin microgels (15‐50 µm) results in large pores (≈40 µm) that allow human corneal mesenchymal stromal cells (MSCs) to readily spread, while control samples of cast collagen or collagen printed in non‐granular support baths do not allow cell spreading. Taken together, these data demonstrate a new method to impart controlled microscale porosity into 3D printed hydrogels using granular microgel support baths.
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Abstract 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.
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Abstract 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.
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Three-dimensional (3D) printing is becoming increasingly prevalent in tissue engineering, driving the demand for low-modulus, high-performance, biodegradable, and biocompatible polymers. Extrusion-based direct-write (EDW) 3D printing enables printing and customization of low-modulus materials, ranging from cell-free printing to cell-laden bioinks that closely resemble natural tissue. While EDW holds promise, the requirement for soft materials with excellent printability and shape fidelity postprinting remains unmet. The development of new synthetic materials for 3D printing applications has been relatively slow, and only a small polymer library is available for tissue engineering applications. Furthermore, most of these polymers require high temperature (FDM) or additives and solvents (DLP/SLA) to enable printability. In this study, we present low-modulus 3D printable polyester inks that enable low-temperature printing without the need for solvents or additives. To maintain shape fidelity, we incorporate physical and chemical cross-linkers. These 3D printable polyester inks contain pendant amide groups as the physical cross-linker and coumarin pendant groups as the photochemical cross-linker. Molecular dynamics simulations further confirm the presence of physical interactions between different pendants, including hydrogen bonding and hydrophobic interactions. The combination of the two types of cross-linkers enhances the zero-shear viscosity and hence provides good printability and shape fidelity.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1088/1758-5090/ac6bbe
