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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3D Bioprinting Highly Elastic PEG‐PCL‐DA Hydrogel for Soft Tissue Fabrication and Biomechanical Stimulation
3D bioprinting is a promising technology to fabricate custom geometries for tissue engineering. However, most bioprintable hydrogels are weak and fragile, difficult to handle, and cannot mimic the mechanical behaviors of the native soft elastic tissues. A visible light crosslinked, single‐network, elastic, and biocompatible hydrogel system based on an acrylate triblock copolymer of poly(ethylene glycol) PEG and polycaprolactone (PCL) (PEG‐PCL‐DA) is developed. To enable its application in the bioprinting of soft tissues, the hydrogel system is modified on its printability and biodegradability. Furthermore, it is hypothesized that this elastic material can better transmit pulsatile forces to cells, leading to enhanced cellular response under mechanical stimulation. This central hypothesis is tested using vascular conduits with smooth muscle cells (SMCs) cultured under pulsatile forces in a custom‐made bioreactor. The results show that vascular conduits made of PEG‐PCL‐DA hydrogel faithfully recapitulate the rapid stretch and recoil under the pulsatile pressure from 1 to 3 Hz frequency, which induces a contractile SMC phenotype, consistently upregulating the core contractile transcription factors. In summary, this work demonstrates the potential of elastic hydrogel for 3D bioprinting of soft tissues by fine‐tuning the printability, and biodegradability, while possessing robust elastic properties suitable for manual handling and biomechanical stimulation.
more » « less- NSF-PAR ID:
- 10495274
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Functional Materials
- ISSN:
- 1616-301X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract 3D bioprinting is an emerging additive manufacturing technique to fabricate constructs for human disease modeling. However, current cell‐laden bioinks lack sufficient biocompatibility, printability, and structural stability needed to translate this technology to preclinical and clinical trials. Here, a new class of nanoengineered hydrogel‐based cell‐laden bioinks is introduced, that can be printed into 3D, anatomically accurate, multicellular blood vessels to recapitulate both the physical and chemical microenvironments of native human vasculature. A remarkably unique characteristic of this bioink is that regardless of cell density, it demonstrates a high printability and ability to protect encapsulated cells against high shear forces in the bioprinting process. 3D bioprinted cells maintain a healthy phenotype and remain viable for nearly one‐month post‐fabrication. Leveraging these properties, the nanoengineered bioink is printed into 3D cylindrical blood vessels, consisting of living co‐culture of endothelial cells and vascular smooth muscle cells, providing the opportunity to model vascular function and pathophysiology. Upon cytokine stimulation and blood perfusion, this 3D bioprinted vessel is able to recapitulate thromboinflammatory responses observed only in advanced in vitro preclinical models or in vivo. Therefore, this 3D bioprinted vessel provides a potential tool to understand vascular disease pathophysiology and assess therapeutics, toxins, or other chemicals.
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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 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.more » « less
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Abstract Developing biomimetic cartilaginous tissues that support locomotion while maintaining chondrogenic behavior is a major challenge in the tissue engineering field. Specifically, while locomotive forces demand tissues with strong mechanical properties, chondrogenesis requires a soft microenvironment. To address this challenge, 3D cartilage‐like tissue is fabricated using two biomaterials with different mechanical properties: a hard biomaterial to reflect the macromechanical properties of native cartilage, and a soft biomaterial to create a chondrogenic microenvironment. To this end, a bath composed of an interpenetrating polymer network (IPN) of polyethylene glycol (PEG) and alginate hydrogel (MPa order compressive modulus) is developed as an extracellular matrix (ECM) with self‐healing properties. Within this bath supplemented with thrombin, human mesenchymal stem cell (hMSC) spheroids embedded in fibrinogen are 3D bioprinted, creating a soft microenvironment composed of fibrin (kPa order compressive modulus) that simulate cartilage's pericellular matrix and allow a fast diffusion of nutrients. The bioprinted hMSC spheroids present high viability and chondrogenic‐like behavior without adversely affecting the macromechanical properties of the tissue. Therefore, the ability to locally bioprint a soft and cell stimulating biomaterial inside of a mechanically robust hydrogel is demonstrated, thereby uncoupling the micro‐ and macromechanical properties of the 3D printed tissues such as cartilage.
