3D bioprinting is an emerging technology to fabricate tissues and organs by precisely positioning cells into 3D structures using printable cell‐laden formulations known as bioinks. Various bioinks are utilized in 3D bioprinting applications; however, developing the perfect bioink to fabricate constructs with biomimetic microenvironment and mechanical properties that are similar to native tissues is a challenging task. In recent years, decellularized extracellular matrix (dECM)‐based bioinks have received an increasing attention in 3D bioprinting applications, since they are derived from native tissues and possess unique, complex tissue‐specific biochemical properties. This review focuses on designing dECM‐based bioinks for tissue and organ bioprinting, including commonly used decellularization and decellularized tissue characterization methods, bioink formulation and characterization, applications of dECM‐based bioinks, and most recent advancements in dECM‐based bioink design.
- Award ID(s):
- 1651385
- NSF-PAR ID:
- 10317312
- Date Published:
- Journal Name:
- Gels
- Volume:
- 7
- Issue:
- 2
- ISSN:
- 2310-2861
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Decellularized extracellular matrix (dECM)‐based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have remained as major limitations for dECM‐based materials. In this study, heart‐derived dECM (h‐dECM) and meniscus‐derived dECM (Ms‐dECM) bioinks in their pristine, unmodified state supplemented with the photoinitiator system of tris(2,2‐bipyridyl) dichlororuthenium(II) hexahydrate and sodium persulfate, demonstrate cytocompatibility with volumetric bioprinting processes. This recently developed bioprinting modality illuminates a dynamically evolving light pattern into a rotating volume of the bioink, and thus decouples the requirement of mechanical strengths of bioprinted hydrogel constructs with printability, allowing for the fabrication of sophisticated shapes and architectures with low‐concentration dECM materials that set within tens of seconds. As exemplary applications, cardiac tissues are volumetrically bioprinted using the cardiomyocyte‐laden h‐dECM bioink showing favorable cell proliferation, expansion, spreading, biomarker expressions, and synchronized contractions; whereas the volumetrically bioprinted Ms‐dECM meniscus structures embedded with human mesenchymal stem cells present appropriate chondrogenic differentiation outcomes. This study supplies expanded bioink libraries for volumetric bioprinting and broadens utilities of dECM toward tissue engineering and regenerative medicine.
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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 Bioprinting is an emerging approach for fabricating cell‐laden 3D scaffolds via robotic deposition of cells and biomaterials into custom shapes and patterns to replicate complex tissue architectures. Bioprinting uses hydrogel solutions called bioinks as both cell carriers and structural components, requiring bioinks to be highly printable while providing a robust and cell‐friendly microenvironment. Unfortunately, conventional hydrogel bioinks have not been able to meet these requirements and are mechanically weak due to their heterogeneously crosslinked networks and lack of energy dissipation mechanisms. Advanced bioink designs using various methods of dissipating mechanical energy are aimed at developing next‐generation cellularized 3D scaffolds to mimic anatomical size, tissue architecture, and tissue‐specific functions. These next‐generation bioinks need to have high print fidelity and should provide a biocompatible microenvironment along with improved mechanical properties. To design these advanced bioink formulations, it is important to understand the structure–property–function relationships of hydrogel networks. By specifically leveraging biophysical and biochemical characteristics of hydrogel networks, high performance bioinks can be designed to control and direct cell functions. In this review article, current and emerging approaches in hydrogel design and bioink reinforcement techniques are critically evaluated. This bottom‐up perspective provides a materials‐centric approach to bioink design for 3D bioprinting.
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Abstract The encapsulation of cells within gel‐phase materials to form bioinks offers distinct advantages for next‐generation 3D bioprinting. 3D bioprinting has emerged as a promising tool for patterning cells, but the technology remains limited in its ability to produce biofunctional, tissue‐like constructs due to a dearth of materials suitable for bioinks. While early demonstrations commonly used viscous polymers optimized for printability, these materials often lacked cell compatibility and biological functionality. In response, advanced materials that exist in the gel phase during the entire printing process are being developed, since hydrogels are uniquely positioned to both protect cells during extrusion and provide biological signals to embedded cells as the construct matures during culture. Here, an overview of the design considerations for gel‐phase materials as bioinks is presented, with a focus on their mechanical, biochemical, and dynamic gel properties. Current challenges and opportunities that arise due to the fact that bioprinted constructs are active, living hydrogels composed of both acellular and cellular components are also evaluated. Engineering hydrogels with consideration of cells as an intrinsic component of the printed bioink will enable control over the evolution of the living construct after printing to achieve greater biofunctionality.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/gels7020070
