Bioink based 3D bioprinting is a promising new technology that enables fabrication of complex tissue structures with living cells. The printability of the bioink depends on the physical properties such as viscosity. However, the high viscosity bioink puts shear stress on the cells and low viscosity bioink cannot maintain complex tissue structure firmly after the printing. In this work, we applied dual crosslinkable bioink using Kappa-carrageenan (κ-CA) to overcome existing shortcomings. κ-CA has properties such as biocompatibility, biodegradability, shear-thinning and ionic gelation but the difficulty of controlling gelation properties makes it unsuitable for application in 3D bioprinting. This problem was solved by synthesizing methacrylated Kappa-carrageenan (MA-κ-CA), which can be dual crosslinked through ionic and UV (Ultraviolet) crosslinking to form hydrogel using NIH-3T3 cells. Through MA substitutions, the rheological properties of the gel could be controlled to reduce the shear stress. Moreover, bioprinting using the cell-laden MA-κ-CA showed cell compatibility with enhanced shape retention capability. The potential to control the physical properties through dual crosslinking of MA-κ-CA hydrogel is expected to be widely applied in 3D bioprinting applications.
Bioink is the main component of 3D bioprinting process and is crucial for the generation of sophisticated 3D structures through precise spatial control. Therefore, bioink’s core material must have characteristics that support good printability as well as biocompatibility. However, there is a lack of bioinks developed that satisfy these characteristics at the same time. In this work, our aim was to develop a bioink that satisfies the needs for both printability and biocompatibility through effectively utilizing hydrocolloid materials. To do so, carboxymethyl cellulose (CMC) and xanthan gum (XG) were used to maintain proper shear properties at high pressure and increase the mechanical properties of bioink without excessively affecting the viscosity, and thus enhance printability and biocompatibility. Various bioink formulations were applied to 3D printing process and the printability optimization was carried out through adjusting the hydrocolloid contents in connection with different cross-linking methods. Through utilization of hydrocolloids, the printability and rheological analysis showed that the bioink has improved mechanical properties and confirmed that the printability could be adjusted by controlling the CMC and XG ratio. Moreover, cell viability and immunocytochemical staining analyses showed cell compatibility with enhanced stability. The proposed convenient method to control the printability with improved biocompatibility suggests more appropriate use of bioink for co-axial 3D bioprinting.
Biodegradable cellular and acellular scaffolds have great potential to regenerate damaged tissues or organs by creating a proper extracellular matrix (ECM) capable of recruiting endogenous cells to support cellular ingrowth. However, since hydrogel-based scaffolds normally degrade through surface erosion, cell migration and ingrowth into scaffolds might be inhibited early in the implantation. This could result in insufficient de novo tissue formation in the injured area. To address these challenges, continuous and microsized strand-like networks could be incorporated into scaffolds to guide and recruit endogenous cells in rapid manner. Fabrication of such microarchitectures in scaffolds is often a laborious and time-consuming process and could compromise the structural integrity of the scaffold or impact cell viability. Here, we have developed a fast single-step approach to fabricate colloidal hydrogels, which are made up of randomly packed human serum albumin-based photo-cross-linkable microparticles with continuous internal networks of microscale voids. The human serum albumin conjugated with methacrylic groups were assembled to microsized aggregates for achieving unique porous structures inside the colloidal gels. The albumin hydrogels showed tunable mechanical properties such as elastic modulus, porosity, and biodegradability, providing a suitable ECM for various cells such as cardiomyoblasts and endothelial cells. In addition, the encapsulated cells within the hydrogel showed improved cell retention and increased survivability in vitro. Microporous structures of the colloidal gels can serve as a guide for the infiltration of host cells upon implantation, achieving rapid recruitment of hematopoietic cells and, ultimately, enhancing the tissue regeneration capacity of implanted scaffolds.
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