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    Highly Elastic Biodegradable Single-Network Hydrogel for Cell Printing
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    Abstract:
    Cell printing is becoming a common technique to fabricate cellularized printed scaffold for biomedical application. There are still significant challenges in soft tissue bioprinting using hydrogels, which requires live cells inside the hydrogels. Moreover, the resilient mechanical properties from hydrogels are also required to mechanically mimic the native soft tissues. Herein, we developed a visible-light cross-linked, single-network, biodegradable hydrogel with high elasticity and flexibility for cell printing, which is different from previous highly elastic hydrogel with double-network and two components. The single-network hydrogel using only one stimulus (visible light) to trigger gelation can greatly simplify the cell printing process. The obtained hydrogels possessed high elasticity, and their mechanical properties can be tuned to match various native soft tissues. The hydrogels had good cell compatibility to support fibroblast growth in vitro. Various human cells were bioprinted with the hydrogels to form cell-gel constructs, in which the cells exhibited high viability after 7 days of culture. Complex patterns were printed by the hydrogels, suggesting the hydrogel feasibility for cell printing. We believe that this highly elastic, single-network hydrogel can be simply printed with different cell types, and it may provide a new material platform and a new way of thinking for hydrogel-based bioprinting research.
    The relatively weak mechanical properties of hydrogels remain a major drawback for their application as load-bearing tissue scaffolds. Previously, we developed cell-laden double-network (DN) hydrogels that were composed of photocrosslinkable gellan gum (GG) and gelatin. Further research into the materials as tissue scaffolds determined that the strength of the DN hydrogels decreased when they were prepared at cell-compatible conditions, and the encapsulated cells in the DN hydrogels did not function as well as they did in gelatin hydrogels. In this work, we developed microgel-reinforced (MR) hydrogels from the same two polymers, which have better mechanical strength and biological properties in comparison to the DN hydrogels. The MR hydrogels were prepared by incorporating stiff GG microgels into soft and ductile gelatin hydrogels. The MR hydrogels prepared at cell-compatible conditions exhibited higher strength than the DN hydrogels and the gelatin hydrogels, the highest strength being 2.8 times that of the gelatin hydrogels. MC3T3-E1 preosteoblasts encapsulated in MR hydrogels exhibited as high metabolic activity as in gelatin hydrogels, which is significantly higher than that in the DN hydrogels. The measurement of alkaline phosphatase (ALP) activity and the amount of mineralization showed that osteogenic behavior of MC3T3-E1 cells was as much facilitated in the MR hydrogels as in the gelatin hydrogels, while it was not as much facilitated in the DN hydrogels. These results suggest that the MR hydrogels could be a better alternative to the DN hydrogels and have great potential as load-bearing tissue scaffolds.
    Gelatin
    Gellan gum
    Citations (52)
    Research on hydrogels has been geared toward biomedical applications from the beginning due to their relatively high biocompatibility. Initially only the hydrophilic nature and the large swelling properties of hydrogels was explored. Continued research on hydrogels has resulted in the development of new types of hydrogels, such as environment-sensitive hydrogels, thermoplastic hydrogels, hydrogel foams, and sol-gel phase-reversible hydrogels. Application of hydrogels ranges from biomedical devices to solute separation. Examples of hydrogel applications in pharmaceutics, biomaterials, and biotechnology are briefly described.
    Biocompatibility
    Pharmaceutics
    Citations (74)
    The relatively weak mechanical properties of hydrogels remain a major drawback for their application as load-bearing tissue scaffolds. Previously, we developed cell-laden double-network (DN) hydrogels that were composed of photocrosslinkable gellan gum (GG) and gelatin. Further research into the materials as tissue scaffolds determined that the strength of the DN hydrogels decreased when they were prepared at cell-compatible conditions, and the encapsulated cells in the DN hydrogels did not function as well as they did in gelatin hydrogels. In this work, we developed microgel-reinforced (MR) hydrogels from the same two polymers, which have better mechanical strength and biological properties in comparison to the DN hydrogels. The MR hydrogels were prepared by incorporating stiff GG microgels into soft and ductile gelatin hydrogels. The MR hydrogels prepared at cell-compatible conditions exhibited higher strength than the DN hydrogels and the gelatin hydrogels, the highest strength being 2.8 times that of the gelatin hydrogels. MC3T3-E1 preosteoblasts encapsulated in MR hydrogels exhibited as high metabolic activity as in gelatin hydrogels, which is significantly higher than that in the DN hydrogels. The measurement of alkaline phosphatase (ALP) activity and the amount of mineralization showed that osteogenic behavior of MC3T3-E1 cells was as much facilitated in the MR hydrogels as in the gelatin hydrogels, while it was not as much facilitated in the DN hydrogels. These results suggest that the MR hydrogels could be a better alternative to the DN hydrogels and have great potential as load-bearing tissue scaffolds.
    Gelatin
    Gellan gum
    Citations (0)
    Research on hydrogels has been geared toward biomedical applications from the beginning due to their relatively high biocompatibility. Initially only the hydrophilic nature and the large swelling properties of hydrogels was explored. Continued research on hydrogels has resulted in the development of new types of hydrogels, such as environment-sensitive hydrogels, thermoplastic hydrogels, hydrogel foams, and sol-gel phase-reversible hydrogels. Application of hydrogels ranges from biomedical devices to solute separation. Examples of hydrogel applications in pharmaceutics, biomaterials, and biotechnology are briefly described.
    Pharmaceutics
    Biocompatibility
    Citations (196)
    Hydrogels are there-dimensional polymer network in which the voids are filled with water.Hydrogels have been widely used in various fields including biomedical engineering.However,they have very limited applicability due to their poor mechanical strength.Therefore,many efforts have been focused on the enhancement of mechanical properties of hydrogels.This review mainly introduces some novel high strength hydrogels,such as slide-ring hydrogels,double network hydrogels,composite hydrogels and others and analyzes the factors affecting mechanical properties of hydrogels.Biocompatible,degradable,injectable,loading growth factor and high strength hydrogels as major research directions.
    Mechanical strength
    Biocompatible material
    Citations (0)