Gels for Bioprinting

A special issue of Gels (ISSN 2310-2861).

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 26510

Special Issue Editor


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Guest Editor
Biomimetic Materials and Tissue Engineering Laboratory, Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA
Interests: bioinspired gels; gels for stem cell delivery; self-assembled micelles for growth factor immobilization; models gels to control cell microenvironment; composite materials with structure at multiple length scales; skeletal tissue engineering
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Special Issue Information

Dear Colleagues,

Bioprinting is an emerging technology for the generation of complex tissue-like structures and organ printing with gradients in microstructure, growth factor, and matrix composition. Printed structures are used for the regeneration of injured tissues, drug screening, and toxicological studies. The bio-ink plays a critical role in the viability of printed cells, retention of bioactivity of growth factors, printing resolution, fusion of droplets, and structural stability of the printed construct. Graded constructs with respect to stiffness, growth factor composition, or porosity can be created using a combination of inks with different properties. Due to their biocompatibility and tunable properties, water soluble oligomers, macromers, and gel precursors have attracted a great amount of interest as bio-inks in nozzle- as well as laser-based printers. This Special Issue highlights hydrogels and their properties used as inks in tissue and organ bioprinting. Relevant topics include theoretical and experimental investigation of fluid dynamics and rheological properties, gelation kinetics, droplet stability and fusion kinetics, mechanical properties, cell lineage determination, phenotypic variations and maturation during droplet gelation and fusion, collective behavior of encapsulated cells in printed constructs, and tissue formation. Other topics of interest include enzymatically degradable inks, bioactive inks, electroactive and conductive inks, inks for patterning, and inks for the fabrication of nanoscale biodevices.

Prof. Dr. Esmaiel Jabbari
Guest Editor

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Published Papers (8 papers)

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Research

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24 pages, 7118 KiB  
Article
Targeted Printing of Cells: Evaluation of ADA-PEG Bioinks for Drop on Demand Approaches
by Emine Karakaya, Faina Bider, Andreas Frank, Jörg Teßmar, Lisa Schöbel, Leonard Forster, Stefan Schrüfer, Hans-Werner Schmidt, Dirk Wolfram Schubert, Andreas Blaeser, Aldo R. Boccaccini and Rainer Detsch
Gels 2022, 8(4), 206; https://doi.org/10.3390/gels8040206 - 24 Mar 2022
Cited by 7 | Viewed by 3158
Abstract
A novel approach, in the context of bioprinting, is the targeted printing of a defined number of cells at desired positions in predefined locations, which thereby opens up new perspectives for life science engineering. One major challenge in this application is to realize [...] Read more.
A novel approach, in the context of bioprinting, is the targeted printing of a defined number of cells at desired positions in predefined locations, which thereby opens up new perspectives for life science engineering. One major challenge in this application is to realize the targeted printing of cells onto a gel substrate with high cell survival rates in advanced bioinks. For this purpose, different alginate-dialdehyde—polyethylene glycol (ADA-PEG) inks with different PEG modifications and chain lengths (1–8 kDa) were characterized to evaluate their application as bioinks for drop on demand (DoD) printing. The biochemical properties of the inks, printing process, NIH/3T3 fibroblast cell distribution within a droplet and shear forces during printing were analyzed. Finally, different hydrogels were evaluated as a printing substrate. By analysing different PEG chain lengths with covalently crosslinked and non-crosslinked ADA-PEG inks, it was shown that the influence of Schiff’s bases on the viscosity of the corresponding materials is very low. Furthermore, it was shown that longer polymer chains resulted in less stable hydrogels, leading to fast degradation rates. Several bioinks highly exhibit biocompatibility, while the calculated nozzle shear stress increased from approx. 1.3 and 2.3 kPa. Moreover, we determined the number of cells for printed droplets depending on the initial cell concentration, which is crucially needed for targeted cell printing approaches. Full article
(This article belongs to the Special Issue Gels for Bioprinting)
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25 pages, 6259 KiB  
Article
pH Modification of High-Concentrated Collagen Bioinks as a Factor Affecting Cell Viability, Mechanical Properties, and Printability
by Jana Stepanovska, Martin Otahal, Karel Hanzalek, Monika Supova and Roman Matejka
Gels 2021, 7(4), 252; https://doi.org/10.3390/gels7040252 - 7 Dec 2021
Cited by 15 | Viewed by 3480
Abstract
The 3D bioprinting of cell-incorporated gels is a promising direction in tissue engineering applications. Collagen-based hydrogels, due to their similarity to extracellular matrix tissue, can be a good candidate for bioink and 3D bioprinting applications. However, low hydrogel concentrations of hydrogel (<10 mg/mL) [...] Read more.
The 3D bioprinting of cell-incorporated gels is a promising direction in tissue engineering applications. Collagen-based hydrogels, due to their similarity to extracellular matrix tissue, can be a good candidate for bioink and 3D bioprinting applications. However, low hydrogel concentrations of hydrogel (<10 mg/mL) provide insufficient structural support and, in highly concentrated gels, cell proliferation is reduced. In this study, we showed that it is possible to print highly concentrated collagen hydrogels with incorporated cells, where the viability of the cells in the gel remains very good. This can be achieved simply by optimizing the properties of the bioink, particularly the gel composition and pH modification, as well as by optimizing the printing parameters. The bioink composed of porcine collagen hydrogel with a collagen concentration of 20 mg/mL was tested, while the final bioink collagen concentration was 10 mg/mL. This bioink was modified with 0, 5, 9, 13, 17 and 20 μL/mL of 1M NaOH solution, which affected the resulting pH and gelling time. Cylindrical samples based on the given bioink, with the incorporation of porcine adipose-derived stromal cells, were printed with a custom 3D bioprinter. These constructs were cultivated in static conditions for 6 h, and 3 and 5 days. Cell viability and morphology were evaluated. Mechanical properties were evaluated by means of a compression test. Our results showed that optimal composition and the addition of 13 μL NaOH per mL of bioink adjusted the pH of the bioink enough to allow cells to grow and divide. This modification also contributed to a higher elastic modulus, making it possible to print structures up to several millimeters with sufficient mechanical resistance. We optimized the bioprinter parameters for printing low-viscosity bioinks. With this experiment, we showed that a high concentration of collagen gels may not be a limiting factor for cell proliferation. Full article
(This article belongs to the Special Issue Gels for Bioprinting)
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17 pages, 3925 KiB  
Article
Homogeneous and Reproducible Mixing of Highly Viscous Biomaterial Inks and Cell Suspensions to Create Bioinks
by Sophie Dani, Tilman Ahlfeld, Franziska Albrecht, Sarah Duin, Petra Kluger, Anja Lode and Michael Gelinsky
Gels 2021, 7(4), 227; https://doi.org/10.3390/gels7040227 - 23 Nov 2021
Cited by 19 | Viewed by 3681
Abstract
Highly viscous bioinks offer great advantages for the three-dimensional fabrication of cell-laden constructs by microextrusion printing. However, no standardised method of mixing a high viscosity biomaterial ink and a cell suspension has been established so far, leading to non-reproducible printing results. A novel [...] Read more.
Highly viscous bioinks offer great advantages for the three-dimensional fabrication of cell-laden constructs by microextrusion printing. However, no standardised method of mixing a high viscosity biomaterial ink and a cell suspension has been established so far, leading to non-reproducible printing results. A novel method for the homogeneous and reproducible mixing of the two components using a mixing unit connecting two syringes is developed and investigated. Several static mixing units, based on established mixing designs, were adapted and their functionality was determined by analysing specific features of the resulting bioink. As a model system, we selected a highly viscous ink consisting of fresh frozen human blood plasma, alginate, and methylcellulose, and a cell suspension containing immortalized human mesenchymal stem cells. This bioink is crosslinked after fabrication. A pre-crosslinked gellan gum-based bioink providing a different extrusion behaviour was introduced to validate the conclusions drawn from the model system. For characterisation, bioink from different zones within the mixing device was analysed by measurement of its viscosity, shape fidelity after printing and visual homogeneity. When taking all three parameters into account, a comprehensive and reliable comparison of the mixing quality was possible. In comparison to the established method of manual mixing inside a beaker using a spatula, a significantly higher proportion of viable cells was detected directly after mixing and plotting for both bioinks when the mixing unit was used. A screw-like mixing unit, termed “HighVisc”, was found to result in a homogenous bioink after a low number of mixing cycles while achieving high cell viability rates. Full article
(This article belongs to the Special Issue Gels for Bioprinting)
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22 pages, 6892 KiB  
Article
3D Printing of Alginate-Natural Clay Hydrogel-Based Nanocomposites
by Rebeca Leu Alexa, Raluca Ianchis, Diana Savu, Mihaela Temelie, Bogdan Trica, Andrada Serafim, George Mihail Vlasceanu, Elvira Alexandrescu, Silviu Preda and Horia Iovu
Gels 2021, 7(4), 211; https://doi.org/10.3390/gels7040211 - 14 Nov 2021
Cited by 13 | Viewed by 3714
Abstract
Biocompatibility, biodegradability, shear tinning behavior, quick gelation and an easy crosslinking process makes alginate one of the most studied polysaccharides in the field of regenerative medicine. The main purpose of this study was to obtain tissue-like materials suitable for use in bone regeneration. [...] Read more.
Biocompatibility, biodegradability, shear tinning behavior, quick gelation and an easy crosslinking process makes alginate one of the most studied polysaccharides in the field of regenerative medicine. The main purpose of this study was to obtain tissue-like materials suitable for use in bone regeneration. In this respect, alginate and several types of clay were investigated as components of 3D-printing, nanocomposite inks. Using the extrusion-based nozzle, the nanocomposites inks were printed to obtain 3D multilayered scaffolds. To observe the behavior induced by each type of clay on alginate-based inks, rheology studies were performed on composite inks. The structure of the nanocomposites samples was examined using Fourier Transform Infrared Spectrometry and X-ray Diffraction (XRD), while the morphology of the 3D-printed scaffolds was evaluated using Electron Microscopy (SEM, TEM) and Micro-Computed Tomography (Micro-CT). The swelling and dissolvability of each composite scaffold in phosfate buffer solution were followed as function of time. Biological studies indicated that the cells grew in the presence of the alginate sample containing unmodified clay, and were able to proliferate and generate calcium deposits in MG-63 cells in the absence of specific signaling molecules. This study provides novel information on potential manufacturing methods for obtaining nanocomposite hydrogels suitable for 3D printing processes, as well as valuable information on the clay type selection for enabling accurate 3D-printed constructs. Moreover, this study constitutes the first comprehensive report related to the screening of several natural clays for the additive manufacturing of 3D constructs designed for bone reconstruction therapy. Full article
(This article belongs to the Special Issue Gels for Bioprinting)
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11 pages, 3536 KiB  
Article
Investigation of Thermal Gel Formation of Methylcellulose in Glycols Using DSC and XRD
by Muhammad Fahad, Maqsood Ahmed Khan and Marianne Gilbert
Gels 2021, 7(4), 205; https://doi.org/10.3390/gels7040205 - 9 Nov 2021
Cited by 12 | Viewed by 2280
Abstract
Novel compositions of methylcellulose in ethylene, propylene and butylene glycol were investigated for their thermal gel formation. These compositions have previously been found useful for inkjet-printing-based additive manufacturing processes as support materials. Experimental techniques such as viscosity measurements between 20 °C–150 °C–20 °C, [...] Read more.
Novel compositions of methylcellulose in ethylene, propylene and butylene glycol were investigated for their thermal gel formation. These compositions have previously been found useful for inkjet-printing-based additive manufacturing processes as support materials. Experimental techniques such as viscosity measurements between 20 °C–150 °C–20 °C, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used and the results showed that the gel formation upon cooling is caused by polymer–polymer association. The results also show that, for methylcellulose, propylene glycol is a better solvent than ethylene glycol and butylene glycol. Since no chemical reaction is involved, these gels can be used as support materials for jetting-based additive manufacturing processes. Full article
(This article belongs to the Special Issue Gels for Bioprinting)
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12 pages, 4982 KiB  
Article
Reinforcement of Alginate-Gelatin Hydrogels with Bioceramics for Biomedical Applications: A Comparative Study
by Alan Avila-Ramirez, Kevin Catzim-Ríos, Carlos Enrique Guerrero-Beltrán, Erick Ramírez-Cedillo and Wendy Ortega-Lara
Gels 2021, 7(4), 184; https://doi.org/10.3390/gels7040184 - 26 Oct 2021
Cited by 5 | Viewed by 2646
Abstract
This study states the preparation of novel ink with potential use for bone and cartilage tissue restoration. 3Dprint manufacturing allows customizing prostheses and complex morphologies of any traumatism. The quest for bioinks that increase the restoration rate based on printable polymers is a [...] Read more.
This study states the preparation of novel ink with potential use for bone and cartilage tissue restoration. 3Dprint manufacturing allows customizing prostheses and complex morphologies of any traumatism. The quest for bioinks that increase the restoration rate based on printable polymers is a need. This study is focused on main steps, the synthesis of two bioceramic materials as WO3 and Na2Ti6O13, its integration into a biopolymeric-base matrix of Alginate and Gelatin to support the particles in a complete scaffold to trigger the potential nucleation of crystals of calcium phosphates, and its comparative study with independent systems of formulations with bioceramic particles as Al2O3, TiO2, and ZrO2. FT-IR and SEM studies result in hydroxyapatite’s potential nucleation, which can generate bone or cartilage tissue regeneration systems with low or null cytotoxicity. These composites were tested by cell culture techniques to assess their biocompatibility. Moreover, the reinforcement was compared individually by mechanical tests with higher results on synthesized materials Na2Ti6O13 with 35 kPa and WO3 with 63 kPa. Finally, the integration of these composite materials formulated by Alginate/Gelatin and bioceramic has been characterized as functional for further manufacturing with the aid of novel biofabrication techniques such as 3D printing. Full article
(This article belongs to the Special Issue Gels for Bioprinting)
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12 pages, 8210 KiB  
Article
Additive Fabrication and Characterization of Biomimetic Composite Bone Scaffolds with High Hydroxyapatite Content
by Hoyeol Lee, Jin Myoung Yoo and Seung Yun Nam
Gels 2021, 7(3), 100; https://doi.org/10.3390/gels7030100 - 23 Jul 2021
Cited by 5 | Viewed by 2709
Abstract
With the increased incidence of bone defects following trauma or diseases in recent years, three-dimensional porous scaffolds fabricated using bioprinting technologies have been widely explored as effective alternatives to conventional bone grafts, which provide cell-friendly microenvironments promoting bone repair and regeneration. However, the [...] Read more.
With the increased incidence of bone defects following trauma or diseases in recent years, three-dimensional porous scaffolds fabricated using bioprinting technologies have been widely explored as effective alternatives to conventional bone grafts, which provide cell-friendly microenvironments promoting bone repair and regeneration. However, the limited use of biomaterials poses a significant challenge to the robust and accurate fabrication of bioprinted bone scaffolds that enable effective regeneration of the target tissues. Although bioceramic/polymer composites can provide tunable biomimetic conditions, their effects on the bioprinting process are unclear. Thus, in this study, we fabricated hydroxyapatite (HA)/gelatin composite scaffolds containing large weight fractions of HA using extrusion-based bioprinting, with the aim to provide an adequate biomimetic environment for bone tissue regeneration with compositional and mechanical similarity to the natural bone matrix. The overall features of the bioprinted HA/gelatin composite scaffolds, including rheological, morphological, physicochemical, mechanical, and biological properties, were quantitatively assessed to determine the optimal conditions for both fabrication and therapeutic efficiency. The present results show that the bioprinted bioceramic/hydrogel scaffolds possess excellent shape fidelity; mechanical strength comparable to that of native bone; and enhanced bioactivity in terms of cell proliferation, attachment, and osteogenic differentiation. This study provides a suitable alternative direction for the fabrication of bioceramic/hydrogel-based scaffolds for bone repair based on bioprinting. Full article
(This article belongs to the Special Issue Gels for Bioprinting)
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20 pages, 3364 KiB  
Review
Bioactive Inks Development for Osteochondral Tissue Engineering: A Mini-Review
by Negar Bakhtiary, Chaozong Liu and Farnaz Ghorbani
Gels 2021, 7(4), 274; https://doi.org/10.3390/gels7040274 - 18 Dec 2021
Cited by 15 | Viewed by 3676
Abstract
Nowadays, a prevalent joint disease affecting both cartilage and subchondral bone is osteoarthritis. Osteochondral tissue, a complex tissue unit, exhibited limited self-renewal potential. Furthermore, its gradient properties, including mechanical property, bio-compositions, and cellular behaviors, present a challenge in repairing and regenerating damaged osteochondral [...] Read more.
Nowadays, a prevalent joint disease affecting both cartilage and subchondral bone is osteoarthritis. Osteochondral tissue, a complex tissue unit, exhibited limited self-renewal potential. Furthermore, its gradient properties, including mechanical property, bio-compositions, and cellular behaviors, present a challenge in repairing and regenerating damaged osteochondral tissues. Here, tissue engineering and translational medicine development using bioprinting technology provided a promising strategy for osteochondral tissue repair. In this regard, personalized stratified scaffolds, which play an influential role in osteochondral regeneration, can provide potential treatment options in early-stage osteoarthritis to delay or avoid the use of joint replacements. Accordingly, bioactive scaffolds with possible integration with surrounding tissue and controlling inflammatory responses have promising future tissue engineering perspectives. This minireview focuses on introducing biologically active inks for bioprinting the hierarchical scaffolds, containing growth factors and bioactive materials for 3D printing of regenerative osteochondral substitutes. Full article
(This article belongs to the Special Issue Gels for Bioprinting)
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