3D printing of an integrated triphasic MBG-alginate scaffold with enhanced interface bonding for hard tissue applications

Zhu, Min; He, Xin; Chen, Xin; Zhu, Yufang; Liu, Zhongtang

doi:10.1007/s10856-020-06459-6

Cited by 19 publications

(16 citation statements)

References 35 publications

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“…Inclusion of MBG containing 15 mol-% Ca (0ZnMBG) in both the 3-9 and 3-6 blend greatly increased the viscosity of the inks and required higher printing pressures ( Figure 2). Similar effect on the viscosity was observed in another study where MBG particles were added to sodium alginate [43]. Higher viscosity can result from a higher solid content due to the addition of particulate material (in our case MBG particles).…”

Section: Discussionsupporting

confidence: 86%

Tailorable Zinc-Substituted Mesoporous Bioactive Glass/Alginate-Methylcellulose Composite Bioinks

et al. 2021

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Bioactive glasses have been used for bone regeneration applications thanks to their excellent osteoconductivity, an osteostimulatory effect, and high degradation rate, releasing biologically active ions. Besides these properties, mesoporous bioactive glasses (MBG) are specific for their highly ordered mesoporous channel structure and high specific surface area, making them suitable for drug and growth factor delivery. In the present study, calcium (Ca) (15 mol%) in MBG was partially and fully substituted with zinc (Zn), known for its osteogenic and antimicrobial properties. Different MBG were synthesized, containing 0, 5, 10, or 15 mol% of Zn. Up to 7 wt.% of Zn-containing MBG could be mixed into an alginate-methylcellulose blend (algMC) while maintaining rheological properties suitable for 3D printing of scaffolds with sufficient shape fidelity. The suitability of these composites for bioprinting applications has been demonstrated with immortalized human mesenchymal stem cells. Uptake of Ca and phosphorus (P) (phosphate) ions by composite scaffolds was observed, while the released concentration of Zn2+ corresponded to the initial amount of this ion in prepared glasses, suggesting that it can be controlled at the MBG synthesis step. The study introduces a tailorable bioprintable material system suitable for bone tissue engineering applications.

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Section: Discussionsupporting

confidence: 86%

Tailorable Zinc-Substituted Mesoporous Bioactive Glass/Alginate-Methylcellulose Composite Bioinks

et al. 2021

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“…Although, in this paper, only the survival of one cell type during the mixing process was investigated, we experienced in several lab projects that various mammalian cell types but also yeasts, bacteria or cells from the plant kingdom show a similarly favourable response. Additionally, we predict that this mixing device is suitable for particle-containing bioinks, for example bioinks with bioglasses, calcium phosphates, or magnetic particles [ 40 , 41 , 42 ]. Future research should consider the static mixing unit for the homogenous mixing of such composite bioinks.…”

Section: Discussionmentioning

confidence: 99%

Homogeneous and Reproducible Mixing of Highly Viscous Biomaterial Inks and Cell Suspensions to Create Bioinks

Dani

Ahlfeld

Albrecht

et al. 2021

Gels

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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.

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“…An excellent print fidelity was achieved by the addition of 9 wt% MC to 3 wt% alg dissolved in phosphate-buffered saline (PBS) or human blood plasma, maintaining viability and functionality of human mesenchymal stem cells (hMSCs), rat pancreatic islets, chondrocytes, or human pre-osteoblasts (hOBs) ( Schütz et al, 2017 ; Duin et al, 2019 ; Hodder et al, 2019 ; Ahlfeld et al, 2020a ; Kilian et al, 2020 ). In composites of algMC with MBG, the addition of up to 10 wt% of MBG, in contrast to up to 1.5 wt% described in literature ( Heras et al, 2020 ; Zhu et al, 2020 ; Tavares et al, 2021 ), resulted in an increased viscosity that has been counteracted by reducing the MC content to 6 wt%, maintaining shape fidelity and facilitating bioprinting of embedded hMSCs ( Guduric et al, 2021 ). Furthermore, MBG can be modified with different therapeutic metal ions, for example Sr 2+ and Zn 2+ , to stimulate cellular processes.…”

Section: Introductionmentioning

confidence: 99%

Composite Bioinks With Mesoporous Bioactive Glasses—A Critical Evaluation of Results Obtained by In Vitro Experiments

Gudurić

Wieckhusen

Bernhardt

et al. 2022

Front. Bioeng. Biotechnol.

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Besides osteoconductivity and a high degradation rate, mesoporous bioactive glasses (MBGs) are specific for their highly ordered channel structure and high specific surface area, making them suitable as drug and/or growth factor delivery systems. On the other hand, the mesoporous channel structure and MBG composition can have an effect on common cell evaluation assays, leading to inconclusive results. This effect is especially important when MBG is mixed in composite bioinks, together with cells. Additionally, the hydrogel component of the ink can influence the degradation of MBG, leading to different ion releases, which can additionally affect the analyses. Hence, our aim here was to show how the MBG structure and composition influence common cell viability and differentiation assays when calcium (Ca)- or magnesium (Mg)-containing glass is part of an alginate-based composite bioink. We suggested pre-labeling of cells with DiI prior to bioprinting and staining with calcein-AM to allow identification of metabolically active cells expressing signals in both green and red channels, allowing the use of fluorescence imaging for cell viability evaluations in the presence of high amounts (7 wt %) of MBGs. The release and uptake of ions during degradation of CaMBG and MgMBG were significantly changed by alginate in the composite bioinks, as confirmed by higher release and uptake from bulk glasses. Additionally, we detected a burst release of Mg2+ from composites only after 24 h of incubation. Furthermore, we demonstrated that released ions and the mesoporous channel structure affect the measurement of lactate dehydrogenase (LDH) and alkaline phosphatase activity (ALP) in bioprinted composite scaffolds. Measured LDH activity was significantly decreased in the presence of CaMBG. On the other hand, the presence of MgMBG induced increased signal measured for the ALP. Taken together, our findings show how composite bioinks containing MBGs can interfere with common analyses, obtaining misleading results.

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3D printing of an integrated triphasic MBG-alginate scaffold with enhanced interface bonding for hard tissue applications

Cited by 19 publications

References 35 publications

Tailorable Zinc-Substituted Mesoporous Bioactive Glass/Alginate-Methylcellulose Composite Bioinks

Tailorable Zinc-Substituted Mesoporous Bioactive Glass/Alginate-Methylcellulose Composite Bioinks

Homogeneous and Reproducible Mixing of Highly Viscous Biomaterial Inks and Cell Suspensions to Create Bioinks

Composite Bioinks With Mesoporous Bioactive Glasses—A Critical Evaluation of Results Obtained by In Vitro Experiments

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