Bioprinting with human stem cells-laden alginate-gelatin bioink and bioactive glass for tissue engineering

Krishna C. R. Kolan, Julie A. Semon, Bradley Bromet, Delbert E. Day, Ming C. Leu

Article ID: 204
Vol 5, Issue 2.2, 2019, Pages 3-15

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Three-dimensional (3D) bioprinting technologies have shown great potential in fabrication of 3D models for different human tissues. Stem cells are an attractive cell source in tissue engineering as they can be directed by material and environmental cues to differentiate into multiple cell types for tissue repair and regeneration. In this study, we investigate the viability of human adipose-derived mesenchymal stem cells (ASCs) in alginate-gelatin hydrogel bioprinted with or without bioactive glass. Highly angiogenic borate bioactive glass (13-93B3) in 50 wt.% is added to polycaprolactone (PCL) to fabricate scaffolds using a solvent-based extrusion 3D bioprinting technique. The fabricated scaffolds with 12x12x1 mm3 in overall dimensions are physically characterized, and the glass dissolution from PCL/glass composite over a period of 28 days is studied. Alginate-gelatin composite is used as a bioink to suspend ASCs, and scaffolds are then bioprinted in different configurations: Bioink only, PCL+bioink, and PCL/glass+bioink, to investigate ASC viability. The results indicate that the solvent-based bioprinting process to fabricate 3D tissue models with bioactive glasses provides more than 80% cell viability immediately after printing and more than 60% viability after 7 days in normal culture conditions. The feasibility of modifying bioink with 13-93B3 glass for bioprinting is also investigated and the results are discussed.


Bioprinting; Alginate-Gelatin Hydrogel; Borate Bioactive Glass; Polymer/Bioactive Glass Composite; Human Adipose-Derived Stem Cells

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Moroni L, Boland T, Burdick J A, et al., 2018, Biofabrication: A Guide to Technology and Terminology. Trends Biotechnol. vol.36(4):384–402.

Ozbolat I T, Hospodiuk M, 2016, Current advances and future perspectives in extrusion-based bioprinting. Biomaterials vol.76:321–343.

Pati F, Gantelius J, Svahn H A, 2016, 3D Bioprinting of Tissue/Organ Models. Angew. Chemie Int. Ed. vol.55(15):4650–4665.

Choudhury D, Anand S, Naing M, 2018, The arrival of commercial bioprinters – Towards 3D bioprinting revolution! Int. J. Bioprinting vol.4(2).

Derakhshanfar S, Mbeleck R, Xu K, et al., 2018, 3D bioprinting for biomedical devices and tissue engineering: A review of recent trends and advances. Bioact. Mater. vol.3(2):144.

Murphy C, Kolan K, Li W, et al., 2017, 3D bioprinting of stem cells and polymer/bioactive glass composite scaffolds for tissue engineering. Int. J. Bioprinting vol.3(1):54–64.

Guo S-Z, Gosselin F, Guerin N, et al., 2013, Solvent-Cast Three-Dimensional Printing of Multifunctional Microsystems. Small vol.9(24):4118–4122.

Kaur G, Dufour J M, 2012, Cell lines: Valuable tools or useless artifacts. Spermatogenesis vol.2(1):1–5.

Ong C S, Yesantharao P, Huang C Y, et al., 2018, 3D bioprinting using stem cells. Pediatr. Res. vol.83(1–2):223–231.

Tasoglu S, Demirci U, 2013, Bioprinting for stem cell research. Trends Biotechnol. vol.31(1):10–19.

Uccelli A, Moretta L, Pistoia V, 2008, Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. vol.8(9):726–36.

D’Andrea F, De Francesco F, Ferraro G A, et al., 2008, Large-scale production of human adipose tissue from stem cells: a new tool for regenerative medicine and tissue banking. Tissue Eng. Part C. Methods vol.14(3):233–42.

Casteilla L, Dani C, 2006, Adipose tissue-derived cells: from physiology to regenerative medicine. Diabetes Metab. vol.32(5 Pt 1):393–401.

Wang Y, Yin P, Bian G-L, et al., 2017, The combination of stem cells and tissue engineering: an advanced strategy for blood vessels regeneration and vascular disease treatment. Stem Cell Res. Ther. vol.8(1):194.

Apelgren P, Amoroso M, Lindahl A, et al., 2017, Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo. PLoS One vol.12(12):e0189428.

Kim Y, Kang K, Yoon S, et al., 2018, Prolongation of liver-specific function for primary hepatocytes maintenance in 3D printed architectures. Organogenesis vol.14(1):1–12.

Kolesky D B, Truby R L, Gladman A S, et al., 2014, 3D Bioprinting of Vascularized, Heterogeneous Cell-Laden Tissue Constructs. Adv. Mater. vol.26(19):3124–3130.

Sasaki J-I, Hashimoto M, Yamaguchi S, et al., 2015, Fabrication of Biomimetic Bone Tissue Using Mesenchymal Stem Cell-Derived Three-Dimensional Constructs Incorporating Endothelial Cells. PLoS One vol.10(6):e0129266.

Wang X, Tolba E, Schröder H C, et al., 2014, Effect of Bioglass on Growth and Biomineralization of SaOS-2 Cells in Hydrogel after 3D Cell Bioprinting. PLoS One vol.9(11):e112497.

Ojansivu M, Rashad A, Ahlinder A E, et al., 2019, Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells. Biofabrication .

Zhang J, Chen Y, Xu J, et al., 2018, Tissue engineering using 3D printed nano-bioactive glass loaded with NELL1 gene for repairing alveolar bone defects. Regen. Biomater. vol.5(4):213–220.

Jung S B, Day D E, 2011, Revolution in wound care? Inexpensive, easy-to-use cotton candy-like glass fibers appear to speed healing in initial venous stasis wound trial. Am. Ceram. Soc. Bull. vol.90(4):25–29.

Jung S, 2010, Borate based bioactive glass scaffolds for hard and soft tissue engineering. Dr. Diss.

Food and Drug Administration, 2016, Department of Health and Human Services.

Lin Y, Brown R F, Jung S B, et al., 2014, Angiogenic effects of borate glass microfibers in a rodent model. J. Biomed. Mater. Res. Part A :n/a-n/a.

Karageorgiou V, Kaplan D, 2005, Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials vol.26(27):5474–5491.

Luo Y, Lode A, Akkineni A R, et al., 2015, Concentrated gelatin/alginate composites for fabrication of predesigned scaffolds with a favorable cell response by 3D plotting. RSC Adv. vol.5(54):43480–43488.

Shi L, Xiong L, Hu Y, et al., 2018, Three-dimensional printing alginate/gelatin scaffolds as dermal substitutes for skin tissue engineering. Polym. Eng. Sci. vol.58(10):1782–1790.

Zhou J, Wang H, Zhao S, et al., 2016, In vivo and in vitro studies of borate based glass micro-fibers for dermal repairing. Mater. Sci. Eng. C vol.60:437–445.

Earl P, Stoecker W, Jung S, 2018, Clinical Case Studies - ETS Wound Care.

Gu Y, Huang W, Rahaman M N, et al., 2013, Bone regeneration in rat calvarial defects implanted with fibrous scaffolds composed of a mixture of silicate and borate bioactive glasses. Acta Biomater. vol.9(11):9126–9136.

Woodruff M A, Hutmacher D W, 2010, The return of a forgotten polymer—Polycaprolactone in the 21st century. Prog. Polym. Sci. vol.35(10):1217–1256.

Lee H, Won Koo Y, Yeo M, et al., 2017, Recent cell printing systems for tissue engineering. Int. J. Bioprint-ing vol.3(1).

Rezaei S, Shakibaie M, Kabir-Salmani M, et al., 2016, Improving the Growth Rate of Human Adipose-Derived Mesenchymal Stem Cells in Alginate/Gelatin Versus Alginate Hydrogels. Iran. J. Biotechnol. vol.14(1):1–8.

Li Z, Huang S, Liu Y, et al., 2018, Tuning Alginate-Gelatin Bioink Properties by Varying Solvent and Their Impact on Stem Cell Behavior. Sci. Rep. vol.8(1):8020.

Kolan K, Li J, Roberts S, et al., 2018, Near-field electrospinning of a polymer/bioactive glass composite to fabricate 3D biomimetic structures. Int. J. Bioprinting vol.5(1).



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