AccScience Publishing / IJB / Volume 7 / Issue 3 / DOI: 10.36922/ijb.v7i3.394
REVIEW

A Systematic Thermal Analysis for Accurately Predicting the Extrusion Printability of Alginate–Gelatin-Based Hydrogel Bioinks

Qi Li1,2† Bin Zhang1,2† Qian Xue1,2 Chunxiao Zhao1,2 Yichen Luo1,2 Hongzhao Zhou1,2* Liang Ma1,2* Huayong Yang1,2 Dapeng Bai1,2
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1 State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, 310058, People’s Republic of China
2 School of Mechanical Engineering, Zhejiang University, Hangzhou, 310058, People’s Republic of China
Published: 22 June 2021
© 2021 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Three-dimensional (3D) bioprinting has significant potential for addressing the global problem of organ shortages. Extrusion printing is a versatile 3D bioprinting technique, but its low accuracy currently limits the solution. This lack of precision is attributed largely to the complex thermal and dynamic properties of bioinks and makes it difficult to provide accurate estimations of the printed results. It is necessary to understand the relationship between printing temperature and materials’ printability to address this issue. This paper proposes a quantitative thermal model incorporating a system’s printing temperatures (syringe, ambient, and bioink) to facilitate accurate estimations of the printing outcomes. A physical model was established to reveal the relationship between temperature, pressure, and velocity in guiding the printing of sodium alginate–gelatin composite hydrogel (a popular bioink) to optimize its extrusion-based printability. The model considered the phenomenon of bioink die swells after extrusion. A series of extrusion experiments confirmed that the proposed model offers enhanced printing outcome estimations compared with conventional models. Two types of nozzles (32- and 23-gauge) were used to print several sets of lines with a linewidth step of 50 μm by regulating the extrudate’s temperature, pressure, and velocity separately. The study confirmed the potential for establishing a reasonable, accurate open-loop linewidth control based on the proposed optimization method to expand the application of extrusion-based bioprinting further.

Keywords
3D bioprinting
Pneumatic extrusion
Thermal effects
Temperature control
Printability
References

1. Donderwinkel I, Hest JC, Cameron NR, 2017, Bio-inks for 3D Bioprinting: Recent Advances and Future Prospects. Polym Chem, 8:4451–71. https://doi.org/10.1039/c7py00826k.

2. Zhang B, Gao L, Ma L, et al., 2019, 3D Bioprinting: A Novel Avenue for Manufacturing Tissues and Organs. Engineering, 5:777–94. https://doi.org/10.1016/j.eng.2019.03.009.

3. He Y, Yang F, Zhao H, et al., 2016, Research on the Printability of Hydrogels in 3D Bioprinting. Sci Rep, 6:29977.

4. Michal S, Smadar C, 2003, Cardiac Tissue Engineering, Ex Vivo: Design Principles in Biomaterials and Bioreactors. Heart Fail Rev, 8:271–6.

5. Campbell J, McGuinness I, Wirz H, et al., 2015, Multimaterial and Multiscale Three-Dimensional Bioprinter. J Nanotechnol Eng Med, 6:021005.

6. Holländer J, Hakala R, Suominen J, et al., 2018, 3D Printed UV Light Cured Polydimethylsiloxane Devices for Drug Delivery. Int J Pharm, 544:433–42. https://doi.org/10.1016/j.ijpharm.2017.11.016.

7. Kang HW, Lee SJ, Ko IK, et al., 2016, A 3D Bioprinting System to Produce Human-Scale Tissue Constructs with Structural Integrity. Nat Biotechnol, 34:312–9. https://doi.org/10.1038/nbt.3413.

8. Liu W, Zhang YS, Heinrich MA, et al., 2017, Rapid Continuous Multimaterial Extrusion Bioprinting. Adv Mater, 29:1604630.

9. McElheny C, Hayes D, Devireddy R, 2017, Design and Fabrication of a Low-Cost Three-Dimensional Bioprinter. J Med Device, 11:041001. https://doi.org/10.1115/1.4037259.

10. Wang L, Xu ME, Luo L, et al., 2018, Iterative Feedback Bio-Printing-Derived Cell-Laden Hydrogel Scaffolds with Optimal Geometrical Fidelity and Cellular Controllability. Sci Rep, 8:2802. https://doi.org/10.1038/s41598-018-21274-4.

11. Ahn G, Park JH, Kang T, et al., 2010, Effect of Pore Architecture on Oxygen Diffusion in 3D Scaffolds for Tissue Engineering. J Biomech Eng, 132:104506.

12. Ng WL, Chua CK, Shen YF, 2019, Print Me An Organ! Why We Are Not There Yet. Prog Polym Sci, 97:101145. https://doi.org/10.1016/j.progpolymsci.2019.101145.

13. Nguyen DG, Funk J, Robbins JB, et al., 2016, Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro. PLoS One, 11:e0158674. https://doi.org/10.1371/journal.pone.0158674.

14. Park SJ, Kim RY, Park BW, et al., 2019, Dual Stem Cell Therapy Synergistically Improves Cardiac Function And Vascular Regeneration Following Myocardial Infarction. Nat Commun, 10:3123. https://doi.org/10.1038/s41467-019-11091-2.

15. Ma L, Li Y, Wu Y, et al., 2020, 3D Bioprinted Hyaluronic Acid-Based Cell-Laden Scaffold for Brain Microenvironment Simulation. Biodes Manuf, 3:164–74. https://doi.org/10.1007/s42242-020-00076-6.

16. Lee V, Singh G, Trasattijohn P, et al., 2014, Design and Fabrication of Human Skin by Three-Dimensional Bioprinting. Tissue Eng Part C Methods, 20:473–84.

17. Peng W, Unutmaz D, Ozbolat IT, 2016, Bioprinting Towards Physiologically Relevant Tissue Models for Pharmaceutics. Trends Biotechnol, 34:722–32. https://doi.org/10.1016/j.tibtech.2016.05.013.

18. Zhang B, Luo Y, Ma L, et al., 2018, 3D Bioprinting: An Emerging Technology Full of Opportunities and Challenges. Biodes Manuf, 1:2–13.

19. Gudapati H, Dey M, Ozbolat I, 2016, A Comprehensive Review on Droplet-Based Bioprinting: Past, Present and Future. Biomaterials, 102:20–42. https://doi.org/10.1016/j.biomaterials.2016.06.012.

20. Ying G, Jiang N, Yu C, et al., 2018, Three-Dimensional Bioprinting of Gelatin Methacryloyl (GelMA). Biodes Manuf, 1:215–24. https://doi.org/10.1007/s42242-018-0028-8.

21. Ma L, Li Y, Wu Y, et al., 2020, The Construction of In Vitro Tumor Models Based on 3D Bioprinting. Biodes Manuf, 3:227–36.

22. Alruwaili M, Lopez JA, McCarthy K, et al., 2019, Liquid phase 3D Bioprinting of Gelatin Alginate Hydrogels: Influence of Printing Parameters on Hydrogel Line Width and Layer Height. Biodes Manuf, 2:172–80. https://doi.org/10.1007/s42242-019-00043-w.

23. Chang R, Nam J, Sun W, 2008, Effects of Dispensing Pressure and Nozzle Diameter on Cell Survival from Solid Freeform Fabrication-Based Direct Cell Writing. Tissue Eng Part A, 14:41–8. https://doi.org/10.1089/ten.2007.0004.

24. Gao T, Gillispie GJ, Copus JS, et al., 2018, Optimization of Gelatin-Alginate Composite Bioink Printability Using Rheological Parameters: A Systematic Approach. Biofabrication, 10:034106. https://doi.org/10.1088/1758-5090/aacdc7.

25. Zhao Y, Li Y, Mao S, et al., 2015, The Influence of Printing Parameters on Cell Survival Rate and Printability in Microextrusion-Based 3D Cell Printing Technology. Biofabrication, 7:045002. https://doi.org/10.1088/1758-5090/7/4/045002.

26. Gong Y, Bi Z, Bian X, et al., 2020, Study on Linear Bio- Structure Print Process Based on Alginate Bio-Ink in 3D Bio- Fabrication. Biodes Manuf, 3:109–21. https://doi.org/10.1007/s42242-020-00065-9.

27. Ouyang L, Yao R, Zhao Y, et al., 2016, Effect of Bioink Properties on Printability and Cell Viability for 3D Bioplotting of Embryonic Stem Cells. Biofabrication, 8:035020. https://doi.org/10.1088/1758-5090/8/3/035020.

28. Kolan KC, Semon JA, Bromet B, et al., 2019, Bioprinting with Human Stem Cell-Laden Alginate-Gelatin Bioink and Bioactive Glass for Tissue Engineering. Int J Bioprint, 5:204. https://doi.org/10.18063/ijb.v5i2.2.204.

29. Zhang Z, Jin Y, Yin J, et al., 2018, Evaluation of Bioink Printability for Bioprinting Applications. Appl Phys Rev, 5:041304.

30. Yin J, Zhao D, Liu J, 2019, Trends on Physical Understanding of Bioink Printability. Biodes Manuf, 2:50–4.

31. Suntornnond R, Tan EY, An J, et al., 2016, A Mathematical Model on the Resolution of Extrusion Bioprinting for the Development of New Bioinks. Materials (Basel), 9:756. https://doi.org/10.3390/ma9090756.

32. Lee JM, Yeong WY, 2014, A Preliminary Model of Time-Pressure Dispensing System for Bioprinting Based on Printing and Material Parameters. Virtual Phys Prototyp, 10:3–8. https://doi.org/10.1080/17452759.2014.979557.

33. Paxton N, Smolan W, Bock T, et al., 2017, Proposal to Assess Printability of Bioinks for Extrusion-Based Bioprinting and Evaluation of Rheological Properties Governing Bioprintability. Biofabrication, 9:044107. https://doi.org/10.1088/1758-5090/aa8dd8.

34. Chen X, Li M, Ke H, 2008, Modeling of the Flow Rate in the Dispensing-Based Process for Fabricating Tissue Scaffolds. J Manuf Sci Eng, 130:021003. https://doi.org/10.1115/1.2789725.

35. Billiet T, Gevaert E, de Schryver T, et al., 2014, The 3D Printing of Gelatin Methacrylamide Cell-Laden Tissue-Engineered Constructs with High Cell Viability. Biomaterials, 35:49–62. https://doi.org/10.1016/j.biomaterials.2013.09.078.

36. Mahmoudi Y, 2014, Effect of Thermal Radiation on Temperature Differential in a Porous Medium Under Local Thermal Non-Equilibrium Condition. Int J Heat Mass Transf, 76:105–21. https://doi.org/10.1016/j.ijheatmasstransfer.2014.04.024.

37. Zhang B, Xue Q, Hu HY, et al., 2019, Integrated 3D Bioprinting-Based Geometry-Control Strategy for Fabricating Corneal Substitutes. J Zhejiang Univ Sci B, 20:945–59. https://doi.org/10.1631/jzus.b1900190.

38. Isaacson A, Swioklo S, Connon CJ, 2018, 3D Bioprinting of a Corneal Stroma Equivalent. Exp Eye Res, 173:188–93. https://doi.org/10.1016/j.exer.2018.05.010.

39. Kong B, Chen Y, Liu R, et al., 2020, Fiber Reinforced GelMA Hydrogel to Induce the Regeneration of Corneal Stroma. Nat Commun, 11:1435.

40. Zhang B, Gao L, Gu L, et al., 2017, High-resolution 3D Bioprinting System for Fabricating Cell-laden Hydrogel Scaffolds with High Cellular Activities. Proc CIRP, 65: 219–24. https://doi.org/10.1016/j.procir.2017.04.017.

41. Shao L, Gao Q, Xie C, et al., 2020, Sacrificial Microgel-Laden Bioink-Enabled 3D Bioprinting of Mesoscale Pore Networks. Biodes Manuf, 3:30–9. https://doi.org/10.1007/s42242-020-00062-y.

42. Gong Y, Wang F, Al-Furjan MS, et al., 2020, Experimental Investigation and Optimal 3D Bioprinting Parameters of SAGel Porous Cartilage Scaffold. Appl Sci, 10:768. https://doi.org/10.3390/app10030768.

43. Khalil S, Sun W, 2007, Biopolymer Deposition for Freeform Fabrication of Hydrogel Tissue Constructs. Mater Sci Eng C, 27:469–78. https://doi.org/10.1016/j.msec.2006.05.023.

44. Tanner RI, 2005, A Theory of Die-Swell Revisited. J Nonnewton Fluid Mech, 129:85–7. 

45. Tanner RI, 1970, A Theory of Die-Swell. J Polym Sci Part A-2 Polym Phys, 8:2067–78.

46. Carreau PJ, Choplin L, Clermont JR, 1985, Exit Pressure Effects in Capillary Die Data. Polym Eng Sci, 25:669–76. https://doi.org/10.1002/pen.760251105.

47. Iwami K, Noda T, Ishida K, et al., 2010, Bio Rapid Prototyping by Extruding/Aspirating/Refilling Thermoreversible Hydrogel. Biofabrication, 2:014108. https://doi.org/10.1088/1758-5082/2/1/014108.

48. Liang JZ, 2008, Effects of Extrusion Conditions on Die-Swell Behavior of Polypropylene/Diatomite Composite Melts. Polym Test, 27:936–40. https://doi.org/10.1016/j.polymertesting.2008.08.001.

49. Chin WC. Managed Pressure Drilling: Modeling, Strategy and Planning. Waltham: Gulf Professional Publishing; 2012. p. 315-85.

50. Allain C, Cloitre M, Perrot P, 1997, Experimental Investigation and Scaling Law Analysis of Die Swell in Semi-Dilute Polymer Solutions. J Nonnewton Fluid Mech, 73:51–66. https://doi.org/10.1016/s0377-0257(97)00051-7.

51. Cooke ME, Rosenzweig DH, 2021, The Rheology of Direct and Suspended Extrusion Bioprinting. APL Bioeng, 5:011502. https://doi.org/10.1063/5.0031475.

52. Quéré D, Azzopardi MJ, Delattre L, 1998, Drops at Rest on a Tilted Plane. Langmuir, 14:2213–6.

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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing