AccScience Publishing / IJB / Volume 10 / Issue 3 / DOI: 10.36922/ijb.1838
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RESEARCH ARTICLE

Design and optimization of 3D-bioprinted cell-laden scaffolds in dynamic culture

Jing Li1† Feng Chen1† Meixia Wang2 Xiaolong Zhu1 Ning He1 Na Li3 Haotian Zhu1 Xiaoxiao Han1*
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1 National Engineering Research Centre for High Efficiency Grinding, Hunan University, Changsha, Hunan, China
2 Department of Pharmacy, College of Biology, Hunan University, Changsha, Hunan, China
3 Radiology Department, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
IJB 2024, 10(3), 1838 https://doi.org/10.36922/ijb.1838
Submitted: 14 September 2023 | Accepted: 29 November 2023 | Published: 25 January 2024
© 2024 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

Light-based 3D printing enables the fabrication of biological scaffolds with high precision, versatility and biocompatibility, particularly the cell-laden scaffolds with architecturally complex geometric features. However, many bioprinted tissue scaffolds suffer from low cell viability due to insufficient oxygen and nutrient supply, which is heavily influenced by scaffold structure and cultivation conditions. Current practice relies mainly on resource-intensive trial-and-error methods to optimize scaffolds’ structures and cultivation parameters. In this study, we developed a comprehensive multi-physics model integrating fluid dynamics, oxygen mass transfer, cell oxygen consumption, and cell growth processes to capture cell growth behaviors in scaffolds, establishing a robust theoretical foundation for scaffold structure optimization. The modeling results showed that a large number of parameters, such as system inlet flow rate, geometric feature size, cell parameters, and material properties, significantly impact oxygen concentration and cell growth within the scaffold. A two-step optimization strategy is proposed in this paper and was applied to obtain optimal geometric parameters of channeled scaffolds to demonstrate the model’s effectiveness for scaffold optimization. The model can be employed for scaffolds with arbitrary shapes and various materials, facilitating the optimal design of sophisticated scaffolds for more advanced tissue engineering.

Keywords
Multi-physics model
Cell-laden scaffolds
Light-based bioprinting
Dynamic culturing
Scaffold structural design
Funding
The authors acknowledge the financial support received from the National Natural Science Foundation of China (52075158) and the Natural Science Foundation of Hunan Province (2021JJ30109).
Conflict of interest
The authors declare no conflicts of interest.
References
  1. Ventola CL. Medical applications for 3D printing: current and projected uses. P&T. 2014;39(10):704-711.
  2. Reddy VS, Ramasubramanian B, Telrandhe VM, Ramakrishna S. Contemporary standpoint and future of 3D bioprinting in tissue/organs printing. Curr Opin Biomed Eng. 2023;27:100461. doi: 10.1016/j.cobme.2023.100461
  3. Murphy SV, Atala AJ. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32:773-785. doi: 10.1038/nbt.2958
  4. Muskan, Gupta D, Negi NP. 3D bioprinting: printing the future and recent advances. Bioprinting. 2022;27:2405-8866. doi: 10.1016/j.bprint.2022.e00211
  5. Matai I, Kaur G, Seyedsalehi A, McClinton A, Laurencin CT. Progress in 3D bioprinting technology for tissue/organ regenerative engineering. Biomaterials. 2020;226:119536. doi: 10.1016/j.biomaterials.2019.119536
  6. Li T, Chang J, Zhu Y, Wu C. 3D printing of bioinspired biomaterials for tissue regeneration. Adv Healthc Mater. 2020;9(23):2000208. doi: 10.1002/adhm.202000208
  7. Javaid M, Haleem A. 3D printing applications towards the required challenge of stem cells printing. Clin Epidemiol Global Health. 2020;8:862-867. doi: 10.1016/j.cegh.2020.02.014
  8. Cidonio G, Glinka M, Dawson JI, Oreffo ROC. The cell in the ink: improving biofabrication by printing stem cells for skeletal regenerative medicine. Biomaterials. 2019;20910-24. doi: 10.1016/j.biomaterials.2019.04.009
  9. Sun Y, Yu K, Gao Q, He Y. Projection-based 3D bioprinting for hydrogel scaffold manufacturing. Bio-Des Manuf. 2022;5:633-639. doi: 10.1007/s42242-022-00189-0
  10. He Y-X, Wang F, Wang X, Zhang J, Wang D, Huang X. A photocurable hybrid chitosan/acrylamide bioink for DLP based 3D bioprinting. Mater Des. 2021;202:109588. doi: 10.1016/j.matdes.2021.109588
  11. Tao J-L, Zhu S, Liao X, et al. DLP-based bioprinting of void-forming hydrogels for enhanced stem-cell-mediated bone regeneration. Mater Today Bio. 2022;17:100487. doi: 10.1016/j.mtbio.2022.100487
  12. Lee A, Hudson AR, Shiwarski DJ, et al. 3D bioprinting of collagen to rebuild components of the human heart. Science. 2019;365:482-487. doi: 10.1126/science.aav9051
  13. Lei D, Yang Y, Liu Z, et al. 3D printing of biomimetic vasculature for tissue regeneration. Mater Horiz. 2019;6(6):1197-1206. doi: 10.1039/C9MH00174C
  14. Grigoryan B, Paulsen SJ, Corbett DC, et al. Multivascular networks and functional intravascular topologies within biocompatible hydrogels. Science. 2019;364:458-464. doi: 10.1126/science.aav9750
  15. He N, Wang X, Shi L, et al. Photoinhibiting via simultaneous photoabsorption and free-radical reaction for high-fidelity light-based bioprinting. Nat Commun. 2023;14(1):3063. doi: 10.1038/s41467-023-38838-2
  16. Bernal PN, Bouwmeester MC, Madrid-Wolff J, et al. Volumetric bioprinting of organoids and optically tuned hydrogels to build liver‐like metabolic biofactories. Adv Mater. 2022;34(15):2110054. doi: 10.1002/adma.202110054
  17. Wang M, Li W, Hao J, et al. Molecularly cleavable bioinks facilitate high-performance digital light processing-based bioprinting of functional volumetric soft tissues. Nat Commun. 2022;13(1):3317. doi: 10.1038/s41467-022-31002-2
  18. Kolesky DB, Homan KA, Skylar-Scott MA, Lewis JA. Three-dimensional bioprinting of thick vascularized tissues. Proc Natl Acad Sci. 2016;113:3179-3184. doi: 10.1073/pnas.1521342113
  19. Han X, Courseaus J, Khamassi J, et al. Optimized vascular network by stereolithography for tissue engineered skin. Int J Bioprint. 2018;4(2). doi: 10.18063/ijb.v4i2.134
  20. Fang Y, Ouyang L, Zhang T, Wang C, Lu B, Sun W. Optimizing bifurcated channels within an anisotropic scaffold for engineering vascularized oriented tissues. Adv Healthc Mater. 2020;9(24):2000782. doi: 10.1002/adhm.202000782
  21. Margolis EA, Friend NE, Rolle MW, Alsberg E, Putnam AJ. Manufacturing the multiscale vascular hierarchy: progress toward solving the grand challenge of tissue engineering. Trends Biotechnol. 2023;41(11):P1400-1416. doi: 10.1016/j.tibtech.2023.04.003
  22. Nascu I, Sebastia‐Saez D, Chen T, Nascu I, Du W. Global sensitivity analysis for a perfusion bioreactor based on CFD modelling. Comput Chem Eng. 2022;163:107829. doi: 10.1016/j.compchemeng.2022.107829
  23. Capuana E, Pavia FC, Lombardo ME, et al. Mathematical and numerical modeling of an airlift perfusion bioreactor for tissue engineering applications. Biochem Eng J. 2021;178:108298. doi: 10.1016/j.bej.2021.108298
  24. Zhu X, Chen F, Cao H-Q, Li L, He N, Han X. Design and fused deposition modeling of triply periodic minimal surface scaffolds with channels and hydrogel for breast reconstruction. Int J Bioprint. 2023;9(2). doi: 10.18063/ijb.685
  25. Allen JW, Bhatia SN. Formation of steady-state oxygen gradients in vitro: application to liver zonation. Biotechnol Bioeng. 2003;82(3):253-262. doi: 10.1002/bit.10569
  26. Brown DA, MacLellan WR, Laks H, Dunn JCY, Wu BM, Beygui RE. Analysis of oxygen transport in a diffusion‐limited model of engineered heart tissue. Biotechnol Bioeng. 2007;97(4):962-975. doi: 10.1002/bit.21295
  27. Yu P, Lee T-S, Zeng Y, Low HT. Fluid dynamics and oxygen transport in a micro-bioreactor with a tissue engineering scaffold. Int J Heat Mass Transfer. 2009;52:316-327. doi: 10.1016/j.ijheatmasstransfer.2008.06.021
  28. Mokhtari-Jafari F, Amoabediny G, Haghighipour N, et al. Mathematical modeling of cell growth in a 3D scaffold and validation of static and dynamic cultures. Eng Life Sci. 2016;16(3):290-298. doi: 10.1002/elsc.201500047
  29. Coletti F, Macchietto S, Elvassore N. Mathematical modeling of three-dimensional cell cultures in perfusion bioreactors. Ind Eng Chem Res. 2006;45:8158-8169. doi: 10.1016/S1570-7946(06)80292-0
  30. Nascu I, Sebastia‐Saez D, Chen T, Du W. A combined computational-fluid-dynamics model and control strategies for perfusion bioreactor systems in tissue engineering. IFAC-PapersOnLine. 2021;54(3):324-329. doi: 10.1016/j.ifacol.2021.08.262
  31. Han X, Bibb R, Harris RA. Design of bifurcation junctions in artificial vascular vessels additively manufactured for skin tissue engineering. J Vis Lang Comput. 2015;28:238-249. doi: 10.1016/j.jvlc.2014.12.005
  32. Han X, Bibb R, Harris RA. Engineering design of artificial vascular junctions for 3D printing. Biofabrication. 2016;8(2):025018. doi: 10.1088/1758-5090/8/2/025018
  33. Nie J, Gao Q, Xie C, et al. Construction of multi-scale vascular chips and modelling of the interaction between tumours and blood vessels. Mater Horiz. 2020;7:82-92. doi: 10.1039/C9MH01283D
  34. Soltani M, Maleki MA, Kaboodrangi AH, Mosadegh B. Optimization of oxygen transport within a tissue engineered vascular graft model using embedded micro-channels inspired by vasa vasorum. Chem Eng Sci. 2018;184:1-13. doi: 10.1016/j.ces.2018.02.044
  35. Poon C. Measuring the density and viscosity of culture media for optimized computational fluid dynamics analysis of in vitro devices. J Mech Behav Biomed Mater. 2022; 126: 105024. doi: 10.1016/j.jmbbm.2021.105024
  36. Haselgrove JC, Shapiro IM, Silverton SF. Computer modeling of the oxygen supply and demand of cells of the avian growth cartilage. Am J Physiol. 1993;265 2 Pt 1:C497-506. doi: 10.1152/ajpcell.1993.265.2.C497
  37. Acevedo CA, Weinstein-Oppenheimer CR, Brown DI, Huebner H, Buchholz R, Young ME. A mathematical model for the design of fibrin microcapsules with skin cells. Bioprocess Biosyst Eng. 2009;32:341-351. doi: 10.1007/s00449-008-0253-1
  38. McMahon D, Anderson PA, Nassar R, et al. C2C12 cells: biophysical, biochemical, and immunocytochemical properties. Am J Physiol. 1994;266 6 Pt 1:C1795-802. doi: 10.1152/ajpcell.1994.266.6.c1795
  39. Schlie S, Gruene M, Dittmar H, Chichkov BN. Dynamics of cell attachment: adhesion time and force. Tissue Eng Part C, Methods. 2012;18(9):688-696. doi: 10.1089/ten.tec.2011.0635
  40. Ricotti L, Taccola S, Pensabene V, et al. Adhesion and proliferation of skeletal muscle cells on single layer poly(lactic acid) ultra-thin films. Biomed Microdevices. 2010;12:809-819. doi: 10.1007/s10544-010-9435-0
  41. Zhou B, Yang B, Liu Q, et al. Effects of univariate stiffness and degradation of DNA hydrogels on the transcriptomics of neural progenitor cells. J Am Chem Soc. 2023;145(16):8954- 8964. doi: 10.1021/jacs.2c13373
  42. Jarrett AM, Lima EABF, Hormuth DA, et al. Mathematical models of tumor cell proliferation: a review of the literature. Expert Rev Anticancer Ther. 2018;18:1271-1286. doi: 10.1080/14737140.2018.1527689
  43. Kim K, Dean D, Mikos AG, Fisher JP. Effect of initial cell seeding density on early osteogenic signal expression of rat bone marrow stromal cells cultured on cross-linked poly(propylene fumarate) disks. Biomacromolecules. 2009;10(7):1810-1817. doi: 10.1021/bm900240k
  44. Yin J, Yan M, Wang Y-c, Fu J, Suo H. 3D bioprinting of low-concentration cell-laden gelatin methacrylate (GelMA) bioinks with a two-step cross-linking strategy. ACS Appl Mater Interfaces. 2018;10(8):6849-6857. doi: 10.1021/acsami.7b16059
  45. Cámara-Torres M, Sinha R, Mota C, Moroni L. Improving cell distribution on 3D additive manufactured scaffolds through engineered seeding media density and viscosity. Acta Biomater. 2020;101:183-195. doi: 10.1016/j.actbio.2019.11.020
  46. Su J, Hua S, Chen A, et al. Three-dimensional printing of gyroid-structured composite bioceramic scaffolds with tuneable degradability. Biomater Adv. 2022;133:112595. doi: 10.1016/j.msec.2021.112595
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing