AccScience Publishing / IJB / Volume 10 / Issue 2 / DOI: 10.36922/ijb.1797
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RESEARCH ARTICLE

Preparation of tunable hollow composite microfibers assisted by microfluidic spinning and its application in the construction of in vitro neural models

Jingyun Ma1* ,  Wei Li1,2 ,  Lingling Tian2 ,  Xinghua Gao2*
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1 Ningbo Institute of Innovation for Combined Medicine and Engineering, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, China
2 Materials Genome Institute, Shanghai University, Shanghai, China
IJB 2024, 10(2), 1797 https://doi.org/10.36922/ijb.1797
Submitted: 11 September 2023 | Accepted: 7 November 2023 | Published: 11 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/ )
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Abstract

Microfluidic spinning, which has recently emerged as an important approach to processing hydrogels, can handle the flow in the fluid channel and generate microfibers in a controlled and mild manner, and therefore, it is suitable for cell loading, long-term culture, and tissue engineering. In this study, we utilized three-dimensional (3D) printing technology to prepare microfluidic chip templates with different microchannel heights in a one-step manner and obtained microfluidic spinning and microfiber assembly microchips. Hollow calcium alginate (CaA)/gelatin methacrylate (GelMA) composite microfibers were successfully prepared using a microfluidic spinning microchip combined with different fluid-injection strategies. The obtained hollow microfibers had one, two, or three lumens, and different inclusions could be added to the fiber walls. Hollow microfibers with a single lumen were used to load human umbilical vein endothelial cells (HUVECs) and exhibited good cell compatibility and barrier functions. We constructed a neural model based on the HUVEC-loaded hollow microfibers using a customized 3D printer. Using this established neural model, we induced the neural differentiation of rat adrenal medullary pheochromocytoma cells (PC12) using nerve growth factor. Axonal length, tubulin expression, and related gene (GAP-43 and TH) expression in PC12 cells were assessed. The current findings underscore the potential of utilizing microfluidic spinning in in vitro blood–brain barrier simulation, neuropharmaceutical and toxin evaluation, and brain-on-a-chip construction.

Keywords
Microfluidic spinning
Hollow microfiber
3D bioprinting
PC12 cells
Neural differentiation
Funding
This work was supported by the Ningbo Natural Science Foundation (grant no. 2022J252) and Ningbo Medical and Health Leading Academic Discipline Project (grant no. 2022-F04).
Conflict of interest
The authors declare no conflicts of interest.
References
  1. Colosi C, Shin SR, Manoharan V, et al. Microfluidic bioprinting of heterogeneous 3D tissue constructs using low-viscosity bioink. Adv Mater. 2016;28(4):677-684. doi: 10.1002/adma.201503310
  2. Xiao Y, Yang C, Guo B, et al. Bioinspired strong and tough organic–inorganic hybrid fibers. Small Struct. 2023;4(10):2300080. doi: 10.1002/sstr.202300080
  3. Shao L, Gao Q, Xie C, Fu J, Xiang M, He Y. Bioprinting of cell-laden microfiber: can it become a standard product? Adv Healthc Mater. 2019;8(9):1900014. doi: 10.1002/adhm.201900014
  4. Zhang YS, Arneri A, Bersini S, et al. Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. Biomaterials. 2016;110:45-59. doi: 10.1016/j.biomaterials.2016.09.003
  5. Jiao J, Wang F, Huang J-J, et al. Microfluidic hollow fiber with improved stiffness repairs peripheral nerve injury through non-invasive electromagnetic induction and controlled release of NGF. Chem Eng J. 2021;426:131826. doi: 10.1016/j.cej.2021.131826
  6. Chen S, Wu C, Liu A, et al. Biofabrication of nerve fibers with mimetic myelin sheath-like structure and aligned fibrous niche. Biofabrication. 2020;12(3):035013. doi: 10.1088/1758-5090/ab860d
  7. Guo Y, Yan J, Xin JH, et al. Microfluidic-directed biomimetic Bulbine torta-like microfibers based on inhomogeneous viscosity rope-coil effect. Lab Chip. 2021;21(13):2594-2604. doi: 10.1039/d1lc00252j
  8. Bosch-Rue E, Delgado LM, Gil FJ, Perez RA. Direct extrusion of individually encapsulated endothelial and smooth muscle cells mimicking blood vessel structures and vascular native cell alignment. Biofabrication. 2020;13(1):015003. doi: 10.1088/1758-5090/abbd27
  9. Yao K, Li W, Li K, et al. Simple fabrication of multicomponent heterogeneous fibers for cell co-culture via microfluidic spinning. Macromol Biosci. 2020;20(3):1900395. doi: 10.1002/mabi.201900395
  10. Liu Y, Xu P, Liang Z, et al. Hydrogel microfibers with perfusable folded channels for tissue constructs with folded morphology. RSC Adv. 2018;8(42):23475-23480. doi: 10.1039/c8ra04192j
  11. Tian L, Ma J, Li W, Zhang X, Gao X. Microfiber fabricated via microfluidic spinning toward tissue engineering applications. Macromol Biosci. 2023;23(3):2200429. doi: 10.1002/mabi.202200429
  12. Song S, Zhou J, Wan J, et al. Three-dimensional printing of microfiber- reinforced hydrogel loaded with oxymatrine for treating spinal cord injury. Int J Bioprint. 2023;9(3):1-14. doi: 10.18063/ijb.692
  13. Liu X, Yue T, Kojima M, Huang Q, Arai T. Bio-assembling and bioprinting for engineering microvessels from the bottom up. Int J Bioprint. 2021;7(3):3-17. doi: 10.18063/ijb.v7i3.366
  14. Xiao Y, Yang C, Zhai X, et al. Bioinspired tough and strong fibers with hierarchical core–shell structure. Adv Mater Interfaces. 2022;10(2):2201962. doi: 10.1002/admi.202201962
  15. Cheng J, Jun Y, Qin J, Lee S-H. Electrospinning versus microfluidic spinning of functional fibers for biomedical applications. Biomaterials. 2017;114:121-143. doi: 10.1016/j.biomaterials.2016.10.040
  16. Nguyen TPT, Tran BM, Lee NY. Microfluidic approach for the fabrication of cell-laden hollow fibers for endothelial barrier research. J Mater Chem B. 2018;6(38):6057-6066. doi: 10.1039/c8tb02031k
  17. Yu Y, Shang L, Guo J, Wang J, Zhao Y. Design of capillary microfluidics for spinning cell-laden microfibers. Nat Protoc. 2018;13(11):2557-2579. doi: 10.1038/s41596-018-0051-4
  18. Sun J, Chen J, Liu K, Zeng H. Mechanically strong proteinaceous fibers: engineered fabrication by microfluidics. Engineering. 2021;7(5):615-623. doi: 10.1016/j.eng.2021.02.005
  19. Yu Y, Wei W, Wang Y, Xu C, Guo Y, Qin J. Simple spinning of heterogeneous hollow microfibers on chip. Adv Mater. 2016;28(31):6649-6655. doi: 10.1002/adma.201601504
  20. Feng F, He J, Li J, Mao M, Li D. Multicomponent bioprinting of heterogeneous hydrogel constructs based on microfluidic printheads. Int J Bioprint. 2019;5(2):39-48. doi: 10.18063/ijb.v5i2.202
  21. Abrishamkar A, Nilghaz A, Saadatmand M, Naeimirad M, deMello AJ. Microfluidic-assisted fiber production: potentials, limitations, and prospects. Biomicrofluidics. 2022;16(6):061504. doi: 10.1063/5.0129108
  22. Du XY, Li Q, Wu G, Chen S. Multifunctional micro/ nanoscale fibers based on microfluidic spinning technology. Adv Mater. 2019;31(52):1903733. doi: 10.1002/adma.201903733
  23. Filippi M, Buchner T, Yasa O, Weirich S, Katzschmann RK. Microfluidic tissue engineering and bio-actuation. Adv Mater. 2022;34(23):2108427. doi: 10.1002/adma.202108427
  24. Aykar SS, Reynolds DE, McNamara MC, Hashemi NH. Manufacturing of poly(ethylene glycol diacrylate)- based hollow microvessels using microfluidics. RSC Adv. 2020;10(7):4095-4102. doi: 10.1039/c9ra10264g
  25. Lee KH, Shin SJ, Park Y, Lee S-H. Synthesis of cell-laden alginate hollow fibers using microfluidic chips and microvascularized tissue-engineering applications. Small. 2009;5(11):1264-1268. doi: 10.1002/smll.200801667
  26. Zhao M, Liu H, Zhang X, Wang H, Tao T, Qin J. A flexible microfluidic strategy to generate grooved microfibers for guiding cell alignment. Biomater Sci. 2021;9(14): 4880-4890. doi: 10.1039/d1bm00549a
  27. Liu H, Wang Y, Yu Y, Chen W, Jiang L, Qin J. Simple fabrication of inner chitosan-coated alginate hollow microfiber with higher stability. J Biomed Mater Res B Appl Biomater. 2019;107(8):2527-2536. doi: 10.1002/jbm.b.34343
  28. Lee KY, Mooney DJ. Alginate: properties and biomedical applications. Prog Polym Sci. 2012;37(1):106-126. doi: 10.1016/j.progpolymsci.2011.06.003
  29. Wu Z, Cai H, Ao Z, Xu J, Heaps S, Guo F. Microfluidic printing of tunable hollow microfibers for vascular tissue engineering. Adv Mater Technol. 2021;6(8):2000683. doi: 10.1002/admt.202000683
  30. Patil P, Szymanski JM, Feinberg AW. Defined micropatterning of ECM protein adhesive sites on alginate microfibers for engineering highly anisotropic muscle cell bundles. Adv Mater Technol. 2016;1(4):1600003. doi: 10.1002/admt.201600003
  31. Pei Z, Gao M, Xing J, et al. Experimental study on repair of cartilage defects in the rabbits with GelMA-MSCs scaffold prepared by three-dimensional bioprinting. Int J Bioprint. 2023;9(2):176-196. doi: 10.18063/ijb.v9i2.662
  32. Chen Z, Lv Z, Zhang Z, Zhang Y, Cui W. Biomaterials for microfluidic technology. Mater Futures. 1(1):012401. doi: 10.1088/2752-5724/ac39ff
  33. Xie R, Zheng W, Guan L, Ai Y, Liang Q. Engineering of hydrogel materials with perfusable microchannels for building vascularized tissues. Small. 2020;16(15):1902838. doi: 10.1002/smll.201902838
  34. Volpi M, Paradiso A, Costantini M, Świȩszkowski W. Hydrogel-based fiber biofabrication techniques for skeletal muscle tissue engineering. ACS Biomater Sci Eng. 2022;8(2):379-405. doi: 10.1021/acsbiomaterials.1c01145
  35. Bertassoni LE, Cecconi M, Manoharan V, et al. Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip. 2014;14(13):2202-2211. doi: 10.1039/c4lc00030g
  36. Klotz BJ, Gawlitta D, Rosenberg A, Malda J, Melchels FPW. Gelatin-methacryloyl hydrogels: towards biofabrication-based tissue repair. Trends Biotechnol. 2016;34(5):394-407. doi: 10.1016/j.tibtech.2016.01.002
  37. Gauvin R, Chen YC, Lee JW, et al. Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography. Biomaterials. 2012;33(15):3824-3834. doi: 10.1016/j.biomaterials.2012.01.048
  38. Wei D, Sun J, Bolderson J, et al. Continuous fabrication and assembly of spatial cell-laden fibers for a tissue-like construct via a photolithographic-based microfluidic chip. ACS Appl Mater Interfaces. 2017;9(17):14606-14617. doi: 10.1021/acsami.7b00078
  39. Nisbet RM, Gotz J. Amyloid-beta and tau in Alzheimer’s disease: novel pathomechanisms and non-pharmacological treatment strategies. J Alzheimers Dis. 2018;64(s1):S517-S527. doi: 10.3233/JAD-179907
  40. Sveinbjornsdottir S. The clinical symptoms of Parkinson’s disease. J Neurochem. 12016;39(Suppl 1):318-324. doi: 10.1111/jnc.13691
  41. Li W, Yao K, Tian L, Xue C, Zhang X, Gao X. 3D printing of heterogeneous microfibers with multi-hollow structure via microfluidic spinning. J Tissue Eng Regen Med. 2022;16(10):913-922. doi: 10.1002/term.3339
  42. Tan J, Sun X, Zhang J, et al. Exploratory evaluation of EGFR-targeted anti-tumor drugs for lung cancer based on lung-on-a-chip. Biosensors (Basel). 2022;12(8):618. doi: 10.3390/bios12080618
  43. Yang X, Li K, Zhang X, et al. Nanofiber membrane supported lung-on-a-chip microdevice for anti-cancer drug testing. Lab Chip. 2018;18(3):486-495. doi: 10.1039/c7lc01224a
  44. Sun X, Li W, Gong X, et al. Investigating the regulation of neural differentiation and injury in PC12 cells using microstructure topographic cues. Biosensors (Basel). 2021;11(10):399. doi: 10.3390/bios11100399
  45. Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254-271. doi: 10.1016/j.biomaterials.2015.08.045
  46. Tian Y, Wang J, Wang L. Microfluidic fabrication of bioinspired cavity-microfibers for 3D scaffolds. ACS Appl Mater Interfaces. 2018;10(35):29219-29226. doi: 10.1021/acsami.8b09212
  47. Tian L, Shi J, Li W, Zhang Y, Gao X. Hollow microfiber assembly-based endocrine pancreas-on-a-chip for sugar substitute evaluation. Adv Healthc Mater. 2023: 2302104. doi: 10.1002/adhm.202302104
  48. Zuo Y, He X, Yang Y, et al. Microfluidic-based generation of functional microfibers for biomimetic complex tissue construction. Acta Biomater. 2016;38:153-162. doi: 10.1016/j.actbio.2016.04.036
  49. Shi X, Ostrovidov S, Zhao Y, et al. Microfluidic spinning of cell-responsive grooved microfibers. Adv Funct Mater. 2015;25(15):2250-2259. doi: 10.1002/adfm.201404531
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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