Microfluidic bubble-generator enables digital light processing 3D printing of porous structures

Abstract

Three-dimensional (3D) printing is an emerging technique that has shown promising success in engineering human tissues in recent years. Further development of vatphotopolymerization printing modalities has significantly enhanced the complexity level for 3D printing of various functional structures and components. Similarly, the development of microfluidic chip systems is an emerging research sector with promising medical applications. This work demonstrates the coupling of a digital light processing (DLP) printing procedure with a microfluidic chip system to produce size-tunable, 3D-printable porosities with narrow pore size distributions within a gelatin methacryloyl (GelMA) hydrogel matrix. It is found that the generation of size-tunable gas bubbles trapped within an aqueous GelMA hydrogel-precursor can be controlled with high precision. Furthermore, the porosities are printed in two-dimensional (2D) as well as in 3D using the DLP printer. In addition, the cytocompatibility of the printed porous scaffolds is investigated using fibroblasts, where high cell viabilities as well as cell proliferation, spreading, and migration are confirmed. It is anticipated that the strategy is widely applicable in a range of application areas such as tissue engineering and regenerative medicine, among others.

Keywords

3D printing / biofabrication / bubble / digital light processing / microfluidics / porous

References

[1] S. V. Murphy, A. Atala, Nat. Biotechnol. 2014, 32, 773.

[2] M. Mobaraki, M. Ghaffari, A. Yazdanpanah, Y. Luo, D. Mills, Bioprinting 2020, 18, e00080.

[3] Y. S. Zhang, R. Oklu, M. R. Dokmeci, A. Khademhosseini, Cold Spring Harb. Perspect. Med. 2018, 8, a025718.

[4] D. Huh, G. A. Hamilton, D. E. Ingber, Trends Cell Biol. 2011, 21, 745.

[5] S. Caddeo, M. Boffito, S. Sartori, Front. Bioeng. Biotechnol. 2017, 5, 40.

[6] L. Moroni, J. A. Burdick, C. Highley, S. J. Lee, Y. Morimoto, S. Takeuchi, J. J. Yoo, Nat. Rev. Mater. 2018, 3, 21.

[7] S.-W. Choi, Y. Zhang, Y. Xia, Langmuir 2010, 26, 19001.

[8] F. J. Maksoud, M. F. V. d. l. Paz, A. J. Hann, J. Thanarak, G. C. Reilly, F. Claeyssens, N. H. Green, Y. S. Zhang, J. Mater. Chem. B 2022, 10, 8111.

[9] S. B. Farid, Bioceramics: for materials science and engineering, Woodhead Publishing, Sawston, UK, 2018.

[10] T. Mays, Stud. Surf. Sci. Catal. 2017, 160, 57.

[11] E. Babaie, S. B. Bhaduri, ACS Biomater. Sci. Eng. 2018, 4, 1.

[12] N. Abbasi, S. Hamlet, R. M. Love, N.-T. Nguyen, J. Sci.: Adv. Mater. Devices 2020, 5, 1.

[13] S. D. Lacey, D. J. Kirsch, Y. Li, J. T. Morgenstern, B. C. Zarket, Y. Yao, J. Dai, L. Q. Garcia, B. Liu, T. Gao, S. Xu, S. R. Raghavan, J. W. Connell, Y. Lin, L. Hu, Adv. Mater. 2018, 30, 1705651.

[14] A. Limper, N. Weber, A. Brodersen, R. Keller, M. Wessling, J. Linkhorst, Electrochem. Commun. 2022, 134, 107176.

[15] L. C. Hwa, S. Rajoo, A. M. Noor, N. Ahmad, M. Uday, Curr. Opin. Solid State Mater. Sci. 2017, 21, 323.

[16] D. Huang, T. Liu, J. Liao, S. Maharjan, X. Xie, M. Perez, I. Anaya, S. Wang, A. T. Mayer, Z. Kang, W. Kong, V. L. Mainardi, C. E Garciamendez-Mijares, G. G. Martinez, M. Moretti, W. Zhang, Z. Gu, A. M Ghaemmaghami, Y. S. Zhang, Proc. Natl. Acad. Sci. 2021, 118, e2016146118.

[17] S.-W. Choi, Y. S. Zhang, M. R. MacEwan, Y. Xia, Adv. Healthc. Mater. 2013, 2, 145.

[18] Y. S. Zhang, C. Zhu, Y. Xia, Adv. Mater. 2017, 29, 1701115.

[19] B. A. Dikici and F. Claeyssens, Front. Bioeng. Biotechnol. 2020, 8, 875.

[20] X. Mu, T. Bertron, C. Dunn, H. Qiao, J. Wu, Z. Zhao, C. Saldana, H. J. Qi, Mater. Horiz. 2017, 4, 442.

[21] Z. Dong, H. Cui, H. Zhang, F. Wang, X. Zhan, F. Mayer, B. Nestler, M. Wegener, P. A. Levkin, Nat. Commun. 2021, 12, 247.

[22] M. Costantini, J. Jaroszewicz, Ł. Kozoń, K. Szlăzak, W. Święszkowski, P. Garstecki, C. Stubenrauch, A. Barbetta, J. Guzowski, Angew. Chem. Int. Ed. 2019, 58, 7620.

[23] M. Marcotulli, M. C. Tirelli, M. Volpi, J. Jaroszewicz, C. Scognamiglio, P. Kasprzycki, K. Karnowski, W. Święszkowski, G. Ruocco, M. Costantini, G. Cidonio, A. Barbetta, Adv. Mater. Technol. 2023, 8, 2201244.

[24] Y. S. Zhang, G. Haghiashtiani, T. Hübscher, D. J. Kelly, J. M. Lee, M. Lutolf, M. C. McAlpine, W. Y. Yeong, M. Zenobi-Wong, J. Malda, Nat. Rev. Dis. Primers. 2021, 1, 75.

[25] C. Yu, J. Schimelman, P. Wang, K. L. Miller, X. Ma, S. You, J. Guan, B. Sun, W. Zhu, S. Chen, Chem. Rev. 2020, 120, 10695.

[26] R. J. Mondschein, A. Kanitkar, C. B. Williams, S. S. Verbridge, T. E. Long, Biomaterials 2017, 140, 170.

[27] A. Bagheri, J. Jin, ACS Appl. Polym. Mater. 2019, 1, 593.

[28] Y. Bao, N. Paunovivć, J. C. Leroux, Adv. Funct. Mater. 2022, 32, 2109864.

[29] W. Li, M. Wang, H. Ma, F. A Chapa-Villarreal, A. O. Lobo, Y. S. Zhang, iScience 2023, 26, 106039.

[30] W. L. Ng, J. M. Lee, M. Zhou, Y.-W. Chen, K.-X. A. Lee, W. Y. Yeong, Y.-F. Shen, Biofabrication 2020, 12, 022001.

[31] W. Li, L. S. Mille, J. A. Robledo, T. Uribe, V. Huerta, Y. S. Zhang, Adv. Healthc. Mater. 2020, 9, 2000156.

[32] A. K. Miri, D. Nieto, L. Iglesias, H. G. Hosseinabadi, S. Maharjan, G. U Ruiz-Esparza, P. Khoshakhlagh, A. Manbachi, M. R. Dokmeci, S. Chen, S. R. Shin, Y. S. Zhang, A. Khademhosseini, Adv. Mater. 2018, 30, 1800242.

[33] M. Wang, W. Li, L. S. Mille, T. Ching, Z. Luo, G. Tang, C. E Garciamendez-Mijares, A. Lesha, M. Hashimoto, Y. S. Zhang, Adv. Mater. 2022, 34, 2107038.

[34] J. Liu, H. H. Hwang, P. Wang, G. Whang, S. Chen, Lab Chip 2016, 16, 1430.

[35] G. Ying, N. Jiang, C. Parra-Cantu, G. Tang, J. Zhang, H. Wang, S. Chen, N.-P. Huang, J. Xie, Y. S. Zhang, Adv. Funct. Mater. 2020, 30, 2003740.

[36] R. Levato, K. S. Lim, W. Li, A. U. Asua, L. B. Peña, M. Wang, M. Falandt, P. N. Bernal, D. Gawlitta, Y. S. Zhang, T. B. Woodfield, J. Malda, Mater. Today Bio. 2021, 12, 100162.

[37] Q. Liu, L. S. Mille, C. Villalobos, I. Anaya, M. Vostatek, S. Yi, W. Li, J. Liao, H. Wu, Y. Song, L. Xiong, Y. S. Zhang, Biodes. Manuf. 2023, 6, 373.

[38] L. Shao, R. Hou, Y. Zhu, Y. Yaoa, Biomater. Sci. 2021, 9, 6763.

[39] M. Wang, W. Li, J. Hao, A. Gonzales III, Z. Zhao, R. S. Flores, X. Kuang, X. Mu, T. Ching, G. Tang, Z. Luo, C. E Garciamendez-Mijares, J. K. Sahoo, M. F. Wells, G. Niu, A. Prajwal Agrawal, Nat. Commun. 2022, 13, 3317.

[40] A. Mata, A. J. Fleischman, S. Roy, J. Micromech. Microeng. 2006, 16, 276.

[41] Y. Xia, G. M. Whitesides, Annu. Rev. Mater. Sci. 1998, 28, 152.

[42] M. Constantini, J. Guzowski, P. J. Zuk, P. Mozetic, S. De Panfilis, J. Jaroszewicz, M. Heljak, M. Massimi, M. Pierron, M. Trombetta, M. Dentini, W. Święszkowski, A. Rainer, P. Garstecki, A. Barbetta, Adv. Funct. Mater. 2018, 28, 1800874.

[43] G. Ying, N. Jiang, C. Yu, Y. S. Zhang, Biodes. Manuf. 2018, 1, 215.

[44] H. Lin, D. Zhang, P. G. Alexander, G. Yang, J. Tan, A. W.-M. Cheng, R. S. Tuan, Biomaterials 2013, 34, 331.

[45] L. Ouyang, J. P. Wojciechowski, J. Tang, Y. Guo, M. M. Stevens, Adv. Healthc. Mater. 2022, 11, 2200027.

[46] J. Gong, C. C. L. Schuurmans, A. M. van Genderen, X. Cao, W. Li, F. Cheng, J. J. He, A. López, V. Huerta, J. Manríquez, R. Li, H. Li, C. Delavaux, S. Sebastian, P. E. Capendale, H. Wang, J. Xie, M. Yu, R. Masereeuw, T. Vermonden, Y. S. Zhang, Nat. Commun. 2020, 11, 1267.

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