Research progress of three-dimensional bioprinting technology in auricle repair and reconstruction_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHEN Xiaolei ¹ , HU Haolei ² ^# ,  LI Yi ² , YUE Wei ² , ZHANG Xiujing ³ , SHEN Dexin ² , MA Wenlai ² , XING Peimei ² , ZHANG Yage ² , GUAN Taihong ²

1. Xinxiang Medical University, Xinxiang Henan, 453003, P. R. China;
2. Department of Otolaryngology, Head and Neck Surgery, the 988th Hospital of Joint Logistics Support Force of Chinese PLA, Zhengzhou Henan, 450042, P. R. China;
3. Fuxing Road Outpatient Department of Jingnan Medical District, General Hospital of Chinese PLA, Beijing, 100089, P. R. China;

Corresponding author：

LI Yi, Email: liyi153@aliyun.com

Keywords：

Three-dimensional bioprinting technology; auricle repair and reconstruction; tissue engineered scaffold; bioink

DOI：

10.7507/1002-1892.202403001

Video：

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Objective To review the research progress on the application of three-dimensional (3D) bioprinting technology in auricle repair and reconstruction. Methods The recent domestic and international research literature on 3D printing and auricle repair and reconstruction was extensively reviewed, and the concept of 3D bioprinting technology and research progress in auricle repair and reconstruction were summarized. Results The auricle possesses intricate anatomical structure and functionality, necessitating precise tissue reconstruction and morphological replication. Hence, 3D printing technology holds immense potential in auricle reconstruction. In contrast to conventional 3D printing technology, 3D bioprinting technology not only enables the simulation of auricular outer shape but also facilitates the precise distribution of cells within the scaffold during fabrication by incorporating cells into bioink. This approach mimics the composition and structure of natural tissues, thereby favoring the construction of biologically active auricular tissues and enhancing tissue repair outcomes. Conclusion 3D bioprinting technology enables the reconstruction of auricular tissues, avoiding potential complications associated with traditional autologous cartilage grafting. The primary challenge in current research lies in identifying bioinks that meet both the mechanical requirements of complex tissues and biological criteria.

Citation： CHEN Xiaolei, HU Haolei, LI Yi, YUE Wei, ZHANG Xiujing, SHEN Dexin, MA Wenlai, XING Peimei, ZHANG Yage, GUAN Taihong. Research progress of three-dimensional bioprinting technology in auricle repair and reconstruction. Chinese Journal of Reparative and Reconstructive Surgery, 2024, 38(6): 763-768. doi: 10.7507/1002-1892.202403001 Copy

1.	Huang Y, Huang X, Li K, et al. Risk factors of isolated microtia: a systematic review and meta-analysis. Plast Reconstr Surg, 2023, 151(4): 651e-663e.
2.	Xu Z, Li Y, Li D, et al. Strategies for ear elevation and the treatment of relevant complications in autologous cartilage microtia reconstruction. Sci Rep, 2022, 12(1): 13536. doi: 10.1038/s41598-022-17007-3.
3.	Lee DJ, Kwon J, Kim YI, et al. Coating Medpor^® implant with tissue-engineered elastic cartilage. J Funct Biomater, 2020, 11(2): 34. doi: 10.3390/jfb11020034.
4.	Enomura M, Murata S, Terado Y, et al. Development of a method for scaffold-free elastic cartilage creation. Int J Mol Sci, 2020, 21(22): 8496. doi: 10.3390/ijms21228496.
5.	Brennan JR, Cornett A, Chang B, et al. Preclinical assessment of clinically streamlined, 3D-printed, biocompatible single- and two-stage tissue scaffolds for ear reconstruction. J Biomed Mater Res B Appl Biomater, 2021, 109(3): 394-400.
6.	Mohamed EN, Elshahat A, Hany HE, et al. Segmentation of the 3D printed mirror image auricular model to ease sculpture of the costal cartilages in total auricular aesthetic reconstruction. Asian J Surg, 2023, 46(12): 5429-5437.
7.	Nandra N, Jovic TH, Ali SR, et al. Models and materials for teaching auricular framework carving: A systematic review. J Plast Reconstr Aesthet Surg, 2023, 87: 98-108.
8.	Zhao T, Liu Y, Wu Y, et al. Controllable and biocompatible 3D bioprinting technology for microorganisms: Fundamental, environmental applications and challenges. Biotechnol Adv, 2023, 69: 108243. doi: 10.1016/j.biotechadv.2023.108243.
9.	McMillan A, McMillan N, Gupta N, et al. 3D bioprinting in otolaryngology: a review. Adv Healthc Mater, 2023, 12(19): e2203268. doi: 10.1002/adhm.202203268.
10.	Placone JK, Engler AJ. Recent advances in extrusion-based 3D printing for biomedical applications. Adv Healthc Mater, 2018, 7(8): e1701161. doi: 10.1002/adhm.201701161.
11.	Gillispie G, Prim P, Copus J, et al. Assessment methodologies for extrusion-based bioink printability. Biofabrication, 2020, 12(2): 022003. doi: 10.1088/1758-5090/ab6f0d.
12.	Shiwarski DJ, Hudson AR, Tashman JW, et al. Emergence of FRESH 3D printing as a platform for advanced tissue biofabrication. APL Bioeng, 2021, 5(1): 010904. doi: 10.1063/5.0032777.
13.	Ji Y, Yang Q, Huang G, et al. Improved resolution and fidelity of droplet-based bioprinting by upward ejection. ACS Biomater Sci Eng, 2019, 5(8): 4112-4121.
14.	Kotlarz M, Ferreira AM, Gentile P, et al. Droplet-based bioprinting enables the fabrication of cell-hydrogel-microfibre composite tissue precursors. Bio-Des Manuf, 2022, 5: 512-528.
15.	Vitalis C, Wenzel T. Leveraging interactions in microfluidic droplets for enhanced biotechnology screens. Curr Opin Biotechnol, 2023, 82: 102966. doi: 10.1016/j.copbio.2023.102966.
16.	Hossain Rakin R, Kumar H, Rajeev A, et al. Tunable metacrylated hyaluronic acid-based hybrid bioinks for stereolithography 3D bioprinting. Biofabrication, 2021, 13(4). doi: 10.1088/1758-5090/ac25cb.
17.	Mondschein RJ, Kanitkar A, Williams CB, et al. Polymer structure-property requirements for stereolithographic 3D printing of soft tissue engineering scaffolds. Biomaterials, 2017, 140: 170-188.
18.	Kérourédan O, Hakobyan D, Rémy M, et al. In situ prevascularization designed by laser-assisted bioprinting: effect on bone regeneration. Biofabrication, 2019, 11(4): 045002. doi: 10.1088/1758-5090/ab2620.
19.	Zhang M, Xu C, Jiang L, et al. A 3D human lung-on-a-chip model for nanotoxicity testing. Toxicol Res (Camb), 2018, 7(6): 1048-1060.
20.	Douillet C, Nicodeme M, Hermant L, et al. From local to global matrix organization by fibroblasts: a 4D laser-assisted bioprinting approach. Biofabrication, 2022, 14(2). doi: 10.1088/17585090/ac40ed.
21.	Kim HY, Jung SY, Lee SJ, et al. Fabrication and characterization of 3D-printed elastic auricular scaffolds: A pilot study. Laryngoscope, 2019, 129(2): 351-357.
22.	Tang P, Song P, Peng Z, et al. Chondrocyte-laden GelMA hydrogel combined with 3D printed PLA scaffolds for auricle regeneration. Mater Sci Eng C Mater Biol Appl, 2021, 130: 112423. doi: 10.1016/j.msec.2021.112423.
23.	Xie ZT, Zeng J, Kang DH, et al. 3D printing of collagen scaffold with enhanced resolution in a citrate-modulated gellan gum microgel bath. Adv Healthc Mater, 2023, 12(27): e2301090. doi: 10.1002/adhm.202301090.
24.	Chang B, Cornett A, Nourmohammadi Z, et al. Hybrid three-dimensional-printed ear tissue scaffold with autologous cartilage mitigates soft tissue complications. Laryngoscope, 2021, 131(5): 1008-1015.
25.	Wang H, Zhang J, Liu H, et al. Chondrocyte-laden gelatin/sodium alginate hydrogel integrating 3D printed PU scaffold for auricular cartilage reconstruction. Int J Biol Macromol, 2023, 253(Pt 1): 126294. doi: 10.1016/j.ijbiomac.2023.126294.
26.	Otto IA, Capendale PE, Garcia JP, et al. Biofabrication of a shape-stable auricular structure for the reconstruction of ear deformities. Mater Today Bio, 2021, 9: 100094. doi: 10.1016/j.mtbio.2021.100094.
27.	Hassan TA, Maher MA, El Karmoty AF, et al. Auricular cartilage regeneration using different types of mesenchymal stem cells in rabbits. Biol Res, 2022, 55(1): 40. doi: 10.1186/s40659-022-00408-z.
28.	Posniak S, Chung JHY, Liu X, et al. Bioprinting of chondrocyte stem cell co-cultures for auricular cartilage regeneration. ACS Omega, 2022, 7(7): 5908-5920.
29.	Landau S, Szklanny AA, Machour M, et al. Human-engineered auricular reconstruction (hEAR) by 3D-printed molding with human-derived auricular and costal chondrocytes and adipose-derived mesenchymal stem cells. Biofabrication, 2021, 14(1). doi: 10.1088/1758-5090/ac3b91.
30.	Jang CH, Koo Y, Kim G. ASC/chondrocyte-laden alginate hydrogel/PCL hybrid scaffold fabricated using 3D printing for auricle regeneration. Carbohydr Polym, 2020, 248: 116776. doi: 10.1016/j.carbpol.2020.116776.
31.	Neufurth M, Wang S, Schröder HC, et al. 3D bioprinting of tissue units with mesenchymal stem cells, retaining their proliferative and differentiating potential, in polyphosphate-containing bio-ink. Biofabrication, 2021, 14(1). doi: 10.1088/1758-5090/ac3f29.
32.	Jakob Y, Kern J, Gvaramia D, et al. Suitability of ex vivo-expanded microtic perichondrocytes for auricular reconstruction. Cells, 2024, 13(2): 141. doi: 10.3390/cells13020141.
33.	Wei X, Zhou W, Tang Z, et al. Magnesium surface-activated 3D printed porous PEEK scaffolds for in vivo osseointegration by promoting angiogenesis and osteogenesis. Bioact Mater, 2023, 20: 16-28.
34.	Lee HA, Park E, Lee H. Polydopamine and its derivative surface chemistry in material science: a focused review for studies at KAIST. Adv Mater, 2020, 32(35): e1907505. doi: 10.1002/adma.201907505.
35.	Yin J, Zhong J, Wang J, et al. 3D-printed high-density polyethylene scaffolds with bioactive and antibacterial layer-by-layer modification for auricle reconstruction. Mater Today Bio, 2022, 16: 100361. doi: 10.1016/j.mtbio.2022.100361.
36.	Xie X, Wu S, Mou S, et al. Microtissue-based bioink as a chondrocyte microshelter for DLP bioprinting. Adv Healthc Mater, 2022, 11(22): e2201877. doi: 10.1002/adhm.202201877.
37.	Huang B, Li P, Chen M, et al. Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications. J Nanobiotechnology, 2022, 20(1): 25. doi: 10.1186/s12951-021-01230-7.
38.	Zeng J, Jia L, Wang D, et al. Bacterial nanocellulose-reinforced gelatin methacryloyl hydrogel enhances biomechanical property and glycosaminoglycan content of 3D-bioprinted cartilage. Int J Bioprint, 2022, 9(1): 631. doi: 10.18063/ijb.v9i1.631.
39.	Bhamare N, Tardalkar K, Parulekar P, et al. 3D printing of human ear pinna using cartilage specific ink. Biomed Mater, 2021, 16(5). doi: 10.1088/1748-605X/ac15b0.
40.	Jia L, Hua Y, Zeng J, et al. Bioprinting and regeneration of auricular cartilage using a bioactive bioink based on microporous photocrosslinkable acellular cartilage matrix. Bioact Mater, 2022, 16: 66-81.
41.	Visscher DO, Lee H, van Zuijlen PPM, et al. A photo-crosslinkable cartilage-derived extracellular matrix bioink for auricular cartilage tissue engineering. Acta Biomater, 2021, 121: 193-203.
42.	Nam GH, Choi Y, Kim GB, et al. Emerging prospects of exosomes for cancer treatment: from conventional therapy to immunotherapy. Adv Mater, 2020, 32(51): e2002440. doi: 10.1002/adma.202002440.
43.	Guo R, Fan J. Extracellular vesicles derived from auricular chondrocytes facilitate cartilage differentiation of adipose-derived mesenchymal stem cells. Aesthetic Plast Surg, 2023, 47(6): 2823-2832.
44.	Chen J, Huang T, Liu R, et al. Congenital microtia patients: the genetically engineered exosomes released from porous gelatin methacryloyl hydrogel for downstream small RNA profiling, functional modulation of microtia chondrocytes and tissue-engineered ear cartilage regeneration. J Nanobiotechnology, 2022, 20(1): 164. doi: 10.1186/s12951-022-01352-6.

1. Huang Y, Huang X, Li K, et al. Risk factors of isolated microtia: a systematic review and meta-analysis. Plast Reconstr Surg, 2023, 151(4): 651e-663e.
2. Xu Z, Li Y, Li D, et al. Strategies for ear elevation and the treatment of relevant complications in autologous cartilage microtia reconstruction. Sci Rep, 2022, 12(1): 13536. doi: 10.1038/s41598-022-17007-3.
3. Lee DJ, Kwon J, Kim YI, et al. Coating Medpor^® implant with tissue-engineered elastic cartilage. J Funct Biomater, 2020, 11(2): 34. doi: 10.3390/jfb11020034.
4. Enomura M, Murata S, Terado Y, et al. Development of a method for scaffold-free elastic cartilage creation. Int J Mol Sci, 2020, 21(22): 8496. doi: 10.3390/ijms21228496.
5. Brennan JR, Cornett A, Chang B, et al. Preclinical assessment of clinically streamlined, 3D-printed, biocompatible single- and two-stage tissue scaffolds for ear reconstruction. J Biomed Mater Res B Appl Biomater, 2021, 109(3): 394-400.
6. Mohamed EN, Elshahat A, Hany HE, et al. Segmentation of the 3D printed mirror image auricular model to ease sculpture of the costal cartilages in total auricular aesthetic reconstruction. Asian J Surg, 2023, 46(12): 5429-5437.
7. Nandra N, Jovic TH, Ali SR, et al. Models and materials for teaching auricular framework carving: A systematic review. J Plast Reconstr Aesthet Surg, 2023, 87: 98-108.
8. Zhao T, Liu Y, Wu Y, et al. Controllable and biocompatible 3D bioprinting technology for microorganisms: Fundamental, environmental applications and challenges. Biotechnol Adv, 2023, 69: 108243. doi: 10.1016/j.biotechadv.2023.108243.
9. McMillan A, McMillan N, Gupta N, et al. 3D bioprinting in otolaryngology: a review. Adv Healthc Mater, 2023, 12(19): e2203268. doi: 10.1002/adhm.202203268.
10. Placone JK, Engler AJ. Recent advances in extrusion-based 3D printing for biomedical applications. Adv Healthc Mater, 2018, 7(8): e1701161. doi: 10.1002/adhm.201701161.
11. Gillispie G, Prim P, Copus J, et al. Assessment methodologies for extrusion-based bioink printability. Biofabrication, 2020, 12(2): 022003. doi: 10.1088/1758-5090/ab6f0d.
12. Shiwarski DJ, Hudson AR, Tashman JW, et al. Emergence of FRESH 3D printing as a platform for advanced tissue biofabrication. APL Bioeng, 2021, 5(1): 010904. doi: 10.1063/5.0032777.
13. Ji Y, Yang Q, Huang G, et al. Improved resolution and fidelity of droplet-based bioprinting by upward ejection. ACS Biomater Sci Eng, 2019, 5(8): 4112-4121.
14. Kotlarz M, Ferreira AM, Gentile P, et al. Droplet-based bioprinting enables the fabrication of cell-hydrogel-microfibre composite tissue precursors. Bio-Des Manuf, 2022, 5: 512-528.
15. Vitalis C, Wenzel T. Leveraging interactions in microfluidic droplets for enhanced biotechnology screens. Curr Opin Biotechnol, 2023, 82: 102966. doi: 10.1016/j.copbio.2023.102966.
16. Hossain Rakin R, Kumar H, Rajeev A, et al. Tunable metacrylated hyaluronic acid-based hybrid bioinks for stereolithography 3D bioprinting. Biofabrication, 2021, 13(4). doi: 10.1088/1758-5090/ac25cb.
17. Mondschein RJ, Kanitkar A, Williams CB, et al. Polymer structure-property requirements for stereolithographic 3D printing of soft tissue engineering scaffolds. Biomaterials, 2017, 140: 170-188.
18. Kérourédan O, Hakobyan D, Rémy M, et al. In situ prevascularization designed by laser-assisted bioprinting: effect on bone regeneration. Biofabrication, 2019, 11(4): 045002. doi: 10.1088/1758-5090/ab2620.
19. Zhang M, Xu C, Jiang L, et al. A 3D human lung-on-a-chip model for nanotoxicity testing. Toxicol Res (Camb), 2018, 7(6): 1048-1060.
20. Douillet C, Nicodeme M, Hermant L, et al. From local to global matrix organization by fibroblasts: a 4D laser-assisted bioprinting approach. Biofabrication, 2022, 14(2). doi: 10.1088/17585090/ac40ed.
21. Kim HY, Jung SY, Lee SJ, et al. Fabrication and characterization of 3D-printed elastic auricular scaffolds: A pilot study. Laryngoscope, 2019, 129(2): 351-357.
22. Tang P, Song P, Peng Z, et al. Chondrocyte-laden GelMA hydrogel combined with 3D printed PLA scaffolds for auricle regeneration. Mater Sci Eng C Mater Biol Appl, 2021, 130: 112423. doi: 10.1016/j.msec.2021.112423.
23. Xie ZT, Zeng J, Kang DH, et al. 3D printing of collagen scaffold with enhanced resolution in a citrate-modulated gellan gum microgel bath. Adv Healthc Mater, 2023, 12(27): e2301090. doi: 10.1002/adhm.202301090.
24. Chang B, Cornett A, Nourmohammadi Z, et al. Hybrid three-dimensional-printed ear tissue scaffold with autologous cartilage mitigates soft tissue complications. Laryngoscope, 2021, 131(5): 1008-1015.
25. Wang H, Zhang J, Liu H, et al. Chondrocyte-laden gelatin/sodium alginate hydrogel integrating 3D printed PU scaffold for auricular cartilage reconstruction. Int J Biol Macromol, 2023, 253(Pt 1): 126294. doi: 10.1016/j.ijbiomac.2023.126294.
26. Otto IA, Capendale PE, Garcia JP, et al. Biofabrication of a shape-stable auricular structure for the reconstruction of ear deformities. Mater Today Bio, 2021, 9: 100094. doi: 10.1016/j.mtbio.2021.100094.
27. Hassan TA, Maher MA, El Karmoty AF, et al. Auricular cartilage regeneration using different types of mesenchymal stem cells in rabbits. Biol Res, 2022, 55(1): 40. doi: 10.1186/s40659-022-00408-z.
28. Posniak S, Chung JHY, Liu X, et al. Bioprinting of chondrocyte stem cell co-cultures for auricular cartilage regeneration. ACS Omega, 2022, 7(7): 5908-5920.
29. Landau S, Szklanny AA, Machour M, et al. Human-engineered auricular reconstruction (hEAR) by 3D-printed molding with human-derived auricular and costal chondrocytes and adipose-derived mesenchymal stem cells. Biofabrication, 2021, 14(1). doi: 10.1088/1758-5090/ac3b91.
30. Jang CH, Koo Y, Kim G. ASC/chondrocyte-laden alginate hydrogel/PCL hybrid scaffold fabricated using 3D printing for auricle regeneration. Carbohydr Polym, 2020, 248: 116776. doi: 10.1016/j.carbpol.2020.116776.
31. Neufurth M, Wang S, Schröder HC, et al. 3D bioprinting of tissue units with mesenchymal stem cells, retaining their proliferative and differentiating potential, in polyphosphate-containing bio-ink. Biofabrication, 2021, 14(1). doi: 10.1088/1758-5090/ac3f29.
32. Jakob Y, Kern J, Gvaramia D, et al. Suitability of ex vivo-expanded microtic perichondrocytes for auricular reconstruction. Cells, 2024, 13(2): 141. doi: 10.3390/cells13020141.
33. Wei X, Zhou W, Tang Z, et al. Magnesium surface-activated 3D printed porous PEEK scaffolds for in vivo osseointegration by promoting angiogenesis and osteogenesis. Bioact Mater, 2023, 20: 16-28.
34. Lee HA, Park E, Lee H. Polydopamine and its derivative surface chemistry in material science: a focused review for studies at KAIST. Adv Mater, 2020, 32(35): e1907505. doi: 10.1002/adma.201907505.
35. Yin J, Zhong J, Wang J, et al. 3D-printed high-density polyethylene scaffolds with bioactive and antibacterial layer-by-layer modification for auricle reconstruction. Mater Today Bio, 2022, 16: 100361. doi: 10.1016/j.mtbio.2022.100361.
36. Xie X, Wu S, Mou S, et al. Microtissue-based bioink as a chondrocyte microshelter for DLP bioprinting. Adv Healthc Mater, 2022, 11(22): e2201877. doi: 10.1002/adhm.202201877.
37. Huang B, Li P, Chen M, et al. Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications. J Nanobiotechnology, 2022, 20(1): 25. doi: 10.1186/s12951-021-01230-7.
38. Zeng J, Jia L, Wang D, et al. Bacterial nanocellulose-reinforced gelatin methacryloyl hydrogel enhances biomechanical property and glycosaminoglycan content of 3D-bioprinted cartilage. Int J Bioprint, 2022, 9(1): 631. doi: 10.18063/ijb.v9i1.631.
39. Bhamare N, Tardalkar K, Parulekar P, et al. 3D printing of human ear pinna using cartilage specific ink. Biomed Mater, 2021, 16(5). doi: 10.1088/1748-605X/ac15b0.
40. Jia L, Hua Y, Zeng J, et al. Bioprinting and regeneration of auricular cartilage using a bioactive bioink based on microporous photocrosslinkable acellular cartilage matrix. Bioact Mater, 2022, 16: 66-81.
41. Visscher DO, Lee H, van Zuijlen PPM, et al. A photo-crosslinkable cartilage-derived extracellular matrix bioink for auricular cartilage tissue engineering. Acta Biomater, 2021, 121: 193-203.
42. Nam GH, Choi Y, Kim GB, et al. Emerging prospects of exosomes for cancer treatment: from conventional therapy to immunotherapy. Adv Mater, 2020, 32(51): e2002440. doi: 10.1002/adma.202002440.
43. Guo R, Fan J. Extracellular vesicles derived from auricular chondrocytes facilitate cartilage differentiation of adipose-derived mesenchymal stem cells. Aesthetic Plast Surg, 2023, 47(6): 2823-2832.
44. Chen J, Huang T, Liu R, et al. Congenital microtia patients: the genetically engineered exosomes released from porous gelatin methacryloyl hydrogel for downstream small RNA profiling, functional modulation of microtia chondrocytes and tissue-engineered ear cartilage regeneration. J Nanobiotechnology, 2022, 20(1): 164. doi: 10.1186/s12951-022-01352-6.

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Research progress of three-dimensional bioprinting technology in auricle repair and reconstruction

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