3D bioprinting lobule-like hepatorganoids with induced vascularization for orthotopic implantation
Orthotopic implantation in vivo is the ultimate target of tissue-engineering organoids research, aiming to achieve sustaining survival after implantation. However, the limited representation of a complex microenvironment in implanted accepter hampers a comprehensive understanding of long-term mainte...
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Elsevier
2025-04-01
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| Series: | Materials Today Bio |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425000730 |
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| author | Jianing Yan Zhichao Ye Yiwei Lu Yuyang Yuan Xiaofeng Wang Tingting Yan Jun Yin Yifan Wang |
| author_facet | Jianing Yan Zhichao Ye Yiwei Lu Yuyang Yuan Xiaofeng Wang Tingting Yan Jun Yin Yifan Wang |
| author_sort | Jianing Yan |
| collection | DOAJ |
| description | Orthotopic implantation in vivo is the ultimate target of tissue-engineering organoids research, aiming to achieve sustaining survival after implantation. However, the limited representation of a complex microenvironment in implanted accepter hampers a comprehensive understanding of long-term maintenance of tissue-engineering organoids, especially in liver. In this research, we developed a 3D bioprinting method using gelatin methacryloyl (GelMA) hydrogel to fabricate lobule-like hepatorganoids, which faithfully mimic the structure of hepatic lobules with lower level of hypoxia (lobule vs 60°, 90°, control; 0.4880 vs 1.009, 0.6778, 0.8704; p < 0.01), high secretion of albumin (lobule vs 60°, 90°, control; 13.47 vs 12.39, 12.65, 10.08 mg/L; p < 0.01) and urea (lobule vs 60°, 90°, control; 5.304 vs 5.233, 4.781, 4.358 mg/L; p < 0.01) in vitro; and promotion of angiogenesis and maintenance of activity following orthotopic implantation. Loaded with a prolonged released system of vascular endothelial growth factor (VEGF) and infused with human umbilical vein endothelial cells (HUVECs), we developed a fabricating method of vascularized lobule-like hepatorganoids (VLH) which possessed promoted vascularization. We identified GAS6/AXL and LAMB3/ITGA3 signaling pathway up-regulated in VLH, which was conducive to vascularization and proliferation. Furthermore, orthotopic implantation model indicated that VLH exhibited prolonged survival in vivo, with elevated level of serological biomarkers and more abundant vascularization in grafts. Eventually, our findings demonstrate that this system effectively forms orthotopic implantation of hepatorganoids and facilitates vascularization, which may notably contribute to the understanding of transplantation, drug screening, and replacement therapy. |
| format | Article |
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| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
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| series | Materials Today Bio |
| spelling | doaj-art-50a18d39abc84d438068d330c5eb8c0b2025-01-27T04:22:08ZengElsevierMaterials Today Bio2590-00642025-04-01311015153D bioprinting lobule-like hepatorganoids with induced vascularization for orthotopic implantationJianing Yan0Zhichao Ye1Yiwei Lu2Yuyang Yuan3Xiaofeng Wang4Tingting Yan5Jun Yin6Yifan Wang7Department of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China; National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou, 310016, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China; National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou, 310016, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China; National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou, 310016, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China; National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou, 310016, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, ChinaDepartment of Plastic Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China; National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou, 310016, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, ChinaThe State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310028, China; Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310028, China; Corresponding author. The State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310028, China.Department of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China; National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou, 310016, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China; Corresponding author. Department of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, 310016, China.Orthotopic implantation in vivo is the ultimate target of tissue-engineering organoids research, aiming to achieve sustaining survival after implantation. However, the limited representation of a complex microenvironment in implanted accepter hampers a comprehensive understanding of long-term maintenance of tissue-engineering organoids, especially in liver. In this research, we developed a 3D bioprinting method using gelatin methacryloyl (GelMA) hydrogel to fabricate lobule-like hepatorganoids, which faithfully mimic the structure of hepatic lobules with lower level of hypoxia (lobule vs 60°, 90°, control; 0.4880 vs 1.009, 0.6778, 0.8704; p < 0.01), high secretion of albumin (lobule vs 60°, 90°, control; 13.47 vs 12.39, 12.65, 10.08 mg/L; p < 0.01) and urea (lobule vs 60°, 90°, control; 5.304 vs 5.233, 4.781, 4.358 mg/L; p < 0.01) in vitro; and promotion of angiogenesis and maintenance of activity following orthotopic implantation. Loaded with a prolonged released system of vascular endothelial growth factor (VEGF) and infused with human umbilical vein endothelial cells (HUVECs), we developed a fabricating method of vascularized lobule-like hepatorganoids (VLH) which possessed promoted vascularization. We identified GAS6/AXL and LAMB3/ITGA3 signaling pathway up-regulated in VLH, which was conducive to vascularization and proliferation. Furthermore, orthotopic implantation model indicated that VLH exhibited prolonged survival in vivo, with elevated level of serological biomarkers and more abundant vascularization in grafts. Eventually, our findings demonstrate that this system effectively forms orthotopic implantation of hepatorganoids and facilitates vascularization, which may notably contribute to the understanding of transplantation, drug screening, and replacement therapy.http://www.sciencedirect.com/science/article/pii/S2590006425000730 |
| spellingShingle | Jianing Yan Zhichao Ye Yiwei Lu Yuyang Yuan Xiaofeng Wang Tingting Yan Jun Yin Yifan Wang 3D bioprinting lobule-like hepatorganoids with induced vascularization for orthotopic implantation Materials Today Bio |
| title | 3D bioprinting lobule-like hepatorganoids with induced vascularization for orthotopic implantation |
| title_full | 3D bioprinting lobule-like hepatorganoids with induced vascularization for orthotopic implantation |
| title_fullStr | 3D bioprinting lobule-like hepatorganoids with induced vascularization for orthotopic implantation |
| title_full_unstemmed | 3D bioprinting lobule-like hepatorganoids with induced vascularization for orthotopic implantation |
| title_short | 3D bioprinting lobule-like hepatorganoids with induced vascularization for orthotopic implantation |
| title_sort | 3d bioprinting lobule like hepatorganoids with induced vascularization for orthotopic implantation |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425000730 |
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