3D‐Printed Titanium Trabecular Scaffolds with Sustained Release of Hypoxia‐Induced Exosomes for Dual‐Mimetic Bone Regeneration
Abstract Current Ti‐6Al‐4V bone implants lack trabecular structure and pro‑angiogenic cues, both essential for regeneration. Herein, a dual biomimetic strategy is devised that integrates a 3D‐printed biomimetic trabecular porous Ti‐6Al‐4V scaffold (BTPS) with exosome‐loaded PEGDA/GelMA hydrogel micr...
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Wiley
2025-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202500599 |
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| author | Lincong Luo Weihan Zheng Jiaying Li Tingting Chen Wanting Xue Tao Lin Mingrui Liu Zi Yan Jiaxin Yang Jiamin Li Jiahao Pu Yaobin Wu Konghe Hu Shiyu Li Wenhua Huang |
| author_facet | Lincong Luo Weihan Zheng Jiaying Li Tingting Chen Wanting Xue Tao Lin Mingrui Liu Zi Yan Jiaxin Yang Jiamin Li Jiahao Pu Yaobin Wu Konghe Hu Shiyu Li Wenhua Huang |
| author_sort | Lincong Luo |
| collection | DOAJ |
| description | Abstract Current Ti‐6Al‐4V bone implants lack trabecular structure and pro‑angiogenic cues, both essential for regeneration. Herein, a dual biomimetic strategy is devised that integrates a 3D‐printed biomimetic trabecular porous Ti‐6Al‐4V scaffold (BTPS) with exosome‐loaded PEGDA/GelMA hydrogel microspheres (PGHExo) designed for sustained release. BTPS is designed using Voronoi algorithms and imaging data, and replicates the geometry and mechanical properties of natural bone. Hypoxia‐induced human umbilical vein endothelial cell (HUVEC) derived exosomes (HExo) are encapsulated in PGHExo microspheres via microfluidic technology, enabling controlled release of HExo, and anchored onto BTPS using polydopamine (pDA) modification (BTPS&pDA@PGHExo). BTPS exhibited an elastic modulus of ≈3.2 GPa and a permeability of 11.52 × 10−8 mm2, mimicking natural bone. In vitro assays demonstrated that BTPS&pDA@PGHExo significantly enhanced osteogenesis and angiogenesis. mRNA‐Seq analysis suggested that BTPS&pDA@PGHExo regulates osteogenic and angiogenic gene expression through the activation of pathways including MAPK, mTOR, HIF‐1, and VEGF. In vivo, BTPS&pDA@PGHExo improved bone volume, density, and neovascularization in a rabbit model. This dual biomimetic strategy offers a promising clinical solution, addressing the limitations of conventional Ti‐6Al‐4V scaffolds and providing an innovative approach for personalized bone defect repair. |
| format | Article |
| id | doaj-art-57de852861b443e0845e23409b3e2e93 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-57de852861b443e0845e23409b3e2e932025-08-20T02:36:40ZengWileyAdvanced Science2198-38442025-06-011223n/an/a10.1002/advs.2025005993D‐Printed Titanium Trabecular Scaffolds with Sustained Release of Hypoxia‐Induced Exosomes for Dual‐Mimetic Bone RegenerationLincong Luo0Weihan Zheng1Jiaying Li2Tingting Chen3Wanting Xue4Tao Lin5Mingrui Liu6Zi Yan7Jiaxin Yang8Jiamin Li9Jiahao Pu10Yaobin Wu11Konghe Hu12Shiyu Li13Wenhua Huang14Yue Bei People's Hospital Postdoctoral Innovation Practice Base Southern Medical University Guangzhou Guangdong 510515 ChinaGuangdong Medical Innovation Platform for Translation of 3D Printing Application The Third Affiliated Hospital of Southern Medical University Southern Medical University Guangzhou Guangdong 510630 ChinaGuangdong Engineering Research Center for Translation of Medical 3D Printing Application Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics National Key Discipline of Human Anatomy School of Basic Medical Sciences Southern Medical University Guangzhou Guangdong 510515 ChinaSchool of Basic Medical Sciences Fujian Medical University Fuzhou Fujian 350108 ChinaGuangdong Engineering Research Center for Translation of Medical 3D Printing Application Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics National Key Discipline of Human Anatomy School of Basic Medical Sciences Southern Medical University Guangzhou Guangdong 510515 ChinaGuangdong Engineering Research Center for Translation of Medical 3D Printing Application Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics National Key Discipline of Human Anatomy School of Basic Medical Sciences Southern Medical University Guangzhou Guangdong 510515 ChinaSchool of Basic Medicine Dali University Dali Yunnan 671003 ChinaGuangdong Medical Innovation Platform for Translation of 3D Printing Application The Third Affiliated Hospital of Southern Medical University Southern Medical University Guangzhou Guangdong 510630 ChinaGuangdong Engineering Research Center for Translation of Medical 3D Printing Application Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics National Key Discipline of Human Anatomy School of Basic Medical Sciences Southern Medical University Guangzhou Guangdong 510515 ChinaSchool of Basic Medical Sciences Guangdong Medical University Dongguan Guangdong 523808 ChinaSchool of Basic Medical Sciences Fujian Medical University Fuzhou Fujian 350108 ChinaGuangdong Engineering Research Center for Translation of Medical 3D Printing Application Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics National Key Discipline of Human Anatomy School of Basic Medical Sciences Southern Medical University Guangzhou Guangdong 510515 ChinaYue Bei People's Hospital Postdoctoral Innovation Practice Base Southern Medical University Guangzhou Guangdong 510515 ChinaDepartment of Microbiology and Immunology College of Basic Medicine and Public Hygiene Jinan University Guangzhou Guangdong 510632 ChinaYue Bei People's Hospital Postdoctoral Innovation Practice Base Southern Medical University Guangzhou Guangdong 510515 ChinaAbstract Current Ti‐6Al‐4V bone implants lack trabecular structure and pro‑angiogenic cues, both essential for regeneration. Herein, a dual biomimetic strategy is devised that integrates a 3D‐printed biomimetic trabecular porous Ti‐6Al‐4V scaffold (BTPS) with exosome‐loaded PEGDA/GelMA hydrogel microspheres (PGHExo) designed for sustained release. BTPS is designed using Voronoi algorithms and imaging data, and replicates the geometry and mechanical properties of natural bone. Hypoxia‐induced human umbilical vein endothelial cell (HUVEC) derived exosomes (HExo) are encapsulated in PGHExo microspheres via microfluidic technology, enabling controlled release of HExo, and anchored onto BTPS using polydopamine (pDA) modification (BTPS&pDA@PGHExo). BTPS exhibited an elastic modulus of ≈3.2 GPa and a permeability of 11.52 × 10−8 mm2, mimicking natural bone. In vitro assays demonstrated that BTPS&pDA@PGHExo significantly enhanced osteogenesis and angiogenesis. mRNA‐Seq analysis suggested that BTPS&pDA@PGHExo regulates osteogenic and angiogenic gene expression through the activation of pathways including MAPK, mTOR, HIF‐1, and VEGF. In vivo, BTPS&pDA@PGHExo improved bone volume, density, and neovascularization in a rabbit model. This dual biomimetic strategy offers a promising clinical solution, addressing the limitations of conventional Ti‐6Al‐4V scaffolds and providing an innovative approach for personalized bone defect repair.https://doi.org/10.1002/advs.2025005993D‐printedangiogenesisbiomimetic trabecular scaffoldbone regeneration, exosomes |
| spellingShingle | Lincong Luo Weihan Zheng Jiaying Li Tingting Chen Wanting Xue Tao Lin Mingrui Liu Zi Yan Jiaxin Yang Jiamin Li Jiahao Pu Yaobin Wu Konghe Hu Shiyu Li Wenhua Huang 3D‐Printed Titanium Trabecular Scaffolds with Sustained Release of Hypoxia‐Induced Exosomes for Dual‐Mimetic Bone Regeneration Advanced Science 3D‐printed angiogenesis biomimetic trabecular scaffold bone regeneration, exosomes |
| title | 3D‐Printed Titanium Trabecular Scaffolds with Sustained Release of Hypoxia‐Induced Exosomes for Dual‐Mimetic Bone Regeneration |
| title_full | 3D‐Printed Titanium Trabecular Scaffolds with Sustained Release of Hypoxia‐Induced Exosomes for Dual‐Mimetic Bone Regeneration |
| title_fullStr | 3D‐Printed Titanium Trabecular Scaffolds with Sustained Release of Hypoxia‐Induced Exosomes for Dual‐Mimetic Bone Regeneration |
| title_full_unstemmed | 3D‐Printed Titanium Trabecular Scaffolds with Sustained Release of Hypoxia‐Induced Exosomes for Dual‐Mimetic Bone Regeneration |
| title_short | 3D‐Printed Titanium Trabecular Scaffolds with Sustained Release of Hypoxia‐Induced Exosomes for Dual‐Mimetic Bone Regeneration |
| title_sort | 3d printed titanium trabecular scaffolds with sustained release of hypoxia induced exosomes for dual mimetic bone regeneration |
| topic | 3D‐printed angiogenesis biomimetic trabecular scaffold bone regeneration, exosomes |
| url | https://doi.org/10.1002/advs.202500599 |
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