A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivo
Introduction: Recently, efforts towards the development of patient-specific 3D printed scaffolds for bone tissue engineering from bioactive ceramics have continuously intensified. For reconstruction of segmental defects after subtotal mandibulectomy a suitable tissue engineered bioceramic bone graft...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1221314/full |
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| author | Christine Knabe Michael Stiller Michael Stiller Marian Kampschulte Janka Wilbig Barbara Peleska Jens Günster Renate Gildenhaar Georg Berger Alexander Rack Ulf Linow Max Heiland Carsten Rendenbach Steffen Koerdt Claudius Steffen Alireza Houshmand Li Xiang-Tischhauser Doaa Adel-Khattab Doaa Adel-Khattab |
| author_facet | Christine Knabe Michael Stiller Michael Stiller Marian Kampschulte Janka Wilbig Barbara Peleska Jens Günster Renate Gildenhaar Georg Berger Alexander Rack Ulf Linow Max Heiland Carsten Rendenbach Steffen Koerdt Claudius Steffen Alireza Houshmand Li Xiang-Tischhauser Doaa Adel-Khattab Doaa Adel-Khattab |
| author_sort | Christine Knabe |
| collection | DOAJ |
| description | Introduction: Recently, efforts towards the development of patient-specific 3D printed scaffolds for bone tissue engineering from bioactive ceramics have continuously intensified. For reconstruction of segmental defects after subtotal mandibulectomy a suitable tissue engineered bioceramic bone graft needs to be endowed with homogenously distributed osteoblasts in order to mimic the advantageous features of vascularized autologous fibula grafts, which represent the standard of care, contain osteogenic cells and are transplanted with the respective blood vessel. Consequently, inducing vascularization early on is pivotal for bone tissue engineering. The current study explored an advanced bone tissue engineering approach combining an advanced 3D printing technique for bioactive resorbable ceramic scaffolds with a perfusion cell culture technique for pre-colonization with mesenchymal stem cells, and with an intrinsic angiogenesis technique for regenerating critical size, segmental discontinuity defects in vivo applying a rat model. To this end, the effect of differing Si-CAOP (silica containing calcium alkali orthophosphate) scaffold microarchitecture arising from 3D powder bed printing (RP) or the Schwarzwalder Somers (SSM) replica fabrication technique on vascularization and bone regeneration was analyzed in vivo. In 80 rats 6-mm segmental discontinuity defects were created in the left femur.Methods: Embryonic mesenchymal stem cells were cultured on RP and SSM scaffolds for 7d under perfusion to create Si-CAOP grafts with terminally differentiated osteoblasts and mineralizing bone matrix. These scaffolds were implanted into the segmental defects in combination with an arteriovenous bundle (AVB). Native scaffolds without cells or AVB served as controls. After 3 and 6 months, femurs were processed for angio-µCT or hard tissue histology, histomorphometric and immunohistochemical analysis of angiogenic and osteogenic marker expression.Results: At 3 and 6 months, defects reconstructed with RP scaffolds, cells and AVB displayed a statistically significant higher bone area fraction, blood vessel volume%, blood vessel surface/volume, blood vessel thickness, density and linear density than defects treated with the other scaffold configurations.Discussion: Taken together, this study demonstrated that the AVB technique is well suited for inducing adequate vascularization of the tissue engineered scaffold graft in segmental defects after 3 and 6 months, and that our tissue engineering approach employing 3D powder bed printed scaffolds facilitated segmental defect repair. |
| first_indexed | 2024-03-13T05:23:30Z |
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| spelling | doaj.art-94b1af3160c64c1c9ef50651de444b052023-06-15T10:25:29ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-06-011110.3389/fbioe.2023.12213141221314A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivoChristine Knabe0Michael Stiller1Michael Stiller2Marian Kampschulte3Janka Wilbig4Barbara Peleska5Jens Günster6Renate Gildenhaar7Georg Berger8Alexander Rack9Ulf Linow10Max Heiland11Carsten Rendenbach12Steffen Koerdt13Claudius Steffen14Alireza Houshmand15Li Xiang-Tischhauser16Doaa Adel-Khattab17Doaa Adel-Khattab18Department of Experimental Orofacial Medicine, Philipps University Marburg, Marburg, GermanyDepartment of Experimental Orofacial Medicine, Philipps University Marburg, Marburg, GermanyDepartment of Prosthodontics, Philipps University Marburg, Marburg, GermanyDepartment of Radiology, Justus Liebig University Giessen, Giessen, GermanyDepartment of Biomaterials and Multimodal Processing, Federal Institute for Materials Research and Testing, Berlin, GermanyDepartment of Prosthodontics, Philipps University Marburg, Marburg, GermanyDepartment of Biomaterials and Multimodal Processing, Federal Institute for Materials Research and Testing, Berlin, GermanyDepartment of Biomaterials and Multimodal Processing, Federal Institute for Materials Research and Testing, Berlin, GermanyDepartment of Biomaterials and Multimodal Processing, Federal Institute for Materials Research and Testing, Berlin, GermanyStructure of Materials Group, ESRF (European Synchroton Radiation Facility), Grenoble, FranceDepartment of Biomaterials and Multimodal Processing, Federal Institute for Materials Research and Testing, Berlin, GermanyDepartment of Oral and Maxillofacial Surgery, Charité University Medical Center Berlin (Charité-Universitätsmedizin Berlin), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Oral and Maxillofacial Surgery, Charité University Medical Center Berlin (Charité-Universitätsmedizin Berlin), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Oral and Maxillofacial Surgery, Charité University Medical Center Berlin (Charité-Universitätsmedizin Berlin), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Oral and Maxillofacial Surgery, Charité University Medical Center Berlin (Charité-Universitätsmedizin Berlin), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Experimental Orofacial Medicine, Philipps University Marburg, Marburg, GermanyDepartment of Experimental Orofacial Medicine, Philipps University Marburg, Marburg, GermanyDepartment of Experimental Orofacial Medicine, Philipps University Marburg, Marburg, GermanyDepartment of Periodontology, Ain Shams University, Cairo, EgyptIntroduction: Recently, efforts towards the development of patient-specific 3D printed scaffolds for bone tissue engineering from bioactive ceramics have continuously intensified. For reconstruction of segmental defects after subtotal mandibulectomy a suitable tissue engineered bioceramic bone graft needs to be endowed with homogenously distributed osteoblasts in order to mimic the advantageous features of vascularized autologous fibula grafts, which represent the standard of care, contain osteogenic cells and are transplanted with the respective blood vessel. Consequently, inducing vascularization early on is pivotal for bone tissue engineering. The current study explored an advanced bone tissue engineering approach combining an advanced 3D printing technique for bioactive resorbable ceramic scaffolds with a perfusion cell culture technique for pre-colonization with mesenchymal stem cells, and with an intrinsic angiogenesis technique for regenerating critical size, segmental discontinuity defects in vivo applying a rat model. To this end, the effect of differing Si-CAOP (silica containing calcium alkali orthophosphate) scaffold microarchitecture arising from 3D powder bed printing (RP) or the Schwarzwalder Somers (SSM) replica fabrication technique on vascularization and bone regeneration was analyzed in vivo. In 80 rats 6-mm segmental discontinuity defects were created in the left femur.Methods: Embryonic mesenchymal stem cells were cultured on RP and SSM scaffolds for 7d under perfusion to create Si-CAOP grafts with terminally differentiated osteoblasts and mineralizing bone matrix. These scaffolds were implanted into the segmental defects in combination with an arteriovenous bundle (AVB). Native scaffolds without cells or AVB served as controls. After 3 and 6 months, femurs were processed for angio-µCT or hard tissue histology, histomorphometric and immunohistochemical analysis of angiogenic and osteogenic marker expression.Results: At 3 and 6 months, defects reconstructed with RP scaffolds, cells and AVB displayed a statistically significant higher bone area fraction, blood vessel volume%, blood vessel surface/volume, blood vessel thickness, density and linear density than defects treated with the other scaffold configurations.Discussion: Taken together, this study demonstrated that the AVB technique is well suited for inducing adequate vascularization of the tissue engineered scaffold graft in segmental defects after 3 and 6 months, and that our tissue engineering approach employing 3D powder bed printed scaffolds facilitated segmental defect repair.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1221314/fullbioactive ceramics3D printed scaffoldbone tissue engineeringbone repaircalcium alkali orthophosphatesangiogenesis |
| spellingShingle | Christine Knabe Michael Stiller Michael Stiller Marian Kampschulte Janka Wilbig Barbara Peleska Jens Günster Renate Gildenhaar Georg Berger Alexander Rack Ulf Linow Max Heiland Carsten Rendenbach Steffen Koerdt Claudius Steffen Alireza Houshmand Li Xiang-Tischhauser Doaa Adel-Khattab Doaa Adel-Khattab A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivo Frontiers in Bioengineering and Biotechnology bioactive ceramics 3D printed scaffold bone tissue engineering bone repair calcium alkali orthophosphates angiogenesis |
| title | A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivo |
| title_full | A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivo |
| title_fullStr | A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivo |
| title_full_unstemmed | A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivo |
| title_short | A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivo |
| title_sort | tissue engineered 3d printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical size discontinuity bony defects in vivo |
| topic | bioactive ceramics 3D printed scaffold bone tissue engineering bone repair calcium alkali orthophosphates angiogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1221314/full |
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