Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration
Rapid vascularization is required for the regeneration of dental pulp due to the spatially restricted tooth environment. Extracellular vesicles (EVs) released from mesenchymal stromal cells show potent proangiogenic effects. Since EVs suffer from rapid clearance and low accumulation in target tissue...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/12/4226 |
| _version_ | 1797565346104737792 |
|---|---|
| author | Siyuan Zhang Anja Lena Thiebes Franziska Kreimendahl Stephan Ruetten Eva Miriam Buhl Michael Wolf Stefan Jockenhoevel Christian Apel |
| author_facet | Siyuan Zhang Anja Lena Thiebes Franziska Kreimendahl Stephan Ruetten Eva Miriam Buhl Michael Wolf Stefan Jockenhoevel Christian Apel |
| author_sort | Siyuan Zhang |
| collection | DOAJ |
| description | Rapid vascularization is required for the regeneration of dental pulp due to the spatially restricted tooth environment. Extracellular vesicles (EVs) released from mesenchymal stromal cells show potent proangiogenic effects. Since EVs suffer from rapid clearance and low accumulation in target tissues, an injectable delivery system capable of maintaining a therapeutic dose of EVs over a longer period would be desirable. We fabricated an EV-fibrin gel composite as an in situ forming delivery system. EVs were isolated from dental pulp stem cells (DPSCs). Their effects on cell proliferation and migration were monitored in monolayers and hydrogels. Thereafter, endothelial cells and DPSCs were co-cultured in EV-fibrin gels and angiogenesis as well as collagen deposition were analyzed by two-photon laser microscopy. Our results showed that EVs enhanced cell growth and migration in 2D and 3D cultures. EV-fibrin gels facilitated vascular-like structure formation in less than seven days by increasing the release of VEGF. The EV-fibrin gel promoted the deposition of collagen I, III, and IV, and readily induced apoptosis during the initial stage of angiogenesis. In conclusion, we confirmed that EVs from DPSCs can promote angiogenesis in an injectable hydrogel in vitro, offering a novel and minimally invasive strategy for regenerative endodontic therapy. |
| first_indexed | 2024-03-10T19:11:49Z |
| format | Article |
| id | doaj.art-2105f048ae2048688b70e75a1db30de8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:11:49Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2105f048ae2048688b70e75a1db30de82023-11-20T03:44:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112422610.3390/ijms21124226Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp RegenerationSiyuan Zhang0Anja Lena Thiebes1Franziska Kreimendahl2Stephan Ruetten3Eva Miriam Buhl4Michael Wolf5Stefan Jockenhoevel6Christian Apel7Department of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute of RWTH Aachen University & Hospital, 52074 Aachen, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute of RWTH Aachen University & Hospital, 52074 Aachen, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute of RWTH Aachen University & Hospital, 52074 Aachen, GermanyElectron Microscopy Facility, Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, GermanyElectron Microscopy Facility, Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, GermanyDepartment of Orthodontics, RWTH Aachen University Hospital, 52074 Aachen, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute of RWTH Aachen University & Hospital, 52074 Aachen, GermanyDepartment of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute of RWTH Aachen University & Hospital, 52074 Aachen, GermanyRapid vascularization is required for the regeneration of dental pulp due to the spatially restricted tooth environment. Extracellular vesicles (EVs) released from mesenchymal stromal cells show potent proangiogenic effects. Since EVs suffer from rapid clearance and low accumulation in target tissues, an injectable delivery system capable of maintaining a therapeutic dose of EVs over a longer period would be desirable. We fabricated an EV-fibrin gel composite as an in situ forming delivery system. EVs were isolated from dental pulp stem cells (DPSCs). Their effects on cell proliferation and migration were monitored in monolayers and hydrogels. Thereafter, endothelial cells and DPSCs were co-cultured in EV-fibrin gels and angiogenesis as well as collagen deposition were analyzed by two-photon laser microscopy. Our results showed that EVs enhanced cell growth and migration in 2D and 3D cultures. EV-fibrin gels facilitated vascular-like structure formation in less than seven days by increasing the release of VEGF. The EV-fibrin gel promoted the deposition of collagen I, III, and IV, and readily induced apoptosis during the initial stage of angiogenesis. In conclusion, we confirmed that EVs from DPSCs can promote angiogenesis in an injectable hydrogel in vitro, offering a novel and minimally invasive strategy for regenerative endodontic therapy.https://www.mdpi.com/1422-0067/21/12/4226extracellular vesicles (EVs)dental pulp regenerationhydrogelangiogenesisrapid vascularizationVEGF |
| spellingShingle | Siyuan Zhang Anja Lena Thiebes Franziska Kreimendahl Stephan Ruetten Eva Miriam Buhl Michael Wolf Stefan Jockenhoevel Christian Apel Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration International Journal of Molecular Sciences extracellular vesicles (EVs) dental pulp regeneration hydrogel angiogenesis rapid vascularization VEGF |
| title | Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration |
| title_full | Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration |
| title_fullStr | Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration |
| title_full_unstemmed | Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration |
| title_short | Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration |
| title_sort | extracellular vesicles loaded fibrin gel supports rapid neovascularization for dental pulp regeneration |
| topic | extracellular vesicles (EVs) dental pulp regeneration hydrogel angiogenesis rapid vascularization VEGF |
| url | https://www.mdpi.com/1422-0067/21/12/4226 |
| work_keys_str_mv | AT siyuanzhang extracellularvesiclesloadedfibringelsupportsrapidneovascularizationfordentalpulpregeneration AT anjalenathiebes extracellularvesiclesloadedfibringelsupportsrapidneovascularizationfordentalpulpregeneration AT franziskakreimendahl extracellularvesiclesloadedfibringelsupportsrapidneovascularizationfordentalpulpregeneration AT stephanruetten extracellularvesiclesloadedfibringelsupportsrapidneovascularizationfordentalpulpregeneration AT evamiriambuhl extracellularvesiclesloadedfibringelsupportsrapidneovascularizationfordentalpulpregeneration AT michaelwolf extracellularvesiclesloadedfibringelsupportsrapidneovascularizationfordentalpulpregeneration AT stefanjockenhoevel extracellularvesiclesloadedfibringelsupportsrapidneovascularizationfordentalpulpregeneration AT christianapel extracellularvesiclesloadedfibringelsupportsrapidneovascularizationfordentalpulpregeneration |