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Open AccessArticle

Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration

1
Department of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute of RWTH Aachen University & Hospital, 52074 Aachen, Germany
2
Electron Microscopy Facility, Institute of Pathology, RWTH Aachen University Hospital, 52074 Aachen, Germany
3
Department of Orthodontics, RWTH Aachen University Hospital, 52074 Aachen, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(12), 4226; https://doi.org/10.3390/ijms21124226
Received: 8 May 2020 / Revised: 8 June 2020 / Accepted: 11 June 2020 / Published: 13 June 2020
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. View Full-Text
Keywords: extracellular vesicles (EVs); dental pulp regeneration; hydrogel; angiogenesis; rapid vascularization; VEGF extracellular vesicles (EVs); dental pulp regeneration; hydrogel; angiogenesis; rapid vascularization; VEGF
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MDPI and ACS Style

Zhang, S.; Thiebes, A.L.; Kreimendahl, F.; Ruetten, S.; Buhl, E.M.; Wolf, M.; Jockenhoevel, S.; Apel, C. Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration. Int. J. Mol. Sci. 2020, 21, 4226. https://doi.org/10.3390/ijms21124226

AMA Style

Zhang S, Thiebes AL, Kreimendahl F, Ruetten S, Buhl EM, Wolf M, Jockenhoevel S, Apel C. Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration. International Journal of Molecular Sciences. 2020; 21(12):4226. https://doi.org/10.3390/ijms21124226

Chicago/Turabian Style

Zhang, Siyuan; Thiebes, Anja L.; Kreimendahl, Franziska; Ruetten, Stephan; Buhl, Eva M.; Wolf, Michael; Jockenhoevel, Stefan; Apel, Christian. 2020. "Extracellular Vesicles-Loaded Fibrin Gel Supports Rapid Neovascularization for Dental Pulp Regeneration" Int. J. Mol. Sci. 21, no. 12: 4226. https://doi.org/10.3390/ijms21124226

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