A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs

Abstract The requirement for immediate vascularization of engineered dental pulp poses a major hurdle towards successful implementation of pulp regeneration as an effective therapeutic strategy for root canal therapy, especially in adult teeth. Here, we demonstrate a novel strategy to engineer pre-v...

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Main Authors: Avathamsa Athirasala, Fernanda Lins, Anthony Tahayeri, Monica Hinds, Anthony J. Smith, Christine Sedgley, Jack Ferracane, Luiz E. Bertassoni
Format: Article
Language:English
Published: Nature Portfolio 2017-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-02532-3
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author Avathamsa Athirasala
Fernanda Lins
Anthony Tahayeri
Monica Hinds
Anthony J. Smith
Christine Sedgley
Jack Ferracane
Luiz E. Bertassoni
author_facet Avathamsa Athirasala
Fernanda Lins
Anthony Tahayeri
Monica Hinds
Anthony J. Smith
Christine Sedgley
Jack Ferracane
Luiz E. Bertassoni
author_sort Avathamsa Athirasala
collection DOAJ
description Abstract The requirement for immediate vascularization of engineered dental pulp poses a major hurdle towards successful implementation of pulp regeneration as an effective therapeutic strategy for root canal therapy, especially in adult teeth. Here, we demonstrate a novel strategy to engineer pre-vascularized, cell-laden hydrogel pulp-like tissue constructs in full-length root canals for dental pulp regeneration. We utilized gelatin methacryloyl (GelMA) hydrogels with tunable physical and mechanical properties to determine the microenvironmental conditions (microstructure, degradation, swelling and elastic modulus) that enhanced viability, spreading and proliferation of encapsulated odontoblast-like cells (OD21), and the formation of endothelial monolayers by endothelial colony forming cells (ECFCs). GelMA hydrogels with higher polymer concentration (15% w/v) and stiffness enhanced OD21 cell viability, spreading and proliferation, as well as endothelial cell spreading and monolayer formation. We then fabricated pre-vascularized, full-length, dental pulp-like tissue constructs by dispensing OD21 cell-laden GelMA hydrogel prepolymer in root canals of extracted teeth and fabricating 500 µm channels throughout the root canals. ECFCs seeded into the microchannels successfully formed monolayers and underwent angiogenic sprouting within 7 days in culture. In summary, the proposed approach is a simple and effective strategy for engineering of pre-vascularized dental pulp constructs offering potentially beneficial translational outcomes.
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spelling doaj.art-ac55dfd1867d4e76a388a1b269be79c72022-12-21T19:08:18ZengNature PortfolioScientific Reports2045-23222017-06-017111110.1038/s41598-017-02532-3A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue ConstructsAvathamsa Athirasala0Fernanda Lins1Anthony Tahayeri2Monica Hinds3Anthony J. Smith4Christine Sedgley5Jack Ferracane6Luiz E. Bertassoni7Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science UniversityDivision of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science UniversityDivision of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science UniversityDepartment of Biomedical Engineering, School of Medicine, Oregon Health and Science UniversitySchool of Dentistry, University of BirminghamDepartment of Endodontology, School of Dentistry, Oregon Health and Science UniversityDivision of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science UniversityDivision of Biomaterials and Biomechanics, Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science UniversityAbstract The requirement for immediate vascularization of engineered dental pulp poses a major hurdle towards successful implementation of pulp regeneration as an effective therapeutic strategy for root canal therapy, especially in adult teeth. Here, we demonstrate a novel strategy to engineer pre-vascularized, cell-laden hydrogel pulp-like tissue constructs in full-length root canals for dental pulp regeneration. We utilized gelatin methacryloyl (GelMA) hydrogels with tunable physical and mechanical properties to determine the microenvironmental conditions (microstructure, degradation, swelling and elastic modulus) that enhanced viability, spreading and proliferation of encapsulated odontoblast-like cells (OD21), and the formation of endothelial monolayers by endothelial colony forming cells (ECFCs). GelMA hydrogels with higher polymer concentration (15% w/v) and stiffness enhanced OD21 cell viability, spreading and proliferation, as well as endothelial cell spreading and monolayer formation. We then fabricated pre-vascularized, full-length, dental pulp-like tissue constructs by dispensing OD21 cell-laden GelMA hydrogel prepolymer in root canals of extracted teeth and fabricating 500 µm channels throughout the root canals. ECFCs seeded into the microchannels successfully formed monolayers and underwent angiogenic sprouting within 7 days in culture. In summary, the proposed approach is a simple and effective strategy for engineering of pre-vascularized dental pulp constructs offering potentially beneficial translational outcomes.https://doi.org/10.1038/s41598-017-02532-3
spellingShingle Avathamsa Athirasala
Fernanda Lins
Anthony Tahayeri
Monica Hinds
Anthony J. Smith
Christine Sedgley
Jack Ferracane
Luiz E. Bertassoni
A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs
Scientific Reports
title A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs
title_full A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs
title_fullStr A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs
title_full_unstemmed A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs
title_short A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs
title_sort novel strategy to engineer pre vascularized full length dental pulp like tissue constructs
url https://doi.org/10.1038/s41598-017-02532-3
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