title: The interplay of dental pulp stem cells and endothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo.
abstract: Securing an adequate blood supply for the survival of cell transplants is critical for a successful outcome in tissue engineering. Interactions between endothelial and progenitor/stem cells are important for vascularization of regenerating tissue. Recently, self-assembling peptide nanofibers were described as a promising environment for pulp regeneration due to their synthetic nature and controlled physicochemical properties. In this study, the peptide hydrogel PuraMatrix™ was used as a scaffold system to investigate the role of dental pulp stem cells (DPSCs) in triggering angiogenesis and the potential for regenerating vascularized pulp in vivo. Human umbilical vein endothelial cells (HUVECs), DPSCs, or cocultures of both cell types were encapsulated in three-dimensional PuraMatrix. The peptide nanofiber microenvironment supported cell survival, cell migration, and capillary network formation in the absence of exogenous growth factors. DPSCs increased early vascular network formation by facilitating the migration of HUVECs and by increasing vascular endothelial growth factor (VEGF) expression. Both the DPSC-monoculture and coculture groups exhibited vascularized pulp-like tissue with patches of osteodentin after transplantation in mice. The cocultured groups exhibited more extracellular matrix, vascularization, and mineralization than the DPSC-monocultures in vivo. The DPSCs play a critical role in initial angiogenesis, whereas coordinated efforts by the HUVECs and DPSCs are required to achieve a balance between extracellular matrix deposition and mineralization. The findings of this study also highlighted the importance of a microenvironment that supports cell-cell interactions and cell migration, which contribute to successful dental pulp regeneration.
authors.affiliation: 1 Department of Endodontics, Comprehensive Dental Care, Faculty of Dentistry, The University of Hong Kong , Hong Kong, China .
authors.forename: Waruna Lakmal
authors.initials: WL
authors.lastname: Dissanayaka
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Hargreaves
authors.forename: Lijian
authors.initials: L
authors.lastname: Jin
authors.forename: Lakshman P
authors.initials: LP
authors.lastname: Samaranayake
authors.forename: Chengfei
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003782:Dental Pulp / Q000098:blood supply / Q000166:cytology* / Q000254:growth & development*; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D007267:Injections; D008297:Male; D008422:Materials Testing; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D012038:Regeneration / Q000502:physiology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D055815:Young Adult
chemical_list: D020100:Hydrogels; D010455:Peptides; C546681:RADA16-I