Investigating the Vascularization of Tissue-Engineered Bone Constructs Using Dental Pulp Cells and 45S5 Bioglass^® Scaffolds

Abstract

Identification of a suitable cell source combined with an appropriate 3D scaffold is an essential prerequisite for successful engineering of skeletal tissues. Both osteogenesis and angiogenesis are key processes for bone regeneration. This study investigated the vascularization potential of a novel combination of human dental pulp stromal cells (HDPSCs) with 45S5 Bioglass® scaffolds for tissue-engineered mineral constructs in vivo and in vitro. 45S5 Bioglass scaffolds were produced by the foam replication technique with the standard composition of 45 wt% SiO2, 24.5 wt% Na2O, 24.5 wt% CaO, and 6 wt% P2O5. HDPSCs were cultured in monolayers and on porous 45S5 Bioglass scaffolds under angiogenic and osteogenic conditions for 2–4 weeks. HDPSCs expressed endothelial gene markers (CD34, CD31/PECAM1, and VEGFR2) under both conditions in the monolayer. A combination of HDPSCs with 45S5 Bioglass enhanced the expression of these gene markers. Positive immunostaining for CD31/PECAM1 and VEGFR2 and negative staining for CD34 supported the gene expression data, while histology revealed evidence of endothelial cell-like morphology within the constructs. More organized tubular structures, resembling microvessels, were seen in the constructs after 8 weeks of implantation in vivo. In conclusion, this study suggests that the combination of HDPSCs with 45S5 Bioglass scaffolds offers a promising strategy for regenerating vascularized bone grafts.

Effects of silicon on osteoclast cell mediated degradation, in vivo osteogenesis and vasculogenesis of brushite cement

“…Although the complete mechanism governing the blood vessel formation in calcium phosphates are yet to be understood, it has been shown that Si upregulates the nitric oxide synthase and increases the VEGF production in bioglasses and calcium silicate materials in dose dependent manner through enhancement of vascular endothelial growth factor receptor (VEGFR-2) and basic fibroblast growth factor receptor (bFGF) in endothelial cells [41,42,43]. In addition, upregulation of endothelial gene markers by human dental pulp stromal cells (HDPSCs) shows the efficacy of bioglasses in regeneration of vascularized bone substitutes in combination of HDPSCs [44]. Increase in expression of VEGF is also reported in human umbilical vein endothelial cells (HUVEC) alone and co-cultured with human dermal fibroblasts (HDFs) due to Si ion release [45].…”

Dental Pulp Cells Isolated from Teeth with Superficial Caries Retain an Inflammatory Phenotype and Display an Enhanced Matrix Mineralization Potential

“…Although, evidence of differentiated functional tissue derived from transplanted DPSCs is limited some studies show that such cells can interact with biologically compatible scaffolds as part of successful tissue engineering strategies (El-Gendy et al, 2015). As an example of this transplantation of DPSCs into SCID mice was shown to result in formation of dentin pulp-like tissue structures (Gronthos et al, 2002).…”

Vertical root fracture resistance of simulated immature permanent teeth filled with MTA using different vehicles

“…There were 2 mm gap between the mounting material and CEJ. This gap is considered to provide physiological distance found clinically between the bone crest and CEJ ( 22 ).…”