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Implant-supported dentures are widely used in patients with defect or loss of dentition because these have higher chewing efficiency and do not damage the adjacent teeth compared with fixed or removable denture. An implant-supported denture carries the risk of failure in some systemic diseases, including osteoporosis, because of a non-ideal local microenvironment. Clinically common physical and chemical modifications are used to change the roughness of the implant surface to promote osseointegration, but they have limitations in promoting osteoinduction and inhibiting bone resorption. Recently, many researchers have focused on the study of bioactive modification of implants and have achieved promising results. Herein we have summarized the progress in bioactive modification strategy to promote osseointegration by regulating the local osteoporotic microenvironment.

Objectives We aimed to accelerate angiogenesis in pulp regeneration by modulating ephrinB2 expression in stem cells from apical papilla (SCAPs). Materials and Methods Stem cells from apical papilla were transducted with ephrinB2‐lentiviral expression vector (ephrinB2‐SCAPs) in experimental group and green fluorescent protein (GFP‐SCAPs) in control group. The transduction efficiency was confirmed by real‐time PCR and Western blot assays. MTT assay was performed to detect the proliferative capacity of SCAPs after transduction. In vitro Matrigel assay and in vivo Matrigel plug assay were carried out to evaluate the angiogenic capacity. Results Results showed that ephrinB2‐SCAPs had significantly higher ephrinB2 expression than GFP‐SCAPs. EphrinB2‐SCAPs upregulated vascular endothelial growth factor (VEGF) secretion under hypoxia. In vitro Matrigel assay demonstrated that human umbilical vein endothelial cells (HUVECs) cocultured with ephrinB2‐SCAPs under hypoxia formed vascular‐like structures earlier than GFP‐SCAPs. Animal experiments confirmed that SCAPs co‐transplanted with HUVECs enabled to generate greater amount of blood vessels than SCAPs alone. EphrinB2‐SCAPs produced increased number of blood vessels with references to GFP‐SCAPs, and those co‐transplanted with HUVECs generated vessels with larger and functional tubule volumes. Conclusions Regulating ephrinB2 expression in SCAPs may act as a new avenue for enhancing angiogenesis in dental pulp regeneration.

Background: Alveolar bone loss is a frequent occurrence. Dental pulp stem cells (DPSCs) which have invasive accessibility and high osteogenic potential is a promising source for cell-based bone regeneration. EphrinB2 is involved in bone homeostasis and osteogenesis. The aim of this study was to investigate the effect and mechanism of ephrinB2 overexpression on osteogenic differentiation of DPSCs and bone defect repair. Methods: EphrinB2 expression was analyzed during osteogenic induction of human DPSCs (hDPSCs). Endogenous ephrinB2 expression in hDPSCs was then upregulated using EfnB2 lentiviral vectors. The effect of ephrinB2 overexpression on osteogenic differentiation capacity of hDPSCs was investigated in vitro, and activation of ephrinB2-EphB4 bidirectional signaling in ephrinB2-overexpressing hDPSCs was detected. In vivo, a canine alveolar bone defect model was established and canine DPSCs (cDPSCs) were cultured, characterized, EfnB2-tranfected, and combined with a PuraMatrix scaffold. Micro-CT analysis was performed to evaluate the therapeutic effect of ephrinB2-overexpressing cDPSCs on bone defect repair. Results: EphrinB2 was upregulated after osteogenic induction of hDPSCs. EphrinB2 overexpression enhanced osteogenic differentiation capacity of hDPSCs in vitro. Moreover, p-ephrinB2 instead of p-EphB4 was upregulated by ephrinB2 overexpression, and activation of ephrinB2-mediated reverse signaling promoted osteogenic differentiation of hDPSCs. In a canine bone defect model, ephrinB2 overexpression in cDPSCs significantly improved trabecular bone volume per tissue volume (BV/TV) and trabecular thickness, as demonstrated by radiographic analysis. Conclusions: EphrinB2 overexpression enhanced osteogenic potential of DPSCs partially via upregulation of ephrinB2mediated reverse signaling and effectively promoted alveolar bone defect repair.

EphrinB2, a membrane protein regulating bone homeostasis, has been demonstrated to induce osteogenic gene expression in periodontal ligament fibroblasts. The aim of this study was to explore the effects of ephrinB2 on osteogenic differentiation of periodontal ligament stem cells and on alveolar bone regeneration in vivo. We assessed the osteogenic gene expression and osteogenic differentiation potential of ephrinB2-modified human and canine periodontal ligament stem cells, in which ephrinB2 expression was upregulated via lentiviral vector transduction. EphrinB2-modified canine periodontal ligament stem cells combined with PuraMatrix were delivered to critical-sized alveolar bone defects in beagles to evaluate bone regeneration. Results showed that ephrinB2 overexpression enhanced osteogenic gene transcription and mineral deposition in both human and canine periodontal ligament stem cells. Animal experiments confirmed that ephrinB2-modified canine periodontal ligament stem cells + PuraMatrix resulted in greater trabecular bone volume per tissue volume and trabecular thickness compared with other groups. Our study demonstrated that ephrinB2 promoted osteogenic differentiation of periodontal ligament stem cells and alveolar bone repair in beagles, highlighting its therapeutic potential for the treatment of alveolar bone damage.

Osteoporosis is a major challenge to oral implants, and this study focused on improving the osseointegration ability of titanium (Ti) implants in osteoporosis environment via surface modification, including doping of strontium ion and preparation of nanoscale surface feature. Our previous studies have shown that strontium (Sr) ions can enhance osteogenic activity. Therefore, we aimed to comprehensively evaluate the effect of hydrothermal treatment of Sr-doped titanium implant coating on bone-binding properties in the microenvironment of osteoporosis in this study. We fabricated Sr-doped nanocoating (AHT-Sr) onto the surface of titanium implants via hydrothermal reaction. The rough Sr-doping had good biological functions and could apparently promote osteogenic differentiation of osteoporotic bone marrow mesenchymal stem cells (OVX-BMSCs). Most importantly, AHT-Sr significantly promoted bone integration in the osteoporosis environment. This study provides an effective approach to implant surface modification for better osseointegration in an osteoporotic environment.

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