Evaluating the efficacy of human dental pulp stem cells and scaffold combination for bone regeneration in animal models: A systematic review and meta-analysis

Abstract: Introduction: Human adult dental pulp stem cells (hDPSC) and stem cells from human exfoliated deciduous teeth (SHED) hold promise in bone regeneration for their easy accessibility, high proliferation rate, self-renewal and osteogenic differentiation capacity. Various organic and inorganic scaffold materials were pre-seeded with human dental pulp stem cells in animals with promising outcomes in new bone formation. Yet, the clinical trial for bone regeneration using dental pulp stem cells is still in infancy. Thus, the aim of this systematic review and meta-analysis is to synthesise the evidence of the efficacy of human dental pulp stem cells and the scaffold combination for bone regeneration in animal bone defect models. Methodology: This study was registered in PROSPERO (CRD2021274976) and PRISMA guideline was followed to include the relevant full-text papers using exclusion and inclusion criteria. Data were extracted for the systematic review. Quality assessment and the risk of bias of the included papers were also carried out using CAMARADES tool. Quantitative bone regeneration data of the experimental (Scaffold + hDPSC/SHED) and the control (Scaffold only) groups were also extracted for meta-analysis. Results 49 papers were included for systematic review and only 27 of them were qualified for meta-analysis. 90% of the included papers were assessed as medium to low risk. In the meta-analysis, qualified studies were grouped by the unit of bone regeneration measurement. Overall, bone regeneration was significantly higher (p < 0.0001) in experimental group (scaffold + hDPSC/SHED) compared to the control group (scaffold only) (SMD: 1.863, 95% CI: 1.121–2.605). However, the effect is almost entirely driven by the % bone formation group (SMD: 3.929, 95% CI: 2.612–5.246) while % BV/TV (SMD: 2.693, 95% CI: -0.001-5.388) shows a marginal effect and both bone mineral density (mg/cm³) and new bone formation (mm²) showed no effects. The funnel plot exhibits no obvious asymmetry representing a lack of remarkable publication bias. Sensitivity analysis also indicated that the results generated in this meta-analysis are robust and reliable. Conclusion This is the first synthesised evidence that showed that irrespective of the types or composition of the scaffolds, DPSCs/SHED and scaffold combination enhanced bone regeneration highly significantly compared to the cell-free scaffold. So, dental pulp stem cells would be a promising tool for treating various bone diseases, and more clinical trials need to be conducted to evaluate the effectiveness of dental pulp stem cell-based therapies.