Key Takeaways & Executive Findings
- •• A local pulsatile PTH delivery system enhances osteogenic differentiation of DPSCs, promoting mandibular bone regeneration. • The system shows excellent biocompatibility with DPSCs, supporting cell adhesion and viability. • In vivo studies confirm effective repair of critical-sized mandibular defects in a rabbit model. • This approach offers a promising strategy for reconstructing large mandibular defects, addressing limitations of current grafting methods.
Abstract
Background Tumors and injuries often lead to large mandibular defects. Accelerating the osteogenesis of large bone defect areas is a major concern in current research. In this study, dental pulp mesenchymal stem cells (DPSCs) were used as seed cells, and the local pulsatile parathyroid hormone (PTH) delivery system was used as an osteogenic-inducing active ingredient to act on DPSCs and osteoblasts, which were applied to the jaw defect area to evaluate its therapeutic effect on bone regeneration. Methods Pulsatile delivery systems, both with and without PTH, were developed following the protocols outlined in our previous study. In vitro, the biocompatibility of the pulsatile delivery system with DPSCs was assessed using the Cell Counting Kit-8 (CCK8) assay and live/dead cell staining. Osteogenic differentiation was evaluated through alkaline phosphatase staining and alizarin red staining. In vivo, critical bone defects with a diameter of 10 mm were created in the mandibles of white rabbits. The osteogenic effect was further assessed through gross observation, X-ray imaging, and histological examination. Results In vitro experiments using CCK8 assays and live/dead cell staining demonstrated that DPSCs successfully adhered to the surface of the PTH pulsatile delivery system, showing no significant difference compared to the control group. Furthermore, alkaline phosphatase staining and Alizarin Red staining confirmed that the localized pulsatile parathyroid hormone delivery system effectively induced the differentiation of DPSCs into osteoblasts, leading to the secretion of abundant calcium nodules. Animal studies further revealed that the PTH pulsatile delivery system promoted the osteogenic differentiation of DPSCs, facilitating the repair of critical mandibular bone defects.
1. Introduction
Reconstruction of mandibular defects caused by tumors, trauma, or infections remains a significant clinical challenge due to the mandible's unique anatomical complexity and functional demands [1]. Various strategies have been developed to address this issue, including autologous bone grafting, allografts, and artificial implants. However, these approaches often face limitations such as inadequate bone availability, donor site morbidity, potential immune rejection, and restricted regenerative capacity at the defect site [2, 3]. In this context, stem cell-based regenerative therapies have emerged as a promising alternative for mandibular reconstruction, offering a source of osteogenic cells to promote bone formation and repair [4].
Mesenchymal stem cells (MSCs) have been extensively studied in bone tissue engineering due to their multilineage differentiation potential and immunomodulatory properties [5]. Among them, dental pulp-derived mesenchymal stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) have garnered significant attention for their potential in tissue formation as well as their robust paracrine signaling and immunomodulatory capabilities [6]. Notably, DPSCs are easily isolated and obtained from extracted or discarded teeth, providing an abundant and accessible cell source for regenerative medicine. This accessibility minimizes the risk of complications, offering distinct advantages over bone marrow and embryonic stem cells [7].
DPSCs, in particular, have demonstrated remarkable osteogenic differentiation potential both in vitro and in vivo. Furthermore, they secrete bioactive molecules that enhance the regenerative capacity of surrounding cells [8]. Numerous studies have indicated that DPSCs and SHEDs can facilitate healing and reconstruction in various jaw-related conditions, including tooth implantation [9], alveolar bone loss due to periodontitis [10], and fractures [11]. These compelling attributes position DPSCs as a highly promising candidate for mandibular tissue engineering.
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Yuanyuan Jia, Mianmian Duan, Yan Yang, Duchenhui Li, Dongxiang Wang, Zhenglong Tang (2026). The local pulsatile parathyroid hormone delivery system induces the osteogenic differentiation of dental pulp mesenchymal stem cells to reconstruct mandibular defects. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-025-04258-w
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Frequently Asked Questions
What is the main objective of this study?
The study aims to evaluate the therapeutic effect of a local pulsatile parathyroid hormone (PTH) delivery system combined with dental pulp mesenchymal stem cells (DPSCs) on bone regeneration in critical mandibular defects.
How was the pulsatile PTH delivery system tested in vitro?
In vitro, the biocompatibility of the system with DPSCs was assessed using CCK8 assay and live/dead cell staining, while osteogenic differentiation was evaluated through alkaline phosphatase and alizarin red staining.
What were the key findings of the in vivo experiments?
In vivo, the PTH pulsatile delivery system promoted osteogenic differentiation of DPSCs and facilitated the repair of critical mandibular bone defects in a rabbit model, as confirmed by gross observation, X-ray imaging, and histological examination.
Why are DPSCs considered advantageous for mandibular reconstruction?
DPSCs are easily isolated from extracted teeth, have high osteogenic potential, and secrete bioactive molecules that enhance regeneration, making them a promising cell source for tissue engineering.
What is the significance of this study for clinical practice?
This study provides a novel strategy combining a pulsatile PTH delivery system with DPSCs to enhance bone regeneration, potentially offering a more effective approach for reconstructing large mandibular defects compared to traditional methods.
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