Dental pulp stem cells promote malignant transformation of oral epithelial cells through mitochondrial transfer.

Oral epithelial dysplasia includes a range of clinical oral mucosal diseases with potentially malignant traits. Dental pulp stem cells (DPSCs) are potential candidates for cell-based therapies targeting various diseases. However, the effect of DPSCs on the progression of oral mucosal precancerous lesions remains unclear. Animal experiments were conducted to assess the effect of human DPSCs (hDPSCs). We measured the proliferation, motility and mitochondrial respiratory function of the human dysplastic oral keratinocyte (DOK) cells cocultured with hDPSCs. Mitochondrial transfer experiments were performed to determine the role mitochondria from hDPSCs in the malignant transformation of DOK cells. hDPSCs injection accelerated carcinogenesis in 4NQO-induced oral epithelial dysplasia in mice. Coculture with hDPSCs increased the proliferation, migration, invasion and mitochondrial respiratory function of DOK cells. Mitochondria from hDPSCs could be transferred to DOK cells, and activated mTOR signaling pathway in DOK cells. Our study demonstrates that hDPSCs activate the mTOR signaling pathway through mitochondrial transfer, promoting the malignant transformation of oral precancerous epithelial lesions.

Role of alpha smooth muscle actin in odontogenic differentiation of dental pulp stem cells.

Pulpotomy is an effective treatment for retaining vital pulp after pulp exposure caused by caries removal and/or trauma. The expression of alpha smooth muscle actin (α-SMA) is increased during the wound-healing process, and α-SMA-positive fibroblasts accelerate tissue repair. However, it remains largely unknown whether α-SMA-positive fibroblasts influence pulpal repair. In this study, we established an experimental rat pulpotomy model and found that the expression of α-SMA was increased in dental pulp after pulpotomy relative to that in normal dental pulp. In vitro results showed that the expression of α-SMA was increased during the induction of odontogenic differentiation in dental pulp stem cells (DPSCs) compared with untreated DPSCs. Moreover, α-SMA overexpression promoted the odontogenic differentiation of DPSCs via increasing mitochondrial function. Mechanistically, α-SMA overexpression activated the mammalian target of rapamycin (mTOR) signaling pathway. Inhibition of the mTOR signaling pathway by rapamycin decreased the mitochondrial function in α-SMA-overexpressing DPSCs and suppressed the odontogenic differentiation of DPSCs. Furthermore, we found that α-SMA overexpression increased the secretion of transforming growth factor beta-1 (TGF-ß1). In sum, our present study demonstrates a novel mechanism by which α-SMA promotes odontogenic differentiation of DPSCs by increasing mitochondrial respiratory activity via the mTOR signaling pathway.

Dual Mg-Reinforced PCL Membrane with a Janus Structure for Vascularized Bone Regeneration and Bacterial Elimination.

Commercially available guided bone regeneration (GBR) membranes often exhibit limited mechanical properties or bioactivity, leading to poor performance in repairing bone defects. To surmount this limitation, we developed a Janus structural composite membrane (Mg-MgO/PCL) reinforced by dual Mg (Mg sheets and MgO NPs) by using a combined processing technique involving casting and electrospinning. Results showed that the addition of Mg sheets and MgO NPs enhanced the mechanical properties of the composite membrane for osteogenic space maintenance, specifically tensile strength (from 10.2 ± 1.2 to 50.3 ± 4.5 MPa) and compression force (from 0 to 0.94 ± 0.09 N mm-1), through Mg sheet reinforcement and improved crystallization. The dense cast side of the Janus structure membrane displayed better fibroblast barrier capacity than a single fiber structure; meanwhile, the PCL matrix protected the Mg sheet from severe corrosion due to predeformation. The porous microfibers side supported preosteoblast cell adhesion, enhanced osteogenesis, and angiogenesis in vitro, through the biomimetic extracellular matrix and sustainable Mg2+ release. Furthermore, the Mg-MgO/PCL membrane incorporating 2 wt % MgO NPs exhibited remarkable antimicrobial properties, inducing over 88.75% apoptosis in Staphylococcus aureus. An in vivo experiment using the rat skull defect model (Φ = 5 mm) confirmed that the Mg-MgO/PCL membrane significantly improved new bone formation postsurgery. Collectively, our investigation provides valuable insights into the design of multifunctional membranes for clinical oral GBR application.

Preparation of 4D printed peripheral vascular stent and its degradation behavior under fluid shear stress after deployment.

Shape memory stents are mild intervention devices for vascular diseases as compared to balloon-dilated ones; however, their degradation behavior under blood shear stress after deployment also deserves further attention. To understand the degradation behavior, we first prepared 4D printed poly(lactic acid) (PLA) stents via 3D printing technology and studied their failure behavior in a dynamic condition after self-expandable deployment. Mechanical property tests showed that the 4D printed stents had a compression force of 0.06-0.39 N mm-1 and a recovery ratio of 85.3-93.4%, respectively, which was verified to be wall thickness dependent. The stents were then implanted in simulated blood vessels with minimal microstructural damage at 60 °C followed by 8-week degradation tests. The results showed the microstructure damage caused by deployment could accelerate the degradation of stents faster than fluid shear stress. Furthermore, we conducted microstructural analysis and numerical simulation on the stent by finite element analysis (FEA) to explain the relationship between stent injury, vascular injury, and stent deployment temperature. A physical model derived from micro-morphologies on the degradation mechanism of PLA was also proposed. These results may provide new insights for the examination of the degradation behavior of 4D printed stents and minimize medical risk.