Titanium Mesh Exposure in Guided Bone Regeneration Procedures: A Systematic Review and Meta-analysis.

PURPOSE: To investigate whether titanium mesh exposure is influenced by the type of titanium mesh, the type of bone graft material, or the associated employment of absorbable membranes. MATERIALS AND METHODS: Electronic literature searches were conducted using four databases: PubMed, EMBASE, Web of Science, and Cochrane. Articles reporting titanium mesh exposure rates were included, and exposure rates in different subgroups were compared to determine whether a factor significantly influenced titanium mesh exposure. The review protocol was registered in the PROSPERO registry (CRD42020210187). RESULTS: Twenty and 12 articles were included in the qualitative and quantitative synthesis, respectively. The weighted exposure rates of employing conventional titanium mesh or 3D-customized titanium mesh were 19.9% and 15.2% (P = .34). When employing autogenous bone combined with anorganic bovine bone material as bone graft material, the weighted exposure rate was 21.7%, whereas when using other bone graft material, the exposure rate was 23.5% (P = .74). The weighted exposure rate of using titanium mesh associated with absorbable membranes is 23.9%, while the weighted exposure rate of using titanium mesh without absorbable membranes is 20.2% (P = .36). Meta-regression showed that when analyzing one factor, the other two confounding factors did not influence the result (P = .28). CONCLUSION: It seemed that the type of titanium mesh, the type of bone graft material, or the combined employment of absorbable membranes did not statistically significantly influence the titanium mesh exposure rate in guided bone regeneration.

Zinc Promotes Patient-Derived Induced Pluripotent Stem Cell Neural Differentiation via ERK-STAT Signaling.

Nerve regeneration remains a challenge. Patient-derived induced pluripotent stem cell (iPSC)-differentiated neural stem cells (NSCs) provide a promising hope. Zinc is closely involved in central nervous system development and metabolism, but its role on iPSC neural differentiation is elusive and zinc detection methods in live cells are limited. In this study, intracellular zinc was detected in real time by a zinc fluorescent chemosensor and was shown to be increased during the iPSC neural induction process. iPSC neural differentiation was promoted with the addition of zinc chloride (ZnCl2) and inhibited with the addition of zinc chelator N,N,N0,N0-tetrakis(2-pyridylmethyl)-ethylenediamine, indicated by western blot and enzyme-linked immunosorbent assay analysis of NSC marker Nestin expression and measurement of neurite-like structures. Mechanistically, the phosphorylation level of ERK1/2 and STAT3 was changed with the zinc level, suggesting that zinc may affect the neural differentiation of iPSCs through ERK-STAT signaling. In conclusion, our study shows the important role of zinc in iPSC neural differentiation and suggests a new idea for iPSC-derived NSC application in nerve regeneration.

Small molecule inhibitor of TGF-ß signaling enables robust osteogenesis of autologous GMSCs to successfully repair minipig severe maxillofacial bone defects.

BACKGROUND: Clinically, for stem cell-based therapy (SCBT), autologous stem cells are considered better than allogenic stem cells because of little immune rejection and no risk of communicable disease infection. However, severe maxillofacial bone defects restoration needs sufficient autologous stem cells, and this remains a challenge worldwide. Human gingival mesenchymal stem cells (hGMSCs) derived from clinically discarded, easily obtainable, and self-healing autologous gingival tissues, have higher proliferation rate compared with autologous bone marrow mesenchymal stem cells (hBMSCs). But for clinical bone regeneration purpose, GMSCs have inferior osteogenic differentiation capability. In this study, a TGF-ß signaling inhibitor SB431542 was used to enhance GMSCs osteogenesis in vitro and to repair minipig severe maxillofacial bone defects. METHODS: hGMSCs were isolated and cultured from clinically discarded gingival tissues. The effects of SB431542 on proliferation, apoptosis, and osteogenic differentiation of hGMSCs were analyzed in vitro, and then, SB431542-treated hGMSCs composited with Bio-Oss® were transplanted into immunocompromised mice subcutaneously to explore osteogenic differentiation in vivo. After that, SB431542-treated autologous pig GMSCs (pGMSCs) composited with Bio-Oss® were transplanted into circular confined defects (5 mm × 12 mm) in minipigs maxillary to investigate severe bone defect regeneration. Minipigs were sacrificed at 2 months and nude mice at 8 weeks to retrieve specimens for histological or micro-CT or CBCT analysis. Effects of SB431542 on TGF-ß and BMP signaling in hGMSCs were investigated by Western Blot or qRT-PCR. RESULTS: One micromolar of SB431542 treatment induced a robust osteogenesis of hGMSCs in vitro, without adverse effect on apoptosis and growth. In vivo, 1 µM SB431542 treatment also enabled striking osteogenesis of hGMSCs subcutaneously in nude mice and advanced new bone formation of pGMSCs in minipig maxillary bone defect model. In addition, SB431542-treated hGMSCs markedly increased bone-related proteins expression, and BMP2 and BMP4 gene expression. Conversely, SMAD3 protein-dependent TGF-ß signal pathway phosphorylation was decreased. CONCLUSIONS: Our study show that osteogenic differentiation of GMSCs treated with TGF-ß signaling inhibitor SB431542 was increased, and SB431542-treated autologous pig GMSCs could successfully repair minipig severe maxillofacial bone defects. This preclinical study brings about a promising large bone regeneration therapeutic potential of autologous GMSCs induced by SB431542 in clinic settings.