Research on guided bone regeneration (GBR) is still ongoing, with evidence mainly from preclinical studies. Various current barrier membranes should fulfill the main design criteria for GBR, such as biocompatibility, occlusivity, spaciousness, clinical manageability and the appropriate integration with the surrounding tissue. These GBR characteristics are required to provide the maximum membrane function and mechanical support to the tissue during bone formation. In this review, various commercially available, resorbable and non-resorbable membranes with different characteristics are discussed and summarized for their usefulness in preclinical studies. Membranes offer promising solutions in animal models; however, an ideal membrane has not been established yet for clinical applications. Every membrane type presents both advantages and disadvantages. Titanium mesh membranes offer superb mechanical properties for GBR treatment and its current efficacy in trials will be a focus in this review. A thorough understanding of the benefits and limitations inherent to various materials in specific clinical applications will be of great value and aid in the selection of an optimal membrane for GBR.

This narrative review explores the extent of the current knowledge of soft tissue barriers around implants from both a basic and clinical perspective, and aims to consolidate this knowledge and highlight the most pertinent questions relating to this area of research.

Connective tissue, one of the main components of peri-implant soft tissue, is key to the formation of the peri-implant mucosal seal and helping to prevent epithelial ingrowth. Rough surfaces (Rs), machined surfaces (Ms) or microgrooved surface (MG) are used in the neck area of commercially available titanium implants. In this paper, we aimed to evaluate the influence of surface topography of titanium substratum on connective tissue fibroblasts to gain a better understanding of this effect. Fibroblasts were cultured on titanium plates with Rs, Ms and MG. Adhesion cell number at day 3 was compared and protein distribution of both F-actin and vinculin was determined to observe cellular structure and adhesion. Cell adhesion strength was compared on each surface. At day 3, the number of fibroblasts attached on each substratum was in the order of MG ≈ Ms > Rs. Fibroblasts strongly expressed vinculin in the peripheral area on Ms and MG, and showed strong F-actin architecture. Decreased expression of vinculin and weaker continuity of F-actin were observed on Rs. Fibroblasts on MG were aligned along the grooves, with a significantly higher cell density, whereas cells on Ms and Rs had no clear orientation. The cell adhesion strength was significantly lower on Rs, and no significant difference was seen between MG and Ms. Both MG and Ms showed greater adhesion cell numbers and adhesion strength of fibroblasts when compared with Rs at day 3. The cell density on MG was greater than those on other substrata.

In the present study, we investigated the hydrothermal treatment of titanium with divalent cation solutions and its effect in promoting the adhesion of gingival epithelial cells and fibroblasts in vitro. Gingival keratinocyte-like Sa3 cells or fibroblastic NIH3T3 cells were cultured for 1 h on experimental titanium plates hydrothermally-treated with CaCl2 (Ca) or MgCl2 (Mg) solution, or distilled water (DW). The number and adhesive strengths of attached cells on the substrata were then analyzed. The number of Sa3 cells adhering to the Ca- and Mg-treated plates was significantly larger than in the DW group, but the strength of this adhesion did not differ significantly between groups. In contrast, NIH3T3 cell adhesion number and strength were increased in both the Ca and Mg groups compared to the DW group. Fluorescent microscopic observation indicated that, in all groups, Sa3 had identical expression levels of integrin β4 and development of actin filaments, whereas NIH3T3 cells in the Ca and Mg groups displayed much stronger punctate cytoplasmic signals for vinculin and more bundle-shaped actin filaments than cells in the DW group. As a result, it was indicated that the hydrothermal treatment of titanium with Ca or Mg solution improved the integration of soft tissue cells with the substrata, which may facilitate the development of a soft tissue barrier around the implant.

Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva‐derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush‐injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells. After crush injury, iNPCs, compared with GMSCs, displayed superior therapeutic effects on axonal regeneration at both the injury site and the distal segment of the injured sciatic nerve. Mechanistically, transplantation of GMSCs, especially iNPCs, significantly attenuated injury‐triggered increase in the expression of c‐Jun, a transcription factor that functions as a major negative regulator of myelination and plays a central role in dedifferentiation/reprogramming of Schwann cells into a progenitor‐like state. Meanwhile, our results also demonstrate that transplantation of GMSCs and iNPCs consistently increased the expression of Krox‐20/EGR2, a transcription factor that governs the expression of myelin proteins and facilitates myelination. Altogether, our findings suggest that transplantation of GMSCs and iNPCs promotes peripheral nerve repair/regeneration, possibly by promoting remyelination of Schwann cells mediated via the regulation of the antagonistic myelination regulators, c‐Jun and Krox‐20/EGR2. Stem Cells Translational Medicine 2017;6:458–470