Background: In dentistry, barrier membranes are used for guided tissue regeneration (GTR) and guided bone regeneration (GBR). Various membranes are commercially available and extensive research and development of novel membranes have been conducted. In general, membranes are required to provide barrier function, biosafety, biocompatibility and appropriate mechanical properties. In addition, membranes are expected to be bioactive to promote tissue regeneration.Objectives: This review aims to organize the fundamental characteristics of the barrier membranes that are available and studied for dentistry, based on their components. Results: The principal components of barrier membranes are divided into nonbiodegradable and biodegradable materials. Nonbiodegradable membranes are manufactured from synthetic polymers, metals or composites of these materials. The first reported barrier membrane was made from expanded polytetrafluoroethylene (e-PTFE). Titanium has also been applied for dental regenerative therapy and shows favorable barrier function. Biodegradable membranes are mainly made from natural and synthetic polymers. Collagens are popular materials that are processed for clinical use by crosslinking. Aliphatic polyesters and their copolymers have been relatively recently introduced into GTR and GBR treatments. In addition, to improve the tissue regenerative function and mechanical strength of biodegradable membranes, inorganic materials such as calcium phosphate and bioactive glass have been incorporated at the research stage. Conclusions: Currently, there are still insufficient guidelines for barrier membrane choice in GTR and GBR, therefore dentists are required to understand the characteristics of barrier membranes.
Background and Objective:The clinical outcomes of guided tissue regeneration (GTR) or guided bone regeneration (GBR) procedures can be impaired if a bacterial infection develops at the surgical site. Membrane exposure is one of the causes of the onset of bacterial infection. Previously, we have fabricated a poly(lactic acid/caprolactone) (PLCL) bilayer membrane composed of a porous layer and a compact layer.The compact layer acts as a barrier against connective tissue and epithelial cells, and we hypothesized that it could also be an effective barrier against bacterial cells. The objective of this study was to evaluate the ability of the PLCL bilayer membrane to block bacterial cell penetration, which would be useful for preventing postoperative infections.Methods: Porphyromonas gingivalis, Streptococcus mutans, and multispecies bacteria collected from human saliva were used in this study. Bacteria were seeded directly on the compact layer of a PLCL bilayer membrane, and bacterial adhesion to the membrane, as well as penetration into the membrane's structure, were assessed.Bacterial adhesion was evaluated by the number of colonies formed at 6, 24, and 72 h, and penetration was observed using a scanning electron microscope at 24 and 72 h.Commercially available membranes, composed of poly(lactic-co-glycolic acid) or type I collagen, were used as controls.Results: P. gingivalis, S. mutans, and the multispecies bacteria obtained from human saliva adhered onto all the membranes after only 6 h of incubation. However, fewer adherent cells were observed for the PLCL bilayer membrane compared with the controls for all experimental periods. The PLCL membrane was capable of blocking bacterial penetration, and no bacterial cells were observed in the structure. In contrast, bacteria penetrated both the control membranes and were observed at depths of up to 80 µm after 72 h of incubation. Conclusion: Membrane characteristics may influence how bacterial colonizationoccurs. The PLCL membrane had reduced bacterial adhesion and blocked bacterial penetration, and these characteristics could contribute to a favorable outcome for regenerative treatments. In the event of membrane exposure at GTR/GBR surgical sites,
Much research has been conducted on fabricating biomimetic biomaterials in vitro. Tissue engineering approaches are often conducted by combining cells, scaffolds, and growth factors. However, the degradation rate of scaffolds is difficult to control and the degradation byproducts occasionally limit tissue regeneration. To overcome these issues, we have developed a novel system using a thermo-responsive hydrogel that forms scaffold-free, three-dimensional (3D) cell constructs with arbitrary size and morphology. 3D cell constructs prepared using bone marrow-derived stromal stem cells (BMSCs) exhibited self-organizing ability and formed bone-like tissue with endochondral ossification. Endothelial cells were then introduced into the BMSC construct and a vessel-like structure was formed within the constructs. Additionally, the bone formation ability was promoted by endothelial cells and cell constructs could be freeze-dried to improve their clinical application. A pre-treatment with specific protein protectant allowed for the fabrication of novel bone substitutes composed only of cells. This 3D cell construct technology using thermo-responsive hydrogels was then applied to other cell species. Cell constructs composed of dental pulp stem cells were fabricated, and the resulting construct regenerated pulp-like tissue within a human pulpless tooth. In this review, we demonstrate the approaches for the in vitro fabrication of bone and dental pulp-like tissue using thermo-responsive hydrogels and their potential applications.
Bone organoids offer a novel path for the reconstruction and repair of bone defects. We previously fabricated scaffold-free bone organoids using cell constructs comprising only bone marrow-derived mesenchymal stem cells (BMSCs). However, the cells in the millimetre-scale constructs were likely to undergo necrosis because of difficult oxygen diffusion and nutrient delivery. Dental pulp stem cells (DPSCs) are capable of differentiating into vascular endothelial lineages and have great vasculogenic potential under endothelial induction. Therefore, we hypothesized that DPSCs can serve as a vascular source to improve the survival of the BMSCs within the bone organoid. In this study, the DPSCs had greater sprouting ability, and the proangiogenic marker expressions were significantly greater than those of BMSCs. DPSCs were incorporated into the BMSC constructs at various ratios (5%–20%), and their internal structures and vasculogenic and osteogenic characteristics were investigated after endothelial differentiation. As a result, the DPSCs are differentiated into the CD31-positive endothelial lineage in the cell constructs. The incorporation of DPSCs significantly suppressed cell necrosis and improved the viability of the cell constructs. In addition, lumen-like structures were visualized by fluorescently labelled nanoparticles in the DPSC-incorporated cell constructs. The vascularized BMSC constructs were successfully fabricated using the vasculogenic ability of the DPSCs. Next, osteogenic induction was initiated in the vascularized BMSC/DPSC constructs. Compared with only BMSCs, constructs with DPSCs had increased mineralized deposition and a hollow structure. Overall, this study demonstrated that vascularized scaffold-free bone organoids were successfully fabricated by incorporating DPSCs into BMSC constructs, and the biomimetic biomaterial is promising for bone regenerative medicine and drug development.
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