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Induced pluripotent stem (iPS) cells, which can be generated from somatic cells by genetic manipulation, are invaluable experimental and therapeutic tools for development of tissue regeneration technologies. Many studies have demonstrated that gene delivery to pluripotent stem cells is useful for basic studies in developmental biology and for driving differentiation toward a specific cell lineage for regenerative applications. Several gene delivery systems using viral and nonviral vectors have been used for stem cell research. These gene delivery systems are designed to accommodate specific research purposes; thus, each of them possesses its own advantages and disadvantages according to the experimental design. In addition, the type of constitutive promoter in the expression vector greatly affects the transcriptional activity of transgenes in pluripotent stem cells. Therefore, it is necessary to consider the characteristics of the vectors and their promoters when selecting a gene delivery system to transfer the target gene into iPS cells. In this mini-review, characteristics of commonly used viral (adenoviral, adeno-associated viral, retroviral, and lentiviral) vectors and a nonviral transposon DNA vector with constitutive promoters are outlined to support the selection of an appropriate gene delivery and expression system for iPS cell research.

Cytokine therapy using basic fibroblast growth factor (FGF-2) has attracted attention as a next-generation periodontal tissue regenerative therapy. Clinical trial studies to date have shown that local application of 0.3 % FGF-2 induces statistically significant new alveolar bone formation. In vitro analyses using cultured periodontal ligament cells showed that FGF-2 maintains stem cells in an undifferentiated state and promotes the proliferation of these stem cells during the initial stages of wound healing. This increases the cell density of periodontal tissue stem cells at the site of healing, promotes angiogenesis, and produces specific extracellular matrix molecules, thereby preparing a local environment suitable for the regeneration of periodontal tissue. Additionally, based on an analysis in beagles, when adipose tissue-derived multi-lineage progenitor cells (ADMPCs) isolated from adipose tissue were transplanted together with fibrin gel to areas of periodontal tissue loss, significant regeneration of periodontal tissue was observed at the transplantation site. These results strongly suggest that adipose tissue, which is abundant in the human body and can be easily and safely collected, is a promising source of stem cells to promote the regeneration of periodontal tissue.

Tooth number, shape, and position are consistent in mammals and are subject to strict genetic control. Multiple signaling pathways including Shh, Tgf, Bmp, Wnt, Fgf, Notch, and NF-kB are known to play critical roles in regulating tooth development. Recent studies show that these signaling pathways interact with each other through positive and negative feedback loops to regulate tooth number, shape, and spatial pattern. Teeth develop via a dynamic and complex reciprocal interaction between dental epithelium and cranial neural crest-derived mesenchyme. These interactions contain a series of inductive and permissive processes that lead to the determination, differentiation, and organization of odontogenic cells, which are controlled by these signaling pathways. It is believed that dozens of different molecules together form complex molecular networks that regulate tooth development. Studies of human congenital disease and transgenic mice suggest that disturbance of the molecular network results in abnormal tooth formation. Since molecular mechanisms involved in tooth development should be reproduced in tooth regeneration, knowledge of tooth development from both human and mouse studies is crucial for exploring tooth regenerative therapies. In this paper, we present an overview of the current literature covering the molecular mechanisms of tooth development, especially those regulating tooth number.

The Medical Device Innovation Center (MDIC) at the National Cheng Kung University has developed a complete and professional digital dentistry design workflow with cutting-edge equipment and software. MDIC certified with ISO13485 can provide total solutions in digital dentistry. An “Intelligent Manufacturing Systems Center” (IMSC) has been established using dental open technologies toward providing digital dentistry training and restoration design services. This digital dental laboratory is able to control the entire digital process from digital impressions to the CAD/CAM creation of the restoration and model milling. An intraoral scanner is used to make digital impressions for 3D geometric models from the chair side or from traditional impressions. In the design phase, three different commercial software packages are considered for the design portion. After importing the digital impression STL data file, one or more of these packages are used to design the restoration. The design is then sent to a five-axis milling machine for production. The CNC machines are chosen for machining or milling of the prosthetics from various materials including wax, PMMA, zirconia, chromium cobalt, resin nano-ceramics, glass ceramics, lithium disilicate, silicate ceramics, and titanium. As a cloud base solution, these design packages allow a connection to a remote manufacturing site. Our R&D team built a web-based cloud solution that can be deployed to each pertinent location. All data from the design package is stored on a private cloud which is then automatically synced to the remote public cloud. Work orders from various sources are then processed by any remote technician. Through the above settings, we may produce several common digital dentistry products including crowns and bridges, veneers, inlays and onlays, temporary crowns, and virtual diagnostic wax-ups. This digital dentistry laboratory is also equipped to handle advanced clinical cases such as implant planning, digital smile design analysis and customized surgical guides, custom abutments, implant bridges and bar designs, and orthodontics. Digital animation is applied for patient education and communication. For academics and training, a comprehensive digital technology training program has been developed to help dentists and dental technicians.

To improve sensitivity of dental caries detection by laser-induced breakdown spectroscopy (LIBS) analysis, it is proposed to utilize emission peaks in the ultraviolet. We newly focused on zinc whose emission peaks appear in ultraviolet because zinc exists at high concentration in the outer layer of enamel. It was shown that by using ratios between heights of an emission peak of Zn and that of Ca, the detection sensitivity and stability are largely improved. It is also shown that early caries are differentiated from healthy part by properly setting a threshold in the detected ratios. The proposed caries detection system can be applied to dental laser systems such as ones based on Er:YAG lasers. When ablating early caries part by laser light, the system notices the dentist that the ablation of caries part has been finished. We also show the intensity of emission peaks of zinc decreased with ablation with Er:YAG laser light.

There are a lot of diseases which show the abnormal elastic property. Although many medical doctors and dentists have noticed the change of tissue elasticity due to the disease, the diagnostic device to examine the tissue elastic property objectively has not well developed.

At Tohoku University, acoustic microscopy (AM) for medicine and biology has been developed and applied for more than 20 years. Application of AM has three major features and objectives. First, specific staining is not required for characterization or observation. Second, it provides the elastic property and information of the subject, because acoustic properties have close correlation with the mechanical property of the subject. Third, it makes the observation easy and rapid. The purpose of this study is to observe carious dentin and periodontal ligament (PDL) using AM. Moreover, I would like to propose the prototype of the portable caries detector.

AM clearly visualizes the color distribution of the acoustic properties of the subject.

The acoustic examination device may be a powerful apparatus not only to visualize the morphological appearance but also to diagnose the disease.

Periodontal ligament stem cells (PDLSCs) have been served as a cell reservoir for tissue regeneration during adulthood. For clinical applications, the challenging steps are to maintain the stem cell properties and to improve the regeneration capacity of PDLSCs during culture. Toll-like receptor 3 (TLR3) signaling has been shown to enhance therapeutic potential in several cell types including mesenchymal stem cells (MSCs) by inducing the secretion of multifunctional trophic factors. However, the role of TLR3 in PDLSCs is still unknown. The aim of this study was to investigate the responses of PDLSCs after TLR3 engagement using TLR3 agonist, poly(I:C). The result indicated that stimulation of TLR3 significantly enhanced pluripotent stem cell gene expression (e.g., REX-1 and SOX2) as well as immunomodulatory molecules (e.g., IFNγ and IDO). Interestingly, inhibition of NF-kB signaling decreased the TLR3-activated IFNγ but increased the TLR3-activated IDO expression, suggesting the multiple pathways in the inductive mechanism. Our finding supports the concept that activated TLR3 could encourage the stem cell and immunosuppressive properties of PDLSCs. Since immunosuppressive properties of stem cells could support tissue healing and regeneration, activation of TLR3 in PDL cells may trigger the effective PDL tissue regeneration.

Periodontal disease is the most prevalent oral disease. The pathogenesis of this disease is mostly due to the robust host immune response, leading to the destruction of tooth-supporting tissue. Several cytokines have been shown to play roles in pathogenesis of periodontal disease; however, inflammatory cytokines can also activate the immunomodulatory properties of mesenchymal stem cells (MSCs), the mechanism to protect and maintain cell survival under inflammatory environment. Therefore, inflammation can exert both negative and positive effects for regulating tissue homeostasis. Interleukin 12 (IL-12) is one of the potent destructive stimulators in pathogenesis of many inflammatory diseases. In periodontitis, the increased level of IL-12 in serum and gingival crevicular fluid was found associated with the severity of the periodontal disease. However, the exact role of IL-12 in periodontitis is still unclear. The aim of this study was to investigate the responses of human periodontal ligament (PDL) cells to exogenous IL-12, especially on the immunomodulatory effects of IL-12. The results demonstrated the presence of IL-12 and IL-12 receptor (IL-12R) in periodontal tissues, and the expression was enhanced in tissues from periodontitis patients. Exogenous IL-12 stimulated the expression of some inflammatory cytokines as well as the immunomodulatory molecules, such as interferon gamma (IFNγ), human leukocyte antigen (HLA), and indoleamine-pyrrole-2,3-dioxygenase (IDO) enzyme. In conclusion, the data suggested the influence of increased IL-12, during periodontal inflammation, on controlling tissue’s homeostasis by upregulating the inflammatory cytokines and modulating the function of immune cells through the expression of immunosuppressive molecules.

The microstructures, mechanical properties, and biocompatibility of various low-cost -type Ti-Mn alloys fabricated by both cold crucible levitation melting (CCLM) and metal injection molding (MIM) were investigated after solution treatment. Mn was chosen as a potential low-cost alloying element for Ti. Among the alloys fabricated by both methods, Ti-9Mn shows the best combination of tensile strength and elongation, and their performances are mostly comparable to or superior to those of Ti-6Al-4V (Ti-64) ELI. However, alloys fabricated by MIM show a higher O and C content, along with precipitated Ti carbides and pores, which all cause the ductility of the alloys fabricated by MIM to be lower than that of the alloys fabricated by CCLM. Furthermore, the cell viability and metallic ion release ratios of the alloys fabricated by CCLM are comparable to those of commercially pure Ti, making this alloy promising for biomedical applications. The Young’s modulus of the alloys is also lower than that of Ti-64 ELI (which is of approximately 110 GPa), which can possibly reduce the stress shielding effect in implanted patients.

The initial cellular response to the dental implant is essential for the subsequent tissue regeneration around the foreign implant surface. There are many cells and proteins involved in the integration process which leads to the final osseointegration between implants and peri-implant bone tissue. With regard to materials used in dental implants, titanium is a prevalent biomaterial applied in orthopedic or dental implants due to its premium mechanical and biological properties and osteoconductivity. The roughness and chemical composition of the titanium surface affect the process and rate of the osseointegration of dental implants. Different studies on the effect of roughness and wettability of titanium surface on the process of early events in the osseointegration are reviewed in this article. In addition, in order to accelerate this wound-healing process, varied surface topography and chemical composition have been produced depending on different types of surface modifications. The desirable dental implant surface design caters for the development of implantology for immediate loading and the improvement of long-term stability. An appropriate understanding of the interaction between cells and implant surfaces is essential for the future design of new surface which could enhance the speed and stability of osseointegration of dental implants.