The mineralized tissues (alveolar bone and cementum) are the major components of periodontal tissues and play a critical role to anchor periodontal ligament (PDL) to tooth-root surfaces. The integrated multiple tissues could generate biological or physiological responses to transmitted biomechanical forces by mastication or occlusion. However, due to periodontitis or traumatic injuries, affect destruction or progressive damage of periodontal hard tissues including PDL could be affected and consequently lead to tooth loss. Conventional tissue engineering approaches have been developed to regenerate or repair periodontium but, engineered periodontal tissue formation is still challenging because there are still limitations to control spatial compartmentalization for individual tissues and provide optimal 3D constructs for tooth-supporting tissue regeneration and maturation. Here, we present the recently developed strategies to induce osteogenesis and cementogenesis by the fabrication of 3D architectures or the chemical modifications of biopolymeric materials. These techniques in tooth-supporting hard tissue engineering are highly promising to promote the periodontal regeneration and advance the interfacial tissue formation for tissue integrations of PDL fibrous connective tissue bundles (alveolar bone-to-PDL or PDL-to-cementum) for functioning restorations of the periodontal complex.

Black rice bran extract (BRBE), containing various biologically active compounds, such as anthocyanin, has antioxidant activity and numerous pharmacological effects. Here, we aimed to confirm the immunostimulatory effects of BRBE in cyclophosphamide (CP)-induced immunosuppressed cells. Our results confirmed that BRBE exerted an immunostimulatory effect. In vitro, BRBE treatment enhanced cell proliferation, activity of natural killer cells and cytotoxic T lymphocytes, and production of CP-repressed cytokines, such as tumor necrosis factor-α, interferon-γ, interleukin (IL)-2, and IL-12, and immunoglobulins G and A in isolated splenocytes. Additionally, in vivo, BRBE treatment increased the number of immune cells, such as white blood cells, lymphocyte counts, mid-range absolute counts, and neutrophils in CP-induced immunosuppressed rats. Furthermore, BRBE increased the serum levels of abovementioned inflammatory cytokines and immunoglobulins in CP-induced immunosuppressed rats. In addition, BRBE protected against CP-mediated spleen and thymic tissue damage. Our findings suggest that BRBE could be potentially used as a component of functional food for immunity enhancement.

Specific orientations of periodontal ligaments (PDLs) to tooth-root surface play an important role in offering positional stabilities of teeth, transmitting and absorbing various stresses under masticatory/occlusal loading conditions, or promoting tissue remodeling by mechanical stimulations to periodontal cells. However, it is still challenging to spatially control PDL orientations and collective PDL cell alignments using 3D scaffold architectures. Here, we investigated the optimization of scaffold topographies in order to control orientations of human PDL cells with predictability in in vitro. The 3D PDL-guiding architectures were designed by computer-aided design (CAD) and microgroove patterns on the scaffold surfaces were created with four different slice intervals such as 25.40 µm (μG-25), 19.05 µm (μG-19), 12.70 µm (μG-12), and 6.35 µm (μG-6) by the digital slicing step. After scaffold design and 3D wax printing, poly-ε-caprolactone (PCL) was casted into 3D printed molds and human PDL cells were cultured for 7 days. In the results, μG-25 with low vertical resolution can angularly organize seeded cells predictably rather than μG-6 created by the highest resolution for high surface quality (or smooth surface). Moreover, nuclear orientations and deformability were quantitatively analyzed and a significant correlation between microgroove pattern intervals and cell alignments was calculated for the topographic optimization. In conclusion, controllable microgroove intervals can specifically organize human PDL cells by 3D printing, which can create various surface topographies with structural consistence. The optimal surface topography (μG-25) can angularly guide human PDL cells, but 6.35 µm-thick patterns (μG-6) showed random organization of cell collectivity.

The periodontal ligament (PDL) is a fibrous connective tissue that anchors the tooth-root surface to the alveolar bone with specific orientations. It plays a crucial role in functional restoration, optimal position stabilities, biomechanical stress transmission, and appropriate tissue remodeling in response to masticatory loading conditions. This pilot study explored spatial microarchitectures to promote PDL orientations while limiting mineralized tissue formation. A computer-designed perio-complex scaffold was developed with two parts: (1) PDL-guiding architectures with defined surface topography and (2) a bone region with open structures. After SEM analysis of micropatterned topographies on PDL-guiding architectures, perio-complex scaffolds were transplanted into two-wall periodontal defects in the canine mandible. Despite the limited bone formation at the 4-week timepoint, bone parameters in micro-CT quantifications showed statistically significant differences between the no-scaffold and perio-complex scaffold transplantation groups. Histological analyses demonstrated that the PDL-guiding architecture regulated fiber orientations and facilitated the functional restoration of PDL bundles in immunohistochemistry with periostin and decorin (DCN). The perio-complex scaffold exhibited predictable and controlled fibrous tissue alignment with specific angulations, ensuring spatial compartmentalization for PDL tissues and bone regenerations. These findings highlighted that the perio-complex scaffold could serve as an advanced therapeutic approach to contribute periodontal tissue regeneration and functional restoration in tooth-supporting structures.

Hematopoietic stem progenitor cells (HSPCs) mobilized to peripheral blood, rather than those remaining in the bone marrow (BM), are commonly used as stem cell source in the clinic. As reactive oxygen species (ROS) are suggested as mediator of HSPC mobilization, we examined the impacts of glucose oxidase (GO) on peripheral mobilization of BM HSPCs and the associated mechanisms. Intravenous injection of GO induced HSPC mobilization even by single treatment, and the GO-mobilized cells maintained their long-term reconstituting and differentiating potentials in conditioned recipients. GO-injected mice lived a normal life without adverse effects such as stem cell senescence, hematopoietic disorders, and blood parameter alteration. The mobilization effect of GO was even evident in animal models showing poor mobilization, such as old, 5-fluorouracil-treated, or alendronate-treated mice. Importantly, combined injection of GO with granulocyte colony-stimulating factor (G-CSF) and/or AMD3100 enhanced more greatly HSPC mobilization than did G-CSF, AMD3100, or both. The GO-stimulated HSPC mobilization was almost completely attenuated by N -acetyl-L-cysteine treatment. Collectively, our results not only highlight the potential role of GO in HSPC mobilization via ROS signaling, but also provide a GO-based new strategy to improve HSPC mobilization in poorly mobilizing allogeneic or autologous donors via combination with G-CSF and/or AMD3100.