Efficient bone regeneration of BMP9-stimulated human periodontal ligament stem cells (hPDLSCs) in decellularized bone matrix (DBM) constructs to model maxillofacial intrabony defect repair.

BACKGROUND: BMP9-stimulated DPSCs, SCAPs and PDLSCs are effective candidates for repairing maxillofacial bone defects in tissue engineering, while the most suitable seed cell source among these three hDMSCs and the optimal combination of most suitable type of hDMSCs and BMP9 have rarely been explored. Moreover, the orthotopic maxillofacial bone defect model should be valuable but laborious and time-consuming to evaluate various candidates for bone regeneration. Thus, inspired from the maxillofacial bone defects and the traditional in vivo ectopic systems, we developed an intrabony defect repair model to recapitulate the healing events of orthotopic maxillofacial bone defect repair and further explore the optimized combinations of most suitable hDMSCs and BMP9 for bone defect repair based on this modified ectopic system. METHODS: Intrabony defect repair model was developed by using decellularized bone matrix (DBM) constructs prepared from the cancellous part of porcine lumbar vertebral body. We implanted DBM constructs subcutaneously on the flank of each male NU/NU athymic nude mouse, followed by directly injecting the cell suspension of different combinations of hDMSCs and BMP9 into the central hollow area of the constructs 7 days later. Then, the quality of the bony mass, including bone volume fraction (BV/TV), radiographic density (in Hounsfield units (HU)) and the height of newly formed bone, was measured by micro-CT. Furthermore, the H&E staining and immunohistochemical staining were performed to exam new bone and new blood vessel formation in DBM constructs. RESULTS: BMP9-stimulated periodontal ligament stem cells (PDLSCs) exhibited the most effective bone regeneration among the three types of hDMSCs in DBM constructs. Furthermore, an optimal dose of PDLSCs with a specific extent of BMP9 stimulation was confirmed for efficacious new bone and new blood vessel formation in DBM constructs. CONCLUSIONS: The reported intrabony defect repair model can be used to identify optimized combinations of suitable seed cells and biological factors for bone defect repair and subsequent development of efficacious bone tissue engineering therapies.

Heterogeneously integrated III-V-on-lithium niobate broadband light sources and photodetectors.

Heterogeneous integration of III-V active devices on lithium niobate-on-insulator (LNOI) photonic circuits enable fully integrated transceivers. Here we present the co-integration of InP-based light-emitting diodes (LEDs) and photodetectors on an LNOI photonics platform. Both devices are realized based on the same III-V epitaxial layers stack adhesively bonded on an LNOI waveguide circuit. The light is evanescently coupled between the LNOI and III-V waveguide via a multiple-section adiabatic taper. The waveguide-coupled LEDs have a 3-dB bandwidth of 40 nm. The photodetector features a responsivity of 0.38 A/W in the 1550-nm wavelength range and a dark current of 9 nA at -0.5 V at room temperature.

Biomechanical Effects of 3D-Printed Bioceramic Scaffolds With Porous Gradient Structures on the Regeneration of Alveolar Bone Defect: A Comprehensive Study.

In the repair of alveolar bone defect, the microstructure of bone graft scaffolds is pivotal for their biological and biomechanical properties. However, it is currently controversial whether gradient structures perform better in biology and biomechanics than homogeneous structures when considering microstructural design. In this research, bioactive ceramic scaffolds with different porous gradient structures were designed and fabricated by 3D printing technology. Compression test, finite element analysis (FEA) revealed statistically significant differences in the biomechanical properties of three types of scaffolds. The mechanical properties of scaffolds approached the natural cancellous bone, and scaffolds with pore size decreased from the center to the perimeter (GII) had superior mechanical properties among the three groups. While in the simulation of Computational Fluid Dynamics (CFD), scaffolds with pore size increased from the center to the perimeter (GI) possessed the best permeability and largest flow velocity. Scaffolds were cultured in vitro with rBMSC or implanted in vivo for 4 or 8 weeks. Porous ceramics showed excellent biocompatibility. Results of in vivo were analysed by using micro-CT, concentric rings and VG staining. The GI was superior to the other groups with respect to osteogenicity. The Un (uniformed pore size) was slightly inferior to the GII. The concentric rings analysis demonstrated that the new bone in the GI was distributed in the periphery of defect area, whereas the GII was distributed in the center region. This study offers basic strategies and concepts for future design and development of scaffolds for the clinical restoration of alveolar bone defect.

SATB2: A versatile transcriptional regulator of craniofacial and skeleton development, neurogenesis and tumorigenesis, and its applications in regenerative medicine.

SATB2 (special AT-rich sequence-binding protein 2) is a member of the special AT-rich binding protein family. As a transcription regulator, SATB2 mainly integrates higher-order chromatin organization. SATB2 expression appears to be tissue- and stage-specific, and is governed by several cellular signaling molecules and mediators. Expressed in branchial arches and osteoblast-lineage cells, SATB2 plays a significant role in craniofacial pattern and skeleton development. In addition to regulating osteogenic differentiation, SATB2 also displays versatile functions in neural development and cancer progression. As an osteoinductive factor, SATB2 holds great promise in improving bone regeneration toward bone defect repair. In this review, we have summarized our current understanding of the physiological and pathological functions of SATB2 in craniofacial and skeleton development, neurogenesis, tumorigenesis and regenerative medicine.

Special AT-rich sequence-binding protein 2 (Satb2) synergizes with Bmp9 and is essential for osteo/odontogenic differentiation of mouse incisor mesenchymal stem cells.

OBJECTIVES: Mouse incisor mesenchymal stem cells (MSCs) have self-renewal ability and osteo/odontogenic differentiation potential. However, the mechanism controlling the continuous self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs remains unclear. Special AT-rich sequence-binding protein 2 (SATB2) positively regulates craniofacial patterning, bone development and regeneration, whereas SATB2 deletion or mutation leads to craniomaxillofacial dysplasia and delayed tooth and root development, similar to bone morphogenetic protein (BMP) loss-of-function phenotypes. However, the detailed mechanism underlying the SATB2 role in odontogenic MSCs is poorly understood. The aim of this study was to investigate whether SATB2 can regulate self-renewal and osteo/odontogenic differentiation of odontogenic MSCs. MATERIALS AND METHODS: Satb2 expression was detected in the rapidly renewing mouse incisor mesenchyme by immunofluorescence staining, quantitative RT-PCR and Western blot analysis. Ad-Satb2 and Ad-siSatb2 were constructed to evaluate the effect of Satb2 on odontogenic MSCs self-renewal and osteo/odontogenic differentiation properties and the potential role of Satb2 with the osteogenic factor bone morphogenetic protein 9 (Bmp9) in vitro and in vivo. RESULTS: Satb2 was found to be expressed in mesenchymal cells and pre-odontoblasts/odontoblasts. We further discovered that Satb2 effectively enhances mouse incisor MSCs self-renewal. Satb2 acted synergistically with the potent osteogenic factor Bmp9 in inducing osteo/odontogenic differentiation of mouse incisor MSCs in vitro and in vivo. CONCLUSIONS: Satb2 promotes self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs. Thus, Satb2 can cooperate with Bmp9 as a new efficacious bio-factor for osteogenic regeneration and tooth engineering.

Role of Special AT-Rich Sequence-Binding Protein 2 in the Osteogenesis of Human Dental Mesenchymal Stem Cells.

Dental mesenchymal stem cells (MSCs) are recognized as a critical factor in repair of defective craniofacial bone owing to the multiple differentiation potential, the ability to regenerate distinct tissues, and the advantage that they can be easily obtained by relatively noninvasive procedures. Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear matrix protein, involved in chromatin remodeling and transcriptional regulation, and has been reported to be as a positive regulator of osteoblast differentiation, bone formation, and bone regeneration in MSCs. In this study, we systematically investigated the capability of SATB2 to promote the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), and stem cells from human exfoliated deciduous teeth (SHED). RNA-seq analysis and quantitative real-time PCR (RT-PCR) revealed that genes regulating osteogenic differentiation were differentially expressed among three cell types and SATB2 was found to be expressed at a relatively high level. When the three cell types overexpressed SATB2 with AdSATB2 infection, alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red S staining, and quantification tended to increase with an increasing infection rate. It showed opposite results after infection with AdsiSATB2. RNA-seq analysis indicated that the expression of downstream osteogenic genes was affected by AdSATB2 infection and quantitative RT-PCR confirmed that nine osteogenic genes (Spp1, Sema7a, Atf4, Ibsp, Col1a1, Sp7, Igfbp3, Dlx3, and Alpl) were upregulated, to various extents, following SATB2 overexpression. In addition, quantitative PCR results indicated that SATB2 affected the expression of MSC markers. These results suggested an important role of SATB2 in the osteogenesis of PDLSCs, DPSCs, and SHED. Further research is warranted to investigate SATB2-mediated regulation of osteogenic differentiation and to evaluate the therapeutic use of SATB2 for the regeneration of defective craniofacial bone tissue.

Triplet Josephson current modulated by Rashba spin-orbit coupling.

We study the Rashba spin-orbit coupling (RSOC) effect on the supercurrent in a clean triplet superconductor/two-dimensional electron gas/triplet superconductor (TS/2DEG/TS) junction, where RSOC is considered in the 2DEG region. Based on the Bogoliubov-de Gennes equation and quantum scattering method, we show that RSOC can lead to a 0-π oscillation of supercurrent and the abrupt current reversal effect. The current direction can be reversed by a tiny modulation of RSOC, and this is attributed to the equal spin pairing of the TS order parameter and the spin precession phase of the quasiparticle traveling in the RSOC region. The RSOC strength can be controlled by an electric field in experiments, thus our findings provide a purely electric means to modulate the supercurrent in TS Josephson junctions.