Additional file 3 of ETV2 promotes osteogenic differentiation of human dental pulp stem cells through the ERK/MAPK and PI3K-Akt signaling pathways

Additional file 3: Figure S3. HE (scale bar = 200 μm) and Masson (scale bar = 50 μm) staining in the rat calvarial defect model (n = 6)

Additional file 4 of ETV2 promotes osteogenic differentiation of human dental pulp stem cells through the ERK/MAPK and PI3K-Akt signaling pathways

Additional file 4: Figure S4. HE (scale bar = 50 μm) and Masson (scale bar = 50 μm) staining were performed to evaluate ectopic bone formation in nude mice (n=4)

Additional file 2 of ETV2 promotes osteogenic differentiation of human dental pulp stem cells through the ERK/MAPK and PI3K-Akt signaling pathways

Additional file 2: Figure S2. Results of western blot analysis showed that ETV2 overexpression induced the the activation of p-ERK and p-AKT at days 3, 7 and 14 of osteogenic differentiation. *P < 0.05, compared with the 0 day group

DataSheet1_Chirality-biased protein expression profile during early stages of bone regeneration.docx

Introduction: Chirality is a crucial mechanical cue within the extracellular matrix during tissue repair and regeneration. Despite its key roles in cell behavior and regeneration efficacy, our understanding of chirality-biased protein profile in vivo remains unclear.Methods: In this study, we characterized the proteomic profile of proteins extracted from bone defect areas implanted with left-handed and right-handed scaffold matrices during the early healing stage. We identified differentially-expressed proteins between the two groups and detected heterogenic characteristic signatures on day 3 and day 7 time points.Results: Proteomic analysis showed that left-handed chirality could upregulate cell adhesion-related and GTPase-related proteins on day 3 and day 7. Besides, interaction analysis and in vitro verification results indicated that the left-handed chiral scaffold material activated Rho GTPase and Akt1, ultimately leading to M2 polarization of macrophages.Discussion: In summary, our study thus improved understanding of the regenerative processes facilitated by chiral materials by characterizing the protein atlas in the context of bone defect repair and exploring the underlying molecular mechanisms of chirality-mediated polarization differences in macrophages.</p

Image1_A three-dimensional actively spreading bone repair material based on cell spheroids can facilitate the preservation of tooth extraction sockets.TIF

Introduction: Achieving a successful reconstruction of alveolar bone morphology still remains a challenge because of the irregularity and complex microenvironment of tooth sockets. Biological materials including hydroxyapatite and collagen, are used for alveolar ridge preservation. However, the healing effect is often unsatisfactory.Methods: Inspired by superwetting biomimetic materials, we constructed a 3D actively-spreading bone repair material. It consisted of photocurable polyether F127 diacrylate hydrogel loaded with mixed spheroids of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs).Results: Biologically, cells in the spheroids were able to spread and migrate outwards, and possessed both osteogenic and angiogenic potential. Meanwhile, ECs also enhanced osteogenic differentiation of MSCs. Mechanically, the excellent physical properties of F127DA hydrogel ensured that it was able to be injected directly into the tooth socket and stabilized after light curing. In vivo experiments showed that MSC-EC-F127DA system promoted bone repair and preserved the shape of alveolar ridge within a short time duration.Discussion: In conclusion, the novel photocurable injectable MSC-EC-F127DA hydrogel system was able to achieve three-dimensional tissue infiltration, and exhibited much therapeutic potential for complex oral bone defects in the future.</p

Image2_A three-dimensional actively spreading bone repair material based on cell spheroids can facilitate the preservation of tooth extraction sockets.TIF

Introduction: Achieving a successful reconstruction of alveolar bone morphology still remains a challenge because of the irregularity and complex microenvironment of tooth sockets. Biological materials including hydroxyapatite and collagen, are used for alveolar ridge preservation. However, the healing effect is often unsatisfactory.Methods: Inspired by superwetting biomimetic materials, we constructed a 3D actively-spreading bone repair material. It consisted of photocurable polyether F127 diacrylate hydrogel loaded with mixed spheroids of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs).Results: Biologically, cells in the spheroids were able to spread and migrate outwards, and possessed both osteogenic and angiogenic potential. Meanwhile, ECs also enhanced osteogenic differentiation of MSCs. Mechanically, the excellent physical properties of F127DA hydrogel ensured that it was able to be injected directly into the tooth socket and stabilized after light curing. In vivo experiments showed that MSC-EC-F127DA system promoted bone repair and preserved the shape of alveolar ridge within a short time duration.Discussion: In conclusion, the novel photocurable injectable MSC-EC-F127DA hydrogel system was able to achieve three-dimensional tissue infiltration, and exhibited much therapeutic potential for complex oral bone defects in the future.</p

Additional file 1 of ETV2 promotes osteogenic differentiation of human dental pulp stem cells through the ERK/MAPK and PI3K-Akt signaling pathways

Additional file 1: Figure S1. The mRNA level of CBFA1 in qRT-PCR (a) and RNA-Seq (b). *P < 0.05

Engineering 3D-Printed Strontium-Titanium Scaffold-Integrated Highly Bioactive Serum Exosomes for Critical Bone Defects by Osteogenesis and Angiogenesis

Currently, healing of large bone defects faces significant challenges such as a bulk of bone regeneration and revascularization on the bone defect region. Here, a “cell-free scaffold engineering” strategy that integrates strontium (Sr) and highly bioactive serum exosomes (sEXOs) inside a three-dimensional (3D)-printed titanium (Ti) scaffold (Sc) is first developed. The constructed SrTi Sc can serve as a sophisticated biomaterial platform for maintaining bone morphological characteristics of the radius during the period of critical bone defect (CBD) repair and further accelerating bone formation and fibroblastic suppression via the controlled release of Sr from the superficial layer of the scaffold. Moreover, compared with sEXO from healthy donors, the sEXO extracted from the serum of the femoral fracture rabbit model at the stage of fracture healing, named BF EXO, is robustly capable of facilitating osteogenesis and angiogenesis. In addition, the underlying therapeutic mechanism is elucidated, whereby altering miRNAs shuttled by BF EXO enables osteogenesis and angiogenesis. Further, the in vivo study revealed that the SrTi Sc + BF EXO composite dramatically accelerated bone repair via osteoconduction, osteoinduction, and revascularization in radial CBD of rabbits. This study broadens the source and biomedical potential of specifically functionalized exosomes and provides a comprehensive clinically feasible strategy for therapeutics on large bone defects

Image_1_Molecular Expression Profile of Changes in Rat Acute Spinal Cord Injury.tif

Background: Spinal cord injury (SCI) is a highly lethal and debilitating disease with a variety of etiologies. To date, there is no effective therapeutic modality for a complete cure. The pathological mechanisms of spinal cord injury at the molecular gene and protein expression levels remain unclear.Methods: This study used single-cell transcriptomic analysis and protein microarray analysis to analyzes changes in the gene expression profiles of cells and secretion of inflammatory factors respectively, around the lesion site in a rat SCI model.Results: Single-cell transcriptomic analysis found that three types of glial cells (microglia, astrocyte, and oligodendrocyte) becomes activated after acute injury, with GO exhibiting a variety of inflammatory-related terms after injury, such as metabolic processes, immune regulation, and antigen presentation. Protein microarray results showed that the levels of four inflammatory cytokines favoring SCI repair decreased while the levels of nine inflammatory cytokines hindering SCI repair increased after injury.Conclusion: These findings thus reveal the changes in cellular state from homeostatic to reactive cell type after SCI, which contribute to understand the pathology process of SCI, and the potential relationship between glial cells and inflammatory factors after SCI, and provides new theoretical foundation for further elucidating the molecular mechanisms of secondary SCI.</p

Single-Phase Dy₂O₃:Tb³⁺ Nanocrystals as Dual-Modal Contrast Agent for High Field Magnetic Resonance and Optical Imaging

Ultrasmall terbium ions (Tb3+) doped dysprosium oxide (Dy2O3) nanocrystals (NCs) of ∼3 nm diameter have been synthesized and applied as a single-phase dual modality contrast agent for high field magnetic resonance imaging (MRI) and optical imaging. The NCs show excellent positive contrast at 7.0 T MRI in phantom and in vivo imaging in a mouse breast tumor model (MCF-7 cells) injected with NCs. In vitro confocal fluorescence microscopy images show the staining of cultured human bronchial epithelial cells (BEAS-2B) with green fluorescent NCs. In vitro cytotoxicity studies in BEAS-2B and L929 cells indicate that the bifunctional NCs have no appreciable toxicity at a concentration of up to 1000 μg/mL. These results suggest the potential application of these NCs as dual modality contrast agents in a combined high field MRI and fluorescence imaging