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It is a big challenge for bone healing under osteoporotic pathological condition with impaired angiogenesis, osteogenesis and remodeling. In the present study, the effect of Ca, Mg, Si containing akermanite bioceramics (Ca2MgSi2O7) extract on cell proliferation, osteogenic differentiation and angiogenic factor expression of BMSCs derived from ovariectomized rats (BMSCs-OVX) as well as the expression of osteoclastogenic factors was evaluated. The results showed that akermanite could enhance cell proliferation, ALP activity, expression of Runx2, BMP-2, BSP, OPN, OCN, OPG and angiogenic factors including VEGF and ANG-1. Meanwhile, akermanite could repress expression of osteoclastogenic factors including RANKL and TNF-α. Moreover, akermanite could activate ERK, P38, AKT and STAT3 signaling pathways, while crosstalk among these signaling pathways was evident. More importantly, the effect of akermanite extract on RANKL-induced osteoclastogenesis was evaluated by TRAP staining and real-time PCR assay. The results showed that akermanite could suppress osteoclast formation and expression of TRAP, cathepsin K and NFATc1. The in vivo experiments revealed that akermanite bioceramics dramatically stimulated osteogenesis and angiogenesis in an OVX rat critical-sized calvarial defect model. All these results suggest that akermanite bioceramics with the effects of Mg and Si ions on osteogenesis, angiogenesis and osteoclastogenesis are promising biomaterials for osteoporotic bone regeneration.

The surface structure of bioceramic scaffolds is crucial for its bioactivity and osteoinductive ability, and in recent years, human periodontal ligament stem cells have been certified to possess high osteogenic and cementogenic differential ability. In the present study, hydroxyapatite (HA) bioceramics with micro-nano-hybrid surface (mnHA [the hybrid of nanorods and microrods]) were fabricated via hydrothermal reaction of the α-tricalcium phosphate granules as precursors in aqueous solution, and the effects of mnHA on the attachment, proliferation, osteogenic and cementogenic differentiations of human periodontal ligament stem cells as well as the related mechanisms were systematically investigated. The results showed that mnHA bioceramics could promote cell adhesion, proliferation, alkaline phosphatase (ALP) activity, and expression of osteogenic/cementogenic-related markers including runt-related transcription factor 2 (Runx2), ALP, osteocalcin (OCN), cementum attachment protein (CAP), and cementum protein (CEMP) as compared to the HA bioceramics with flat and dense surface. Moreover, mnHA bioceramics stimulated gene expression of low-density lipoprotein receptor-related protein 5 ( LRP5 ) and β-catenin , which are the key genes of canonical Wnt signaling. Moreover, the stimulatory effect on ALP activity and osteogenic and cementogenic gene expression, including that of ALP, OCN, CAP, CEMP, and Runx2 of mnHA bioceramics could be repressed by canonical Wnt signaling inhibitor dickkopf1 (Dkk1). The results suggested that the HA bioceramics with mnHA could act as promising grafts for periodontal tissue regeneration.

BackgroundThis study aimed to retrospectively review the clinical efficacy of open reduction and internal fixation (ORIF) for treatment of high-energy transsyndesmotic ankle fracture dislocation—the “Logsplitter” injury.MethodsBetween December 2006 and December 2014, 41 patients (29 males and 12 females; mean age, 41.46 ± 13.42 years) with Logsplitter injury were treated by ORIF procedure. Patients were grouped as typical injury (mainly vertical axial stress) and untypical injury (mainly rotational stress) according to the injury mechanism and the degree of the talus wedged into the distal tibiofibular joint.ResultsAfter the follow-up of 32.48 ± 24.18 weeks, average American Orthopedic Foot and Ankle Society (AOFAS) score at final follow-up was 78.54 ± 10.66 and the excellent and good rate of 82.9%. Three patients in typical group developed nonunion, and other three cases had infection vs. none in untypical group (both P = 0.053). Burwell-Charnely scoring system revealed anatomic reduction of fracture was achieved in 22 cases, fair reduction in 16 cases, and poor in only 3 cases. Patients in untypical group had better fracture reduction (P = 0.015) and lower incidence rate of posttraumatic ankle arthritis (P = 0.042) than typical cases as well as the range of motion (P < 0.01).ConclusionsThe ORIF may be an optimal approach to treat Logsplitter injuries. Patients with untypical injury had better fracture reduction, range of motion, and low incidence rate of posttraumatic ankle arthritis than those typical ones, and the postoperative outcome was affected by the injury and treatment characteristics.

In this study, we proposed a novel convolutional neural network (CNN) architecture for classification of benign and malignant breast cancer (BC) in histological images. To improve the delivery and use of feature information, we chose the DenseNet as the basic building block and interleaved it with the squeeze-and-excitation (SENet) module. We conducted extensive experiments with the proposed framework by using the public domain BreakHis dataset and demonstrated that the proposed framework can produce significantly improved accuracy in BC classification, compared with the state-of-the-art CNN methods reported in the literature.

Intervertebral disc degeneration (IDD) has been considered as the primary pathological mechanism that underlies low back pain. Understanding the molecular mechanisms underlying human IDD is imperative for making strategies to treat IDD-related diseases. Herein, we report the molecular programs, lineage progression patterns, and paths of cellular communications during the progression of IDD using single-cell RNA sequencing (scRNA-seq) on nucleus pulposus (NP) cells from patients with different grades of IDD undergoing discectomy. New subtypes of cells and cell-type-specific gene signatures of the metabolic homeostatic NP cells (Met NPC), adhesive NP cells (Adh NPC), inflammatory response NP cells (IR NPC), endoplasmic reticulum stress NP cells (ERS NPC), fibrocartilaginous NP cells (Fc NPC), and CD70 and CD82+ progenitor NP cells (Pro NPC) were identified. In the late stage of IDD, the IR NPC and Fc NPC account for a large proportion of NPC. Importantly, immune cells including macrophages, T cells, myeloid progenitors, and neutrophils were also identified, and further analysis showed that significant intercellular interaction between macrophages and Pro NPC occurred via MIF (macrophage migration inhibitory factor) and NF-kB signaling pathways during the progression of IDD. In addition, dynamic polarization of macrophage M1 and M2 cell subtypes was found in the progression of IDD, and gene set functional enrichment analysis suggested a significant role of the macrophage polarization in regulating cell metabolism, especially the Pro NPC. Finally, we found that the NP cells in the late degenerative stage were mainly composed of the cell types related to inflammatory and endoplasmic reticulum (ER) response, and fibrocartilaginous activity. Our results provided new insights into the identification of NP cell populations at single-cell resolution and at the relatively whole-transcriptome scale, accompanied by cellular communications between immune cells and NP cells, and discriminative markers in relation to specific cell subsets. These new findings present clues for effective and functional manipulation of human IDD-related bioremediation and healthcare.

3D‐printed polycaprolactone (PCL) scaffolds have been extensively studied for application in bone tissue engineering. However, PCL‐based scaffolds with enhanced bioactivity and intelligent delivery capability for bone repair remains challenging. Herein, CuS nanoparticle‐PEG soft hydrogel‐coated 3D hard polycaprolactone scaffolds (denoted as CuS‐PEG‐PCL scaffold) are rationally designed for efficient bone regeneration. CuS nanoparticles cross‐linked PEG hydrogel (CuS‐PEG‐hydrogel) endows the PCL‐based scaffold with excellent photothermal properties and stable soft elasticity, while the PCL scaffold provides excellent mechanical performance. Upon exposure to 1064 nm near‐infrared (NIR) light irradiation, dexamethasone sodium phosphate (Dexp), stored in the CuS‐PEG‐PCL scaffold, can be controllably released, which efficiently promotes osteogenic differentiation of bone mesenchymal stem cells (BMSCs). In addition, the combination of mild heating at 42 ± 0.5 °C further promoted osteogenic differentiation of BMSCs. Subsequently, this Dexp‐loaded CuS‐PEG‐PCL scaffold (D‐CuS‐PEG‐PCL scaffold) with NIR light treatment at the tibial defect of rats presented the highest bone regeneration capacity. These findings demonstrate that the Dexp‐loaded CuS‐PEG‐hydrogel can effectively modify the 3D printed PCL scaffold. Therefore, this multifunctional scaffold with a soft‐hard hybrid structure has the potential to become an advanced drug delivery vehicle in the treatment of large bone defects.

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