Natural Affinity Driven Modification by Silicene to Construct a "Thermal Switch" for Tumorous Bone Loss.

Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.

Bacterial Cellulose-Based Bandages with Integrated Antibacteria and Electrical Stimulation for Advanced Wound Management.

Bandages for daily wounds are the most common medical supplies, but there are still ingrained defects in their appearance, comfort, functions, as well as environmental pollution. Here, novel bandages based on bacterial cellulose (BC) membrane for wound monitoring and advanced wound management are developed. The BC membrane is combined with silver nanowires (AgNWs) by using vacuum filtration method to achieve transparent, ultrathin (≈7 µm), breathable (389.98-547.79 g m-2  d-1 ), and sandwich-structured BC/AgNWs bandages with superior mechanical properties (108.45-202.35 MPa), antibacterial activities against Escherichia coli and Staphylococcus aureus, biocompatibility, and conductivity (9.8 × 103 -2.0 × 105  S m-1 ). Significantly, the BC/AgNWs bandage is used in the electrical stimulation (direct current, 600  microamperes for 1 h every other day) treatment of full-thickness skin defect in rats, which obviously promotes wound healing by increasing the secretion of vascular endothelial growth factor (VEGF). The BC bandage is used for monitoring wounds and achieve a high accuracy of 94.7% in classifying wound healing stages of hemostasis, inflammation, proliferation, and remodeling, by using a convolutional neural network. The outcomes of this study not only provide two BC-based bandages as multifunctional wound management, but also demonstrate a new strategy for the development of the next generation of smart bandage.

Endothelial Cell-Derived Lactate Triggers Bone Mesenchymal Stem Cell Histone Lactylation to Attenuate Osteoporosis.

Blood vessels play a role in osteogenesis and osteoporosis; however, the role of vascular metabolism in these processes remains unclear. The present study finds that ovariectomized mice exhibit reduced blood vessel density in the bone and reduced expression of the endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Endothelial cell (EC)-specific deletion of Pkm2 impairs osteogenesis and worsens osteoporosis in mice. This is attributed to the impaired ability of bone mesenchymal stem cells (BMSCs) to differentiate into osteoblasts. Mechanistically, EC-specific deletion of Pkm2 reduces serum lactate levels secreted by ECs, which affect histone lactylation in BMSCs. Using joint CUT&Tag and RNA sequencing analyses, collagen type I alpha 2 chain (COL1A2), cartilage oligomeric matrix protein (COMP), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and transcription factor 7 like 2 (TCF7L2) as osteogenic genes regulated by histone H3K18la lactylation are identified. PKM2 overexpression in ECs, lactate addition, and exercise restore the phenotype of endothelial PKM2-deficient mice. Furthermore, serum metabolomics indicate that patients with osteoporosis have relatively low lactate levels. Additionally, histone lactylation and related osteogenic genes of BMSCs are downregulated in patients with osteoporosis. In conclusion, glycolysis in ECs fuels BMSC differentiation into osteoblasts through histone lactylation, and exercise partially ameliorates osteoporosis by increasing serum lactate levels.

In Situ Enzymatic Reaction Generates Magnesium-Based Mineralized Microspheres with Superior Bioactivity for Enhanced Bone Regeneration.

Bone is a naturally mineralized tissue with a remarkable hierarchical structure, and the treatment of bone defects remains challenging. Microspheres with facile features of controllable size, diverse morphologies, and specific functions display amazing potentials for bone regeneration. Herein, inspired by natural biomineralization, a novel enzyme-catalyzed reaction is reported to prepare magnesium-based mineralized microspheres. First, silk fibroin methacryloyl (SilMA) microspheres are prepared using a combination of microfluidics and photo-crosslinking. Then, the alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) is successfully used to induce the formation of spherical magnesium phosphate (MgP) in the SilMA microspheres. These SilMA@MgP microspheres display uniform size, rough surface structure, good degradability, and sustained Mg2+ release properties. Moreover, the in vitro studies demonstrate the high bioactivities of SilMA@MgP microspehres in promoting the proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis shows that the osteoinductivity of SilMA@MgP microspheres may be related to the activation of the PI3K/Akt signaling pathway. Finally, the bone regeneration enhancement units (BREUs) are designed and constructed by inoculating BMSCs onto SilMA@MgP microspheres. In summary, this study demonstrates a new biomineralization strategy for designing biomimetic bone repair materials with defined structures and combination functions.

Predictive Factors for Late-Onset Neurological Deficits in Patients with Posttuberculous Thoracic Kyphosis.

Background: Patients with severe posttuberculous (TB) kyphosis might suffer from late-onset neurological deficits, and surgical correction may improve neurological function. However, there is a lack of predictive factors for neurological function in these patients. Objective: This study was aimed at identifying the risk factors for late-onset neurological deficits in spinal TB patients at initial and final assessments. Methods: Seventy-eight patients with severe kyphosis caused by old thoracic tuberculosis were retrospectively analyzed. Patients with active spinal TB and other spinal diseases were excluded from the analysis. The kyphosis Cobb angle, sagittal deformity angular ratio (S-DAR), and level of apex were measured and calculated on X-ray. The spinal cord cross-sectional area ratio (CSAR), spinal cord sagittal diameter ratio (SDR), and spinal cord angle (SCA) were measured on preoperative T2-weighted magnetic resonance imaging (MRI). According to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) at the time of admission, the patients were divided into the symptomatic group (N = 60 patients, AIS grades A to D) and the asymptomatic group (N = 18 patients, AIS grade E). All of the symptomatic patients underwent surgery, and the patients from both groups had at least 2 years of follow-up. Relationships among the radiological parameters and initial and final AIS grades were evaluated via univariate and multivariate analyses. Results: The mean duration of kyphotic deformity was 37.4 years in the symptomatic group. There were no significant differences between the two groups in terms of CSAR, kyphosis Cobb angle, S-DAR, level of apex, or the segments that were involved. Patients from the symptomatic group exhibited significantly greater SDR and smaller SCA than those from the asymptomatic group (p < 0.01 and p < 0.01, respectively). The multivariate logistic regression identified SDR and SCA as independent factors influencing the likelihood of spinal cord injury at the initial and final assessments. Conclusions: Severe posttuberculous kyphosis may lead to significant neurological symptoms many years following the initial treatment. The predictive factors for late-onset neurological deficits include larger SDR and smaller SCA.

Hemi-atlas resection by combined approach: case report, literature review, and technical note.

PURPOSE: Hemivertebra within the craniovertebral junction is a rare but complex spinal deformity. Torticollis caused by hemi-atlas is extremely rare. There is no consensus on the treatment of these patients. We present our experience with one case of hemi-atlas excision and torticollis correction via a combined anterior-posterior surgical approach and short-segment fixation. METHODS: An 11-year-old girl with progressive torticollis due to hemi-atlas underwent surgery consisting of combined anterior-posterior hemivertebra resection and instrumentation and had a follow up of 20 months. Pre- and postoperative radiographic features, as well as clinical outcomes, were evaluated. RESULTS: The patient had complete recovery of torticollis at a 20-month follow-up. Radiographs showed favorable deformity correction, well-balanced coronal and sagittal alignment, and solid bony fusion. CONCLUSION: For patients with congenital cervical hemivertebra within the craniovertebral junction, combined anterior-posterior hemivertebra resection with instrumentation allows for satisfactory deformity correction and good cosmetic improvement.

Exosomes from human umbilical cord mesenchymal stem cells inhibit ROS production and cell apoptosis in human articular chondrocytes via the miR-100-5p/NOX4 axis.

Cyclic strain-induced chondrocyte damage is actively involved in the pathogenesis of osteoarthritis and arthritis. MicroRNAs (miRNAs) carried by exosomes have been implicated in various diseases. However, the role of miR-100-5p in cyclic strain-induced chondrocyte damage remains to be elucidated. miR-100-5p and NADPH oxidase 4 (NOX4) were silenced or overexpressed in human primary articular chondrocytes. PKH-67 Dye was used to trace exosome endocytosis. Reactive oxygen species (ROS) production was monitored using DCFH-DA. Cell apoptosis was measured using a flow cytometer. Quantitative RT-PCR and Western blots were used to evaluate gene expression. Cyclic strain promoted ROS production and apoptosis in primary articular chondrocytes in a time-dependent manner. HucMSCs-derived exosomal miR-100-5p inhibited cyclic strain-induced ROS production and apoptosis in primary articular chondrocytes. miR-100-5p directly targeted NOX4. Overexpressing NOX4 attenuated hucMSCs-derived exosomes-mediated protective effects in primary articular chondrocytes. Cyclic strain promotes ROS production and apoptosis in primary articular chondrocytes, which was abolished by hucMSCs-derived exosomal miR-100-5p through its target NOX4. The findings highlight the importance of miR-100-5p/NOX4 axis in primary articular chondrocytes injury and provide new insights into therapeutic strategies for articular chondrocytes injury and osteoarthritis.

A New Insight of Kartogenin Induced the Mesenchymal Stem Cells (MSCs) Selectively Differentiate into Chondrocytes by Activating the Bone Morphogenetic Protein 7 (BMP-7)/Smad5 Pathway.

BACKGROUND Rotator cuff injury is the most common cause of shoulder disability, and although the repair technique has improved, the rate of rotator cuff reduction after repair is still high. The fibrocartilage region, which appears to be histologically inserted, cannot be regenerated. In recent years, studies have reported that mesenchymal stem cells (MSCs) have enhanced cartilage regeneration in the tendon and bone interface after rotator cuff repair, which has become a hot topic of research. MATERIAL AND METHODS Two mesenchymal stem cell types, SMSC (synovial-derived mesenchymal stem cells) and BMSC (bone marrow-derived mesenchymal stem cells) were intervened using kartogenin (KGN). The cytotoxicity was evaluated and the proliferation of the 2 cells was observed. Four commonly used cartilage phenotype genes were detected by quantitative real-time polymerase chain reaction, and the cartilage differentiation of MSCs induced by KGN was explored. The bidirectional regulation of the expression of BMP-7 and the downstream gene Smad5 was observed by constructing a lentiviral overexpression vector containing the target gene BMP-7. To explore whether BMP-7/Smad5 pathway activation promotes differentiation of SMSCs into chondrocytes. RESULTS KGN can induce the selective differentiation of endogenous MSCs into chondrocytes by activating the BMP-7/Smad5 pathway, which promotes the regeneration of interfacial cartilage, and improves the quality of tendon healing of the tendon after rotator cuff repair. CONCLUSIONS This study found a new biological intervention method to promote the effect of tendon on bone healing after rotator cuff repair.