Conductive and Enhanced Mechanical Strength of Mo2Ti2C3 MXene-Based Hydrogel Promotes Neurogenesis and Bone Regeneration in Bone Defect Repair.

Bone defects are common with increasing high-energy fractures, tumor bone invasion, and implantation revision surgery. Bone is an electroactive tissue that has electromechanical interaction with collogen, osteoblasts, and osteoclasts. Hydrogel provides morphological plasticity and extracellular matrix (ECM) 3D structures for cell survival, and is widely used as a bone engineering material. However, the hydrogels have poor mechanical intensity and lack of cell adhesion, slow gelation time, and limited conductivity. MXenes are novel nanomaterials with hydrophilic groups that sense cell electrophysiology and improve hydrogel electric conductivity. Herein, gelatin had multiple active groups (NH2, OH, and COOH) and an accelerated gelation time. Acrylamide has Schiff base bonds to cross-link with gelatin and absorb metal ions. Deacetylated chitosan improved cell adhesion and active groups to connect MXene and acrylamide. We constructed Mo2Ti2C3 MXene hydrogel with improved elastic modulus and viscosity, chemical cross-linking structure, electric conductivity, and good compatibility. Mo2Ti2C3 MXene hydrogel exhibits outstanding osteogenesis in vitro. Mo2Ti2C3 MXene hydrogel promotes osteogenesis via alkaline phosphatase (ALP) and alizarin red S (ARS) staining, improving osteogenic marker genes and protein expressions in vitro. Mo2Ti2C3 MXene hydrogel aids new bone formation in the in vivo calvarial bone defect model via micro-CT and histology. Mo2Ti2C3 MXene hydrogel facilitates neurogenesis factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression, and aids newly born neuron marker Tuj-1 and sensory neuron marker serotonin (5-HT) and osteogenesis pathway proteins, runt-related transcription factor 2 (Runx2), osteocalcin (OCN), SMAD family member 4 (SMAD4), and bone morphogenetic protein-2 (BMP2) in the bone defect repair process. Mo2Ti2C3 MXene hydrogel promotes osteogenesis and neurogenesis, which extends its biomedical application in bone defect reconstruction.

Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling.

Dysregulation of bone homeostasis is closely related to the pathogenesis of osteoporosis. Suppressing bone resorption by osteoclasts to attenuate bone loss has been widely investigated, but far less effort has been poured toward promoting bone formation by osteoblasts. Here, we aimed to explore magnesium ascorbyl phosphate (MAP), a hydrophilic and stable ascorbic acid derivative, as a potential treatment option for bone loss disorder by boosting osteoblastogenesis and bone formation. We found that MAP could promote the proliferation and osteoblastic differentiation of human skeletal stem and progenitor cells (SSPCs) in vitro. Moreover, MAP supplementation by gavage could alleviate bone loss and accelerate bone defect healing through promoting bone formation. Mechanistically, we identified calcium/calmodulin-dependent serine/threonine kinase IIα (CaMKIIα) as the target of MAP, which was found to be directly bound and activated by MAP, then with a concomitant activation in the phosphorylation of ERK1/2 (extracellular regulated kinase 1/2) and CREB (cAMP-response element binding protein) as well as an elevation of C-FOS expression. Further, blocking CaMKII signaling notably abolished these effects of MAP on SSPCs and bone remodeling. Taken together, our data indicated that MAP played an important role in enhancing bone formation through the activation of CaMKII/ERK1/2/CREB/C-FOS signaling pathway and may be used as a novel therapeutic option for bone loss disorders such as osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).

Efficacy of the Dynesys Hybrid Surgery for Patients with Multi-Segmental Lumbar Spinal Stenosis.

Objective: The efficacy of hybrid (Dynesys and fusion) surgery and the traditional transforaminal lumbar interbody fusion surgery was compared in patients with multi-segmental lumbar spinal stenosis. Methods: A total of 68 patients with multi-segmental lumbar spinal stenosis subjected to surgery were recruited between January 2013 and October 2020 in the First Affiliated Hospital of Southern University of Science and Technology. The patients were divided into a hybrid group (N = 33) and a TLIF group (N = 35) by surgery. After surgery, follow-up was conducted for 12 months. Between the two groups, the following parameters were compared: general conditions, clinical symptom scores, imaging parameters, and early complications. Results: A statistically significant difference in the duration of surgery was noted between the two groups. After 12 months of follow-up, the range of motion disappeared in the TLIF group, while 63.53% was preserved in the hybrid group with statistically significant differences. A statistically significant difference was identified in the Oswestry Disability Index one week after surgery. Nonetheless, no statistically significant differences were observed at the 12-month post-surgical follow-up. Pfirrmann grade showed a 3.03% upper adjacent segment degeneration rate in the hybrid group (1/33) at 12-month follow-up and 2.86% (1/35) in the TLIF group. Notably, no early complications (screw loosening and wound infection) were identified in the two groups. Conclusion: The Dynesys hybrid surgery combined the advantages of two systems of dynamic stabilization and rigid fusion. Besides, hybrid surgery is potentially a novel approach for the treatment of multi-segmental lumbar spinal stenosis.

Prognostic factors and its predictive value in patients with metastatic spinal cancer.

BACKGROUND: The spine is the most common location of metastatic diseases. Treating a metastatic spinal tumor depends on many factors, including patients' overall health and life expectancy. The present study was conducted to investigate prognostic factors and clinical outcomes in patients with vertebral metastases. AIM: To investigate prognostic factors and their predictive value in patients with metastatic spinal cancer. METHODS: A retrospective analysis of 109 patients with metastatic spinal cancer was conducted between January 2015 and September 2017. The prognoses and survival were analyzed, and the effects of factors such as clinical features, treatment methods, primary lesions and affected spinal segments on the prognosis of patients with metastatic spinal cancer were discussed. The prognostic value of Frankel spinal cord injury functional classification scale, metastatic spinal cord compression (MSCC), spinal instability neoplastic score (SINS) and the revised Tokuhashi score for prediction of prognosis was explored in patients with metastatic spinal tumors. RESULTS: Age, comorbidity of metastasis from elsewhere, treatment methods, the number of spinal tumors, patient's attitude toward tumors and Karnofsky performance scale score have an effect on the prognosis of patients (all P < 0.05). With respect to classification of spinal cord injury, before operation, the proportion of grade B and grade C was higher in the group of patients who died than in the group of patients who survived, and that of grade D and grade E was lower in the group of patients who died than in the group of patients who survived (all P < 0.05). At 1 mo after operation, the proportion of grade A, B and C was higher in the group of patients who died than in the group of patients who survived, and that of grade E was lower in patients in the group of patients who died than in the group of patients who survived (all P < 0.05). MSCC occurred in four (14.3%) patients in the survival group and 17 (21.0%) patients in the death group (P < 0.05). All patients suffered from intractable pain, dysfunction in spinal cord and even paralysis. The proportion of SINS score of 1 to 6 points was lower in the death group than in the survival group, and the proportion of SINS score of 7 to 12 points was higher in the death group than in the survival group (all P < 0.05). The proportion of revised Tokuhashi score of 0 to 8 points and 9 to 11 points were higher in the death group than in the survival group, and the proportion of revised Tokuhashi score of 12 to 15 points was lower in the death group than in the survival group (all P < 0.05). Frankel spinal cord injury functional classification scale, MSCC, SINS and revised Tokuhashi score were important factors influencing the surgical treatment of patients with metastatic spinal cancer (all P < 0.05). CONCLUSION: Frankel spinal cord injury functional classification scale, MSCC, SINS and revised Tokuhashi score were helpful in predicting the prognosis of patients with metastatic spinal cancer.