Transplantation of Wnt5a-modified Bone Marrow Mesenchymal Stem Cells Promotes Recovery After Spinal Cord Injury via the PI3K/AKT Pathway.

Spinal cord injury (SCI) is a severe neurological condition that can lead to paralysis or even death. This study explored the potential benefits of bone marrow mesenchymal stem cell (BMSC) transplantation for repairing SCI. BMSCs also differentiate into astrocytes within damaged spinal cord tissues hindering the cell transplantation efficacy, therefore it is crucial to enhance their neuronal differentiation rate to facilitate spinal cord repair. Wnt5a, an upstream protein in the non-classical Wnt signaling pathway, has been implicated in stem cell migration, differentiation, and neurite formation but its role in the neuronal differentiation of BMSCs remains unclear. Thus, this study investigated the role and underlying mechanisms of Wnt5a in promoting neuronal differentiation of BMSCs both in vivo and in vitro. Wnt5a enhanced neuronal differentiation of BMSCs in vitro while reducing astrocyte differentiation. Additionally, high-throughput RNA sequencing revealed a correlation between Wnt5a and phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT) signaling, which was confirmed by the use of the PI3K inhibitor LY294002 to reverse the effects of Wnt5a on BMSC neuronal differentiation. Furthermore, transplantation of Wnt5a-modified BMSCs into SCI rats effectively improved the histomorphology (Hematoxylin and eosin [H&E], Nissl and Luxol Fast Blue [LFB] staining), motor function scores (Footprint test and Basso-Beattie-Bresnahan [BBB]scores)and promoted neuron production, axonal formation, and remodeling of myelin sheaths (microtubule associated protein-2 [MAP-2], growth-associated protein 43 [GAP43], myelin basic protein [MBP]), while reducing astrocyte production (glial fibrillary acidic protein [GFAP]). Therefore, targeting the Wnt5a/PI3K/AKT pathway could enhance BMSC transplantation for SCI treatment.

Injectable, Electroconductive, Free Radical Scavenging Silk Fibroin/Black Phosphorus/Glycyrrhizic Acid Nanocomposite Hydrogel for Enhancing Spinal Cord Repair.

Spinal cord injury (SCI) often leads to a severe permanent disability. A poor inflammatory microenvironment and nerve electric signal conduction block are the main reasons for difficulty in spinal cord nerve regeneration. In this study, black phosphorus (BP) and glycyrrhizic acid (GA) are integrated into methacrylate-modified silk fibroin (SF) to construct a bifunctional injectable hydrogel (SF/BP/GA) with appropriate conductivity and the ability to inhibit inflammation to promote neuronal regeneration after SCI. This work discovers that the SF/BP/GA hydrogel can reduce the oxidative damage mediated by oxygen free radicals, promote the polarization of macrophages toward the anti-inflammatory M2 phenotype, reduce the expression of inflammatory factors, and improve the inflammatory microenvironment. Moreover, it induces neural stem cell (NSC) differentiation and neurosphere formation, restores signal conduction at the SCI site in vivo, and ameliorates motor function in mice with spinal cord hemisection, revealing a significant neural repair effect. An injectable, electroconductive, free-radical-scavenging hydrogel is a promising therapeutic strategy for SCI repair.

Evaluation of the Anatomical Reference Point in Posterior Minimally Invasive Atlantoaxial Spine Surgery: A Cadaveric Anatomical Study.

OBJECTIVE: Minimally invasive atlantoaxial surgery offers the benefits of reduced trauma and quicker recovery. Previous studies have focused on feasibility and technical aspects, but the lack of comprehensive safety information has limited its availability and widespread use. This study proposes to define the feasibility and range of surgical safety using the intersection of the greater occipital nerve and the inferior border of the inferior cephalic oblique as a reference point. METHODS: Dissection was performed on 10 fresh cadavers to define the anatomical reference point as the intersection of the greater occipital nerve and the inferior border of the inferior cephalic oblique muscle. The study aimed to analyze the safety range of minimally invasive atlantoaxial fusion surgery by measuring the distance between the anatomical reference point and the transverse foramen of the axis, the distance between the anatomical reference point and the superior border of the posterior arch of the atlas, and the distance between the anatomical reference point and the spinal canal. Measurements were compared using Student's t test. RESULTS: The point where the occipital greater nerve intersects with the inferior border of the inferior cephalic oblique muscle was defined as the anatomical marker for minimally invasive posterior atlantoaxial surgery. The distance between this anatomical marker and the transverse foramen of the axis was measured to be 9.32 ± 2.04 mm. Additionally, the distance to the superior border of the posterior arch of the atlas was found to be 21.29 ± 1.93 mm, and the distance to the spinal canal was measured to be 11.53 ± 2.18 mm. These measurement results can aid surgeons in protecting the vertebral artery and dura mater during minimally invasive posterior atlantoaxial surgery. CONCLUSIONS: The intersection of the greater occipital nerve with the inferior border of the inferior cephalic oblique muscle is a safe and reliable anatomical landmark in minimally invasive posterior atlantoaxial surgery.

A pH/GSH/Glucose Responsive Nanozyme for Tumor Cascade Amplified Starvation and Chemodynamic Theranostics.

Nanozymes have brought enormous opportunities for disease theranostics. Here, a self-enhanced catalytic nanocrystal based on a bismuth-manganese core-shell nanoflower containing glucose oxide (GOx), termed BDS-GOx@MnOx, was designed for 4T1 tumor theranostics in vitro and in vivo. The BDS-GOx@MnOx nanozymes enable enhanced starvation treatment (ST) and chemotherapy (CDT) with high efficacy and exhibit sensitive tumor microenvironment (TME) responsive character for tumor therapy as well as for tumor-enhanced computer tomography (CT) and magnetic resonance (MR) diagnostic imaging. The characters and mechanism of the BDS-GOx@MnOx nanozymes have also been systematically studied and revealed.

Copper-containing chitosan-based hydrogels enabled 3D-printed scaffolds to accelerate bone repair and eliminate MRSA-related infection.

Bone defect combined with drug-resistant bacteria-related infection is a thorny challenge in clinic. Herein, 3D-printed polyhydroxyalkanoates/ß-tricalcium phosphate (PHA/ß-TCP, PT) scaffolds were prepared by fused deposition modeling. Then copper-containing carboxymethyl chitosan/alginate (CA/Cu) hydrogels were integrated with the scaffolds via a facile and low-cost chemical crosslinking method. The resultant PT/CA/Cu scaffolds could promote not only proliferation but also osteogenic differentiation of preosteoblasts in vitro. Moreover, PT/CA/Cu scaffolds exhibited a strong antibacterial activity towards a broad-spectrum of bacteria including methicillin-resistant Staphylococcus aureus (MRSA) through inducing the intercellular generation of reactive oxygen species. In vivo experiments further demonstrated that PT/CA/Cu scaffolds significantly accelerated bone repair of cranial defects and efficiently eliminated MRSA-related infection, showing potential for application in infected bone defect therapy.

Conducting molybdenum sulfide/graphene oxide/polyvinyl alcohol nanocomposite hydrogel for repairing spinal cord injury.

A sort of composite hydrogel with good biocompatibility, suppleness, high conductivity, and anti-inflammatory activity based on polyvinyl alcohol (PVA) and molybdenum sulfide/graphene oxide (MoS2/GO) nanomaterial has been developed for spinal cord injury (SCI) restoration. The developed (MoS2/GO/PVA) hydrogel exhibits excellent mechanical properties, outstanding electronic conductivity, and inflammation attenuation activity. It can promote neural stem cells into neurons differentiation as well as inhibit the astrocytes development in vitro. In addition, the composite hydrogel shows a high anti-inflammatory effect. After implantation of the composite hydrogel in mice, it could activate the endogenous regeneration of the spinal cord and inhibit the activation of glial cells in the injured area, thus resulting in the recovery of locomotor function. Overall, our work provides a new sort of hydrogels for SCI reparation, which shows great promise for improving the dilemma in SCI therapy.

Kinematic Alterations After Anterior Cruciate Ligament Reconstruction via Transtibial Techniques With Medial Meniscal Repair Versus Partial Medial Meniscectomy.

BACKGROUND: The treatment strategies for meniscal injuries during anterior cruciate ligament (ACL) reconstruction remain a topic of debate. HYPOTHESIS: After ACL reconstruction, knee kinematics would be affected by different medial meniscal treatment (partial medial meniscectomy [PMM] and medial meniscal repair [MMR]). STUDY DESIGN: Controlled laboratory study. METHODS: A total of 161 patients underwent primary single-bundle ACL reconstruction and simultaneous medial meniscal treatment. Of these, 32 patients were eligible to participate in the kinematic assessment at 24.8 ± 1.7 months after surgery. Patients were divided into 2 groups: (1) those who underwent MMR (Group MMR; n = 18) and (2) those who underwent PMM (Group PMM; n = 14). Twenty healthy participants (Group Intact) were recruited who were comparable in age, body mass index, and sex. The kinematic parameters were collected using an optical tracking system during treadmill gait. Range of motion and kinematic parameters at key events during the gait cycle were compared between the 3 groups. The primary outcomes were the differences in adduction/abduction and internal/external rotation. RESULTS: Patients in Group PMM walked with increased adduction as compared with those in Group Intact during the early stance phase (P = .003; η2 = 0.172) and midstance phase (P = .003; η2 = 0.167). In terms of internal/external rotation, patients in Group PMM walked with significantly larger tibial external rotation when compared with Group MMR by approximately 3.4° to 3.7° (loading response: P = .026, η2 = 0.090; midstance: P = .035, η2 = 0.093) and Group Intact (P = .028; η2 = 0.095) in the early stance phase. In addition, there was significantly increased anterior tibial translation in Groups MMR and PMM compared with Group Intact. CONCLUSION: ACL reconstruction (via transtibial technique) with concurrent PMM demonstrated larger adduction and external tibial rotation at 24 months of follow-up during level walking. CLINICAL RELEVANCE: Patients undergoing different medial meniscal treatment strategies in the presence of ACL reconstruction showed distinct knee kinematics. These results suggest that MMR is strongly recommended during ACL reconstructive surgery to reduce the abnormal kinematics close to that of the ACL-intact condition.

Strontium-substituted hydroxyapatite grown on graphene oxide nanosheet-reinforced chitosan scaffold to promote bone regeneration.

The strontium-substituted hydroxyapatite (SrHA) is a commonly used material in bone regeneration for its good osteoconductivity and high alkaline phosphatase (ALP) activity. Scaffolds used in bone defects require a high compressive modulus. However, the SrHA nanoparticle-doped scaffold cannot properly fit the required mechanical properties. Therefore, a lot of effort has been used to fabricate synthetic bone scaffolds with biocompatibility, suitable mechanical properties, antibacterial ability and osteoconductivity. Here, we used a facile hydrothermal method to synthesize graphene oxide (GO)-reinforced SrHA nanoparticles. The incorporation of GO can be used as nucleation and growth active sites of hydroxyapatite. In addition, GO is easy to self-assemble into a layered structure in the dispersion, which can effectively regulate the deposition of hydroxyapatite on the surface of GO. The scaffold was fabricated using a freeze-drying method by incorporating SrHA/GO nanoparticles into chitosan (CS) and quaternized chitosan (QCS) mixed solutions. The compressive modulus of the CS/QCS/SrHA/GO scaffold reached 438.5 kPa, which was 4-fold higher than that of the CS/QCS scaffold. The CS/QCS/SrHA/GO scaffold exhibited significantly higher in vitro mineralization levels and ALP activity. In vivo rat skull repair indicated that the CS/QCS/SrHA/GO scaffold had a significant role in promoting bone regeneration. This study provides a new strategy for modifying hydroxyapatite to satisfy the biomedical demand of bone tissue engineering scaffolds.

Effectiveness and safety of thymectomy plus prednisone compares with prednisone monotherapy for the treatment of non-thymomatous Myasthenia Gravis: Protocol for a systematic review.

BACKGROUND: The pathogenesis of myasthenia gravis (MG) has strong connection with thymic abnormalities. Thymic hyperplasia or thymoma can be found with most patients. Thymectomy is currently one of the regular treatment in clinic, which is, however, still controversial for non-thymomatous MG. This research will assess the effectiveness and safety of thymectomy plus prednisone compared to prednisone monotherapy for the treatment of non-thymomatous MG systematically. METHODS: According to eligibility and ineligibility criteria, 8 databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan-fang Database, Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (CSTJ), will be searched to gather the up-to-standard articles from September 2000 to September 2025. Inclusion criteria are as follows: randomized controlled trials of thymectomy plus prednisone for the treatment of non-thymomatous MG. The quantitative myasthenia gravis score (QMG) and the dose of prednisone required will be accepted as the main outcomes. Data synthesis, subgroup analysis, sensitivity analysis, and meta-regression analysis will be conducted using RevMan 5.3 software. We will use Egger or Begg test to evaluate symmetry on a funnel plot which is made to assess reporting bias, and use trial sequential analysis (TSA) to exclude the probability of false positives. RESULTS: This systematic review will measure the QMG and the dose of prednisone required, the myasthenia gravis activities of daily living scale scores (MG-ADL), treatment-associated complications, incidence of myasthenic crisis and other aspects to comprehensively assess the clinical benefits of thymectomy plus prednisone for MG patients without thymoma. CONCLUSION: The conclusion of this study will achieve convincing evidence to evaluate the effectiveness and safety of thymectomy plus prednisone for the treatment of non-thymomatous MG. PROSPERO REGISTRATION NUMBER: CRD 42020167735.

An in vitro and in vivo comparison of Mg(OH)2-, MgF2- and HA-coated Mg in degradation and osteointegration.

Magnesium hydroxide (Mg(OH)2), magnesium fluoride (MgF2), and hydroxyapatite (HA) films on Mg are widely studied owing to their easy preparation and favorable corrosion protection. Nevertheless, the most suitable film with the best performance for biomedical applications between the three films remains unknown. Therefore, the performance of the three coatings from in vitro to in vivo must be systematically investigated. In this study, Mg(OH)2, MgF2, and HA films were fabricated on pure Mg. Electrochemical analysis and the hydrogen evolution test suggested that the HA film showed the best in vitro corrosion resistance, followed by MgF2 and Mg(OH)2 films. In vitro cell culture indicated that the extract of the MgF2-coated sample was most beneficial for the osteogenic differentiation of MC3T3-E1 cells and the vascularization of human umbilical vein endothelial cells (HUVECs), which might be ascribed to the existence of the F element in the film. The result of this subcutaneous implantation showed that the HA film exhibited the best in vivo corrosion resistance and induced the lightest inflammatory response. Femoral implantation data revealed that the HA film exhibited the best osseointegration. Furthermore, the major organs and blood indicators of all of the tested rats were normal in 8 weeks. In summary, though the in vitro biological performance of the MgF2 film was the best among the three films, the HA film showed the best in vivo performance, suggesting that it is a more promising modification method for orthopedic applications.

Mild microwave ablation combined with HSP90 and TGF­ß1 inhibitors enhances the therapeutic effect on osteosarcoma.

Osteosarcoma is the most common malignant bone tumour and the second leading cause of cancer­related death in children and adolescents. Microwave ablation has an excellent therapeutic effect on bone tumours by instantaneously increasing the temperature in the tumour; however, there is a risk of damaging the surrounding healthy tissues by exposure to a high temperature when the treatment power is too large. In the present study, two anti­tumour reagents, a heat shock protein 90 (HSP90) inhibitor (PF­04929113) and a transforming growth factor­ß1 (TGF­ß1) inhibitor (SB­525334) were employed to enhance the therapeutic effect of mild­power microwave ablation. It was revealed that microwaving to 48˚C combined with HSP90 and TGF­ß1 inhibitors significantly increased the apoptotic rate of VX2 cells. The same results were observed during in vivo experiments using New Zealand rabbits to model osteosarcoma. In addition, the results indicated that the expression of cytochrome c, caspase­3 and caspase­9 were upregulated in response to the treatment, which indicated that the mitochondrial apoptotic signalling pathway had been activated. These findings may provide a novel strategy for the development of microwave ablation in osteosarcoma treatment, which could effectively kill tumour cells without damaging the surrounding normal tissues.

Bilayer pifithrin-α loaded extracellular matrix/PLGA scaffolds for enhanced vascularized bone formation.

Small intestinal submucosa extracellular matrix (SIS-ECM) composite materials are catching eyes in tissue engineering but have been rarely studied in bone repair. In this study, we developed the unique bilayer bone scaffolds by assembling decellularized SIS-ECM and poly(lactic-co-glycolic acid) (PLGA) nanofibers through the electrospinning technique. To strengthen the bioactivity of the scaffolds, pifithrin-α (PFTα), a p53 inhibitor that can reduce the repressive function of p53 in osteogenesis, was preloaded in the PLGA electrospinning solution. We found that the resultant SIS-ECM/PLGA/PFTα scaffolds exhibited porous morphology, good biocompatibility, and enhanced osteoinductivity. Specifically, the SIS-ECM/PLGA/PFTα scaffolds could promote the osteogenic differentiation and mineralization of the preosteoblasts MC3T3-E1 in a PFTα does dependent manner in vitro. Furthermore, the SIS-ECM/PLGA/PFTα scaffolds were better than the pure SIS-ECM and SIS-ECM/PLGA scaffolds in terms of vessel and new bone tissue formation after 4 weeks post-implantation in vivo. These overall findings indicated that the bilayer PFTα loaded SIS-ECM/PLGA scaffolds facilitated vascularized bone regeneration, showing promising potential for bone tissue engineering.

AgBiS2 nanoparticles with synergistic photodynamic and bioimaging properties for enhanced malignant tumor phototherapy.

Bismuth (Bi)-based nanoagents for synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) are attracting attention and are highly desired for malignant tumor diagnosis and treatment, but producing these materials is still a challenge. Here, we designed theranostic nanoparticles (NPs) based on AgBiS2 for computed tomography (CT) imaging and phototherapy of malignant tumors. These AgBiS2 NPs could effectively convert light into heat (with a high photothermal conversion efficiency of 36.51%) and significantly increase the generation of intracellular reactive oxygen species (ROS) under near infrared (NIR) laser irradiation. Remarkably, the combined PTT/PDT successfully inhibited the growth of a highly malignant osteosarcoma in vivo. In addition, AgBiS2 NPs exhibited an enhanced CT contrast ability for tumor imaging and killed clinically derived Staphylococcus aureus (S. aureus) to prevent infection. In conclusion the ability of AgBiS2 NPs to be used in phototherapy and CT imaging and their antibacterial abilities indicate that they are promising candidates for malignant tumor theranostics.

Biofunctions of antimicrobial peptide-conjugated alginate/hyaluronic acid/collagen wound dressings promote wound healing of a mixed-bacteria-infected wound.

The increase in severe infections caused by antibiotic drug resistance and the decrease in the number of new antibacterial drugs approved for use in the last few decades are driving the need for the development of new antimicrobial strategies. Antimicrobial peptides (AMPs) are a potential new class of antimicrobial drugs that are expected to solve the problem of global antibiotic drug resistance. Herein, the AMP Tet213 was immobilised onto the substrates of alginate (ALG), hyaluronic acid (HA), and collagen (COL) to form the ALG/HA/COL-AMP wound dressing. This wound dressing exhibited a high degree of swelling and the appropriate porosity, mechanical properties, and biodegradability. The Tet213-immobilised ALG/HA/COL dressings exhibited antimicrobial activity against three pathogenic bacterial strains (Gram-negative E. coli and Gram-positive MRSA and S. aureus) and facilitated the proliferation of NIH 3T3 fibroblast cells. In addition, the ALG/HA/COL-AMP antimicrobial dressings promoted wound healing, re-epithelialisation, collagen deposition, and angiogenesis. Moreover, the wound-healing effects of ALG/HA/COL-AMP surpassed the gauze and ALG/HA/COL compared to commercially available silver-based dressings (Aguacel Ag). These results suggest that the Tet213-conjugated ALG/HA/COL wound dressing, with its multiple biological activities, is a promising wound-dressing material.

Synergistic Photothermal and Photodynamic Therapy for Effective Implant-Related Bacterial Infection Elimination and Biofilm Disruption Using Cu9S8 Nanoparticles.

Implant-related bacterial infections are one of the most common but tricky problems in orthopedic clinics because the formation of biofilms inhibits the penetration of antibiotics to kill bacteria effectively; thus, a new strategy is urgently needed. Antibacterial nanomaterials [e.g., copper (Cu)-based nanoparticles (NPs)] combined with near-infrared (NIR) irradiation show enhanced antibacterial activity against clinical bacteria. However, their antibacterial efficiency toward implant-related infections and against biofilm formation remains unclear. Here, unique polyethylene glycol-modified Cu9S8 NPs with good biocompatibility were synthesized. We found that the Cu9S8 NPs exhibited high photothermal performance and could increase the generation of reactive oxygen species under NIR irradiation (808 nm, 1 W cm-2). The Cu9S8 NPs with NIR irradiation successfully destroyed the bacterial structure, resulting in the death of the clinically derived Staphylococcus aureus growing on titanium (Ti) plates. Moreover, this excellent antibacterial activity was indicated to have a synergistic effect with photothermal therapy (PTT) and photodynamic therapy (PDT) by comparison to Cu9S8 with heating treatment in a water bath with similar temperature changes compared to NIR + Cu9S8. Finally, the biofilm formation on the Ti plates was effectively disrupted by NIR + Cu9S8 treatment, while Cu9S8 with thermal treatment showed a mild impact. Hence, Cu9S8 NP-based PTT and PDT can provide a promising approach to eliminating implant-related bacteria and disrupting bacterial biofilms.