The World's First Implantation of a Personalized Microporous Titanium Sternum with Motile Costal Clip Connections: A Case Report.

Extensive chest wall defects occur in 28% of all sternal resection cases and are a major challenge in thoracic surgery. These cases are generally considered "critical defects" requiring primary or secondary reconstruction using various types of flaps, mesh repairs, bone autografts, or endoprosthesis. The past decade witnessed rapid advances in the application of personalized endoprostheses in thoracic surgery. Surgeons began to use carbon or titanium grafts for personalized sternum replacement. The main advantages of these implants are superior cosmetic effect, biocompatibility, and low risk of infection. Herein, we present a case of a 55-year-old patient with an indication for extended sternum resection due to metastatic thyroid cancer. The patient underwent extended sternum resection, followed by the implantation of a personalized microporous titanium sternum equipped with graspers for atraumatic rib fixation.

Very early migration of a calcar-guided short stem: a randomized study of early mobilization and the influence of a calcium phosphate coating with 60 patients.

This study analyzed the migration of a calcar-guided short stem to determine the course of very early migration, as well as evaluated the effect of an additional calcium phosphate (CP) coating on a titanium plasma spray (TPS) coating, which has not been analyzed previously. Sixty patients were enrolled in this study and were treated with the A2 calcar-guided short stem. The implant coating was randomized with either the TPS or an additional CP coating, and radiostereometric analysis was performed with the baseline measurement before initial weight-bearing, along with follow-up examinations at 1 week, 6 weeks, 3 months, and 6 months. Implant migrations were 0.27 mm (standard deviation [SD], 0.13 mm) and 0.74 mm (SD, 1.11 mm) at 1 week and 6 months post-surgery, respectively, and 65% and 87% of the implants reached their final position 1 week and 6 weeks after surgery, respectively. After 6 weeks, 3 months, and 6 months, a significant increase was noted in the migration of the CP coating group vs. that of the TPS coating group. Upon the final observation at 6 months, the groups displayed on average a 0.74-mm migration. Most of the analyzed implants ceased migration within the first week post-surgery, but the CP coating demonstrated a higher and more prolonged migration compared to the TPS coating.

Comparison between bioabsorbable magnesium and titanium compression screws for hallux valgus treated with distal metatarsal osteotomies: A meta-analysis.

OBJECTIVES: In this review, we discuss the efficacy and safety of biodegradable magnesium screws compared to titanium screws in the treatment of hallux valgus (HV) in patients undergoing distal metatarsal osteotomy (DMO). MATERIALS AND METHODS: Eligible scientific articles published prior to October 2022 were retrieved from the PubMed, Springer, ScienceDirect, and Cochrane Library databases. The terms used for searching included "hallux valgus", "distal metatarsal osteotomies", and "bioabsorbable magnesium screw" which were limited in the title or abstract through the text. The title and abstract were checked one by one to exclude the non-related studies. For primary identified studies and relevant systematic reviews, the full texts were accessed and browsed to finally include the eligible studies. No restriction was set on publication language and publication status. RESULTS: Two randomized-controlled trials (RCTs) and three non-RCTs that met the inclusion criteria were included. There was no significant difference in the American Orthopaedic Foot and Ankle Society (AOFAS) score, postoperative HV angle (HVA), intermetatarsal angle (IMA), Visual Analog Scale (VAS) score, soft tissue irritation, implant fracture, reoperation, and infection rates between two groups. CONCLUSION: Bioabsorbable magnesium compression screws show comparable clinical or radiological results to titanium compression screws in the treatment of HV in patients undergoing DMO.

Novel Nerve-Sparing In Situ Assembly of an Expandable Titanium Cage to Maximize Endplate Coverage After Posterior Corpectomy for Comminuted Lumbar Burst Fractures.

BACKGROUND AND OBJECTIVES: The ability to maximize corpectomy cage endcap size and vertebral endplate coverage after corpectomy for lumbar burst fractures (L1-L5) is limited by the presence of lumbar nerve roots and the larger cross-sectional area of the lumbar endplates relative to the restrictive corridor for cage insertion. This work aims to provide details and clinical examples of a novel operative technique for 3-column reconstruction and stabilization of comminuted lumbar burst fractures. METHODS: Through a standard posterior midline approach and following posterior instrumentation and lateral extracavitary corpectomy, an in-situ assembly of a modular corpectomy cage that respects adjacent neural structures, restores segmental alignment, and maximizes endplate coverage across a lordotic segment is completed. RESULTS: Radiographic evidence of anatomic spinal reconstruction and stabilization with complete or near-complete endplate coverage without incurrence of new clinical deficit after this novel treatment of lumbar burst fractures. CONCLUSION: The fixation approach described in this report may be a valuable modification to a long-standing technique used for treating comminuted lumbar burst fractures (L1-L5) from a posterior-only approach without incurring additional neurological deficits and by improving endplate and apophyseal ring coverage.

Schottky Junction Nanozyme Based on Mn-Bridged Co-Phthalocyanines and Ti3C2Tx Nanosheets Boosts Integrative Type I and II Photosensitization for Multimodal Cancer Therapy.

Cancer phototheranostics have the potential for significantly improving the therapeutic effectiveness, as it can accurately diagnose and treat cancer. However, the current phototheranostic platforms leave much to be desired and are often limited by tumor hypoxia. Herein, a Schottky junction nanozyme has been established between a manganese-bridged cobalt-phthalocyanines complex and Ti3C2Tx MXene nanosheets (CoPc-Mn/Ti3C2Tx), which can serve as an integrative type I and II photosensitizer for enhancing cancer therapeutic efficacy via a photoacoustic imaging-guided multimodal chemodynamic/photothermal/photodynamic therapy strategy under near-infrared (808 nm) light irradiation. The Schottky junction not only possessed a narrow-bandgap, enhanced electron-hole separation ability and exhibited a potent redox potential but also enabled improved H2O2 and O2 supplying performances in vitro. Accordingly, the AS1411 aptamer-immobilized CoPc-Mn/Ti3C2Tx nanozyme illustrated high accuracy and excellent anticancer efficiency through a multimodal therapy strategy in in vitro and in vivo experiments. This work presents a valuable method for designing and constructing a multifunctional nanocatalytic medicine platform for synergistic cancer therapy of solid tumors.

Anti-tumoral Titanium(IV) Complexes Stabilized with Phenolato Ligands and Structure-Activity Relationship.

Titanocene dichloride and budotitane have opened a new chapter in medicinal chemistry of titanium(IV) complexes being novel non-platinum antitumor metallic agents. Numerous efforts have led to the discovery of the diamino bis-phenolato titanium(IV) complexes. Among which, the [ONNO] and [ONON] type ligands namely Salan, Salen and Salalen coordinated titanium(IV) alkoxyl complexes have demonstrated significantly enhanced aqueous stability, their in vitro and in vivo antitumor efficacy, mechanism of action, structure-activity relationships and combined tumor therapy have been intensively investigated. Replacement of the labile alkoxyls with a second chelator resulted in structural rigid titanium(IV) complexes, which showed exceedingly good aqueous stability and potent antitumor activity both in vitro and in vivo. The unique ligand system successfully allowed the access of isotopic [45Ti]Titanium(IV) complexes, post-synthetic modification, facile synthetic protocols and antitumor congeneric zirconium(IV) and hafnium(IV) complexes. This review presents recent research progress in the field of antitumor group 4 metal complexes stabilized with phenolato ligands; especially their structure-activity relationships are summarized.

The 3D-Printed Titanium Truss Cage for the Treatment of Concurrent Complex Malunion, Synostosis and Large Bone Defect Following Forearm Injuries: A Case Report.

A 28-year-old man sustained a complex forearm injury from high-energy trauma, causing ulnar nerve injury, a bone defect, forearm malunion and synostosis. A 3D-printed titanium truss cage was used to solve these problems. This patient achieved union of the bone defect, was pain-free and had no recurrent synostosis 2 years after reconstructive surgery. The advantages of the 3D-printed titanium truss cage included anatomical fit, immediate mobilisation and low morbidity of the donor side of the bone graft. This study reported a promising result from using 3D-printed titanium truss cages to manage complex forearm bony problems. Level of Evidence: Level V (Therapeutic).

Brixia system of screws: a titanium modular system with wide applicability for reinforced sternal closure in cardiac and thoracic surgery.

The use of cannulated screws and titanium plates to reinforce the sternal closure or to treat sternal dehiscence after median sternotomy has already been suggested in several articles. The system proposed here has some important advantages over those already described. Moreover, thanks to its characteristics, this system can also be used to treat pathologies affecting the entire rib cage. The system consists of a first threaded cannulated screw that is inserted in the bone or chondral cartilage and accommodates a cap screw that is tightened into the first screw and fixes a plate according to the following scheme: a threaded cannulated screw/plate/cap screw (Brixia system of screws). This system allows the plates to be fixed on the anterior face of the ribs and/or sternum without the need to enlarge dissection of the tissue, thereby lowering the danger of haemorrhage and injury to the thoracic organs. For this reason, it is particularly suitable for treating post-sternotomy sternal dehiscence, but it can be used to reinforce the primary sternal closure (after median or transversal sternotomy) in high-risk patients with sternal dehiscence. Owing to the modular nature of the system, singular components can also be utilized independently.

Multifunctional Au Modified Ti3C2-MXene for Photothermal/Enzyme Dynamic/Immune Synergistic Therapy.

Ti3C2-MXene-based composites provide multifunctional interfaces in diagnosis and treatment of tumors. Herein, we proposed a multifunctional nanoplatform based on Ti3C2-MXene-Au nanocomposites, which combines photothermal properties and peroxidase-like activity, accomplishing synergistic photothermal therapy (PTT) and enzyme dynamic therapy (EDT) accompanied by photoacoustic (PA) and thermal dual-mode imaging in vivo. Furthermore, PTT induces immunogenic cell death, and EDT promotes cell apoptosis, facilitating dendritic cell (DC) maturation and T cell infiltration into the tumor. On this basis, the antibody OX40 (αOX40) was utilized to further contribute immune therapy for reversing the immunosuppressive tumor microenvironment by activating CD4+ and CD8+ T cells. In summary, a triune of PTT/EDT/antitumor immune therapy is achieved by combining Ti3C2-MXene-Au nanocomposites and αOX40, which possesses several strong features of good biocompatibility, NIR-controlled targeting, significant cancer cell killing, and satisfactory biosafety in vitro and in vivo. Our work might highlight the promising application of MXene-based nanoplatforms for cancer therapy.

Testicular yolk sac tumour metastasis to the L2 vertebra.

The role of surgery for metastases to the vertebra from yolk sac tumours has not been established. The main treatment for disseminated disease is chemotherapy. We present a man in his 30s with a left orchiectomy for a testicular mixed germ cell tumour with a prominent yolk sac component who, 12 months later, developed an asymptomatic metastasis to the L2 vertebra unresponsive to chemotherapy and radiotherapy. The patient underwent resection of the L2 vertebral body, leaving a small residual tumour anterior to the vertebra attached to the great vessels. Pathology confirmed the diagnosis of a metastatic testicular yolk sac tumour in the vertebra. The postoperative MRI 6 months later demonstrated significant expansion of the tumour at the soft tissues anterior to the expandable titanium cage encasing the great vessels and extending to the paraspinal areas. Additional salvage surgery was not recommended because of the advanced stage of the tumour.

Qualitative Assessment of Titanium versus Carbon Fiber/Polyetheretherketone Pedicle Screw-Related Artifacts: A Cadaveric Study.

BACKGROUND: Dorsal instrumentation and decompression are the mainstays of spinal tumor treatment. Replacing titanium screws with carbon fiber-reinforced polyetheretherketone (CFRP) screws can reduce imaging artifacts on neural structures and perturbations of radiation dose. Further reduction of metal content in such screws might enhance the benefit. The aim of this study was to assess the artifacts produced by all-titanium screws (Ti-Ti), CFRP thread-titanium screw heads (C-Ti), and all-CFRP screws (C-C). METHODS: A cadaveric spine was used to place Ti-Ti, C-Ti, and C-C consecutively from T2 to S1. Computed tomography and 1.5T and 3T magnetic resonance imaging were performed for each screw system. Axial T1- and T2-weighted sequences of representative thoracic and lumbar regions were assessed for artifacts. The artifacts were classified as not relevant, considerable, or severe. RESULTS: We evaluated 92 screws and made 178 artifact assessments. The artifacts were clearly visible in computed tomography scans but did not influence the visualization of intraspinal structures. Severe magnetic resonance imaging artifacts were found in 28% (17/60, mostly in the thoracic spine) of Ti-Ti, 2% (1/60, all T1 sequences) of C-Ti, and 0% of C-C, and considerable artifacts were found in 47% (28/60) of Ti-Ti, 10% (6/60, only 1 T2 sequence) of C-Ti, and 0% of C-C screws (P < 0.001). CONCLUSIONS: CFRP pedicle screws reduced the artifact intensity in spinal structures compared with titanium screws, and may be beneficial for planning radiotherapy and for follow-up imaging. C-C demonstrated an enhanced effect on dorsal structures.

Cranioplasty with hydroxyapatite or acrylic is associated with a reduced risk of all-cause and infection-associated explantation.

OBJECTIVE: Cranioplasty remains an essential procedure following craniectomy but is associated with high morbidity. We investigated factors associated with outcomes following first alloplastic cranioplasty. METHODS: A single-centre, retrospective cohort study of patients undergoing first alloplastic cranioplasty at a tertiary neuroscience centre (01 March 2010-01 September 2021). Patient demographics and craniectomy/cranioplasty details were extracted. Primary outcome was all-cause explantation. Secondary outcomes were explantation secondary to infection, surgical morbidity and mortality. Multivariable analysis was performed using Cox proportional hazards regression or binary logistic regression. RESULTS: Included were 287 patients with a mean age of 42.9 years [SD = 15.4] at time of cranioplasty. The most common indication for craniectomy was traumatic brain injury (32.1%, n = 92). Cranioplasty materials included titanium plate (23.3%, n = 67), hydroxyapatite (22.3%, n = 64), acrylic (20.6%, n = 59), titanium mesh (19.2%, n = 55), hand-moulded PMMA cement (9.1%, n = 26) and PEEK (5.6%, n = 16). Median follow-up time after cranioplasty was 86.5 months (IQR 44.6-111.3). All-cause explantation was 12.2% (n = 35). Eighty-three patients (28.9%) had surgical morbidity. In multivariable analysis, the risk of all-cause explantation and explantation due to infection was reduced with the use of both hydroxyapatite (HR 0.22 [95% CI 0.07-0.71], p = .011, HR 0.22 [95% CI 0.05-0.93], p = .040) and acrylic (HR 0.20 [95% CI 0.06-0.73], p = .015, HR 0.24 [95% CI 0.06-0.97], p = .045), respectively. In addition, risk of explantation due to infection was increased when time to cranioplasty was between three and six months (HR 6.38 [95% CI 1.35-30.19], p = .020). Mean age at cranioplasty (HR 1.47 [95% CI 1.03-2.11], p = .034), titanium mesh (HR 5.36 [95% CI 1.88-15.24], p = .002), and use of a drain (HR 3.37 [95% CI 1.51-7.51], p = .003) increased risk of mortality. CONCLUSIONS: Morbidity is high following cranioplasty, with over a tenth requiring explantation. Hydroxyapatite and acrylic were associated with reduced risk of all-cause explantation and explantation due to infection. Cranioplasty insertion at three to six months was associated with increased risk of explantation due to infection.

Study on TiO2 Nanofilm That Reduces the Heat Production of Titanium Alloy Implant in Microwave Irradiation and Does Not Affect Fracture Healing.

Background: Metal implants can produce heat and damage adjacent tissues under microwave irradiation, which makes local metal implants in the body a contraindication for microwave therapy. However, with the wide application of titanium alloy implants which have low permeability and low conductivity, this concept has been challenged. Our team members have confirmed through previous research that continuous low-power microwave irradiation does not cause thermal damage to the surrounding tissues of the titanium alloy. Is there any other way to further increase the dose of microwave irradiation while reducing the heat production of titanium alloy implants? In this study, the effect of TiO2 nanofilm on reducing the heat production of titanium alloy implants in microwave field was verified by animal experiments, and the effect of TiO2 nanofilm on fracture healing was observed. Methods: 30 rabbits were selected. In the experiment of temperature measurement, 10 rabbits were randomly divided into experimental group (n = 5) and control group (n = 5), and the contralateral lower limb of the rabbits in experimental group was set as the sham operation group. The right femurs in the experimental group were implanted with Ti6Al4V plates coated with TiO2 nanofilm, and the right femurs in the control group were implanted with common titanium alloy plates without TiO2 nanofilm. The same surgical procedure was used in the sham operation group, but no plate was implanted. The temperature of the deep tissue above the metal implant was measured with an anti-interference thermocouple thermometer during 20 minutes of microwave irradiation. The other 20 rabbits were randomly divided into two groups, experimental group (n = 10) and control group (n = 10). The femoral shaft fracture models were established again. Ti6Al4V plates coated with TiO2 nanofilm and common titanium alloy plates were implanted in the two groups, respectively, and both groups were exposed to continuous microwave irradiation with a power of 40 W or 60 W for 30 days after operation. The fracture healing was evaluated by X-ray at 0 day, 14 days, and 30 days after microwave irradiation, respectively. The animals were sacrificed at 30 days after operation for histopathological assessment. Results: The temperature in the experimental group, control group, and sham operation group increased significantly after 40 W and 60 W microwave irradiation (2.18 ± 0.15°C~6.02 ± 0.38°C). When exposed to 40 W microwave, the temperature rise of the control group was 4.0 ± 0.34°C, which was significantly higher than that of the experimental group 2.82 ± 0.15°C (P < 0.01) and the sham operation group 2.18 ± 0.33°C (P < 0.01). There was no significant difference in temperature rise between the experimental group and the sham operation group (P = 0.21). When exposed to 60 W microwave, the temperature rise of the control group was 6.02 ± 0.38°C, which was significantly higher than that of the experimental group 3.66 ± 0.14°C (P < 0.01) and sham operation group 2.96 ± 0.22°C (P < 0.01), and there was no significant difference between the experimental group and the sham operation group (P = 0.32). X-ray evaluation showed that there was no significant difference in callus maturity between the experimental group and the control group at 14 days (P = 0.554), but there was significant difference in callus maturity between the two groups at 30 days (P = 0.041). The analysis of bone histologic and histomorphometric data at 30 days was also consistent with this. Conclusion: Under the animal experimental condition, compared with the common titanium alloy implant, the TiO2 nanofilm can reduce the heat production of the titanium alloy implant in the 2450 MHz microwave field and has no adverse effect on fracture healing. This study opens up a promising new idea for the application of microwave therapy to metal implants in human body.

Plate-associated localized osteitis in mini-pig by biofilm-forming Methicillin-resistant Staphylococcus aureus (MRSA): establishment of a novel experimental model.

PURPOSE: The increasing number of implant-associated infections during trauma and orthopedic surgery caused by biofilm-forming Staphylococcus aureus in combination with an increasing resistance of conventional antibiotics requires new therapeutic strategies. One possibility could be testing for different therapeutic strategies with differently coated plates. Therefore, a clinically realistic model is required. The pig offers the best comparability to the human situation, thus it was chosen for this model. The present study characterizes a novel model of a standardized low-grade acute osteitis with bone defect in the femur in mini-pigs, which is stabilized by a titanium locking plate to enable further studies with various coatings. METHODS: A bone defect was performed on the femur of 7 Aachen mini-pigs and infected with Methicillin-resistant S. aureus (MRSA ATCC 33592). The defect zone was stabilized with a titanium plate. After 14 days, a plate change, wound debridement and lavage were performed. Finally, after 42 days, the animals were lavaged and debrided again, followed by euthanasia. The fracture healing was evaluated radiologically and histologically. RESULTS: A local osteitis with radiologically visible lysis of the bone could be established. The unchanged high Colony-forming Units (CFU) in lavage, the significant differences in Interleukin (IL)-6 in blood compared to lavage and the lack of increase in Alkaline Phosphates (ALP) in serum over the entire observation period show the constant local infection. CONCLUSION: The study shows the successful induction of local osteitis with lysis of the bone and the lack of enzymatic activity to mineralize the bone. Therefore, this standardized mini-pig model can be used in further clinical studies, to investigate various coated implants, bone healing, biofilm formation and immune response in implant-associated osteitis.

Nanoscale Modification of Titanium Implants Improves Behaviors of Bone Mesenchymal Stem Cells and Osteogenesis In Vivo.

The surficial micro/nanotopography and physiochemical properties of titanium implants are essential for osteogenesis. However, these surface characters' influence on stem cell behaviors and osteogenesis is still not fully understood. In this study, titanium implants with different surface roughness, nanostructure, and wettability were fabricated by further nanoscale modification of sandblasted and acid-etched titanium (SLA: sandblasted and acid-etched) by H2O2 treatment (hSLAs: H2O2 treated SLA). The rat bone mesenchymal stem cells (rBMSCs: rat bone mesenchymal stem cells) are cultured on SLA and hSLA surfaces, and the cell behaviors of attachment, spreading, proliferation, and osteogenic differentiation are further analyzed. Measurements of surface characteristics show hSLA surface is equipped with nanoscale pores on microcavities and appeared to be hydrophilic. In vitro cell studies demonstrated that the hSLA titanium significantly enhances cell response to attachment, spreading, and proliferation. The hSLAs with proper degree of H2O2 etching (h1SLA: treating SLA with H2O2 for 1 hour) harvest the best improvement of differentiation of rBMSCs. Finally, the osteogenesis in beagle dogs was tested, and the h1SLA implants perform much better bone formation than SLA implants. These results indicate that the nanoscale modification of SLA titanium surface endowing nanostructures, roughness, and wettability could significantly improve the behaviors of bone mesenchymal stem cells and osteogenesis on the scaffold surface. These nanoscale modified SLA titanium scaffolds, fabricated in our study with enhanced cell affinity and osteogenesis, had great potential for implant dentistry.

Surgical Treatment Strategies for Pyogenic Spondylodiscitis of the Thoracolumbar Spine. / Operative Behandlungsstrategien der pyogenen Spondylodiszitis der thorakolumbalen Wirbelsäule.

BACKGROUND: Despite advances, the morbidity and mortality rates of patients with spondylodiscitis remains high, with an increasing incidence worldwide. Although conservative therapy has progressed, several cases require surgical intervention. However, the indication and opportunities for surgical treatment are still disputable. METHODS: In a joint consensus, the members of the 'Spondylodiscitis' working group of the Spine Section of the German Society for Orthopaedics and Trauma Surgery considered current literature, particularly the newly published S2k guideline of the AWMF, and examined the surgical indications and treatment strategies for thoracolumbar spondylodiscitis. RESULTS: Surgical intervention for spondylodiscitis is only required in a small percentage of patients. In studies comparing conservative and surgical therapies, most patients benefitted from surgery, regardless of the surgical technique selected. Presently, the standard procedure is a combined dorsoventral approach, in which a monolateral attempt should always be made. The choice of material (PEEK, titanium) for ventral support does not influence the clinical result.

Titaniumdioxide mediated sonophotodynamic therapy against prostate cancer.

In this study, we aimed to investigate of antitumor efficiency of titanium dioxide mediated photodynamic (PDT), sonodynamic (SDT), and sonophotodynamic (SPDT) therapies with a possible mechanism against the PC3 prostate cancer cell line. SPDT is a new approach to cancer treatment that combines sonodynamic and photodynamic therapies. On the other hand, Titanium dioxide (TiO2) has been used in many applications in pharmaceutical products and cosmetics, industrial products, and medicines. TiO2 nanoparticles will be useful for the treatment of cancer with PDT and SDT as the sensitizers in medicine. In this study, TiO2 nanoparticles were used for an in vitro comparison between the PDT, SDT, SPDT damages on prostate cancer cell lines. For this purpose, the cells were incubated in RPMI-1640 media with various concentrations of TiO2 and subjected to 0,5 W/cm2 ultrasound and/or 0,5 mJ/cm2 light irradiation. The prostate cancer cells were irradiated with light and exposed with the US and both for SPDT in the presence and/or absence of TiO2. Cell viability was measured using by MTT test after treatments. Investigate to apoptosis mechanism, Propidium iodide and Hoechst 33342 staining were used and the results showed that apoptotic cell bodies were increased compared with other groups. According to western blot analyses, caspase-3, caspase-8, PARP, and Bax levels were decreased after treatments, whereas the expression levels of caspase-9 were increased. Biochemical results showed that after treatments MDA levels were increased while SOD, CAT, GSH levels were decreased. In conclusion, TiO2-mediated SPDT may provide a promising approach for prostate cancer therapy and might play a key role in the apoptotic mechanism of these treatments.

W-Doped TiO2 Nanorods for Multimode Tumor Eradication in Osteosarcoma Models under Single Ultrasound Irradiation.

Sonosensitizers play crucial roles in the controlled production of reactive oxygen species (ROS) under ultrasound (US) irradiation with high tissue-penetration depth for noninvasive solid tumor therapy. It is desirable to fabricate structurally simple yet multifunctional sonosensitizers from ultrafine nanoparticles for ROS-based multimode therapy to overcome monomode limitations such as low ROS production yields and endogenous reductive glutathione (GSH) to ROS-based treatment resistance. We report the facile high-temperature solution synthesis of ultrafine W-doped TiO2 (W-TiO2) nanorods for exploration of their sonodynamic, chemodynamic, and GSH-depleting activities in sonodynamic-chemodynamic combination tumor therapy. We found that W5+ and W6+ ions doped in W-TiO2 nanorods play multiple roles in enhancing their ROS production. First, W doping narrows the band gap from 3.2 to 2.3 eV and introduces oxygen and Ti vacancies for enhancing their sonodynamic performance. Second, W5+ doping endows W-TiO2 nanorods with Fenton-like reaction activity to produce •OH from endogenous H2O2 in the tumor. Third, W6+ ions reduce endogenous GSH to glutathione disulfide (GSSG) and, in turn, form W5+ ions that further enhance their chemodynamic activity, which greatly modifies thae oxidation-reduction tumor microenvironment in the tumor. In vivo experiments display the excellent ability of W-TiO2 nanorods for enhanced tumor eradication in human osteosarcoma models under single US irradiation. Importantly, the ultrafine nanorod morphology facilitates rapid excretion from the body, displaying no significant systemic toxicity. Our work suggests that multivalent metal doping in ultrafine nanomaterials is an effective and simple strategy for the introduction of new functions for ROS-based multimode therapy.

A novel anatomic titanium mesh cage for reducing the subsidence rate after anterior cervical corpectomy: a finite element study.

Fusion with a titanium mesh cage (TMC) has become popular as a conventional method after cervical anterior corpectomy, but postoperative TMC subsidence has often been reported in the literature. We designed a novel anatomic cervical TMC to reduce the postoperative subsidence rate. According to the test process specified in the American Society of Testing Materials (ASTM) F2267 standard, three-dimensional finite element analysis was used to compare the anti-subsidence characteristics of a traditional TMC (TTMC) and novel TMC (NTMC). Through analysis, the relative propensity values of a device to subside (Kp) of the TTMC and NTMC were 665.5 N/mm and 1007.2 N/mm, respectively. A higher Kp measurement is generally expected to indicate that the device is more resistant to subsidence into a vertebral body. The results showed that the novel anatomic titanium mesh cage (NTMC) significantly improved the anti-subsidence performance after anterior cervical corpectomy and fusion (ACCF), which was approximately 51.3% higher than that of the traditional titanium mesh cage.

Homology and Immune Checkpoint Dual-Targeted Sonocatalytic Nanoagents for Enhancing Sonodynamic Tumor Therapy.

Sonocatalytic nanoagents (SCNs), a kind of sonosensitizers, could catalyze oxygen to generate abundant reactive oxygen species (ROS) under stimulations of noninvasive and deep-penetrating ultrasound (US), which is commonly used for sonodynamic therapy (SDT) of tumors such as malignant melanoma. However, poor bioavailability of most SCNs and fast quenching of extracellular-generating ROS from SDT limit further applications of SCNs in the SDT of tumors. Herein, we synthesized a new kind of TiO2-based SCN functionalized with the malignant melanoma cell membrane (B16F10M) and programmed cell death-ligand 1 antibody (aPD-L1) for homology and immune checkpoint dual-targeted and enhanced sonodynamic tumor therapy. Under US irradiation, the synthesized SCN can catalytically generate a large amount of 1O2. In vitro experiments validate that functionalized SCNs exhibit precise targeting effects, high tumor cell uptake, and intracellular sonocatalytic killing of the B16F10 cells by a large amount of localized ROS. Utilizing the melanoma animal model, the functionalized SCN displays visible long-term retention in the tumor area, which assists the homology and immune checkpoint synergistically dual-targeted and enhanced in vivo SDT of the tumor. We suggest that this highly bioavailable and dual-functionalized SCN may provide a promising strategy and nanoplatform for enhancing sonodynamic tumor therapies.