Coatless modification of 3D-printed Ti6Al4V implants through tailored Cu ion implantation combined with UV photofunctionalization to enhance cell attachment, osteogenesis and angiogenesis.

The three-dimensional-printed Ti6Al4V implant (3DTi) has been widely accepted for the reconstruction of massive bone defects in orthopedics owing to several advantages, such as its tailored shape design, avoiding bone graft and superior bone-implant interlock. However, the osteoinduction activity of 3DTi is inadequate when applied clinically even though it exhibits osteoconduction. This study developes a comprehensive coatless strategy for the surface improvement of 3DTi through copper (Cu) ion implantation and ultraviolet (UV) photofunctionalization to enhance osteoinductivity. The newly constructed functional 3DTi (UV/Ti-Cu) achieved stable and controllable Cu doping, sustained Cu2+ releasing, and increased surface hydrophilicity. By performing cellular experiments, we determined that the safe dose range of Cu ion implantation was less than 5×1016 ions/cm2. The implanted Cu2+ enhanced the ALP activity and the apatite formation ability of bone marrow stromal cells (BMSCs) while slightly decreasing proliferation ability. When combined with UV photofunctionalization, cell adhesion and proliferation were significantly promoted and bone mineralization was further increased. Meanwhile, UV/Ti-Cu was conducive to the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, theoretically facilitating vascular coupling osteogenesis. In conclusion, UV/Ti-Cu is a novel attempt to apply two coatless techniques for the surface modification of 3DTi. In addition, it is considered a potential bone substrate for repairing bone defects.

Erratum: Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects.

[This corrects the article DOI: 10.1016/j.bioactmat.2023.11.001.].

A Dose-Dependent Spatiotemporal Response of Angiogenesis Elicited by Zn Biodegradation during the Initial Stage of Bone Regeneration.

Zinc (Zn) plays a crucial role in bone metabolism and imbues biodegradable Zn-based materials with the ability to promote bone regeneration in bone trauma. However, the impact of Zn biodegradation on bone repair, particularly its influence on angiogenesis, remains unexplored. This study reveals that Zn biodegradation induces a consistent dose-dependent spatiotemporal response in angiogenesis,both in vivo and in vitro. In a critical bone defect model, an increase in Zn release intensity from day 3 to 10 post-surgery is observed. By day 10, the CD31-positive area around the Zn implant significantly surpasses that of the Ti implant, indicating enhanced angiogenesis. Furthermore,angiogenesis exhibits a distance-dependent pattern closely mirroring the distribution of Zn signals from the implant. In vitro experiments demonstrate that Zn extraction fosters the proliferation and migration of human umbilical vein endothelial cells and upregulates the key genes associated with tube formation, such as HIF-1α and VEGF-A, peaking at a concentration of 22.5 µM. Additionally, Zn concentrations within the range of 11.25-45 µM promote the polarization of M0-type macrophages toward the M2-type, while inhibiting polarization toward the M1-type. These findings provide essential insights into the biological effects of Zn on bone repair, shedding light on its potential applications.

Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects.

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%-77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivo and in vitro. Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects, with a ferroptosis-mediated anti-osteosarcoma effect.

Study on Nitrogen Injection Fire Prevention and Extinguishing Technology in Spontaneous Combustion Gob Based on Gob-Side Entry Retaining.

Under the gob-side entry retaining mining mode with roof cutting and pressure relief (GERRC), the gob and retained roadway section are interconnected to create an open area. Owing to the increased airflow, the coal remnants in the gob are more prone to spontaneous combustion. This study aimed to investigate the distribution of oxygen concentration within a gob and identify optimal parameters for nitrogen injection. The engineering context was the "110 method" introduced in the 1201 working face of the South Five mining area at Daxing. Computational fluid dynamics simulation software was used to analyze the effects of various nitrogen injection treatment parameters on the overall performance of the gob, including their impact on oxygen distribution. The simulation results showed that air leakage within the gob primarily originates from the working face adjacent to the intake roadway, as well as gaps within the retained roadway. The increased air leakage causes the high O2 concentration range in the gob to expand, and the retained roadway section is connected to an area with a high concentration of oxygen near the working face, which increases the risk of residual coal spontaneous combustion. The results show that the optimal nitrogen injection conditions for inerting and reducing the risk of spontaneous combustion within the gob require an injection quantity of 500 m3/h, with the injection point located at a depth of 60 m. With these parameters, the range of the oxidation zone was significantly reduced. To monitor the O2 concentration and temperature change curves in the gob during the project implementation, a bundle tube monitoring system was used, considering the actual mining situation. By varying the nitrogen injection spacing and quantity, we found that injecting nitrogen at a spacing of 30 m and at a quantity of 500 m3/h effectively placed most areas of the gob in the suffocation zone, reducing the risk of spontaneous combustion of residual coal. The accuracy of the simulation was verified. The study offers valuable insights into improving safety in coal mines and reducing spontaneous combustion incidents, providing important reference significance for fire prevention and control.

Research on controlling gas overrun in a working face based on gob-side entry retaining by utilizing ventilation type "Y".

To determine the characteristics of air leakage concerning a "Y" type ventilation in gob-side entry retaining with roof cutting, pressure relief, and the law of a resulted gas accumulation (GA), research is conducted by employing the CFD simulation incorporated with the gauged parameters of working face (WF) mining to analyze the air leakage of "Y" type ventilation. For this purpose, the 1201 fully mechanized coal mining face in the south Wu mining location of the Daxing coal mine is taken as an illustrative example to study the air leakage in the "Y" type ventilation. So, the gas concentration (GC) issue surpassing the limit in the upper corner of the goaf was simulated. The results show that the goaf is formed into an open space when roof cutting and pressure relief technology along the goaf is implemented. The air pressure at the upper corner of the WF would be the lowest, which is only 1.12 Pa. The airflow of air leakage under a pressure difference would move from the gob-side entry retaining to the goaf. Moreover, the simulation of mine ventilation indicates that the volume of air leakage positively correlates with the length of gob-side entry retaining. When the WF is advanced 500 m ahead, the maximum volume of air leakage would reach 247 m3/min within the range of 500-1300 m, and then the rate of air leakage gradually would decrease. When the WF is advanced at 1300 m, the air leakage would become the smallest, which is 175 m3/min. When gas control is under consideration, the effect of gas extraction would be best with the buried pipe whose depth and diameter are set to 4.0 m and 400 mm, respectively. So, the GC in the upper corner would become 0.37%. After the high-level borehole with a 120 mm diameter is mined, the GC in the deep goaf decreased to 3.52%, and the GC at the upper corner became further reduced to 0.21%. While the high-level borehole gas is extracted by employing the extraction system of the high-concentration gas, the extraction system of low-concentration gas is utilized to extract the upper corner gas of the WF, thus, the problem of gas overrun was resolved satisfactorily. During the recovery period of the mining, the GC at each gauging point was less than 0.8%, which effectively guided the secure production in the Daxing coal mine and provided a theoretical foundation to control gas overrun during the mining process.

The biological properties of 3D-printed degradable magnesium alloy WE43 porous scaffolds via the oxidative heat strategy.

As a biodegradable material, magnesium alloy has a modulus similar to that of bone, and given the biological activity of its degradation products, it has the potential to be a bone grafting material. Oxidation heat treatment is a very effective passivation method that may reduce the rate of magnesium alloy degradation. Oxidation heat treatment increases the rare earth oxide content of the scaffold as well as the corrosion resistance of the scaffold. The overall cytotoxicity of the as-printed scaffolds (APSs) and oxidation heat-treated scaffolds (OHSs) showed that OHSs accelerated cell proliferation. In the apoptosis experiment, the OHS group had a cell survival rate between that of the control group and of the as-printed group. In the osteogenic induction experiment, the alkaline phosphatase activity and the quantity of mineralized nodules were greater in the APS and OHS groups than in the control group. Marker proteins for bone growth were expressed at higher levels in the APS and OHS groups than in the control group. Therefore, oxidation heat-treated 3D printing scaffolds with good biocompatibility and osteogenic properties have great potential to be made into advanced biomaterials that can be used to fix bone defects.

A sustained release of alendronate from an injectable tetra-PEG hydrogel for efficient bone repair.

Significant efforts on construction of smart drug delivery for developing minimally invasive gelling system to prolong local delivery of bisphosphonates are considered as promising perspectives for the bone-related diseases, which provide the hydrogels with unique bioactivities for bone repair in clinic. Herein, we have constructed an alendronate (ALN)-conjoined injectable tetra-PEG hydrogel with excellent biocompatibility, uniform network, and favorable mechanical properties in one-pot strategy. In views of the quick ammonolysis reaction between N-hydroxysuccinimide (NHS)-ester of tetra-PEG-SG and amine groups of tetra-PEG-NH2 polymer and ALN molecules, the uniform networks were formed within seconds along with the easy injection, favorable biocompatibility and mechanical properties for hydrogel scaffolds. On account of the simultaneous physical encapsulation and chemical linkage of the ALN within the hydrogels, the ALN-conjoined tetra-PEG hydrogel exhibited a sustained drug release delivery that could persistently and effectively facilitate viability, growth, proliferation, and osteogenesis differentiation of stem cells, thereby allowing the consequent adaptation of hydrogels into the bone defects with irregular shapes, which endowed the ALN-conjoined tetra-PEG hydrogel with depot formulation capacity for governing the on-demand release of ALN drugs. Consequently, the findings imply that these drug-based tetra-PEG hydrogels mediate optimal release of therapeutic cargoes and effective promotion of in situ bone regeneration, which will be broadly utilized as therapeutic scaffolds in tissue engineering and regenerative medicine.

Effect of micro-arc oxidation surface modification of 3D-printed porous titanium alloys on biological properties.

Background: Three-dimensional (3D) printing technology has been widely used in orthopedics; however, it is still limited to the change of macroscopic structures. In order to further improve the biological properties of 3D-printed porous titanium scaffolds, this study introduced micro-arc oxidation (MAO) technology to modify the surface of porous titanium scaffolds and construct bioactive coatings on the surface of porous titanium scaffolds to improve the biocompatibility and osseointegration ability of the material. Methods: For in vitro experiments, human bone marrow stem cells (hBMSCs) were seeded onto untreated scaffolds (control group) and MAO-treated scaffolds (experimental group). After 24 h of co-culture, cytotoxicity was observed using live/dead staining, and cell/scaffold constructs were retrieved and processed for the assessment of cell morphology by using scanning electron microscopy (SEM). Cell proliferation was detected using the Cell Counting Kit-8 (CCK-8) assay after 3, 7, and 14 days of co-culture. The levels of alkaline phosphatase (ALP) in the cell supernatant were detected after 7 and 14 days of co-culture. For in vivo experiments, micro-computed tomography (micro-CT) and Masson Goldner's staining were used to evaluate bone ingrowth and osseointegration at 4 and 8 weeks postoperatively. Results: In vitro experiment results confirmed that the two groups of scaffolds were non-cytotoxic and the cell adhesion status on the MAO-treated scaffolds was better. Over time, cell proliferation and ALP levels were higher in the MAO-treated group than in the untreated scaffolds. In the in vivo experiments, the MAO-treated scaffolds showed better bone ingrowth and osseointegration than the untreated group at different time points. Conclusions: The MAO-treated porous titanium scaffold formed a uniform and dense bioactive coating on the surface, which was more conducive to cell adhesion, proliferation, and differentiation and showed better osseointegration and bone ingrowth in vivo.

High efficacy of tetra-PEG hydrogel sealants for sutureless dural closure.

Advances in meticulous dural closure technique remain a great challenge for watertight dural closure in the aged society, because the cerebrospinal fluid (CSF) leakage after spinal surgery is often accompanied with the disgusting wound infection, meningitis and pseudomeningocele. Here, a tetra-poly (ethylene glycol) (PEG)-based hydrogel sealant is developed with collective advantages of facile operation, high safety, quick set time, easy injectability, favorable mechanical strength and powerful tissue adhesion for effective sutureless dural closure during the surgery procedure. Impressively, this tetra-PEG sealant can instantaneously adhere to the irregular tissue surfaces even in a liquid environment, and effectively prevent or block off the intraoperative CSF leakage for sutureless dural closure and dura regeneration. Together, this sutureless tetra-PEG adhesive can be utilized as a very promising alternative for high-efficient watertight dural closure of the clinical patients who incidentally or deliberately undergo the durotomy during the spinal surgery.

Practical strategy to construct anti-osteosarcoma bone substitutes by loading cisplatin into 3D-printed titanium alloy implants using a thermosensitive hydrogel.

Surgical resection and perioperative adjuvant chemotherapy-based therapies have improved the prognosis of patients with osteosarcoma; however, intraoperative bone defects, local tumour recurrence, and chemotherapy-induced adverse effects still affect the quality of life of patients. Emerging 3D-printed titanium alloy (Ti6Al4V) implants have advantages over traditional implants in bone repair, including lower elastic modulus, lower stiffness, better bone conduction, more bone in-growth, stronger mechanical interlocking, and lager drug-loading capacity by their inherent porous structure. Here, cisplatin, a clinical first-line anti-osteosarcoma drug, was loaded into Ti6Al4V implants, within a PLGA-PEG-PLGA thermo-sensitive hydrogel, to construct bone substitutes with both anti-osteosarcoma and bone-repair functions. The optimal concentrations of cisplatin (0.8 and 1.6 mg/mL) were first determined in vitro. Thereafter, the anti-tumour effect and biosafety of the cisplatin/hydrogel-loaded implants, as well as their bone-repair potential were evaluated in vivo in tumour-bearing mouse, and bone defect rabbit models, respectively. The loading of cisplatin reduced tumour volume by more than two-thirds (from 641.1 to 201.4 mm3) with negligible organ damage, achieving better anti-tumour effects while avoiding the adverse effects of systemic cisplatin delivery. Although bone repair was hindered by cisplatin loading at 4 weeks, no difference was observed at 8 weeks in the context of implants with versus without cisplatin, indicating acceptable long-term stability of all implants (with 8.48%-10.04% bone in-growth and 16.94%-20.53% osseointegration). Overall, cisplatin/hydrogel-loaded 3D-printed Ti6Al4V implants are safe and effective for treating osteosarcoma-caused bone defects, and should be considered for clinical use.

Three-dimensional-printed individualized porous implants: A new "implant-bone" interface fusion concept for large bone defect treatment.

Bone defect repairs are based on bone graft fusion or replacement. Current large bone defect treatments are inadequate and lack of reliable technology. Therefore, we aimed to investigate a simple technique using three-dimensional (3D)-printed individualized porous implants without any bone grafts, osteoinductive agents, or surface biofunctionalization to treat large bone defects, and systematically study its long-term therapeutic effects and osseointegration characteristics. Twenty-six patients with large bone defects caused by tumor, infection, or trauma received treatment with individualized porous implants; among them, three typical cases underwent a detailed study. Additionally, a large segmental femur defect sheep model was used to study the osseointegration characteristics. Immediate and long-term biomechanical stability was achieved, and the animal study revealed that the bone grew into the pores with gradual remodeling, resulting in a long-term mechanically stable implant-bone complex. Advantages of 3D-printed microporous implants for the repair of bone defects included 1) that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility, and 2) that osseointegration between the host bone and implants was achieved without bone grafting. Our osseointegration method, in which the "implant-bone" interface fusion concept was used instead of "bone-bone" fusion, subverts the traditional idea of osseointegration.

Sustainable release of vancomycin from micro-arc oxidised 3D-printed porous Ti6Al4V for treating methicillin-resistant Staphylococcus aureus bone infection and enhancing osteogenesis in a rabbit tibia osteomyelitis model.

Elimination of infection and enhancement of osteogenesis by orthopaedic implants are two critical factors in the treatment of complex bone infections. A prolonged and expensive procedure requiring two surgical steps and a 6-8-week period of joint immobilisation is utilised as a primary treatment for revision arthroplasty of an infected prosthesis, greatly affecting long-term patient care for the ageing population. Here, we evaluated the effects of vancomycin-loaded in micro-arc oxidised (MAO) three-dimensional (3D) printed porous Ti6Al4V scaffolds on osteogenesis. This system showed a high loading capacity and sustained vancomycin release kinetics, as demonstrated using high-performance liquid chromatography. In vivo, 0.1 mL of 108 colony forming units (CFU) methicillin-resistant Staphylococcus aureus was injected into the tibias of rabbits to induce severe osteomyelitis. Physical, haematological, radiographic, microbiological, and histopathological analyses were performed to evaluate the effects of treatment. Rabbits with vancomycin-loaded in MAO scaffolds showed the inhibition of bone infection and enhancement of osteogenesis, resulting in better outcomes than in the other groups. Overall, these findings demonstrated the potential of this 3D printed porous Ti6Al4V, with good osteogenesis and sustained vancomycin release properties, for application in the treatment of complex bone infections.

Functionalization of 3D-printed titanium alloy orthopedic implants: a literature review.

Titanium alloy orthopedic implants produced by 3D printing combine the dual advantages of having a complex structure that cannot be manufactured by traditional techniques and the excellent physical and chemical properties of titanium and its alloys; they have been widely used in the field of orthopedics in recent years. The inherent porous structure of 3D-printed implants and the original modification processes for titanium alloys provide conditions for the functionalization of implants. To meet the needs of orthopedic surgeons and patients, functionalized implants with long-term stability and anti-infection or anti-tumor properties have been developed. The various methods of functionalization deserve to be summarized, compared and analyzed. Therefore, in this review, we will collect and discuss existing knowledge on the functionalization of 3D-printed titanium alloy orthopedic implants.

Single balloon versus double balloon bipedicular kyphoplasty: a systematic review and meta-analysis.

INTRODUCTION: Kyphoplasty has been widely used to treat vertebral compression fractures (VCFs). In standard procedure of kyphoplasty, two balloons were inserted into the vertebral body through bipedicular and inflated simultaneously, while using a single balloon two times is also a common method in clinic to lessen the financial burden of patients. However, the effect and safety of single balloon versus double balloon bipedicular kyphoplasty are still controversy. METHODS: In this systematic review and meta-analysis, eligible studies were identified through a comprehensive literature search of PubMed, Cochrane library EMBASE, Web of Science, Wanfang, CNKI, VIP and CBM until January 1, 2018. Results from individual studies were pooled using a random or fixed effects model. RESULTS: Seven articles were included in the systematic review and five studies were consisted in meta-analysis. We observed no significant difference between single balloon and double balloon bipedicular kyphoplasty in visual analog scale (VAS), angle (kyphotic angle and Cobb angle), consumption (operation time, cement volume and volume of bleeding), vertebral height (anterior height, medium height and posterior height) and complications (cement leakage and new VCFs), while the cost of single balloon bipedicular kyphoplasty is lower than that of double balloon bipedicular kyphoplasty. The results of our meta-analysis also demonstrated that single balloon can significantly improve the VAS, angle and vertebral height of patients suffering from VCFs. CONCLUSION: This systematic review and meta-analysis collectively concludes that single balloon bipedicular kyphoplasty is as effective as double balloon bipedicular kyphoplasty in improving clinical symptoms, deformity and complications of VCFs but not so expensive. These slides can be retrieved under Electronic Supplementary Material.

Is it Beneficial to Reuse the Balloon in Percutaneous Kyphoplasty for the Treatment of Non-Neoplastic Vertebral Compression Fractures?

BACKGROUND Percutaneous kyphoplasty (PKP) has been widely used to treat vertebral compression fractures (VCFs). Bilateral percutaneous punctures are always performed to access the fractured vertebrae. However, the procedure has expensive clinical costs, especially the cost for the device, which creates a heavy financial burden for patients. MATERIAL AND METHODS Data from 49 patients who have single-level non-neoplastic vertebral compression fracture (VCF) were collected for 12 months after treated by PKP, including 21 cases that used bilateral puncture with single balloon (S group) and 28 cases that used bilateral puncture with double balloon (D group). We assessed the clinical (visual analogue scale, VAS) and radiological (vertebral height and kyphotic angle, KA) outcomes. Cost data (gross medical cost, cost for the device and cost for drugs) were obtained from the medical bill of each patient. RESULTS Baseline patient variables were similar between the two groups except the compensation (S group

Curcumin ameliorates cardiac dysfunction induced by mechanical trauma.

Curcumin, a phytochemical component derived from turmeric (Carcuma longa), has been extensively investigated because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play critical roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This research was designed to identify the protective effect of curcumin on posttraumatic cardiac dysfunction and investigate its underlying mechanism. Noble-Collip drum was used to prepare a mechanical trauma (MT) model of rats, and the hemodynamic responses of traumatized rats were observed by ventricular intubation 12h after trauma. Myocardial apoptosis was determined through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay. Tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) generated by monocytes and myocardial cells were identified through enzyme-linked immunosorbent assay (ELISA), and the intracellular alteration of Ca2+ in cardiomyocytes was examined through confocal microscopy. In vivo, curcumin effectively ameliorated MT-induced secondary cardiac dysfunction and significantly decreased the apoptotic indices of the traumatized myocardial cells. In vitro, curcumin inhibited TNF-α production by monocytes and reduced the circulating TNF-α levels. With curcumin pretreatment, ROS production and Ca2+ overload in H9c2 cells were attenuated when these cells were incubated with traumatic plasma. Therefore, curcumin can effectively ameliorate MT-induced cardiac dysfunction mainly by inhibiting systemic inflammatory responses and by weakening oxidative stress reaction and Ca2+ overload in cardiomyocytes.

Protective Effect of Quercetin on Posttraumatic Cardiac Injury.

Quercetin is an important dietary flavonoid present in fruits and vegetables and has attracted attention because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play important roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This study investigates the protective effect of quercetin on trauma-induced secondary cardiac injury and the mechanisms involved. Widely accepted nonlethal mechanical trauma models were established. In vivo, cardiomyocyte apoptosis and cardiac dysfunction in rats were assessed using TUNEL staining and a biological mechanic experiment system. In vitro, cell viability, tumour necrosis factor-α (TNF-α), reactive oxygen species (ROS) and [Ca(2+)]i of H9c2 cells were detected using an MTT assay, ELISA, and 2',7'-dichlorofluorescin diacetate and fluo-4 acetoxymethyl ester assays respectively. Quercetin pretreatment (20 mg/kg i.p.; 0.5 h before trauma) significantly improved posttraumatic cardiomyocyte apoptosis and cardiac dysfunction. Pretreatment with quercetin (20 µM; 24 h before trauma plasma addition) significantly attenuated trauma-induced viability decreases, TNF-α increases, ROS overproduction and [Ca(2+)]i overload in H9c2 cells. In conclusion, quercetin may reverse posttraumatic cardiac dysfunction by reducing cardiomyocyte apoptosis through the suppression of TNF-α increases, ROS overproduction and Ca(2+) overload in cardiomyocytes, representing a potential preventive approach for the treatment of secondary cardiac injury after mechanical trauma.