Poly(methyl methacrylate) (PMMA), the most common bone cement, has been used as a graft substitute in orthopedic surgeries such as vertebroplasty. However, an undesirable minor crack in the bone–cement interface provoked by shrinkage during polymerization and high elastic modulus of conventional PMMA bone cement dramatically increases the risk of vertebral body refracture postsurgery. Thus, herein, a hydrophilous expandable bone cement was synthesized based on a PMMA commercial cement (Mendec Spine Resin), acrylic acid (AA), and styrene (St). The two synthesized cements (PMMA-PAA, PMMA-PAA-PSt) showed excellent volumetric swelling in vitro and cohesive bone–cement contact in rabbit femur cavity defect. The elastic modulus and compressive strength of the new cements were lower than PMMA. Furthermore, the in vitro analysis indicated that the new cements had lower cytotoxicity than PMMA, including superior proliferation and lower apoptotic rates of Sprague–Dawly rat-derived osteoblasts. Western blotting for protein expression and RT-PCR analysis of osteogenesis-specific genes were conducted on SD rat-derived osteoblasts from both PMMA and new cements films; the results showed that new cements enhanced the expression of osteogenesis-specific genes. Scanning electron microscopy demonstrated improved morphology and attachment of osteoblast on new cement discs compared to the PMMA discs. Additionally, the histological morphologies of the bone–cement interface from the rabbit medial femoral condyle cavity defect model revealed direct and cohesive contact with the bone in the new cement groups in contrast to a minor crack in the PMMA cement group. The sign of a new bone growing into the cement has been found in the new cements after 12 weeks, thereby indicating the osteogenic capacity in vivo. In conclusion, the synthesized hydrophilous expandable bone cements based on PMMA and poly(acrylic acid) (PAA) are promising candidates for vertebroplasty.Keywords: expandable hydrophilous bone cement; poly(methyl methacrylate); polyacrylic acid; polystyrene; vertebroplasty;

Diabetes-induced reactive oxygen species (ROS) overproduction would result in compromised osteointegration of titanium implant (TI) and high rate of implant failure, yet the underlying mechanisms remain elusive. Adiponectin (APN) is a fat-derived adipocytokine with strong antioxidant, mitochondrial-protective and anti-diabetic efficacies. We hypothesized that mitochondrial dysfunction under diabetes may account for the oxidative stress in osteoblasts and titanium-bone interface (TBI) instability, which could be ameliorated by APN. To test this hypothesis, we incubated primary rat osteoblasts on TI and tested the cellular behaviors when subjected to normal milieu (NM), diabetic milieu (DM), DM + APN, DM + AICAR (AMPK activator) and DM + APN + Compound C (AMPK inhibitor). In vivo, APN or APN + Compound C were administered to diabetic db/db mice with TI implanted in their femurs. Results showed that diabetes induced structural damage, dysfunction and content decrease of mitochondria in osteoblasts, which led to ROS overproduction, dysfunction and apoptosis of osteoblasts accompanied by the inhibition of AMPK signaling. APN alleviated the mitochondrial damage by activating AMPK, thus reversing osteoblast impairment and improving the osteointegration of TI evidenced by Micro-CT and histological analysis. Furthermore, AICAR showed beneficial effects similar to APN treatment, while the protective effects of APN were abolished when AMPK activation was blocked by Compound C. This study clarifies mitochondrial dysfunction as a crucial mechanism in the impaired bone healing and implant loosening in diabetes, and provides APN as a novel promising active component for biomaterial-engineering to improve clinical performance of TI in diabetic patients.Statement of SignificanceThe loosening rate of titanium implants in diabetic patients is high. The underlying mechanisms remain elusive and, with the rapid increase of diabetic morbility, efficacious strategies to mitigate this problem have become increasingly important. Our study showed that the mitochondrial impairment and the consequent oxidative stress in osteoblasts at the titanium-bone interface (TBI) play a critical role in the diabetes-induced poor bone repair and implant destabilization, which could become therapeutic targets. Furthermore, adiponectin, a cytokine, promotes the bio-functional recovery of osteoblasts and bone regeneration at the TBI in diabetes. This provides APN as a novel bioactive component used in material-engineering to promote the osteointegration of implants, which could reduce implant failure, especially for diabetic patients.Download high-res image (277KB)Download full-size image

•Ta coating was deposited on 3D printed porous Ti implant by chemical vapor deposition.•Diabetes-induced ROS-p38 pathway caused osteoblast dysfunction and apoptosis.•Ta coating promoted the osteointegration of Ti implant in diabetic conditions.•Ta coating on Ti implant suppressed the ROS-mediated p38 pathway.•Ta coatings may be a strategy to enhance the implants fixation in diabetic patients.Clinical evidence indicates a high failure rate for titanium implants (TiI) in diabetic patients, involving the overproduction of reactive oxygen species (ROS) at the implant/bone interface. Tantalum coating on titanium (TaTi) has exerted better tissue integration properties than TiI, but its biological performance under diabetic conditions remains elusive. To investigate whether TaTi may ameliorate diabetes-induced implant destabilization and the underlying mechanisms, primary rabbit osteoblasts cultured on 3-dimensional printed TiI and TaTi were exposed to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor), and DS + SB203580 (a specific p38 MAPK inhibitor). An in vivo study was performed on diabetic sheep implanted with TiI or TaTi. Diabetes induced mitochondrial-derived ROS overproduction and caused cellular dysfunction and apoptosis, together with the activation of p38 MAPK in osteoblasts on TiI surface. Importantly, TaTi significantly attenuated ROS production and p38 MAPK phosphorylation and exerted more osseointegrative cell behavior than TiI, as shown by improved osteoblast adhesion, increased cell proliferation and differentiation and decreased apoptosis. These results were confirmed in vivo by the enhanced bone healing efficacy of TaTi. Moreover, treatment with NAC or SB203580 on TiI not only inhibited the activation of p38 MAPK but also improved cell function and alleviated apoptotic injury, whereas TaTi combined with NAC or SB203580 failed to further improve osteoblast functional recovery compared with TaTi alone. These results demonstrated that the tantalum coating markedly improved diabetes-induced impaired osteogenesis of TiI, which may be attributed to the suppression of the ROS-mediated p38 MAPK pathway.Tantalum coating on 3D-printed porous titanium implants attenuates the dysfunction of osteoblasts on implant surface and improves the osteointegration under diabetic conditions. Ta: tantalum. Ti: titanium.

To evaluate effectiveness of carboxymethylcellulose/polyethylene oxide (CMC/PEO) gel in improving clinical outcomes after the first-time lumbar discectomy.Ninety-three patients with herniated lumbar disc at L4–L5 or L5–S1 were enrolled and randomized into two groups: CMC/PEO gel treatment group and control group. All the patients underwent laminotomy and discectomy by posterior approach. The preoperative and postoperative Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) scores for lower-back pain and leg pain were analyzed and compared between two groups at 30- and 60-day time points.No patient presented with any clinically measurable adverse event during surgery. There were no significant differences between the treated group and the control group on the preoperative ODI and VAS scores. In general, the ODI and VAS scores decreased in both groups at all the time points. At the 30-day time point, the VAS scores for back pain and leg pain and the ODI scores in treatment group were lower by 9.9 % (P = 0.0302), 27.0 % (P = 0.0002) and 16.3 % (P = 0.0007) than those in control group. And at the 60-day time point, the ODI and VAS scores further decreased in both groups. The VAS scores for leg pain in treatment group were lower by 4.5 % than that in the control group (P = 0.0149). However, no significant difference was detected between two groups on the ODI and VAS scores for back pain.The results demonstrated that CMC/PEO gel is effective in reducing posterior dural adhesions in the spine with no apparent safety issues. It can improve patients’ postoperative clinical outcome.

The aim of this study is to compare the rate of screw loosening and clinical outcomes of expandable pedicle screws (EPS) with those of conventional pedicle screws (CPS) in patients treated for spinal stenosis (SS) combined with osteoporosis.One hundred and fifty-seven consecutive patients with SS received either EPS fixation (n = 80) or CPS fixation (n = 77) to obtain lumbosacral stabilization. Patients were observed for a minimum of 24 months. Outcome measures included screw loosening, fusion rate, Japanese Orthopaedic Association (JOA) scores and Oswestry disability index (ODI) scoring system, and complications.In the EPS group, 20 screws became loose (4.1%) in 6 patients (7.5%), and two screws (0.4%) had broken. In the CPS group, 48 screws became loose (12.9%) in 15 patients (19.5%), but no screws were broken. The fusion rate in the EPS group (92.5%) was significantly higher than that of the CPS group (80.5%). The rate of screw loosening in the EPS group (4.1%) was significantly lower than that of the CPS group (12.9%). Six EPS (1.8%) screws were removed. In the EPS group, two screws had broken but without neural complications. Twelve months after surgeries, JOA and ODI scores in the EPS group were significantly improved. There were four cases of dural tears, which healed after corresponding treatment.EPS can decrease the risk of screw loosening and achieve better fixation strength and clinical results in osteoporotic lumbar spine fusion.

Cordyceps sinensis has been known as a traditional medicine in China, and C. sinensis plus strontium could prevent osteoporosis in ovariectomized rats. The present study shows that daily oral administration of C. sinensis at higher doses in adult hind limb suspension rats can prevent disuse-induced bone loss and deterioration of trabecular microarchitecture.Cordyceps sinensis induces estradiol production and prevents osteoporosis in ovariectomized rats. This study was to examine whether C. sinensis can prevent disuse-induced osteoporosis.Rats were randomly divided into six groups, and five groups were treated with hind limb suspension (HLS). One HLS group received alendronate (2.0 mg/kg/day) orally, and to the three other HLS groups to each group, a different amount of C. sinensis (100, 300, and 500 mg/kg/day) was orally administered for 8 weeks before and after HLS. The remaining HLS group was set as a control without treatment. Each group consisted of 10 males and females. The body weights, biochemical parameters in serum and urine, bone mineral density (BMD), bone mineral content (BMC), mechanical testing, and bone microarchitecture were examined.Treatments with higher C. sinensis dosage (300 and 500 mg/kg/day) or alendronate had a positive effect on body weights, mechanical strength, BMD, and BMC compared to the other HLS groups. C. sinensis decreased markers of bone turnover dose dependently and increased the osteocalcin levels in HLS rats. The result of micro-CT analysis from the L4 vertebra showed that C. sinensis (500 mg/kg) significantly prevented the reduction of the bone volume fraction, connectivity density, trabeculae number, and thickness as well as improved the trabeculae separation and structure model index in HLS rats.The present study demonstrates that administration of C. sinensis at higher doses over an 8-week period can prevent the disuse osteoporosis in rats. It implies that C. sinensis might be an alternative therapy for prevention of disuse-induced osteoporosis also in humans.

The purpose of this study was to analyze the local treatment effects of rhBMP-2 combined with fibrin sealant (FS) on bone mineral density, microarchitectural and mechanical properties in osteoporotic ovine spine.Postmenopausal osteoporosis was induced in eight sheep through ovariectomy (OVX) and a low-calcium diet for a period of 12 months. According to the Latin square design, L3–L6 vertebrae were randomly assigned to four treatment groups: A (rhBMP-2/FS), B (rhBMP-2), C (FS) and D (blank control). All materials were injected into the assigned vertebra transpedicularly. All animals were euthanized 3 months after treatment. Bone mineral density (BMD), microarchitectural and mechanical properties were assessed. ANOVA analysis of variance was used to determine effects of rhBMP-2/FS (α = 0.05).The BMD in group A (rhBMP-2/FS) was 18.8, 30.4 and 27.9% higher than that in group B, C and D, respectively. Analysis of bone structure by micro-CT revealed higher trabecular bone volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) in the rhBMP-2/FS group (P < 0.01). In addition, vertebrae treated with rhBMP-2/FS exhibited higher yield stress, ultimate stress, energy absorption and bone modulus compared to the control groups.Local administration of rhBMP-2/FS showed a positive trend in improving BMD, microarchitectural parameters and mechanical strength of osteoporotic vertebra. Slow release of rhBMP-2 using FS appeared to be an effective method of protein delivery. The local treatment of osteoporosis in the spine can increase bone strength and reduce fracture risk quickly.

To help decide the best starting point for lumbar spine pedicle screw insertion in the Chinese population using three different techniques (Roy-Camille, Magerl, and Du). Three-dimensional CT reconstructions were created from 40 adult lumbar vertebral segments. Three different starting points for lumbar pedicle screw insertion were used. The direction of the pedicle screw through each hole was simulated on three-dimensional reconstructed images. Precise CT measurements were made to assess the distance from the simulated screw and the medial and lateral pedicle walls at the smallest transverse section of each pedicle. To measure a pedicle transverse section angle (TSA) lines were drawn on a CT scan in the direct axis of the pedicle, tangential to the medial, and separately lateral, walls of the pedicles at the isthmus. The angle these lines made with an anterior to posterior line, which directly bisected the mid-portion of the vertebral body was called the TSA. The greater the difference between the TSA between the medial and lateral walls provides the greatest flexibility for the insertion angle of the pedicle screw. Additionally, the distance from a line drawn in the direct central axis of the pedicle was measured from the point of exit from the pedicle to the entry point of each of three insertion techniques (Du, Mageral, and Roy-Camille), to help understand potential risk factors. There were statistically significant differences between the distances from the entrance point to the direct pedicle axis among the three methods (P < 0.001). Du’s insertion point was the shortest from L1 to L4. The distances measured following Magerl’s technique were shortest at L5 (P < 0.05). There was no significant difference of the safe range of the TSA between the three methods from L1 and L2 (P > 0.05), but significant differences at L3, L4, and L5 (P < 0.05). At L3 and L4 the safe ranges of TSA using Du and Magerl’s methods were significantly larger than those measured by Roy-Camille (P < 0.05). At L5 the safe ranges of TSA for the Magerl technique were the greatest among the three methods (P < 0.05). These results demonstrate that Du’s method provides the safest starting point to place pedicle screws from L1 to L4, as its distance from the entrance point to the pedicle axis is the shortest and the safe range of TSA the largest of the three techniques. Magerl’s technique can be safely used in the pedicles from L3 to L5, and is the safest choice at L5. Roy-Camille’s technique is most applicable at L1 and L2, but has the highest risk when applied from L3 to L5.

BackgroundFemoral neck fracture is one of the common clinical traumas, especially amongst elder patients. This study aims to test, compare and evaluate the bone–screw interface strengths, the fatigue strengths, and the stabilities of our newly designed expansive cannulated screw (ECS) and the common cannulated compression screw (CCS) in the fixation of femoral neck fracture, which is a summary of recent research.MethodsTwenty-four pairs (48) of fresh femur specimens were randomly divided into four groups with six pairs (12) in each. To simulate one-legged standing, the maximum compressive strength and the single-screw axial pull-out force were compared between the fixed femoral necks treated with two ECSs and two CCSs, two ECSs and three CCSs or three ECSs and three CCSs, respectively. The screws were also subjected to 1 000 000 cycles of a loaded fatigue test and the results were recorded.FindingsWhen the same number of screws was used, the ECS showed significantly greater maximum compressive strength than the CCS (P < 0.05), but no significant difference in fixation effectiveness was detected between the two ECSs and the three CCSs groups. The maximum axial pull-out strength of the ECS was also significantly greater that of the CCS (P < 0.01); however, there was no sign of fatigue in both the ECS and CCS after 1 000 000 cycles of loaded fatigue test.InterpretationThe ECS shows better fixation performance than the currently and commonly used CCS; under certain circumstances, fixation with two ECSs can achieve the same effect as that with traditional three CCSs.