PEDF peptide plus hyaluronic acid stimulates cartilage regeneration in osteoarthritis via STAT3-mediated chondrogenesis.

Aims: Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods: Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results: The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion: The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC.

Biomechanical characteristics of self-expanding sinus stents during crimping and deployment_A comparison between different biomaterials.

Self-expanding sinus stents are often used in functional endoscopic sinus surgery to treat inflamed sinuses. The PROPEL self-expanding sinus stent offers mechanical support to the sinus cavity to prevent restenosis. The stent is made of a bioabsorbable material (PLGA) that disappears after wound healing. However, complications such as foreign body sensation and severe stent migration/expulsion have been reported after implantation. Little is known about the contact characteristics of self-expanding sinus stents from when the stent is crimped into the insertion device through to deployment into the sinus cavity. This current study developed a test platform to analyze the biomechanical behavior of the stent during this process. Three common bioabsorbable materials, PLGA, PCL and Mg alloy, were evaluated to understand how the choice of material affects the biomechanical characteristics of self-expanding sinus stents. The results showed that the material can have a considerable influence on the contact characteristics during crimping and deployment. When crimped, the PLGA and Mg alloy stents showed much higher plastic strain and contact stress than the PCL stent. When deployed, the PCL stent had the largest contact area (4.3 mm2) and the lowest contact pressure (0.1 MPa) on the inner surface of the sinus canal. The results indicate that PCL could be a suitable choice for self-expanding sinus stents. This current study provides a method for observing the biomechanical characteristics of sinus stents during stent crimping and deployment.

Complications following all-inside anterior cruciate ligament reconstruction.

PURPOSE: We conducted a comprehensive analysis of possible perioperative complications following all-inside anterior cruciate ligament reconstruction (ACLR). Additional techniques and tips are proposed to prevent and manage complications. METHODS: Complications following all-inside ACLR performed between December 2015 and December 2020 were retrospectively analysed. Altogether, 348 operations were performed and 275 patients were enrolled with a minimum 12-month follow-up period. Only semitendinosus autograft was utilised in most patients, and semitendinosus-gracilis autograft and allograft were used in five and 31 patients, respectively. Simultaneous meniscal repair, partial meniscectomy, and chondral surgery were performed in 29.5%, 21.1%, and 4.4% of patients, respectively. Complications were observed based on the patient's clinical condition, plain film, and magnetic resonance imaging. Clinical outcomes were assessed pre-operatively and at 12 months post-operatively, using the International Knee Documentation Committee form, Lysholm and Tegner activity scores, and KT1000 side-to-side difference. RESULTS: Intraoperative and post-operative complications developed in 65 patients (23.6%). The most common complication was cortical button malposition on the femoral side (19.3%). Intra-operative breakage of the retrograde drill was found in two cases (0.73%), with three cases (1.1%) of over-drilling with destruction of the outer cortex. Post-operatively, four (1.5%), 13 (4.7%), and 16 (5.8%) cases of infection, full-thickness re-rupture, and loss of extension, respectively, were recorded. Functional outcome scales showed significant post-operative improvement. CONCLUSION: Cortical button malposition was the most common but easily preventable complication. All-inside ACLR could be safe and promising after the suggested additional operative techniques and proper perioperative management which decrease complication rates and improve favourable outcomes.

The potential role of herbal extract Wedelolactone for treating particle-induced osteolysis: an in vivo study.

BACKGROUND: Osteolysis is one of the most prevalent clinical complications affecting people who undergo total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the oral administration of WDL as a potential treatment for particle-induced osteolysis using a well-established mice calvarial disease model. METHODS: Thirty-two C57BL/6 J mice were randomized into four groups: Sham, vehicle, osteolysis group with oral WDL treatment for 4 weeks (WDL 4w), and osteolysis group treated for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mineral density (BMD), bone volume/tissue volume (BV/TV) and trabecular bone thickness (Tb.Th). Osteoclast numbers were also measured from histological slides by two investigators who were blind to the treatment used. RESULTS: The results from micro-CT observation showed that BMD in the WDL 8w group improved significantly over the vehicle group (p < 0.05), but there was no significant difference between WDL 4w and 8w for BV/TV and Tb.Th. Osteoclast numbers in the WDL 4w group were also lower than the vehicle group (p < 0.05), but the difference between WDL 8w and 4w groups was not significant. CONCLUSIONS: Particle-induced osteolysis is an inevitable long-term complication after TJR. The results of this animal study indicate that an oral administration of WDL can help reduce the severity of osteolysis without adverse effects.

Evaluation of graphene-derived bone scaffold exposure to the calvarial bone_in-vitro and in-vivo studies.

Graphene is a novel material which has recently been gaining great interest in the biomedical fields. Our previous study observed that graphene-derived particles help induce bone formation in a murine calvarial model. Here, we further developed a blended graphene-contained polycaprolactone (PCL/G) filament for application in a 3D-printed bone scaffold. Since implants are expected to be for long-term usage, in vitro cell culture and in vivo scaffold implants were evaluated in a critical-size bone defect calvarial model for over 60 weeks. Graphene greatly improved the mechanical strength by 30.2% compared to pure PCL. The fabricated PCL/G scaffolds also showed fine cell viability. In animal model, an abnormal electroencephalogram power spectrum and early signs of aging, such as hair graying and hair loss, were found in the group with a PCL/G scaffold compared to pure PCL scaffold. Neither of the abnormal symptoms caused death of all animals in both groups. The long-term use of graphene-derived biomaterials for in-vivo implants seems to be safe. But the comprehensive biosafety still needs further evaluation.

Influence of Vincristine, Clinically Used in Cancer Therapy and Immune Thrombocytopenia, on the Function of Human Platelets.

Vincristine is a clinically used antimicrotubule drug for treating patients with lymphoma. Due to its property of increasing platelet counts, vincristine is also used to treat patients with immune thrombocytopenia. Moreover, antiplatelet agents were reported to be beneficial in thrombotic thrombocytopenic purpura (TTP). Therefore, we investigated the detailed mechanisms underlying the antiplatelet effect of vincristine. Our results revealed that vincristine inhibited platelet aggregation induced by collagen, but not by thrombin, arachidonic acid, and the thromboxane A2 analog U46619, suggesting that vincristine exerts higher inhibitory effects on collagen-mediated platelet aggregation. Vincristine also reduced collagen-mediated platelet granule release and calcium mobilization. In addition, vincristine inhibited glycoprotein VI (GPVI) signaling, including Syk, phospholipase Cγ2, protein kinase C, Akt, and mitogen-activated protein kinases. In addition, the in vitro PFA-100 assay revealed that vincristine did not prolong the closure time, and the in vivo study tail bleeding assay showed that vincristine did not prolong the tail bleeding time; both findings suggested that vincristine may not affect normal hemostasis. In conclusion, we demonstrated that vincristine exerts antiplatelet effects at least in part through the suppression of GPVI signaling. Moreover, this property of antiplatelet activity of vincristine may provide additional benefits in the treatment of TTP.

Are functional outcomes and reoperation rates really better than those of cementless stems in displaced femoral neck fractures? An updated systematic review and meta-analysis of randomized controlled trials in current-generation stem designs.

BACKGROUND: The aim of the study was to conduct a systematic review and meta-analysis to compare the functional outcomes and reoperation rates of cemented and cementless hip arthroplasty for treating displaced femoral neck fractures in elderly patients. METHODS: Systematic searches were conducted of literature up to December 2018 on PubMed, Embase, Cochrane, and Web of Science for randomized controlled trials (RCTs) concerning current-generation stem designs only. Two reviewers independently determined eligibility, extracted the outcome data and assessed the risk of bias of eligible studies. The follow-up data and complication rates were pooled by using random-effects models and fixed-effects models, with mean differences and risk ratios for continuous and dichotomous variables, respectively. RESULTS: Eight RCTs involving 1361 patients (1361 hips) were included in the meta-analysis. Cemented stems were associated with fewer implant-related complications (odds ratio [OR] = 0.303; 95% confidence interval [CI], 0.185%-0.496%; p < 0.001) and reoperations (OR = 0.492; 95% CI, 0.247%-0.977%; p = 0.043). There were no statistically significant differences between groups in functional outcomes, including those assessed by the EuroQol(EQ)-5D and Harris Hip Score, mortality rates, major systemic complications, minor local complications, operation times, intraoperative blood losses, and lengths of hospital stays. CONCLUSION: In treating displaced femoral neck fracture in elderly patients with hip arthroplasty with current-generation stems, cemented stems were found to have fewer implant-related complications and reoperations than those of cementless stems. Functional outcomes and mortality rates were similar between the groups.

Influence of Antibiotic-Loaded Acrylic Bone Cement Composition on Drug Release Behavior and Mechanism.

Periprosthetic joint infection (PJI) is a devastating complication after total joint replacement with considerable morbidity and large economic burdens. Antibiotic-Loaded Bone Cement (ALBC) has been developed as a valuable tool for local administration and is becoming one of the most effective methods for the prevention and treatment of orthopedic infections. Controlling antibiotic release from ALBC is critical to achieve effective infection control, however, the antibiotic elution rates are generally low, and the mechanisms are poorly understood. Thus, the present study aims to investigate the effects of the basic acrylic bone cement components, including liquid/powder (monomer-to-polymer) ratios, radiopacifier, initiator, and doses of antibiotics on the porosity, antibiotic elution rates and mechanical properties of polymethylmethacrylate (PMMA) based ALBC. The obtained results from the in vitro studies suggested that a reduction in the liquid/powder ratio and an increase in the radiopacifier ratio and gentamicin doses led to increased porosity and release of antibiotic, while the initiator ratio exerted no effect on elution rates. In conclusion, we hope that by varying the composition of ALBC, we could considerably enhance the antibiotic elution rates by increasing porosity, while maintaining an adequate mechanical strength of the bone cements. This finding might provide insights into controlling antibiotic release from ALBC to achieve effective infection control after total joint replacement surgery.

A Retrospective Study of Unicompartmental Knee Arthroplasty Functional Outcome and the Incidence of Medial Meniscus Posterior Root Tear in Spontaneous Osteonecrosis of the Knee.

BACKGROUND: Spontaneous osteonecrosis of the knee (SONK) can lead to severe knee osteoarthritis predominantly localized to the medial compartment. We aimed to determine whether unicompartmental knee arthroplasty was an effective treatment for primary SONK. METHODS: We analyzed the functional outcomes in 23 patients with SONK (with a magnetic resonance imaging- (MRI-) confirmed diagnosis) who underwent UKA at a single center. The mean follow-up time was 67 months post-UKA. RESULTS: Significant improvements in function were indicated by reduced Oxford Knee and Visual Analogue Scale scores after UKA, and there were no specific complications after the procedures. The incidence of MRI-identified medial meniscus posterior root tear (MMPRT) was 69.6% (16/23). CONCLUSION: Unicompartmental arthroplasty for SONK is less destructive to the native knee structure than total knee arthroplasty but can achieve comparable prognosis with strict patient selection. While the precise etiology of SONK is unknown, one theory posits that a MMPRT may change the biomechanical circumstances of the knee joint, leading to osteonecrosis. Although not confirmatory, the high prevalence rate suggests that MMPRT may have a key role in the development of SONK. UKA is an effective treatment option for SONK, resulting in significant functional improvement. Long-term (>10 years) outcomes should be investigated.

Gender differences in femoral trochlea morphology.

PURPOSE: This study aimed to analyze the morphology of the anterior femoral condyle using a quantitative three-dimensional reconstruction method. The morphological data were compared between genders. METHODS: Computed tomography scans of femurs were taken from 90 healthy subjects and then reconstructed in 3D modeling software. Coaxial cutting planes were created at 10° increments to measure the lateral and medial anterior condylar heights (LACH and MACH, respectively), lateral and medial trochlear groove widths (LTW and MTW, respectively), and for trochlear groove tracking. The absolute values and normalized data were compared between male and female subjects. The sulcus angle and deepest point of the trochlear groove at each cross-section were also analyzed to determine the differences in the depth of the trochlear groove. RESULTS: The absolute dimensions of LACH, MACH, LTW, and MTW were significantly smaller in the female subjects, by 10.5%, 36.9%, 10.3%, and 11.0%, respectively, than in the males (p < 0.05). After normalization, no significant difference was found in the condylar height between the genders. However, the female subjects had a significantly larger value of approximately 7.9% for the normalized trochlear width. CONCLUSION: Male subjects had greater condylar heights and widths than the female subjects. Although the trajectory of the trochlear groove varied greatly among the subjects, the trochlear groove appeared to be wider and shallower in the female subjects than in the male subjects. These results provide important information for the design of femoral trochlea to fit Asian female patients. LEVEL OF EVIDENCE: III.

Enhanced expression of coxsackievirus and adenovirus receptor in lipopolysaccharide-induced inflammatory macrophages is through TRIF-dependent innate immunity pathway.

AIMS: Inflammatory macrophages have been proposed as a therapeutic target for joint disorders caused by inflammation. This study aimed to investigate the expression and regulation of coxsackievirus-adenovirus receptor (CAR) in lipopolysaccharide (LPS)-stimulated inflammatory macrophages whereby to evaluate the feasibility of virus-directed enzyme prodrug therapy (VDEPT). MAIN METHODS: Macrophage cell lines (RAW264.7 and J774A.1) and primary macrophage cells derived from rat spleen were used to evaluate the expression of CAR protein or CAR mRNA. Specific inhibitors for TLR4 pathway were used to investigate the regulation of CAR expression. CAR expression in rat joints was documented by immunohistochemistry. Conditionally replicating adenovirus, CRAd-EGFP(PS1217L) or CRAd-NTR(PS1217H6), and non-replicating adenovirus CTL102 were used to transduce genes for enhanced green fluorescent protein (EGFP) or nitroreductase (NTR), respectively. The expression of EGFP, NTR, and the toxicity induced by CB1954 activation were evaluated. KEY FINDINGS: The in vitro experiments revealed that CAR upregulation was mediated through the TLR4/TRIF/IRF3 pathway in LPS-stimulated inflammatory macrophage RAW264.7 and J774A.1 cells. The inflammatory RAW264.7 cells upregulated CAR expression following LPS stimulation, leading to higher infectability, increased NTR expression, and enhanced sensitization to CB1954. In animal experiments, the induction of CAR expression was observed in the CD68-expressing primary macrophages and in the CD68-expressing macrophages within joints following LPS stimulation. SIGNIFICANCE: In conclusion, we report an enhanced CAR expression in inflammatory macrophages in vitro and in vivo through the immune response elicited by LPS. Thus, the TLR4/TRIF/IRF3 pathway of macrophages, when activated, could facilitate the therapeutic application of adenovirus-mediated VDEPT.

Effect of material selection on tibial post stresses in posterior-stabilized knee prosthesis.

AIMS: The material and design of knee components can have a considerable effect on the contact characteristics of the tibial post. This study aimed to analyze the stress distribution on the tibial post when using different grades of polyethylene for the tibial inserts. In addition, the contact properties of fixed-bearing and mobile-bearing inserts were evaluated. METHODS: Three different grades of polyethylene were compared in this study; conventional ultra high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (HXLPE), and vitamin E-stabilized polyethylene (VEPE). In addition, tibial baseplates with a fixed-bearing and a mobile-bearing insert were evaluated to understand differences in the contact properties. The inserts were implanted in neutral alignment and with a 10° internal malrotation. The contact stress, von Mises stress, and equivalent plastic strain (PEEQ) on the tibial posts were extracted for comparison. RESULTS: The stress and strain on the tibial post for the three polyethylenes greatly increased when the insert was placed in malrotation, showing a 38% to 56% increase in von Mises stress and a 335% to 434% increase in PEEQ. The VEPE insert had the lowest PEEQ among the three materials. The mobile-bearing design exhibited a lower increase in stress and strain around the tibial posts than the fixed-bearing design. CONCLUSION: Using VEPE for the tibial component potentially eliminates the risk of material permanent deformation. The mobile-bearing insert can help to avoid a dramatic increase in plastic strain around the tibial post in cases of malrotation. The mobility allows the pressure to be distributed on the tibial post and demonstrated lower stresses with all three polyethylenes simulated. Cite this article: Bone Joint Res 2020;9(11):768-777.

Dynamic Hip Screw with Trochanter-Stabilizing Plate Compared with Proximal Femoral Nail Antirotation as a Treatment for Unstable AO/OTA 31-A2 and 31-A3 Intertrochanteric Fractures.

BACKGROUND: The dynamic hip screw (DHS) with the addition of an angular stable trochanter-stabilizing plate (TSP) has been considered the ideal treatment for the unstable intertrochanteric fracture type. However, there have been few comparisons between DHS+TSP augmentation with intramedullary (IM) nailing. The aim of this retrospectively registered study was to compare the clinical outcomes of patients with the unstable type of intertrochanteric fractures treated with DHS+TSP or IM nailing (proximal femoral nail antirotation (PFNA)). METHODS: From June 2013 to April 2018, 358 patients with proximal femur fracture AO/OTA type 31A2 and 31A3 treated with PFNA or DHS+TSP and followed for ≥10 months postoperatively were included. The surgical-dependent outcome evaluation included the operation time, intraoperative blood loss, postoperative decrease in hemoglobin, and blood transfusion amount. Functional status was also measured. Radiographic findings and postoperative complications were recorded and analyzed. RESULT: The operation time was significantly shorter in the DHS+TSP group than that in the PFNA group for both A2 and A3 fractures (A2 type: 84.0 vs.96.4 min; p < 0.05; A3 type: 102.4 vs.116.1 min; p < 0.05). Postoperative decrease in hemoglobin was more significant in the PFNA group than that in the DHS+TSP group for both fracture types (A2 type: -1.88 vs. -1.29 (mg/dL); p < 0.05; A3 type: -1.63 vs. -1.04 (mg/dL); p < 0.05). However, the patients treated with DHS+TSP had significantly more residual pain than those treated with PFNA during the final follow-up (Visual Analog Scale score, A2 type: 28.4 vs.23.2; p < 0.05; A3 type: 27.5 vs.23.6; p < 0.05) and complained of greater implant irritation. CONCLUSION: We found that DHS+TSP was associated with less operation time and less postoperative decrease in hemoglobin but more residual pain and implant irritation than those of PFNA. As a treatment for unstable intertrochanteric fracture, DHS+TSP provided ideal surgical outcomes which were not inferior to the PFNA.

Resistin enhances IL-1ß and TNF-α expression in human osteoarthritis synovial fibroblasts by inhibiting miR-149 expression via the MEK and ERK pathways.

Resistin is a cysteine-rich adipokine that promotes the release of inflammatory cytokines, particularly interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), which are critical pro-inflammatory mediators in osteoarthritis (OA) pathogenesis. We describe evidence of significantly higher levels of resistin, IL-1ß, and TNF-α expression in OA knee synovial tissue compared with that from non-OA knees. Resistin-induced enhancement of IL-1ß and TNF-α expression in human OA synovial fibroblasts (OASFs) were attenuated by MEK and ERK inhibitors, as well as their respective siRNAs. Our data reveal that resistin enhances the expression of TNF-α and IL-1ß in OASFs by inhibiting miR-149 expression via MEK and ERK signaling. Our findings elucidate the inter-relationships between resistin and pro-inflammatory mediators during OA pathogenesis and could help to facilitate the development of synovium-targeted therapy in OA.

Is all-inside with suspensory cortical button fixation a superior technique for anterior cruciate ligament reconstruction surgery? A systematic review and meta-analysis.

BACKGROUND: To compare the clinical results of all-inside anterior cruciate ligament reconstruction (ACLR) using suspensory cortical button fixation and full tibial tunnel drilling. METHODS: Systematic searches were conducted of published literature up to November 2019 on PubMed, Embase, and Cochrane for studies comparing all-inside ACLR using suspensory cortical button fixation and full tibial tunnel ACLR. Two reviewers independently determined eligibility, extracted the outcome data, and assessed the risk of bias of the eligible studies. The clinical outcome and graft reruptures were pooled by using random effects with mean differences and risk ratios for continuous and dichotomous variables, respectively. RESULT: A total of nine studies (five randomized controlled trials and four comparative studies) involving 613 patients were included in the meta-analysis. The postoperative functional outcome, knee laxity measured with arthrometer, and graft reruptures were comparable between patients with all-inside ACLR using suspensory cortical button fixation and full tibial tunnel ACLR. However, a significantly greater thickness of autologous tendon was used and less change in drilling tunnel diameter was noted in patients with suspensory cortical button graft fixation. CONCLUSIONS: All-inside ACLR with suspensory cortical button fixation was not clinically superior to full tibial tunnel ACLR with interference screw fixation in functional outcomes, knee laxity measured with arthrometer, or rerupture rate. However, the advantage of using suspensory cortical button fixation was that a thicker graft could be used for reconstruction, and brought less tibia tunnel widening compared with bioabsorbable interference screw fixation.

Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways.

The development of osteoarthritis (OA) is characterized by synovial inflammation and the upregulation of vascular cell adhesion molecule type 1 (VCAM-1) in human osteoarthritis synovial fibroblasts (OASFs). This increase in VCAM-1 expression promotes monocyte adhesion to OASFs. The adipokine resistin is known to promote the release of inflammatory cytokines during OA progression. In this study, we identified significantly higher levels of resistin and CD68 (a monocyte surface marker) expression in human OA tissue compared with in healthy control tissue. We also found that resistin enhances VCAM-1 expression in human OASFs and facilitates the adhesion of monocytes to OASFs. These effects were attenuated by inhibitors of PKCα, p38, and JNK; their respective siRNAs; and by a microRNA-381 (miR-381) mimic. In our anterior cruciate ligament transection (ACLT) rat model of OA, the inhibition of resistin activity prevented ACLT-induced damage to the OA rat cartilage and pathological changes in resistin and monocyte expression. We also found that resistin affects VCAM-1 expression and monocyte adhesion in human OASFs by inhibiting miR-381 synthesis via the PKCα, p38, and JNK signaling pathways. Our clarification of the crucial role played by resistin in the pathogenesis of OA may lead to more effective therapy that reduces OA inflammation.

In vitro and in vivo Biological Responses to Graphene and Graphene Oxide: A Murine Calvarial Animal Study.

BACKGROUND: Graphene and its derivatives have recently gained popularity in the biomedical field. Previous studies have confirmed that both the mechanical strength and wear resistance of graphene-containing polyethylene have been greatly improved. Therefore, it is being considered as an alternative for artificial joint replacement liners. Based on the literature, the wear debris generated from the traditional polymers used for orthopedic liners could lead to particle-induced osteolysis and, consequently, failure of joint replacement. However, the biological response of this novel graphene-based polymer is still unclear. Therefore, the current study aimed to investigate the in vitro and in vivo biological effects of graphene and graphene oxide (GO) particles on bone. MATERIALS AND METHODS: The biological responses of graphene and GO particles were tested via in vitro and murine calvarial in vivo models. In the in vitro model, murine macrophage cells were mixed with particles and hydrogel and printed into two differently designed scaffolds; the induced proinflammatory cytokines were then tested. In the murine in vivo model, the particle size distribution was measured via SEM, and these particles were then administrated in the calvarial area, referring to our established model. A micro-CT and histological analysis were performed to examine the biological effects of the particles on bone health. The data were analyzed via the one-way analysis of variance to determine the differences between the groups. RESULTS: Both graphene and GO induced significantly higher TNF-α and IL-6 secretion compared with the control in the three-dimensional in vitro model. In the murine calvarial in vivo test, the graphene and GO particles increased the bone mass compared with the sham groups in the micro-CT analysis. Bone formation was also observed in the histological analysis. CONCLUSION: In these in vivo and in vitro studies, the graphene and GO wear debris did not seem to induce harmful biological response effect to bone. Bone formation around the skull was observed in the calvarial model instead. Graphene-containing biomaterials could be a suitable new material for application in orthopedic prostheses due to their benefit of eliminating the risk of particle-induce osteolysis.

Ruthenium complex, TQ­5, protects against LPS­induced macrophage inflammation and acute liver injury in mice via downregulating NF­κB pathways.

A newly synthesized ruthenium metal complex, TQ­5, exhibited antithrombotic and antiplatelet effects in our previous study. In the present study, the anti­inflammatory/hepatoprotective effects and mechanisms of action of TQ­5 were investigated in lipopolysaccharide (LPS)­induced RAW 264.7 macrophages in vitro and in acute liver injury in mice in vivo. The results demonstrated that TQ­5 suppressed the LPS­induced production of nitric oxide, tumor necrosis factor­α (TNF­α), interleukin­1ß (IL­1ß) and inducible nitric oxide synthase (iNOS), without inducing cytotoxicity or damaging the morphology of the RAW 264.7 macrophages. In addition, the role of TQ­5 in mediating mitogen­activated protein kinases and nuclear factor κB (NF­κB) pathways involved in the inflammation process of LPS­stimulated RAW264.7 cells was investigated. Although TQ­5 did not alter the phosphorylation of extracellular signal­related kinase, p38 or c­Jun N­terminal kinase in LPS­treated cells, it suppressed the phosphorylation of Akt in a concentration­dependent manner. TQ­5 significantly reversed the LPS­induced degradation of inhibitor of NF­κBα and phosphorylation of p65. The mRNA expression levels of iNOS, TNF­α and IL­1ß were also suppressed by TQ­5. TQ­5 improved LPS­induced liver injury in mice by inhibiting the expression of TNF­α, IL­1ß and iNOS and phosphorylation of NF­κBp65. These findings suggest that Akt/NF­κB signaling may be a promising target for TQ­5 to combat LPS­induced inflammation. Therefore, TQ­5 may act as a potential agent for the development of anti­inflammatory drugs to treat acute liver failure.

Surgical treatment of postburn heterotopic ossification around the elbow: Three case reports.

RATIONALE: Heterotopic ossification (HO), which is defined as the formation of new bone in tissues that do not normally ossify, is an infrequent yet debilitating complication of burns. Herein, we report three patients who suffered from elbow HO after burn injury due to a dust explosion event. This is a case report that includes the most cases involved in a single mass casualty incident in the presented literature. PATIENT CONCERNS: Case 1: A 28-year-old man presented with second-to-third degree 88% total body surface area (TBSA) burns after the explosion event. He complained of decreased progressive bilateral elbow range of motion (ROM) for 1.5 months after the burn injury.Case 2: A 28-year-old woman presented with second-to-third degree 50% TBSA burns and complained of decreased progressive bilateral elbow ROM with intolerable pain on elbow extension for 1 month after the burn injury.Case 3: A 22-year-old man presented with second-to-third degree 90% TBSA burns and complained of significantly decreased left elbow ROM with intolerable pain 5 months after the burn injury. DIAGNOSIS: The follow-up radiograph of the symptomatic elbow of these three patients revealed heterotopic ossification formation. Three-dimensional reconstruction computed tomography performed preoperatively showed that HO mainly affected the humeroulnar joint. INTERVENTIONS: We treated all three patients with surgical elbow HO resection and ulnar nerve transposition, followed by immediate passive ROM exercise since postoperative day 1 and continuous physical therapy. OUTCOMES: In case 1, the documented ROM gain on the last follow-up (18.5 months after surgery) was 30° in the right elbow and 118° in the left elbow. In case 2, the follow-up time was 21 months and the documented ROM gain on the last follow-up was 120° in the right elbow and 90° in the left elbow. In case 3, the follow-up time was 20 months and the documented left elbow ROM gain on the last follow-up was 40°. LESSONS: We discuss our experience of treating postburn HO and review the recent literature. The postburn HO treatment results of early surgical excision combined with immediate postoperative physical therapy were satisfactory.

Treatment of unstable distal-third clavicule fractures using minimal invasive closed-loop double endobutton technique.

BACKGROUND: Clavicle fractures are common clinical problems, accounting for approximately 10% of all fractures. Neer's type II fractures disrupt the integrity of the coracoclavicular ligament and, therefore, are inherently unstable, requiring an extended period time to achieve bone union and being associated with a high rate of non- or malunion. Restoration of the stability of the distal clavicle is an important factor to decrease the rate of non- or malunion. As such, the aim of our study was to describe our technique of indirect osteosynthesis, using a minimally invasive closed-loop double endobutton (TightRope) technique for fixation of unstable (Neer's type II) distal clavicle factures, and to evaluate the short-term clinical outcomes. METHODS: Fifteen patients with a Neer's type II fracture of the distal clavicle were treated surgically using the TightRope fixation, between January 2016 and December 2017. Clinical and radiological results were assessed using the American Shoulder and Elbow Surgeons Shoulder Score (ASES) and the Constant score. RESULTS: Definitive fracture healing was achieved in most of the patients. No major complication was identified over a mean follow-up of 9 months, and none of the patients required additional surgery related to the index procedure. At the last follow-up, all patients had recovered functional range of motion of the shoulder, with high Constant and ASES scores, and low pain score. CONCLUSION: The use of TightRope fixation provided sufficient stability to reduce the medially displaced fragment of the Neer's type II fracture, with satisfactory radiological and clinical outcomes achieved over a mean follow-up of 9 months. Future studies on the long-term outcomes are needed.