Search

Objective. The purpose of this study was to evaluate the usefulness of preoperative planning of the femurofibular angle (FFA) in medial open-wedge high tibial osteotomy (OWHTO) for mild medial knee osteoarthritis. Methods. Thirty-two patients (32 knees) with mild medial knee OA were retrospectively reviewed. The patients underwent preoperative planning of the FFA for OWHTO. For preoperative planning, a full-length weight-bearing X-ray photograph of the lower limb was opened within Adobe Photoshop Software, and a targeted corrective mechanical axis line of the lower limb and its intersecting point at the lateral tibial plateau surface was drawn using rectangle selection and filling tools. A frame, which encircled the tibia and fibula, was created around the predicted osteotomy plane and then rotated until the ankle center was on the targeted mechanical axis line. Subsequently, a distal femoral condyle line and a proximal fibula axis line were drawn, and the angle between the two lines was measured and defined as the femurofibular angle (FFA). During biplane OWHTO, the preoperatively determined FFA was used to complete the correction of the mechanical axis. During follow-up, the postoperative mechanical weight-bearing line (WBL) of the lower limb, the mechanical femorotibial angle (mFTA), and the FFA were measured and compared with the preoperatively determined values. Results. The mechanical WBL shifted from a preoperative value of 25.36 ± 5.02 % to a postoperative value of 56.19 ± 0.10 % from the medial border along the mediolateral width of the tibial plateau, and it was 56.57 ± 0.08 % at the final follow-up ( P < 0.01 ). The preoperatively determined value was 56.25%, and no significant difference was found compared with postoperative week-one and final follow-up values ( P > 0.05 ). The mFTA was corrected from a preoperative varus of 4.02 ± 0.63 ° to a postoperative week-one valgus of 2.37 ± 0.28 ° , and it had a valgus of 2.48 ± 0.39 ° at the final follow-up ( P < 0.01 ). No significant difference in the valgus was found compared with the postoperative week-one, final follow-up and preoperatively determined valgus of 2.34 ± 0.26 ° ( P > 0.05 ). The postoperative week-one and final follow-up FFAs were 90.34 ± 1.53 ° and 90.33 ± 1.52 ° , respectively, and no significant difference was found compared with the preoperatively determined value of 90.12 ± 1.72 ° and the intraoperative setting value of 90.25 ± 1.67 ° ( P > 0.05 ). All corrected values were within the acceptable range of preoperative planning. Conclusion. Preoperative planning of the FFA may be useful in OWHTO for patients with mild medial knee OA. Satisfactory correction of the postoperative targeted mechanical axis line of the lower limb can be obtained.

The aim of this study was to explore the effect of Chinese herbal SanHuang decoction (SH) on biofilm formation of antibiotic-resistant Staphylococci on titanium surface, and to explore its mechanism. Biofilm-forming ATCC 35984, ATCC 43300 and MRSE 287 were used in this study. The MICs of SH and vancomycin against Staphylococci were determined by the broth microdilution method. Six groups were designed, namely control group (bacteria cultured with medium), 1/8MIC SH group (1MIC SH was diluted by 1/8 using TSB or saline), 1/4MIC SH group, 1/2MIC SH group, 1MIC SH group and vancomycin group (bacteria cultured with 1MIC vancomycin). The inhibitory effect on bacterial adhesion and biofilm formation were observed by the spread plate method, CV staining, SEM, and CLSM. Real-time PCR was performed to determine the effect of SH on the expression levels of ica AD and ica R gene in ATCC 35984 during the biofilm formation. The strains were found to be susceptible to SH and vancomycin with MIC of 38.75 mg/ml and 2.5 μg/ml, respectively. SH with 1 MIC and 1/2 MIC could inhibit the bacteria adhesion, showing only scattered adhesion from SEM. CLSM showed that SH with 1 MIC and 1/2 MIC inhibited the biofilm formation. The quantitative results of the spread plate method and CV staining showed that there was significant differences between the SH groups (P P ica AD decreased, and the expression of ica R increased correspondingly (P Staphylococci. Its probable mechanistic activity may be through the inhibition of polysaccharide intercellular adhesin synthesis by down-regulating the expression of ica AD gene.

Clinical study has shown that external socking and washing with the Chinese herbal SanHuang decoction (SH) can control the orthopedic-biofilm related infections. However, the antibiofilm activities of SH in vitro have not been investigated. The aim of the current study was to explore the effect of SH on adhesion and biofilm formation of antibiotic-resistant staphylococci on titanium surface, and to explore its probable mechanistic effects on staphylococcal strains. Biofilm-forming ATCC 35984 (methicillin-resistant Staphylococcus epidermidis, MRSE) and ATCC 43300 (methicillin-resistant Staphylococcus aureus, MRSA) strains were used in this study. The minimum inhibitory concentrations (MICs) of SH and vancomycin against planktonic bacterial strains were determined by the broth microdilution method. Different sub-MIC of SH with TSB (Tryptic soy broth) were used as the basis for experimental grouping (SH group). TSB culture medium alone (TSB group) or TSB containing vancomycin (vancomycin group) incubated with bacteria were considered as the negative or positive control group, respectively. The inhibitory effect of different treatment on bacterial adhesion and biofilm formation were observed by the spread plate method, CV (crystal violet) staining, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM). Real time PCR analysis was performed to determine the effect of SH on the expression levels of ica AD and ica R gene in ATCC 35984 during the biofilm formation. The strains were found to be susceptible to SH decoction with MIC and MBC values of 38.75 mg/ml and 77.5 mg/ml, respectively. The MIC values for vancomycin was 2.5 μg/ml. SH treatment with 1 MIC and 1/2 MIC could inhibit the bacteria adhesion on the titanium surface, showing only scattered bacterial adhesion from SEM. CLSM showed that SH with 1 MIC and 1/2 MIC could also inhibit the bacterial biofilm formation. The quantitative results of the spread plate method and CV staining showed that there was significant differences between the SH groups (P < 0.05). Further, with an increase in SH concentration, the inhibitory effect became more obvious at different culture time points, when compared with TSB control group (P < 0.05). Among the groups, vancomycin had the strongest inhibitory effect on bacterial adhesion and biofilm formation (P < 0.01). Meanwhile, with an increase in SH concentration, the expression levels of ica A and ica D decreased, and the expression of ica R increased correspondingly (P < 0.05). In conclusions, a certain concentration of SH can inhibit the adhesion and biofilm formation of antibiotic-resistant Staphylococcal strains on the titanium surface, but the effect was not as good as vancomycin. Its probable mechanistic activity may be through the inhibition of polysaccharide intercellular adhesin synthesis by down-regulating the expression of ica AD gene, thus inhibiting bacterial biofilm formation.

To investigate the effectiveness of non-absorbable suture cerclage combined with patella claw fixation for the treatment of inferior patella fractures.Between September 2016 and January 2019, 22 patients with inferior patella fractures were treated. There were 12 males and 10 females, with a mean age of 49.1 years (range, 32-67 years). The causes of injury were traffic accident in 8 cases, falling in 12 cases, and other causes in 2 cases. The interval from injury to operation was 3-7 days (mean, 4.4 days). For the operation, 3 or 4 longitudinal tunnels were drilled backward from the surface of the proximal fracture fragment with Kirschner wires; under the guidance of lumbar puncture needles and steel wires, non-absorbable suture passed through the tunnels and encircled the inferior fracture fragment, then tighten to achieve a satisfactory reduction of the fracture; finally, the patella claw was used to strengthen the fixation. During the follow-up, complications were observed, maximum motion range of the knee joint was measured, X-ray examination was performed and fracture healing time was recorded. The knee function was evaluated according to Böstman scores.All the 22 patients were followed up 12-36 months (mean, 19.4 months). No infection, joint stiffness, bone nonunion, loss of reduction, or displacement of internal fixation occurred. All fractures were clinically healed, and the bone healing time was 2-3 months (mean, 2.6 months). At last follow-up, the maxium motion range of knee joint was 130°-135°, with an average of 132.6°. The Böstman score of the affected knee was 28-30 (mean, 29.2). All cases were graded as excellent results.Non-absorbable suture cerclage combined with patella claw fixation for inferior patella fractures has the advantages of simple operation, reliable fixation, and few complications, and the clinical results are satisfactory.探讨不可吸收缝合线捆扎骨折块结合髌骨爪固定治疗髌骨下极骨折的临床疗效。.2016 年 9 月—2019 年 1 月，收治 22 例髌骨下极骨折患者。其中男 12 例，女 10 例；年龄 32～67 岁，平均 49.1 岁。致伤原因：交通事故伤 8 例，跌伤 12 例，其他伤 2 例。根据 Rockwood 分型均为Ⅲ型。受伤至手术时间 3～7 d，平均 4.4 d。手术以克氏针由髌骨近侧骨折块表面向后下钻取 3～4 个骨道；在腰椎穿刺针及钢丝引导下，以不可吸收缝合线纵向穿过髌骨骨道并环绕下极骨折块捆扎复位；最后再以髌骨爪纵向环抱髌骨加强固定。术后观察并发症发生情况，测量膝关节最大活动度，行 X 线片检查并记录骨折愈合时间，按照 Böstman 髌骨骨折功能评分评估患膝关节功能恢复情况。.22 例患者均获随访，随访时间 12～36 个月，平均 19.4 个月。随访期间无感染、关节僵直、骨不连、复位丢失及内固定物移位等并发症发生。骨折均获临床愈合，愈合时间为 2～3 个月，平均 2.6 个月。末次随访时，膝关节最大活动度为 130°～135°，平均 132.6°。患膝 Böstman 髌骨骨折功能评分为 28～30 分，平均 29.2 分；功能评价均获优。.不可吸收缝合线捆扎结合髌骨爪固定治疗髌骨下极骨折具有操作简便、固定可靠、并发症少的优点，临床疗效满意。.

To observe the effectiveness of arthroscopic reconstruction of medial patellofemoral ligament (MPFL) with a single bundle of autogenous half peroneal longus tendon, and medial displacement of lateral hemitibial tuberosity for the treatment of recurrent dislocation of patella.Retrospectively analyse the clinical data of 24 patients (24 knees) with recurrent patellar dislocation with tibial tuberosity-trochlear groove distance (TT-TG) values more than 15 mm who were admitted between September 2014 and September 2018. Of which 7 were male and 17 were female; aged 16-35 years old with an average of 25.8 years. The disease duration ranged from 15 to 46 months, with an average of 26.7 months. All patients had a history of knee trauma, and a positive result of apprehension test on the affected knee. All patients underwent the surgery of arthroscopic reconstruction of MPFL with a single bundle of autogenous half peroneal longus tendon, and medial displacement of lateral hemitibial tuberosity. Before and after operation, Kujala score was used to evaluate patellofemoral joint function, Lysholm score was used to evaluate knee joint function; CT and MRI were used to measure and compare the changes of congruence angle (CA), patellar tilt angle (PTA), and lateral patella displacement (LPD) in order to evaluate patella stability.All incisions healed by first intention, and no infection or neurovascular injury occurred. Deep vein thrombosis of the lower extremities occurred in 2 cases at 4 and 7 days after operation respectively, and the thrombosis disappeared after symptomatic treatment. All the 24 patients were followed up 12-14 months (mean, 12.9 months). During follow-up, no patellar dislocation reoccurred in the affected knee. At last follow-up, the apprehension test was negative in every patients. The TT-TG, CA, PTA, and LPD were significantly improved when compared with those before operation (Arthroscopic reconstruction of MPFL with a single bundle of autogenous half peroneal longus tendon combined with medial displacement of lateral hemitibial tuberosity has the advantages of minimal invision and reliable effectiveness. It can be used as one of the effective surgical methods for the treatment of recurrent dislocation of patella.观察关节镜辅助下取自体腓骨长肌腱外侧半经髌骨单隧道单束单股重建内侧髌股韧带（medial patellofemoral ligament，MPFL），结合外侧半胫骨结节内移术治疗复发性髌骨脱位的临床疗效。.回顾分析 2014 年 9 月—2018 年 9 月收治的 24 例（24 膝）胫骨结节-股骨滑车沟间距（tibial tuberosity-trochlear groove distance，TT-TG）值15 mm 的复发性髌骨脱位患者临床资料。其中男 7 例，女 17 例；年龄 16～35 岁，平均 25.8 岁。病程 15～46 个月，平均 26.7 个月。患者均有患膝关节外伤史，患侧膝关节恐惧试验阳性。关节镜辅助下，取自体腓骨长肌腱外侧半经髌骨单隧道单束单股重建 MPFL，同时结合外侧半胫骨结节内移术治疗。手术前后采用 Kujala 评分评价髌股关节功能，采用 Lysholm 评分评价膝关节功能；采用 CT、MRI 测量并比较髌股适合角（congruence angle，CA）、髌骨倾斜角（patellar tilt angle，PTA）及外侧髌骨移位值（lateral patella displacement，LPD）变化情况，评价髌骨稳定性。.术后患者切口均Ⅰ期愈合，无感染及神经血管损伤等并发症发生。2 例分别于术后 4、7 d 出现下肢深静脉血栓形成，经对症处理后血栓消失。24 例患者均获随访，随访时间 12～14 个月，平均 12.9 个月。随访期间患侧膝关节均未再发生髌骨脱位；末次随访时患者恐惧试验均为阴性。末次随访时，患者膝关节 TT-TG 值、CA、PTA、LPD 均较术前显著改善（关节镜辅助下取自体腓骨长肌腱外侧半经髌骨单隧道单束单股重建 MPFL，结合外侧半胫骨结节内移治疗复发性髌骨脱位，具有创伤小、疗效可靠等优点，是一种有效手术方式。.

To investigate the clinical efficacy of pre-operative simulation using a three-dimensional (3D) printing model for surgical treatment of old and complex tibial plateau fractures. Forty-two patients with old and complex tibial plateau fractures were retrospectively reviewed from January 2014 to January 2018, which were divided into a conventional planning group (n = 22) and a planning with 3D printing group (n = 20). In the planning with 3D printing group, preoperative equal-ratio fracture models prepared using the 3D printing technique were used to perform pre-operative simulation and guide the real surgical operation. In the conventional planning group, the operation was performed based on pre-operative computed tomography (CT) images. Surgery duration, blood loss and the number of fluoroscopy during operations were recorded. During follow-up, the quality of fracture reduction and complications were also recorded. Knee functions were evaluated using the hospital for special surgery (HSS) scoring system. The operation time, blood loss and the number of fluoroscopy during operation in the planning with 3D printing group were less than that in the conventional planning group (P P = 0.05). The complication rate was 15% in the planning with 3D printing group and 31.82% in the conventional planning group. At the final follow-up evaluation, the mean HSS score was 86.05 ± 7.67 in the planning with 3D printing group and 79.09 ± 6.75 in the conventional planning group (P = 0.003). The rate of excellent results in the planning with 3D printing group was 70% and in the conventional planning group was 45.45% (P = 0.083). In conclusion, pre-operative simulation using a 3D printing model may be helpful for the treatment of old and complex tibial plateau fractures, which may be conducive to the pre-operative planning and to making the surgical procedure accurate and personalized. However, its clinical effectiveness need to be further assessed by a prospective randomized-controlled study.

Background: Arthroscopic narrow posteromedial gap of the knee may cause the failure of meniscus operation. The posteromedial complex (PMC) of the knee, including the posterior part of MCL and posterior oblique ligament, has a restrictive effect on the opening of the posteromedial gap of the knee in the half-extension position. Thus, we evaluated the radiological and clinical results of pie-crusting release of PMC for arthroscopic meniscal surgery in tight knees.Methods : Sixty patients with posterior injury of the medial meniscus were reviewed. All patients accepted arthroscopic pie-crusting release of the PMC. Fourty patients accepted meniscoplasty, and 20 patients accepted meniscuc suturing. To evaluate the arthroscopic opening of the medial gap in 20°half-extension under 11-kg valgus stress, the width of the medial space before and after release were measured. During follow-up, the medial stability was evaluated by radiographic measurements of the joint space width (JSW) in 20°half-extension. MRI was conducted to evaluate the healing of MCL and meniscus. Knee functions were evaluated using VAS, Lysholm, IKDC and Tegner scoring systems. Results: In all patients, meniscus operations were performed without iatrogenic cartilage injury. After PMC release, the arthroscopic width of the medial space was 5.7 ±0.5 mm, showing larger than that before release (2.5 ± 0.5 mm) (p < 0.01). The follow-up time was 21.93±7.04 months, there was no residual valgus laxity of the knee. The radiographic JSW was 5.97 ± 0.8 mm preoperatively, 9.2 ± 1.1 mm in the postoperative 1st week, and 6.1±0.9 mm in the postoperative 3rd months, showing no differences between pre- and postoperative 3rd month (p > 0.05). For sutured meniscus, MRI showed healing in 15 patients while five had two-grade abnormal signals. VAS, Lysholm, IKDC and Tegner scores were 1.80±0.51, 80.08±3.74, 82.17±4.64 and 5.48±0.59, respectively, showing significant differences compared with the preoperative scores (5.57±0.69, 48.17±4.22, 51.42±4.02 and 3.20±0.68, respectively) (P < 0.01).Conclusion s: Pie-crusting release of PMC can increase the posteromedial space and improve the visual field of the knee under arthroscopy, and this technique do neither produce residual valgus instability of the knee nor affect clinical outcome at the final follow-up.

Distal femoral resection in total knee arthroplasty (TKA) is commonly performed using intramedullary jigs with a pre-operatively planned valgus cut angle (VCA). For valgus knees with lateral femoral condyle hypoplasia, the method of determining the accurate VCA has not been clarified. The aim of the present study is to introduce a method that can accurately determine the distal femoral VCA in the valgus knee arthroplasty. Twenty patients with valgus deformity caused by lateral femoral condylar hypoplasia underwent primary TKA with individually measured VCA. The VCA was defined as the acute crossing angle of the anatomical and mechanical axes of the femur on a pre-operative X-ray film, and the two axes almost always crossed at the distal femoral diaphysis, but not the centre of the knee as generally described. The entry point of the femoral intramedullary guide rod was determined on the extension of the femoral anatomical axis and was usually medial to the centre of the knee. According to the pre- and post-operative X-ray films, the mechanical lateral distal femoral angle (mLDFA), and coronal alignment of the femoral components were measured. The post-operative knee pain and function were evaluated using the Visual Analog Scale and Knee Society Score, respectively. The mean VCA measured according to the above method was 6.4° ± 1.0° (4.7–8.2°), and the femoral entry point was located at a mean distance of 7.4 ± 2.1 mm (4.5–10.9 mm) medial to the centre of the knee joint. The mean mLDFA before and after operation was 77.4° ± 5.7° (74–82°) and 88.4° ± 1.7° (86–90°), respectively, showing a statistically significant difference (P

Background/Aims: Krüppel-like factor 2 (KLF2) plays an essential role in the inhibition of endothelial cell and macrophage activation during the inflammatory process. However, the roles of KLF2 in chondrocytes and the pathological progression of osteoarthritis (OA) remain unknown. The aim of this study was to investigate the function of KLF2 in the inhibition of cartilage matrix destruction in chondrocytes. Methods: RT-PCR and western blot analysis was used to determine the expression of KLF2 in human chondrocytes. Luciferase assay, ELISA assay and MMP-13 enzymatic activity assays were used to investigate the effects of KLF2 in regulating MMP-13 expression. Western blot analysis was used to examine the effects of KLF2 in suppressing degradation of type Ⅱ collagen. Results: KLF2 is expressed in primary chondrocytes and is downregulated in OA chondrocytes. Expression of KLF2 in primary chondrocytes was reduced in response to IL-1β. Overexpression of KLF2 robustly inhibited IL-1β-induced MMP-13 expression. Conversely, knockdown of KLF2 markedly exacerbated MMP-13 expression. Mechanistically, KLF2 could suppress the activation of MMP-13 promoter. However, knockdown of KLF2 could promote the activation of MMP-13 promoter. Importantly, overexpression of KLF2 ameliorated the degradation of type Ⅱ collagen while silencing of KLF2 exacerbated the degradation of type Ⅱ collagen induced by IL-1β. Conclusions: KLF2 may be a potential therapeutic target for OA treatment.

Treating skin and soft tissue infections of severe limb traumas can be challenging. Crucial concerns focus on inhibiting biofilm formation by antibiotic‑resistant bacteria, and preventing scar formation by fibroblastic hyperproliferation. The local use of toluidine blue O (TBO)‑mediated photodynamic therapy (PDT) may be a promising strategy for treating such lesions. The present study used Staphylococcus epidermidis (strain ATCC 35984) to assess the effects of TBO‑PDT on bacterial adherence and biofilm formation, using confocal laser scanning microscopy (CLSM), tissue culture plating (TCP) and scanning electron microscopy (SEM). Primary human fibroblast cells were used to evaluate the cytotoxicity of TBO‑PDT using the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay and CLSM. Six different treatment groups were investigated: Medium only [tryptone soy broth (TSB) or Dulbecco's modified Eagle's medium (DMEM)]; red light control (light dose, 30 J/cm2); TBO group (50 mM TBO); TBO‑PDT1 (TBO irradiated with 10 J/cm2); TBO‑PDT2 (TBO irradiated with 20 J/cm2); and TBO‑PDT3 (TBO irradiated with 30 J/cm2). The results of the S. epidermidis adhesion assay indicated that the TSB, light and TBO groups exhibited significant bacterial adherence, compared with the TBO‑PDT groups. Analysis of biofilm formation revealed significant light dose‑dependent differences between the TBO‑PDT groups and the TSB, light, and TBO groups. Furthermore, SEM indicated fewer colony masses in the TBO‑PDT groups compared with the control groups. The MTT assay for fibroblastic cell toxicity demonstrated ~1.1, 4.6, 14.5, 29.7 and 43.4% reduction in optical density for the light, TBO, TBO‑PDT1, TBO‑PDT2 and TBO‑PDT3 groups, respectively, compared with the DMEM control group. There was no difference in toxicity between the light and control groups, however, there were significant differences among the TBO‑PDT groups. Finally, alterations in fibroblast morphology and cell spreading were revealed by CLSM, following TBO‑PDT treatment. TBO‑PDT inhibited bacterial adhesion and biofilm formation, and exhibited significant cytotoxic effects on human fibroblasts. These results indicate that the local use of TBO‑PDT in limb lesions may be a useful treatment method for inhibiting bacterial biofilm formation and fibroblastic hyperproliferation, which may prevent infectious hypertrophic scar formation.

Honglue Tan,1 Shengbing Yang,2 Pengyi Dai,1 Wuyin Li,1 Bing Yue2 1Luoyang Orthopedics and Traumatology Institution, Luoyang Orthopedic-Traumatological Hospital, Luoyang, 2Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China Abstract: As a commonly used implant material, calcium sulfate cement (CSC), has some shortcomings, including low compressive strength, weak osteoinduction capability, and rapid degradation. In this study, silica-based mesoporous materials such as SBA-15 were synthesized and combined with CSC to prepare CSC/SBA-15 composites. The properties of SBA-15 were characterized by X-ray diffraction, transmission electron microscopy, and nitrogen adsorption–desorption isotherms. SBA-15 was blended into CSC at 0, 5, 10, and 20 wt%, referred to as CSC, CSC-5S (5% mass ratio), CSC-10S (10% mass ratio), and CSC-20S (20% mass ratio), respectively. Fourier-transform infrared spectroscopy and compression tests were used to determine the structure and mechanical properties of the composites, respectively. The formation of hydroxyapatite on composite surfaces was analyzed using scanning electron microscopy and X-ray diffraction after soaking in simulated body fluid. BMP-2 was loaded into the composites by vacuum freeze-drying, and its release characteristics were detected by Bradford protein assay. The in vitro degradation of the CSC/SBA-15 composite was investigated by measuring weight loss. The results showed that the orderly, nanostructured, mesoporous SBA-15 possessed regular pore size and structure. The compressive strength of CSC/SBA-15 increased with the increase in SBA-15 mass ratio, and CSC-20S demonstrated the maximum strength. Compared to CSC, hydroxyapatite that formed on the surfaces of CSC/SBA-15 was uniform and compact. The degradation rate of CSC/SBA-15 decreased with increasing mass ratio of SBA-15. The adsorption of BMP-2 increased and released at a relatively slow rate; the release rate of BMP-2 in CSC-20S was the slowest, and presented characteristics of low doses of release. In vitro experiments demonstrated that the physical properties of pure CSC incorporated with SBA-15 could be improved significantly, which made the CSC/SBA-15 composite more suitable for bone repair and bone-tissue engineering. Keywords: calcium sulfate cement (CSC), SBA-15, physical characterization, BMP-2

Scaffolds play a critical role in bone tissue engineering. Composite scaffolds made of biodegradable polymers and bioactive inorganic compounds have demonstrated superior properties in bone defect repair. In this study, highly bioactive, resorbable poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)-based scaffolds were prepared using combinational 3-dimensional (3D) printing and surface-doping protocol. Structural and morphological characterization of the composite scaffolds demonstrated the homogenous surface-coating of mesoporous bioactive glass (MBG) throughout their porous framework. These hierarchical scaffolds showed bioactivity superior to that of scaffolds made of pure PHBHHx. MBG coating appeared to provide a better environment for human mesenchymal stem cells (hMSCs) attachment, activity, and osteogenic differentiation. Our study indicates that MBG-coated PHBHHx (PHBM) scaffolds may be excellent candidates for use in bone tissue engineering.

Background Treatments of infections are not always successful because of multi-antibiotic-resistant organisms. It is therefore particularly urgent to provide more effective anti-infective strategy against these organisms. 5-Aminolevulinic acid (ALA), with the chemical structure C5H9NO3, is the only photodynamic therapy agent that is a biochemical precursor of a photosensitizer (protoporphyrin IX [PpIX]), which is naturally produced by the body. 5-Aminolevulinic acid–mediated photodynamic therapy (ALA-PDT) has been shown to have a strong effect on the treatment of localized cancerous and precancerous lesions, and further study demonstrated its efficacy for gram-positive and gram-negative bacteria. However, its effect on biofilm formed by antibiotic-resistant strains has not been reported. Methods In this study, we evaluated the effectiveness of ALA-PDT on biofilms formed by methicillin-resistant Staphylococcus aureus (ATCC 43300) and methicillin-resistant S epidermidis (MRSE 287). The strains were cultured with 40 mM of ALA in 24-well microtiter plates containing coverslips at 37°C for 24 h in the dark. PpIX fluorescence in biofilms formed by the two strains was observed by confocal laser scanning microscopy (CLSM). ALA-treated biofilms were irradiated at different doses (0, 100, 200, and 300 J/cm2) using a semiconductor laser. Biofilm exposed only to Tryptone Soy Broth or irradiation (300 J/cm2) was investigated. Viability determination, CLSM, and scanning electron microscopy were used to investigate the photodynamic inactivation of ALA-PDT. Results ALA was absorbed and converted to PpIX by both methicillin-resistant S aureus and methicillin-resistant S epidermidis. No cell inactivation was detectable in biofilms of either strain incubated with ALA without exposure to light, incubated with Tryptone Soy Broth only, or irradiated with red light only. However, a significant number of cells within biofilms were inactivated during irradiation with different doses of red light in the presence of 40 mM of ALA in a dose-dependent manner. The drastic reduction in cell survival within biofilms and the disruption of biofilms were confirmed by CLSM and scanning electron microscopy. Conclusions ALA-PDT has the potential to eliminate the biofilm of Staphylococcus, especially antibiotic-resistant strains, effectively. It will be suitable for the treatment of superficial local infections such as surface wounds, burns, oral and dental infections, dermatologic infections such as acne and rosacea, and soft tissue and bone infections with bone exposure.

Background Implantation-associated infections have increased significantly with the recent widespread use of medical implants. Treatments for these infections are not always successful because these infections are sometimes caused by multiantibiotic-resistant organisms. It is therefore particularly urgent to provide doctors with more effective antimicrobial agents against these antibiotic-resistant organisms. Human β-defensin 3 (hBD-3) has been shown to have strong broad-spectrum antibacterial activity. However, its effect on methicillin-resistant Staphylococcus epidermidis (MRSE) and methicillin-resistant Staphylococcus aureus (MRSA) in medical implant biofilm formation has not been reported. Methods In this study, we evaluated the effects of hBD-3 on S epidermidis ATCC 35984 (methicillin-resistant strain), MRSE287, and MRSA (ATCC43300) by evaluating bacterial adhesion, biofilm formation, and maturation. In addition, we used the spread plate method, confocal laser scanning microscopy, scanning electron microscopy, and real-time polymerase chain reaction to evaluate the effect of hBD-3. Results After evaluating biofilm adhesion and formation, we found that the number of each strain on the titanium surface was decreased in those groups exposed to 1MIC (minimum inhibitory concentration) of hBD-3 and was significantly lower than the number of colonies of the control. In the initial maturation of the biofilm, the numbers of each strain on the titanium surface from the 2MIC to 6MIC groups were significantly lower than the control. When the concentrations were further increased, hBD-3 was significantly effective against drug-resistant bacteria from the biofilms. Conclusions HBD-3 has the potential to eliminate the biofilm formation of Staphylococcus , especially antibiotic-resistant strains, effectively.

In this study, type I collagen was fixed onto plasma-sprayed porous titanium coatings by either adsorptive immobilization or covalent immobilization. Surface characterization by scanning electron microscopy (SEM), diffuse reflectance Fourier transform infrared spectroscopy (DR-FTIR) and X-ray photoelectron spectroscopy (XPS) confirmed the biochemical modification of the titanium coatings. The immobilizing effects of type I collagen, including variations in the amount and stability of collagen, were investigated using Sirius red staining. A greater amount of collagen was found on the covalently immobilized titanium coating, and higher stability was achieved relative to the absorptive immobilization surface. Human mesenchymal stem cells (hMSCs) were used to evaluate the cytocompatibility of the modified titanium coatings. Type I collagen immobilized on titanium coating led to enhance cell-material interactions and improved hMSC functions, such as attachment, proliferation, and differentiation. Interestingly, covalently immobilized collagen on titanium coating showed a greater capability to regulate the osteogenic activity of hMSCs than did absorbed collagen, which was explained in terms of the increased amount and higher stability of the covalently linked collagen. The type I collagen covalently immobilized titanium coatings with improved biological function may exhibit better osteointegration in clinical application.

Mammalian β-defensins are small cationic peptides of approximately 2-6 kDa that have been implicated in mediating innate immune defenses against microbial infection. Previous studies have reported that mouse β-defensin-14 (MBD‑14), based on structural and functional similarities, appears to be an ortholog of human β-defensin-3 (HBD-3). The aim of this study was to identify the signaling pathways that contribute to the expression of MBD-14 in mouse osteoblasts (OBs) upon contact with methicillin-resistant Staphylococcus aureus (S. aureus) supernatant (SAS) to provide a theoretical basis for the use of MDB-14 as a therapeutic agent in the treatment of intramedullary infection with S. aureus in vivo. The bacterial exoproducts released by S. aureus mainly include a large amount of enterotoxins. Using mouse OBs, the release and regulation of MBD-14 was evaluated by real-time polymerase chain reaction (PCR) and enzyme‑linked immunosorbent assay (ELISA) following exposure to SAS. The activation of the p38 mitogen‑activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB) pathways was determined by western blot analysis. OBs treated with lipopolysaccharide (LPS) were used as the positive control. The results revealed that SAS significantly promoted the phosphorylation of p38 MAPK, NF-κB and the inhibitory subunit of NF-κBα (IκBα) in a time-dependent manner. The treatment of OBs with SB203580 (an inhibitor of p38 MAPK) and pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) prior to stimulation with SAS significantly inhibited the phosphorylation and mRNA expression of p38 MAPK and NF-κB p65, simultaneously reducing the release of MBD-14. Our findings suggest that the release of MBD-14 is mediated at least in part through the activation of p38 MAPK and NF-κB in response to S. aureus‑secreted bacterial exoproducts. Moreover, our data demonstrate the innate immune capacity of OBs under conditions of bacterial challenge to enhance the local expression of this MBD-14, a peptide with anti‑staphylococcal activity.

Titania nanotube-based local drug delivery is an attractive strategy for combating implant-associated infection. In our previous study, we demonstrated that the gentamicin-loaded nanotubes could dramatically inhibit bacterial adhesion and biofilm formation on implant surfaces. Considering the overuse of antibiotics may lead to the evolution of antibiotic-resistant bacteria, we synthesized a new quaternized chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) with a 27% degree of substitution (DS; referred to as 27% HACC) that had a strong antibacterial activity and simultaneously good biocompatibility with osteogenic cells. Titania nanotubes with various diameters (80, 120, 160, and 200 nm) and 200 nm length were loaded with 2 mg of HACC using a lyophilization method and vacuum drying. Two standard strain, methicillin-resistant Staphylococcus aureus (American Type Culture Collection 43300) and Staphylococcus epidermidis (American Type Culture Collection 35984), and two clinical isolates, S. aureus 376 and S. epidermidis 389, were selected to investigate the bacterial adhesion at 6 h and biofilm formation at 24, 48, and 72 h on the HACC-loaded nanotubes (NT-H) using the spread plate method, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM). Smooth titanium (Smooth Ti) was also investigated and compared. We found that NT-H could significantly inhibit bacterial adhesion and biofilm formation on its surface compared with Smooth Ti, and the NT-H with 160 nm and 200 nm diameters had stronger antibacterial activity because of the extended HACC release time of NT-H with larger diameters. Therefore, NT-H can significantly improve the antibacterial ability of orthopedic implants and provide a promising strategy to prevent implant-associated infections.

Biomaterial-associated infections remain a serious complication in orthopaedic surgery. Treatments, including the local use of antibiotic-loaded polymethylmethacrylate (PMMA) bone cement, are not always successful because of multiantibiotic-resistant organisms. In this study, we synthesised a new quaternised chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) that contains a series of substitutions of quaternary ammonium and demonstrated that HACC with a 26% degree of substitution (DS; referred to as 26%HACC) had a strong antibacterial activity and simultaneously good biocompatibility with osteogenic cells. We loaded 26%HACC at 20% by weight into PMMA bone cement to investigate whether HACC in PMMA prevents bacterial biofilm formation on the surface of bone cements. Chitosan-loaded PMMA (at the same weight ratio), gentamicin-loaded PMMA and PMMA with no antibiotic were also investigated and compared. Two clinical isolates, Staphylococcus epidermidis 389 and methicillin-resistant S. epidermidis (MRSE287), and two standard strains, S. epidermidis (ATCC35984) and methicillin-resistant Staphylococcus aureus (ATCC43300), were selected to evaluate the bacterial biofilm formation at 6, 12 and 24 h using the spread plate method, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The results showed that 26%HACC-loaded PMMA inhibited biofilm formation on its surface, while the PMMA control and chitosan-loaded PMMA were unable to inhibit biofilm formation. The gentamicin-loaded PMMA decreased the number of viable methicillin-resistant Staphylococcus strains, but its ability to inhibit biofilm formation was lower than 26%HACC-loaded PMMA. Real-time PCR demonstrated that 26%HACC-loaded PMMA markedly downregulated the expression of icaAD, which encodes essential enzymes for polysaccharide intercellular adhesion (PIA) biosynthesis, upregulated the expression level of icaR, which negatively mediates icaAD expression, and also downregulated the expression of MecA, which encodes membrane-bound enzymes known to be penicillin-binding proteins. Our study indicates that 26%HACC-loaded PMMA prevents biofilm formation of Staphylococcus, including antibiotic-resistant strains, on the surface of bone cement, and downregulates the virulence-associated gene expression of antibiotic-resistant staphylococcus, thus providing a promising new strategy for combating implant infections and osteomyelitis.

Bone infections are common in trauma-induced open fractures with bone defects. Therefore, developing anti-infection scaffolds for repairing bone defects is desirable. This study develoepd novel Mg-based porous composite scaffolds with a basal matrix composed of poly(lactic-co-glycolicacid) (PLGA) and tricalcium phosphate (TCP). A unique low-temperature rapid prototyping technology was used to fabricate the scaffolds, including PLGA/TCP (PT), PLGA/TCP/5%Mg (PT5M), PLGA/TCP/10%Mg (PT10M) and PLGA/TCP/15%Mg (PT15M). The bacterial adhesion and biofilm formation of Staphylococcus aureus were evaluated. The results indicated that the Mg-based scaffolds significantly inhibited bacterial adhesion and biofilm formation compared to PT and the PT10M and PT15M exhibited significantly stronger anti-biofilm ability than PT5M. In vitro degratation tests revealed that the degradation of the Mg-based scaffolds caused an increase of pH, Mg2+ concentration and osmolality and the increased pH may be one of the major contributing factors to the antibacterial function of the Mg-based scaffolds. Additionally, the PT15M exhibited an inhibitory effect on cell adhesion and proliferation of MC3T3-E1 cells. In conclusion, the PLGA/TCP/Mg scaffolds could inhibit bacterial adhesion and biofilm formation and the PT10M scaffold was considered to be an effective composition with considerable antibacterial ability and good cytocompatibility.

Rui Ma,1 Songchao Tang,2 Honglue Tan,1 Wentao Lin,1 Yugang Wang,1 Jie Wei,2 Liming Zhao,2 Tingting Tang1 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 2Key Laboratory for Ultrafine Materials of Ministry of Education and The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China Abstract: A bioactive composite was prepared by incorporating 40 wt% nano-­hydroxyapatite (nHA) into polyetheretherketone (PEEK) through a process of compounding, injection, and molding. The mechanical and surface properties of the nHA/PEEK composite were characterized, and the in vitro osteoblast functions in the composite were investigated. The mechanical properties (elastic modulus and compressive strength) of the nHA/PEEK composite increased significantly, while the tensile strength decreased slightly as compared with PEEK. Further, the addition of nHA into PEEK increased the surface roughness and hydrophilicity of the nHA/PEEK composite. In cell tests, compared with PEEK and ultra-high-molecular-weight polyethylene, it was found that the nHA/PEEK composite could promote the functions of MC3T3-E1 cells, including cell attachment, spreading, proliferation, alkaline phosphatase activity, calcium nodule formation, and expression of osteogenic differentiation-related genes. Incorporation of nHA into PEEK greatly improved the bioperformance of PEEK. The nHA/PEEK composite might be a promising orthopedic implant material. Keywords: polyetheretherketone, nano-hydroxyapatite, biocomposite, osteoblast functions, orthopedic implant material

Infection of open tibial fractures with contamination remains a challenge for orthopedic surgeons. Local use of antibiotic-impregnated polymethylmethacrylate (PMMA) beads and blocks is a widely used procedure to reduce the risk of infection. However, the development of antibiotic-resistant organisms make the management of infection more difficult. Our in vitro study demonstrated that quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan [HACC])-loaded PMMA bone cement exhibits strong antibacterial activity toward antibiotic-resistant bacteria. Therefore, the present study aimed to investigate the in vivo antibacterial activity of quaternized chitosan-loaded PMMA. Twenty-four adult female New Zealand White rabbits were used in this study. The right proximal tibial metaphyseal cavity was prepared, 10 7 CFU of methicillin-resistant Staphylococcus epidermidis was inoculated, and PMMA-only, gentamicin-loaded PMMA (PMMA-G), chitosan-loaded PMMA (PMMA-C), or HACC-loaded PMMA (PMMA-H) bone cement cylinders were inserted. During the follow-up period, the infections were evaluated using X rays on days 21 and 42 and histopathological and microbiological analyses on day 42 after surgery. Radiographic indications of bone infections, including bone lysis, periosteal reactions, cyst formation, and sequestral bone formation, were evident in the PMMA, PMMA-G, and PMMA-C groups but not in the PMMA-H group. The radiographic scores and gross bone pathological and histopathological scores were significantly lower in the PMMA-H group than in the PMMA, PMMA-G, and PMMA-C groups ( P < 0.05). Explant cultures also indicated significantly less bacterial growth in the PMMA-H group than in the PMMA, PMMA-G, and PMMA-C groups ( P < 0.01). We concluded that PMMA-H bone cement can inhibit the development of bone infections in this animal model inoculated with antibiotic-resistant bacteria, thereby demonstrating its potential application for treatment of local infections in open fractures.

In this study, a nanocalcium silicate (n-CS)/polyetheretherketone (PEEK) bioactive composite was prepared using a process of compounding and injection-molding. The mechanical properties, hydrophilicity, and in vitro bioactivity of the composite, as well as the cellular responses of MC3T3-E1 cells (attachment, proliferation, spreading, and differentiation) to the composite, were investigated. The results showed that the mechanical properties and hydrophilicity of the composites were significantly improved by the addition of n-CS to PEEK. In addition, an apatite-layer formed on the composite surface after immersion in simulated body fluid (SBF) for 7 days. In cell culture tests, the results revealed that the n-CS/PEEK composite significantly promoted cell attachment, proliferation, and spreading compared with PEEK or ultrahigh molecular weight polyethylene (UHMWPE). Moreover, cells grown on the composite exhibited higher alkaline phosphatase (ALP) activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes than cells grown on PEEK or UHMWPE. These results indicated that the incorporation of n-CS to PEEK could greatly improve the bioactivity and biocompatibility of the composite. Thus, the n-CS/PEEK composite may be a promising bone repair material for use in orthopedic clinics.

Chondroblastoma of the patella is rare. Aneurysmal bone cysts, which develop from a prior lesion such as a chondroblastoma, are seldom seen in the patella. The authors report a case of a 36-year-old man who presented with 2 years of right knee pain without calor, erythema, pain on palpation, or abnormal range of motion. Radiological studies suggested aneurysmal bone cyst. The lesion was excised with curettage and the residual cavity filled with autogenous bone graft. Histopathology revealed chondroblastoma associated with a secondary aneurysmal bone cyst. In the follow-up period, the patient demonstrated normal joint activities with no pain. Normal configuration of the patella and bone union were shown on plain radiographs. The authors present a review of the literature of all cases of patellar chondroblastoma with aneurysmal bone cyst. This case is the 14th report of aneurysmal bone cyst arising in a chondroblastoma of the patella. According to the literature, computed tomography and magnetic resonance imaging are useful in the study of these lesions. The pathologic diagnosis is based on the presence of chondroblastoma and aneurysmal bone cyst. Treatment of this lesion includes patellectomy, curettage alone, and curettage with bone grafting. Despite the risk of recurrence of this lesion in the patella, the authors first recommend curettage followed by filling the cavity with bone graft. To protect the anterior tension of the patella intraoperatively, the bone window should be made at the medial edge of the patella to perform the curettage and bone grafting.

Wen-tao Lin,1 Hong-lue Tan,1 Zhao-ling Duan,2 Bing Yue,1 Rui Ma,1 Guo He,2 Ting-ting Tang1 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 2State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China Abstract: Titania nanotubes loaded with antibiotics can deliver a high concentration of antibiotics locally at a specific site, thereby providing a promising strategy to prevent implant-associated infections. In this study we have fabricated titania nanotubes with various diameters (80, 120, 160, and 200 nm) and 200 nm length via electrochemical anodization. These nanotubes were loaded with 2 mg of gentamicin using a lyophilization method and vacuum drying. A standard strain, Staphylococcus epidermidis (American Type Culture Collection 35984), and two clinical isolates, S. aureus 376 and S. epidermidis 389, were selected to investigate the anti-infective ability of the gentamicin-loaded nanotubes (NT-G). Flat titanium (FlatTi) and nanotubes with no drug loading (NT) were also investigated and compared. We found that NT-G could significantly inhibit bacterial adhesion and biofilm formation compared to FlatTi or NT, and the NT-G with 160 nm and 200 nm diameters had stronger antibacterial activity because of the extended drug release time of NT-G with larger diameters. The NT also exhibited greater antibacterial ability than the FlatTi, while nanotubes with 80 nm or 120 nm diameters had better effects. Furthermore, human marrow derived mesenchymal stem cells were used to evaluate the effect of nanotubular topographies on the osteogenic differentiation of mesenchymal stem cells. Our results showed that NT-G and NT, especially those with 80 nm diameters, significantly promoted cell attachment, proliferation, spreading, and osteogenic differentiation when compared to FlatTi, and there was no significant difference between NT-G and NT with the same diameter. Therefore, nanotube modification and gentamicin loading can significantly improve the antibacterial ability and osteogenic activity of orthopedic implants. Keywords: titania nanotubes, gentamicin, bacteria adhesion, biofilm formation, osteogenic activity

Layer-by-layer (LBL) self-assembly technique has been proved to be a highly effective method to immobilize the main components of the extracellular matrix such as collagen and hyaluronic acid on titanium-based implants and form a polyelectrolyte multilayer (PEM) film by electrostatic interaction. However, the formed PEM film is unstable in the physiological environment and affects the long-time effectiveness of PEM film. In this study, a modified LBL technology has been developed to fabricate a stable collagen/hyaluronic acid (Col/HA) PEM film on titanium coating (TC) by introducing covalent immobilization. Scanning electron microscopy, diffuse reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were used to characterize the PEM film. Results of Sirius red staining demonstrated that the chemical stability of PEM film was greatly improved by covalent cross-linking. Cell culture assays further illustrated that the functions of human mesenchymal stem cells, such as attachment, spreading, proliferation and differentiation, were obviously enhanced by the covalently immobilized Col/HA PEM on TCs compared with the absorbed Col/HA PEM. The improved stability and biological properties of the Col/HA PEM covalently immobilized TC may be beneficial to the early osseointegration of the implants.

The infection of orthopedic implantation devices with Staphylococcus is a serious concern within the biomaterial community. Treatments are not always successful because of antibiotic-resistant bacteria and serious biofilm infections. Human β-defensin 3 (hBD-3) is considered to be the most promising class of defensin antimicrobial peptides and its effect on antibiotic-resistant Staphylococcus biofilms, combined with ultrasound (US)-targeted microbubble (MB) destruction (UTMD), has not been reported. In the study, we found that biofilm densities, the percentage of live cells and the viable counts of two tested Staphylococcus recovered from the biofilm were significantly decreased in the maximum concentration hBD-3 combined with UTMD compared with those of any other groups. Furthermore, results suggested that UTMD could also enhance 1MIC hBD-3 activity inhibiting the biofilm-associated genes expression of icaAD and the methicillin-resistance genes expression of MecA by simultaneously promoting the icaR expression. UTMD may have great potential for improving antibiotic activity against biofilm infections.

Chitosan (CS) is a linear polysaccharide with good biodegradability, biocompatibility and antimicrobial activity, which makes it potentially useful for biomedical applications, including an antimicrobial agent either alone or blended with other polymers. However, the poor solubility of CS in most solvents at neutral or high pH substantially limits its use. Quaternary ammonium CS, which was prepared by introducing a quaternary ammonium group on a dissociative hydroxyl group or amino group of the CS, exhibited improved water solubility and stronger antibacterial activity relative to CS over an entire range of pH values; thus, this quaternary modification increases the potential biomedical applications of CS in the field of anti-infection. This review discusses the current findings on the antimicrobial properties of quaternized CS synthesized using different methods and the mechanisms of its antimicrobial actions. The potential antimicrobial applications in the orthopedic field and perspectives regarding future studies in this field are also considered.

In this study, type I collagen was fixed onto plasma-sprayed porous titanium coatings by either adsorptive immobilization or covalent immobilization. Surface characterization by scanning electron microscopy (SEM), diffuse reflectance Fourier transform infrared spectroscopy (DR-FTIR) and X-ray photoelectron spectroscopy (XPS) confirmed the biochemical modification of the titanium coatings. The immobilizing effects of type I collagen, including variations in the amount and stability of collagen, were investigated using Sirius red staining. A greater amount of collagen was found on the covalently immobilized titanium coating, and higher stability was achieved relative to the absorptive immobilization surface. Human mesenchymal stem cells (hMSCs) were used to evaluate the cytocompatibility of the modified titanium coatings. Type I collagen immobilized on titanium coating led to enhance cell-material interactions and improved hMSC functions, such as attachment, proliferation, and differentiation. Interestingly, covalently immobilized collagen on titanium coating showed a greater capability to regulate the osteogenic activity of hMSCs than did absorbed collagen, which was explained in terms of the increased amount and higher stability of the covalently linked collagen. The type I collagen covalently immobilized titanium coatings with improved biological function may exhibit better osteointegration in clinical application.

Despite improvements in intraoperative antimicrobial procedures, in surgical techniques and in implant design for joint replacement, periprosthetic infection after arthroplasty is still one of the most challenging problems encountered by orthopedic surgeons. Systemic antibiotics are not sufficiently effective to eradicate such deep infections because of the impaired blood circulation and low antibiotic concentration at the implantation site. As a local drug delivery system, antibiotic-impregnated PMMA (polymethylmethacrylate) bone cements have been widely used for prophylaxis or treatment of deep infections after total joint replacement. However, the effectiveness of antibiotic-loaded PMMA in preventing infections after arthroplasty is still controversial. Furthermore, the outcomes of established deep infections treated with this technique are not consistent. The local use of antibiotics has led to the emergence of antibiotic-resistant bacterial strains and has adverse effects on the function of osteogenic cells. Recently, many efforts have been made to identify new antibacterial agents that can be loaded into PMMA. These antimicrobial agents should exhibit good antibacterial activity against antibiotic-resistant strains and should simultaneously enhance osteointegration between the PMMA and the bone tissue. PMMA loaded with chitosan or chitosan derivatives has been demonstrated to induce improved osteogenic activity and to exhibit antibacterial activity in a preclinical study.

Gentamicin-loaded polymethylmethacrylate (PMMA), widely used for primary cemented arthroplasty and revision surgery for preventing or treating infections, may lead to the evolution of antibiotic-resistant bacteria and dysfunction of osteogenic cells, which further influence the osteointegration of bone cement. In a previous study, we reported that a new quaternized chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) that was loaded into PMMA significantly inhibited the formation of biofilms caused by methicillin-resistant Staphylococcus strains. In the present study, we further investigated the surface morphology, hydrophilicity, apatite formation ability and osteogenic activity of HACC-loaded PMMA. Chitosan-loaded PMMA, gentamicin-loaded PMMA and PMMA without antibiotic were also investigated and compared. The results showed that, compared to other PMMA-based cements, HACC-loaded PMMA had improved properties such as a lower polymerization temperature, prolonged setting time, porous structures after immersion in phosphate-buffered saline, higher hydrophilicity, more apatite formation on the surface after immersion in simulated body fluid, and better attachment and spreading of the human-marrow-derived mesenchymal stem cells. We also found better stem cell proliferation, osteogenic differentiation, and osteogenesis-associated genes expression on the surface of the HACC-loaded PMMA compared to the gentamicin-loaded PMMA. Therefore, this new anti-infective bone cement had improved physical properties and osteogenic activity, which may lead to better osteointegration of the bone cement in cemented arthroplasty.

To investigate the clinical efficacy, complications and necessity of removing internal fixation in treatment of fresh Tossy type III acromioclavicular joint dislocations and Neer type II distal clavicle fractures with clavicular hook plate.From June 2005 to June 2008, 24 patients with fresh Tossy type III acromioclavicular joint dislocations and 20 patients with fresh Neer type II distal clavicle fractures were treated. There were 32 males and 12 females with an age range of 18-66 years (38.5 years on average), involving 18 left shoulders and 26 right shoulders. The injury was caused by traffic accident in 31 cases and by falling in 13 cases. The mean time from injury to operation was 4 days (range, 2-8 days). All patients were treated by reduction with clavicular hook plate fixation. The coracoclavicular ligaments were not sutured. The shoulder functions were evaluated according to University of California-Los Angeles (UCLA) score system and analysed before and after removing internal fixation.Wound infection occurred in 2 cases 1 week after operation and healed after symptomatic management, the other incisions healed by first intention. One case accepted hook plate fixation again because of loosening hooking-up 1 week after operation. One case accepted hook plate removal and Kirschner wire fixation because of severe shoulder's pain on the postoperative third day. Thirty-eight patients were followed up for 8-32 months (18 months on average), there was no plate breakage. Clavicle fractures got bony union after 3-6 months (4.2 months on average). At last follow-up (before plate removal), according to UCLA shoulder function score system, the results were excellent in 11 cases, good in 22 cases, and fair in 5 cases; the excellent and good rate was 86.8%. Because of shoulder's pain, plates were removed in 20 patients 3-16 months (10 months on average) after operation. The cases were followed up 3-8 months (5 months on average) after removing plate. No dislocation and fracture occurred again. There was statistically significant difference (P0.01) in the functional scores of shoulder between before (30.55 +/- 4.00) and after removing internal fixation (33.85 +/- 1.95).Clavicular hook plate fixation is an effective treatment for fresh Tossy type III acromioclavicular joint dislocations and Neer type II distal clavicle fractures. Normative operating, correct plate moulding, functional rehabilitation after operation are key factors in preventing complications and reaching good clinical efficacy. For the patients with postoperative symptoms, the plate should be removed to improve the shoulder's function.

Shengbing Yang,1,* Shuogui Xu,2,* Panyu Zhou,2,* Jing Wang,3 Honglue Tan,4 Yang Liu,5 TingTing Tang,4 ChangSheng Liu1,3,5 1The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Changhai Hospital, Department of Orthopedics, the Second Military Medical University, Shanghai, People’s Republic of China; 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine China, Shanghai, People’s Republic of China; 5Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China *These authors contributed equally to this workAbstract: Osteoinductive and biodegradable composite biomaterials for bone regeneration were prepared by combining poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) with siliceous mesostructured cellular foams (SMC), using the porogen leaching method. Surface hydrophilicity, morphology, and recombinant human bone morphogenetic protein 2 adsorption/release behavior of the SMC/PHBHHx scaffolds were analyzed. Results of scanning electron microscopy indicated that the SMC was uniformly dispersed in the PHBHHx scaffolds, and SMC modification scaffolds have an interconnected porous architecture with pore sizes ranging from 200 to 400 µm. The measurements of the water contact angles suggested that the incorporation of SMC into PHBHHx improves the hydrophilicity of the composite. In vitro studies with simulated body fluid show great improvements to bioactivity and biodegradability versus pure PHBHHx scaffolds. Cell adhesion and cell proliferation on the scaffolds was also evaluated, and the new tools provide a better environment for human mesenchymal stem cell attachment, spreading, proliferation, and osteogenic differentiation on PHBHHx scaffolds. Moreover, micro-computed tomography and histological evaluation confirmed that the SMC/PHBHHx scaffolds improved the efficiency of new bone regeneration with excellent biocompatibility and biodegradability and faster and more effective osteogenesis in vivo. Keywords: stem cells, mesoporous, scaffolds, bone regeneration, rhBMP-2

Owing to their tissue-like elasticity, poly(ethylene glycol) (PEG)-based hydrogels are highly desirable as three-dimensional scaffolds for tissue regeneration. Also, their high permeability can mimic the native extracellular matrix. However, their applications are limited by their poor mechanical properties and bioinert nature, which restrict cell adhesion and spreading. This study aims to address both limitations by developing a novel hierarchical nanocomposite hydrogel (NC gel) composed of polyethylene glycol diacrylate (PEGDA) and hydroxyl mesoporous silica nanoparticles (MSNs-OH) via in situ free-radical polymerization. Structural and physicochemical characterization shows that MSNs-OH act as both reinforcing agents and adhesion sites in the hydrogel system, which significantly enhances mechanical properties and cellular affinity. Compared with the unmodified PEG hydrogels, which are fractured easily, MSNs-OH provide the PEG-based NC gels with flexibility due to interactions with PEGDA. Furthermore, the increased protein adsorption capability, the integration of hierarchical macro–mesoporous structure, as well as the introduction of silica, provide a favorable environment for the adhesion and spreading of rat marrow stem cells (RMSCs). These NC hydrogels show promise as scaffolds for tissue engineering.

Summary Our previous studies have demonstrated that the quaternised chitosan-loaded polymethylmethacrylate (PMMA) is a promising new antibacterial bone cement. The aim of this study was to evaluate biomechanical properties of quaternised chitosan-loaded PMMA in vitro and interface histology between cement and bone in vivo. In this study, hydroxypropyltrimethyl ammonium chloride chitosan (HACC) with 26% degree of substitution (referred to as 26% HACC) was loaded into PMMA bone cement at a 20% mass ratio, and the specimens of 26% HACC-loaded PMMA bone cement (PMMA–H) were prepared for compressive and bending mechanical test according to ISO 5883-2002 standard prior to and after the 4-week immersion in PBS. The chitosan-loaded PMMA bone cement (PMMA–C) at the same mass ratio, pure PMMA, and gentamicin-loaded PMMA (PMMA–G) were also prepared and tested as controls. Then each of four kinds of bone cements was implanted into the rabbit femoral condyle and the osseointegration of the cement–bone interface was evaluated after its implantation over 6 weeks. The results show that biomechanical properties of both PMMA–C and PMMA–H were reduced significantly compared with the PMMA or PMMA–C, and the elastic modulus of PMMA–H was close to that of human cancellous bone. Histological observation in animal studies indicates that there was better osseointegration at the cement–bone interface in the PMMA–H group than that in the PMMA, PMMA–G, or PMMA–C groups. More new bone formation was found around PMMA–H bone cement as compared with that in the other three groups. Our findings indicated that the biomechanical properties of PMMA–H were reduced but close to that of neighbouring bone. The PMMA–H had good biocompatibility and osseointegration potential, implying its suitability for vertebral augmentation of osteoporotic vertebral compression fractures and fixation of prosthesis in cemented joint replacement.