Microencapsulation of rifampicin: A technique to preserve the mechanical properties of bone cement

Two‐stage exchange with antibiotic‐loaded bone cement spacers remains the gold standard for chronic periprosthetic joint infection (PJI). Rifampicin is highly efficient on stationary‐phase staphylococci in biofilm; however, its addition to PMMA to manufacture spacers prevents polymerization and reduces mechanical properties. Isolation of rifampicin during polymerization by microencapsulation could allow manufacturing rifampicin‐loaded bone cement maintaining elution and mechanical properties. Microcapsules of rifampicin with alginate, polyhydroxybutyratehydroxyvalerate (PHBV), ethylcellulose and stearic acid (SA) were synthesized. Alginate and PHBV microcapsules were added to bone cement and elution, compression, bending, hardness, setting time and microbiological tests were performed. Repeated measures ANOVA and Bonferroni post‐hoc test were performed, considering a p < 0.05 as statistical significance. Bone cement specimens containing alginate microcapsules eluted more rifampicin than PHBV microcapsules or non‐encapsulated rifampicin over time (p < 0.012). Microencapsulation of rifampicin allowed PMMA to preserve mechanical properties in compression and bending tests. Cement with alginate microcapsules showed similar behavior in hardness tests to control cement over the study period (73 ± 1.68H_D). PMMA with alginate microcapsules exhibited the largest zones of inhibition in microbiological tests. Statistically significant differences in mean diameters of zones of inhibition between PMMA loaded with alginate‐rifampicin (p = 0.0001) and alginate‐PHBV microcapsules (p = 0.0001) were detected. Rifampicin microencapsulation with alginate is the best choice to introduce rifampicin in PMMA preserving mechanical properties, setting time, elution, and antimicrobial properties. The main applicability of this study is the opportunity for obtaining rifampicin‐loaded PMMA by microencapsulation of rifampicin in alginate microparticles, achieving high doses of rifampicin in infected tissues, increasing the successful of PJI treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:459–466, 2018.

     

No efficacy of silver bone cement in the prevention of methicillin‐sensitive Staphylococcal infections in a rabbit contaminated implant bed model

Data from literature showed that a new type of metallic silver PMMA cement had good results in infection prophylaxis. This study investigated the in vivo efficacy of silver cement in the prevention of methicillin‐sensitive Staphylococcal infections, compared to plain and tobramycin‐containing cement. In 48 rabbits, 0.6% silver, 1% silver, plain, or tobramycin PMMA cement was injected into the femoral medullary canal after contamination with 10⁵, 10⁶, or 10⁷ colony forming units (CFU) Staphylococcus aureus. After 14 days, bone was collected for bacteriology and histopathology. All plain and silver cement rabbits were infected, whereas only two tobra rabbits were infected (p < 0.001). The number of bacteria cultured (¹⁰logCFU) from bone adjacent to the cement, was 6.4 ± 0.3 and 6.1 ± 0.3 for the 0.6% and 1% silver rabbits. For the rabbits with plain and tobra cement, this was 6.2 ± 0.2 (p > 0.95) and 0.0 ± 0.0 (p < 0.001), respectively. Two tobra rabbits had a positive culture of a distal bone sample. Histological sections of plain, 0.6%, and 1% silver rabbits all showed signs of infection; these signs were absent in the tobra rabbits. Silver and plain cement were not effective in preventing infection, whereas tobra cement was effective. As silver cement predominantly exhibits an antimicrobial effect at the direct cement surface, this cement seems less useful in situations where there are bacteria present in surrounding tissues, like revision surgery. Whether silver cement has relevance in the prevention of bacterial colonization of cement remains to be determined. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1002–1007, 2009     

Use of a gentamicin‐impregnated collagen sheet (Collatamp®) following implantation of a sacral nerve stimulator for faecal incontinence

Aim Gentamicin‐impregnated collagen (Collatamp^®) is well described for the prevention of infection in surgery. This technical note describes its intraoperative use as a prophylactic measure to prevent infection following implantation of a sacral nerve stimulator for faecal incontinence. Method Following implantation of the Interstim II Neurostimulator (Medtronic Neuromodulation, 710 Medtronic Parkway, Minneapolis, USA) in a subcutaneous pocket overlying the gluteal muscle, a single sheet of 10 cm × 10 cm gentamicin‐impregnated collagen is placed within the wound covering the implant. The subcutaneous tissue and skin are then closed in separate layers. Results To date eight patients [median age 46.5 (30–59) years] have received prophylactic cover with gentamicin‐impregnated collagen following permanent sacral nerve stimulator implantation. At a median interval of 89.5 (51–128) days, none of these patients developed a wound infection at the site of the neurostimulator implant. Conclusion Gentamicin‐impregnated collagen (Collatamp^®) used in the implantation of a sacral nerve stimulator may be a useful addition to the technique.     

基于Mimics软件计算椎体强化术后椎体内骨水泥体积及骨水泥/椎体体积比的新方法

目的:建立基于Mimics软件计算椎体强化术后椎体内骨水泥量与骨水泥/椎体体积比的新方法,并验证其准确性与可靠性.方法:2012年1月～3月共有12例骨质疏松性椎体压缩骨折患者在我院接受椎体强化术(14个椎体),均使用标准化定量推注管道注入骨水泥,由2名脊柱外科医师准确记录骨水泥量,将他们记录的平均值定义为椎体内实际骨水泥量.术后对患者手术节段进行CT薄层扫描,再将CT数据输入Mimics软件,利用Mimics软件计算测量注入椎体的骨水泥量及椎体体积,并计算出椎体内骨水泥/椎体的体积比,将2名检测者计算出的骨水泥量平均值定义为椎体内骨水泥估计量,将计算出的椎体内骨水泥估计量与椎体内实际骨水泥量进行对比分析,判断这一新方法的准确性.并对2名不同检测者按照同样操作流程测量出的骨水泥体积及椎体体积进行比较,以判断这一新方法的可靠性.结果:12例患者(14个椎体)手术均顺利完成,术中未见明显骨水泥渗漏,2名医师记录的椎体内实际骨水泥量为4.99±0.60ml,检测者A测量出的骨水泥体积和椎体体积分别为5.01±0.61ml、26.66±2.93ml,检测者B测量出的骨水泥体积和椎体体积分别为5.02±0.59ml、26.64±2.92ml,检测者A及B测量出骨水泥体积的平均值(椎体内骨水泥估计量)为5.02±0.60ml,椎体内骨水泥/椎体体积比为0.19±0.03(0.13～0.23).椎体内骨水泥估计量与椎体内实际骨水泥量相比无显著性差异(P＞0.05),骨水泥估计量及椎体体积计算量在2名不同检测者之间也无显著性差异(P＞0.05).结论:Mimics软件可精确计算椎体内骨水泥量,并测量出骨水泥/椎体体积比,这一方法具有较好的准确性及可靠性,有利于进一步开展椎体强化术骨水泥量的相关研究.     

Efficacy of a porous‐structured titanium subdermal barrier for preventing infection in percutaneous osseointegrated prostheses

Infections of percutaneous osseointegrated prostheses (POP) cause prolonged morbidity and device failure because once established, they are refractory to antibiotic therapy. To date, only limited translational animal studies have investigated the efficacy of POP designs in preventing infections. We developed an animal model to evaluate the efficacy of a porous‐coated titanium (Ti) subdermal barrier to achieve skin–implant integration and to prevent periprosthetic infection. In a single‐stage “amputation and implantation” surgery, 14 sheep were fitted with percutaneous devices with an attached porous‐coated Ti subdermal barrier. Nine sheep were implanted with a smooth Ti subdermal barrier construct and served as controls, with one control sheep removed from the study due to a fractured bone. Clinical, microbiological, and histopathological data showed that the porous Ti barrier prevented superficial and deep tissue infections in all animals (14/14, 100%) at the 9‐month endpoint. In contrast, animals with the smooth Ti implant construct had a 25% (2/8) infection rate. Survival analysis indicated a significant difference between the groups (log‐rank test, p = 0.018). Data also indicated that although skin marsupialization was evident in both implant types, animals in the control group had a four times greater marsupialization rate. We concluded that osseointegrated implants incorporating porous‐coated Ti subdermal barriers may have the ability to prevent infection by maintaining a healthy, biologically attached epithelial barrier at the skin–implant interface in load‐bearing animals up to a 9‐month terminus. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1304–1311, 2012     

Repair of rat calvarial defects using Si‐doped hydroxyapatite scaffolds loaded with a bone morphogenetic protein‐2‐related peptide

Tissue engineering promises therapies ideal for treating conventional large bone injuries and defects. In the present study, we developed a novel Si‐HA scaffold loaded with a synthetic BMP‐2‐related peptide, P28, and tested its ability to repair a critical‐sized calvarial defect. We created a calvarial defect (5 mm in diameter) in the parietal bone of 32 rats and implanted one of the following biomaterials: No implant (control), Si‐HA, P28/Si‐HA, or rhBMP‐2/Si‐HA. As assessed by micro CT imaging and histological evaluations, the P28/Si‐HA scaffold promoted bone recovery to a similar degree as the rhBMP‐2/Si‐HA scaffold. In addition, both P28/Si‐HA and rhBMP‐2/Si‐HA promoted recovery better than Si‐HA alone. The novel P28/Si‐HA scaffold might represent a promising biomaterial for future bone tissue engineering applications. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1874–1882, 2016.     

Controlled‐release of bone morphogenetic protein‐2 from a microsphere coating applied to acid‐etched Ti6AL4V implants increases biological bone growth in vivo

A central clinical challenge regarding the surgical treatment of bone and joint conditions is the eventual loosening of an orthopedic implant as a result of insufficient bone ingrowth at the bone–implant interface. We investigated the in vivo effectiveness of a coating containing recombinant human bone morphogenetic protein‐2 (rhBMP‐2)‐loaded microspheres applied to acid‐etched Ti6Al4V cylinders for implantation. Three groups of rabbits (24 per group) were used for implantation: (1) acid‐etched Ti6Al4V implants coated with a mixture of rhBMP‐2‐loaded microspheres (125 ng rhBMP‐2/mg microspheres) and α‐butyl cyanoacrylate; (2) acid‐etched, uncoated implants; and (3) bare, smooth uncoated implants. After implantation, 12 rabbits from each group were used for bone ingrowth determination at 4, 5, 6, 7, 8, and 12 weeks (2 rabbits per time point), while the remainder were used for histological analysis and push‐out testing at 12 weeks. Scanning electron microscopy showed significant improvement in bone growth of the rhBMP‐2 microspheres/α‐butyl cyanoacrylate group compared with the other groups (p < 0.01). Histological analysis and push‐out testing also demonstrated enhanced bone growth of the rhBMP‐2 group over that in the other two groups (p < 0.01). The rhBMP‐2 group showed the most significant bone growth, suggesting that coating acid‐etched implants with a mixture of rhBMP‐2‐loaded microspheres and α‐butyl cyanoacrylate may be an effective method to improve the osseointegration of orthopedic implants. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:744–751, 2014.     

Time course of peri‐implant bone regeneration around loaded and unloaded implants in a rat model

The time‐course of cancellous bone regeneration surrounding mechanically loaded implants affects implant fixation, and is relevant to determining optimal rehabilitation protocols following orthopaedic surgeries. We investigated the influence of controlled mechanical loading of titanium‐coated polyether‐ether ketone (PEEK) implants on osseointegration using time‐lapsed, non‐invasive, in vivo micro‐computed tomography (micro‐CT) scans. Implants were inserted into proximal tibial metaphyses of both limbs of eight female Sprague–Dawley rats. External cyclic loading (60 or 100 μm displacement, 1 Hz, 60 s) was applied every other day for 14 days to one implant in each rat, while implants in contralateral limbs served as the unloaded controls. Hind limbs were imaged with high‐resolution micro‐CT (12.5 μm voxel size) at 2, 5, 9, and 12 days post‐surgery. Trabecular changes over time were detected by 3D image registration allowing for measurements of bone‐formation rate (BFR) and bone‐resorption rate (BRR). At day 9, mean %BV/TV for loaded and unloaded limbs were 35.5 ± 10.0% and 37.2 ± 10.0%, respectively, and demonstrated significant increases in bone volume compared to day 2. BRR increased significantly after day 9. No significant differences between bone volumes, BFR, and BRR were detected due to implant loading. Although not reaching significance (p = 0.16), an average 119% increase in pull‐out strength was measured in the loaded implants. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:997–1006, 2017.

     

The benefit of bone marrow concentrate in addition to a glass‐reinforced hydroxyapatite for bone regeneration: An in vivo ovine study

This study evaluates the ability of a Glass Reinforced Hydroxyapatite Composite (GRHC), in a new microporous pellet formulation with autologous bone marrow concentrate (BMC), to enhance bone regeneration and new bone formation. Ninety non‐critical sized bone defects were created in the femurs of nine Merino breed sheep and randomly left unfilled (group A), filled with GRHC pellets alone (group B) or filled with GRHC pellets combined with BMC (group C). The sheep were sacrificed at 3 weeks (three sheep), 6 weeks (three sheep) and 12 weeks (three sheep) and histological analysis (Light Microscopy‐LM), scanning electron microscopy (SEM) and histomorphometric analysis (HM) were performed. At 3, 6, and 12 weeks, HM revealed an average percentage of new bone of 48, 72, 83%; 25, 73, 80%, and 16, 38, 78% for Groups C, B and A respectively (significantly different only at 3 weeks p < 0.05). LM and SEM evaluation revealed earlier formation of well‐organized mature lamellar bone in Group C. This study demonstrates that the addition of a bone marrow concentrate to a glass reinforced hydroxyapatite composite in a pellet formulation promotes early bone healing. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1176–1182, 2017.

     

Encouraging patients to self‐care – the preliminary development and validation of the VeLUSET©, a self‐efficacy tool for venous leg ulcer patients,aged 60 years and over

Venous leg ulceration has a high recurrence rate. Patients with healed or frequently recurring venous ulceration are required to perform self‐care behaviours to prevent recurrence or promote healing, but evidence suggests that many find these difficult to perform. Bandura's self‐efficacy theory is a widely used and robust behaviour change model and underpins many interventions designed to promote self‐care in a variety of chronic conditions. By identifying areas where patients may experience difficulty in performing self‐care, interventions can be developed to strengthen their self‐efficacy beliefs in performing these activities successfully. There are currently a variety of self‐efficacy scales available to measure self‐efficacy in a variety of conditions; but not a disease‐specific scale for use with venous ulcer patients. The aim of this study, therefore, was to develop and validate a disease‐specific, patient‐focused self‐efficacy scale for patients with healed venous leg ulceration. This scale will need further validation studies; however, it is ready for use in clinical practice and will enable practitioners to identify those patients who may need additional support in performing self‐care activities to prevent recurrence.     

Synthetic hydrogel scaffold is an effective vehicle for delivery of INFUSE (rhBMP2) to critical‐sized calvaria bone defects in rats

Medtronic's INFUSE Bone Graft provides surgeons with a potent tool for stimulating bone formation. Current delivery vehicles that rely on Absorbable Collagen Sponges (ACS) require excessive quantities of the active ingredient in INFUSE, recombinant human Bone Morphogenic Protein‐2 (rhBMP2), to achieve physiologically relevant concentrations of the growth factor, driving up the cost of the product and increasing the likelihood of undesirable side effects in neighboring tissues. We demonstrate that a simple light‐mediated, thiol‐ene chemistry can be used to create an effective polymer delivery vehicle for rhBMP2, eliminating the use of xenographic materials and reducing the dose of rhBMP2 required to achieve therapeutic effects. Comprised entirely of synthetic components, this system entraps rhBMP2 within a biocompatible hydrogel scaffold that is degraded by naturally occurring remodeling enzymes, clearing the way for new tissue formation. When tested side‐by‐side with ACS in a critical‐sized bone defect model in rats, this polymeric delivery system significantly increased bone formation over ACS controls. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 401–406, 2013     

Role of ultrasound compared to age‐related formulas for uncuffed endotracheal intubation in a pediatric population

Background: It is often difficult to determine the correct size of endotracheal tubes (ETT) needed for intubating pediatric patients. Therefore, we evaluated the role of ultrasound in pediatric patients to compare the correct size of an uncuffed (ETT) with the minimal transverse diameter of the subglottic airway (MTDSA) measured by ultrasound and with tube size predicted by different age‐related formulas. Methods: A total of 50 pediatric patients ≤5 years were enrolled. As a standard, we defined the adequate ETT size with no audible leakage below a ventilation pressure of 15 mbar and with an audible leakage above 25 mbar. The maximum allowed difference between the prediction method result and the ETT that fit was defined as 0.3 mm. Ultrasound was performed before the intubation procedure; the intubating anesthesiologists were blinded to the results of the ultrasound measurement. Agreement between the two age‐based formulas most commonly used at our department and MTDSA with the correct ETT size (standard) was analyzed using a Bland–Altman plot. Correlation and regression analyses were performed and the numbers of correct intubation trials recorded. Results: The frequency of bias ≤0.3 mm between each method and the correct ETT in the first attempt was <50% and the mean number of reintubations 1.6 ± 1.3. In contrast to age‐related formulas, however, the ultrasonographically determined MTDSA was not significantly different from the correct ETT. MTDSA was highly associated with the outer diameter of the ETT (r = 0.869, R² = 0.754). Conclusions: Measuring MTDSA by ultrasound facilitates selection of the appropriate ETT in pediatric patients and may reduce the number of reintubations.     

Comparing the hydrosurgery system to conventional debridement techniques for the treatment of delayed healing wounds: a prospective,randomised clinical trial to investigate clinical efficacy and cost‐effectiveness

In these uncertain times of high health care costs, clinicians are looking for cost‐effective devices to employ in their everyday practices. In an effort to promote cost‐effective and proper wound repair, the hydrosurgical device allows accurate debridement of only unwanted tissue while precisely conserving viable structures for eventual repair. This prospective, randomised study compared procedures using the hydrosurgery system (VERSAJET?) with conventional debridement in order to assess clinical efficacy and cost‐effectiveness when treating subjects with chronic wounds. A total of 40 subjects were recruited. There was no difference in time to achieve stable wound closure between the treatment groups (P = 0·77). There were no significant differences between the two groups in terms of cost of the first operative procedure (P = 0·28), cost of surgical procedures during the study (P = 0·51), cost of study treatment (P = 0·29) or cost to achieve stable wound closure (P = 0·85). There were no differences in quantitative bacterial counts after debridement with either methods (P = 0·376). However, the time taken for the first excision procedure was significantly faster using the hydrosurgery system (VERSAJET) when compared with conventional debridement (P < 0·001). The total excision time for all procedures was significantly less for the Hydrosurgery group than for the conventional group (P = 0·005). Also, the Hydrosurgery group demonstrated significantly less intraoperative blood loss than conventional group for all procedures (P = 0·003). In this study, although there were no differences in time to stable wound closure or bacterial reduction between the two groups, the hydrosurgery system (VERSAJET) did offer advantages in terms of operative times and intraoperative blood loss and was cost‐neutral, despite the handpiece cost.     

Preliminary investigations on a new gentamicin and vancomycin‐coated PMMA nail for the treatment of bone and intramedullary infections: An experimental study in the rabbit

To evaluate a new gentamicin–vancomycin‐ impregnated (2:1) PMMA coating nail as a drug delivery device to treat bone and intramedullary infections, methicillin‐resistant Staphylococcus aureus (MRSA) was used to induce femoral osteomyelitis in 20 New Zealand male rabbits. Four weeks after inoculum, the animals were submitted to debridement of infected femur canal, divided into four groups of five animals each and treated according to the following protocols: Group 1, insertion of a steel AISI316 intramedullary nail; Group 2, insertion of a gentamicin–vancomycin‐impregnated PMMA nail; Group 3, no therapy; and Group 4 no fixation device and 1‐week systemic antibiotic therapy with teicoplanin i.m. At 7 weeks after inoculum, the femurs were explanted sterilely. The radiological score showed that the lowest and best radiological score was observed in Group 2 that was significantly different from the other groups. The highest bacterial load in the femoral canal was found in Group 1, which was significantly different from Group 2 and Group 4 (p < 0.05). Histology showed that Group 2 produced a marked improvement (p < 0.005) of the bone injuries induced by the osteomyelitis in comparison with the other groups (Smeltzer score). The current findings showed that tested device might effectively lead to MRSA infection healing after surgical debridement and immediate implantation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:785–792, 2008