In Vitro Testing and Clinical Handling of a Novel Implant Positioning Technology for Proximal Humeral Plating.

BACKGROUND AND OBJECTIVES: Fractures of the proximal humerus are common, particularly in elderly populations. Anatomical locking plates target stabilization with a multitude of screws spanning into the humeral head. Sound implant placement and screw length determination are key for a successful clinical outcome but are difficult to obtain from planar X-rays. A novel implant positioning technology for proximal humerus plating (Xin1) outputs screw lengths suggestions and plate position based on hole projections in conventional X-ray images. This study investigated the performance of a prototype Xin1 system in a postmortem (in vitro) experiment as well as in a clinical handling test. MATERIALS AND METHODS: For in vitro testing, twelve shoulders from six anatomical specimens were randomized into two groups to compare the Xin1 technique to the conventional operation in terms of surgical precision, procedure time and X-ray exposure. For the clinical trial, 11 patients undergoing plating of the proximal humerus were included. The aim was to investigate clinical handling of the Xin1 marker clip and to retrospectively evaluate the system performance in a real-life fracture situation. Image pairs before and after insertion of the proximal screws were retrospectively processed to investigate the influence of potential bone fragment shifts on the system output. RESULTS: In the postmortem experiment, the use of the system significantly improved the surgical precision (52% error reduction), procedure time (38% shorter) and radiation exposure (64% less X-rays). Clinical handling demonstrated seamless embedding of the marker clip into existing clinical workflows without adverse events reported. Retrospective X-ray analysis on six eligible patients revealed differences in the calculated screw lengths of ≤2 mm before and after screw insertion for five patients. In one patient, the screw lengths differed up to 8 mm, which might indicate displacement of the head fragment. CONCLUSIONS: Results suggest a strong potential of the Xin1 assistance technology to enhance the surgical procedure and patient outcomes in the rising incidence of osteoporotic humeral fractures. Robust performance in a real-life fracture situation was observed. In-depth validation of the system is, however, needed before placing it into clinical practice.

Continuous Implant Load Monitoring to Assess Bone Healing Status-Evidence from Animal Testing.

Background and Objectives: Fracture healing is currently assessed through qualitative evaluation of radiographic images, which is highly subjective in nature. Radiographs can only provide snapshots in time, which are limited due to logistics and radiation exposure. We recently proposed assessing the bone healing status through continuous monitoring of the implant load, utilizing an implanted sensor system, the Fracture Monitor. The device telemetrically transmits statistically derived implant parameters via the patient's mobile phone to assist physicians in diagnostics and treatment decision-making. This preclinical study aims to systematically investigate the device safety and performance in an animal setting. Materials and Methods: Mid-shaft tibial osteotomies of different sizes (0.6-30 mm) were created in eleven Swiss mountain sheep. The bones were stabilized with either a conventional Titanium or stainless-steel locking plate equipped with a Fracture Monitor. Data were continuously collected over the device's lifetime. Conventional radiographs and clinical CT scans were taken longitudinally over the study period. The radiographs were systematically scored and CTs were evaluated for normalized bone volume in the defect. The animals were euthanized after 9 months. The sensor output was correlated with the radiologic parameters. Tissue samples from the device location were histologically examined. Results: The sensors functioned autonomously for 6.5-8.4 months until energy depletion. No macroscopic or microscopic adverse effects from device implantation were observed. The relative implant loads at 4 and 8 weeks post-operation correlated significantly with the radiographic scores and with the normalized bone volume metric. Conclusions: Continuous implant load monitoring appears as a relevant approach to support and objectify fracture healing assessments and carries a strong potential to enable patient-tailored rehabilitation in the future.

Continuous Rod Load Monitoring to Assess Spinal Fusion Status-Pilot In Vivo Data in Sheep.

Background and Objectives: Spinal fusion is an effective and widely accepted intervention. However, complications such as non-unions and hardware failures are frequently observed. Radiologic imaging and physical examination are still the gold standards in the assessment of spinal fusion, despite multiple limitations including radiation exposure and subjective image interpretation. Furthermore, current diagnostic methods only allow fusion assessment at certain time points and require the patient's presence at the hospital or medical practice. A recently introduced implantable sensor system for continuous and wireless implant load monitoring in trauma applications carries the potential to overcome these drawbacks, but transferability of the principle to the spine has not been demonstrated yet. Materials and Methods: The existing trauma sensor was modified for attachment to a standard pedicle-screw-rod system. Two lumbar segments (L2 to L4) of one Swiss white alpine sheep were asymmetrically instrumented. After facetectomy, three sensors were attached to the rods between each screw pair and activated for measurement. The sheep was euthanized 16 weeks postoperatively. After radiological assessment the spine was explanted and loaded in flexion-extension to determine the range of motion of the spinal segments. Sensor data were compared with mechanical test results and radiologic findings. Results: The sensors measured physiological rod loading autonomously over the observation period and delivered the data daily to bonded smartphones. At euthanasia the relative rod load dropped to 67% of the respective maximum value for the L23 segment and to 30% for the L34 segment. In agreement, the total range of motion of both operated segments was lower compared to an intact reference segment (L23: 0.57°; L34: 0.49°; intact L45: 4.17°). Radiologic assessment revealed fusion mass in the facet joint gaps and bilateral bridging bone around the joints at both operated segments. Conclusions: Observations of this single-case study confirm the basic ability of continuous rod load measurement to resolve the spinal fusion process as indicated by a declining rod load with progressing bone fusion. A strong clinical potential of such technology is eminent, but further data must be collected for final proof of principle.

3D statistical model of the pelvic ring - a CT-based statistical evaluation of anatomical variation.

The pelvic ring is a highly complex construct with a central role for human stability and mobility. The observable interindividual differences in skeletal anatomy are caused by anatomical variation in the innominate bones as well as the sacrum, further to differences in the spatial arrangement of these bones to each other. The aim of this study was to generate a 3D statistical model of the entire pelvic ring in order to analyse the observed interindividual differences and anatomical variation. A series of 50 anonymized pelvic CT scans of uninjured Japanese adults [30 males, 20 females, average age of 74.9 years, standard deviation (SD) 16.9 years] were processed and analysed, resulting in a 3D statistical overall mean model and separate male and female mean models. Principal component analysis (PCA) of the overall statistical model predominantly showed size variation (20.39%) followed by shape variation (14.13%), and a variation of the spatial arrangement of the sacrum to the innominate bones in different anatomical peculiarities (11.39 and 8.85%). In addition, selected internal and external pelvic parameters were manually measured with the objective of further evaluating and quantifying the observed interindividual as well as the known sex-specific differences. A separate statistical model of the grey value distribution based on the given Hounsfield unit (HU) values was calculated for assessing bone mass distribution, thus an indication of bone quality utilizing grey values as a quantitative description of radiodensity was obtained. A consistent pattern of grey value distribution was shown, with the highest grey values observed between the sacro-iliac joint and the acetabulum along the pelvic brim. Low values were present in the sacral ala, in the area of the iliac fossa as well as in the pubic rami next to the symphysis. The present model allows a differentiated analysis of the observed interindividual variation of the pelvic ring and an evaluation of the grey value distribution therein. Besides providing a better understanding of anatomical variation, this model could be also used as a helpful tool for educational purposes, preoperative planning and implant design.

Analysis of sacro-iliac joint screw fixation: does quality of reduction and screw orientation influence joint stability? A biomechanical study.

INTRODUCTION: Treatment of posterior pelvic ring injuries is frequently associated with pain or/and high mortality rates. Percutaneous sacro-iliac (SI) screw fixation has proved to be one of the methods of choice, providing minimal operative time, blood loss and wound-related morbidity. However, fixation failures due to secondary fracture dislocation or screw backing out have been reported. There is a little knowledge regarding the impact of varying screw orientation and quality of reduction on the fixation strength. PURPOSE: The purpose of the present study was biomechanical investigation of joint stability after SI screw fixation and its dependence on quality of reduction and screw orientation. METHODS: Thirty-two artificial hemi-pelvices were assigned to four study groups and simulated SI dislocations were fixed with two SI screws in oblique or transverse screw orientation and anatomical or non-anatomical reduction in group A (oblique/anatomical), B (transverse/anatomical), C (oblique/non-anatomical) and D (transverse/non-anatomical). Mechanical testing was performed under progressively increasing cyclic axial loading until fixation failure. SI joint movements were captured via optical motion tracking. Fixation performance was statistically evaluated at a level of significance p = 0.05. RESULTS: The highest cycles to failure were observed in group A (14038 ± 1057), followed by B (13909 ± 1217), D (6936 ± 1654) and C (6706 ± 1295). Groups A and B revealed significantly longer endurance than C and D (p ≤ 0.01). CONCLUSIONS: Different screw orientations in the presented model do not influence substantially SI joint stability. However, anatomical reduction is not only mandatory to restore a malalignment, but also to increase the SI screw fixation strength and prevent fixation failures.

Propionibacterium acnes and Staphylococcus lugdunensis cause pyogenic osteomyelitis in an intramedullary nail model in rabbits.

Propionibacterium acnes and coagulase-negative staphylococci (CoNS) are opportunistic pathogens implicated in prosthetic joint and fracture fixation device-related infections. The purpose of this study was to determine whether P. acnes and the CoNS species Staphylococcus lugdunensis, isolated from an "aseptically failed" prosthetic hip joint and a united intramedullary nail-fixed tibial fracture, respectively, could cause osteomyelitis in an established implant-related osteomyelitis model in rabbits in the absence of wear debris from the implant material. The histological features of P. acnes infection in the in vivo rabbit model were consistent with localized pyogenic osteomyelitis, and a biofilm was present on all explanted intramedullary (IM) nails. The animals displayed no outward signs of infection, such as swelling, lameness, weight loss, or elevated white blood cell count. In contrast, infection with S. lugdunensis resulted in histological features consistent with both pyogenic osteomyelitis and septic arthritis, and all S. lugdunensis-infected animals displayed weight loss and an elevated white blood cell count despite biofilm detection in only two out of six rabbits. The differences in the histological and bacteriological profiles of the two species in this rabbit model of infection are reflective of their different clinical presentations: low-grade infection in the case of P. acnes and acute infection for S. lugdunensis. These results are especially important in light of the growing recognition of chronic P. acnes biofilm infections in prosthetic joint failure and nonunion of fracture fixations, which may be currently reported as "aseptic" failure.

Decreasing implant load indicates spinal fusion when measured continuously.

Reliable and timely assessment of bone union between vertebrae is considered a key challenge after spinal fusion surgery. Recently, a novel sensor concept demonstrated the ability to objectively assess posterolateral fusion based on continuous implant load monitoring. The aim of this study was to investigate systematically the concept in a mono-segmental fusion model using an updated sensor setup. Three sheep underwent bilateral facetectomy at level L2-L3 and L4-L5. The segments were stabilized using two unconnected pedicle-screw-rod constructs per level. Sensing devices were attached to the rods between each pedicle screw pair and the loads were continuously monitored over 16 weeks. After euthanasia, the spines were biomechanically tested for their range of motion and high-resolution CT scans were performed to confirm the fusion success. After an initial increase in implant load until reaching a maximum (100 %) at approximately week 4, eleven out of twelve sensors measured a constant decrease in implant load to 52 ± 9 % at euthanasia. One sensor measurement was compromised by newly forming bone growing against the sensor clamp. Bridging bone at each facet and minor remnant segmental motion (<0.7°) confirmed the fusion of all motion segments. Data obtained by continuous measurement of implant loading of spinal screw-rod constructs enables objective monitoring of spinal fusion progression. The sensor concept provides valuable real-time information, offering quantifiable data as an alternative to traditional imaging techniques. However, the design of the current sensor concept needs to be matured, tailored to, and validated for the human spine.

Fatigue performance of angle-stable tibial nail interlocking screws.

PURPOSE: Tibial nail interlocking screw failure often occurs during delayed fracture consolidation or at early weight bearing of nailed unstable fractures, in general when high implant stress could not be reduced by other means. Is there a biomechanical improvement in long-term performance of angle stable locking screws compared to conventional locking screws for distal locking of intramedullary tibial nails? METHODS: Surrogate bones of human tibiae were cut in the distal third and distal locking of the 10 mm intramedullary tibial nail was performed with either two angle stable locking screws or two conventional locking screws in the mediolateral plane. Six specimens per group were mechanically tested under quasi-static and cyclic axial loading with constantly increasing force. RESULTS: Angle stable locking screw constructs exhibited significantly higher stiffness values (7,809 N/mm ± 647, mean ± SD) than conventional locking screw constructs (6,614 N/mm ± 859, p = 0.025). Angle stable locking screw constructs provided a longer fatigue life, expressed in a significantly higher number of cycles to failure (187,200 ± 18,100) compared to conventional locking screw constructs (128,700 ± 7,000, p = 0.004). CONCLUSION: Fatigue performance of locking screws can be ameliorated by the use of angle stable locking screws, being especially important if the nail acts as load carrier and an improved stability during fracture healing is needed.

Biomechanical performance of different cable and wire cerclage configurations.

PURPOSE: Cerclage technology is regaining interest due to the increasing number of periprosthetic fractures. Different wiring techniques have been formerly proposed and have hibernated over years. Hereby, they are compared to current cerclage technology. METHODS: Seven groups (n = 6) of different cable cerclage (Ø1.7 mm, crimp closure) configurations (one single cerclage looped once around the shells, one single cerclage looped twice, two cerclages each looped once) and solid wire cerclages (Ø1.5 mm, twist closure) (same configurations as cable cerclages, and two braided wires, twisted around each other looped once) fixed two cortical half shells of human femoral shaft mounted on a testing jig. Sinusoidal cyclic loading with constantly increasing force (0.1 N/cycle) was applied starting at 50 N peak load. Cerclage pretension (P), load leading to onset of plastic deformation (D) and load at total failure (T) were identified. Statistical differences between the groups were detected by univariate ANOVA. RESULTS: Double looped cables (P442N ± 129; D1334N ± 319; T2734N ± 330) performed significantly better (p < 0.05) than single looped cables (P292N ± 56; D646N ± 108; T1622N ± 171) and were comparable to two single cables (P392N ± 154; D1191N ± 334; T2675N ± 361). Double looped wires (P335N ± 49; D752N ± 119; T1359N ± 80) were significantly better (p < 0.05) than single looped wires (P181N ± 16; D343N ± 33; T606N ± 109) and performed similarly to single looped cables. Braided wires (P119N ± 26; D225N ± 55; T919N ± 197) exhibited early loss of pretension and plastic deformation. CONCLUSION: Double looped cerclages provided a better fixation stability compared to a single looped cerclage. Double looped wires were comparable to a single looped cable. The use of braided wires could not be recommended mechanically.

Prognostic and therapeutic potential of microRNAs for fracture healing processes and non-union fractures: A systematic review.

BACKGROUND: Approximately 10% of all bone fractures result in delayed fracture healing or non-union; thus, the identification of biomarkers and prognostic factors is of great clinical interest. MicroRNAs (miRNAs) are known to be involved in the regulation of the bone healing process and may serve as functional markers for fracture healing. AIMS AND METHODS: This systematic review aimed to identify common miRNAs involved in fracture healing or non-union fractures using a qualitative approach. A systematic literature search was performed with the keywords 'miRNA and fracture healing' and 'miRNA and non-union fracture'. Any original article investigating miRNAs in fracture healing or non-union fractures was screened. Eventually, 82 studies were included in the qualitative analysis for 'miRNA and fracture healing', while 19 were selected for the 'miRNA and fracture non-union' category. RESULTS AND CONCLUSIONS: Out of 151 miRNAs, miR-21, miR-140 and miR-214 were the most investigated miRNAs in fracture healing in general. miR-31-5p, miR-221 and miR-451-5p were identified to be regulated specifically in non-union fractures. Large heterogeneity was detected between studies investigating the role of miRNAs in fracture healing or non-union in terms of patient population, sample types and models used. Nonetheless, our approach identified some miRNAs with the potential to serve as biomarkers for non-union fractures, including miR-31-5p, miR-221 and miR-451-5p. We provide a discussion of involved pathways and suggest on alignment of future research in the field.

Underneath the cerclage: an ex vivo study on the cerclage-bone interface mechanics.

INTRODUCTION: Cerclages regain interest due to a rising number of periprosthetic fractures. The contact distribution at the circumferential cerclage-bone interface is still unknown. Local interface pressure depends on the amount of contact area. Cortical damage at the interface would provoke cerclage loosening. Therefore, the contact area, the bone pressure along the interface and the cortical resistance underneath loaded cerclages were determined in an ex vivo model. MATERIALS AND METHODS: Human diaphyseal femoral bone was used with differing cross-sectional geometry. Bone contact points of fixed 1.5 mm wire and 1.7 mm cable cerclages were identified from axial radiographs. Pressure distribution at the cerclage-bone interface was recorded with a pressure-measuring film using a distraction setup with two cortical half shells. Bone shells with installed cerclages were separated with up to 400 N force and were subsequently analyzed histologically to detect cortical damage. RESULTS: Both cerclage types exhibited a point contact fixation with non-loaded spanned zones in-between. Cables cover larger contact areas. Both cerclages exhibited an inhomogeneous interface pressure distribution depending on the bone surface geometry. Histology revealed intact cortical bone without cortical affection after loading of both cerclage types. CONCLUSION: Point contact fixation of the cerclages installs non-loaded, spanned zones where the periosteum is not compressed, rendering a strangulation of the blood supply unlikely. Cortical bone withstands static concentric pressure produced by the cerclage. Cortical groove formation is attributed to instability under functional load and not to weakness of the cortex itself.

Angulated locking plate in periprosthetic proximal femur fractures: biomechanical testing of a new prototype plate.

INTRODUCTION: To improve proximal plate fixation of periprosthetic femur fractures, a prototype locking plate with proximal posterior angulated screw positioning was developed and biomechanically tested. METHODS: Twelve fresh frozen, bone mineral density matched human femora, instrumented with cemented hip endoprosthesis were osteotomized simulating a Vancouver B1 fracture. Specimens were fixed proximally with monocortical (LCP) or angulated bicortical (A-LCP) head-locking screws. Biomechanical testing comprised quasi-static axial bending and torsion and cyclic axial loading until catastrophic failure with motion tracking. RESULTS: Axial bending and torsional stiffness of the A-LCP construct were (1,633 N/mm ± 548 standard deviation (SD); 0.75 Nm/deg ± 0.23 SD) at the beginning and (1,368 N/mm ± 650 SD; 0.67 Nm/deg ± 0.25 SD) after 10,000 cycles compared to the LCP construct (1,402 N/mm ± 272 SD; 0.54 Nm/deg ± 0.19 SD) at the beginning and (1,029 N/mm ± 387 SD; 0.45 Nm/deg ± 0.15) after 10,000 cycles. Relative movements for medial bending and axial translation differed significantly between the constructs after 5,000 cycles (A-LCP 2.09° ± 0.57 SD; LCP 5.02° ± 4.04 SD; p = 0.02; A-LCP 1.25 mm ± 0.33 SD; LCP 2.81 mm ± 2.32 SD; p = 0.02) and after 15,000 cycles (A-LCP 2.96° ± 0.70; LCP 6.52° ± 2.31; p = 0.01; A-LCP 1.68 mm ± 0.32; LCP 3.14 mm ± 0.68; p = 0.01). Cycles to failure (criterion 2 mm axial translation) differed significantly between A-LCP (15,500 ± 2,828 SD) and LCP construct (5,417 ± 7,236 SD), p = 0.03. CONCLUSION: Bicortical angulated screw positioning showed less interfragmentary osteotomy movement and improves osteosynthesis in periprosthetic fractures.

An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection.

Local antibiotic therapy is increasingly being recognised for its role in preventing and treating orthopaedic device-related infection (ODRI). A bioresorbable, injectable gentamicin-loaded hydrogel has been developed to deliver local antibiotics at the time of surgery with potential for both prevention and treatment of ODRI. In a prophylaxis model, the antibiotic hydrogel was compared with systemic perioperative antibiotic prophylaxis alone in twelve sheep (six per group) at the time of intramedullary (IM) nail insertion to the tibia, which was inoculated with methicillin-sensitive Staphylococcus aureus (MSSA). In a treatment model of single-stage revision surgery, adjunctive antibiotic-loaded hydrogel was compared with systemic antibiotics alone in a single stage revision of MSSA infection associated with a tibia intramedullary nail in eleven sheep (five/six per group). The primary endpoint was quantitative microbiological results of soft tissue, bone and sonicate fluid from explanted hardware at the time of euthanasia. At euthanasia, the control sheep that received no local antibiotics in the prophylaxis model were all culture-positive (median 1x108, range 7x106-3x108 colony forming units, CFU) while only two of six sheep receiving local gentamicin had any culture positive biopsies (median 1x101, range 0 - 1x105 CFU). For the treatment model, sheep receiving only systemic antibiotics were all culture-positive (median 8x105, range 2x103- 9x106 CFU) while only two of six sheep treated with gentamicin-loaded hydrogel had any culture positive biopsies (median 3x102, range 0 - 7x104 CFU). Local gentamicin concentrations measured in extracellular fluid in the tibial canal show a burst release of gentamicin from the hydrogel. Serum gentamicin concentrations peaked in both models at one day post application and were below detection limit thereafter. This study has demonstrated the effective use of a locally delivered antibiotic hydrogel for both the prevention and treatment of ODRI that is superior to that of systemic antibiotics alone. Future studies will endeavour to translate from preclinical to clinical research trials.

Generic Implant Positioning Technology Based on Hole Projections in X-Ray Images.

Implant placement plays a key role in trauma and orthopedics. In this paper, a generic technological concept for implant positioning assistance is outlined. The system utilizes conventional radiographic devices for imaging and tracking and embeds into surgical workflows without the need for complex navigation equipment. It is based on feature extraction from cylindrical hole-projections in X-ray images for determining spatial alignment of implant and anatomy. Basic performance of a prototype system was experimentally verified in terms of tracking accuracy and robustness under varying conditions. In a second step, the system was developed into a set of application modules, each serving a pressing clinical need: Plating of the proximal humerus, cephalic nail and dynamic hip-screw placement, general anatomic plating, distal nail interlocking with adjustment of femoral anteversion and corrective osteotomies. Module prototypes were tested according to their degree of maturity from feasibility assessment in wet-labs to clinical handling tests. Orientation tracking of reference objects yielded an accuracy and precision of 0.1±0.71 deg (mean±standard deviation) with a maximum error of 4.68 deg at unfavorable conditions. This base-performance translated, e.g., into a precision of ±1.2 mm (standard deviation) screw-tip to joint distance at proximal humerus plating, or into a precision of lag screw positioning in the femoral head of ±0.6 mm in craniocaudal and ±1.6 mm in anterioposterior direction. The concept revealed strong potential to improve surgical outcomes in a broad range of orthopedic applications due to its generic and simplistic nature. Comprehensive validation activities must follow for clinical introduction.

Antibiofilm efficacy of focused high-energy extracorporeal shockwaves and antibiotics in vitro.

AIMS: Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on Staphylococcus aureus biofilms in vitro in the presence and absence of antibiotic agents. METHODS: S. aureus biofilms were grown on titanium discs (13 mm × 4 mm) in a bioreactor for 48 hours. Shockwaves were applied with either 250, 500, or 1,000 impulses onto the discs surrounded by either phosphate-buffered saline or antibiotic (rifampin alone or in combination with nafcillin). The number of viable bacteria was determined by quantitative culture after sonication. Representative samples were taken for scanning electron microscopy. RESULTS: The application of fhESWT led to a ten-fold reduction in bacterial counts on the metal discs for all impulse numbers compared to the control (p < 0.001). Increasing the number of impulses did not further reduce bacterial counts in the absence of antibiotics (all p > 0.289). Antibiotics alone reduced the number of bacteria on the discs; however, the combined application of the fhESWT and antibiotic administration further reduced the bacterial count compared to the antibiotic treatment only (p = 0.032). CONCLUSION: The use of fhESWT significantly reduced the colony-forming unit (CFU) count of a S. aureus biofilm in our model independently, and in combination with antibiotics. Therefore, the supplementary application of fhESWT could be a helpful tool in the treatment of IFIs in certain cases, including infected nonunions. Cite this article: Bone Joint Res 2021;10(1):77-84.

Anatomical evaluation of the transpubic screw corridor based on a 3D statistical model of the pelvic ring.

Retrograde transpubic screw fixation is a common procedure for the treatment of anterior pelvic ring fractures. With its sparing surgical approach and significant pain relief after screw fixations allowing early mobilisation, it has gained importance especially in the treatment of insufficiency fractures in elderly patients. However, positioning of transpubic screw osteosynthesis is not always possible due to narrowness and curvature of the screw corridor. The aim of the present study was to evaluate availability and length of the screw corridor using a 3D statistical model of the pelvic ring consisting out of 150 uninjured pelves. Virtual bore probes with a diameter of 7.5 mm were analysed as to accessibility, length and grey value distribution in Hounsfield Unit (HU). A transpubic corridor with a diameter of ≥ 7.5 mm was available in 185 of 300 investigated superior pubic rami with mean screw length of 131.7 mm. Accessibility of the screw corridor was higher in males than in females. However, screw length showed no systematic differences between the sexes or ethnicities. Analysis of the grey value distribution demonstrated the strongest bone to be located at the lateral ilium and the supraacetabular region.

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections.

As viruses with high specificity for their bacterial hosts, bacteriophages (phages) are an attractive means to eradicate bacteria, and their potential has been recognized by a broad range of industries. Against a background of increasing rates of antibiotic resistance in pathogenic bacteria, bacteriophages have received much attention as a possible "last-resort" strategy to treat infections. The use of bacteriophages in human patients is limited by their sensitivity to acidic pH, enzymatic attack and short serum half-life. Loading phage within a biomaterial can shield the incorporated phage against many of these harmful environmental factors, and in addition, provide controlled release for prolonged therapeutic activity. In this review, we assess the different classes of biomaterials (i.e., biopolymers, synthetic polymers, and ceramics) that have been used for phage delivery and describe the processing methodologies that are compatible with phage embedding or encapsulation. We also elaborate on the clinical or pre-clinical data generated using these materials. While a primary focus is placed on the application of phage-loaded materials for treatment of infection, we also include studies from other translatable fields such as food preservation and animal husbandry. Finally, we summarize trends in the literature and identify current barriers that currently prevent clinical application of phage-loaded biomaterials.

Identification and Characterization of Serum microRNAs as Biomarkers for Human Disc Degeneration: An RNA Sequencing Analysis.

Circulating microRNAs (miRNAs) have been associated with various degenerative diseases, including intervertebral disc (IVD) degeneration. Lumbar disc herniation (LDH) often occurs in young patients, although the underlying mechanisms are poorly understood. The aim of this work was to generate RNA deep sequencing data of peripheral blood samples from patients suffering from LDH, identify circulating miRNAs, and analyze them using bioinformatics applications. Serum was collected from 10 patients with LDH (Disc Degeneration Group); 10 patients without LDH served as the Control Group. RNA sequencing analysis identified 73 differential circulating miRNAs (p < 0.05) between the Disc Degeneration Group and Control Group. Gene ontology enrichment analysis (p < 0.05) showed that these differentially expressed miRNAs were associated with extracellular matrix, damage reactions, inflammatory reactions, and regulation of apoptosis. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes were involved in diverse signaling pathways. The profile of miR-766-3p, miR-6749-3p, and miR-4632-5p serum miRNAs was significantly enriched (p < 0.05) in multiple pathways associated with IVD degeneration. miR-766-3p, miR-6749-3p, and miR-4632-5p signature from serum may serve as a noninvasive diagnostic biomarker for LHD manifestation of IVD degeneration. Furthermore, several dysregulated miRNAs may be involved in the pathogenesis of IVD degeneration. Further study is needed to confirm the functional role of the identified miRNAs.

Development of generic Asian pelvic bone models using CT-based 3D statistical modelling.

BACKGROUND/OBJECTIVE: Artificial bone models (ABMs) are used in orthopaedics for research of biomechanics, development of implants and educational purposes. Most of the commercially available ABMs approximate the morphology of Europeans, but they may not depict the Asian anatomy. Therefore, our aim was to develop the first Asian ABM of the pelvis and compare it with the existing pelvic ABM (Synbone®; Caucasian male). METHODS: One hundred clinical computed tomography (CTs) of adult pelvises (male n â€‹= â€‹50, female n â€‹= â€‹50) of Malay, Chinese and Indian descent were acquired. CTs were segmented and defined landmarks were placed. Three 3D statistical pelvic model and mean models (overall, male, female) were generated. Anatomical variations were analysed using principal component analysis. To measure gender-related differences and differences to the existing ABM, distances between the anterior superior iliac spines (ASIS), the anterior inferior iliac spines (AIIS), the promontory and the symphysis (conjugate vera, CV) as well as the ischial spines (diameter transversa, DT) were quantified. RESULTS: Principal component analysis displayed large variability regarding the pelvic shape and size. Female and male statistical models were similar in ASIS (225 â€‹± â€‹20; 227 â€‹± â€‹13 â€‹mm; P â€‹= â€‹0.4153) and AIIS (185 â€‹± â€‹11; 187 â€‹± â€‹10 â€‹mm; P â€‹= â€‹0.3982) and differed in CV (116 â€‹± â€‹10; 105 â€‹± â€‹10 â€‹mm; P â€‹< â€‹0.0001) and DT (105 â€‹± â€‹7; 88 â€‹± â€‹8 â€‹mm; P â€‹< â€‹0.0001). Comparing the unisex mean model with the pre-existing ABM, the ASIS (226; 275 â€‹mm; P â€‹< â€‹0.0001), the AIIS (186; 209 â€‹mm; P â€‹< â€‹0.0001) and the CV (111; 105 â€‹mm; P â€‹< â€‹0.0001) differed significantly. Both models were similar regarding DT (97; 95 â€‹mm; P â€‹= â€‹0.6927). The analysis revealed notable gender- and size-dependent anatomical variations within the Asian population. Chinese, Malay and Indian descents did not differ notably. The overall Asian model was smaller than the existing ABM. THE TRANSLATION POTENTIAL OF THIS ARTICLE: Owing to the large differences between the Asian ABM and the pre-existing ABM, as well as differences between genders, the use of an Asian- and gender-specific ABM is important to consider in research, biomechanics and implant development for this population.