New dynamic suture material for tendon transfer surgeries in the upper extremity - a biomechanical comparative analysis.

BACKGROUND: Early mobilization after tendon surgery is crucial to avoid commonly observed postoperative soft tissue adhesions. Recently, a new suture was introduced (DYNACORD; DC) with a salt-infused silicone core designed to minimize laxity and preserve consistent tissue approximation in order to avoid gap formation and allow early mobilization. AIMS: To compare the biomechanical competence of DC against a conventional high strength suture (FiberWire; FW) in a human cadaveric tendon transfer model with an early rehabilitation protocol. METHODS: Sixteen tendon transfers (flexor digitorum superficialis (FDS) IV to flexor pollicis longus (FPL)) were performed in 8 pairs human cadaveric forearms using either DC or FW. Markings were set 0.8 cm proximally and 0.7 cm distally to the level of the interweaving zone of the transfer. All specimens underwent repetitive thumb flexion against resistance in 9 intermittent series of 300 cycles each, simulating an aggressive postoperative rehabilitation protocol. After each series, the distance of the proximal marker to the interweaving zone (proximal), the length of the interweaving zone (intermediate) and the distance of the distal marker to the interweaving zone (distal) were measured. RESULTS: Pooled data over all nine series, normalized to the immediate postoperative status, demonstrated no significant differences between FW and DC (p ≥ 0.355) for the proximal and distal markers. However, at the intermediate zone, DC was associated with significant length shortening (p < 0.001) compared to FW without significant length changes (p = 0.351). Load to catastrophic failure demonstrated significant higher forces in FW (p = 0.011). Nevertheless, due to failure mainly proximal or distal of the transfer zone, these loads are not informative. CONCLUSION: From a biomechanical perspective, DC preserved tissue approximation and might be considered as a valid alternative to conventional high-strength sutures in tendon transfer surgery. DC might allow for a shorter interweaving zone and a more aggressive early postoperative rehabilitation program, possibly avoiding commonly observed postoperative soft tissue adhesions and stiffness.

Valgus malalignment causes increased forces on a medial collateral ligament reconstruction under dynamic valgus loading: A biomechanical study.

PURPOSE: To investigate the forces on a medial collateral ligament (MCL) reconstruction (MCLR) relative to the valgus alignment of the knee. METHODS: Eight fresh-frozen human cadaveric knees were subjected to dynamic valgus loading at 400 N using a custom-made kinematics rig. After resection of the superficial medial collateral ligament, a single-bundle MCLR with a hamstring tendon autograft was performed. A medial opening wedge distal femoral osteotomy was performed and fixed with an external fixator to gradually adjust the alignment in 5° increments from 0° to 10° valgus. For each degree of valgus deformity, the resulting forces acting on the MCLR were measured through a force sensor and captured in 15° increments from 0° to 60° of knee flexion. RESULTS: Irrespective of the degree of knee flexion, increasing valgus malalignment resulted in significantly increased forces acting on the MCLR compared to neutral alignment (p < 0.05). Dynamic loading at 5° valgus resulted in increased forces on the MCLR at all flexion angles ranging between 16.2 N and 18.5 N (p < 0.05 from 0° to 30°; p < 0.01 from 45° to 60°). A 10° valgus malalignment further increased the forces on the MCLR at all flexion angles ranging between 29.4 N and 40.0 N (p < 0.01 from 0° to 45°, p < 0.05 at 60°). CONCLUSION: Valgus malalignment of the knee caused increased forces acting on the reconstructed MCL. In cases of chronic medial instabilities accompanied by a valgus deformity ≥ 5°, a realigning osteotomy should be considered concomitantly to the MCLR to protect the graft and potentially reduce graft failures. LEVEL OF EVIDENCE: Level III.

Exposure of Hoffa Fractures Is Improved by Posterolateral and Posteromedial Extensile Approaches: A Qualitative and Quantitative Anatomical Study.

BACKGROUND: The current literature lacks recommendations regarding surgical approaches to best visualize and reduce Hoffa fractures. The aims of this study were to (1) define surgical corridors to the posterior portions of the lateral and medial femoral condyles and (2) compare the articular surface areas visible with different approaches. METHODS: Eight fresh-frozen human cadaveric knees (6 male and 2 female donors; mean age, 68.2 ± 10.2 years) underwent dissection simulating 6 surgical approaches to the distal femur. The visible articular surface areas for each approach were marked using an electrocautery device and subsequently analyzed using image-processing software. The labeled areas of each femoral condyle were statistically compared. RESULTS: At 30° of flexion, visualization of the posterior portions of the lateral and medial femoral condyles was not possible by lateral and medial parapatellar approaches, as only the anterior 29.4% ± 2.1% of the lateral femoral condyle and 25.6% ± 2.8% of the medial condyle were exposed. Visualization of the lateral femoral condyle was limited by the posterolateral ligamentous structures, hence a posterolateral approach only exposed its central (13.1% ± 1.3%) and posterior (12.4% ± 1.1%) portions. Posterolateral extension by an osteotomy of the lateral femoral epicondyle significantly improved the exposure to 53.4% ± 2.7% and, when combined with a Gerdy's tubercle osteotomy, to 70.9% ± 4.1% (p < 0.001). For the posteromedial approach, an arthrotomy between the anteromedial retinaculum and the superficial medial collateral ligament, and one between the posterior oblique ligament and the medial gastrocnemius tendon, allowed visualization of the central (13.5% ± 2.2%) and the posterior (14.6% ± 2.3%) portions of the medial femoral condyle, while a medial femoral epicondyle osteotomy significantly improved visualization to 66.1% ± 5.5% (p < 0.001). CONCLUSIONS: Visualization of the posterior portions of the femoral condyles is limited by the specific anatomy of each surgical corridor. Extension by osteotomy of the femoral epicondyles and Gerdy's tubercle significantly improved articular surface exposure of the femoral condyles. CLINICAL RELEVANCE: Knowledge of the surgical approach-specific visualization of the articular surface of the femoral condyles might be helpful to properly reduce small Hoffa fragments.

Fracture-related infection.

Musculoskeletal trauma leading to broken and damaged bones and soft tissues can be a life-threating event. Modern orthopaedic trauma surgery, combined with innovation in medical devices, allows many severe injuries to be rapidly repaired and to eventually heal. Unfortunately, one of the persisting complications is fracture-related infection (FRI). In these cases, pathogenic bacteria enter the wound and divert the host responses from a bone-healing course to an inflammatory and antibacterial course that can prevent the bone from healing. FRI can lead to permanent disability, or long courses of therapy lasting from months to years. In the past 5 years, international consensus on a definition of these infections has focused greater attention on FRI, and new guidelines are available for prevention, diagnosis and treatment. Further improvements in understanding the role of perioperative antibiotic prophylaxis and the optimal treatment approach would be transformative for the field. Basic science and engineering innovations will be required to reduce infection rates, with interventions such as more efficient delivery of antibiotics, new antimicrobials, and optimizing host defences among the most likely to improve the care of patients with FRI.

Advanced CT visualization improves the accuracy of orthopaedic trauma surgeons and residents in classifying proximal humeral fractures: a feasibility study.

PURPOSE: Osteosynthesis of proximal humeral fractures remains challenging with high reported failure rates. Understanding the fracture type is mandatory in surgical treatment to achieve an optimal anatomical reduction. Therefore, a better classification ability resulting in improved understanding of the fracture pattern is important for preoperative planning. The purpose was to investigate the feasibility and added value of advanced visualization of segmented 3D computed tomography (CT) images in fracture classification. METHODS: Seventeen patients treated with either plate-screw-osteosynthesis or shoulder hemi-prosthesis between 2015 and 2019 were included. All preoperative CT scans were segmented to indicate every fracture fragment in a different color. Classification ability was tested in 21 orthopaedic residents and 12 shoulder surgeons. Both groups were asked to classify fractures using three different modalities (standard CT scan, 3D reconstruction model, and 3D segmented model) into three different classification systems (Neer, AO/OTA and LEGO). RESULTS: All participants were able to classify the fractures more accurately into all three classification systems after evaluating the segmented three-dimensional (3D) models compared to both 2D slice-wise evaluation and 3D reconstruction model. This finding was significant (p < 0.005) with an average success rate of 94%. The participants experienced significantly more difficulties classifying fractures according to the LEGO system than the other two classifications. CONCLUSION: Segmentation of CT scans added value to the proximal humeral fracture classification, since orthopaedic surgeons were able to classify fractures significantly better into the AO/OTA, Neer, and LEGO classification systems compared to both standard 2D slice-wise evaluation and 3D reconstruction model.

One size may not fit all: patient-specific computational optimization of locking plates for improved proximal humerus fracture fixation.

BACKGROUND: Optimal treatment options for proximal humerus fractures (PHFs) are still debated because of persisting high fixation failure rates experienced with locking plates. Optimization of the implants and development of patient-specific designs may help improve the primary fixation stability of PHFs and reduce the rate of mechanical failures. Optimizing the screw orientations in locking plates has shown promising results; however, the potential benefit of subject-specific designs has not been explored yet. The purpose of this study was to evaluate by means of finite element (FE) analyses whether subject-specific optimization of the screw orientations in a fixed-angle locking plate can reduce the predicted cutout failure risk in unstable 3-part fractures. METHODS: FE models of 19 low-density proximal humeri were generated from high-resolution computed tomographic images using a previously developed and validated computational osteosynthesis framework. The specimens were virtually osteotomized to simulate unstable malreduced 3-part fractures and fixed with the PHILOS plates using 6 proximal locking screws. The average principal compressive strain in cylindrical bone regions around the screw tips-a biomechanically validated surrogate for the risk of cyclic screw cutout failure-was defined as the main outcome measure. The angles of the 6 proximal locking screws were optimized via parametric analysis for each humerus individually, resulting in subject-specific screw orientations (SSO). The average peri-implant strains of the SSO were statistically compared with the previously reported cohort-specific (CSO) and original PHILOS screw orientations (PSO) for females vs. males. RESULTS: The optimized SSO significantly reduced the peri-screw bone strain vs. CSO (6.8% ± 4.0%, P = .006) and PSO (25.24% ± 7.93%, P < .001), indicating lower cutout risk for subject-specific configurations. The benefits of SSO vs. PSO were significantly higher for women than men. CONCLUSION: The findings of this study suggest that subject-specific optimization of the locking screw orientations could lead to lower cutout risk and improved PHF fixation. These computer simulation results require biomechanical and clinical corroboration. Further studies are needed to evaluate whether the potential benefit in stability could justify the increased efforts related to implementation of individualized implants. Nevertheless, computational exploration of the biomechanical factors influencing the outcome of fracture fixations could help better understand the fixation failures and reduce their incidence.

Screw tightness and stripping rates vary between biomechanical researchers and practicing orthopaedic surgeons.

BACKGROUND: Screws are the most frequently inserted orthopaedic implants. Biomechanical, laboratory-based studies are used to provide a controlled environment to investigate revolutionary and evolutionary improvements in orthopaedic techniques. Predominantly, biomechanical trained, non-surgically practicing researchers perform these studies, whilst it will be orthopaedic surgeons who will put these procedures into practice on patients. Limited data exist on the comparative performance of surgically and non-surgically trained biomechanical researchers when inserting screws. Furthermore, any variation in performance by surgeons and/or biomechanical researchers may create an underappreciated confounder to biomechanical research findings. This study aimed to identify the differences between surgically and non-surgically trained biomechanical researchers' achieved screw tightness and stripping rates with different fixation methods. METHODS: Ten orthopaedic surgeons and 10 researchers inserted 60 cortical screws each into artificial bone, for three different screw diameters (2.7, 3.5 and 4.5 mm), with 50% of screws inserted through plates and 50% through washers. Screw tightness, screw hole stripping rates and confidence in screw purchase were recorded. Three members of each group also inserted 30 screws using an augmented screwdriver, which indicated when optimum tightness was achieved. RESULTS: Unstripped screw tightness for orthopaedic surgeons and researchers was 82% (n = 928, 95% CI 81-83) and 76% (n = 1470, 95% CI 75-76) respectively (p < 0.001); surgeons stripped 48% (872/1800) of inserted screws and researchers 18% (330/1800). Using washers was associated with increased tightness [80% (95% CI 80-81), n = 1196] compared to screws inserted through plates [76% (95% CI 75-77), n = 1204] (p < 0.001). Researchers were more accurate in their overall assessment of good screw insertion (86% vs. 62%). No learning effect occurred when comparing screw tightness for the first 10 insertions against the last 10 insertions for any condition (p = 0.058-0.821). Augmented screwdrivers, indicating optimum tightness, reduced stripping rates from 34 to 21% (p < 0.001). Experience was not associated with improved performance in screw tightness or stripping rates for either group (p = 0.385-0.965). CONCLUSIONS: Surgeons and researchers showed different screw tightness under the same in vitro conditions, with greater rates of screw hole stripping by surgeons. This may have important implications for the reproducibility and transferability of research findings from different settings depending on who undertakes the experiments.

An Enzybiotic Regimen for the Treatment of Methicillin-Resistant Staphylococcus aureus Orthopaedic Device-Related Infection.

Orthopaedic device-related infection (ODRI) presents a significant challenge to the field of orthopaedic and trauma surgery. Despite extensive treatment involving surgical debridement and prolonged antibiotic therapy, outcomes remain poor. This is largely due to the unique abilities of Staphylococcus aureus, the most common causative agent of ODRI, to establish and protect itself within the host by forming biofilms on implanted devices and staphylococcal abscess communities (SACs). There is a need for novel antimicrobials that can readily target such features. Enzybiotics are a class of antimicrobial enzymes derived from bacteria and bacteriophages, which function by enzymatically degrading bacterial polymers essential to bacterial survival or biofilm formation. Here, we apply an enzybiotic-based combination regimen to a set of in vitro models as well as in a murine ODRI model to evaluate their usefulness in eradicating established S. aureus infection, compared to classical antibiotics. We show that two chimeric endolysins previously selected for their functional efficacy in human serum in combination with a polysaccharide depolymerase reduce bacterial CFU numbers 10,000-fold in a peg model and in an implant model of biofilm. The enzyme combination also completely eradicates S. aureus in a SAC in vitro model where classical antibiotics are ineffective. In an in vivo ODRI model in mice, the antibiofilm effects of this enzyme regimen are further enhanced when combined with a classical gentamicin/vancomycin treatment. In a mouse model of methicillin-resistant S. aureus (MRSA) ODRI following a fracture repair, a combined local enzybiotic/antibiotic treatment regimen showed a significant CFU reduction in the device and the surrounding soft tissue, as well as significant prevention of weight loss. These outcomes were superior to treatment with antibiotics alone. Overall, this study demonstrates that the addition of enzybiotics, which are distinguished by their extremely rapid killing efficacy and antibiofilm activities, can enhance the treatment of severe MRSA ODRI.

Humanized Mice Exhibit Exacerbated Abscess Formation and Osteolysis During the Establishment of Implant-Associated Staphylococcus aureus Osteomyelitis.

Staphylococcus aureus is the predominant pathogen causing osteomyelitis. Unfortunately, no immunotherapy exists to treat these very challenging and costly infections despite decades of research, and numerous vaccine failures in clinical trials. This lack of success can partially be attributed to an overreliance on murine models where the immune correlates of protection often diverge from that of humans. Moreover, S. aureus secretes numerous immunotoxins with unique tropism to human leukocytes, which compromises the targeting of immune cells in murine models. To study the response of human immune cells during chronic S. aureus bone infections, we engrafted non-obese diabetic (NOD)-scid IL2Rγnull (NSG) mice with human hematopoietic stem cells (huNSG) and analyzed protection in an established model of implant-associated osteomyelitis. The results showed that huNSG mice have increases in weight loss, osteolysis, bacterial dissemination to internal organs, and numbers of Staphylococcal abscess communities (SACs), during the establishment of implant-associated MRSA osteomyelitis compared to NSG controls (p < 0.05). Flow cytometry and immunohistochemistry demonstrated greater human T cell numbers in infected versus uninfected huNSG mice (p < 0.05), and that T-bet+ human T cells clustered around the SACs, suggesting S. aureus-mediated activation and proliferation of human T cells in the infected bone. Collectively, these proof-of-concept studies underscore the utility of huNSG mice for studying an aggressive form of S. aureus osteomyelitis, which is more akin to that seen in humans. We have also established an experimental system to investigate the contribution of specific human T cells in controlling S. aureus infection and dissemination.

A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.

Symptomatic intervertebral disc (IVD) degeneration (IDD) is a major socioeconomic burden and is characterized by inflammation and tissue degradation. Due to the lack of causative therapies, there is an urgent need for innovative experimental organ culture models to study the mechanisms involved in the progression of the disease, find therapeutic targets, and reduce the need for animal models. We here present a novel, three-dimensional organ culture model protocol mimicking the proinflammatory and catabolic microenvironment, which is present during IDD. Initially, bovine caudal IVDs were dissected, cleaned, and cultured in the tissue culture medium. Dynamic physiologic or pathologic loading was applied in a custom-made bioreactor for 2 hours per day. IVDs were assigned to a control group (high glucose medium, physiological loading, phosphate-buffered saline injection) and a pathological group (low glucose medium, pathological loading, tumor necrosis factor-alpha injection) for four days. Gene expression analysis from collected nucleus pulposus cells of the IVDs and enzyme-linked immunosorbent assay of the conditioned organ culture media was performed. Our data revealed a higher expression of inflammatory markers and reduced disc heights after loading in the pathological group compared to the control group. This protocol is reliable to simulate IVD inflammation and degeneration and can be further expanded to broaden its application scope.

Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis.

BACKGROUND: Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation, and promote production of extracellular matrix (ECM). For clinical translation of secretome-based treatment, characterization of the secretome composition is needed to better understand the induced biological processes and identify potentially effective secretomes. METHODS: This study aimed to investigate the proteome released by bone marrow-derived MSCs following exposure to a healthy, traumatic, or degenerative human IVD environment by mass spectroscopy and quantitative immunoassay analyses. Exposure of MSCs to the proinflammatory stimulus interleukin 1ß (IL-1ß) was used as control. RESULTS: Compared to MSC baseline secretome, there were 224 significantly up- or downregulated proteins following healthy, 179 following traumatic, 223 following degenerative IVD, and 160 proteins following IL-1ß stimulus. Stimulation of MSCs with IVD conditioned media induced a more complex MSC secretome, involving more biological processes, compared to stimulation with IL-1ß. The MSC response to stimulation with IVD conditioned medium was dependent on their pathological status. CONCLUSIONS: The MSC secretome seemed to match the primary need of the IVD: homeostasis maintenance in the case of healthy IVDs, versus immunomodulation, adjustment of ECM synthesis and degradation disbalance, and ECM (re) organization in the case of traumatic and degenerative IVDs. These findings highlight the importance of cell preconditioning in the development of tailored secretome therapies. The secretome of human bone marrow-derived mesenchymal stromal cells (MSCs) stimulated with intervertebral disc (IVD) conditioned medium was analyzed by proteomic profiling. Depending on the pathological state of the IVD, the MSC secretome protein composition indicated immunomodulatory or anabolic activity of the secretome. These findings may have implications for tailored secretome therapy for the IVD and other tissues.

Impact of low bone mass and antiresorptive therapy on antibiotic efficacy in a rat model of orthopedic device-related infection.

A significant proportion of orthopedic devices are implanted in osteoporotic patients, but it is currently unclear how estrogen deficiency and/or exposure to antiresorptive bisphosphonates (BPs) influence orthopedic device-related infection (ODRI), or response to therapy. The aim of this study is to characterize the bone changes resulting from Staphylococcus epidermidis infection in a rodent ODRI model and to determine if ovariectomy (OVX) or BP treatment influences the infection or the success of antibiotic therapy. A sterile or S. epidermidis-contaminated screw was implanted into the proximal tibia of skeletally mature female Wistar rats (n = 6-9 per group). Bone changes were monitored over 28 days using in vivo micro-computed tomography scanning. OVX was performed 12 weeks before screw implantation. The BP zoledronic acid (ZOL) was administered 4 days before screw insertion. A combination antibiotic regimen (rifampin plus cefazolin) was administered from Days 7-21. In skeletally healthy animals, S. epidermidis induced marked changes in bone, with peak osteolysis occurring at Day 9 and woven bone deposition and periosteal mineralization from Day 14 onwards. Antibiotic therapy cleared the infection in the majority of animals (2/9 infected) but did not affect bone responses. OVX did not affect the pattern of infection-induced changes in bone, nor bacterial load, but reduced antibiotic efficacy (5/9 infected). ZOL treatment did not protect from osteolysis in OVX animals, or further affect antibiotic efficacy (5/9 infected) but did significantly increase the bacterial load. This study suggests that both BPs and OVX can influence host responses to bone infections involving S. epidermidis.

Sound-induced morphogenesis of multicellular systems for rapid orchestration of vascular networks.

Morphogenesis, a complex process, ubiquitous in developmental biology and many pathologies, is based on self-patterning of cells. Spatial patterns of cells, organoids, or inorganic particles can be forced on demand using acoustic surface standing waves, such as the Faraday waves. This technology allows tuning of parameters (sound frequency, amplitude, chamber shape) under contactless, fast and mild culture conditions, for morphologically relevant tissue generation. We call this method Sound Induced Morphogenesis (SIM). In this work, we use SIM to achieve tight control over patterning of endothelial cells and mesenchymal stem cells densities within a hydrogel, with the endpoint formation of vascular structures. Here, we first parameterize our system to produce enhanced cell density gradients. Second, we allow for vasculogenesis after SIM patterning control and compare our controlled technology against state-of-the-art microfluidic culture systems, the latter characteristic of pure self-organized patterning and uniform initial density. Our sound-induced cell density patterning and subsequent vasculogenesis requires less cells than the microfluidic chamber. We advocate for the use of SIM for rapid, mild, and reproducible morphogenesis induction and further explorations in the regenerative medicine and cell therapy fields.

Comparison of Ligament-Repair Techniques for the Syndesmosis: A Simulated Cadaveric Weight-Bearing Computed Tomography Analysis.

Although the literature describes a variety of reconstructive techniques for the syndesmosis, only few studies offer comparative data. Therefore, the authors compared 2 different ligament repair techniques for the syndesmosis. Sixteen paired fresh-frozen human cadaveric lower limbs were embedded in polymethyl methacrylate mid-calf and placed in a custom-made weightbearing simulation frame. Computed tomography scans of each limb were obtained in a simulated foot-flat loading (75N) and single-leg stance (700N) in 5 different foot positions (previously reported data). One of each pair was then reconstructed via 1 of 2 methods: a free medial Achilles tendon autograft or a long peroneal tendon ligament repair. The specimens were rescanned, compared with their respective intact states and directly with each other. Measurements of fibular diastasis, rotation, anteroposterior translation, mediolateral translation, and fibular shortening were performed on the axial cuts of the computed tomography scans, 1 cm proximal to the roof of the plafond. There was no significant difference in fibular positioning with direct comparison of the reconstructions. Comparisons with their respective intact states, however, showed differences in their abilities to control reduction, most notably in the externally rotated and dorsiflexed positions of the foot. Neither reconstruction was clearly superior in restoring physiologic conditions. Only with a comparison of each technique to its respective intact state were differences between the techniques revealed, a benefit of this particular testing method.

Preclinical ex-vivo Testing of Anti-inflammatory Drugs in a Bovine Intervertebral Degenerative Disc Model.

Discogenic low back pain (LBP) is a main cause of disability and inflammation is presumed to be a major driver of symptomatic intervertebral disc degeneration (IDD). Anti-inflammatory agents are currently under investigation as they demonstrated to alleviate symptoms in patients having IDD. However, their underlying anti-inflammatory and regenerative activity is poorly explored. The present study sought to investigate the potential of Etanercept and Tofacitinib for maintaining disc homeostasis in a preclinical intervertebral disc (IVD) organ culture model within IVD bioreactors allowing for dynamic loading and nutrient exchange. Bovine caudal IVDs were cultured in a bioreactor system for 4 days to simulate physiological or degenerative conditions: (1) Phy-physiological loading (0.02-0.2 MPa; 0.2 Hz; 2 h/day) and high glucose DMEM medium (4.5 g/L); (2) Deg+Tumor necrosis factor α (TNF-α)-degenerative loading (0.32-0.5 MPa; 5 Hz; 2 h/day) and low glucose DMEM medium (2 g/L), with TNF-α injection. Etanercept was injected intradiscally while Tofacitinib was supplemented into the culture medium. Gene expression in the IVD tissue was measured by RT-qPCR. Release of nitric oxide (NO), interleukin 8 (IL-8) and glycosaminoglycan (GAG) into the IVD conditioned medium were analyzed. Cell viability in the IVD was assessed using lactate dehydrogenase and ethidium homodimer-1 staining. Immunohistochemistry was performed to assess protein expression of IL-1ß, IL-6, IL-8, and collagen type II in the IVD tissue. Etanercept and Tofacitinib downregulated the expression of IL-1ß, IL-6, IL-8, Matrix metalloproteinase 1 (MMP1), and MMP3 in the nucleus pulposus (NP) tissue and IL-1ß, MMP3, Cyclooxygenase-2 (COX2), and Nerve growth factor (NGF) in the annulus fibrosus (AF) tissue. Furthermore, Etanercept significantly reduced the IL-1ß positively stained cells in the outer AF and NP regions. Tofacitinib significantly reduced IL-1ß and IL-8 positively stained cells in the inner AF region. Both, Etanercept and Tofacitinib reduced the GAG loss to the level under physiological culture condition. Etanercept and Tofacitinib are able to neutralize the proinflammatory and catabolic environment in the IDD organ culture model. However, combined anti-inflammatory and anabolic treatment may be required to constrain accelerated IDD and relieving inflammation-induced back pain.

General treatment principles for fracture-related infection: recommendations from an international expert group.

Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Thereafter, this needs to be adapted according to culture results as soon as possible. Finally, a minimum follow-up of 12 months after cessation of therapy is recommended. Standardized patient outcome measures purely focusing on FRI are currently not available but the patient-reported outcomes measurement information system (PROMIS) seems to be the preferred tool to assess the patients' short and long-term outcome. This review summarizes the current general principles which should be considered during the whole treatment process of patients with FRI based on recommendations from the FRI Consensus Group.Level of evidence: Level V.

Computed Tomography Analysis for Quantification of Displacement of the Distal Fibula in Different Foot Positions With Weightbearing and Sequentially Increased Instability: An Anatomic Cadaveric Study on Syndesmosis.

Syndesmotic injuries are quite common, but accurate diagnosis and treatment can be difficult, in part because of individual anatomic variation and complex movements of the fibula in the incisura. The current cadaveric study was designed to investigate changes in the position of the fibula in the incisura during simulated weightbearing in different foot positions and with sequential sectioning of syndesmotic and deltoid ligaments. Sixteen paired, fresh-frozen cadaveric limbs were embedded in polymethylmethacrylate mid-calf and placed in a weightbearing simulation frame. Computed tomography scans were obtained while the legs were in a simulated foot-flat position (75 N) and single-leg stance (700 N) in 5 foot positions: neutral, 15° external rotation, 15° internal rotation, 20° dorsiflexion, and 20° plantar flexion. The anterior-inferior tibiofibular ligament, posterior tibiofibular ligament complex, deltoid, and interosseous membranes were sectioned sequentially and rescanned. Measurements of fibular diastasis, rotation, anterior-posterior and medial-lateral translation, and fibular shortening were performed. The most destructive state resulted in the largest displacement at the syndesmosis. The degree of subluxation in all ligament states was dependent on the foot position. External rotation created statistically significant displacement at all levels of injury. There were no significant differences between sides of the same donor. Our data demonstrate the importance of foot position in reduction at the syndesmosis under weightbearing. The current ex vivo model could be used to evaluate other aspects of this injury or the value of reconstructive techniques in the future.

Screw configuration in proximal humerus plating has a significant impact on fixation failure risk predicted by finite element models.

BACKGROUND: Proximal humeral fractures occur frequently, with fixed angle locking plates often being used for their treatment. No current quantitative evidence for the effect of different screw configurations exists, and the large number of variations makes biomechanical testing prohibitive. Therefore, we used an established and validated finite element osteosynthesis test kit to quantify the effect of variations in screw configuration on predicted failure risk of PHILOS plate fixation for unstable proximal humerus fractures. METHODS: Twenty-six low-density humerus models were osteotomized to create malreduced unstable 3-part fractures that were virtually fixed with PHILOS plates. Twelve screw configurations were simulated: 6 using 2 screw rows, 4 using 3 rows, and 1 with either 8 or 9 screws. Three physiological loading cases were modeled and an established finite element analysis methodology was used. The average peri-screw bone strain, previously demonstrated to predict fatigue cutout failure, was used to compare the different configurations. RESULTS: Significant differences in peri-screw strains, and thus predicted failure risk, were seen with different combinations. The 9-screw configuration demonstrated the lowest peri-screw strains. Fewer screw constructs showed lower strains when placed further apart. The calcar screws (row E) significantly (P < .001) reduced fixation failure risk. CONCLUSION: Screw configurations significantly impact predicted cutout failure risk for locking plate fixations of unstable proximal humerus fractures in low-density bone. Although requiring clinical corroboration, the result of this study suggests that additional screws reduce peri-screw strains, the distance between them should be maximized whenever possible and the calcar screws should be used.

The influence of screw length on predicted cut-out failures for proximal humeral fracture fixations predicted by finite element simulations.

BACKGROUND: The aim of this study was to identify the effect of screw length on predictions of fixation failure in three-part proximal humeral fractures using a finite element-based osteosynthesis modelling toolkit. METHODS: A mal-reduced unstable three-part AO/OTA 11-B3.2 fracture with medial comminution was simulated in forty-two digitally processed proximal humeri covering a spectrum of bone densities and fixed with the PHILOS plate using three distal and six proximal locking screws. Four test groups were generated based on the screw tip to joint surface distance (TJD), with all proximal screws being shortened from 4 mm TJD to be 8, 12 or 16 mm TJD. Average bone strains around the screw tips, correlating with biomechanical cyclic cut-out-type failure, were evaluated in three physiological loading protocols representing simple shoulder motions. Six further groups were tested, where five of the proximal screws were inserted to 4 mm TJD and the sixth screw to 8 mm TJD. RESULTS: Exponential increases in the predicted risk of fixation failure were seen with increased tip-to-joint distances (p < 0.001). When one of the proximal screws was placed 8 mm from the joint, with the remaining five at 4 mm distance, significant increases (p < 0.001) were registered in the strains around the screw tips in all except the two superior screws. This effect was maximal around the calcar screws (p < 0.001) and for lower density samples (p < 0.001). CONCLUSIONS: These results suggest that longer screws provide reduced risk of cut-out failure, i.e. distalisation and/or varisation of the head fragment, and thus may decrease failure rates in proximal humeral fractures treated with angular stable plates. These findings require clinical corroboration and further studies to investigate the risk of screw perforation.

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device-related infection.

Orthopedic device-related infection (ODRI), including both fracture-related infection (FRI) and periprosthetic joint infection (PJI), remain among the most challenging complications in orthopedic and musculoskeletal trauma surgery. ODRI has been convincingly shown to delay healing, worsen functional outcome and incur significant socio-economic costs. To address this clinical problem, ever more sophisticated technologies targeting the prevention and/or treatment of ODRI are being developed and tested in vitro and in vivo. Among the most commonly described innovations are antimicrobial-coated orthopedic devices, antimicrobial-loaded bone cements and void fillers, and dual osteo-inductive/antimicrobial biomaterials. Unfortunately, translation of these technologies to the clinic has been limited, at least partially due to the challenging and still evolving regulatory environment for antimicrobial drug-device combination products, and a lack of clarity in the burden of proof required in preclinical studies. Preclinical in vivo testing (i.e. animal studies) represents a critical phase of the multidisciplinary effort to design, produce and reliably test both safety and efficacy of any new antimicrobial device. Nonetheless, current in vivo testing protocols, procedures, models, and assessments are highly disparate, irregularly conducted and reported, and without standardization and validation. The purpose of the present opinion piece is to discuss best practices in preclinical in vivo testing of antimicrobial interventions targeting ODRI. By sharing these experience-driven views, we aim to aid others in conducting such studies both for fundamental biomedical research, but also for regulatory and clinical evaluation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:271-287, 2019.