Showing papers by "Georg N. Duda published in 2021"

Functionalized Bead Assay to Measure Three-dimensional Traction Forces during T-cell Activation

Abstract: When T-cells probe their environment for antigens, the bond between the T-cell receptor (TCR) and the peptide-loaded major histocompatibility complex (MHC) is put under tension, thereby influencing the antigen discrimination. Yet, the quantification of such forces in the context of T-cell signaling is technically challenging. Here, we developed a traction force microscopy platform which allows for quantifying the pulls and pushes exerted via T-cell microvilli, in both tangential and normal directions, during T-cell activation. We immobilized specific T-cell activating antibodies on the marker beads used to read out the hydrogel deformation. Microvilli targeted the functionalized beads, as confirmed by superresolution microscopy of the local actin organization. Moreover, we found that cellular components, such as actin, TCR, and CD45 reorganize upon interaction with the beads, such that actin forms a vortex-like ring structure around the beads and TCR is enriched at the bead surface, whereas CD45 is excluded from bead-microvilli contacts.

Association of Machine Learning-Based Predictions of Medial Knee Contact Force With Cartilage Loss Over 2.5 Years in Knee Osteoarthritis.

Abstract: OBJECTIVE The relationship between in vivo knee load predictions and longitudinal cartilage changes has not been investigated. We undertook this study to develop an equation to predict the medial tibiofemoral contact force (MCF) peak during walking in persons with instrumented knee implants, and to apply this equation to determine the relationship between the predicted MCF peak and cartilage loss in patients with knee osteoarthritis (OA). METHODS In adults with knee OA (39 women, 8 men; mean ± SD age 61.1 ± 6.8 years), baseline biomechanical gait analyses were performed, and annualized change in medial tibial cartilage volume (mm3 /year) over 2.5 years was determined using magnetic resonance imaging. In a separate sample of patients with force-measuring tibial prostheses (3 women, 6 men; mean ± SD age 70.3 ± 5.2 years), gait data plus in vivo knee loads were used to develop an equation to predict the MCF peak using machine learning. This equation was then applied to the knee OA group, and the relationship between the predicted MCF peak and annualized cartilage volume change was determined. RESULTS The MCF peak was best predicted using gait speed, the knee adduction moment peak, and the vertical knee reaction force peak (root mean square error 132.88N; R2 = 0.81, P < 0.001). In participants with knee OA, the predicted MCF peak was related to cartilage volume change (R2 = 0.35, β = -0.119, P < 0.001). CONCLUSION Machine learning was used to develop a novel equation for predicting the MCF peak from external biomechanical parameters. The predicted MCF peak was positively related to medial tibial cartilage volume loss in patients with knee OA.

Initial mechanical conditions within an optimized bone scaffold do not ensure bone regeneration – an in silico analysis

Abstract: Large bone defects remain a clinical challenge because they do not heal spontaneously. 3-D printed scaffolds are a promising treatment option for such critical defects. Recent scaffold design strategies have made use of computer modelling techniques to optimize scaffold design. In particular, scaffold geometries have been optimized to avoid mechanical failure and recently also to provide a distinct mechanical stimulation to cells within the scaffold pores. This way, mechanical strain levels are optimized to favour the bone tissue formation. However, bone regeneration is a highly dynamic process where the mechanical conditions immediately after surgery might not ensure optimal regeneration throughout healing. Here, we investigated in silico whether scaffolds presenting optimal mechanical conditions for bone regeneration immediately after surgery also present an optimal design for the full regeneration process. A computer framework, combining an automatic parametric scaffold design generation with a mechano-biological bone regeneration model, was developed to predict the level of regenerated bone volume for a large range of scaffold designs and to compare it with the scaffold pore volume fraction under favourable mechanical stimuli immediately after surgery. We found that many scaffold designs could be considered as highly beneficial for bone healing immediately after surgery; however, most of them did not show optimal bone formation in later regenerative phases. This study allowed to gain a more thorough understanding of the effect of scaffold geometry changes on bone regeneration and how to maximize regenerated bone volume in the long term.

Biomechanical Assessment of the Validity of Sheep as a Preclinical Model for Testing Mandibular Fracture Fixation Devices.

Abstract: Mandibular fracture fixation and reconstruction are usually performed using titanium plates and screws, however, there is a need to improve current fixation techniques. Animal models represent an important step for the testing of new designs and materials. However, the validity of those preclinical models in terms of implant biomechanics remains largely unknown. In this study, we investigate the biomechanics of the sheep mandible as a preclinical model for testing the mechanical strength of fixation devices and the biomechanical environment induced on mandibular fractures. We aimed to assess the comparability of the biomechanical conditions in the sheep mandible as a preclinical model for human applications of fracture fixation devices and empower analyses of the effect of such defined mechanical conditions on bone healing outcome. We developed 3D finite element models of the human and sheep mandibles simulating physiological muscular loads and three different clenching tasks (intercuspal, incisal, and unilateral). Furthermore, we simulated fractures in the human mandibular body, sheep mandibular body, and sheep mandibular diastema fixated with clinically used titanium miniplates and screws. We compared, at the power stroke of mastication, the biomechanical environment (1) in the healthy mandibular body and (2) at the fracture sites, and (3) the mechanical solicitation of the implants as well as the mechanical conditions for bone healing in such cases. In the healthy mandibles, the sheep mandibular body showed lower mechanical strains compared to the human mandibular body. In the fractured mandibles, strains within a fracture gap in sheep were generally not comparable to humans, while similar or lower mechanical solicitation of the fixation devices was found between the human mandibular body fracture and the sheep mandibular diastema fracture scenarios. We, therefore, conclude that the mechanical environments of mandibular fractures in humans and sheep differ and our analyses suggest that the sheep mandibular bone should be carefully re-considered as a model system to study the effect of fixation devices on the healing outcome. In our analyses, the sheep mandibular diastema showed similar mechanical conditions for fracture fixation devices to those in humans.

Mechanobiological Principles Influence the Immune Response in Regeneration: Implications for Bone Healing.

Abstract: A misdirected or imbalanced local immune composition is often one of the reasons for unsuccessful regeneration resulting in scarring or fibrosis. Successful healing requires a balanced initiation and a timely down-regulation of the inflammation for the re-establishment of a biologically and mechanically homeostasis. While biomaterial-based approaches to control local immune responses are emerging as potential new treatment options, the extent to which biophysical material properties themselves play a role in modulating a local immune niche response has so far been considered only occasionally. The communication loop between extracellular matrix, non-hematopoietic cells, and immune cells seems to be specifically sensitive to mechanical cues and appears to play a role in the initiation and promotion of a local inflammatory setting. In this review, we focus on the crosstalk between ECM and its mechanical triggers and how they impact immune cells and non-hematopoietic cells and their crosstalk during tissue regeneration. We realized that especially mechanosensitive receptors such as TRPV4 and PIEZO1 and the mechanosensitive transcription factor YAP/TAZ are essential to regeneration in various organ settings. This indicates novel opportunities for therapeutic approaches to improve tissue regeneration, based on the immune-mechanical principles found in bone but also lung, heart, and skin.

Bone morphogenetic protein 2-induced cellular chemotaxis drives tissue patterning during critical-sized bone defect healing: an in silico study

Abstract: Critical-sized bone defects are critical healing conditions that, if left untreated, often lead to non-unions. To reduce the risk, critical-sized bone defects are often treated with recombinant human BMP-2. Although enhanced bone tissue formation is observed when BMP-2 is administered locally to the defect, spatial and temporal distribution of callus tissue often differs from that found during regular bone healing or in defects treated differently. How this altered tissue patterning due to BMP-2 treatment is linked to mechano-biological principles at the cellular scale remains largely unknown. In this study, the mechano-biological regulation of BMP-2-treated critical-sized bone defect healing was investigated using a multiphysics multiscale in silico approach. Finite element and agent-based modeling techniques were combined to simulate healing within a critical-sized bone defect (5 mm) in a rat femur. Computer model predictions were compared to in vivo microCT data outcome of bone tissue patterning at 2, 4, and 6 weeks postoperation. In vivo, BMP-2 treatment led to complete healing through periosteal bone bridging already after 2 weeks postoperation. Computer model simulations showed that the BMP-2 specific tissue patterning can be explained by the migration of mesenchymal stromal cells to regions with a specific concentration of BMP-2 (chemotaxis). This study shows how computational modeling can help us to further understand the mechanisms behind treatment effects on compromised healing conditions as well as to optimize future treatment strategies.

Surgical cup placement affects the heating up of total joint hip replacements

Abstract: The long-term success of highly effective total hip arthroplasty (THA) is mainly restricted by aseptic loosening, which is widely associated with friction between the head and cup liner. However, knowledge of the in vivo joint friction and resulting temperature increase is limited. Employing a novel combination of in vivo and in silico technologies, we analyzed the hypothesis that the intraoperatively defined implant orientation defines the individual joint roofing, friction and its associated temperature increase. A total of 38,000 in vivo activity trials from a special group of 10 subjects with instrumented THA implants with an identical material combination were analyzed and showed a significant link between implant orientation, joint kinematics, joint roofing and friction-induced temperature increase but surprisingly not with acting joint contact force magnitude. This combined in vivo and in silico analysis revealed that cup placement in relation to the stem is key to the in vivo joint friction and heating-up of THA. Thus, intraoperative placement, and not only articulating materials, should be the focus of further improvements, especially for young and more active patients.

Proinflammatory and bone protective role of calcitonin gene-related peptide alpha in collagen antibody-induced arthritis.

Abstract: OBJECTIVES Calcitonin gene-related peptide alpha (αCGRP) represents an immunomodulatory neuropeptide implicated in pain perception. αCGRP also functions as a critical regulator of bone formation and is overexpressed in patients with rheumatoid arthritis (RA). In the present study, we investigated the role of αCGRP in experimental RA regarding joint inflammation and bone remodelling. METHODS Collagen II-antibody-induced arthritis (CAIA) was induced in wild type (WT) and αCGRP-deficient (αCGRP-/-) mice. Animals were monitored over 10 and 48 days with daily assessments of the semiquantitative arthritis score and grip strength test. Joint inflammation, cartilage degradation and bone erosions were assessed by histology, gene expression analysis and µCT. RESULTS CAIA was accompanied by an overexpression of αCGRP in WT joints. αCGRP-/- mice displayed reduced arthritic inflammation and cartilage degradation. Congruently, the expression of TNF-α, IL-1β, CD80 and MMP13 was induced in WT, but not αCGRP-/- animals. WT mice displayed an increased bone turnover during the acute inflammatory phase, which was not the case in αCGRP-/- mice. Interestingly, WT mice displayed a full recovery from the inflammatory bone disease, whereas αCGRP-/- mice exhibited substantial bone loss over time. CONCLUSION This study demonstrates a proinflammatory and bone protective role of αCGRP in CAIA. Our data indicate that αCGRP not only enhances joint inflammation, but also controls bone remodelling as part of arthritis resolution. As novel αCGRP inhibitors are currently introduced clinically for the treatment of migraine, their potential impact on RA progression warrants further clinical investigation.

Public Interest in Knee Pain and Knee Replacement during the SARS-CoV-2 Pandemic in Western Europe.

Abstract: Due to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic, a large number of elective knee replacement procedures had to be postponed in both early and late 2020 in most western countries including Germany and the UK. It is unknown how public interest and demand for total knee arthroplasties was affected. Public interest in knee pain, knee osteoarthritis and knee arthroplasty in Germany and the UK was investigated using Google Trend Analysis. In addition, we monitored for changes in patient composition in our outpatient department. As of early March in Germany and of late March in the UK, until the lockdown measures, a 50 to 60% decrease in relative search frequency was observed in all categories investigated compared to the beginning of the year. While public interest for knee pain rapidly recovered, decreased interest for knee osteoarthritis and replacement lasted until the easing of measures. Shortly prior to and during the first lockdown mean search frequency for knee replacement was significantly decreased from 39.7% and 36.6 to 26.9% in Germany and from 47.7% and 50.9 to 23.7% in the UK (Germany: p = 0.022 prior to lockdown, p < 0.001 during lockdown; UK: p < 0.0001 prior to and during lockdown). In contrast, mean search frequencies did not differ significantly from each other for any of the investigated time frames during the second half of 2020 in both countries. Similarly, during the first lockdown, the proportion of patients presenting themselves to receive primary knee arthroplasty compared to patients that had already undergone knee replacement declined markedly from 64.7% to 46.9%. In contrast, patient composition changed only marginally during the lockdown measures in late 2020 in both Germany and the UK. We observed a high level of public interest in knee arthroplasty despite the ongoing pandemic. The absence of a lasting decline in interest in primary knee arthroplasty suggests that sufficient symptom reduction cannot be achieved without surgical care for a substantial number of patients.

Scaffold-Dependent Mechanical and Architectural Cues Guide Osteochondral Defect Healing in silico

Abstract: Osteochondral defects in joints require surgical intervention to relieve pain and restore function. However, no current treatment enables a complete reconstitution of the articular surface. It is known that both mechanical and biological factors play a key role on osteochondral defect healing, however the underlying principles and how they can be used in the design of treatment strategies remain largely unknown. To unravel the underlying principles of mechanobiology in osteochondral defect healing, i.e., how mechanical stimuli can guide biological tissue formation, we employed a computational approach investigating the scaffold-associated mechanical and architectural properties that would enable a guided defect healing. A previous computer model of the knee joint was further developed to simulate healing of an empty osteochondral defect. Then, scaffolds were implanted in the defect and their architectures and material properties were systematically varied to identify their relevance in osteochondral defect healing. Scaffold mechanical and architectural properties were capable of influencing osteochondral defect healing. Specifically, scaffold material elastic modulus values in the range of cancellous bone (low GPa range) and a scaffold architecture that provided stability, i.e., resistance against displacement, in both the main loading direction and perpendicular to it supported the repair process. The here presented model, despite its simplifications, is regarded as a powerful tool to screen for promising properties of novel scaffold candidates fostering osteochondral defect regeneration prior to their implementation in vivo.

Retention of Posterior Cruciate Ligament Alone May Not Achieve Physiological Knee Joint Kinematics After Total Knee Arthroplasty: A Retrospective Study.

Abstract: Background The apparently physiological kinematics of the bicruciate-stabilized total knee arthroplasty (BCS TKA) systems have been attributed to the anterior and posterior post-cam mechanism. Although comparisons between TKA designs with either a retained or a sacrificed cruciate ligament have been conducted, we are not aware of any analyses of 2 implants with identical bearing geometry but different cruciate-ligament strategies under equal loading conditions. Knowledge about the kinematic effect of the different cruciate ligament strategies would potentially be valuable to facilitate preoperative planning and decision-making with regard to selecting the most appropriate implant for a patient. Methods This retrospective study included 20 patients: 10 treated with a BCS and 10 treated with a cruciate retaining (CR) TKA. Fluoroscopic analyses during high-flexion activities (unloaded flexion-extension and loaded lunge) were conducted at 24 months postsurgery. All patients completed the Knee Society Score, Forgotten Joint Score, and High-Flexion Knee Score questionnaires preoperatively and postoperatively. Results The BCS cohort showed greater femoral lateral rollback as well as a medial pivot in both activities. In contrast, the CR cohort showed a significant increase in anterior translation on the medial compartment as well as almost absent femoral lateral rollback. Higher clinical scores were observed in the BCS cohort. Conclusions At 24 months postsurgery, despite equal bearing geometry, retention of the posterior cruciate ligament in the CR cohort apparently was insufficient to reduce anterior shift. The BCS cohort showed expected knee joint kinematics; however, the kinematics in this cohort could eventually benefit from a smooth transition between the interchanging surfaces. Further investigation should be focused on the surgical technique and its interaction with the TKA design. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Prevention of Bone Destruction by Mechanical Loading Is Not Enhanced by the Bruton's Tyrosine Kinase Inhibitor CC-292 in Myeloma Bone Disease.

Abstract: Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton's tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD.

Bursa-Derived Cells Show a Distinct Mechano-Response to Physiological and Pathological Loading in vitro

Abstract: The mechano-response of highly loaded tissues such as bones or tendons is well investigated, but knowledge regarding the mechano-responsiveness of adjacent tissues such as the subacromial bursa is missing. For a better understanding of the physiological role of the bursa as a friction-reducing structure in the joint, the study aimed to analyze whether and how bursa-derived cells respond to physiological and pathological mechanical loading. This might help to overcome some of the controversies in the field regarding the role of the bursa in the development and healing of shoulder pathologies. Cells of six donors seeded on collagen-coated silicon dishes were stimulated over 3 days for 1 or 4 h with 1, 5, or 10% strain. Orientation of the actin cytoskeleton, YAP nuclear translocation, and activation of non-muscle myosin II (NMM-II) were evaluated for 4 h stimulations to get a deeper insight into mechano-transduction processes. To investigate the potential of bursa-derived cells to adapt their matrix formation and remodeling according to mechanical loading, outcome measures included cell viability, gene expression of extracellular matrix and remodeling markers, and protein secretions. The orientation angle of the actin cytoskeleton increased toward a more perpendicular direction with increased loading and lowest variations for the 5% loading group. With 10% tension load, cells were visibly stressed, indicated by loss in actin density and slightly reduced cell viability. A significantly increased YAP nuclear translocation occurred for the 1% loading group with a similar trend for the 5% group. NMM-II activation was weak for all stimulation conditions. On the gene expression level, only the expression of TIMP2 was down-regulated in the 1 h group compared to control. On the protein level, collagen type I and MMP2 increased with higher/longer straining, respectively, whereas TIMP1 secretion was reduced, resulting in an MMP/TIMP imbalance. In conclusion, this study documents for the first time a clear mechano-responsiveness in bursa-derived cells with activation of mechano-transduction pathways and thus hint to a physiological function of mechanical loading in bursa-derived cells. This study represents the basis for further investigations, which might lead to improved treatment options of subacromial bursa-related pathologies in the future.

Is initial interfragmentary compression made to last? An ovine bone in vitro study.

Abstract: Interfragmentary compression, a major principle of fracture treatment, is clinically not quantified and might be lost quickly even without functional loads. We designed an experimental study hypothesizing that (1) compression can be controlled using either lag screw or compression plate, and expecting similar initial compression, (2) loss of interfragmentary compression through relaxation within one hour is reduced with neutralization locking plate next to lag screw compared to compression plate. Twelve ovine femora (N=6) and humeri (N=6) were assigned into groups: Group 1 received a 45° oblique osteotomy at mid-diaphysis and was fixated using a 3.5 mm interfragmentary lag screw and locking compression plate (3.5 mm LCP, DePuy Synthes) as neutralization plate. Group 2 received a transverse osteotomy and was fixated with dynamic compression using compression plate (LCP). Interfragmentary pressure and relative bone fragment displacements were recorded over one hour. Median loss of compression over one hour time (relaxation) were 0.52% in Group 1, and 0.17% in Group 2 (p>0.05). Median rotational displacements amounted to 0.46° for Group 1, and 0.31° for Group 2, and axial displacement to a median of −20 μm in Group 1 and 25 μm in Group 2. Ovine bone interfragmentary stress relaxation maintains compression over the first hour for lag screw with neutralization plate for an oblique fracture line or compression plate for a transverse fracture line. Measured compression forces around 100 N could be overcome by physiological tension loading in bending or torsion, necessitating for instance tension band plating, additional lag screws or absolutive stability.

A Higher Initial Tensioning Force of an ACL Graft Results in a Higher Graft Force After Screw Fixation Irrespective of the Screw Diameter: A Biomechanical Study.

Abstract: BACKGROUND The intra-articular graft force (IAGF) in anterior cruciate ligament reconstruction decreases quickly over the first hours after surgery. Nevertheless, little is known about whether the initial extra-articular tensioning force (EATF) and screw diameter affect the graft force after fixation. PURPOSE To investigate the effects of different EATFs on the IAGF of a soft tissue graft fixated via a bioabsorbable interference screw over 100 minutes after fixation and to evaluate the effects of different screw diameters within 1 mm of the tunnel width during this process. STUDY DESIGN Controlled laboratory study. METHODS In this biomechanical study, a porcine quadruple-strand soft tissue graft was inserted into the tibial anterior cruciate ligament tunnel. On the extra-articular side, 3 loads were applied during retrograde insertion of the bioabsorbable interference screw (6, 7, and 8 mm): 20 N, 80 N, and maximum manual EATF (Nmax). Nine study groups consisting of 10 tibiae each were created to test the effects of different EATFs and screw sizes. The IAGF was measured up to 100 minutes after the EATF was released. RESULTS An EATF ≥80 N resulted in a larger IAGF for all screw sizes at 100 minutes. There were no significant associations between the IAGF at 100 minutes and different screw diameters. Inserting the tibial screw significantly increased the IAGF in all groups, with the exception of Nmax applied in groups with 7- or 8-mm screws. When compared with the end of screw insertion, after the release of the EATF, the IAGF dropped by 55% to 77 % at 100 minutes. CONCLUSION An initial EATF ≥80 N is associated with a significantly larger IAGF at 100 minutes in this cadaveric simulation. The IAGF in soft tissue grafts decreased substantially after the retrograde placement of an interference screw. A recommendation regarding screw diameter with respect to the IAGF cannot be given. CLINICAL RELEVANCE To obtain a higher residual graft force after bioabsorbable interference screw fixation, an initial EATF ≥80 N should be applied according to this model. The significant decrease in graft force after the release of the EATF indicates that the reconstructed knee cannot be mechanically stabilized after the surgery.

Gait Adaptations at 8 Years After Reconstruction of Unilateral Isolated and Combined Posterior Cruciate Ligament Injuries.

Abstract: Background:It remains unclear how posterior cruciate ligament (PCL) reconstruction influences long-term lower extremity joint biomechanics.Purpose:To determine whether patients who underwent PCL re...

Dynamic Knee Joint Line Orientation Is Not Predictive of Tibio-Femoral Load Distribution During Walking.

Abstract: Some approaches in total knee arthroplasty aim for an oblique joint line to achieve an even medio-lateral load distribution across the condyles during the stance phase of gait. While there is much focus on the angulation of the joint line in static frontal radiographs, precise knowledge of the associated dynamic joint line orientation and the internal joint loading is limited. The aim of this study was to analyze how static alignment in frontal radiographs relates to dynamic alignment and load distribution, based on direct measurements of the internal joint loading and kinematics. A unique and novel combination of telemetrically measured in vivo knee joint loading and simultaneous internal joint kinematics derived from mobile fluoroscopy ("CAMS-Knee dataset") was employed to access the dynamic alignment and internal joint loading in 6 TKA patients during level walking. Static alignment was measured in standard frontal postoperative radiographs while external adduction moments were computed based on ground reaction forces. Both static and dynamic parameters were analyzed to identify correlations using linear and non-linear regression. At peak loading during gait, the joint line was tilted laterally by 4°-7° compared to the static joint line in most patients. This dynamic joint line tilt did not show a strong correlation with the medial force (R 2: 0.17) or with the mediolateral force distribution (pseudo R 2: 0.19). However, the external adduction moment showed a strong correlation with the medial force (R 2: 0.85) and with the mediolateral force distribution (pseudo R 2: 0.78). Alignment measured in static radiographs has only limited predictive power for dynamic kinematics and loading, and even the dynamic orientation of the joint line is not an important factor for the medio-lateral knee load distribution. Preventive and rehabilitative measures should focus on the external knee adduction moment based on the vertical and horizontal components of the ground reaction forces.

Quantification of morning stiffness to assess disease activity and treatment effects in rheumatoid arthritis.

Abstract: Objectives The clinical parameter “morning stiffness” is widely used to assess the status of rheumatoid arthritis (RA), but its accurate quantitative assessment in a clinical setting has not yet been successful. This lack of individual quantification limits both personalized medication and efficacy evaluation in the treatment of RA. Methods We have developed a novel technology to assess passive resistance of the metacarpophalangeal (MCP) III joint (stiffness) and its Passive Range of Motion (PRoM). Within this pilot study, nineteen female postmenopausal RA patients and nine healthy controls were examined in the evening as well as in the morning of the following day. To verify the specificity of the biomechanical quantification, eleven patients with RA were assessed both prior to and ∼3 h after glucocorticoid therapy. Results While the healthy controls showed only minor changes between afternoon and morning, in RA patients mean±SD PRoM decreased significantly by 18 ± 22% and stiffness increased significantly by 20 ± 18% in the morning compared with the previous afternoon. We found a significant positive correlation between RA activity and biomechanical measures. Glucocorticoids significantly increased mean PRoM by 16 ± 11% and reduced mean stiffness by 23 ± 22%. Conclusion This technology allowed mechanical stiffness to be quantified in MCP joints, and has demonstrated high sensitivity in respect to disease status as well as medication effect in RA patients. Such non-invasive, low risk, and rapid assessment of biomechanical joint stiffness opens a novel avenue for judging therapy efficacy in patients with RA, and potentially also in other non-RA inflammatory joint diseases.

Mice Lacking the Calcitonin Receptor Do Not Display Improved Bone Healing.

Abstract: Despite significant advances in surgical techniques, treatment options for impaired bone healing are still limited. Inadequate bone regeneration is not only associated with pain, prolonged immobilization and often multiple revision surgeries, but also with high socioeconomic costs, underlining the importance of a detailed understanding of the bone healing process. In this regard, we previously showed that mice lacking the calcitonin receptor (CTR) display increased bone formation mediated through the increased osteoclastic secretion of sphingosine-1-phosphate (S1P), an osteoanabolic molecule promoting osteoblast function. Although strong evidence is now available for the crucial role of osteoclast-to-osteoblast coupling in normal bone hemostasis, the relevance of this paracrine crosstalk during bone regeneration is unknown. Therefore, our study was designed to test whether increased osteoclast-to-osteoblast coupling, as observed in CTR-deficient mice, may positively affect bone repair. In a standardized femoral osteotomy model, global CTR-deficient mice displayed no alteration in radiologic callus parameters. Likewise, static histomorphometry demonstrated moderate impairment of callus microstructure and normal osseous bridging of osteotomy ends. In conclusion, bone regeneration is not accelerated in CTR-deficient mice, and contrary to its osteoanabolic action in normal bone turnover, osteoclast-to-osteoblast coupling specifically involving the CTR-S1P axis, may only be of minor relevance during bone healing.

Patient-specific resurfacing implant knee surgery in subjects with early osteoarthritis results in medial pivot and lateral femoral rollback during flexion: a retrospective pilot study

Abstract: Metallic resurfacing implants have been developed for the treatment of early, small, condylar and trochlear osteoarthritis (OA) lesions. They represent an option for patients who do not fulfill the criteria for unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA) or are too old for biological treatment. Although clinical evidence has been collected for different resurfacing types, the in vivo post-operative knee kinematics remain unknown. The present study aims to analyze the knee kinematics in subjects with patient-specific episealer implants. This study hypothesized that patient-specific resurfacing implants would lead to knee kinematics close to healthy knees, resulting in medial pivot and a high degree of femoral rollback during flexion. Retrospective study design. Fluoroscopic analysis during unloaded flexion–extension and loaded lunge was conducted at > 12 months post-surgery in ten episealer knees, and compared to ten healthy knees. Pre- and post-operative clinical data of the episealer knees were collected using a visual analog scale (VAS), the EQ 5d Health, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaires. A consistent medial pivot was observed in both episealer and healthy knees. Non-significant differences were found in the unloaded (p = 0.15) and loaded (p = 0.51) activities. Although lateral rollback was observed in both groups, it was significantly higher for the episealer knees in both the unloaded (p = 0.02) and loaded (p = 0.01) activities. Coupled axial rotation was significantly higher in the unloaded (p = 0.001) but not in the loaded (p = 0.06) activity in the episealer knees. Improved scores were observed at 1-year post-surgery in the episealer subjects for the VAS (p = 0.001), KOOS (p = 0.001) and EQ Health (p = 0.004). At 12 month follow-up, a clear physiological knee kinematics pattern of medial pivot, lateral femoral rollback and coupled axial external femoral rotation during flexion was observed in patients treated with an episealer resurfacing procedure. However, higher femoral rollback and axial external rotation in comparison to healthy knees was observed, suggesting possible post-operative muscle weakness and consequent insufficient stabilization at high flexion.

Was macht eine gute Osteosynthese aus

Abstract: Was macht eine „gute Osteosynthese“ aus? Obwohl die Frage trivial erscheint, ergeben sich bei genauerer Betrachtung doch mannigfaltige Faktoren, welche einen Einfluss auf die Frakturheilung haben, sodass sie sich letztendlich doch nicht so einfach beantworten lasst. Bereits bei der Anamnese und initialen Diagnostik werden die ersten Weichen gestellt. Eine adaquate Analyse der Fraktur mit einem schlussigen praoperativen Konzept zur Stabilisierung unter den wissenschaftlich aktuellsten Erkenntnissen und eine nachfolgend adaquate Umsetzung der Planung im Operationssaal machen den Erfolg einer Osteosynthese und damit die „gute Osteosynthese“ aus. Dabei spielen digitale Unterstutzungen eine immer wesentlichere Rolle. Diese Ubersichtsarbeit setzt sich intensiv mit dem Thema auseinander und fasst die wichtigsten Elemente der notwendigen Kaskade zusammen.