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Bisphosphonates (BP) are considered a treatment option for osteoarthritis (OA) due to reduction of OA-induced microtrauma in the bone marrow, stabilization of subchondral bone (SB) layer and pain reduction. The effects of high-dose alendronate (ALN) treatment on SB and articular cartilage after destabilization of the medial meniscus (DMM) or Sham surgery of male C57Bl/6J mice were analyzed. We performed serum analysis; histology and immunohistochemistry to assess the severity of OA and a possible pain symptomatology. Subsequently, the ratio of bone volume to total volume (BV/TV), epiphyseal trabecular morphology and the bone mineral density (BMD) was analyzed by nanoCT. Serum analysis revealed a reduction of ADAMTS5 level. The histological evaluation displayed no protective effect of ALN-treatment on cartilage erosion. NanoCT-analysis of the medial epiphysis revealed an increase of BV/TV in ALN-treated mice. Only the DMM group had significantly higher SB volume accompanied by decreased subchondral bone surface. Furthermore Nano-CT analysis revealed an increase in trabecular density and number, a decreased BMD and reduced osteophyte formation in the ALN mice. ALN treatment affected bone micro-architecture by reducing osteophytosis with simultaneous increasing subchondral bone plate thickness, trabecular thickness and BMD. Accordingly, ALN cannot be considered as a potential treatment strategy in general, however in a subgroup of patients with high bone turnover in an early-stage of OA, ALN might be an option when applied during a restricted time frame., (© 2024. The Author(s).)

The clinical need for bone adhesives as an alternative to osteosynthesis is evident. However, this is a challenging problem due to the moist environment in surgical sites with bone surfaces covered with blood and biomolecules like lipids or proteins. A nanoparticle-loaded hydrogel that is based on a freeze-dried powder of silica-coated calcium phosphate/carboxymethyl cellulose nanoparticles (CaP/CMC/SiO 2 ) and an aqueous solution of sodium alginate (2 wt%) was developed and optimized with respect to the gluing ability in air and in water. The final paste was crosslinked within about one minute by calcium ions released from the calcium phosphate nanoparticles and contained about 20 wt% nanoparticles and 80 wt% water. The mechanical properties of the hydrogel were determined by extensive rheological tests. The thixotropic pasty hydrogel can be applied with a syringe. The adhesion strength was about 84 kPa between moist bone fragments in air. The hydrogel kept fragments of cortical bone well connected for >3 months during complete submersion in water. Besides water, the material consists only of biocompatible and biodegradable components (calcium phosphate, CMC, alginate). It carries only a very low dose of these materials into the bone site (mainly calcium phosphate nanoparticles). In-vitro cell culture with hMSCs that differentiated to osteoblasts confirmed a good biocompatibility of the bone adhesive formulation., (© 2024. The Author(s).)

Background: Gotfried positive reduction offers an alternative strategy for femoral neck fracture (FNF) when achieving anatomical reduction is challenging. However, the biomechanical consequences of positive reduction remain unclear. The purpose of this study was to investigate the biomechanical behavior of positive reduction across different Pauwels classification, providing a reference for quantifying positive reduction in clinical practice., Methods: Three-dimensional (3D) models of FNF were established and categorized according to the Pauwels classifications (Pauwels I, II, and III), each of them contained seven models with different reduction qualities, including an anatomical reduction model, two negative reduction models, and four positive reduction models, all of which were stabilized with dynamic hip screws (DHS) and cannulated screws (CS). We investigated the maximal von-Mises stress of internal fixation and proximal femoral, femoral fragment displacement, and maximal von-Mises strain at the proximal fragment fracture site when a 2100 N load was applied to the femoral head., Results: The maximum von-Mises stress on the internal fixators in each Pauwels group was lowest in the anatomical reduction model. In the Pauwels I group, positive reduction exceeding 3 mm resulted in the maximum von-Mises stress on the internal fixators surpassing that of the negative reduction model. For the Pauwels II group, positive reduction beyond 2 mm led to the maximum von-Mises stress on the internal fixators exceeding that of the negative reduction model. In the Pauwels III group, positive reduction beyond 1 mm caused the maximum von-Mises stress on the internal fixators to be higher than that of the negative reduction model. The maximum von-Mises strain at the fracture site of proximal femur fragment increased with positive reduction. Varus displacement increased in positive reduction models as the Pauwels angle rose, potentially exacerbating rotation deformity in Pauwels III group., Conclusion: Excessive positive reduction may increase the risk of FNF failure after internal fixation. From a biomechanical stability perspective, positive reduction should be limited to 3 mm or below in the Pauwels I group, restricted to not exceed 2 mm in the Pauwels II group, and should not exceed 1 mm in the Pauwels III group. Negative reduction should be avoided in all Pauwels groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Li, Böker, Schilling and Lehmann.)

Introduction: The scapholunate interosseous ligament is pivotal for wrist stability, and its impairment can result in instability and joint degeneration. This study explores the application of real-time MRI for dynamic assessment of the scapholunate joint during wrist motion with the objective of determining its diagnostic value in efficacy in contrast to static imaging modalities., Materials and Methods: Ten healthy participants underwent real-time MRI scans during wrist ab/adduction and fist-clenching maneuvers. Measurements were obtained at proximal, medial, and distal landmarks on both dynamic and static images with statistical analyses conducted to evaluate the reliability of measurements at each landmark and the concordance between dynamic measurements and established static images. Additionally, inter- and intraobserver variabilities were evaluated., Results: Measurements of the medial landmarks demonstrated the closest agreement with static images and exhibited the least scatter. Distal landmark measurements showed a similar level of agreement but with increased scatter. Proximal landmark measurements displayed substantial deviation, which was accompanied by an even greater degree of scatter. Although no significant differences were observed between the ab/adduction and fist-clenching maneuvers, both inter- and intraobserver variabilities were significant across all measurements., Conclusions: This study highlights the potential of real-time MRI in the dynamic assessment of the scapholunate joint particularly at the medial landmark. Despite promising results, challenges such as measurement variability need to be addressed. Standardization and integration with advanced image processing methods could significantly enhance the accuracy and reliability of real-time MRI, paving the way for its clinical implementation in dynamic wrist imaging studies.

Biofunctionalized hydrogels are widely used in tissue engineering for bone repair. This study examines the bone regenerative effect of the blood-derived growth factor preparation of Hypoxia Preconditioned Serum (HPS) and its fibrin-hydrogel formulation (HPS-F) on drilled defects in embryonic day 19 chick femurs. Measurements of bone-related growth factors in HPS reveal significant elevations of Osteopontin, Osteoprotegerin, and soluble-RANKL compared with normal serum (NS) but no detection of BMP-2/7 or Osteocalcin. Growth factor releases from HPS-F are measurable for at least 7 days. Culturing drilled femurs organotypically on a liquid/gas interface with HPS media supplementation for 10 days demonstrates a 34.6% increase in bone volume and a 52.02% increase in bone mineral density (BMD) within the defect area, which are significantly higher than NS and a basal-media-control, as determined by microcomputed tomography. HPS-F-injected femur defects implanted on a chorioallantoic membrane (CAM) for 7 days exhibit an increase in bone mass of 123.5% and an increase in BMD of 215.2%, which are significantly higher than normal-serum-fibrin (NS-F) and no treatment. Histology reveals calcification, proteoglycan, and collagen fiber deposition in the defect area of HPS-F-treated femurs. Therefore, HPS-F may offer a promising and accessible therapeutic approach to accelerating bone regeneration by a single injection into the bone defect site.

The high prevalence of sarcopenia in an aging population has an underestimated impact on quality of life by increasing the risk of falls and subsequent hospitalization. Unfortunately, the application of the major established key therapeutic-physical activity-is challenging in the immobile and injured sarcopenic patient. Consequently, novel therapeutic directions are needed. The transcription factor Forkhead-Box-Protein O3 (FOXO3) may be an option, as it and its targets have been observed to be more highly expressed in sarcopenic muscle. In such catabolic situations, Foxo3 induces the expression of two muscle specific ubiquitin ligases ( Atrogin-1 and Murf-1 ) via the PI3K/AKT pathway. In this review, we particularly evaluate the potential of Foxo3 -targeted gene therapy. Foxo3 knockdown has been shown to lead to increased muscle cross sectional area, through both the AKT-dependent and -independent pathways and the reduced impact on the two major downstream targets Atrogin-1 and Murf-1 . Moreover, a Foxo3 reduction suppresses apoptosis, activates satellite cells, and initiates their differentiation into muscle cells. While this indicates a critical role in muscle regeneration, this mechanism might exhaust the stem cell pool, limiting its clinical applicability. As systemic Foxo3 knockdown has also been associated with risks of inflammation and cancer progression, a muscle-specific approach would be necessary. In this review, we summarize the current knowledge on Foxo3 and conceptualize a specific and targeted therapy that may circumvent the drawbacks of systemic Foxo3 knockdown. This approach presumably would limit the side effects and enable an activity-independent positive impact on skeletal muscle.

Adding robotic surgery to bionic reconstruction might open a new dimension. The objective was to evaluate if a robotically harvested rectus abdominis (RA) transplant is a feasible procedure to improve soft-tissue coverage at the residual limb (RL) and serve as a recipient for up to three nerves due to its unique architecture and to allow the generation of additional signals for advanced myoelectric prosthesis control. A transradial amputee with insufficient soft-tissue coverage and painful neuromas underwent the interventions and was observed for 18 months. RA muscle was harvested using robotic-assisted surgery and transplanted to the RL, followed by end-to-end neurroraphy to the recipient nerves of the three muscle segments to reanimate radial, median, and ulnar nerve function. The transplanted muscle healed with partial necrosis of the skin mesh graft. Twelve months later, reliable, and spatially well-defined Hoffmann-Tinel signs were detectable at three segments of the RA muscle flap. No donor-site morbidities were present, and EMG activity could be detected in all three muscle segments. The linear discriminant analysis (LDA) classifier could reliably distinguish three classes within 1% error tolerance using only the three electrodes on the muscle transplant and up to five classes outside the muscle transplant. The combination of these surgical procedure advances with emerging (myo-)control technologies can easily be extended to different amputation levels to reduce RL complications and augment control sites with a limited surface area, thus facilitating the usability of advanced myoelectric prostheses.

Hard-tissue histology-the analysis of thin two-dimensional (2D) sections-is hampered by the opaque nature of most biological specimens, especially bone. Therefore, the cutting process cannot be assigned to regions of interest. In addition, the applied cutting-grinding method is characterized by significant material loss. As a result, relevant structures might be missed or destroyed, and 3D features can hardly be evaluated. Here, we present a novel workflow, based on conventual microCT scans of the specimen prior to the cutting process, to be used for the analysis of 3D structural features and for directing the sectioning process to the regions of interest. 3D printed fiducial markers, embedded together with the specimen in resin, are utilized to retrospectively register the obtained 2D histological images into the 3D anatomical context. This not only allows to identify the cutting position, but also enables the co-registration of the cell and extracellular matrix morphological analysis to local 3D information obtained from the microCT data. We have successfully applied our new approach to assess hard-tissue specimens of different species. After matching the predicted microCT cut plane with the histology image, we validated a high accuracy of the registration process by computing quality measures namely Jaccard and Dice similarity coefficients achieving an average score of 0.90 ± 0.04 and 0.95 ± 0.02, respectively. Thus, we believe that the novel, easy to implement correlative imaging approach holds great potential for improving the reliability and diagnostic power of classical hard-tissue histology., (© 2023. The Author(s).)