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Background: Aseptic nonunion of femoral shafts after intramedullary nailing (IMN) can be a challenging condition that may lead to long-term disability and the need for multiple surgical procedures. This study compared the clinical and radiological outcomes between exchange nailing and augmentative plating with bone grafting. Methods: In this multicenter, prospective, single-blind, randomized controlled trial, patients with aseptic nonunion of the femoral shaft after IMN were randomly assigned to receive exchange nailing or augmentative plating. The primary outcomes measured were the time to bone union and union rate 12 months after revision surgery. The secondary outcomes included operative time, blood loss, hospitalization duration, pain level using the visual analog scale (VAS), knee range of motion (ROM), and complication rates. Results: The augmentative plating group had a significantly shorter mean time to union (5.39 ± 1.29 months) compared with the exchange nailing group (7.38 ± 1.97 months; p < 0.001). The union rates at 12 months were 100% in the augmentative plating group and 89.65% in the exchange nail group. Augmentative plating resulted in a shorter operation time (99.46 ± 11.08 min vs. 106.45 ± 12.22 min; p = 0.025) and reduced blood loss (514.79 ± 45.87 mL vs. 547.72 ± 54.35 mL; p = 0.016). Significant pain reduction was observed in the augmentative plating group, with preoperative VAS scores decreasing from 6.04 ± 2.28 to 2.64 ± 1.50, compared with a decrease from 5.66 ± 2.21 to 3.66 ± 2.19 in the exchange nailing group (p = 0.047). Knee ROM improved significantly in the augmentative plating group (p = 0.0176). The complication rate was lower in the augmentative plating group (3.57%) than in the exchange nail group (17.24%). Conclusions: Augmentative plating with autologous bone grafting is superior to exchange nailing for treating aseptic nonunion of femoral shafts. It is associated with faster healing, higher union rates, better clinical and functional outcomes, and fewer complications. We recommend this technique as the preferred treatment option for such complex cases. [ABSTRACT FROM AUTHOR]

Inflammation has been recognized as major factor for successful bone regeneration. On the other hand, a prolonged or overshooting inflammatory response can also cause fracture healing failure. The nucleotide-binding oligomerization domain (NOD)-like receptor protein (NLRP)3 inflammasome plays a crucial role in inflammatory cytokine production. However, its role during fracture repair remains elusive. We investigated the effects of Nlrp3 deficiency on the healing of closed femoral fractures in Nlrp3−/− and wildtype mice. The callus tissue was analyzed by means of X-ray, biomechanics, µCT and histology, as well as immunohistochemistry and Western blotting at 2 and 5 weeks after surgery. We found a significantly reduced trabecular thickness at 2 weeks after fracture in the Nlrp3−/− mice when compared to the wildtype animals. However, the amount of bone tissue did not differ between the two groups. Additional immunohistochemical analyses showed a reduced number of CD68-positive macrophages within the callus tissue of the Nlrp3−/− mice at 2 weeks after fracture, whereas the number of myeloperoxidase (MPO)-positive granulocytes was increased. Moreover, we detected a significantly lower expression of vascular endothelial growth factor (VEGF) and a reduced number of microvessels in the Nlrp3−/− mice. The expression of the absent in melanoma (AIM)2 inflammasome was increased more than 2-fold in the Nlrp3−/− mice, whereas the expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 was not affected. Our results demonstrate that Nlrp3 deficiency does not markedly affect femoral fracture healing in mice. This is most likely due to the unaltered expression of pro-inflammatory cytokines and pro-osteogenic growth factors. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the osteogenic potential of mesenchymal stromal cell (MSC) spheroids combined with the basic fibroblast growth factor (bFGF) in a mouse femur fracture model. To begin, MSC spheroids were generated, and the expression of key trophic factors (bFGF Bmp2, and Vegfa) was assessed using quantitative PCR (qPCR). A binding assay confirmed the interaction between the bFGF and the spheroids' extracellular matrix. The spheroid cultures significantly upregulated bFGF, Bmp2, and Vegfa expression compared to the monolayers (p < 0.001), and the binding assay demonstrated effective bFGF binding to the MSC spheroids. Following these in vitro assessments, the mice were divided into five groups for the in vivo study: (1) no treatment (control), (2) spheroids alone, (3) bFGF alone, (4) bFGF-loaded spheroids (bFGF-spheroids), and (5) non-viable (frozen) bFGF-loaded spheroids (bFGF-dSpheroids). Bone formation was analyzed by a micro-CT, measuring the bone volume (BV) and bone mineral content (BMC) of the mice four weeks post-fracture. A high dose of the bFGF (10 µg) significantly promoted bone formation regardless of the presence of spheroids, as evidenced by the increases in BV (bFGF, p = 0.010; bFGF-spheroids, p = 0.006; bFGF-dSpheroids, p = 0.032) and BMC (bFGF, p = 0.023; bFGF-spheroids, p = 0.004; bFGF-dSpheroids, p = 0.014), compared to the controls. In contrast, a low dose of the bFGF (1 µg) combined with the MSC spheroids significantly increased BV and BMC compared to the control (BV, p = 0.012; BMC, p = 0.015), bFGF alone (BV, p = 0.012; BMC, p = 0.008), and spheroid (BV, p < 0.001; BMC, p < 0.001) groups. A low dose of the bFGF alone did not significantly promote bone formation (p > 0.05). The non-viable (frozen) spheroids loaded with a low dose of the bFGF resulted in a higher BV and BMC compared to the spheroids alone (BV, p = 0.003; BMC, p = 0.017), though the effect was less pronounced than in the viable spheroids. These findings demonstrate the synergistic effect of the bFGF and MSC spheroids on bone regeneration. The increased expression of the BMP-2 and VEGF observed in the initial experiments, coupled with the enhanced bone formation in vivo, highlight the therapeutic potential of this combination. Future studies will aim to elucidate the underlying molecular mechanisms and assess the long-term outcomes for bone repair strategies. [ABSTRACT FROM AUTHOR]

Fracture-related infection (FRI) is a devastating event, directly affecting fracture healing, impairing patient function, prolonging treatment, and increasing healthcare costs. Time plays a decisive role in prognosis, as biofilm maturation leads to the development of antibiotic resistance, potentially contributing to infection chronicity and increasing morbidity and mortality. Research exploring the association between biofilm maturation and antibiotic resistance in orthopaedics primarily addresses aspects related to quality of life and physical function; however, little exists on life-threatening conditions and mortality. Understanding the intrinsic relationship between biofilm maturation, bacterial resistance, and mortality is critical in all fields of medicine. In the herein narrative review, we summarize recent evidence regarding biofilm formation, antibiotic resistance, and infection chronicity (BARI), the three basic components of the "triangle of death" of FRI, and its implications. Preoperative, perioperative, and postoperative prevention strategies to avoid the "triangle of death" of FRI are presented and discussed. Additionally, the importance of the orthopaedic trauma surgeon in understanding new tools to combat infections related to orthopaedic devices is highlighted. [ABSTRACT FROM AUTHOR]

Background: Electromagnetic field therapy is gaining attention for its potential in treating bone disorders, with Extracorporeal Magnetotransduction Therapy (EMTT) emerging as an innovative approach. EMTT offers a higher oscillation frequency and magnetic field strength compared to traditional Pulsed Electromagnetic Field (PEMF) therapy, showing promise in enhancing fracture healing and non-union recovery. However, the mechanisms underlying these effects remain unclear. Results: This study demonstrates that EMTT significantly enhances osteoblast bone formation at multiple levels, from gene expression to extracellular matrix mineralization. Key osteoblastogenesis regulators, including SP7 and RUNX2, and bone-related genes such as COL1A1, ALPL, and BGLAP, were upregulated, with expression levels surpassing those of the control group by over sevenfold (p < 0.001). Enhanced collagen synthesis and mineralization were confirmed by von Kossa and Alizarin Red staining, indicating increased calcium and phosphate deposition. Additionally, calcium imaging revealed heightened calcium influx, suggesting a cellular mechanism for EMTT's osteogenic effects. Importantly, EMTT did not compromise cell viability, as confirmed by live/dead staining and WST-1 assays. Conclusion: This study is the first to show that EMTT can enhance all phases of osteoblastogenesis and improve the production of critical mineralization components, offering potential clinical applications in accelerating fracture healing, treating osteonecrosis, and enhancing implant osseointegration. [ABSTRACT FROM AUTHOR]

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration and quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of the NewClip narrow locking plate system with early weight-bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with the NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation. Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and a final follow-up at twelve months revealed complete osseous healing without complications. Conclusions: The use of this type of plate in treating isolated fibular fractures with early weight-bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes, warranting further investigation with larger cohorts. [ABSTRACT FROM AUTHOR]

This document discusses the importance of developing engineering technologies to prevent musculoskeletal injuries and improve treatment and rehabilitation strategies. It highlights recent advancements in implant design, surgical techniques, rehabilitation protocols, and injury prevention technologies. The document also introduces a special issue of Bioengineering dedicated to advanced engineering technologies in orthopedic research, featuring eight papers on topics such as posture control in the elderly, artificial intelligence preoperative planning, shape memory implants for osteoporotic fractures, in vitro joint testing systems, pedicle screw performance, knee arthroplasty designs, gait analysis for fracture healing, and shoulder arthrometry. The papers aim to improve the prevention of injuries, enhance implant compatibility, optimize post-operative function, and provide innovative diagnostic and therapeutic technologies for musculoskeletal diseases. [Extracted from the article]

Introduction: Sacral fractures are rare but are increasing in incidence among trauma patients. They are associated with a wide variety of complications, most commonly neurologic defects. Case Report: A 59-year old woman initially underwent open reduction internal fixation (ORIF) for a sacral fracture, after which the patient developed an infection, wound complications, and hardware failure. The revision of the iliosacral screws proved challenging in that the standard screw and washer could not achieve sufficient compression of the fracture. Therefore, a modified midfoot mesh plate was cut to size and used as a washer to gain more surface area, achieving fixation. The plate was applied laterally and cut to cover as much surface area as possible without unnecessary bony overhang. A trans-iliac trans-sacral screw was then inserted in the standard fashion, thus allowing the plate to act as a washer. This resulted in an excellent outcome with appropriate fracture healing. Conclusion: We describe the case of an iliosacral screw revision in which a modified midfoot mesh plate was used as a washer. This resulted in appropriate fixation in the revision settings. The principles described to achieve this fixation can be broadly applied in the setting of orthopedic fractures. [ABSTRACT FROM AUTHOR]

Proximal humerus fractures (PHFs) are among the most common upper-extremity fractures, with a rising incidence linked to the growing elderly population. Treatment options include non-surgical and surgical methods, but the best approach for geriatric PHFs remains debated. Patient selection for treatment must consider clinical and functional outcomes and the potential complications of surgery. Osteoporosis, a key factor in elderly PHFs, meaning those in patients over 65 years old, often results from low-energy trauma and necessitates treatments that enhance bone healing. Bone cement, such as calcium phosphate, is widely used to improve fracture stability and healing. However, the benefits of surgical fixation with bone cement augmentation (BCA) for elderly PHF patients remain controversial. Hence, in this article, we searched databases including MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science to analyze the evidence on locking plate fixation (LPF) with BCA for proximal humeral fractures. We aim to provide readers with updates concerning the above issues. [ABSTRACT FROM AUTHOR]

Microwave (MW) sensing is regarded as a promising technique for various medical monitoring and diagnostic applications due to its numerous advantages and the potential to be developed into a portable device for use outside hospital settings. The detection of skull fractures and the monitoring of their healing process would greatly benefit from a rapidly and frequently usable application that can be employed outside the hospital. This paper presents a simulation- and experiment-based study on skull fracture detection with the MW technique using realistic models for the first time. It also presents assessments on the most promising frequency ranges for skull fracture detection within the Industrial, Scientific and Medical (ISM) and ultrawideband (UWB) ranges. Evaluations are carried out with electromagnetic simulations using different head tissue layer models corresponding to different locations in the human head, as well as an anatomically realistic human head simulation model. The measurements are conducted with a real human skull combined with tissue phantoms developed in our laboratory. The comprehensive evaluations show that fractures cause clear differences in antenna and channel parameters (S11 and S21). The difference in S11 is 0.1–20 dB and in S21 is 0.1–30 dB, depending on the fracture width and location. Skull fractures with a less than 1 mm width can be detected with microwaves at different fracture locations. The detectability is frequency dependent. Power flow representations illustrate how fractures impact on the signal propagation at different frequencies. MW-based detection of skull fractures provides the possibility to (1) detect fractures using a safe and low-cost portable device, (2) monitor the healing-process of fractures, and (3) bring essential information for emerging portable MW-based diagnostic applications that can detect, e.g., strokes. [ABSTRACT FROM AUTHOR]

Lower extremity fractures pose challenges due to prolonged healing times and limited assessment methods. Integrating wearable sensors with machine learning can help overcome these challenges by providing objective assessment and predicting fracture healing. In this retrospective study, data from a gait monitoring insole on 25 patients with closed lower extremity fractures were analyzed. Continuous underfoot loading data were processed to isolate steps, extract metrics, and feed them into three white-box machine learning models. Decision tree and Lasso regression aided feature selection, while a logistic regression classifier predicted days until fracture healing within a 30-day range. Evaluations via 10-fold cross-validation and leave-one-out validation yielded stable metrics, with the model achieving a mean accuracy, precision, recall, and F1-score of approximately 76%. Feature selection revealed the importance of underfoot loading distribution patterns, particularly on the medial surface. Our research facilitates data-driven decisions, enabling early complication detection, potentially shortening recovery times, and offering accurate rehabilitation timeline predictions. [ABSTRACT FROM AUTHOR]

Background: The surgical treatment of bony non-unions is traditionally performed with additional bone grafts when atrophic and/or stronger implants when hypertrophic. In the case of the clavicle shaft, however, in our experience, a more controversial method where no additional bone graft is needed leads to equally good consolidation rates, independent of the non-union morphology. This method requires the meticulous anatomical reconstruction of the initial fracture and fixation according to the AO principle of relative stability. Methods: A retrospective review following the STROBE guidelines was performed on a consecutive cohort of all patients who received surgical treatment of a midshaft clavicle non-union at the Medical Center of the University of Freiburg between January 2003 and December 2023. Patients were identified using a retrospective systematical query in the Hospital Information System (HIS) using the International Statistical Classification of Diseases and Related Health Problems Version 10 (ICD-10) codes of the German Diagnosis Related Groups (G-DRG). Two groups were formed to compare the consolidation rates of patients who received additional bone grafting from the iliac crest with those of patients who did not. A 3.5 mm reconstruction LCP plate was used in all patients. Consolidation rates were evaluated using follow-up radiographs and outcomes after material removal with a mean follow-up of 31.5 ± 44.3 months (range 0–196). Results: Final data included 50 patients, predominantly male (29:21); age: 46.0 ± 13.0 years, BMI 26.1 ± 3.7. Autologous bone grafts from the iliac crest were used in 38.0% (n = 19), while no bone addition was used in 62.0% (n = 30). Six patients were lost to follow-up. Radiological consolidation was documented after a mean of 15.1 ± 8.0 months for the remaining 44 patients. Consolidation rates were 94.4% (n = 17) in patients for whom additional bone grafting was used and 96.2% (n = 25) in patients for whom no graft was used. There was no relevant difference in the percentage of atrophic or hypertrophic non-unions between both groups (p = 0.2425). Differences between groups in the rate of consolidation were not significant (p = 0.7890). The complication rate was low, with 4.5% (n = 2). Conclusions: Independent of the non-union morphology, non-unions of the clavicle midshaft can be treated successfully with 3.5 mm locking reconstruction plates without the use of additional bone grafting in most cases. [ABSTRACT FROM AUTHOR]

Recent pressure on scientists and industries to use renewable resources, as well as the need to produce environmentally friendly materials, has led researchers and manufacturers to use natural fibres as possible reinforcements for their composites. Although they seem to be "ideal" due to their low cost, light weight and interesting energy absorption properties, they cannot be compared to synthetic fibres. To solve this problem, hybridization techniques can be considered, since the combination of synthetic and natural fibres allows for good performances. The aim of this study was to characterize the delamination and in-plane crashworthiness behaviour of carbon, flax and hybrid composites from experimental and numerical points of view. Double Cantilever Beam and Four-Point End Notched Flexure tests were carried out to determine the interlaminar fracture modes. In-plane crashworthiness tests were then performed to investigate the delamination phenomenon and the energy absorption capacity considering two different geometries: flat and corrugated. Numerical models were created and validated on both geometries, comparing the obtained load–displacement curves with the experimental ones. Crush force efficiency and specific energy absorption were quantified to provide a proper comparison of the investigated materials. The good results achieved represent a promising starting point for the design of future and more complex structures. [ABSTRACT FROM AUTHOR]

Rhodiola rosea, a long-lived herbaceous plant from the Crassulaceae group, contains the active compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key regulatory proteins including runt-related transcription factor 2 and osterix. Additionally, salidroside facilitates angiogenesis via the hypoxia-inducible factor 1-alpha and vascular endothelial growth factor pathway, crucial for coupling bone development with vascular support. Its antioxidant properties offer protection against bone loss by reducing oxidative stress and promoting osteogenic differentiation through the nuclear factor erythroid 2-related factor 2 pathway. Salidroside has the capability to counteract the negative effects of glucocorticoids on bone cells and prevents steroid-induced osteonecrosis. Additionally, it exhibits multifaceted anti-inflammatory actions, notably through the inhibition of tumor necrosis factor-alpha and interleukin-6 expression, while enhancing the expression of interleukin-10. This publication presents a comprehensive review of the literature on the impact of salidroside on various aspects of bone tissue metabolism, emphasizing its potential role in the prevention and treatment of osteoporosis and other diseases affecting bone physiology. [ABSTRACT FROM AUTHOR]

Background and Objectives: Osteoporotic vertebral compression fractures (OVCFs) are prevalent among the elderly, often leading to significant pain, morbidity, and mortality. Effective management of underlying osteoporosis is essential to prevent subsequent fractures. This study aimed to compare the clinical and radiographic outcomes of teriparatide and denosumab treatments in patients with OVCFs to determine their relative effectiveness in improving patient outcomes. Materials and Methods: This retrospective study included 78 patients diagnosed with an acute thoracolumbar OVCF who received either teriparatide (35 patients) or denosumab (43 patients) within three months of a fracture. Clinical outcomes were assessed using the visual analog scale (VAS) for back pain, Oswestry disability index (ODI), and EQ-5D quality of life scores at baseline, 6 months, and 12 months. Bone mineral density (BMD) and radiographic outcomes were evaluated initially and at 12 months post-treatment. Results: Both treatment groups demonstrated significant improvements in VAS, ODI, and EQ-5D scores over 12 months. No significant differences were observed between the teriparatide and denosumab groups in terms of clinical outcomes or radiographic measurements at any time point. Fracture union and BMD improvements were similarly observed in both groups. The teriparatide group had a lower baseline BMD, but this did not affect the overall outcomes. Conclusions: Both teriparatide and denosumab are effective in improving clinical and radiographic outcomes in patients with OVCFs. Despite concerns about denosumab's potential to hinder fracture healing, our study found no significant differences between the two treatments. These findings support the use of denosumab for early treatment of OVCFs to prevent subsequent fractures without compromising fracture healing. Further prospective studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Nitroimidazoles comprise a class of broad-spectrum anti-microbial drugs with efficacy against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. Among these drugs, metronidazole (MTZ) is commonly used with other antibiotics to prevent infection in open fractures. However, the effect of MTZ on bone remains understudied. In this paper, we evaluated six nitroimidazole drugs for their impact on osteoblast differentiation and identified MTZ as having the highest osteogenic effect. MTZ enhanced bone regeneration at the femur osteotomy site in osteopenic ovariectomized (OVX) rats at the human equivalent dose. Moreover, in OVX rats, MTZ significantly improved bone mass and strength and improved microarchitecture compared to the vehicle-treated rats, which was likely achieved by an osteogenic mechanism attributed to the stimulation of the Wnt pathway in osteoblasts. To mitigate the reported neurological and genotoxic effects of MTZ, we designed an injectable sustained-release in situ gel formulation of the drug that improved fracture healing efficacy by 3.5-fold compared to oral administration. This enhanced potency was achieved through a significant increase in the circulating half-life and bioavailability of MTZ. We conclude that MTZ exhibits osteogenic effects, further accentuated by our sustained-release delivery system, which holds promise for enhancing bone regeneration in open fractures. [ABSTRACT FROM AUTHOR]

Fracture resistance is an important parameter used to predict the performance of indirect dental restorations. The purpose of this in vitro study was to assess the fracture load of posterior milled nanoceramic crowns, in comparison with the lithium disilicate crowns, after fatigue loading, for two different restoration occlusal thicknesses. Forty test metal dies were fabricated by duplicating a master metal model consisting of an anatomic abutment preparation of the maxillary first premolar for a single crown. The dies were divided into two groups of 20 each for the fabrication of nanoceramic (Lava Ultimate) and lithium disilicate (IPS e.max CAD) single crowns. Each material group was further divided into two sub-groups of 10 dies each, based on crown occlusal thickness, of 0.5-mm and 0.75-mm (n = 10). Dental Type V stone dies poured from polyvinyl siloxane impressions of the test metal dies were laboratory scanned in order to design and mill 40 ceramic crowns. The crowns were cemented on to the test metal dies with a self-adhesive resin luting cement. All crowns were thermocycled (2500 cycles) and mechanically loaded (250,000 cycles) in a chewing simulator followed by static loading until failure, and the values noted. The data were statistically analyzed by 2-way ANOVA and Tukey HSD post-hoc multiple comparison tests (α = 0.05). The mean fracture loads ranged from 1022 to 1322 N for nanoceramic crowns and from 1145 to 1441 N for the lithium disilicate crowns. Two-way ANOVA revealed insignificant differences between the nanoceramic and lithium disilicate crowns (p > 0.05) in terms of fracture load. Significant differences were noted in the fracture resistance of crowns based on occlusal thickness (303 N; p = 0.013) regardless of the material used. Multiple comparisons by Tukey HSD post-hoc test showed insignificant differences between the four material-occlusal thickness groups (p > 0.05). The nanoceramic crowns were found to be comparable with lithium disilicate crowns in terms of fracture load. The mean fracture loads of all of the tested crowns were within the normal physiological masticatory load limits. Based on the fracture-resistance results, nanoceramic crowns seem to be suitable for clinical use for the tested occlusal thicknesses. [ABSTRACT FROM AUTHOR]

Background and Objectives: Management of acetabular fractures is aimed at anatomically reducing and fixing all displaced or unstable fractures, as the accuracy of fracture reduction has been demonstrated to strongly correlate with clinical outcomes. However, there is a noticeable gap in the literature concerning the perioperative and postoperative care of patients with acetabular fractures, which ultimately can be potential risk factors for adverse outcomes and permanent disabilities. This study aimed to systematically review the available literature regarding rehabilitation practices, including weight-bearing protocols, across time points in surgically treated acetabular fracture patients and correlate these practices with functional outcomes. Methods: We systematically reviewed the Medline and PubMed databases and the Cochrane Central Register of Controlled Trials in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The inclusion criteria were studies with adult patients (19+ years), publications from the last 10 years, articles focusing on rehabilitation or mentioning any aspect related to rehabilitation (such as weight-bearing or muscle training), and describing the surgical management of acute, isolated acetabulum fractures. Specific information was collected, including the fracture classification, time to surgery, surgical approach, surgical time, blood loss, fixation strategy, quality of reduction, postoperative rehabilitation protocol, complication rate, type(s) of complication, and outcome measurement(s). The choice(s) of surgical approach, surgical time, blood loss, and fixation strategy were stratified based on the fracture classification. The complication rate and type(s) of complication were calculated for all studies. Fractures were classified based on the Letournel classification. Results: A total of 494 articles were identified from the initial search, of which 22 (1025 patients) were included in the final review. The most common rehabilitation protocol favored isometric quadriceps and abductor strengthening exercises starting on the first postoperative day, with passive hip movement at 1–3 days postoperatively and active hip movement ranging from the first postoperative day to 4 weeks postoperatively. Partial weight-bearing with a walker or a pair of crutches was permitted from 1 to 12 weeks after surgery, and full weight-bearing was allowed depending on the patient's general condition and fracture healing state (generally at the end of 3 months). In only three studies did the patients start bearing weight in the early postoperative period (≤1 week). Meta-regression analysis was not performed due to the discrepancy between studies that reported a weight-bearing protocol ≤1 week and >1 week postoperatively. Conclusions: Our study suggests that an accelerated postoperative rehabilitation protocol, including early permissive weight-bearing, does not appear to increase the risk of loss of reduction or the rate of complications after surgical treatment of acetabular fractures. However, a proper meta-analysis was not possible, and the heterogeneity of the included studies did not allow us to conclude anything about the potential biomechanical and clinical benefits nor the negative effects related to this rehabilitation regimen in terms of functional results. There is an inconsistent use of PROMs for objectively calculating the effect size of the accelerated protocol compared with restricted weight-bearing regimes. We pose the need for higher-level evidence to proof our hypothesis. [ABSTRACT FROM AUTHOR]

Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing and the current stem cell interventions that disrupt or augment the bone healing process and, finally, considers the future direction/therapeutic options related to stem cells and bone healing. [ABSTRACT FROM AUTHOR]

Water distribution systems (WDSs) are essential elements for the prosperity and development of societies around the globe. However, over time, the pipeline network starts to age and deteriorate, which results in an increasing rate of breaks and water loss due to leakages. Many countries have started government-funded plans to upgrade and rehabilitate their WDS network components to overcome these challenges. This study proposes an optimization framework that addresses these issues and offers potential benefits. It aims to achieve the optimal upgrading strategies considering network operation (hydraulic) performance and upgrading cost, including investment and non-revenue water costs. The upgrade of the WDS network in the model consists of replacing pipes and controlling the pressure-reducing valve (PRV) settings to reduce leakages. The proposed framework is demonstrated using a small-sized benchmark WDS. The study's outcomes provide the utilities' operators and municipalities' decision-makers with a guiding tool to choose the optimal upgrading strategy for their WDS networks at the lowest cost and optimum operation performance. The methodology involves simulating various leakage scenarios and applying optimization techniques to find the best combination of pipe replacements and PRV settings. This approach ensures a balance between minimizing leakage rates and controlling upgrading costs. The framework achieved a reduction of leakage up to 20% from the original leakage with a 70% probability for the tested benchmark network. The optimization framework can also offer a range of upgrading strategies, with a trade-off between the WDS network leakage reduction and the required cost of the upgrading strategy. [ABSTRACT FROM AUTHOR]

Simple Summary: Fractures in the long bones are common injuries caused by accidents. This study looked at how these injuries heal after surgery. Two factors were checked: a substance in the blood called alkaline phosphatase and X-rays of the leg. After surgery, we found that the level of alkaline phosphatase went up, representing the bone healing. Along with this result, the X-rays also suggested the same information, that is, bone healing. We consider that by checking both the blood and the X-rays, doctors can better understand how leg bones heal after surgery. However, further studies with more patients are necessary to confirm this finding. Background/Objectives: Tibial diaphysis fractures are common injuries resulting from high-to-low-energy traumas in patients of all age groups, but few reports currently provide complementary parameters for the assessment of bone healing processes in the postoperative period. Serum alkaline phosphatase (ALP) and the scores from the Radiographic Union Scale for Tibial Fractures (RUST) can promote new horizons in this context. Therefore, the aim of this study was to assess the behavior of ALP and RUST through within-subject comparisons from immediately post-surgery to 49 days after tibial diaphysis fracture repair. Methods: This article included four case studies where patients underwent the same procedures. Adults of both sexes aged 18 to 60 years with tibial fractures requiring surgery were included. After surgical intervention (T1), the patients were followed for 49 days after surgery, returning for follow-up appointments on the 21st (T2) and 49th (T3) days. At the follow-up appointments, new X-ray images were obtained, and blood samples were collected for ALP measurement. Results: Serum ALP levels increased by T2 following tibial reamed intramedullary nailing surgery. While this increase persisted into T3 for two patients, a decline was observed during the same period for the other two patients. Both events are indicative of the bone consolidation process, and RUST scores at the T3 corroborate this perspective for all patients included in this study. Considering that delta ALP (T3-T1 value) was lower in patients who exhibited the highest RUST score, we suggest that a synchronized analysis between ALP and RUST allows medics to diagnose bone consolidation. Conclusions: Therefore, it can be concluded that the analysis of ALP alongside RUST may be complementary for evaluating bone consolidation following tibial reamed intramedullary nailing surgery, but future studies are needed to confirm this assertion. [ABSTRACT FROM AUTHOR]

Bone healing occurs through three consecutive and interdependent phases. While the acute inflammatory response is vital to fracture healing, chronic and systemic inflammation negatively affect the healing process. The bone tissue relies heavily on the immune system for its normal physiology and turnover. The interactions are more pronounced in injury states, such as fractures and autoimmune disorders. Recently, the field of osteoimmunology, the study of the molecular interplay of the immune and skeletal systems, has gained much-needed attention to develop new therapeutic strategies to accelerate fracture healing and prevent the complications of fracture healing. This review provides an overview of the process of fracture healing and discusses the role of immune cells, their interplay with the released cytokines, and the current state of the art in the field of osteoimmunology. [ABSTRACT FROM AUTHOR]

Plasma stimulation is a form of waterless fracturing as it requires that only the wellbore be filled with an aqueous fluid. The technique creates multiple fractures propagating in different directions around the wellbore. The intent of this paper is to present an experimental and numerical investigation of the degree of competitiveness of plasma stimulation with hydraulic fracturing, especially in the case of stimulating tight formation. Several cases were run experimentally. The samples included limestone and sandstone to investigate plasma fracturing in different rock types. In addition, the main goal of the experiments was to study the creation of fracture(s) under confining stresses, the type of rock, the amount of electrical energy used in the experiment, and the length of the wire to generate the plasma reaction. A laboratory plasma equipment was designed and used to accomplish the experimental work. The experiments were then numerically matched using a finite element numerical simulator, HOSS developed by LANL (Los Alamos National Lab). HOSS was developed to simulate high-strain-rate fractures such as those created by plasma stimulation. It accounts for mixed-mode fracture mechanics which are tensile and shear fractures. The simulator governing equations obey the conservation of mass and momentum in a solid-mechanics sense and account for the nonlinear deformation of rock material. The matching of the experiment allowed us to validate the HOSS simulation of the process and showed that the numerical results are in good agreement with the experimental work. Using the HOSS simulator, we also investigated the effect of higher energy levels and/or short release time on a cement rock model. The pressure profile that is developed due to the energy release can vary in the peak pressure and the release time. The results showed that the plasma fracturing technique is an effective stimulation method in sandstone and limestone. Plasma fractures were developed in the rock samples and extended from the sample wellbore to the outer boundaries. The shape of the pressure pulse has an impact on the developed fractures. Moreover, the effect of plasma stimulation on natural fractures was studied numerically. It was found that natural fractures can arrest the plasma-generated fractures that propagate from the wellbore to the outer boundaries. However, new fractures may develop in the rock starting from the natural fracture tips. [ABSTRACT FROM AUTHOR]

Abnormal skin healing resulting in chronic wounds or hypertrophic scarring remains a major healthcare burden. Here, the antifibrotic angiotensin II type 2 receptor (AT2R) signaling pathway was modulated to determine its impact on cutaneous wound healing. Balb/c mice received two splinted full-thickness wounds. Topical treatments with the selective AT2R agonist compound 21 (C21) and/or selective antagonist PD123319 or saline vehicle were administered until sacrifice on post-wounding days 7 or 10. The rate of wound re-epithelialization was accelerated by PD123319 and combination treatments. In vitro, C21 significantly reduced human fibroblast migration. C21 increased both collagen and vascular densities at days 7 and 10 post-wounding and collagen I:III ratio at day 10, while PD123319 and combination treatments decreased them. Genes associated with regeneration and repair were upregulated by C21, while PD123319 treatment increased the expression of genes associated with inflammation and immune cell chemotaxis. C21 treatment reduced wound total leukocyte and neutrophil staining densities, while PD123319 increased these and macrophage densities. Overall, AT2R activation with C21 yields wounds that mature more quickly with structural, cellular, and gene expression profiles more closely approximating unwounded skin. These findings support AT2R signal modulation as a potential therapeutic target to improve skin quality during wound healing. [ABSTRACT FROM AUTHOR]

Background: Teriparatide is an anabolic agent for osteoporosis and is believed to improve the bone healing process. Previous studies showed that teriparatide could enhance not only fracture healing but also spine fusion. It has been reported that use of teriparatide could promote the spine fusion process and decrease mechanical complications. However, there was no consensus regarding optimal treatment duration. The purpose of this study was to compare surgical outcomes between short-duration and long-duration teriparatide treatment after lumbar fusion surgery in elderly patients. Materials and Methods: All consecutive patients older than 60 years who underwent 1-level lumbar fusion surgery for degenerative diseases between January 2015 and December 2019 were retrospectively reviewed. Based on the duration of teriparatide treatment (daily subcutaneous injection of 20 µg teriparatide), patients were subdivided into two groups: a short-duration (SD) group (<6 months) and a long-duration (LD) group (≥6 months). Mechanical complications, such as screw loosening, cage subsidence, and adjacent vertebral fractures, were investigated. Postoperative 1-year union rate was also evaluated on computed tomography. Clinical outcomes were recorded using visual analog scale (VAS) and Oswestry Disability Index (ODI). Between-group differences for these radiographic and clinical outcomes were analyzed. Results: Ninety-one patients were reviewed in this study, including sixty patients in the SD group and thirty-one patients in the LD group. Their mean age was 72.3 ± 6.2 years, and 79 patients were female. Mean T-score was −3.3 ± 0.8. Cage subsidence (6.7% vs. 3.2%), screw loosening (28.3% vs. 35.5%), and adjacent vertebral fracture (6.7% vs. 9.7%) were not significantly different between the SD and LD groups. Union rate at 1-year postoperative was 65.0% in the SD group and 87.1% in the LD group (p = 0.028). Both groups showed improvement in VAS and ODI after surgery. However, the differences of VAS from preoperative to 6 months and 1 year postoperative were significantly higher in the LD group. Conclusions: Longer teriparatide treatment after lumbar fusion surgery resulted in a higher union rate at 1-year postoperative than the shorter treatment. Also, it could be more beneficial for clinical outcomes. [ABSTRACT FROM AUTHOR]

The controlled dynamization of fractures can promote natural fracture healing by callus formation, while overly rigid fixation can suppress healing. The advent of locked plating technology enabled new strategies for the controlled dynamization of fractures, such as far cortical locking (FCL) screws or active plates with elastically suspended screw holes. However, these strategies did not allow for the use of non-locking screws, which are typically used to reduce bone fragments to the plate. This study documents the first in vivo study on the healing of ovine tibia osteotomies stabilized with an advanced active plate (AAP). This AAP allowed plate application using any combination of locking and non-locking screws to support a wide range of plate application techniques. At week 9 post-surgery, tibiae were harvested and tested in torsion to failure to assess the healing strength. The five tibiae stabilized with an AAP regained 54% of their native strength and failed by spiral fracture through a screw hole, which did not involve the healed osteotomy. In comparison, tibiae stabilized with a standard locking plate recovered 17% of their strength and sustained failure through the osteotomy. These results further support the stimulatory effect of controlled motion on fracture healing. As such, the controlled dynamization of locked plating constructs may hold the potential to reduce healing complications and may shorten the time to return to function. Integrating controlled dynamization into fracture plates that support a standard fixation technique may facilitate the clinical adoption of dynamic plating. [ABSTRACT FROM AUTHOR]

Fractures of the lateral condyle of the humerus are one of the most common fractures in children, accounting for between 10% and 20% of fractures involving the elbow, with a peak incidence at 6 years of age. Treatment is often surgical for displaced fractures > 2 mm, according to Milch and Jakob classification. There is no consensus in the literature about the appropriate surgical management of these fractures. Objectives: The aim of this study is to describe, propose, and evaluate outcomes and complications of the surgical technique of reduction and osteosynthesis using trans-bone suture with resorbable threads. Methods: Patients with lateral condyle fractures treated with this surgical technique from 2015 to 2019 were included in this retrospective study, with a minimum follow-up of 24 months. For clinical and functional assessment of the elbow, Mayo Elbow Scores were recorded; we assessed the time of fracture healing, carrying angles, and Baumann angle of the affected limb compared to the healthy contralateral elbow for radiographic data. Complications have also been described. Results: We achieved satisfactory results; 36 patients with lateral condyle fractures were included in this study. Radiological healing was achieved in all cases. There was only one complication. No cases required additional surgical procedures. Almost all patients achieved a complete flexion of 110 degrees or more and complete extension. Conclusions: This surgical technique has good functional outcomes and fracture healing, a lower incidence of complications when compared to other surgical techniques, and no mechanical failure with good clinical and radiological results. [ABSTRACT FROM AUTHOR]

A low-energy hit, such as a slight fall from a bed, results in a bone fracture, especially in the hip, which is a life-threatening risk for the older adult and a heavy burden for the social economy. Patients with low-energy traumatic bone fractures usually suffer a higher level of bony catabolism accompanied by osteoporosis. Bone marrow-derived stem cells (BMSCs) are critical in osteogenesis, leading to metabolic homeostasis in the healthy bony microenvironment. However, whether the BMSCs derived from the patients who suffered osteoporosis and low-energy traumatic hip fractures preserve a sustained mesodermal differentiation capability, especially in osteogenesis, is yet to be explored in a clinical setting. Therefore, we aimed to collect BMSCs from clinical hip fracture patients with osteoporosis, followed by osteogenic differentiation comparison with BMSCs from healthy young donors. The CD markers identification, cytokines examination, and adipogenic differentiation were also evaluated. The data reveal that BMSCs collected from elderly osteoporotic patients secreted approximately 122.8 pg/mL interleukin 6 (IL-6) and 180.6 pg/mL vascular endothelial growth factor (VEGF), but no PDGF-BB, IL-1b, TGF-b1, IGF-1, or TNF-α secretion. The CD markers and osteogenic and adipogenic differentiation capability in BMSCs from these elderly osteoporotic patients and healthy young donors are equivalent and compliant with the standards defined by the International Society of Cell Therapy (ISCT). Collectively, our data suggest that the elderly osteoporotic patients-derived BMSCs hold equivalent differentiation and proliferation capability and intact surface markers identical to BMSCs collected from healthy youth and are available for clinical cell therapy. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Three-dimensional printing turns a digital model in a computer file into a physical interpretation of the object. This technology is promising in both human and veterinary medicine, enabling the production of anatomical models, customized surgical instruments, implants, and prostheses. Minimally invasive plate osteosynthesis (MIPO) techniques have been developed to accelerate fracture healing by preserving soft tissue as well as the environment at the fracture site. Achieving acceptable alignment with MIPO can be challenging, because fractures are typically reduced indirectly and implants are inserted submuscularly, starting at one end of the broken bone. In our study, we presented results of comminuted feline radial fracture repair using MIPO with locking bone plates as a reduction tool. The implants were pre-contoured on 3D-printed bone models of the antebrachium of an adult male and a female domestic shorthair cat. A pre-contoured bone plate is a valuable tool for fracture reduction in MIPO. (1) Background: Due to the unique structural and functional characteristics of the forelimb in cats, fractures of the radius and ulna are best repaired using internal fixation and stabilization in accordance with AO principles. This study presents the results of reduction of 42 cadaveric comminuted feline radial fractures reduced by minimally invasive plate osteosynthesis (MIPO). (2) Methods: Radius fractures were created on 21 pairs of forelimbs with intact bones. MIPO was then performed using two locking bone plates pre-contoured on 3D-printed bone models of the antebrachium of a male and a female cat. Pre- and postoperative radiographs were taken, and radius length and anatomical lateral distal radial angle (aLDRA) were measured. (3) Results: All fractures were classified as complex diaphyseal fractures of the radius. The radial bone length did not change significantly after surgery (F1,18 = 0.01, p = 0.933). However, the aLDRA was modified after surgery (F1,18 = 7.51, p = 0.013), but this change was only observed in females, in whom the aLDRA was significantly reduced (p = 0.035) compared to the value determined by the shape of the plate. In males, the pre- and postoperative aLDRA values were similar (p = 0.824). In 40 cases, alignment, adjacency of bone fragments, and apparatus were judged to be satisfactory. In two cases, the plate was fixed to the proximal radius and distal ulna due to misidentification of the distal radius. In both cases, revision surgery and correct fixation of the radius gave proper alignment, adjacency, and apparatus. (4) Conclusion: A pre-contoured plate on a 3D-printed model of the male and female domestic cat antebrachium was suitable for the reduction and stabilization of comminuted radial fractures in a cohort of domestic cat cadavers without the need to print individual antebrachial bone models for each patient. [ABSTRACT FROM AUTHOR]

Osteoporosis, characterized by reduced bone density and increased fracture risk, affects over 200 million people worldwide, predominantly older adults and postmenopausal women. The disruption of the balance between bone-forming osteoblasts and bone-resorbing osteoclasts underlies osteoporosis pathophysiology. Standard treatment includes lifestyle modifications, calcium and vitamin D supplementation and specific drugs that either inhibit osteoclasts or stimulate osteoblasts. However, these treatments have limitations, including side effects and compliance issues. Natural products have emerged as potential osteoporosis therapeutics, but their mechanisms of action remain poorly understood. In this study, we investigate the efficacy of natural compounds in modulating molecular targets relevant to osteoporosis, focusing on the Mitogen-Activated Protein Kinase (MAPK) pathway and the gut microbiome's influence on bone homeostasis. Using an in silico and in vitro methodology, we have identified quercetin as a promising candidate in modulating MAPK activity, offering a potential therapeutic perspective for osteoporosis treatment. [ABSTRACT FROM AUTHOR]

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments. [ABSTRACT FROM AUTHOR]

Bone marrow (BM) acts as a dynamic organ within the bone cavity, responsible for hematopoiesis, skeletal remodeling, and immune system control. Bone marrow adipose tissue (BMAT) was long simply considered a filler of space, but now it is known that it instead constitutes an essential element of the BM microenvironment that participates in homeostasis, influences bone health and bone remodeling, alters hematopoietic stem cell functions, contributes to the commitment of mesenchymal stem cells, provides effects to immune homeostasis and defense against infections, and participates in energy metabolism and inflammation. BMAT has emerged as a significant contributor to the development and progression of various diseases, shedding light on its complex relationship with health. Notably, BMAT has been implicated in metabolic disorders, hematological malignancies, and skeletal conditions. BMAT has been shown to support the proliferation of tumor cells in acute myeloid leukemia and niche adipocytes have been found to protect cancer cells against chemotherapy, contributing to treatment resistance. Moreover, BMAT's impact on bone density and remodeling can lead to conditions like osteoporosis, where high levels of BMAT are inversely correlated with bone mineral density, increasing the risk of fractures. BMAT has also been associated with diabetes, obesity, and anorexia nervosa, with varying effects on individuals depending on their weight and health status. Understanding the interaction between adipocytes and different diseases may lead to new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite medical advancements, post-operative infections in osteosynthesis remain common, causing complications like delayed healing and implant failure. Investigating microbial colonization after surgery in small animals, this study aims to understand infection rates and influencing factors. Results from 71 explants show correlations between infection, patient characteristics, and surgical variables. Notably, factors like body weight, implant type, and additional injuries impact infection development. Surprisingly, while microorganisms were present in nearly half of the cases, only 7.3% led to clinical complications. These findings highlight the complexity of post-operative infections and suggest that microbial presence does not always lead to complications, offering insights for improved treatment strategies in veterinary medicine, potentially reducing patient suffering and healthcare costs. Despite recent advancements in antibiotics, hygienic measures, and peri-operative systemic antibiotics, post-operative infections in osteosynthesis remain prevalent and continue to be among the most common surgical complications, leading to delayed fracture healing, osteomyelitis, implant loosening, and loss of function. Osteosynthesis implants are routinely utilized in veterinary medicine and the current study investigates the microbial colonization of implants following osteosynthesis in small animals, along with its incidence and influencing factors. The results are analyzed in regard to correlations between infection, patient, disease progression, and radiographic images, as well as other factors that may promote infection. Seventy-one explants from sixty-five patients were examined and evaluated for microbial colonization. Factors like body weight and age, location and type of plate and additional injuries like lung lesions, the surgeon's experience, or the number of people present during the surgical procedure seem to influence the development of an infection. Of the animals, 60% showed osteolytic changes and 73.3% of those with dysfunctional mobility had an implant infection. Microorganisms were detected in almost 50% of the explants, but a clinically relevant infection was only present in five patients (7.3%), suggesting that the presence of microorganisms on an implant does not necessarily lead to treatment complications. [ABSTRACT FROM AUTHOR]

Background: Fracture healing is a very complex and well-orchestrated regenerative process involving many cell types and molecular pathways. Despite the high efficiency of this process, unsatisfying healing outcomes, such as non-union, occur for approximately 5–10% of long bone fractures. Although there is an obvious need to identify markers to monitor the healing process and to predict a potential failure in callus formation to heal the fracture, circulating bone turnover markers' (BTMs) utility as biomarkers in association with radiographic and clinical examination still lacks evidence so far. Methods: A systematic review on the association between BTMs changes and fracture healing in long bone non-union was performed following PRISMA guidelines. The research papers were identified via the PubMed, Cochrane, Cinahl, Web of Science, Scopus, and Embase databases. Studies in which the failure of fracture healing was associated with osteoporosis or genetic disorders were not included. Results: A total of 172 studies were collected and, given the inclusion criteria, 14 manuscripts were included in this review. Changes in circulating BTMs levels were detected during the healing process and across groups (healed vs. non-union patients and healthy vs. patients with non-union). However, we found high heterogeneity in patients' characteristics (fracture site, gender, and age) and in sample scheduling, which made it impossible to perform a meta-analysis. Conclusions: Clinical findings and radiographic features remain the two important components of non-union diagnosis so far. We suggest improving blood sample standardization and clinical data collection in future research to lay the foundations for the effective use of BTMs as tools for diagnosing non-union. [ABSTRACT FROM AUTHOR]

Background: Among the risk factors for nonunion are unchangeable patient factors such as the type of injury and comorbidities, and factors that can be influenced by the surgeon such as fracture treatment and the postoperative course. While there are numerous studies analyzing unchangeable factors, there is poor evidence for factors that can be affected by the physician. This raises the need to fill the existing knowledge gaps and lay the foundations for future prevention and in-depth treatment strategies. Therefore, the goal of this study was to illuminate knowledge about nonunion in general and uncover the possible reasons for their development; Methods: This was a retrospective analysis of 327 patients from 2015 to 2020 from a level I trauma center in Germany. Information about patient characteristics, comorbidities, alcohol and nicotine abuse, fracture classification, type of osteosynthesis, etc., was collected. Matched pair analysis was performed, and statistical testing performed specifically for atrophic long-bone nonunion; Results: The type of osteosynthesis significantly affected the development of nonunion, with plate osteosynthesis being a predictor for nonunion. The use of wire cerclage did not affect the development of nonunion, nor did the use of NSAIDs, smoking, alcohol, osteoporosis and BMI; Conclusion: Knowledge about predictors for nonunion and strategies to avoid them can benefit the medical care of patients, possibly preventing the development of nonunion. [ABSTRACT FROM AUTHOR]

Fracture healing is a complex series of events that requires a local inflammatory reaction to initiate the reparative process. This inflammatory reaction is important for stimulating the migration and proliferation of mesenchymal progenitor cells from the periosteum and surrounding tissues to form the cartilaginous and bony calluses. The proinflammatory cytokine interleukin (IL)-17 family has gained attention for its potential regenerative effects; however, the requirement of IL-17 signaling within mesenchymal progenitor cells for normal secondary fracture healing remains unknown. The conditional knockout of IL-17 receptor a (Il17ra) in mesenchymal progenitor cells was achieved by crossing Il17raF/F mice with Prx1-cre mice to generate Prx1-cre; Il17raF/F mice. At 3 months of age, mice underwent experimental unilateral mid-diaphyseal femoral fractures and healing was assessed by micro-computed tomography (µCT) and histomorphometric analyses. The effects of IL-17RA signaling on the osteogenic differentiation of fracture-activated periosteal cells was investigated in vitro. Examination of the intact skeleton revealed that the conditional knockout of Il17ra decreased the femoral cortical porosity but did not affect any femoral trabecular microarchitectural indices. After unilateral femoral fractures, Il17ra conditional knockout impacted the cartilage and bone composition of the fracture callus that was most evident early in the healing process (day 7 and 14 post-fracture). Furthermore, the in vitro treatment of fracture-activated periosteal cells with IL-17A inhibited osteogenesis. This study suggests that IL-17RA signaling within Prx1+ mesenchymal progenitor cells can influence the early stages of endochondral ossification during fracture healing. [ABSTRACT FROM AUTHOR]

Delayed fracture healing can have devastating functional consequences, including pseudoarthrosis. Many factors can contribute to delayed healing, including decreased vascularity, micro-motion at the fracture site, large fracture gaps, multiple traumas at the same site, compromised metabolic status, surgical complications, and other conditions. A 61-year-old female patient was referred to our hospital with left distal humeral pseudarthrosis, accompanied by chronic pain and disability. Two years prior, the patient suffered a traumatic incident. At another medical facility, the patient underwent open reduction and internal fixation surgery with simultaneous ulnar nerve transposition. She showed favorable postoperative recovery. Unfortunately, approximately one year later, the patient sustained a second trauma to the same arm. This led to peri-implant fracture and post-traumatic aseptic degradation of the osteosynthesis system which was subsequently removed. Twelve months after the last surgery, the patient was referred to our hospital and, after thorough consideration of the therapeutic options, we decided to perform left elbow arthroplasty with left distal humeral reconstruction by using Zimmer's Comprehensive Segmental Revision System. This approach is generally reserved for tumors, and only a handful of cases of megaprostheses for non-tumoral indications have been previously reported. The surgery and perioperative care of our patient were optimal, there were no complications, and the patient recovered arm functionality following rehabilitation. [ABSTRACT FROM AUTHOR]

Angiogenesis is vital for bone fracture healing and plays a significant role in the fate of orthopedic implants. The growth and maintenance of new blood vessels at the fracture site of patients is essential, which promotes the clinical outcome of plasma sprayed Ti (PST) coated orthopedic implants. In order to endow the PST coating with pro-angiogenic effects, deferoxamine-loaded chitosan-based hydrogel was fabricated on the coating surface. Polydopamine-modified chitosan (CS/PDA) hydrogel exhibited enhanced bonding strength to PST coatings as evidenced by scratch test. The deferoxamine-loaded CS/PDA (CS/PDA-DFO) exhibited a sustained drug-release property, and the cumulative concentration of released DFO reached 20.21 μg/mL on day 7. PST-CS/PDA with higher wettability and active group quantity enhanced the viability and adhesion characteristics of human umbilical vein endothelial cells (HUVECs) and upregulated the secretion level of nitric oxide and vascular endothelial growth factor. Moreover, the introduction of DFO in PST-CS/PDA further enhanced the pro-angiogenic effects. Above all, this study offers a novel approach for developing hydrogel coating on orthopedic implants showing enhanced bonding strength and pro-angiogenic effects. [ABSTRACT FROM AUTHOR]

In orthopaedics, erythropoietin (EPO) is applied in the preoperative management of anaemic patients, but also as a stimulating factor to assist bone regeneration due to its angiogenic and osteoinductive potential. Since orthopaedists mainly rely on their clinical experience to assess bone healing, additional and more objective methods such as studying the dynamics of bone markers are needed. Therefore, the aim of this study was to investigate the plasma activity of bone-specific alkaline phosphatase (BALP), the N-terminal propeptide of type I collagen (PINP), the C-terminal telopeptide of type I collagen (CTX), and deoxypyridinoline (DPD) during the first 2 months of healing of comminuted fractures in cats, either non-stimulated or locally stimulated with recombinant human erythropoietin (rhEPO). The study included twelve cats of mixed breeds, aged 7.2 ± 4 months, weighing 2.11 ± 1.1 kg, with comminuted diaphyseal fractures of the femur. Surgical treatment with plate osteosynthesis was performed in all animals. The cats were randomly divided into two groups—a control (n = 6) and an EPO group (n = 6). The locally applied EPO leads to the increased activity of bone formation markers (BALP and PINP) during the second week after the osteosynthesis, preceding the peaks in the control group by two weeks. The studied bone resorption markers (DPD, CTX) varied insignificantly during the studied period. In conclusion, erythropoietin could serve as a promoter of bone healing in comminuted fractures in cats. [ABSTRACT FROM AUTHOR]

Featured Application: Interfragmentary movement is crucial in promoting callus formation during secondary fracture healing. Fixation stiffness is a critical factor, with excessive flexibility and rigidity hindering optimal healing. The concepts of flexible fixation, techniques for regulating implant stiffness, and material selection, favoring a lower Young's modulus like titanium alloys, are emphasized. A novel TiNbSn alloy with a low Young's modulus has been introduced as a potential solution that has shown efficacy in promoting osteosynthesis and superior mechanical properties. The bone healing process is influenced by various physiological factors. Fracture fixation traditionally relied on rigid metallic implants. However, excessively rigid constructs can lead to complications, necessitating revision surgery. This review focuses on approaches to improve bone healing by introducing adequate interfragmentary movement (IFM) at the fracture site. IFM promotes secondary fracture healing and callus formation. Studies suggest that rigid fixation may impair fracture healing by inhibiting callus formation and causing stress shielding. Titanium alloy locking plates have been shown to be biomechanically superior to stainless steel. Flexible fixation and techniques to regulate implant stiffness are crucial for managing fractures with bridge plating. Materials with a lower Young's modulus balance biomechanical properties. A novel TiNbSn alloy with a low Young's modulus has been developed to address stress shielding issues. It is effective in promoting osteosynthesis, bone healing, and superior mechanical properties compared with materials with higher Young's moduli. The enhanced formation of bone and callus associated with TiNbSn alloy suggests its promise for use in fracture treatment plates. Understanding the biomechanics of fracture healing, optimizing fixation stiffness, and exploring innovative materials like TiNbSn alloys, are crucial for advancing approaches to accelerate and enhance bone healing. [ABSTRACT FROM AUTHOR]

Finite element analysis has become an essential tool for simulating and understanding crack growth. This technique holds significant importance in the field of mechanical engineering, where it finds wide application in the design and optimization of structural components and material properties. This work began with the identification of critical zones and estimated the number of load life repeats through fatigue analysis, specifically applied to automotive rims utilizing innovative finite element methods. To investigate crack behavior, we are used the Extended Finite Element Method (XFEM) with the volumetric approach to compute the Stress Intensity Factor (SIF). The results obtained by our study align closely with experimental tests in terms of detecting the critical zone where a crack can appear. Our findings contribute to the understanding of fatigue behavior in automotive rims, offering new insights into their structural integrity and performance under various load conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: In feline tibia fractures, limited tissue coverage may lead to complications such as open fractures and delayed healing. Non-union, attributed to factors such as poor blood supply, malnutrition, bone misalignment, infections, and bone damage, necessitates bone grafting for repair. While autografts are preferred, they may be insufficient for extensive defects, prompting the use of allografts and xenografts created through xenotransplantation processes such as deproteinized bovine bone. Past graft options were limited, but contemporary alternatives encompass a broader range, incorporating xenografts, demineralized bone matrix (DBM), and calcium-based materials. When combined with growth factors or cells, these materials significantly enhance their effectiveness. This case describes the treatment of a cat's tibia defect using an autologous cancellous bone graft, recombinant human bone morphogenetic protein-2, and a xenograft derived from canines mixed with DBM. Despite the initial use of external skeletal fixation and antibiotic therapy for infection, a significant defect persisted even after bone healing was complete, necessitating a multifaceted approach involving additional plate placement, autograft, and xenograft. As a result, the long-term prognosis was favorable with no complications observed in the subject's bone healing. A 17-month-old domestic short-hair cat was referred due to a non-union in the left tibia. The initial repair, conducted 3 months prior at another animal hospital, involved an intramedullary (IM) pin and wire to address a comminuted fracture. Unfortunately, the wire knot caused a skin tract, resulting in osteomyelitis. Although the wire knot was removed at that hospital, the draining tract persisted, continuously discharging exudate. Upon evaluation, the first surgery was reassessed and revised, involving the removal of the IM pin and the application of external skeletal fixation alongside an antibiotic susceptibility test. After 118 days post-revision surgery, while some cortical continuity was observed, a significant bone defect persisted, posing a substantial risk of refracture should the implant be removed. A second revision surgery was performed, utilizing a bone plate combined with cancellous bone autograft, recombinant human bone morphogenetic protein-2, and xenograft featuring a canine-derived cancellous chip mixed with demineralized bone matrix. Remarkably, the bone completed its healing within 105 days following the subsequent surgery. Radiography demonstrated successful management of the large bone defect up to the 2-year postoperative check-up. During telephone follow-ups for 3.5 years after surgery, no complications were identified, and the subject maintained a favorable gait. [ABSTRACT FROM AUTHOR]

The effects of hydrogen on the tensile properties, fatigue life, and tensile and fatigue fracture morphologies of nitrogen-added ultrahigh-strength transformation-induced plasticity (TRIP)-aided martensitic (TM) steels were investigated. The total elongation and number of cycles to failure (Nf) of the hydrogen-charged TM steels decreased with the addition of nitrogen; in particular, adding 100 ppm of nitrogen decreased the total elongation and Nf of the TM steels. The quasi-cleavage cracking around the AlN occurred near the sample surface, which is the crack propagation region, although dimples appeared at the center of the fracture surface in the tensile samples. The initial fatigue crack initiated at the AlN precipitate or matrix/AlN interface, located at the notch root. During crack propagation, new cracks were initiated at the AlN precipitates or matrix/AlN interfaces, while quasi-cleavage crack regions were observed around the AlN precipitates. The decrease in the total elongation and Nf of the hydrogen-charged TM steel with 100 ppm of added nitrogen might be attributable to the crack initiation around the AlN precipitates formed by a large amount of hydrogen trapped at the AlN precipitates and matrix/AlN interfaces, and to the dense distribution of AlN, which promoted crack linkage. [ABSTRACT FROM AUTHOR]

Multiple fatigue cracks are generally present in practical engineering due to the existence of welding; the size and number of cracks of orthotropic steel bridge decks are greatly uncertain. The component failure conditions caused by these cracks may have correlations. Currently, it is still a challenging issue to develop a physical model of multiple fatigue crack propagation in bridge decks and perform a fatigue reliability assessment, which is also the motivation that drives the innovation of this study. A fatigue reliability evaluation method is presented for orthotropic steel bridge decks, considering the coupling effect of multiple cracks and the randomness of vehicle loading. A numerical simulation method for multifatigue crack growth is developed by combining the ABAQUS and FRANC3D programs. The equivalent crack depth under different spacing and depths of collinear cracks is calculated by using numerical simulation and the multicrack equivalent characterization method. The critical damage accumulation function of multiple fatigue cracks is established using linear elastic fracture mechanics. Subsequently, the critical damage accumulation function of multiple fatigue cracks is established based on linear elastic fracture mechanics. In order to solve the time-consuming problem of traditional Monte Carlo method, the iHL-RF method and AK-MCS method are developed for fatigue reliability analysis. The results show that compared with the single-crack model, the fatigue reliability of orthotropic steel deck will be crucially reduced considering the coupling effect of double cracks. The MCS, iHL-RF and AK-MCS methods can effectively solve the fatigue reliability analysis problem. Compared with the MCS method, the reliability calculation time based on AK-MCS method is significantly reduced. The AK-MCS method-based method reduces the time for calculating the reliability of orthotropic steel decks by 50% compared with the iHL-RF method. The reliability analysis of orthotropic steel deck bridge based on AK-MCS method is proved to be efficient and accurate. [ABSTRACT FROM AUTHOR]

Background: Multi-comminuted, intra-articular fractures of the distal humerus still pose a challenge to modern orthopedics due to unsatisfactory treatment results and a high percentage (over 50%) of postoperative complications. When surgical treatment is chosen, such fractures are fixed using two plates with locking screws, which can be used in three spatial configurations: either parallel or one of two perpendicular variants (posterolateral and posteromedial). The evaluation of the fracture healing conditions for these plate configurations is unambiguous. The contradictions between the conclusions of biomechanical studies and clinical observations were the motivation to undertake a more in-depth biomechanical analysis aiming to indicate the weak points of two-plate fracture stabilization. Methods: Research was conducted using the finite element method based on an experimentally validated model. Three variants of distal humerus fracture (Y, λ, and H) were fixed using three different plate configurations (parallel, posterolateral, and posteromedial), and they were analyzed under six loading conditions, covering the whole range of flexion in the elbow joint (0–145°). A joint reaction force equal to 150 N was assumed, which corresponds with holding a weight of 1 kg in the hand. The biomechanical conditions of bone union were assessed based on the interfragmentary movement (IFM) and using criteria formulated by Steiner et al. Results: The IFMs were established for particular regions of all of the analyzed types of fracture, with distinction to the normal and tangential components. In general, the tangential component of IFM was greater than normal. A strong influence of the elbow joint's angular position on the IFM was observed, with excessive values occurring for flexion angles greater than 90°. In most cases, the smallest IFM values were obtained for the parallel plaiting, while the greatest values were obtained for the posteromedial plating. Based on IFM values, fracture healing conditions in particular cases (fracture type, plate configuration, loading condition, and fracture gap localization) were classified into one of four groups: optimal bone union (OPT), probable union (PU), probable non-union (PNU), and non-union (NU). Conclusions: No plating configuration is able to ensure distal humerus fracture union when the full elbow flexion is allowed while holding a weight of 1 kg in the hand. However, flexion in the range of 0–90° with such loadings is acceptable when using parallel plating, which is a positive finding in the context of the early rehabilitation process. In general, parallel plating ensures better conditions for fracture healing than perpendicular plate configurations, especially the posteromedial version. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids induce osteoporosis, while bisphosphonates treat it, yet both can lead to atypical femoral fractures. Patients on both agents may face challenges in healing from such fractures due to their pathophysiology and pharmacological effects. Methods: Intramedullary nail surgery was performed on 20 limbs in 19 patients with atypical femoral fractures and autoimmune diseases, who had received bisphosphonates for GC-induced osteoporosis. The average durations of glucocorticoid and bisphosphonate use were 17 and 9 years (standard deviation: 7.59 and 4.35), respectively, and the mean follow-up period was 66 months. Fifteen and five limbs were fractured at the subtrochanter and diaphysis, respectively. The surgical techniques (type of nail) and additional procedures performed in these cases were examined. The post-operative alignment and reduction status on radiographs were examined to determine their relationship with post-operative outcomes. Results: Cephalomedullary long nails were inserted in nine limbs and antegrade intramedullary nails in 11 limbs. As an additional surgical procedure, open reduction, bone grafting and drilling were carried out on six, two, and five limbs, respectively. Regarding malalignment on radiographs, AP images showed varus in four limbs, and lateral images showed extension in two limbs. Regarding the cortical discontinuity, the distal fragment of the 11th limb shifted posteriorly in the lateral view. Gaps at the fracture sites were observed in 11 limbs. As a result, bone union was confirmed in 13 limbs. Five of the seven nonunion limbs required additional surgery. When comparing union and nonunion, open reduction and drilling were involved in nonunion limbs. Conclusion: The surgical outcomes of atypical femoral fractures in patients with autoimmune disease and on long-term glucocorticoids and bisphosphonates were poor. Although it is not possible to affirm for sure based on these results alone, management with prophylactic surgery before complete fracture is considered to be required to improve outcomes. [ABSTRACT FROM AUTHOR]

Fatigue fractures in materials are the main cause of approximately 80% of all material failures, and it is believed that such failures can be predicted and mathematically calculated in a reliable manner. It is possible to establish prediction modalities in cases of fatigue fractures according to three fundamental variables in fatigue, such as volume, number of fracture cycles, as well as applied stress, with the integration of Weibull constants (length characteristic). In this investigation, mechanical fatigue tests were carried out on specimens smaller than 4 mm2, made of different industrial materials. Their subsequent analysis was performed through precision computed tomography, in search for microfractures. The measurement of these microfractures, along with their metrics and classifications, was recorded. A convolutional neural network trained with deep learning was used to achieve the detection of microfractures in image processing. The detection of microfractures in images with resolutions of 480 × 854 or 960 × 960 pixels is the primary objective of this network, and its accuracy is above 95%. Images that have microfractures and those without are classified using the network. Subsequently, by means of image processing, the microfracture is isolated. Finally, the images containing this feature are interpreted using image processing to obtain their area, perimeter, characteristic length, circularity, orientation, and microfracture-type metrics. All values are obtained in pixels and converted to metric units (μm) through a conversion factor based on image resolution. The growth of microfractures will be used to define trends in the development of fatigue fractures through the studies presented. [ABSTRACT FROM AUTHOR]

Statins, widely prescribed for lipid disorders, primarily target 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase competitively and reversibly, resulting in reduced low-density lipoprotein cholesterol (LDL-C). This mechanism proves effective in lowering the risk of lipid-related diseases such as ischemic cerebrovascular and coronary artery diseases. Beyond their established use, statins are under scrutiny for potential applications in treating bone diseases. The focus of research centers mainly on simvastatin, a lipophilic statin demonstrating efficacy in preventing osteoporosis and aiding in fracture and bone defect healing. Notably, these effects manifest at elevated doses (20 mg/kg/day) of statins, posing challenges for systematic administration due to their limited bone affinity. Current investigations explore intraosseous statin delivery facilitated by specialized carriers. This paper outlines various carrier types, characterizing their structures and underscoring various statins' potential as local treatments for bone diseases. [ABSTRACT FROM AUTHOR]

Composites of poly(vinyl alcohol) (PVA) in the shape of braids, in combination with crystals of hydroxyapatite (HAp), were analyzed to perceive the influence of this bioceramic on both the quasi-static and viscoelastic behavior under tensile loading. Analyses involving energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM) allowed us to conclude that the production of a homogeneous layer of HAp on the braiding surface and the calcium/phosphate atomic ratio were comparable to those of natural bone. The maximum degradation temperature established by thermogravimetric analysis (TGA) showed a modest decrease with the addition of HAp. By adding HAp to PVA braids, an increase in the glass transition temperature (Tg) is noticed, as demonstrated by dynamic mechanical analysis (DMA) and differential thermal analysis (DTA). The PVA/HAp composite braids' peaks were validated by Fourier transform infrared (FTIR) spectroscopy to be in good agreement with common PVA and HAp patterns. PVA/HAp braids, a solution often used in the textile industry, showed superior overall mechanical characteristics in monotonic tensile tests. Creep and relaxation testing showed that adding HAp to the eight and six-braided yarn architectures was beneficial. By exhibiting good mechanical performance and most likely increased biological qualities that accompany conventional care for bone applications in the fracture healing field, particularly multifragmentary ones, these arrangements can be applied as a fibrous fixation system. [ABSTRACT FROM AUTHOR]