Search Results (266)

Stroke is a major cause of lower-limb paresis, and clinical practice has long shown that early, repetitive gait training can accelerate motor recovery. End-effector gait trainers mounted on a wheeled walker provide a portable and low-cost alternative to bulky treadmill-based exoskeletons. This paper presents a geared five-bar linkage as the trajectory-generating mechanism of a Walker Gait Trainer (WGT), a single-actuator rehabilitation device for over-ground use. The two cranks of the five-bar linkage are linked by a gear train made up of two identical spur gears and an intermediate idler. This arrangement reduces the dimensional synthesis problem from four defect constraints, Grashof, order, and two circuit constraints, to a single order constraint, because branch and circuit defects are removed by design when both cranks are compelled to rotate continuously. Dimensional synthesis is formulated as a path-generation problem based on seven precision points obtained from normative gait data, and the mechanism dimensions are found through a systematic design-by-analysis search carried out interactively in the GIM kinematic simulation environment, using the closed-form kinematic model developed in this study. The final mechanism is then reconstructed in GIM as a kinematic cross-check of the closed-form model. The geared five-bar linkage reproduces the typical teardrop ankle path of healthy gait with one fewer link than conventional six-bar designs, while also adding the gear ratio as an extra parameter for shaping the trajectory, which is not available in six-bar topologies. The paper also presents the full device integration, in which the input crank is powered by a single speed-controlled actuator mounted on the walker frame, together with a three-dimensional CAD assembly model. Full article

Background. When free margins can be achieved and adjacent joints can be preserved, limb salvage surgery is the preferred treatment for intercalary paediatric bone tumours in the lower extremity. Biological reconstruction techniques include allograft, free vascularised fibular graft (FVFG), and allograft combined with FVGF (Capanna technique). This review summarises current evidence on outcomes and complications, and proposes directions for future research to refine patient selection. Methods. A systematic review was conducted using PubMed, Scopus, Embase, and Cochrane Library. Eligible studies reported outcomes of allograft, FVFG, or combined techniques for intercalary lower limb reconstruction in children or adolescents. Results. Twenty-five articles met the inclusion criteria (8 allograft, 7 FVFG, 14 Capanna); four studies reported two techniques. In total, 391 patients were included (allograft 147, FVFG 51, Capanna 193). Mean defect lengths were 14.9 cm (allograft), 14.5 cm (FVFG), and 14.7 cm (Capanna). Time to union was 8.5 months for allografts, 11.4 for Capanna, and 12.5 for FVFG. Non-union occurred in 14.7%, 13.2%, and 10.3%, and delayed union in 13.6%, 4.8%, and 7.9% for FVFG, allograft, and Capanna, respectively. Fractures were 40.5% for FVFG, 18.4% for allograft, and 23.5% for Capanna. Infections were least common with FVFG (2.7%). Conclusions. The reconstruction strategy should be tailored to anatomical location, defect size, and patient-specific factors. Although infections rates were lowest with FVFG, time to union was longer and the postoperative fracture rate was higher compared to the allograft or Capanna technique. Allografts demonstrated the shortest time to union and lowest fracture risk. The Capanna technique may be beneficial when factors including chemotherapy, poor host bone quality, or high mechanical load are present, but comes at a cost of morbidity and complexity. Full article

Background/Objectives: Reconstruction of complex soft-tissue defects in the lower extremity remains a significant challenge in reconstructive surgery, necessitating reliable vascularized tissue coverage when local options are exhausted. Since 1984, the free ALT flap has been recognized for its versatility, consistent vascular anatomy and low donor-site morbidity. Methods: A two-pronged approach was used, consisting of a systematic review of 18 clinical studies (published 2015–2025, n > 3400) and a retrospective analysis of 20 patients treated for high-energy traumatic defects at a single center (2017–2021). Primary endpoints included flap survival, complication rates, and functional outcomes. Results: The retrospective cohort demonstrated a 90% flap survival rate, which was not significantly different from the figure of 92.4% reported in the literature (p = 0.661). The overall complication rate was 40%, significantly higher than the 7.4% literature average (p < 0.001). Most complications were localized wound-healing disorders, such as partial necrosis, associated with the zone of injury in trauma. Despite these complications, a 100% limb salvage rate was achieved. Good functional outcomes, defined as regaining weight-bearing capacity, were observed in 80% of patients, consistent with the literature benchmarks (84.8%, p = 0.532). Conclusions: Within the limitations of this retrospective cohort and systematic review, the findings suggest that the free ALT flap is a reliable option for lower-extremity reconstruction, providing high flap survival and favorable functional outcomes despite a relatively high rate of localized wound complications in complex trauma cases. Full article

Cynops orientalis, a member of the Salamandridae family, can regenerate severely injured limbs throughout its lifespan. The molecular mechanisms regulating limb regeneration in C. orientalis remain largely unknown. SERCA1 (sarcoplasmic/endoplasmic reticulum calcium ATPase 1) is a major sarco/endoplasmic reticulum calcium pump in skeletal muscle, and our previous transcriptomic sequencing results showed increased SERCA1 mRNA expression during the early stages of newt limb regeneration. In the present study, we investigated the role and regulatory mechanism of SERCA1 during newt limb regeneration by using a limb-amputation model, shRNA-mediated knockdown, Thapsigargin-mediated SERCA1 inhibition, miRNAomics analysis, dual-luciferase reporter assays and Agomir therapy. Knockdown of SERCA1 expression or suppression of SERCA1 activity impaired skeletal muscle cell dedifferentiation, disrupted AEC and blastema formation, reduced cell proliferation, and significantly delayed limb regeneration compared with control animals. Through miRNAomics analysis and in vitro dual-luciferase reporter assays, we identified miR-20487-5p as a negative regulator of SERCA1 expression in C. orientalis. In vivo treatment with miR-20487-5p Agomir down-regulated SERCA1 expression resulted in limb-regenerative defects. Mechanistically, shRNA-SERCA1 or miR-20487-5p Agomir treatment reduced ERK phosphorylation in regenerating limb tissue, suggesting an association between the miR-20487-5p/SERCA1 axis and MAPK/ERK activation. Taken together, our study supports the significant role of the miR-20487-5p/SERCA1/MAPK/ERK axis in early newt limb regeneration. This study expands the current understanding of molecular mechanisms initiating newt limb regeneration. Full article

Background and Clinical Significance: Reconstruction of large segmental bone defects following oncologic resection in pediatric patients remains a major challenge. Although distraction osteogenesis with bone transport is a well-established biological reconstructive option, regenerate formation may be compromised in patients receiving chemotherapy. The accordion maneuver, consisting of alternating cycles of compression and distraction, has been described as a method to stimulate bone regeneration, primarily in association with external fixation systems. However, its use in internal bone transport systems using intramedullary lengthening nails following oncologic resection, particularly in the setting of perioperative chemotherapy, remains rarely reported. Case Presentation: We report a case of a 12-year-old boy with high-grade telangiectatic osteosarcoma of the distal femur who underwent neoadjuvant chemotherapy followed by limb-salvage surgery, resulting in a 14 cm segmental bone defect. Reconstruction was performed using plate-assisted bone transport with a motorized intramedullary magnetic nail. During distraction osteogenesis, delayed and asymmetric regenerate formation developed. An accordion maneuver was subsequently initiated, resulting in progressive improvement in regenerate density and corticalization without the need for revision surgery. Conclusions: This case highlights the successful application of the accordion maneuver using internal bone transport following oncologic resection. It represents a minimally invasive technique to stimulate bone healing and may reduce the need for revision surgery; however, larger series are needed to confirm this potential benefit, particularly in biologically compromised patients receiving chemotherapy. Full article

Colony-stimulating factor-1 receptor (CSF1R) provides essential signals for macrophage and osteoclast proliferation, differentiation, and survival, but the roles of CSF1R+ macrophages and osteoclasts during limb morphogenesis are understudied. Here, we utilized a pharmacological model by feeding the CSF1R inhibitor PLX5622 to pregnant mice across gestation to examine how CSF1R disruption impacts embryonic limb development. CSF1R-expressing cells were significantly depleted in response to PLX5622 exposure, including a complete loss of embryonic osteoclasts and osteoclastic activity in the developing limb bones. Although the gross morphology of limb nerves, muscles, cartilage, and bone appeared intact between embryonic day 11.5 (E11.5) and E15.5, prenatal PLX5622 exposure resulted in a completely penetrant truncated phenotype for all postnatal day 1 (P1) limb bones analyzed, suggesting that CSF1R+ cells play important roles in mediating limb bone formation during late embryogenesis. Interestingly, strain-specific defects were observed in the heel, where most of the CD1 mice presented with absent talus and underdeveloped calcaneus bones, while the C57BL/6 mice presented with milder developmental disruptions in both bones. Taken together, our data demonstrate that PLX5622 effectively depletes CSF1R-expressing macrophages and osteoclasts in embryonic limbs and suggest an essential role for embryonic CSF1R+ cells in driving limb bone morphogenesis. Full article

Background: Massive post-traumatic segmental bone defects exceeding 5 cm—particularly those resulting from Gustilo–Anderson type IIIB open fractures—present a formidable reconstructive challenge. Autologous bone graft, though biologically superior, is restricted in this context by limited harvest volume and donor-site morbidity. Nonvascularized structural bone allografts provide unrestricted graft volume and immediate mechanical support, but data on their performance in severely compromised post-traumatic environments remain sparse. Methods: This retrospective case series evaluated three patients with massive distal femoral bone loss following high-energy trauma. All were managed with a staged protocol: radical debridement and temporary joint-spanning external fixation at index surgery, followed by definitive reconstruction with a matched nonvascularized structural allograft and retrograde intramedullary nailing once the host bed was aseptic and soft-tissue coverage was established. Results: Limb salvage was achieved in all three patients at a mean follow-up of 18 months. Two patients attained stable biological integration and restored anatomical alignment; one of these progressed to full unassisted weight-bearing by four months postoperatively. The third patient developed symptomatic pseudarthrosis at the distal host–graft junction. The proximally integrated allograft had preserved sufficient femoral bone stock to serve as anchorage for a segmental total knee arthroplasty performed two years after the index reconstruction, ultimately preventing amputation. Conclusions: Nonvascularized structural allografts combined with rigid intramedullary nailing constitute a reproducible limb salvage strategy for massive femoral defects. The allograft functions not only as a vehicle for primary biological union, but as a structural reserve—maintaining femoral axis and bone stock that remains available for secondary arthroplasty reconstruction should union fail. Full article

Fatigue and muscle wasting are common clinical manifestations of inherited and acquired neuromuscular disorders, including peripheral neuropathies, neuromuscular junction disorders, and myopathies. These conditions encompass a wide disease spectrum with variable prognoses, making accurate diagnosis essential for appropriate management. Congenital myasthenic syndromes (CMSs) are rare, inherited disorders characterized by impaired neuromuscular transmission. Although symptoms often begin in infancy or early childhood, later onset during adolescence or adulthood is increasingly recognized. Clinical phenotypes vary according to the underlying molecular defect, but fatigable weakness predominantly affecting axial and proximal limb muscles is a hallmark feature. We report an adolescent male who developed progressive proximal muscle weakness and wasting over several years, resulting in significant functional impairment. Initial evaluation suggested limb–girdle muscular dystrophy. However, comprehensive investigations, including whole-exome sequencing, identified a heterozygous CHRNB1 mutation consistent with postsynaptic CMS. Targeted pharmacological therapy led to clinical improvement. This case highlights the importance of considering CMS in patients presenting with limb–girdle weakness and underscores the value of genetic testing in establishing an accurate diagnosis and guiding treatment. Full article

Reparative macrophage polarization and macrophage-derived reactive oxygen species (ROS) are required for ischemia-induced revascularization in peripheral artery disease (PAD). Our previous study showed that mitochondrial fission protein dynamin-related protein 1 (DRP1) promotes reparative polarization and metabolic reprogramming in macrophages and post-ischemic neovascularization. However, the redox-dependent mechanism governing DRP1 activation in this context remains elusive. Here, using a mouse hindlimb ischemia (HLI) model of PAD, we identify cysteine sulfenylation (CysOH) of DRP1 as a critical redox modification induced in ischemic bone marrow (BM)-derived cells. BM chimeric mice reconstituted with CRISPR/Cas9-generated “redox-dead” DRP1-C631A knock-in mutant (Drp1^C/A) BM exhibited markedly reduced limb perfusion recovery and CD31⁺ capillary density in ischemic muscles following HLI. These defects were associated with enhanced Ly6G⁺ neutrophil accumulation, pro-inflammatory F4/80⁺CD80⁺ M1-like macrophages and reduced anti-inflammatory F4/80⁺CD206⁺ M2-like macrophages in ischemic muscle. Mechanistically, using an in vitro PAD model, hypoxia serum starvation (HSS) rapidly induced NADPH oxidase 2-dependent cytosolic ROS production and DRP1-CysOH formation in wild-type macrophages. In contrast, Drp1^C/A macrophages failed to undergo DRP1-CysOH-dependent mitochondrial fission under HSS, resulting in aberrant metabolic reprogramming characterized by enhanced glycolysis and mitochondrial ROS, pro-inflammatory p-NF-κB and M1-genes, and suppressed anti-inflammatory p-AMPK, efferocytosis and M2-genes. Thus, our findings establish DRP1 sulfenylation as a previously unrecognized redox-sensing mechanism that links ischemia-induced ROS to reparative macrophage reprogramming and revascularization, identifying a novel therapeutic target for PAD. Full article

Renal tubular disorders are often overlooked causes of acquired or inherited bone hypomineralization and fragility fractures in adults. The proximal tubule reabsorbs glucose, phosphate, low-molecular-weight proteins, amino acids, bicarbonate, and much of the sodium, potassium, chloride, and calcium. The distal nephron—the thick ascending limb of the loop of Henle, the distal convoluted tubule, and the collecting duct—regulates urine concentration and dilution, maintains acid-base balance via urinary proton secretion, and controls electrolytes, including sodium, potassium, magnesium, and calcium. Tubular defects may cause hyperphosphaturia (high urinary phosphate), hypercalciuria (high urinary calcium), or chronic metabolic acidosis (renal tubular acidosis, RTA). These changes weaken bone mineralization, disrupt bone turnover, and raise the risk of muscle weakness and fractures. This review summarizes acquired and genetic tubulopathies linked to hyperphosphaturia, hypercalciuria, and RTA and outlines a practical diagnostic approach for outpatients with bone fragility and suspected renal tubulopathy. Full article

This prospective case series evaluated the short-term outcomes following percutaneous cementoplasty as the sole palliative treatment for appendicular osteosarcoma in 10 dogs. Synthetic self-hardening calcium phosphate bone substitute was injected into the osseous defect under fluoroscopic guidance after curettage of the bone tumor. Clinician assessment included a numerical rating score for lameness, offloading, and ease of lifting the contralateral limb as well as the 4A-VET postoperative pain scale. Owner assessment was obtained using three descriptive questionnaires, the Helsinki Chronic Pain Index (HCPI), the Canine Brief Pain Inventory (CBPI) and the Canine Symptom Assessment Scale (CSAS). Measures were recorded preoperatively and at 2, 4, 8, and 12 weeks following surgery. Early improvement in the 4A-Vet score was noted at the 2-, 4-, 8-, and 12-week time points for all major pain and function metrics. Similarly, the CBPI pain severity and interference scores demonstrated early postoperative improvement during the 2- and 4-week time points with partial attenuation by 8 and 12 weeks. Panting, difficulty sleeping, whining/moaning, and lack of appetite were significantly reduced when assessed via the CSAS. Cementoplasty as a monotherapy, affording early pain relief and improved structural integrity, supports its role as a palliative limb-preserving option for dogs unable to undergo amputation. Full article

Background/Objectives: Reconstruction of defects in the ankle, foot and heel is complex because of the limited availability of local tissue and multiple comorbidities like diabetes mellitus and peripheral vascular disease. Even though free and pedicled flaps are widely used, their comparative effectiveness remains incompletely defined. Methods: This study presents a narrative analysis of 21 studies. From each study, we extracted data related to flap type, characteristics of the patient, indications, and outcomes: flap survival, limb salvage, functional recovery and complications. Results: Free flaps were mainly used for the management of large, complex, infected, or weight-bearing plantar defects and generally showed high rates of survival (~95–97%) with good functional outcomes and limb salvage rates. On the other hand, pedicled flaps and perforator-based flaps were principally used for small-to-medium defects and showed comparable survival rates in selected cohorts (up to ~98–100%), although direct comparison is limited by differences in defect complexity and patient selection. Overall, the functional outcomes appeared comparable across techniques in appropriately selected patients. However, long-term complications, such as ulceration in weight-bearing heel regions, remained frequent (reported rates were up to 39–41% in some free flap series). Sensory recovery and vascular status were key elements of long-term success, often exceeding flap type in predicting outcomes. Conclusions: Both free and pedicled flaps are effective options for reconstructing lower limb defects when appropriately indicated. While pedicled flaps remain preferred for smaller defects and high-risk patients, free flaps are generally better suited for extensive and more complex defects. The outcomes are influenced by several factors: individualized reconstruction strategy, characteristics of the defects, vascular status and patient comorbidities. Full article

(1) Background: The reconstruction of periacetabular defects after tumor resection remains one of the most challenging procedures in orthopaedic oncology. The modular LUMiC^® system was designed to improve fixation stability and reduce implant-related complications compared with earlier hemipelvic prostheses. We investigated patient and implant survival after LUMiC^® reconstruction, complication types and functional outcomes. (2) Methods: Eighteen patients (8 men, 10 women; mean age 58.9 years) underwent LUMiC^® endoprosthetic reconstruction between 2011 and 2025. Kaplan–Meier analysis was used to estimate patient and implant survival. Complications were categorized according to Henderson. Functional results were evaluated at follow-up using MSTS and TESS. (3) Results: Mean follow-up was 35.52 months (SD 36.89). Overall implant survival was 72.2%. Instability (27.8%) and infection (16.7%) were the leading complications. Two-thirds of patients required at least one revision (mean 3.1 revisions per case). Metastatic disease reduced patient survival (p = 0.012) but did not affect implant longevity (p = 0.31). Functional outcomes were available for only 3 of 18 patients and should therefore be regarded as exploratory. Mean MSTS was 58.9% (SD 21.43) and mean TESS was 73.4% (SD 6.836). (4) Conclusions: Despite high revision rates, the LUMiC^® prosthesis provides durable fixation. Early revision does not appear to compromise implant survival. However, the small and heterogeneous cohort represents a limiting factor of this study. Full article

Background: The latissimus dorsi free flap is a workhorse for extensive lower-extremity soft tissue defects. Conventionally, the skin paddle is designed according to the anticipated defect and left in place on the muscle as a single composite unit. This report describes an alternative approach in which the skin paddle is secondarily mobilized through subcutaneous undermining and rotated as a separate propeller-type local extension flap on random-pattern vascularization, without a specifically identified perforator—a technique that has not been previously reported. Case Presentation: A 38-year-old male with a high-energy distal lower-extremity defect exposing bone, Achilles tendon, and hardware underwent free latissimus dorsi reconstruction with an empirically designed skin paddle over the constant perforator zone. The skin paddle was subsequently mobilized and rotated as a separate propeller-type extension flap to cover the Achilles region, with additional areas managed using split-thickness skin graft and a reverse soleus flap. Results: The latissimus dorsi flap and skin paddle remained viable, providing stable coverage of the defect. The additional reverse soleus flap achieved durable medial coverage, and the limb was ultimately preserved with satisfactory soft-tissue stability. Conclusion: A random-pattern latissimus dorsi skin paddle designed within the anatomically constant perforator zone can provide a feasible new option offering intraoperative flexibility in complex lower-extremity trauma when perforator mapping is impractical. Full article

Unlike newborns, tendon injuries in adults usually lead to fibrotic scarring rather than functional regeneration. This difference is primarily due to the loss of neonatal extracellular matrix (nECM) signaling in adulthood. In this study, we investigated the molecular mechanisms by which a key neonatal ECM proteoglycan, biglycan (Bgn), orchestrates the behavior of tendon stem/progenitor cells (TSPCs) within a scaffold-free 3D cell sheet microenvironment that recapitulates native tendon architecture. Through immunofluorescence screening, we confirmed that Bgn is the predominant proteoglycan in neonatal rat Achilles tendons. Functional validation showed that adding Bgn to cell sheet cultures promoted TSPCs proliferation, maintained stem cell properties, induced tendon differentiation, and encouraged anisotropic alignment—effects similar to those of intact neonatal ECM. Immunodepletion experiments confirmed the causal role of Bgn. Notably, transplanting Bgn-conditioned TSPCs sheets into a rat full-thickness Achilles tendon defect model significantly restored final tensile load, collagen maturation, and gait function. These outcomes were statistically indistinguishable from those of the uninjured contralateral limb. These findings confirm that Bgn-functionalized cell sheet therapy is a viable translational strategy that can effectively recreate a natural 3D regenerative microenvironment. This work sheds light on the mechanisms involved in the determination of stem cell fate by the ECM and establishes Bgn-functionalized cell sheet therapy as a translatable, scaffold-free strategy for overcoming fibrotic repair and restoring functional tendon architecture. Full article