The objective of this study was to evaluate scaphoid, lunate and capitate kinematics after disruption to the primary and secondary scapholunate ligamentous stabilizers, and to assess the effectiveness of scapholunate ligament reconstruction in restoring carpal kinematics post-operatively. Seven upper extremities were harvested, and the scapholunate interosseous ligament (SLIL) was divided. Specimens were mounted onto a computer-controlled dynamic wrist simulator, and simulations of flexion-extension, radial-ulnar deviation, and dart-thrower's motion were undertaken by simulated force application to the wrist tendons. Three-dimensional kinematics of the scaphoid, lunate and capitate were measured using bi-plane X-ray fluoroscopy in the native and ligament deficient state. The SLIL was then reconstructed by either dorsal transarticular loop tenodesis (DTLT), or by the three-ligament tenodesis (3LT) technique, and re-evaluated. SLIL deficiency resulted in significant differences in carpal kinematics compared to that in the healthy wrist across all wrist motions (p < 0.05). The DTLT procedure corrected increased scaphoid ulnar deviation and pronation in the SLIL deficient wrist, but did not significantly improve scaphoid flexion or volar translation of the scaphoid. The 3LT reconstructive technique restored scaphoid flexion and ulnar deviation but did not correct pronation, the increased lunate extension, nor the volar and ulnar translation observed in the ligament deficient wrist. Three-dimensional scaphoid, lunate and capitate motion depends on SLIL integrity, with tears to this ligament resulting in pathological kinematics, which may be partially mitigated with DTLT and 3LT surgical reconstruction. These findings suggest that this surgical reconstruction of the SLIL may not mitigate long-term degenerative joint conditions at the wrist.

A high proportion of individuals with Achilles tendinopathy continue to demonstrate long-term symptoms and functional impairments after exercise treatment. Thus, there is a need to delineate patient presentations that may require alternative treatment. The objective of this study was to evaluate if the presence of metabolic risk factors relates to tendon symptoms, psychological factors, triceps surae structure, and lower limb function in individuals with Achilles tendinopathy. One hundred and fifty-eight individuals (88 female) with diagnosed midportion Achilles tendinopathy were divided into three groups based on the number of metabolic risk factors linked to cardiovascular disease present at baseline: two or more factors, one factor, no factors. Metabolic risk factors were determined by clinical evaluation and past medical history. Achilles tendinopathy symptoms (Victorian Institute of Sport Assessment-Achilles, Patient Reported Outcome Measurement Information System, movement-evoked pain ratings), psychological factors (Tampa Scale for Kinesiophobia), triceps surae structure (B-mode ultrasound of tendon and muscle morphology, continuous shear wave elastography of tendon mechanical properties), and lower limb function (test battery) were compared among groups. Individuals with two or more metabolic risk factors had worse symptoms with loading (p = 0.011), smaller Achilles tendon size relative to body mass (p = 0.002), and worse lower limb function compared to individuals without metabolic risk factors (p < 0.02). No differences were observed between individuals with one metabolic risk factor and those without metabolic risk factors. Future consideration of multiple metabolic risk factors for individuals with Achilles tendinopathy could facilitate understanding the underlying impairments of tendon pathology and recovery that may be addressed with treatment.

Achilles tendon ruptures significantly impair long-term patient function, with two-thirds of patients experiencing persistent functional deficits. Although nonsurgical treatment has gained popularity due to its perceived lower risk of complications, the specific effects of this approach on tendon healing, muscle function, and overall performance remain poorly understood. Directly comparing surgical and nonsurgical treatment options in a clinical population is challenging given the diverse nature of the patient population. Preclinical models are essential to isolate the mechanisms underlying these treatments, enabling a detailed examination of the structural and functional outcomes that are difficult to assess in human studies. Here, we surgically induced Achilles tendon ruptures in 20 adult male Sprague Dawley rats and repaired the rupture in half of these animals. Then, functional outcomes were assessed by measuring plantar flexor torque across the ankle's range of motion using a custom-developed small animal dynamometer, and structural changes were evaluated through measurements of Achilles tendon elongation and plantar flexor muscle mass. We found that surgical treatment led to 11%-35% increased functional plantar flexor torque outcomes compared to nonsurgical treatment. Additionally, plantar flexor muscle mass decreased by 21% in nonsurgically treated animals compared to only 12% in the surgically treated group. Our results suggest that surgically repairing a tendon rupture restores plantar flexor function more effectively than nonsurgical treatment; however, persistent functional deficits in both groups indicate that enhanced rehabilitation strategies are necessary for full functional restoration.

Ewing sarcoma (ES) is a malignant bone tumor prevalent among children and adolescents. Disulfidptosis represents a novel form of cell death; however, the mechanism of disulfidptosis in ES remains unclear. Our aim is to explore the disulfidptosis-related prognostic signature in ES. Utilizing transcriptomic and clinical data of ES, disulfidptosis-related hub genes (DRHGs) were identified by differential gene expression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis. A disulfidptosis-related risk score model (DRRS) was constructed based on these DRHGs. The performance of DRRS was assessed using survival analysis and receiver operating characteristic curve analysis. Immune cell infiltration in different risk subgroups and correlations between DRRS and antitumor reagents were also analyzed. In this study, we developed a disulfidptosis-related prognostic feature based on LRPPRC (leucine rich pentatricopeptide repeat containing), IQGAP1 (IQ motif containing GTPase activating protein 1), NDUFS1 (NADH:ubiquinone oxidoreductase core subunit S1), and TLN1 (talin 1), which may serve as a predictive and independent risk factor for ES. ES patients in the high-risk group exhibited a poorer prognosis, had a higher proportion of myeloid-derived suppressor cells (MDSCs) and M2 type of tumor-associated macrophages, and showed heightened sensitivity to some antitumor agents such as nilotinib and olaparib. This study is the first to construct a disulfidptosis-related prognostic signature that may predict the prognosis and immune response in ES patients, thereby providing a new reference for understanding the mechanisms of ES and guiding immunotherapy.

Drug-resistant organisms (DROs) necessitate the development of new therapies. Antimicrobial blue light (ABL) is a promising option, utilizing photoexcitation of endogenous bacterial components to generate reactive oxygen species, leading to bacterial death. The aim of this study is to investigate the effects of a novel isotropic optical fiber under in-vitro conditions on multidrug-resistant gram-negative Pseudomonas aeruginosa (MDR-Pa) and methicillin-resistant Staphylococcus aureus (MRSA). Time-to-kill assays were conducted in tubes containing 10 mL of 0.9% NaCl solution with an inoculum of 1 × 10⁵ CFU/mL for MDR-Pa or MRSA. The experiments were repeated at least three times per strain. Experimental tubes had either one (low power, LP) or two (high power, HP) optical fibers delivering five ABL wavelengths (405, 415, 435, 450, and 475 nm) over 60 min. Control tubes lacked optical fibers. Samples were taken at 0, 10, 20, 30, and 60 min, streaked on agar, and incubated to determine CFU/mL. Bactericidal reduction was defined as a ≥ 99.9% (≥ 3 log) reduction in CFU/mL. One-way ANOVA were conducted. The novel isotropic optical fiber was able to exhibit bactericidal effects for MDR-Pa only under HP-ABL with a logCFU/mL ± SD difference of -3.71 ± 0.01 at 60 min (p = 0.03). Conversely, the optical fiber exhibited bactericidal effects on MRSA under both LP-ABL and HP-ABL with a logCFU/mL±SD difference of -3.73 ± 0.08 at 60 min (p = 0.03) and -3.07 ± 0.28 at 20 min (p = 0.02), respectively. The isotropic optical fiber demonstrated bactericidal effects on MRSA and MDR-Pa in in-vitro studies and shows potential as a therapeutic option for DROs.

Endothelial progenitor cells (EPCs) have proven to be a highly effective cell therapy for critical-sized bone defects. Cryopreservation can enable long-term storage of EPCs, allowing their immediate availability on demand. This study compares the therapeutic potential of EPCs before and after cryopreservation in a small animal critical-sized bone defect model. Five-millimeter segmental defects were created in the right femora of Fischer 344 rats, followed by stabilization with a miniplate and screws. The animals received 2 × 10 fresh EPCs (n = 7) or 2 × 10 cryopreserved EPCs (n = 9) delivered on a gelatin scaffold. Cryopreserved EPCs were stored for 7 days at -80°C prior to thawing and loading onto the gelatin scaffold. Biweekly radiographs were taken until the animals were euthanized 10 weeks after surgery. The operated femora were then evaluated using microscopic-computed tomography (micro-CT) and biomechanical testing. All animals treated with fresh (n = 7/7) or cryopreserved (n = 9/9) EPCs achieved radiographic union at 10 weeks. Animals treated with fresh EPCs had statistically significant higher radiographic scores at 2 weeks (p < 0.05) but showed no statistically significant differences thereafter (p > 0.05). Micro-CT analysis showed no statistically significant differences between the groups in bone volume (BV) or BV normalized to total volume (p > 0.05), with excellent bone formation in both groups. Finally, there were no differences in biomechanical outcomes between the groups (p > 0.05). These results demonstrate that cryopreserved EPCs are highly effective and equivalent to fresh EPCs for healing critical-sized bone defects in a rat model of nonunion.

Osteochondral defects (OCD) pose a significant clinical challenge due to the limited self-repair capacity of cartilage, leading to pain, joint dysfunction, and progression to osteoarthritis. Cellular implantations of adult mesenchymal stem cells (MSCs) enhanced with treatment of factors, such as small molecule Kartogenin (KGN) to promote chondrogenic differentiation, are promising but these cells often encounter hypertrophy during differentiation, compromising long-term stability. Induced pluripotent stem cell-derived MSCs (iMSCs) offer greater proliferative and differentiation capacity than MSCs and may provide a superior source of cells for cartilage repair. We hypothesized that treatment of iMSCs with TGFβ3 and KGN would enhance chondrogenic differentiation and that implanting these pellets into a rat OCD model would promote de novo cartilage regeneration and reduce pain behavior. We pellet cultured iMSCs derived from articular chondrocytes and treated with various conditions of TGFβ3 and KGN. We then assessed the in vivo performance of the pellets using a trochlear osteochondral defect in male Lewis rats. Co-treatment of iMSC pellets with TGFβ3 and KGN showed more pronounced chondrogenic differentiation than sequential treatment and exhibited stronger expression of chondrogenic genes. Implantation of the TGFβ3/KGN-treated iMSC pellets into OCD resulted in modest repair, as observed via gross morphology, effectively prevented the onset of joint hyperalgesia, and helped to maintain normal gait out to 12 weeks post-implantation compared to untreated OCD rats. Our study highlights the potential of KGN to enhance iMSC pellet chondrogenesis, offering a scaffold-free, cell-based therapy that could simplify clinical translation and improve outcomes for patients with cartilage injuries.

Incomplete tendon healing and postponed muscle weakness after Achilles tendon rupture and surgical repair lead to poor performance in patient activities. Although the effectiveness of postoperative early functional rehabilitation has been proven, the priority and each effect of specific methods in early rehabilitation remain unclear. We hypothesized early muscle contraction exercises without joint motion would promote tendon healing and prevent calf muscle atrophy; in contrast, early static stretching after surgical repair would not contribute to tendon healing and induce calf muscle atrophy. C57Bl/6 mice underwent Achilles tendon rupture and suture repair, followed by different methods of post-surgery interventions: a non-exercise group, a Static stretching group, and an Electrical muscle stimulation group. 3 and 5 weeks after surgery, we assessed ex vivo tendon mechanical properties, collagen fiber alignment, and histological muscle properties. Electrical Muscle Stimulation restored the recovery of tendon mechanical properties and muscle strength more quickly than Static stretching. Static stretching had no additional effect on them compared to the non-exercise. Our results suggested that calf muscle contraction was essential as a post-surgery early functional rehabilitation to load tensile forces on tendons and improve Achilles tendon healing. Additionally, early muscle contractions naturally promote restoring muscle function after the rupture, but further research is needed to optimize muscle contraction protocols.

Effective surgical planning is crucial for maximizing patient outcomes following complex orthopedic procedures such as proximal femoral osteotomy. In silico simulations can be used to assess how surgical variations in proximal femur geometry, such as femur neck-shaft and anteversion angles, affect postoperative system mechanics. This study investigated the sensitivity of femur mechanics to postoperative neck-shaft angles, anteversion angles, and osteotomy contact areas using patient-specific finite element analysis informed by neuromusculoskeletal models. A sequential neuromusculoskeletal modeling and finite element analysis pipeline was used to simulate postoperative mechanics in three pediatric patients with varying demographic and anatomic features. Nine surgical configurations derived from permutations of the clinical envelope of neck-shaft angles and anteversion angles were simulated for the stance phase of gait. The outcome mechanics assessed were peak von Mises stresses on the bone-implant contact surfaces as well as interfragmentary movement and strain on the osteotomy location. Peak von Mises stress and interfragmentary movement and strain were on average 38% more sensitive to surgical variation in neck-shaft angle compared to anteversion angle. A significant negative correlation was detected between contact area and interfragmentary movement (r = -0.90, p < 0.0001) and strain (r = -0.45, p = 0.017). Overall findings suggest neck-shaft angle significantly influences postoperative femur mechanics and highlight the importance of maximizing contact area to limit interfragmentary motion and foster an optimal mechanical environment for bone healing and callus formation following proximal femoral osteotomy. Between-patient variation in sensitivity to proximal femoral geometry reinforced the importance of patient-specific surgical planning.

Compression neuropathy is a prevalent medical condition, including common types such as carpal tunnel syndrome, cubital tunnel syndrome, sciatica, and many others. While the neurological consequences are well understood, the effects on bone properties and the potential downstream impact on fracture risk remain less clear. This study aimed to assess the influence of compressive neuropathy on bone properties using a rabbit model of sciatic nerve compression. We hypothesized that compressive neuropathy could adversely alter bone properties. Five New Zealand white rabbits underwent surgery to induce perineural scarring in the sciatic nerve, with the contralateral limb serving as a sham control. Bone mineral density (BMD), mechanical strength, and bone signaling proteins were evaluated through microcomputed tomography (μCT), four-point bending tests, and ELISA assays, respectively. Sciatic nerve histology was analyzed using VEGF and Nissl staining to assess axon and Schwann cell densities and quantified using image analysis software. The results showed no significant differences in BMD, biomechanical properties, or key bone signaling proteins (OPG and RANKL) between the affected and control tibias. These findings suggest that compression neuropathy does not significantly impact bone properties in the rabbit model.

Previous studies suggest a relationship between femoroacetabular impingement (FAI) and femoral neck stress fractures (FNSF), due to pathologic biomechanics in the setting of femoral head abutment (cam morphology) and/or acetabular overcoverage (pincer morphology). The purpose of this study is to evaluate the association between cam or pincer morphology and FNSF, compared to a control group of patients without hip pain. A retrospective review of the electronic medical record at a single institution was queried for patients with FNSF over a 10-year time period from January 2011-2021. These patients were compared to a control group with diagnostic radiographs and a chief complaint that was not hip pain presenting to the institution's emergency department. Hip morphology was evaluated radiographically. A multivariate logistic regression was used to investigate an association between FNSF and cam or pincer morphology. Eighty-three patients with FNSF and a mean age of 38.6 years were compared to 55 healthy controls with a mean age of 35.8 years. Patients in the FNSF group were more often female, white, and had lower BMI. These patients were also more likely to have associated cam morphology (p = 0.010). Binary logistic regression demonstrated a statistically significant independent association between both cam (OR 5.2, p = 0.01) and pincer (OR 4.6, p = 0.022) morphology with FNSF when controlling for demographic variables. Black race and higher BMI were protective factors for FNSF (OR 0.09, OR 0.84, p < 0.01). In summary, radiographic cam morphology, superolateral acetabular overcoverage, female sex, and lower BMI are risk factors for sustaining FNSF, while the black race was found to be protective.

Flexible flatfoot is common among school-age children and significantly affects walking efficiency, balance stability, and joint-movement coordination in children. The demands on the skeletal structure and muscle function are increased during running; however, the impact of a flexible flatfoot on children's running capabilities is unclear. In this study, we aimed to investigate the effects of flexible flatfoot on the running function of school-age children. Participants with flat feet (n = 28) and typical feet (n = 27) ran on a flat surface at their chosen maximum pace. At the same time, the kinematic and dynamic parameters of their lower limb joints were monitored. A two-sample statistical analysis assessed the differences in the lower limbs' three-dimensional kinematic and dynamic parameters during running. The findings revealed a significant reduction in running velocity, stride length, and frequency, and an increased proportion in the support phase (p < 0.05) in children with flexible flat feet. The navicular drop time decreased, whereas the dynamic navicular drop height increased (p < 0.05). A notable decrease in the maximum plantar flexion and eversion torque, power, and power absorption of the ankle joint was observed (p < 0.01). Furthermore, the maximum flexion torque of the knee and hip joints and hip joint power absorption decreased (p < 0.05). The peak ground reaction force in the anteroposterior directions was reduced (p < 0.01). These results indicate that flexible flatfoot can impair the running efficiency of school-age children and lead to diminished motor stability and reduced propulsive and braking capabilities.

The role of the infrapatellar fat pad (IPFP) in knee osteoarthritis is not understood. This study aimed to identify relationships between MRI-based signal abnormalities in the IPFP and measures of structural pathology and symptom severity in PFJOA, as well as investigate the influence of obesity and sex on these relationships. Seventy participants (ages 28-80) with isolated PFJOA underwent bilateral knee MRI scan acquisitions and completed the Knee Injury and Osteoarthritis Outcome Score (KOOS). MR images were scored for abnormal IPFP area and signal intensity, joint effusion, synovial proliferation, and patellar and trochlear cartilage damage. Repeated measures correlations were performed to assess associations between abnormal area and signal of IPFP and PFJOA pathology and KOOS, respectively. Associations were interrogated across weight-based groups based on BMI and sex-based groups. Between abnormal IPFP and PFJOA pathology, we observed no significant associations. Between abnormal IPFP and patient-reported outcomes, we observed weak to moderate significant negative associations between the size of the abnormal IPFP area and all KOOS subscales. In a sex-based analysis of IPFP and KOOS associations, we observed significant moderate negative correlations between IPFP and KOOS scores across all subcategories in female participants. In male participants, abnormal IPFP was not associated with KOOS scores. The IPFP is significantly related to PFJOA patient-reported pain and function, and this correlation is stronger in high-risk OA groups.

The goal of medial open-wedge high tibial osteotomy (MOW-HTO) is to redistribute load by realigning the lower limb. This surgery is indicated for mild to moderate medial compartment osteoarthritis with varus deformity in cases unresponsive to conservative treatment. Procedures for accompanying cartilage lesions, such as multiple drilling on the medial femoral condyle (MFC), are often performed simultaneously, potentially affecting bone metabolism along with load redistribution and union progression. This study assessed changes in bone metabolism following MOW-HTO. Two-year follow-up data were collected from 51 knees undergoing MOW-HTO between March 2019 and December 2020. Single-photon emission computed tomography and conventional CT (SPECT/CT) were performed on postoperative Day 1, 3 months, 1 year, and 2 years. Maximum standardized uptake value (SUVmax) was measured in each compartment and the osteotomy gap. At 1 year postoperatively, SUVmax decreased in the medial femur and tibia zones (p < 0.001). SUVmax decreased in the lateral osteotomy gap zones at 1 year (p = 0.001 anterior; p = 0.002 posterior), while medial zones showed a sustained increase. At the posteromedial zone, SUVmax decreased at 2 years (p = 0.012). Subjects were divided into two groups: those with MFC drilling (group one) and those without (group two). SUVmax was higher in group one throughout the 2 years (p < 0.001). Unloading effects were notable in the medial compartment. MFC drilling increased SUVmax, creating different patterns between groups. SUVmax decrease in the osteotomy gap occurred earlier in the lateral zone.

Patient-specific flanged acetabular components are utilized to treat failed total hip arthroplasties with severe acetabular defects. We previously developed and published a finite element model that investigated the impact of hip joint center lateralization on construct biomechanics during gait conditions. This model consisted of a patient-specific implant designed to address a superior-medial defect created in a standard pelvic geometry. This study aims to utilize the same model and examine how cortical shell thickness and ischial cancellous bone density affect the strain distribution in the bone and bone-implant micromotion. Using published studies and bone density analyses of patients who had undergone total hip arthroplasties with flanged acetabular components, we established a thickness range for the cortical shell (1.5, 1, and 0.75 mm) and two levels of ischial cancellous bone density (100% and 25%). We compared the resulting bone strains against the fatigue strength of the bone (0.3% strain) as a criterion for local bone failure and the bone-implant micromotion against the threshold associated with bone ingrowth (20 µm). A thinner pelvic cortical shell and lower ischial cancellous bone density increased areas of bone at risk of failure, particularly at the ischial screws (from 6% to 38%), and decreased areas compatible with bone ingrowth. These findings agree with our clinical knowledge that compromised ischial bone and inadequate ischial fixation negatively impact the survivorship of flanged acetabular components. This series establishes our modeling approach of a computational model that can be utilized to guide implant design to best treat unique acetabular defects.

Enthesitis, or inflammation specific to sites in the body where tendon inserts into bone, can arise in isolated joints from overuse or in multiple joints as a complication of an autoimmune condition such as psoriatic arthritis or spondyloarthritis. However, the pathogenesis of enthesitis is not well understood, so treatment strategies are limited. A clinically relevant animal model of enthesitis would allow investigators to determine mechanisms driving the disease and evaluate novel therapies. Therefore, we developed a murine model of inducible enthesis-specific inflammation by constitutively activating the NF-κB pathway in Gli1+ cells. Gli1Cre mice were crossed with IKKβ-overexpression mice and given tamoxifen injections 5 days postnatally to induce enthesitis. Sixteen weeks of IKKβ overexpression in enthesis cells led to impaired mechanical properties, subtle histologic changes, and changes to expression of extracellular matrix- and inflammation-related genes. Increased loading from treadmill overuse activity did not exacerbate this phenotype. Clinical significance: The new murine model may have utility for studying the pathogenesis of enthesitis and approaches to treat the condition.

Radiostereometric Analysis (RSA) is the most accurate method for determining early micromotions of orthopedic implants. Computed Tomography Radiostereometric Analysis (CT-RSA) is a method that can be used to determine implant and bone micromovements using low-dose CT scans. This study aimed to evaluate the reliability of the CT-RSA method in measuring the interfragmental mobility in patients who have undergone a correction osteotomy due to a malunited distal radius fracture. Twenty-four patients were included and operated with a radiolucent volar plate. Markers were embedded in the plate and bone. RSA and CT examinations were obtained postoperatively up to 1-year postoperative. Micromovements of the distal radius segment relative to the proximal were compared between the methods with paired analysis and Bland-Altman plots. The limits of clinical significance were: dorsal/volar tilt < 10°, radial shortening < 5 mm, radial inclination ≥ 15°, and radial shift < 5 mm. For the dorsal/volar tilt, the paired analysis between the two methods, showed a mean difference (95% CI) of -0.06° (-0.67 to 0.55), for radial compression-0.04 mm (-0.09 to 0.01), for radial inclination 0.21° (-0.06 to 0.48), and for radial shift -0.07 mm (-0.21 to 0.07). The paired analysis for micromotions showed that the thresholds of clinical significance are excluded from the difference's 95% CI. The Bland-Altman plots showed comparable results up to 1 year, considering clinically relevant thresholds. In conclusion, the CT-RSA method is comparable to that of marker-based RSA in measuring micromotions after wrist osteotomy, as the differences between the methods are not clinically significant.

Exercise influences clinical Achilles tendon health in humans, but animal models of exercise-related Achilles tendon changes are lacking. Moreover, previous investigations of the effects of treadmill running exercise on rat Achilles tendon demonstrate variable outcomes. Our objective was to assess the functional, structural, cellular, and biomechanical impacts of treadmill running exercise on rat Achilles tendon with sensitive in and ex vivo approaches. Three running levels were assessed over the course of 8 weeks: control (cage activity), moderate-speed (treadmill running at 10 m/min, no incline), and high-speed (treadmill running at 20 m/min, 10° incline). We hypothesized that moderate-speed treadmill running would beneficially impact tendon biomechanics through increased tenocyte cellularity, metabolism, and anabolism whereas high-speed treadmill running would cause a tendinopathic phenotype with compromised tendon biomechanics due to pathologic tenocyte differentiation, metabolism, and catabolism. Contrary to our hypothesis, treadmill running exercise at these speeds had a nominal effect on the rat Achilles tendon. Treadmill running modestly influenced tenocyte metabolism and nuclear aspect ratio as well as viscoelastic tendon properties but did not cause a tendinopathic phenotype. These findings highlight the need for improved models of exercise- and loading-related tendon changes that can be leveraged to develop strategies for tendinopathy prevention and treatment.

This study investigates the therapeutic potential of Msx1-overexpressing bone marrow mesenchymal stem cells (BMSCs) in enhancing tendon-bone healing in rotator cuff injuries. BMSCs were genetically modified to overexpress Msx1 and were evaluated in vitro for their proliferation, migration, and differentiation potential. Results demonstrated that Msx1 overexpression significantly increased BMSC proliferation and migration while inhibiting osteogenic and chondrogenic differentiation. In a rat model of acute rotator cuff injury, Msx1-BMSCs embedded in a hydrogel scaffold were implanted at the tendon-bone junction. Micro-CT analysis revealed substantial new bone formation in the Msx1-BMSC group, and histological evaluation showed organized collagen and cartilage structures at the repair site. Biomechanical testing further confirmed enhanced structural strength in the Msx1-BMSC-treated group. These findings suggest that Msx1 modification enhances BMSC-mediated repair by promoting cell proliferation and migration, facilitating tendon-bone integration. This Msx1-based approach presents a promising strategy for advancing regenerative therapies for rotator cuff injuries.

Hip abductors are essential for hip function. To understand abduction weakness, it is important to know which muscles contribute to abduction force. Our aim was to investigate the effects of an experimentally induced weakness of the different muscles (tensor fasciae latae [TFL], gluteus medius and minimus (Gmed/min), gluteus maximus [Gmax]) on the abduction force. Ten participants received sequential nerve blocks of the TFL, the Gmed/min, and the Gmax. Subsequently, abduction force was measured in the lateral decubitus position in three sagittal positions of the hip (30° flexion, neutral, 30° extension). In 30° flexion, the average abduction force was 220 N without block, 187 N with block of the TFL, 83 N with block of the Gmed/min, and 97 N with block of the Gmax, respectively. In neutral position, average abduction force was 213 N without block, 200 N with block of the TFL, 82 N with block of the Gmed/min, and 115 N with block of the Gmax, respectively. In 30° extension, average abduction force was 116 N without block, 146 N with block of TFL, 61 N with block of the Gmed/min, and 94 N with block of the Gmax, respectively. An induced weakness of the TFL reduces abduction force only in 30° of hip flexion by 15%. It is not highly relevant as an abductor. An induced weakness of the Gmax reduces abduction force in flexion by 43%-56%, depending on the position. It is, therefore, highly relevant as an abductor of the hip.

Periprosthetic joint infection (PJI) is a leading cause and major complication of joint replacement failure. As opposed to standard-of-care systemic antibiotic prophylaxis for PJI, we developed and tested titanium femoral intramedullary implants with titania nanotubes (TNTs) coated with the antibiotic gentamicin and slow-release agent chitosan through electrophoretic deposition (EPD) in a mouse model of PJI. We hypothesized that these implants would enable local gentamicin delivery to the implant surface and surgical site, effectively preventing bacterial colonization. In the mouse PJI model, C57BL/6 mice received implants with TNTs coated with chitosan (chitosan group; control group) or with TNTs coated with chitosan and gentamicin (chitosan + gentamicin group; experimental group). Following implant placement, the surgical site was inoculated with 1 × 10 CFUs of Xen36 bioluminescent Staphylococcus aureus. All the mice in the chitosan group and none in the chitosan + gentamicin group had evidence of infection based on CFU analysis and bioluminescence imaging through the 14-day assessment postsurgery. Correspondingly, scanning electron microscopy analysis at the implant surface demonstrated bacterial biofilm only in the chitosan group. Furthermore, periosteal reaction and peri-implant bone loss at the femur were significantly reduced in the chitosan + gentamicin group. The chitosan + gentamicin group had reduced pain behavior, improved weight-bearing, and increased weight compared to the chitosan-control group. This study provides preclinical evidence supporting the efficacy of implants with TNTs coated with chitosan and gentamicin through EPD for preventing bacterial colonization and biofilm formation in a mouse model of PJI.