Search Results (1,952)

Bone regeneration focuses on the creation of functional tissue to repair bone defects. Creating a biodegradable scaffold hydrogel that combines a hemostatic agent with bioactive ceramics can afford the biological and mechanical benefits of both components. In the present study, we developed an injectable gelatin–alginate dual-composite hydrogel, loaded with two functional fillers: hydroxyapatite (HA) and the hemostatic agent montmorillonite (MMT). HA (microparticles and nanoparticles) was incorporated at concentrations of 10–30 mg/mL, with and without MMT at 20 mg/mL. The effects of functional fillers and their concentration on the microstructure and resulting physical and mechanical properties were studied, and a qualitative model summarising these effects was developed. All formulations exhibited clinically appropriate gelation times (5–29 s). n-HA significantly prolonged gelation time, reaching 29 ± 3 s at 30 mg/mL, while MMT reduced gelation time at all concentrations. The tensile strength of the unloaded hydrogel reached 20 kPa and increased to 57 kPa with 30 mg/mL of n-HA. The tensile strength even increased further with the addition of MMT (77 kPa). The results indicate that the combination of HA and MMT produced dual micro-composite hydrogels with moderate reinforcement, whereas the combination of n-HA and MMT generated dual nano–micro composites with combined reinforcing effects. The latter exhibited the highest strength and sealing ability while maintaining clinically relevant gelation times and controlled swelling behaviour. In conclusion, the combination of MMT with n-HA or HA enables the creation of functional hydrogels with controlled properties, tailored to specific applications in bone regeneration. Full article

Regenerative medicine based on Mg alloy implants is considered a modern approach to address bone defects. It represents a promising alternative to traditional grafting strategies (auto-, allo-, and xenografts) by potentially mitigating complications such as donor-site morbidity and limited supply, which are discussed in this paper. In line with this global topic, attention is devoted to an innovative manufacturing route for Mg-Nd and Mg-Zn implants for the treatment of small bone defects. First, the proposed manufacturing method is described in detail, including the materials used and the manufacturing steps, and then a comparison between the reference (cast alloys) and implant samples is performed. The mechanical properties, weight loss in simulated body fluid (SBF), surface analysis (contact angle and roughness measurements), and cytotoxicity were evaluated to determine whether the developed implants are suitable for consideration as future bone implants. The main conclusions of the study were that both Mg-based implants exhibited mechanical properties (compressive strength and Young’s modulus) with values very close to those of the human bone, reduced mass loss (a fact that is in a direct relationship with an increase in corrosion resistance due to MgF₂ conversion coating, which is a secondary result of the proposed manufacturing route), and finally, a good biocompatibility sustained by cell culture and cytotoxicity assessment, as well as by apoptosis and necrosis analysis on a human patella-derived osteoblastic cell line. Full article

Background/Objectives: An Aneurysmal Bone Cyst (ABC) is a rare benign osteolytic bone lesion with locally destroying growth. It occurs mostly in the first two decades of life, rarely in older patients, and commonly affects the metaphysis. Clinical presentation includes pain and pathologic fractures. While most ABCs occur as primary lesions, there is an entity of secondary (reactive) ABC following osseous lesions such as fractures. We report a rare case of a secondary aneurysmal bone cyst of the distal radius following a distal radius fracture 4 years prior, with subsequent treatment and reconstruction. Methods: A 67-year-old female patient presented with a pathologic distal forearm fracture with radiologically expansive lytic bone lesion of the metaphysis of the distal radius, suspicious of an ABC. A biopsy and primary fracture management with an external fixator were performed due to the unclear dignity of the lesion. The diagnosis of an ABC was confirmed in the biopsy. The tumor resection and reconstruction were performed with a vascularized free fibula graft (ipsilateral, double barrel), using patient-specific 3D-printed osteotomy templates. Results: Follow-up radiographs showed excellent bone union with progressive remodeling. The functional outcome was very good with almost the same range of motion and grip strength as the contralateral side. No limitation in everyday life and no donor site morbidity was reported. Conclusions: ABC is a rare benign bone tumor the treatment of which consists of complete resection and reconstruction. Reconstruction of the distal radius can be achieved with a fibula graft. In our case, an excellent result was achieved with patient-specific osteotomy templates. Only a few cases of ABC in the distal radius and at this age have been reported; nevertheless, it should be considered as a differential diagnosis for osteolytic bone lesions Full article

Background: The extracellular matrix (ECM) plays a central role in the mechanical strength and functional integration of tissue-engineered matrix (TEM), particularly in cardiovascular and load-bearing applications. Mesenchymal stromal cells (MSCs) from different sources may vary in their ECM-forming potential. Methods: In this study, adipose-derived (hADMSC), bone marrow-derived (hBMSC), and umbilical cord-derived MSCs (hUCMSC) were compared with human dermal fibroblasts (HDFBs) as a reference. Cells were seeded onto polyglycolic acid (PGA)/poly-4-hydroxybutyrate (P4HB) scaffolds and cultured for 3 weeks under static or hydrodynamic conditions using orbital shaking. TEM development was assessed macroscopically, histologically (using H&E and Masson’s trichrome stains), and by polarized light microscopy (Picrosirius Red), alongside biochemical assays that quantified DNA, glycosaminoglycan (GAGs), and hydroxyproline (HYP). Results: Hydrodynamically stimulated culture consistently improved ECM deposition across all groups. TEMs exposed to hydrodynamic stimulation (hydrodynamic conditions) were thicker, more uniformly filled, and exhibited increased collagen deposition compared with static TEMs, which remained thinner and showed persistent scaffold remnants. Polarized light analysis demonstrated that dynamic loading promoted collagen maturation in all groups, as evidenced by an increased prevalence of thick, birefringent collagen fibers indicative of mature collagen. Biochemical analyses showed that HDFB-derived TEMs produced the highest total collagen and ECM content under both static and hydrodynamic conditions; however, these matrices remained comparatively thin and densely packed. In contrast, MSC-derived TEMs formed thicker and more spatially distributed ECM in response to hydrodynamic stimulation. Conclusion: Among the MSC sources, hUCDMSC-derived TEMs exhibited the most advanced collagen maturation and the most uniform collagen distribution under hydrodynamically stimulated culture, whereas hADMSC-derived TEMs showed the greatest matrix thickening and volumetric ECM expansion with intermediate collagen maturation. hBMSC-derived TEMs displayed clear responsiveness to hydrodynamic stimulation but remained limited in overall collagen deposition and fiber maturation. These findings underscore that both hydrodynamic stimulation and cell source are critical not only for maximizing ECM deposition, but also for ensuring physiologically relevant collagen maturation and matrix organization in grafts suitable for clinical translation. Full article

Objectives: Hormonal changes during the postmenopausal period of life predispose women to changes in fat tissue distribution and the risk of insulin resistance, and may lead to deterioration of bone metabolism. Physical activity plays a significant role in improving metabolic health and may inhibit bone mass decrease. The purpose of this study was to analyze the relationships between bone health, body composition, maximal oxygen uptake (VO₂max), and carbohydrate metabolic indices in non-diabetic postmenopausal women. Methods: Fifty-seven postmenopausal women were included in the study (64.9 ± 4.8 years). The areal bone mineral density (aBMD) of femoral neck and L1–L4, femur strength index (FSI), total fat (FM), lean body mass (LBM), VO₂max, serum insulin, and glucose concentrations were determined. The insulin resistance index (HOMA-IR) was also calculated. The main statistical analyses were performed using hierarchical multiple linear regression models. Results: Body mass index (BMI), FM and LBM positively correlated with aBMD results (p ≤ 0.01) and FM negatively with FSI levels (p < 0.05). VO₂max showed a positive association with FSI and this relationship was confirmed in hierarchical multiple regression analysis (p < 0.05). Regression analysis revealed that the base model including age and BMI explained the variance in the femoral neck aBMD (p ≤ 0.01) and L1–L4 aBMD (p ≤ 0.01), respectively. In the case of the femoral neck aBMD model, adjustment for VO₂max increased the explained variance. Alternative models with carbohydrate metabolic indicators did not increase the explained variance. Conclusion: Our results suggest that aerobic capacity may be related to the level of femur bone strength. Somatic characteristics and carbohydrate metabolic status appear to play a role in the correlations between femur bone health and VO₂max. Full article

This study developed a transdermal drug delivery system for Rheumatoid Arthritis (RA) using a dual-network hydrogel microneedle patch loaded with methotrexate nanocrystals (DHMN@MTX-NCs), and explored its synergistic therapy with Adalimumab (ADA) for a painless, long-acting, and targeted RA treatment. This study synthesized Methacrylated Hyaluronic Acid and Methacrylated Gelatin. MTX-NCs were prepared by solvent-antisolvent precipitation and incorporated into a dual-network hydrogel microneedle patch via centrifugal molding. Evaluations included pharmaceutical properties, mechanical strength, drug release, in vitro anti-inflammatory effects on RAW 264.7 cells, and therapeutic efficacy in a rat RA model. The experimental results show that the prepared MTX-NCs present a spherical shape, an average size of 325.72 nm, a PDI of 0.154, and a drug-loading capacity of 61.3%. The microneedle patch exhibited high puncture efficiency and suitable swelling. In vitro, DHMN@MTX-NCs combined with ADA most strongly inhibited macrophage migration, upregulated IL-10, and downregulated TNF-α, IL-1β, NO, iNOS, and COX-2. In vivo, both monotherapy and combination therapy reduced joint swelling, bone erosion, and histopathological damage. Ultimately, the study demonstrated the synergistic anti-inflammatory efficacy of DHMN@MTX-NCs combined with ADA, providing a novel, non-invasive, and targeted therapeutic strategy for RA. Full article

Aim: To develop clear, evidence-based, and standardized guidelines for the design, selection, and clinical use of implant abutments and prosthetic components in order to optimize the biological, mechanical, and esthetic performance of the implant supracrestal complex. Methods: A panel of 10 expert clinicians and researchers in prosthodontics participated in the Osstem Global Consensus Meeting. For the present consensus meeting, a scoping review was performed in advance and discussed among the participants. A comprehensive search of the literature was performed up to June 2025. Two reviewers (M.T. and F.G.) independently conducted screening, data extraction, and quality assessment using the Newcastle–Ottawa Scale. The evidence was synthesized and discussed by the panel of expert clinicians during the consensus meeting. After that, guidelines were developed using a 14-question questionnaire to formulate consensus-based clinical recommendations. The participants answered structured questions and discussed discrepancies to achieve a consensus. Results: The panel of expert clinicians reached a consensus on several prosthetic key points. Concave abutment profiles and emergence angles <30° promoted peri-implant tissue stability, while convex designs and wider angles increased risks of bone loss and peri-implantitis. Titanium remains the reference abutment material in posterior sites, while zirconia provides superior esthetics anteriorly, and hybrid abutments balance strength and esthetics. Conclusions: Prosthetic design and abutment material selection critically affect peri-implant tissue stability and esthetic outcomes. The evidence supports screw-retained designs, platform switching, and the “one abutment–one time” approach for predictable long-term success. Full article

Knee biomechanical demands vary across different sports due to sport- and position-specific patterns of muscle recruitment. To return to performance, athletes must adequately restore knee kinematics to regain control over the same sport mechanics that led to the initial anterior cruciate ligament (ACL) injury. ACL graft selection should therefore minimize donor site morbidity and support sport-specific demands. This study aims to address the available evidence and guide surgical graft choice in athletes. A literature search of PubMed, MEDLINE, Scopus, and Web of Science (up to September 2025) assessed BPTB, hamstring, and quadriceps tendon autografts. Outcomes included revision, graft survival, return to sport, time to return, PROMs, anterior knee pain, donor site morbidity, and prognostic factors (age, sex). Sports were classified as pivoting, contact/collision, or endurance/non-pivoting. The results were synthesized narratively. In pivoting and cutting sports, bone–patellar tendon–bone (BPTB) autografts offer high survival rates but are associated with a high incidence of anterior knee pain, which is a substantial drawback in kneeling or flexion-intensive sports. Hamstring tendon (HT) grafts carry higher revision rates in female and younger patients, though they have low donor site morbidity that does not appear to affect long-term athletic performance. Quadriceps tendon (QT) grafts are emerging as a promising option for pivoting athletes. However, conflicting results indicate that the revision risk is comparable to that of HT grafts and possible long-standing extensor mechanism weakness. Contact and collision sports demonstrate similar trends, but kneeling and contact injuries are more common in this group. Thus, while prioritizing powerful hamstring strength, anterior knee pain symptoms should still be carefully considered. The diameter of the HT autograft should exceed 7.5 mm to ensure comparable revision outcomes with BPTB. QT grafts remain a limited-evidence attractive option. Endurance and non-pivoting athletes require fewer pivoting mechanics but rely heavily on muscle symmetry and repetitive motion. BPTB grafts are less suitable in this category due to alterations in sprint mechanics, muscle asymmetry, and repetitive patellofemoral joint loading. HT grafts provide favorable rates of return to sport, whereas evidence regarding QT graft use in non-pivoting athletes remains limited. Full article

In this research, Fe-P scaffolds were successfully fabricated by the powder metallurgy method for the first time, using NaCl as the space holder for bone tissue engineering applications, with apparent porosities of approximately 70%. The Fe₃P powder was successfully synthesized by the mechanochemical method under an argon atmosphere using an initial mixture of Fe and P powders. The XRD patterns show that Fe₃P was obtained after sintering the milled powders at 1000 °C. Fe, Fe₃P, and Fe-50 wt% Fe₃P composite scaffolds and bulk pellets were prepared by sintering the milled powder at 1000 °C. Furthermore, the mechanical properties (compression strength) and bioactivity of the Fe-P scaffolds were determined. According to the compression test results, the composite scaffold showed higher compressive strength, lower fracture strain, and higher elastic modulus than the Fe and Fe₃P scaffolds, indicating that adding Fe₃P to Fe improves the mechanical properties. Moreover, among the scaffolds prepared by sintering at 1000 °C, the Fe scaffold exhibited the highest corrosion rate compared to the Fe₃P and composite samples, while the corrosion resistance of the composite sample was 3 times higher than that of the Fe sample. The ICP analysis showed that the amount of Fe released from the bulk pellets during soaking in PBS solution after four weeks was 3220 μg/dL, 4003 μg/dL, and 4774 μg/dL for the composite, Fe₃P, and Fe samples, respectively. The composite sample showed the highest cell viability, while the Fe sample had the lowest. The compressive strength (12.62 MPa) and fracture strain (5.98%) of the porous sintered composite scaffold at 1000 °C were within the range of trabecular bone, while the compressive strength of the composite sample was 17 times higher than that of the Fe sample. Furthermore, the MTS test showed that all the samples had good viability, while the composite sample had the best cell viability. The scaffolds were not cytotoxic. It can be concluded that the mechanical and biological properties of the composite sample were superior to those of the Fe and Fe₃P samples and that it may be a promising candidate for bone tissue engineering applications, especially for trabecular bone replacement. Full article

Titanium dioxide nanotubes (TNTs) have favorable biocompatibility and nanoscale morphologies, and they have been extensively explored for titanium implant surface modifications. However, they are limited by their mechanical strength and weak interfacial adhesion between the nanotube layer and the titanium substrate. This restricts their clinical applications. In this study, a two-step electrochemical anodization method is developed to achieve in situ tantalum (Ta) doping into TNT arrays to enhance their mechanical performance without altering their nanotubular structure. The surface morphology, element and crystal phase composition, surface roughness, wettability, and mechanical properties of the Ta-doped TNTs were then thoroughly characterized. Scanning electron microscopy revealed that the Ta doping did not change the nanotube architecture. In addition, X-ray diffraction confirmed anatase TiO₂ formation in all the samples. X-ray photoelectron spectroscopy demonstrated that Ta⁵⁺ doping significantly reduced oxygen vacancies, and this was a concentration-dependent effect. Nanoindentation and scratch tests showed that the hardness, the Young’s modulus of the nanotube layer, and the adhesion strength between the nanotubes and the titanium substrate were markedly improved compared to those of the undoped TNTs. These mechanical enhancements may be attributed to lattice densification due to Ta doping. In vitro cell assays further demonstrated that the Ta-TNTs promoted rat bone marrow mesenchymal stem cell adhesion, proliferation, and osteogenic differentiation. This was evidenced by increased alkaline phosphatase activity, enhanced mineralization, and upregulated gene expression levels. The results suggest that the Ta-doped TNTs offer a pathway for the development of mechanically robust and bioactive implant surfaces for dental and orthopedic applications. Full article

Introduction: This study evaluated the impact of standard inpatient rehabilitation on physical and mental health outcomes in patients with multiple myeloma (MM). Since prior data showed that physical activity (PA) is beneficial for patients with MM, this study assessed (1) the onset and (2) durability of these benefits with and without rehabilitation. Methods: Sixty patients with MM, undergoing a three-week rehabilitation program in the rehabilitation clinic of the University of Freiburg between April 2022 and September 2023, were assessed at three time points: baseline (T0), post-rehabilitation (T1), and 3-months post-rehabilitation (T2). Six patients, declining rehabilitation, were also examined. Tests included the timed-up-and-go-test (TUGT), handgrip strength, laboratory parameters, subjective fitness-rating, validated questionnaires for PA, fatigue, depression, and health-related quality of life (HRQoL: SF-12, R-MCI). Results: Patients showed meaningful improvements in physical function, TUGT, and grip strength from T0 to T1. Fatigue, depression, and HRQoL improved considerably. After their return home (T2), 80% of patients remained physically active. Patients reported substantially higher subjective physical fitness at T2 compared to T0, improving to 5.0 from 3.1 on a 10-point scale, respectively. Non-rehabilitation-undergoing patients were fitter at baseline but did not improve in any tests/questionnaires at T1. Conclusions: Structured three-week rehabilitation led to a substantial improvement in both the physical and psychological well-being of patients with MM, despite their compromised bone health. These effects persisted 3-months after patients’ dismission home. The non-rehabilitation group showed no comparable improvement, underscoring the potential benefit of structured rehabilitation in enhancing HRQoL, fatigue, and depression. Continued post-rehabilitation support is pertinent to sustain these benefits. Full article

Background/Objectives: Successful cementless total knee arthroplasty (TKA) requires adequate bone quality. However, reliable tools for intraoperative assessment remain limited. This study aimed to introduce a novel visual grading system for evaluating femoral bone during surgery and to assess its correlation with actual bone mechanical properties and suitability for cementless fixation. Methods: We prospectively recruited 193 patients receiving posterior-stabilized TKA. Intraoperatively, femoral cutting surfaces were classified into four visual grades (Excellent, Good, Fair, Poor) considering pore appearance and contour integrity. Femoral bone specimens were harvested during box preparation, and bone mechanical properties were measured through indentation testing. Spearman correlation was used to evaluate the relationship between visual grades and bone mechanical properties. Fisher’s exact test was used to evaluate the distribution pattern of cementless suitable and cemented mandatory classifications across visual grading. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic accuracy for each visual grade cutoff. Results: Visual grade strongly correlated with bone mechanical properties (Spearman’s ρ = 0.881, p < 0.01). Cementless suitable cases were predominantly distributed in Good/Excellent visual grades, while cemented mandatory cases were mostly found in Fair/Poor grades. However, 8% of Good visual grade specimens exhibited strength warranting cemented fixation, and 18% of Fair visual grade specimens demonstrated adequate mechanical properties for cementless fixation. Using the Good visual grade as a cutoff threshold, ROC analysis showed excellent diagnostic accuracy (AUC = 0.941) with high sensitivity (89%) and specificity (94%). Conclusions: The authors’ novel intraoperative visual assessment system demonstrated significant correspondence to measured bone mechanical properties in the distal femur and showed high accuracy in determining suitability for cementless TKA in Asian individuals. Given the ethnic homogeneity of this cohort, further validation in diverse populations is required to generalize these findings. Full article

Standard materials for middle clavicle implants are limited to Titanium and Stainless Steel; their high Young’s Modulus promotes stress shielding, which causes complications such as malunion or implant failure. This study investigates alternative materials, Cobalt Chromium, Polyether ether ketone (PEEK), Magnesium, and Polylactic Acid (PLA), along with the standard materials, to understand their stress distributions, assess the likelihood of stress shielding, and evaluate their viability through the use of ANSYS 2025 R1 Finite Element Analysis (FEA). The materials are tested with four plate variations: Superior Plate, Anteroinferior Plate, Thin Dual Plate, and Thick Dual Plate, subjected to a simultaneous load of 100 N compressive, 100 N bending, and 1 Nm torsional, and were compared according to their maximum von Mises Stresses in plate, bone, and fracture line. High Young’s Modulus materials (Titanium, Stainless Steel, and Cobalt Chromium) had maximum von Mises plate stresses ranging from 200 to 265 MPa. In contrast, lower Young’s Modulus materials (Magnesium, PEEK, and PLA) showed maximum von Mises stresses of only around 115 to 170 MPa. PLA showed insufficient material strength, with bone stresses being around 30 MPa greater than plate stresses. PEEK showed viability but failed in material strength for the superior plate variation, as its maximum von Mises Stress of 168.13 MPa exceeded the yield strength of 125 MPa. Magnesium showed the best results, with bone and plate stresses near each other, and passed all viability criteria, demonstrating good material strength and a low risk of stress shielding. The results reinforce the use of Titanium and Stainless Steel as standards, show the viability of Cobalt Chromium for patients needing increased stability but with risks of stress shielding, demonstrate Magnesium for bioabsorbability and low stress shielding risk, suggest PEEK for low load applications, and reveal that PLA has insufficient strength. The study provides a comprehensive comparison of different materials with various variations, which provides a foundation for future studies to analyze material behavior. Full article

This study aimed to develop and characterize novel 3D-printed chitosan methacryloyl (CSMA) hydrogel-functionalized nano-hydroxyapatite/polycaprolactone (nHA/PCL) scaffolds for controlled release of bone marrow mesenchymal stem cell-exosomes (BMSC-Exos), with the objective of enhancing osteogenic and angiogenic capabilities in vitro. We fabricated a biomimetic, highly porous scaffold composed of nHA/PCL using high-temperature fused deposition modeling. An interfacial bioactive layer was formed via ultraviolet-induced crosslinking of CSMA hydrogel on the scaffold and loaded bone marrow mesenchymal stem cell-exosomes. We characterized the composite scaffold to evaluate its physicochemical properties, cytocompatibility, cell migration ability, osteogenic capacity, and angiogenic capacity. The 3D-printed 20%nHA/PCL scaffold has a porosity of approximately 75%, with its surface containing four elements: carbon, oxygen, calcium, and phosphorus. The compressive strength is (13.76 ± 1.33) MPa. The CSMA hydrogel exhibits good injectability and degrades slowly over time. Exosomes with a negative charge are released slowly within the extracellular matrix hydrogel. The contact angle of the scaffold material is below 90 degrees, and the hemolysis rate is below 5%. In vitro assays demonstrated that the nHA/PCL-CSMA-Exos composite exhibited excellent biocompatibility, markedly enhanced cell proliferation and migration, and robust pro-angiogenic and osteogenic activity. The fabricated nHA/PCL-CSMA-Exos composite scaffolds demonstrated excellent physicochemical properties, biocompatibility, and cell migration ability, promoting angiogenesis, bone tissue formation and mineralization. Full article

Background/Objectives: Persistent strength deficits and psychological impairments may compromise return to sport (RTS) after anterior cruciate ligament reconstruction (ACLR). We investigate the relationship between thigh muscle isokinetic strength recovery at six months after ACLR and long-term psychological outcomes related to RTS in competitive male soccer players. Methods: Sixty male soccer players who underwent primary ACLR with bone–patellar tendon–bone autograft were retrospectively analyzed. Isokinetic testing of quadriceps and hamstrings was performed one week before surgery and six months post-surgery at 90°/s and 180°/s. Limb symmetry index (LSI) was calculated both pre- and post-operatively. At long-term follow-up (mean ≈ 4 years after RTS), athletes completed questionnaires assessing RTS status, ACL re-injuries, sport-related perceptions, and kinesiophobia using the Tampa Scale for Kinesiophobia (TSK). Statistical analyses were conducted to explore associations between post-operative LSI and TSK scores and to compare psychological and neuromuscular outcomes between athletes with and without ACL re-injury. Results: Absolute quadriceps and hamstring peak torque values significantly increased from pre- to post-surgery, with quadriceps strength deficits persisting only in the operated limb. However, quadriceps LSI significantly decreased post-operatively, while hamstring LSI remained stable. Pearson correlation analysis revealed a weak positive association between post-operative quadriceps LSI at 90°/s and TSK scores (r = 0.34). Overall, RTS rate was 91.7%, but a second ACL injury occurred in 18.2% of athletes. No significant differences were observed between re-injured and non-re-injured athletes in TSK scores or post-operative LSI values at either angular velocity (all p > 0.29). High kinesiophobia (TSK ≥ 37) was present in 56.7% of the cohort at long-term follow-up. Conclusions: Despite significant strength gains, quadriceps limb symmetry worsened six months after ACLR, with deficits confined to the operated limb, suggesting persistent neuromuscular inhibition. These physical deficits coexist with long-term kinesiophobia despite high RTS rates. The weak associations between strength symmetry and psychological outcomes highlight the multifactorial nature of RTS and support the need for an integrated physical, psychological, and neuro-cognitive approach to rehabilitation and RTS decision-making. Full article