Search Results (26,774)

Repairing large bone defects remains a significant clinical challenge due to the limitations of current treatments, including infection risk, donor site morbidity, and insufficient vascularization. The autograft is still the gold standard for large bone defects. In this study, we developed chitosan-based (CS-based) scaffolds, incorporating with hydroxyapatite (HAp) and fluorapatite (FAp) ceramics, fabricated by UV crosslinking and freeze-drying, and loaded with P28 peptide, alone or in combination with vascular endothelial growth factor (VEGF), to evaluate the effect of dual bioactive factor delivery. We hypothesized that CS-based scaffolds would optimize ceramic composition and co-delivery of P28 and VEGF, and can enhance early-stage osteogenic differentiation and support bone regeneration. The CS-based scaffolds were characterized by their physicochemical properties, including swelling behavior, mechanical strength, porosity, and in vitro degradation. Biological evaluations were performed including cell proliferation assays, ALP activity, ARS staining, and RT-qPCR, to assess osteogenic differentiation. The results showed that the scaffolds had high porosity, excellent swelling behavior, and degraded within 8 weeks. Dual delivery of P28 and VEGF significantly enhanced early osteogenic markers, indicating a complementary effect. These findings demonstrated that CS-based scaffolds with an optimized ceramic ratio and bioactive factor incorporation have the potential to facilitate bone regeneration. Full article

Purpose: This review aims to synthesize current knowledge of anatomical variations of the popliteofibular ligament (PFL) and evaluate the clinical relevance of the classification system proposed by Olewnik et al. in the context of the diagnosis, surgical treatment, and rehabilitation of posterolateral corner (PLC) injuries. Methods: A comprehensive analysis of anatomical, surgical, and radiological studies concerning the PFL was conducted. The implications of PFL morphological variants were examined across clinical applications, with an emphasis on reconstructive strategies, imaging interpretation, and rehabilitation planning. Emerging research directions, including AI-supported imaging and personalized algorithms, were also explored. Results: Olewnik’s classification identifies three distinct types of PFL, each with unique structural and biomechanical properties. Recognizing these variants enhances intraoperative orientation, facilitates tailored surgical techniques, and supports individualized rehabilitation protocols. Variant-specific biomechanics, identified via cadaveric studies and imaging, are essential for optimizing functional outcomes and minimizing postoperative instability. Furthermore, the classification offers a platform for developing future diagnostic and decision-support tools using artificial intelligence. Conclusions: The Olewnik et al. classification system should be adopted as a modern anatomical standard for the PFL. Its integration into clinical practice has the potential to improve surgical precision, reduce complication rates, and enhance patient-specific treatment planning. This framework also supports future advancements in orthopedic imaging, education, and AI-driven diagnostics. Beyond descriptive anatomy, we provide a pragmatic surgical algorithm for PLC repair/reconstruction that accounts for scar- and fibrosis-dominated fields and the limited bone stock of the fibular head. Full article

Introduction: Osteogenesis imperfecta (OI) presents significant surgical challenges due to bone fragility, narrow medullary canals, and complex deformities. While telescoping rods like the Fassier–Duval (FD) system are commonly used in growing patients, they are unsuitable when the canal diameter is too small or when patients approach skeletal maturity. The Simple Locking Intramedullary (SLIM) nail offers a solid, non-telescoping alternative in these cases. Methods: We describe the surgical technique for SLIM nail implantation and highlight key technical pearls developed through institutional experience, focusing on preoperative planning, intraoperative strategies, and the management of unique anatomical challenges in OI patients. Results: Three cases illustrate the application of these techniques: the first case demonstrates SLIM nail insertion in a 3-year-old child with a narrow IM canal to correct significant bowing; reaming was performed retrograde from the osteotomy site for the proximal segment and antegrade for the distal segment. The second case is a 15-year-old OI patient with a disengaged FD rod and narrow IM canal showing insertion of SLIM rod, and the third case is a 16-year-old patient with femoral deformity and telescoping rod who needed revision with SLIM nail and supplemental plate fixation. Conclusions: The SLIM nail is a viable option for select OI patients. Full article

Bone tissue restoration requires biomaterials, which combine osteoinductivity and the capability to prevent surgical site infections. Magnesium-substituted biphasic calcium phosphate (Mg-BCP) represents a promising solution, as magnesium substitution increases the biodegradation rate of calcium phosphate ceramics and provides inherent antibacterial properties. This study aimed to achieve wet precipitation synthesis of magnesium-substituted (1–10 mol%) biphasic calcium phosphate and to evaluate its drug delivery potential and antibacterial performance. Porous Mg-BCP granules were fabricated via the gelation of Mg-BCP suspension in sodium alginate followed by polymer removal. Drug delivery potential was evaluated using methylene blue as a model compound, with methylcellulose encapsulation implemented to ensure prolonged release. Magnesium content directly ruled the phase composition: low concentrations (1%) favored hydroxyapatite phase prevalence, while higher concentrations led to the β-tricalcium phosphate formation. Further assessment of drug delivery potential revealed that direct drug loading resulted in burst release, whereas methylcellulose encapsulation successfully enabled prolonged drug delivery. Mg-5BCP formulation demonstrated significant antimicrobial activity with growth inhibition of 17.7 ± 4.1% against C. albicans, 20.8 ± 7.0% against E. faecalis, and 12.9 ± 7.5% against E. coli. Therefore, Mg-5BCP–methylcellulose composite granules present a versatile platform for antibacterial drug delivery for bone tissue engineering applications. Full article

Background/Objectives: Multi-scenario calculational methods have been used to evaluate proton teletherapy plan robustness but few studies have been performed to determine the accuracy of these calculational methods. This study evaluates a multi-scenario method by comparing calculations to measurements made in phantoms that simulate the effects of possible uncertainties. Methods: Plans were made using four phantoms in which the delivered dose was highly sensitive to positional and penetration uncertainties. The effects of alignment and penetration uncertainties on the dose distributions of each of those phantoms were simulated by performing calculations using nine different uncertainty scenarios and comparing the calculations to measurements with induced physical alignment displacements. Measured dose distributions were obtained by exposing films placed inside the phantoms and extracting multiple linear profiles. The maximum and minimum doses obtained for each of the calculational scenarios were compared with the measured dose profiles. In addition, comparisons of DVHs for nominal and uncertainty scenarios were performed. Results: The results showed that, under the influence of uncertainties, the minimum dose for the four phantoms decreased by more than 20 Gy, the V_95% coverage fluctuated by more than 10%, but the maximum dose parameter changed by less than 5 Gy. This was expected, as no margins for uncertainties were applied around the targets. The envelope bounded by the maximum and minimum possible calculated doses contained most of the measurements, although the shapes of the dose profiles displayed some mismatches for wedge and head phantoms. There were a few points where the measured maximum dose for bone and lung slab phantom cases was slightly higher than the maximum dose calculated from the nine scenarios. Conclusions: This study demonstrates that a nine-scenario method can adequately evaluate the robustness of simple mono-directional plans containing heterogeneities. Full article

A bioresorbable cannulated bone screw was developed using PLA/PCL-based composites reinforced with hydroxyapatite (HA) and titanium dioxide (TiO₂), two additives previously reported to enhance mechanical compliance, biocompatibility, and molding feasibility in biodegradable polymer systems. The design incorporated a crest-trimmed thread and a strategically positioned gate in the thin-wall zone opposite the hexagonal socket to preserve torque-transmitting geometry during micromolding. To investigate shrinkage behavior, a Taguchi orthogonal array was employed to systematically vary micromolding parameters, generating a structured dataset for training a back-propagation neural network (BPNN). Analysis of variance (ANOVA) identified melt temperature as the most influential factor affecting shrinkage quality, defined by a combination of shrinkage rate and dimensional variation. A hybrid AI framework integrating the BPNN with genetic algorithms and particle swarm optimization (GA–PSO) was applied to predict the optimal shrinkage conditions. This is the first use of BPNN–GA–PSO for cannulated bone screw molding, with the shrinkage rate as a targeted output. The AI-predicted solution, interpolated within the Taguchi design space, achieved improved shrinkage quality over all nine experimental groups. Beyond the specific PLA/PCL-based systems studied, the modeling framework—which combines geometry-specific gate design and normalized shrinkage prediction—offers broader applicability to other bioresorbable polymers and hollow implant geometries requiring high-dimensional fidelity. This study integrates composite formulation, geometric design, and data-driven modeling to advance the precision micromolding of biodegradable orthopedic devices. Full article

Excessive osteoclast activity in bone remodeling can lead to an imbalance between bone resorption and formation, a common occurrence in abnormal bone metabolic diseases. This research investigates the effect of Coptidis rhizoma water extract (CRW) on osteoclastogenesis provoked by RANKL in vitro and bone destruction mediated by ovariectomy (OVX) in vivo. CRW, prepared from dried Coptidis rhizoma (CR), was analyzed for its active compounds—coptisine and berberine—using HPLC analysis. CRW markedly decreased the size and number of TRAP-positive multinucleated cells (TRAP⁺ MNCs), suppressed F-actin ring formation, and diminished bone resorption in RANKL-treated cultures. In the early phase of differentiation, CRW suppressed the phosphorylation of MAPKs p38, JNK, and ERK, as well as NF-κB p65, Iκ-Bα, and Akt. CRW also down-regulated RANKL-mediated induction of c-Fos and NFATc1 and attenuated the activation of NFATc1- dependent genes, such as OSCAR, ATP6V0D2, ACP5 (TRAP), OC-STAMP, DC-STAMP, CTSK (cathepsin K), CALCR (calcitonin receptor), and MMP-9. In ovariectomized rats, micro-CT and histological analyses showed that CRW alleviated femoral bone destruction. These findings indicate that CRW restrains osteoclast differentiation and function and may have therapeutic potential for disorders driven by excessive osteoclast activity. Full article

Background: This study investigates the diagnostic reliability of an artificial intelligence (AI)-based software (Diagnocat) in caries, dental restorations, missing teeth, and periodontal bone loss on panoramic radiographs (PRs), comparing its performance with evaluations from three independent dental experts serving as ground truth. Methods: A total of 104 PRs were analyzed using Diagnocat, which assigned a likelihood score (0–100%) for each condition. The same images were independently evaluated by three experts. The diagnostic performance of Diagnocat was evaluated using sensitivity, specificity, and receiver operating characteristic (ROC) curve analysis, while inter-rater agreement was assessed through Cohen’s kappa (κ). Results: Diagnocat showed high overall sensitivity (99.2%), identifying nearly all conditions marked as present by human evaluators. Specificity was low (8.7%), indicating a tendency to overdiagnose. Overall accuracy was 96%, likely influenced by the coexistence of multiple conditions. Sensitivity ranged from 77% to 96%, while specificity varied: dental restorations (66%), missing teeth (68%), periodontal bone loss (71%), and caries signs (47%). The agreement was fair for dental restorations (κ = 0.39) and missing teeth (κ = 0.37), but poor for caries signs (κ = −0.15) and periodontal bone loss (κ = −0.62). Conclusions: Diagnocat shows promise as a screening tool due to its high sensitivity, but low specificity and poor agreement for certain conditions warrant cautious interpretation alongside clinical evaluation. Full article

Background: Wedge-shaped implants have been proposed as a minimally invasive solution for narrow alveolar ridges, aiming to avoid bone augmentation. While the short-term results are promising, long-term clinical evidence remains limited. Methods: This multicenter prospective single-arm cohort study reports the 7-year outcomes of tissue-level wedge-shaped implants (1.8 mm thickness) placed without grafting in horizontally atrophic ridges (mean thickness 3.73 ± 0.36 mm). Clinical and radiographic evaluations were performed on 45 implants (34 patients). Results: At the 7-year post-loading follow-up, the implant survival rate was 95.5%, with two failures recorded—one early loss and one due to peri-implantitis. Peri-implant mucositis was observed in 5 implants (11.4%), while peri-implantitis was diagnosed in 3 implants (6.8%). No mechanical complications were reported. The mean marginal bone loss (MBL) was 1.45 ± 1.41 mm, measured relative to the implant shoulder. Multivariate linear regression identified older age (β = +0.040; p = 0.012) and mandibular implant placement (β = +1.39; p = 0.007) as significant predictors of greater bone loss. Conclusions: Wedge-shaped implants demonstrated high long-term survival and stable marginal bone levels in narrow ridges without the need for bone augmentation. Age and mandibular location negatively influenced long-term bone stability, while smoking, gender, and history of periodontitis were not significant predictors. Full article

The purpose of this narrative review is to critically appraise recent advances in sports injury rehabilitation—primarily focusing on biopsychosocial (BPS) approaches alongside emerging technological innovations—and identify current gaps and future directions. A literature search was conducted in PubMed, Scopus, and Web of Science for the years 2018–2024. Eligible records were English-language, human studies comprising systematic reviews, clinical trials, and translational investigations on wearable sensors, artificial intelligence (AI), virtual reality (VR), regenerative therapies (platelet-rich plasma [PRP], bone marrow aspirate concentrate [BMAC], stem cells, and prolotherapy), and BPS rehabilitation models; single-patient case reports, editorials, and non-scholarly sources were excluded. The synthesis yielded four themes: (1) BPS implementation remains underutilised owing to a lack of validated tools, variable provider readiness, and system-level barriers; (2) wearables and AI can enhance real-time monitoring and risk stratification but are limited by data heterogeneity, non-standardised pipelines, and sparse external validation; (3) VR/gamification improves engagement and task-specific practice, but evidence is dominated by pilot or laboratory studies with scarce longitudinal follow-up data; and (4) regenerative interventions show mechanistic promise, but conclusions are constrained by methodological variability and regulatory hurdles. Conclusions: BPS perspectives and emerging technologies have genuine potential to improve outcomes, but translation to practice hinges on (1) pragmatic or hybrid effectiveness–implementation trials, (2) standardisation of data and intervention protocols (including core outcome sets and effect-size reporting), and (3) integration of psychological and social assessment into routine pathways supported by provider training and interoperable digital capture. Full article

Matrix metalloproteinases (MMPs) are a family of endopeptidases recognized for their involvement in the degradation of the extracellular matrix and their important role in the pathogenesis of periodontitis. This chronic inflammatory condition causes the degradation of dental supporting tissues, resulting in bone loss. In patients with periodontitis, the expression and activation of MMPs, especially MMP-8 and MMP-9, significantly influence tissue degradation. In periodontitis treatment, various natural or synthetic metalloproteinase inhibitors (MMPIs) and antibiotics are used in sub-antimicrobial doses. However, while the evidence supports a role for MMPIs in reducing inflammation, preserving connective tissue, and improving the results of conventional periodontitis treatment, their clinical application is limited. In this review, we summarize MMPIs, their characteristics, and the mechanisms of action that may support their use in the treatment of periodontitis. In conclusion, MMPIs are a therapeutic alternative with great potential in the management of periodontitis, especially when combined with mechanical treatments, although further research is needed to optimize their clinical use. Full article

The purpose of this study was to evaluate normal values of healthy human bone marrow (n = 56) and identify gender- and age-related variations using cell lineage markers and maturational curves. Using 10-color quantitative flow cytometry, various cell types were identified, including B cells, T cells, NK cells, granulocytes, monocytes, erythroblasts, plasma cells, basophils, mast cells, and dendritic cells. Results revealed significant age-related declines in the absolute counts of nucleated cells (p = 0.001), including CD34+ immature B cells (p = 0.006) and CD34- immature B cells (p = 0.004). Declines were also observed for T cells (p = 0.002), cytotoxic T cells (p < 0.001), double-negative T cells (p = 0.0001), NK cells (p = 0.007), CD16- NK cells (p < 0.001), metamyelocytes (p = 0.002), neutrophils (p = 0.001), basophils (p = 0.009), promonocytes (p = 0.001), mature monocytes (p = 0.007), and plasmacytoid dendritic cells (p = 0.001). Gender differences showed males had more intermediate monocytes (p = 0.009) compared to females. In summary, this study provides normal values for hematopoietic cells, highlighting age- and gender-related disparities critical for understanding hematopoietic dynamics. Full article

Background: Osteosarcoma is an aggressive bone tumor with a high risk of lung metastasis, which severely affects patient survival. EMT plays a major role in tumor spread, therapy resistance, and cancer stemness. This review explores how EMT contributes to osteosarcoma metastasis and the underlying molecular mechanisms. Methods: We reviewed recent studies on EMT-related signaling pathways, transcription factors, and regulatory RNAs in osteosarcoma. We also examined the role of the tumor microenvironment. Results: EMT promotes cell detachment, migration, and lung colonization. Key pathways such as TGF-β, MAPK, PI3K/Akt, STAT3, Notch, and Wnt/β-catenin are involved. Non-coding RNAs further regulate EMT by interacting with these pathways. The tumor microenvironment, including hypoxia and immune cells, also supports EMT and metastasis. Conclusions: EMT is a key driver of metastasis and poor outcomes in osteosarcoma. Targeting EMT and its regulators may help prevent lung spread and improve treatment. Future strategies combining EMT inhibition with existing therapies could be promising for clinical application. Full article

Introduction: The elbow is a rare site for bone tumors, and for this reason, the literature provides little data on the epidemiology of metastatic lesions involving the distal humerus, proximal ulna, and radius. Before performing surgery of the metastatic bone, it is first necessary to consider both patients’ and metastatic lesions’ features in order to better choose the best possible treatment. This systematic review aims to collect data on elbow metastases, delineate primary tumors leading to such metastases, guide surgical treatment decisions, and evaluate reconstructive techniques and associated complications. Material and Methods: A systematic literature review was conducted in April 2024, searching the PubMed, MEDLINE, and Cochrane Library databases using specific search terms related to elbow metastases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was followed. Eligible studies reported at least one patient with metastatic bone disease involving the elbow region and specified the undertaken treatment. For studies reporting multiple skeletal sites, only elbow-specific data were extracted. We excluded recurrences of primary elbow tumors. The methodological quality of included studies was assessed with the modified Coleman Methodology Score (mCMS). Results: In total, 28 articles (103 patients) were included. The studies were predominantly case reports (68%), with a mean mCMS of 31. Gender was reported for only 41 patients: 71% were male and 29% female. The mean age at diagnosis of elbow metastatic lesion was 55 years old. Renal cell carcinoma was the most common primary tumor (28%), followed by breast (9%) and lung cancer (6%). The distal humerus was the most frequently affected site (85%). A surgical approach was adopted in 90% of cases, whereas 10% of patients were managed conservatively. Forty-five patients underwent wide tumor resection followed by reconstructive surgery while forty-eight patients received a surgical treatment for either pathological fractures or impending fractures. Conclusions: When treating elbow metastasis, a thorough evaluation of the patient is crucial, considering the patient’s functional status, pain management needs, and overall prognosis; all these features influence the treatment of choice. The selected treatment should aim to provide optimal functional outcomes and minimize complications. For patients with pathological or impending fractures, single or double plate fixation is typically the preferred approach. For patients with severe, symptomatic lesions unresponsive to conservative therapy, resection followed by the implantation of a modular prosthesis usually offers the best clinical and functional outcomes. Full article

Objectives: Invasive aspergillosis (IA) poses significant risks to patients with malignancies or transplantation; however, estimates of burden-of-illness in patients with IA are sparse. We sought to assess in-hospital and outpatient healthcare resource utilization, all-cause treatment costs, and mortality in patients admitted with IA with hematologic or non-hematologic malignancies, bone marrow transplant/hematopoietic cell transplantation (BMT/HCT), or solid organ transplantation (SOT). Methods: This claims study utilized United States IQVIA data. Adults admitted for IA were identified by diagnosis codes during the patient selection period (October 2015–November 2022). IA patients were stratified into cohorts including recent hematologic or non-hematologic malignancies, or a history of BMT/HCT or SOT. We assessed hospital and intensive care unit (ICU) length-of-stay (LOS), all-cause index hospital treatment costs, and inpatient mortality or need for hospice in each cohort, as well as the need for re-admission and total treatment costs for up to six-months after admission, and all-cause mortality at end of study follow-up. Results: Among 1190 patients admitted for IA, 317 had hematologic malignancies, 155 non-hematologic malignancies, 133 BMT/HCT and 173 SOT. Across these cohorts, IA was associated with protracted (median LOS = 12–18 days; ICU LOS = 10–13 days) and costly (median = USD 79,058–USD 172,342) index hospitalizations ending in death or hospice in 28.1% (89/317) to 36.1% (48/133) of patients. Among those surviving to discharge, between 53.1% (34/64) and 63.4% (97/153) were re-admitted within six months. Total median treatment costs at six months ranged from USD 213,378 to USD 397,857. All-cause mortality was 33.6% (52/155) to 40.6% (54/133) at end of study follow-up. Conclusions: Hospitalizations for IA in patients with malignancies or transplantation are long, costly, and end with readmission, hospice, or death in more than one-third of patients. Full article