The purpose of this clinical practice guideline is to provide evidence-based recommendations for the treatment of pediatric flexible flatfoot, developed in accordance with the Appraisal of Guidelines for Research and Evaluation II framework and with evidence certainty assessed using the GRADE framework and the Oxford Centre for Evidence-Based Medicine levels of evidence system. A multidisciplinary guideline development group under the Limb Reconstruction Committee of the Orthopedics Branch of China International Exchange and Promotion Association for Medical and Health Care systematically searched and reviewed evidence from primary studies including randomized controlled trials, cohort studies, and comparative studies, supplemented by existing systematic reviews and expert society surveys, to evaluate the effectiveness of conservative and surgical interventions and to guide clinicians and families on the content of an optimal treatment pathway. The guideline targets children and teenagers with flexible flatfoot and addresses interventions available to orthopedic surgeons, podiatrists, rehabilitation physicians, and orthotists, including observation, rehabilitative exercises, foot orthoses, subtalar arthroereisis, calcaneal osteotomy, and criterion-based progression to surgery. Structured conservative management should be considered the mainstay of care for all symptomatic children, with a minimum 6-month trial before surgical referral. However, there is limited evidence on the optimal type, dose, and duration of conservative treatment, and what constitutes an adequate trial of nonoperative care remains undefined. Foot orthoses can be helpful for symptomatic relief when pain or functional limitation is present, and rehabilitative exercise programs may allow superior normalization rates compared to orthoses alone. Pain-free ambulation and return to unrestricted sport are key milestones for both conservative and surgical pathways. However, no validated progression or discharge criteria exist to guide the transition from one treatment phase to the next. While the certainty of evidence was low to very low for most components of the treatment pathway, all 15 recommendation statements were formulated through two rounds of Delphi consensus polling, with 13 achieving the predefined ≥75% agreement threshold. This guideline also highlights the need for standardized diagnostic definitions, multicenter registry data, and age-stratified surgical indications not systematically addressed in previously published literature.

Background:We aimed to determine whether a nurse-led digital care program improves postoperative outcomes compared to usual care in patients receiving external fixation. Specifically, we assessed its impact on complication rates, pain, function, psychological well-being, patient satisfaction, and adherence. Methods:We conducted a single-center, parallel-group randomized controlled trial involving 100 adult patients (aged 18-75) undergoing external fixation for trauma or reconstructive procedures. Participants were randomized 1:1 to receive either a nurse-led digital care program or standard postoperative care. The digital intervention included daily symptom logging, structured educational modules, video consultations, and in-app nurse communication. The primary outcome was the occurrence of at least one postoperative complication by 24 weeks. Complication burden, defined as the number of postoperative complications per participant, was assessed as a supportive summary. Secondary outcomes included pain (VAS), function (LEFS), psychological status (HADS), and patient satisfaction. Data were collected at baseline, 4, 12, and 24 weeks. Analyses were performed using linear mixed-effects models. Results:At 24 weeks, complication rates were similar between the digital and control groups (difference: -0.02; 95% CI, -0.205 to 0.165; p=0.829). Improvements in pain, LEFS scores and HADS were also similar between groups at 24 weeks. Patient satisfaction, particularly regarding ease of use and communication with nurses, was significantly higher in the digital group. Per-protocol analysis confirmed these findings. Conclusions:The nurse-led digital care program did not reduce postoperative complications by 24 weeks. It was associated with modest improvements in pain and function at 4 and 12 weeks, with no sustained differences at 24 weeks. Patient satisfaction favored the digital care program. As a single centre trial among smartphone users, these findings should be interpreted as preliminary evidence of acceptability in this specific clinical context. Multicenter evaluation across diverse settings and patient populations is needed before broader implementation can be considered.

Chondrocyte senescence accelerates osteoarthritis (OA) progression, with dysregulated glycolysis potentially driving this process through lactate accumulation and histone lactylation. However, the mechanistic connection between lactate-induced lactylation and cellular senescence in OA chondrocytes remains poorly understood. This study elucidates this relationship and explores its therapeutic relevance. Using clinical OA cartilage, animal models, and IL-1β-stimulated chondrocytes, we demonstrated enhanced glycolysis and senescence activities. Increased glycolytic activity and lactate accumulation promoted cellular senescence in the OA microenvironment. Elevated lactate levels increased global lactylation, with H4K12la as the predominant mark. H4K12la-targeted CUT&TAG analysis identified TRIM29 as a key regulator. H4K12la promotes TRIM29 transcription, which activates the PI3K-AKT pathway via direct and EGFR-mediated mechanisms, leading to autophagy inhibition and senescence. Interventions such as SIRT1 overexpression or intra-articular oxamate injection reduced lactylation, inhibited glycolysis, and mitigated cartilage degeneration. These findings demonstrate that glycolytic lactate-induced H4K12la fosters senescence through TRIM29-mediated PI3K-AKT activation, highlighting the inhibition of glycolysis or lactylation as a promising therapeutic strategy for OA.

PURPOSE:Open-wedge high tibial osteotomy (OWHTO) is established for young, active patients with medial knee osteoarthritis. Patient-specific 3D-printed guide plates have been introduced to improve surgical precision and efficiency, but evidence of clinical and economic benefit is limited. We aimed to determine whether a 3D-printed patient-specific guide plate improves efficiency, functional outcomes, and cost-effectiveness compared to standard OWHTO. METHODS:In this multicenter randomized trial, patients scheduled for OWHTO were allocated to either conventional planning (control) or surgery using a patient-specific 3D-printed guide plate between November 2020 and June 2024. The primary endpoint was the 12-month Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Secondary outcomes included knee range of motion (flexion in degrees), 30-s chair-stand test (number of stands), operative time, and health economic measures (direct costs and quality-adjusted life years). Analyses were by intention-to-treat using appropriate statistical tests. RESULTS:A total of 180 patients (mean age 55 years, 56.7% male) were randomized equally between groups. At 12 months, mean WOMAC pain was 15.2 (SD 8.4) in the guide-plate group and 15.6 (SD 8.7) in controls, with no significant difference (p = 0.74). The guide-plate group showed significantly greater knee flexion (mean 128° vs. 122°; p = 0.04) and a higher 30-s chair-stand count (14.2 vs. 12.5 stands; p = 0.02) than controls. There were no other significant between-group differences in clinical scores. Mean total cost per patient was not statistically significant in the ITT analysis (p = 0.094). Quality-adjusted life years did not differ between groups, yielding no cost-effectiveness advantage. These findings echo prior reports that OWHTO techniques with higher costs have similar patient outcomes. CONCLUSION:Using a 3D-printed patient-specific guide plate did not improve the primary pain outcome or overall functional outcome compared to standard OWHTO. It yielded minor gains in knee flexion and chair-stand performance, but at greater cost. No overall cost-effectiveness benefit was observed. Routine use of this technology for OWHTO is not supported by our findings. LEVEL OF EVIDENCE:Level I, randomized controlled trial. TRIAL REGISTRATION:Chinese Clinical Trial Registry (https://www.chictr.org.cn/): ChiCTR2000038619.

Objectives: Osteonecrosis of the femoral head (ONFH) represents a severe complication of glucocorticoids (GCs) therapy in clinical settings. MicroRNAs (miRNAs) are critically involved in the progression of GCs-induced ONFH, with ferroptosis playing a central role in its pathology. However, the regulatory effects of specific miRNAs targeting ferroptosis in ONFH have not been previously explored. The aim of this study was to elucidate the effect and the specific molecular mechanisms of miR-370-3p in the progression of GCs-induced ONFH. Methods: In this study, we first established a rat model of GCs-induced ONFH and analyzed changes in osteogenesis and ferroptosis. Subsequently, we performed miRNA sequencing on bone marrow-derived mesenchymal stem cells (BMSCs) after dexamethasone treatment. In vitro, we assessed the effects of miR-370-3p on cell proliferation, osteogenic activities, and ferroptosis in BMSCs. We used dual luciferase assays to identify the target gene of miR-370-3p, examining its regulatory effects on osteogenesis and ferroptosis. In vivo, we estimated the effect of miR-370-3p on the femoral head by isolating exosomes from BMSCs overexpressing miR-370-3p and administering them to rats. Results: We observed that impaired osteogenesis and enhanced ferroptosis are principal pathogenic factors in the progression of GCs-induced ONFH. We identified miR-370-3p as a significant regulatory element in bone marrow-derived mesenchymal stem cells (BMSCs) through miRNA sequencing following GCs treatment. Moreover, miR-370-3p could protect BMSCs viability against GCs impairment in vitro and enhance Ki67 expression in the femoral head. The osteogenic capacity of BMSCs was strengthened by miR-370-3p under GCs condition. In addition, miR-370-3p was found to reduce ferroptosis activities, including iron overload and lipid peroxidation. Mechanically, we found that toll-like receptor 4 (TLR4) was the target of miR-370-3p. And miR-370-3p could exert critical regulatory effects by targeting TLR4/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis under GCs intervention. Importantly, inhibition of ferroptosis partially restored osteogenic capacity of BMSCs in vitro. In a rat model of GCs-induced ONFH, miR-370-3p played a critical protective role in the femoral head by enhancing osteogenesis and inhibiting ferroptosis. Conclusion: miR-370-3p could regulate the changes in osteogenesis and ferroptosis in the progression of GCs-induced ONFH through targeting TLR4/SLC7A11/GPX4 axis. The translational potential of this article: This study is the first to unveil the regulatory interaction between miRNA and ferroptosis in GC-induced ONFH, providing valuable insights into its pathogenesis and identifying potential therapeutic targets.

Purpose:Congenital pseudarthrosis of the tibia (CPT) is a rare condition typically manifesting within the first decade of life. The primary objectives of surgical intervention for CPT include achieving long-term bony union of the tibia, preventing or minimizing limb length discrepancies (LLD), avoiding mechanical axis deviations of the tibia and adjacent joints, and preventing refracture. This study aims to conduct a systematic review of current treatment methods for CPT to determine the most effective non-surgical and surgical management strategies for pediatric patients with this condition.Methods:A review of the literature was performed according to the PRISMA guidelines. A comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases was performed over the years 1989 to 2024. Randomized controlled trials, cohort studies and case-control studies on the surgical treatments of CPT in children were included. Random-effects models were used to estimate the pooled primary union rate, primary union time and refracture rate. Then a consensus statement of surgical treatment of CPT in children was achieved based on Delphi methodology which included 2 rounds of electronic questionnaires and 1 round of virtual consensus meeting.Results:Seventy-four studies were included, 23 of which on intramedullary rods (IMR) involving 364 patients, 15 on Ilizarov methods with 230 patients, and 23 studies combining IMR with Ilizarov involving 458 patients. The pooled primary union rate for IMR, Ilizarov method, and Ilizarov combined with IMR was 69% (95% CI: 0.55-0.82), 89% (95% CI: 0.77-0.98) and 85% (95% CI: 0.74-0.94), respectively. The pooled primary union time for IMR, Ilizarov method, and Ilizarov combined with IMR was 8.95 months (95% CI: 6.53-11.37), 7.14 months (95% CI: 5.53-8.74), and 5.62 months (95% CI: 4.89-6.35), respectively. The pooled refracture rate among primary unions for IMR, Ilizarov method, and Ilizarov combined with IMR was 85% (95% CI: 0.60-1.00), 81% (95% CI: 0.56-0.98), and 60% (95% CI: 0.26-0.90), respectively. After 2 rounds of electronic questionnaires and 1 round of virtual consensus meeting, a consensus statement and guidelines of surgical treatment of CPT in children was provided.Conclusion:The CPAM-LRC consensus panel provided recommendations to improve management of pediatric patients with CPT in clinical practice. Combined techniques for pediatric patients after fracture or the formation of pseudarthrosis commonly include excision of the pseudarthrosis site, external fixation, intramedullary fixation, and autogenous bone grafting. Vascularized fibular graft and cross-union can be considered a viable alternative to corticocancellous autograft. Use of recombinant bone morphogenic protein (rhBMP) is not currently conclusive.

Stress-induced apoptosis presents an obstacle to bone marrow mesenchymal stem cell (BMSC) transplantation to repair steroid-induced osteonecrosis of the femoral head (SONFH). Thus, appropriate intervention strategies should be explored to mitigate this. In our previous study, we discovered a new subgroup of BMSCs—the oxidative stress-resistant BMSCs (OSR-BMSCs)—which can survive the oxidative stress microenvironment in the osteonecrotic area, through a mechanism that currently remains unclear. In this study, we found that B-lymphoid tyrosine kinase (BLK) may be the crucial factor regulating the oxidative stress resistance of OSR-BMSCs, as it is highly expressed in these cells. Knockdown of BLK eliminated oxidative stress resistance, aggravated oxidative stress-induced apoptosis, reduced the survival of OSR-BMSCs in the oxidative stress microenvironment of the osteonecrotic area, and greatly weakened the transplantation efficacy of OSR-BMSCs for SONFH. By contrast, BLK was weakly expressed in oxidative stress-sensitive BMSCs (OSS-BMSCs). Overexpression of BLK in susceptible OSS-BMSCs allowed them to acquire oxidative stress resistance, inhibited oxidative stress-induced apoptosis, promoted their survival in the osteonecrotic area, and improved the transplantation efficacy of OSS-BMSCs for SONFH. Mechanistically, BLK concurrently activates redox and apoptotic signaling networks through its tyrosine kinase activity, which confers oxidative stress resistance to BMSCs and inhibits their stress-induced apoptosis of BMSCs. Herein, we report that OSR-BMSCs have intrinsic oxidative stress resistance that is conferred and mediated by BLK. This finding provides a potential new intervention strategy for improving the survival of transplanted BMSCs and the therapeutic efficacy of BMSC transplantation for SONFH.

Stress-induced apoptosis presents an obstacle to bone marrow mesenchymal stem cell (BMSC) transplantation to repair steroid-induced osteonecrosis of the femoral head (SONFH). Thus, appropriate intervention strategies should be explored to mitigate this. In our previous study, we discovered a new subgroup of BMSCs-the oxidative stress-resistant BMSCs (OSR-BMSCs)-which can survive the oxidative stress microenvironment in the osteonecrotic area, through a mechanism that currently remains unclear. In this study, we found that B-lymphoid tyrosine kinase (BLK) may be the crucial factor regulating the oxidative stress resistance of OSR-BMSCs, as it is highly expressed in these cells. Knockdown of BLK eliminated oxidative stress resistance, aggravated oxidative stress-induced apoptosis, reduced the survival of OSR-BMSCs in the oxidative stress microenvironment of the osteonecrotic area, and greatly weakened the transplantation efficacy of OSR-BMSCs for SONFH. By contrast, BLK was weakly expressed in oxidative stress-sensitive BMSCs (OSS-BMSCs). Overexpression of BLK in susceptible OSS-BMSCs allowed them to acquire oxidative stress resistance, inhibited oxidative stress-induced apoptosis, promoted their survival in the osteonecrotic area, and improved the transplantation efficacy of OSS-BMSCs for SONFH. Mechanistically, BLK concurrently activates redox and apoptotic signaling networks through its tyrosine kinase activity, which confers oxidative stress resistance to BMSCs and inhibits their stress-induced apoptosis of BMSCs. Herein, we report that OSR-BMSCs have intrinsic oxidative stress resistance that is conferred and mediated by BLK. This finding provides a potential new intervention strategy for improving the survival of transplanted BMSCs and the therapeutic efficacy of BMSC transplantation for SONFH.

BACKGROUND:Tetanus toxin, produced by Clostridium tetani, is the second deadliest known toxin. Antibodies capable of neutralizing tetanus toxin (TeNT) are vital for preventing and treating tetanus disease. METHODS:Herein, we screened thirty-six single variable domains on a heavy chain (VHHs) binding to the light chain (L) and the translocation domain (HN) (L-HN) fragment of TeNT from a phage-display library. Then, the L-HN-specific clones were identified, humanized, and fused with a human fragment crystallizable region (hFc) to form humanized VHH-hFc fusion proteins. RESULTS:The humanized VHH-hFc fusion proteins TL-16-h1-hFc, TL-25-h1-hFc, and TL-34-h1-hFc possessed potent efficacy with high binding affinity, specificity, and neutralizing activity. Only 0.3125 μg was required for TL-16-h1-hFc or TL-25-h1-hFc, and 0.625 μg was required for TL-34-h1-hFc to provide full protection against 10 × Lethal Dose 50 (LD50) TeNT. In the prophylactic setting, 125 μg/kg of TL-16-h1-hFc or TL-25-h1-hFc provided full protection even when they were injected 12 days before exposure to 10 × LD50 TeNT, while TL-34-h1-hFc was less effective. In the therapeutic setting, 25 μg/kg of TL-16-h1-hFc or TL-25-h1-hFc could provide complete protection when administered 24 h after exposure to 5 × LD50 TeNT, while TL-34-h1-hFc required 50 μg/kg. CONCLUSION:Our results suggest that TL-16-h1-hFc, TL-25-h1-hFc, and TL-34-h1-hFc provide a bright future for the development of anti-TeNT preventive or therapeutic drugs.

Immune checkpoint inhibitors like programmed cell death 1 (PD-1) antibodies have revolutionized cancer treatment, but patient response rates remain limited. Sialic acid-binding Ig-like lectin 15 (Siglec-15) has emerged as a promising new immune checkpoint target. Through phage display technology using a Bactrian camel immunized with recombinant human Siglec-15, we generated six anti-Siglec-15 camelid nanobodies and constructed chimeric heavy-chain antibodies by fusing the VHH domains with human IgG-Fc. Following expression in HEK293-F cells and purification, three antibodies (S1, S5, S6) demonstrated specific binding to both human and murine Siglec-15 in ELISA and biolayer interferometry assays. In a xenograft model established by subcutaneous inoculation of NCI-H157-S15 cells into BALB/c nude mice, these antibodies showed distinct tumor targeting and significant blockade of Siglec-15 interactions with CD44, MAG, sialyl-Tn, and LRR4C ligands. All three antibodies exhibited anti-tumor effects, with S1 showing the most potent activity. S1-treated mice had significantly smaller tumor volumes and weights compared to controls. The S1, S5, and S6 treatment groups showed enhanced anti-tumor immunity, with reduced TGF-β, IL-6, and IL-10 levels. Notably, S1 treatment significantly increased tumor-associated macrophages in tumor tissues (p < 0.05). In conclusion, S1 exhibits remarkable anti-tumor activity and has the potential to be developed as a cancer immunotherapy targeting Siglec-15.

Background: The lengthy period of external fixation for bone consolidation increases the risk of complications during distraction osteogenesis (DO). Both pro-angiogenic and osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) contribute to bone regeneration during DO. The underlying mechanism of Schwann cells (SCs) in promoting bone regeneration during DO remains poorly understood. Methods: The impacts of RSC-96 on the proliferation, migration, and osteogenic differentiation of BMSCs in the coculture system were investigated. The pro-angiogenic potential of BMSCs was evaluated by migration and tube formation assay. Quantitative real-time PCR was used to analyze angiogenic and osteogenic markers. ELISA was used to detect the secretion of various neurotrophins. Protein expressions of Activate protein kinase B (AKT)/β-catenin signaling were assessed by western blot. In vivo, dynamic expression levels of neurotrophic factors were detected in a preclinical rat DO model. Promotive effects of vascularization and mineralization provided by RSC-96 derived conditioned medium (CM) in a rat DO model were verified radiologically, biomechanically and histologically. Result: Coculture system with RSC-96 promoted osteogenic ability of BMSCs, with increased cell viability, alkaline phosphatase staining, mineralized nodule formation, and osteogenic gene expression. Additionally, increased angiogenic gene expression of BMSCs and angiogenic capacity of endothelial cells demonstrated enhanced pro-angiogenic potential of BMSCs. Secretion of angiogenic and neurotrophic factors were enhanced in the coculture system. These effects were accompanied by activation of AKT/GSK-3β/β-catenin signaling, as evidenced by western blot analysis and the inhibitory effect of AKT inhibitor. The mRNA expression of neurotrophic factors peaked at the end of the distraction phase during DO. Furthermore, RSC-96 derived CM accelerated bone regeneration, resulting in improved biomechanical parameters, radiological features and histological manifestations, along with increased vascularization in the distraction area. Conclusion: Through activation of AKT/GSK-3β/β-catenin signaling, SCs enhanced the coupled angio- and osteogenesis effects of BMSCs. The preclinical evidence demonstrates that SCs derived CM with increased neurotrophins secretion can be a promising treatment approach to accelerate bone regeneration in the DO process.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is a bone disorder marked by decreased bone density and an elevated risk of fracture. The Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway plays a pivotal role in regulating osteoblast proliferation and differentiation, serving as a central molecular mechanism in bone homeostasis and making it a potential therapeutic target for GIOP. YS-49, an l-naphthylmethyl analog of higenamine, has demonstrated that it can influence various cellular processes through activating the PI3K/AKT signaling pathway.This study investigated the role and mechanism of YS-49 in osteoblast differentiation. METHODS: MC3T3-E1 cells were utilized to evaluate cell viability, apoptosis, reactive oxygen species (ROS) levels, malondialdehyde (MDA), superoxide dismutase (SOD) levels, Determinationosteogenic differentiation, and mineralization after treatment with YS-49 and dexamethasone (Dex). Osteogenic differentiation of MC3T3-E1 cells was assessed by Western blot and alkaline phosphatase (ALP) staining, with the former specifically analyzing YS-49-induced activation of the PI3K/AKT signaling pathway. Additionally, a GIOP mouse model was established, and the therapeutic effects of YS-49 were evaluated via bone mineral density (BMD), micro-computed tomography (micro-CT), enzyme linked immunosorbent assay (ELISA), and histopathological analysis. RESULTS: YS-49 enhanced cell viability, inhibited ROS production, and suppressed apoptosis in Dex-treated MC3T3-E1 cells. Moreover, it promoted osteogenic differentiation and mineralization by activating the PI3K/AKT signaling pathway. In vivo, YS-49 treatment significantly mitigated Dex-induced bone loss, as evidenced by the increased BMD, enhanced trabecular structure, and upregulation of the expression of osteogenic markers. CONCLUSION: YS-49 promotes osteogenesis and prevents glucocorticoid-induced bone loss by activating the PI3K/AKT signaling pathway, collectively positioning it as a promising novel therapeutic agent for GIOP treatment.

Bone regeneration and repair is a complex physiological process of bone formation. To date, existing research has greatly enhanced our understanding of bone regeneration and repair, achieving significant success in treating bone injuries. However, extensive bone defects, bone nonunion, and metabolic bone diseases remain incompletely solved challenges in modern medicine. With the emergence of High-Throughput Screening (HTS) technology, previous studies have identified numerous small molecule compounds with potential for inducing bone formation and enhancing bone metabolism. However, the effects of these small molecules on bone regeneration and repair through related signaling pathways have not been systematically elaborated. Therefore, in this literature review, we focus on summarizing the classical signaling pathways affecting bone regeneration and repair, as well as the research progress and applications of related small molecule drugs.

Large bone defects regularly result in prolonged pain and functional impairment in patients, providing a considerable challenge in medical treatment. Current research in biomaterials for bone defect repair is increasingly centered on integrating osteogenic performance with antibacterial properties inside nanomaterials. In this study, a biomimetic hydrogel with an osteogenic microenvironment is developed primarily based on 2D black phosphorus (BP) nanosheets incorporated into poly-amino acid calcium alginate. Compared to methods using black phosphorus alone, this BP@L-lysine-Polyglutamic acid calcium alginate gel hydrogel (BP@CALG) exhibits reduced cytotoxicity, enhanced mechanical stability, and superior antibacterial properties, thereby synergistically augmenting its osteogenic potential and antibacterial efficacy. Through near-infrared (NIR) irradiation, the hydrogel's osteoinductive and antibacterial abilities are further optimized by means of controllable photothermal activation. Notably, BP@CALG demonstrates immunomodulatory capabilities that facilitate osteogenesis through macrophage polarization. By steering M0 macrophages toward the regenerative M2 phenotype and simultaneously inhibiting pro-inflammatory M1 differentiation, the scaffold effectively controls excessive inflammation. This dual mechanism promotes bone regeneration both directly through osteogenic signaling pathways and indirectly via immune microenvironment regulation.

BACKGROUND:Limited stem cells, low vascularization efficiency, and weak osteoinductive activity plague the repair and reconstruction of bone defects with cell-free scaffolds. METHODS:Herein, injectable platelet-rich fibrin (i-PRF) was loaded into a alginate methacryloyl (AlgMA)/gelatin methacryloyl (GelMA)-methylcellulose (AGM) bioink system and constructed a porous hydrogel scaffold by 3D bioprinting. The addition of nanosilicate-laponite (Lap) further enhanced this scaffold and synergized with i-PRF to promote efficient and personalized cranial regeneration. RESULTS:At the biochemical level, Lap significantly enhanced the ability of the scaffold to retard growth factor release, and multiple physiologically proportional growth factors in the scaffold synergistically promoted rapid neoangiogenesis and concomitantly recruited endogenous bone marrow mesenchymal stem cells (BMSCs). More importantly, the bioactive ions released by Lap markedly promoted the proliferation of BMSCs and consistently induced the osteogenic differentiation of BMSCs. At the immunological level, i-PRF-AGM@Lap significantly attenuates the inflammatory response by promoting macrophage M2 polarization. Mechanistically, miRNA sequencing and functional validation experiments demonstrated that bioactive ions released by Lap could synergize with growth factors in i-PRF to promote osteogenic differentiation of BMSCs through the miR-21 and miR-125a-mediated transforming growth factor-β/Smads signaling pathway. CONCLUSION:The results of this study provide a new idea for the personalized treatment of bone defects.

Accurate alignment correction is closely correlated with functional results after corrective osteotomy for knee joint deformities. Traditionally, osteotomy procedures were performed on the basis of the surgeon's experience and direct visual estimation. However, discrepancies between the planned and achieved corrections usually exist due to pre- and intraoperative errors. Digitized orthopedic surgery is an exciting field that utilizes computer science and medical engineering to facilitate personalized surgical treatment. Its potential in corrective osteotomy for treating knee joint deformity deserves a comprehensive review. This review searched the relevant literature in the Web of Science, Scopus, and PubMed, and focused on three aspects: three-dimensional (3D) printed patient-specific instrumentation, computer navigation system, and surgical robots. The characteristics and research status of digitized corrective osteotomy for treating knee joint deformities are outlined. The first-hand experiences from relevant papers and potential future advances in clinical, educational, and research areas were summarized. Current concerns about the already used approaches were clarified. Technological innovations in corrective osteotomy have steadily evolved with the aim of ensuring surgical precision and alignment accuracy, simplifying operational procedures, and improving patient outcomes. Digitized orthopedic surgery has favorable potential in terms of surgical practice, skill training, and delivery of healthcare information. Surgical navigation systems with synthetic functions of planning, training, and robotic assistance should be developed.

To develop evidence-based consensus guidelines for idiopathic clubfoot treatment in children by integrating a comprehensive evidence synthesis with expert consensus. We performed a PRISMA-compliant umbrella review of published systematic reviews, meta-analyses, and clinical guidelines on idiopathic clubfoot management. Inclusion criteria covered any intervention and outcomes for idiopathic clubfoot. Two reviewers independently screened studies and assessed quality using the Joanna Briggs Institute checklist. Data were extracted and qualitatively synthesized due to heterogeneity, grouping evidence by clubfoot type, treatment modality, and outcome domain. A 25-member expert panel then formulated consensus recommendations via a modified Delphi process (two survey rounds and a final consensus meeting) with a 75