ObjectiveMetagenomic Next Generation Sequencing (mNGS) offers a rapid, unbiased, and culture-independent approach to pathogen identification by analyzing all nucleic acids present in clinical samples. Despite its growing use, the diagnostic utility of mNGS in bone infections remains inadequately characterized. This study aimed to assess the diagnostic accuracy of mNGS compared to conventional microbial cultures and to explore its associations with clinical severity and patient outcomes.MethodsWe retrospectively enrolled 135 adult patients treated for suspected bone infections between October 2023 to January 2025 at Union Hospital, Tongji Medical College. Among these, 101 patients were classified as the infection group (IG) based on clinical and laboratory criteria, encompassing osteomyelitis, post-traumatic limb infections, and diabetic foot infections. mNGS results were compared to traditional cultures in terms of sensitivity, specificity, predictive values, and discordant cases. The IG was further stratified into mNGS-positive (n = 95) and mNGS-negative (n = 6) subgroups. Clinical parameters—including leukocyte differentials, C-reactive protein (CRP), procalcitonin (PCT), albumin, length of hospital stay, and mortality—were analyzed in relation to mNGS findings.ResultsAmong all patients, 74.81% were confirmed to have infections. mNGS demonstrated a markedly higher sensitivity than culture (94.06% vs. 47.52%, p = 0.000) while maintaining comparable specificity (85.29% vs. 76.47%, p = 0.549). Age showed a potential trend in influencing mNGS positivity (p = 0.092). Although not statistically significant, mNGS-positive patients tended to have longer hospitalizations (p = 0.098), suggesting possible associations with infection complexity or pathogen load.ConclusionmNGS substantially enhances the diagnostic yield for bone infections, particularly in polymicrobial, low-abundance, or culture-negative scenarios. mNGS-negative patients had significantly shorter hospital stays and a lower rehospitalization rate. Its rapid and comprehensive pathogen detection may enable more timely and targeted antimicrobial therapy, potentially improving patient outcomes and reducing healthcare burden. These findings support the integration of mNGS as a valuable adjunct to conventional diagnostic workflows in orthopedic infectious diseases.

Diabetic wounds present a complex pathological microenvironment that severely impairs healing. To address this challenge, we developed a supramolecular double-network hydrogel (CGRP@Rh-GelMA) consisting of a self-assembled rhein network and an in situ UV-crosslinked gelatin methacryloyl (GelMA) framework. This design endowed the hydrogel with strong mechanical robustness, wet-tissue adhesion, and sustained dual-drug release of rhein and calcitonin gene-related peptide (CGRP). In vitro, CGRP@Rh-GelMA exhibited broad-spectrum antibacterial activity and potent reactive oxygen species (ROS)-scavenging capacity. The hydrogel was also associated with reduced neutrophil extracellular trap (NETosis)-related markers, including myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit), as well as a shift in macrophage phenotype toward a reparative M2-like state, thereby contributing to a pro-healing immune microenvironment. In addition, CGRP@Rh-GelMA enhanced endothelial cell migration and vascular network formation in vitro, indicating pro-angiogenic potential. In a diabetic rat wound model, CGRP@Rh-GelMA accelerated wound repair, accompanied by improved immune microenvironment remodeling and neovascularization, resulting in enhanced granulation tissue formation, more organized collagen deposition, and re-epithelialization. Proteomic profiling further revealed inflammation-related pathway changes consistent with suppression of NF-κB signaling and NETosis. Collectively, these findings suggest that CGRP@Rh-GelMA is a mechanically robust and multifunctional biomaterial platform for diabetic wound healing by coordinately promoting immune and vascular repair responses. A CGRP@Rh-GelMA supramolecular double-network hydrogel was developed, in which self-assembled rhein serves as both a bioactive component and a structural network, while photocrosslinked GelMA enhances mechanical stability, wet-tissue adhesion, and sustained dual-drug release. The rhein-containing hydrogel showed antibacterial and ROS-scavenging activities and was associated with reduced NETosis-related markers, including MPO and H3Cit. CGRP-containing hydrogel treatment was associated with a shift in macrophage phenotype toward a reparative M2-like state, elevated VEGF expression, and enhanced angiogenesis-related cellular responses. The hydrogel accelerated diabetic wound healing, and proteomic analysis revealed pathway changes consistent with suppression of NF-κB signaling and NETosis.

Mechano-immunology is an interdisciplinary field that examines how mechanical forces-including endogenous tissue stresses and exogenous stimuli-modulate immune cell function in the maintenance of homeostasis and the progression of disease. As the primary load-bearing framework of the body, the musculoskeletal system depends on coordinated mechanical loading to sustain immune balance and tissue repair. With aging, reduced physical activity, progressive matrix stiffening, and impaired mechanosensing in immune-cells converge to disrupt this mechano-immune axis, undermining immune clearance, inflammatory regulation, and regenerative capacity within musculoskeletal tissues. These alterations collectively contribute to the onset and progression of osteoarthritis, osteoporosis, and other degenerative musculoskeletal disorders. This review summarizes current advances in understanding the mechanisms of mechano-immunology within the musculoskeletal system under physiological conditions and delineates its involvement in the initiation and progression of degenerative diseases. Emerging strategies, including exercise-based interventions, controlled mechanical stimulation, and biomaterial engineering approaches targeting mechano-immune pathways, are also discussed as potential means to restore musculoskeletal homeostasis during aging.

The exposed bone wound is defined as a kind of wound with bone denuded of periosteum and the deficiency of full-thickness skin and muscles. The wound have no matrix microenvironment and is prone to infection and, hence, hard to heal. Granulation tissue is significant during wound healing, providing a matrix and resisting infection. 3D printing is adopted to fabricate dermis and epidermis regeneration. However, the porosity of most 3D-printed scaffolds is low, leading to a poor drug-loading capacity. To address these limitations, this study developed an alginate-based hierarchical porous scaffold fabricated via cryogenic bi-nozzle 3D printing, enabling dual-factor spatial delivery of VEGF and LL-37 to simultaneously promote angiogenesis and immunomodulation. The alternating dual nozzle printing allows the scaffolds to carry two biological factors with spatial distribution while maintaining the structure integrity. In vitro studies demonstrated enhanced tube formation and endothelial migration, while in vivo implantation in rabbit exposed bone wounds revealed accelerated granulation tissue regeneration and re-epithelialization. The drug-loaded scaffolds can induce the tube formation of vascular endothelial cells, assist inflammatory cells in resisting infection, and ultimately form a fully functional granulation tissue. These results demonstrate the potential clinical applicability of this immunomodulatory dual-factor scaffold for challenging exposed bone wound repair.

Although previous studies have indicated a potential association between the gut microbiota and intervertebral disc degeneration (IVDD), the precise nature of this relationship remains unclear. The objective of this study is to further explore the potential causal relationship between gut microbiota and IVDD using a bidirectional Mendelian randomization approach, with the aim of identifying potential microbial characteristics associated with IVDD. Using the data from genome-wide association studies (GWAS) involving 412 gut microbiota species and 227,388 controls and 29,508 cases of IVDD. Inverse variance weighted (IVW) was used as the primary Mendelian randomization (MR) analysis, complemented by weighted median, MR-Egger regression, weighted mode and simple mode methods. Extensive sensitivity analyses were performed to confirm the robustness of the results and to assess heterogeneity and horizontal pleiotropy. This study revealed a positive genetic predisposition between 6 types of gut microbiota and IVDD through the IVW method, indicating that increased levels of these microbiota may lead to a higher risk of IVDD. Conversely, 6 types of gut microbiota were found to have negative effects on IVDD, suggesting that increased levels of these microbiota may have a protective effect against IVDD. Reverse MR analysis results revealed such possibilities as 1 positive and 5 negative causal relationships between IVDD and gut microbiota. The results of Cochran’s Q test, MR-Egger regression, and MR-PRESSO analysis from the bidirectional Mendelian randomization all yielded p-values greater than 0.05, indicating that there is no significant heterogeneity or pleiotropy in the genetic effect analysis between gut microbiota and IVDD. We used a bidirectional Mendelian randomization approach to identify various gut microbiota associated with IVDD. Our findings lay the foundation for further exploration of the pathogenesis and treatment strategies of gut microbiota and IVDD, and provide new possibilities for research on biomarkers of IVDD-related metabolic microbiota.

Background: Intervertebral disc degeneration (IVDD) is caused by an imbalance between the catabolic and anabolic processes within intervertebral disc tissue. Several studies have suggested a potential association between cerebrospinal fluid metabolites (CFMs) and the development of IVDD. However, the existing evidence on the relationship between CFM and IVDD is limited and inconsistent. Methods: The data on 338 cerebrospinal fluid metabolites and intervertebral disc degeneration analyzed in this study were sourced from their respective genome-wide association studies (GWAS). MR analysis employed single nucleotide polymorphisms (SNPs) closely associated with disease as instrumental variables (IVs). The inverse variance weighted (IVW) method was employed as the primary statistical approach, complemented by MR-Egger, the Weighted median, Simple mode, and the Weighted mode for result validation. Comprehensive sensitivity analyses were performed to confirm the robustness of the results and assess for heterogeneity and horizontal pleiotropy. Results: Using the IVW method, this study revealed positive causal effects between 11 cerebrospinal fluid metabolites (CFMs) and intervertebral disc degeneration (IVDD), indicating that elevated levels of these 11 CFMs increase the risk of IVDD. Conversely, negative causal effects were identified for 6 CFMs, suggesting that higher levels of these CFMs have a protective effect against IVDD. Reverse MR analysis indicated 1 positive and 18 negative causal relationships between IVDD and CFMs. Conclusions: Our bidirectional Mendelian analysis provides compelling evidence of a causal relationship between CFMs and IVDD. These findings enhance our understanding of IVDD pathogenesis and highlight the potential for preventive therapies targeting CFMs. Further research is needed to clarify the mechanisms of these CFMs on IVDD.

Intervertebral disc degeneration (IVDD), a major cause of low back pain, poses significant global health and socioeconomic challenges. Current therapies have limited effectiveness in reversing degeneration, which underscores the need for advanced treatment strategies. Exosomes, which are nanoscale extracellular vesicles, have emerged as promising therapeutic agents for IVDD due to their unique biological properties. They exert their effects through multiple mechanisms, such as regulating the extracellular matrix, promoting cell proliferation, and exerting anti‐inflammatory effects. This review summarizes recent advances in exosome‐based therapies for IVDD. It encompasses their mechanisms, cell sources, engineering technologies, and progress in clinical translation. Additionally, the challenges and opportunities related to their future clinical application are discussed, and their potential to revolutionize the treatment of IVDD is highlighted.

Aseptic loosening is the primary cause of bone prosthesis failure, commonly attributed to inadequate osseointegration due to coatings misaligned with bone regeneration. Here, we modify the titanium surface with a mussel-inspired peptide to form a 3,4-dihydroxyphenylalanine (DOPA)-rich coating, then graft N3-K15-PVGLIG-K23 (P1) and N3-Y5-PVGLIG-K23 (P2), which are composed of anti-inflammatory (K23), angiogenic (K15), osteogenic (Y5), and inflammation-responsive (PVGLIG) sequences, onto the surface via click chemistry, forming the DOPA-P1@P2 coating. DOPA-P1@P2 promotes bone regeneration through sequential regulation. In the initial stage, the outermost K23 induces M2 macrophage polarization, establishing a pro-regenerative immune microenvironment. Subsequently, K15 and Y5, exposed by the release of K23, enhance angiogenesis and osteogenesis. In the final stage, DOPA-P1@P2 outperforms the TiO₂ control, showing a 161% increase in maximal push-out force, a 207% increase in bone volume fraction, and a 1409% increase in bone-to-implant contact. These findings show that DOPA-P1@P2 efficiently enhances interfacial osseointegration by sequentially regulating bone regeneration, providing viable insights into coating design.

ObjectiveThe objective of this study is to investigate the clinical efficacy of proximal femoral locking plates in comparison to cannulated compression screws for the treatment of femoral neck fractures.MethodsA retrospective analysis of clinical data from 50 patients with femoral neck fractures treated at the Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2018 to June 2023. Patients were divided into 25 in the PFLP group and 25 in the CCS group. A comparison was made between the two groups in terms of the following variables: basic characteristics, perioperative information, and information during follow-up visits.ResultsThe basic characteristics of the two groups were found to exhibit no statistically significant differences (P > 0.05). The PFLP group had significantly longer surgical times and greater Intraoperative hemorrhage loss compared to the CCS group (P < 0.05). The statistical analysis revealed that there were no significant differences in intraoperative fluoroscopy times and Garden index between the two groups (P > 0.05). The PFLP group exhibited a markedly superior fracture healing time, femoral neck shortening, and Harris hip scores in comparison to the CCS group (P < 0.05). The postoperative complication rates were 12% in the PFLP group and 20% in the CCS group, with no statistically significant difference (P > 0.05).ConclusionThe results of this retrospective study suggest that the PFLP group demonstrated superior outcomes compared to the CCS group in several key areas, including fracture healing time, preservation of femoral neck length, recovery of hip function, and incidence of postoperative complications.

Background: Although clinical studies have indicated a possible association between dyslipidemia and osteoporosis, the underlying genetic basis and mechanistic pathways remain insufficiently defined. Most prior research has concentrated on conventional lipid markers, which are prone to confounding and limit causal inference. Exploring lipidomic profiles offers a more comprehensive view of lipid metabolism and may reveal novel genetic links beyond traditional lipid traits. Additionally, alterations in immune cell function, often triggered by metabolic disturbances, may contribute to osteoporosis development; however, the potential mediating role of immune cells in the lipid–bone axis has not been systematically investigated. Methods: A total of 179 lipid species across 13 lipid classes were analyzed in 7174 Finnish individuals from the GeneRISK cohort. Genome-Wide Association Study (GWAS) summary statistics for osteoporosis and 731 immune cell immunophenotypes were sourced from the GWAS Catalog. A two-step, two-sample Mendelian randomization analysis, using inverse variance weighting (IVW), was conducted to explore the potential causal effects of lipids on osteoporosis and the mediating role of immune cells in the relationship between lipids and osteoporosis. Results: Mendelian randomization analysis indicated that triacylglycerol levels of 48:0 were possibly associated with an increased risk of osteoporosis (IVW: odds ratio [OR] 1.1320, 95% CI 1.0401–1.2321; p = 0.004), while triacylglycerol levels of 48:3 appeared to be associated with a reduced risk of osteoporosis (IVW: OR 0.9053, 95% CI 0.8364–0.9800; p = 0.014). Two statistically significant mediating effects were identified: First, IgD− CD38dim %B cells appeared to partially negatively mediate the association between triacylglycerol levels of 48:3 and osteoporosis, with a negative mediating effect of −0.00669 (95% CI: −0.0214, 0.00805), which accounted for 6.73% of the total effect. That is, the protective effect of triacylglycerol levels of 48:3 against osteoporosis was attenuated by IgD− CD38dim %B cells. Second, HLA DR++ monocytes% leukocytes also partially negatively mediated this relationship, with a mediating effect of −0.023 (95% CI: −0.0434, −0.00266), accounting for 23.2% of the total effect. This indicates that other immune cells, HLA DR++ monocytes %leukocytes, resisted the protective effect of triacylglycerol levels of 48:3 against osteoporosis, with a weakening effect stronger than that of IgD− CD38dim %B cells. Conclusions: Our findings contribute to the growing understanding of the potential causal relationships and shared pathogenic mechanisms between dyslipidemia and osteoporosis. The results suggest that the potential genetic effects of plasma lipid metabolites on osteoporosis may be partially down-regulated by specific kinds of immune cells.

Polymers are large molecules composed of repeating subunits called monomers, which can be de-rived from both natural sources and synthetic processes. Due to their exceptional physicochemical properties and functional characteristics, polymers have garnered significant attention in the bio-medical field, particularly in tissue engineering. 3D printing technology, a process that manufactures three-dimensional objects by sequentially adding material based on digital models, has been widely recognized for its integration with polymers in bone tissue engineering (BTE). This review provides an overview of 3D-printed polymeric biomaterials in BTE. It begins with a discussion of the fundamental process of bone regeneration, followed by a component's selection for polymers and 3D printing technologies. Additionally, this review comprehensively addresses the functional properties design of 3D-printed polymeric biomaterials. Finally, the current status, challenges, and future directions for the application of 3D-printed polymeric biomaterials in BTE are discussed.

Cellular senescence is a significant contributor to intervertebral disc aging and degeneration. However, the application of senotherapies, such as senomorphics targeting senescence markers and the senescence-associated secretory phenotype (SASP), remains limited due to challenges in precise delivery. Given that the natural killer group 2D (NKG2D) ligands are increased on the surface of senescent nucleus pulposus (NP) cells, the NKG2D-overexpressing NP cell membranes (NNPm) are constructed, which is expected to achieve a dual targeting effect toward senescent NP cells based on homologous membrane fusion and the NKG2D-mediated immunosurveillance mechanism. Then, mesoporous silica nanoparticles carrying a peroxisome proliferator-activated receptor-ɣ coactivator 1α (PGC1α)inducer (SP) are coated with NNPm (SP@NNPm) and it is found that SP@NNPm selectively targets senescent NP cells, and the SP cores exhibit pH-responsive drug release. Moreover, SP@NNPm effectively induces PGC1α-mediated mitochondrial biogenesis and mitigates senescence-associated markers induced by oxidative stress and the SASP, thereby alleviating puncture-induced senescence and disc degeneration. This dual-targeting nanotherapeutic system represents a novel approach to delivery senomorphics for disc degeneration treatment.

Low back pain (LBP) is most commonly caused by intervertebral disc degeneration (IVDD). Pyroptosis, apoptosis, and necroptosis are crucial in IVDD pathogenesis; however, possible simultaneous occurrence in IVDD and co-regulation between the pathways and the regulatory mechanisms have not been investigated. PANoptosis is a regulated cell death (RCD) pathway with the key characteristics of pyroptosis, apoptosis, and necroptosis. This study revealed that tert-butyl hydroperoxide (TBHP) altered the expression of key proteins involved in PANoptosis in nucleus pulposus cells (NPCs). Furthermore, the natural product Kongensin A (KA), which has potential anti-necrotic and anti-inflammatory properties, inhibited PANoptosis. TAK1, often referred to as mitogen-activated protein kinase kinase kinase 7 (Map3k7), is a key regulator of innate immunity, cell death, inflammation, and cellular homeostasis; however, the physiological roles and regulatory mechanisms underlying IVDD remain unclear. In this study, we discovered that KA can upregulate TAK1 expression in NPCs, -which inhibits PANoptosis by suppressing oxidative stress. In conclusion, our results suggest that KA inhibits PANoptosis and delays IVDD progression in NPCs by upregulating TAK1 expression to maintain mitochondrial redox balance. Consequently, targeting TAK1 may be a promising therapeutic approach for IVDD therapy.

Aseptic loosening is the primary cause of orthopaedic implant failure. Previous designs for implant coatings failed to follow the physiological process of bone regeneration, leading to inadequate osseointegration at the bone–implant interface. We engineered a novel self-adaptive titanium-based coating (DOPA-P1@P2) by combining a mussel-inspired biomimetic strategy with bioorthogonal click chemistry techniques. Both in vitro and in vivo results confirmed that DOPA-P1@P2 exhibited excellent biocompatibility and effectively enhanced osseointegration. Specifically, the outermost K23 layer of DOPA-P1@P2 promotes M2 macrophage polarization in the first stage of bone regeneration, creating a favourable immune microenvironment. Following the release of K23, the sequential exposure of the K15 and Y5 layers promoted angiogenesis and osteogenesis during the second stage of bone regeneration. In the third stage of bone regeneration, the DOPA-P1@P2 group exhibited a 161% increase in maximal push-out force, a 207% increase in BV/TV, and a remarkable 1409% increase in BIC, compared to the TiO2 control group. In summary, DOPA-P1@P2 effectively promoted bone regeneration through sequential regulation, thus enhancing osseointegration at the bone–implant interface.

The intervertebral disc is not isolated from other tissues. Recently, abundant research has linked intervertebral disc homeostasis and degeneration to various systemic diseases, including obesity, metabolic syndrome, and diabetes. Organokines are a group of diverse factors named for the tissue of origin, including adipokines, osteokines, myokines, cardiokines, gastrointestinal hormones, and hepatokines. Through endocrine, paracrine, and autocrine mechanisms, organokines modulate energy homeostasis, oxidative stress, and metabolic balance in various tissues to mediate cross-organ communication. These molecules are involved in the regulation of cellular behavior, inflammation, and matrix metabolism under physiological and pathological conditions. In this review, we aimed to summarize the impact of organokines on disc homeostasis and degeneration and the underlying signaling mechanism. We focused on the regulatory mechanisms of organokines to provide a basis for the development of early diagnostic and therapeutic strategies for disc degeneration.

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain that incurs large socioeconomic burdens. Growing evidence reveals that macroautophagy/autophagy dysregulation contributes to IVDD, but the exact role of autophagy and its regulatory mechanisms remain largely unknown. Here, we found that mechanical overloading impaired the autophagic flux of nucleus pulposus (NP) cells in vivo and in vitro. Mechanistically, the impairment of autophagic flux was attributed to lysosomal dysfunction induced by overloading. Overloading could also lead to lysosomal membrane permeabilization and consequent lysosome-dependent cell death. As critical effectors of lysosomal quality control pathways, CHMP4B (charged multivesicular body protein 4B) and TFEB (transcription factor EB) were downregulated in overloading-treated NP cells and degenerative discs. Restoring lysosomal function by CHMP4B or TFEB overexpression attenuated autophagic flux impairment of NP cells and protected against overloading-induced IVDD. Additionally, human IVDD was associated with impaired autophagy, and defective lysosomal quality control was also linked to human IVDD. Collectively, these findings highlighted that lysosomal defects were crucial for mechanical overloading-induced autophagic flux impairment and death of NP cells, suggesting the potential therapeutic relevance of restoring lysosomal function for IVDD.Abbreviations: ADAMTS4: ADAM metallopeptidase with thrombospondin type 1 motif 4; Ad: adenovirus; AO: acridine orange; BafA1: bafilomycin A1; CHMP4B: charged multivesicular body protein 4B; CTSD: cathepsin D; CV%: coefficient of variation; DMSO: dimethyl sulfoxide; ESCRT: endosomal sorting complex required for transport; HE: haemotoxylin and eosin; IVDD: intervertebral disc degeneration; LAMP: lysosomal associated membrane protein; LMP: lysosomal membrane permeabilization; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MFI: mean fluorescence intensity; MMP3: matrix metallopeptidase 3; MRI: magnetic resonance imaging; NP: nucleus pulposus; PG: Pfirrmann grade; PI: propidium iodide; RT-qPCR: reverse transcription-quantitative PCR; SOFG: safranin O fast green; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TFEB: transcription factor EB.

Objective Enhance the efficiency of tibial transverse transport by employing customized 3D-printed osteotomy guide plates and striving to improve precision through CT evaluation for enhanced guide design. Methods 17 diabetic foot patients were treated with the plate for tibial transverse transport. Preoperatively, we collected DICOM data from the affected tibia's CT and designed the geometric parameters of the tibial cortical bone window. A customized 3D-printed osteotomy guide plate was then fabricated using 3D printing technology. Postoperative X-ray and CT evaluations, conducted at two and five weeks post-surgery, assessed five crucial geometric parameters of the bone window. Measurements included the distance from the upper edge of the tibial cortical bone window to the tibial plateau, the distance from the anterior edge of the tibial cortical bone window to the bone ridge, the height of the tibial cortical bone window, the center-to-center distance between the 4.0mm diameter Schanz pin and the osteotomy Kirschner pin, and the center-to-center distance of the 4.0mm diameter Schanz pin. These measured parameters were subsequently compared to the preoperative design parameters. Results CT measurements showed no significant differences (P > 0.05) from preoperative design parameters across the five evaluated aspects. The average osteotomy duration was 35 ± 15 minutes with no bone window fractures. The bone window aligned effectively with the tibial shaft, achieving complete incorporation after distraction. A 4 to 8-month postoperative follow-up confirmed full healing of the tibial surgical wound and diabetic foot wounds. Conclusion Utilizing customized 3D-printed osteotomy guide plates in tibial transverse bone transport surgery enables accurate translation of preoperative virtual designs into real-time procedures, enhancing surgical efficiency and quality.

Inadequate osseointegration at the interface is a key factor in orthopedic implant failure. Mechanistically, traditional orthopedic implant interfaces fail to precisely match natural bone regeneration processes in vivo. In this study, a novel biomimetic coating on titanium substrates (DPA-Co/GFO) through a mussel adhesion-mediated ion coordination and molecular clicking strategy is engineered. In vivo and in vitro results confirm that the coating exhibits excellent biocompatibility and effectively promotes angiogenesis and osteogenesis. Crucially, the biomimetic coating targets the integrin α2β1 receptor to promote M2 macrophage polarization and achieves a synergistic effect between immunomodulation and vascularized bone regeneration, thereby maximizing osseointegration at the interface. Mechanical push-out tests reveal that the pull-out strength in the DPA-Co/GFO group is markedly greater than that in the control group (79.04 ± 3.20 N vs 31.47 ± 1.87 N, P < 0.01) and even surpasses that in the sham group (79.04 ± 3.20 N vs 63.09 ± 8.52 N, P < 0.01). In summary, the novel biomimetic coating developed in this study precisely matches the natural process of bone regeneration in vivo, enhancing interface-related osseointegration and showing considerable potential for clinical translation and applications.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma (OS). However, the landscape and dynamics of immune cells in OS are poorly characterized. By analyzing single-cell RNA sequencing (scRNA-seq) data, which characterize the transcription state at single-cell resolution, we produced an atlas of the immune microenvironment in OS. The results suggested that a cluster of regulatory dendritic cells (DCs) might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells. We also found that major histocompatibility complex class I (MHC-I) molecules were downregulated in cancer cells. The findings indicated a reduction in tumor immunogenicity in OS, which can be a potential mechanism of tumor immune escape. Of note, CD24 was identified as a novel "don't eat me" signal that contributed to the immune evasion of OS cells. Altogether, our findings provide insights into the immune landscape of OS, suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.