Diabetic bone defects (DBD) are difficult to heal because persistent inflammation, metabolic dysfunction and fibrotic repair disrupt the transition from injury to regeneration. Here, we report PP@ILES, a peptide functionalized electroconductive nanofibrous scaffold that combines local electrical cues with immobilized and gradually released bioactive peptide signals to remodel the diabetic defect niche. Single cell RNA sequencing and mechanistic analyses showed that PP@ILES reshaped macrophage and fibroblast states at the early repair stage. In macrophages, PP@ILES was associated with reduced mTORC1 activity, enhanced mitochondrial oxidative metabolism and fatty acid oxidation, increased CD206 expression, and decreased iNOS, TNF alpha and glycolytic output. In fibroblasts, PP@ILES attenuated activation through KLF4 associated downregulation of alpha SMA, limiting scar like fibrotic remodeling. In diabetic rats with 5 mm cranial defects, PP@ILES promoted bone regeneration and mature lamellar bone formation with reduced fibrotic tissue compared with conductive scaffold alone or peptide scaffold alone. These findings suggest that coordinated regulation of immune metabolism, fibrotic remodeling and osteogenesis through an electrobiochemical scaffold may provide a promising strategy for diabetic bone repair.

Defective macrophage efferocytosis sustains inflammation and compromises bone repair in diabetic defects, yet strategies that restore efferocytic immune homeostasis remain limited. Here, we engineered an ultrasound-responsive piezoelectric hydrogel (Gel BC@ZnO) by incorporating zinc oxide (ZnO) nanoparticles into a bacterial cellulose (BC)-reinforced gelatin methacryloyl (GelMA) network to provide localized bioelectric cues. Gel BC@ZnO exhibited good cytocompatibility, structural stability, and robust ultrasound-triggered piezoelectric output. Under diabetic-mimicking conditions, ultrasound activation generated bioelectric signals that engaged Piezo1, induced Piezo1-dependent Ca2+ influx, and rescued macrophage efferocytosis. This efferocytic reactivation attenuated ROS accumulation, shifted macrophages toward a pro-regenerative phenotype, enhanced osteogenic differentiation, and suppressed osteoclast genesis, thereby restoring bone-remodeling homeostasis. In a diabetic femoral condyle defect model, Gel BC@ZnO combined with ultrasound accelerated bone repair, increased local Piezo1 expression, promoted collagen deposition and osteogenic marker expression, and rebuilt a favorable immune microenvironment. These results define a bioelectric signal-Piezo1-Ca2+-efferocytosis axis for diabetic bone regeneration and establish a non-invasive, ultrasound-controllable immunomodulatory strategy for compromised bone repair.

Femoral neck fractures are prone to mechanical failure and severe complications due to high inter-fragmentary shear forces. The Femoral Neck System (FNS) provides angular-stable biomechanical fixation, where precise intra-osseous implant positioning directly determines long-term clinical outcomes. Ti-Robot orthopedic navigation enables preoperative three-dimensional trajectory planning and intra-operative guided screw placement, which may improve implant accuracy while reducing surgical soft tissue trauma. A critical methodological caveat applies to this comparison: the two surgical arms differ simultaneously in navigation modality, fracture reduction technique, and soft tissue dissection extent; observed intergroup outcomes cannot be attributed solely to robotic technology. To compare intra-operative efficiency, fluoroscopic radiation burden, postoperative CT-verified implant precision, 6, 12, and 18-month hip functional recovery, and adverse complication profiles between combined Ti-Robot-guided closed percutaneous FNS fixation and conventional open reduction freehand FNS fixation for femoral neck fractures. This single-center retrospective consecutive cohort study enrolled 80 patients aged 18–65 years with femoral neck fractures treated between January 2023 and December 2024; 40 patients underwent Ti-Robot-assisted percutaneous FNS fixation, and 40 received conventional open reduction FNS fixation. Primary outcome measure was the Harris Hip Score (HHS) collected at 6, 12, and 18 months postoperatively. Secondary outcomes included total operative duration, intra-operative blood loss, fluoroscopic imaging metrics (total shot count + cumulative screening time), postoperative CT implant trajectory deviation, bolt angular parallelism error, first-attempt screw placement success rate, serial 0–10 VAS pain scores, institutional hospital length of stay (LOS), and 18-month fracture-related complication incidence. All participants completed full 18-month clinical and imaging follow-up. Statistical analyses were performed using Python; normality-directed variable-specific testing was applied, with no formal correction conducted for multiple secondary outcome comparisons. Patients treated with Ti-Robot-guided percutaneous fixation demonstrated statistically superior HHS values at all three 6/12/18-month follow-up time intervals (all p < 0.05). Median postoperative CT-measured FNS bolt deviation from a unified blinded radiologist-defined femoral neck central reference axis was 0.9 mm in the robotic cohort versus 1.9 mm in the conventional open cohort (p < 0.001). The robotic group exhibited drastically reduced fluoroscopic shot counts and cumulative screening time, alongside significantly shortened median operative duration (67.0 min vs. 88.0 min; p < 0.001). Intraoperative blood loss was numerically lower in robotic patients without reaching statistical significance (p = 0.160). Serial postoperative VAS pain scores were markedly reduced across all follow-up intervals for the percutaneous robotic group. Hospital LOS followed fixed institutional discharge protocols: all robotic patients were discharged on postoperative day 3, and all open-surgery patients on day 5 (p < 0.001); this near-zero inter-patient variance represents an administrative pathway artifact rather than a marker of individual clinical recovery. While the robotic cohort showed numerical reductions in screw loosening, non-union, and femoral head avascular necrosis (AVN) events at 18 months, all between-group differences for these rare complications lacked statistical significance due to limited sample power. The combined workflow of TiRobot three-dimensional navigation and percutaneous minimally invasive FNS fixation delivers superior implant placement precision, lower intraoperative fluoroscopic radiation exposure, shorter operative time, and sustained mid-term hip functional recovery across the 6, 12, and 18-month follow-up intervals relative to conventional open reduction FNS fixation for Pauwels type III femoral neck fractures. All observed intergroup differences reflect a composite effect of robotic guidance and limited soft tissue dissection. Future standardized randomized controlled trials utilizing identical closed percutaneous approaches in both robotic and freehand arms are required to isolate clinical benefits uniquely attributable to TiRobot navigation.

Biomimetic mineralization as a promising method offers a bottom-up strategy for creating new organic-inorganic hybrid materials for treating bone defects. However, it is insufficient for bone regeneration, a complex biological procedure involving an interaction between osteogenesis and microenvironment. Herein, a biomimetic mineralized scaffold derived from decellularized adipose tissue modified with polyphenol tannic acid (TA@mDAT) is developed, drawing inspiration from the regulation of the microenvironment and the biomimetic strategy. Besides its enhanced mechanical properties by mineralization, the shape-memory effect of the biomimetic mineralized decellularized adipose tissue (mDAT) is also improved, due to the crosslinking structure between decellularized adipose tissue (DAT) and tannic acid (TA). Besides, the TA@mDAT scaffold exhibits excellent biocompatibility and immunomodulation effect, high efficacy in guiding bone regeneration via intramembranous and endochondral ossification, and enhanced H-type vessel formation. Furthermore, the enhanced expression of Dll4 and Hey1 involving the Notch1 signaling pathway is detected in the regenerated bone, indicating that the Dll4-Notch1 signaling pathway may play an important role in bone regeneration. Thus, this work provides a promising method for bone regeneration by triggering periosteal osteogenesis and H-type vessel formation and revealing a potential mechanism in the osteogenic process.

The residual bone tumor and defects which is caused by surgical therapy of bone tumor is a major and important problem in clinicals. And the sequential treatment for irradiating residual tumor and repairing bone defects has wildly prospects. In this study, we developed a general modification strategy by gallic acid (GA)-assisted coordination chemistry to prepare black calcium-based materials, which combines the sequential photothermal therapy of bone tumor and bone defects. The GA modification endows the materials remarkable photothermal properties. Under the near-infrared (NIR) irradiation with different power densities, the black GA-modified bone matrix (GBM) did not merely display an excellent performance in eliminating bone tumor with high temperature, but showed a facile effect of the mild-heat stimulation to accelerate bone regeneration. GBM can efficiently regulate the microenvironments of bone regeneration in a spatial-temporal manner, including inflammation/immune response, vascularization and osteogenic differentiation. Meanwhile, the integrin/PI3K/Akt signaling pathway of bone marrow mesenchymal stem cells (BMSCs) was revealed to be involved in the effect of osteogenesis induced by the mild-heat stimulation. The outcome of this study not only provides a serial of new multifunctional biomaterials, but also demonstrates a general strategy for designing novel blacked calcium-based biomaterials with great potential for clinical use.

Exogenous electrical-field stimulation has been demonstrated as a pivotal means for accelerating chronic wound healing. However, its inhomogeneous electrical-field distribution along the depth axis would result in localized overstimulation and insufficient cellular activation, motivating the need of innovative electrical stimulation modalities to achieve controllable cellular modulation. In this work, we develop a spatially uniform microcurrent stimulation driven by a self-powered wearable Ag2Se thermoelectric patch integrated with a conductive hydrogel. The mechanically adaptive hydrogel conforms seamlessly to complex wound topographies, functioning as a conductive medium to deliver physiologically-relevant microcurrent across the interfaces of hydrogel-cells for cellular activation. Sustained stimulation of ∼6 μA microcurrent, generated by thermoelectric device harnessing natural skin-ambient temperature gradients, multifunctionally promotes the migration and proliferation of fibroblasts cells, and regulates the expression of cytokines and signaling pathways related to wound repair. These consequences effectively mitigate inflammation and expedite neovascularization and tissue-remodeling, demonstrating the biomimetic microcurrent stimulation as a sustainable therapeutic strategy for the diabetic wound healing.

BACKGROUND:Acetabular roof was a crucial structure for maintaining the stability of hip joint; however, its important role was not especially emphasized in the Letournel-Judet classification system. Acetabular roof was segmented into the roof column and roof wall in Three-column classification and fracture in this area alone was defined as A3 injury. The purpose of this study was to explore the characteristics and surgical strategy of A3 injury. METHODS:Patients with roof column/wall fractures received surgical management from January 2015 to 2019 January at nine level-1 trauma centers were retrospectively analyzed. Fracture data, surgical incision, operation time, blood loss, fracture healing and relevant complications were recorded to explore fracture characteristics and appropriate surgical strategy. Reduction quality was assessed based on postoperative radiographic examination. Merle d'Aubigné score was used to assess the functional outcome during the follow-up. RESULTS:A total of 60 patients met the inclusion criteria in this study. Mean operation time was 112.83±21.77 min, and mean intraoperative blood loss was 396.67±182.00 ml. Satisfactory reduction quality was obtained in 49 cases (81.67%). All fractures healed well at an average mean of 3.07 months. Satisfactory outcomes were obtained in 46 cases (76.67%), and mean Merle d'Aubigné score was 15.53±1.33 points at the final follow-up. Reduction quality and functional outcome showed no statistical difference in three subtypes (P<0.05). Reduction quality and functional outcome presented positive correlation in three subtype fractures (P<0.05). The complication rate was 11.67% (7/60) in this study. CONCLUSION:The injury mechanism of A3 injury was the direct impaction from femoral head on acetabular roof. Reduction and fixation of A3 injury were technique demanding, and poor prognosis may be accompanied even treated by experienced surgeons. Appropriate surgical strategies (Table 5) based on fracture characteristics in three subtypes of A3 injury were the premise of accepted prognosis.

Opportunistic chest CT (OC-CT) presents significant potential for early osteoporosis screening. However, its application remains limited to specific patient populations, and the optimal vertebral level for osteoporosis detection has yet to be determined. This study aimed to determine the optimal vertebral level and assess the feasibility of OC-CT, with dual-energy X-ray absorptiometry (DXA) being the gold standard. We retrospectively included 1236 participants aged 50 years or above and who completed both DXA and routine chest CT scans within 6 months. Receiver operation characteristic (ROC) analysis was used to evaluate the diagnostic performance in detecting low bone mass and osteoporosis. Among 15,007 vertebrae analyzed, CTAV at the 1st-12th thoracic (T1-T12) and the 1st lumbar (L1) vertebrae exhibited good discrimination for low bone loss and osteoporosis with the area under the ROC curve exceeding 0.80. Notably, T8 was the only vertebra to achieve sensitivity above 0.80 for both conditions: a cut-off value of 163.5 Hu yielded 81% sensitivity and 84% specificity for low bone mass, while 132.3 Hu yielded 82% sensitivity and 75% specificity for osteoporosis. These findings indicated that OC-CT demonstrated comparable diagnostic performance to DXA for bone mass evaluation in individuals aged 50 years or above. T8 was recommended as the optimal vertebral level for opportunistic bone mass evaluation, and T7 and T10 vertebrae were the preferred alternatives when T8 was not available. We also provided a user-friendly self-check table for rapid bone mass evaluation to facilitate clinical utility.

Research on the use of green solvents for the preparation of polymer separation membranes has received much attention from industry and academia. For the first time, we used 3-methoxy-N,N-dimethylpropionamide (MDMP) as a low-toxic solvent for the preparation of polyvinylidene fluoride (PVDF) membranes, in which MDMP has good water solubility and can be used to prepare polymer membranes using the non-solvent-induced phase separation (NIPS) method. Various properties of the membranes, such as pure water permeability, surface and cross-sectional structure, and overall porosity, were investigated. We also investigated the solubility of MDMP in other polymeric membrane materials, and the results showed that MDMP had good solubility to most membrane materials, except polyacrylonitrile (PAN). In addition, the use of different membrane materials in the presence of MDMP showed different surface and cross-sectional structures, and therefore, as a low-toxic solvent, MDMP will have important applications in the field of polymer membrane preparation.

The repair of osteoporotic bone defects remains inadequately addressed, primarily due to a disruption in bone homeostasis, characterized by insufficient bone formation and excessive bone resorption. Current research either focuses on promoting bone formation or inhibiting bone resorption, however, the bone repair efficacy of these single-target therapeutic strategies is limited. Herein, a "two-way regulation" bone homeostasis strategy is proposed utilizing piezoelectric composite membranes (DAT/KS), capable of simultaneously regulating osteogenesis and osteoclastogenesis, with high piezoelectric performance, good biocompatibility, and excellent degradability, to promote bone regeneration under osteoporotic conditions. The DAT/KS membrane under ultrasound (US) treatment enables the controlled modulation of piezoelectric stimulation and the release of saikosaponin D (SSD), which promotes osteogenic differentiation while simultaneously inhibiting osteoclast differentiation and function, thereby effectively restoring bone homeostasis and enhancing osteoporotic bone repair. Mechanistic insights reveal the promotion of both canonical and non-canonical Wnt signaling in bone marrow mesenchymal stem cells (BMSCs), which determines their osteogenic differentiation fate, and the downregulation of the NF-κB signaling in bone marrow mononuclear macrophages (BMMs). This study presents optimized sono-piezoelectric biomaterials capable of bidirectionally regulating both osteogenic and osteoclastic differentiation, providing a new potential therapeutic approach for pathological bone injuries.

The pathological microenvironment in diabetic wounds is delineated by heightened inflammatory responses and persistent proinflammatory macrophage activity, which significantly hinders the wound healing process. Exogenous electrical stimulation (ES), by modulating the electric field distribution in wounds, has shown significant potential in treating inflammatory wounds. However, this approach relies on additional power sources and complex circuit designs. Here, a bionic neuro-immuno-regulatory (BNIR) system was proposed for reshaping the endogenous electric fields (EFs) through collecting ion flow. The BNIR system comprises microporous structure scaffolds and nanosheets, enabling swift biofluid collection and electrical signal transmission, with the ability to promote cell proliferation and migration and exhibit antioxidant properties. More importantly, the BNIR system induced the transition of M1 macrophages to M2 macrophages through neuro-immuno-regulatory. In diabetic rat skin wounds, the BNIR system significantly enhanced healing by simultaneously neuro-immuno-regulatory, promoting angiogenesis, scavenging ROS, and facilitating tissue remodeling. This work aims to advance the development of a bionic system for electrosensitive tissue repair.

The purpose of this study was to compare the efficacy of femoral neck system (FNS) and cannulated screws with a medial plate (CSMP) for Pauwels type III femoral neck fractures in young adults. In this retrospective analysis, 70 patients aged 18–65 with Pauwels type III femoral neck fractures were divided into two groups according to internal fixation: 37 in the FNS group and 33 in the CSMP group. Postoperative complications and functional outcomes were mainly studied. The mean follow-up was 25.3 ± 3.7 months. The FNS group exhibited significantly shorter fluoroscopy time, less blood loss, and shorter surgical time than the CSMP group (all P < 0.001). The CSMP group had a shorter fracture union time than the FNS group (P = 0.032). The length of femoral neck shortening at 6-, 12-, and 18-months was significantly lower in the CSMP group (all P < 0.05). Harris Hip Score (HHS) at 6 months was higher in the CSMP group (P = 0.042). However, no significant differences were observed between the two groups regarding the length of femoral neck shortening at 3 months or Harris Hip Score (HHS) at 3-, 12-, and 18 months (all P > 0.05). The VAS scores at 18 months showed no significant difference between the two groups (P = 0.247). Additionally, no significant differences were noted in other complications. There is a significant difference in the Harris Hip Score at 18 months between the femoral neck shortening and the non-shortening groups (P < 0.001). Logistic regression analysis identified fracture comminution (OR = 7.764, 95

Diabetic oral ulcers pose a significant challenge in healing due to persistent inflammation. Despite local therapeutic interventions remaining the primary mode of treatment, the dynamic nature of the oral cavity, characterized by continuous muscular activity and salivary secretion, poses barriers to sustained drug retention and thereby limits therapeutic efficacy. To address this issue, an approach has been devised that aims to facilitate transdermal delivery of bioactive components to promote the healing of diabetic oral ulcers. A multifunctional soluble microneedle (MN) patch is prepared using γ-polyglutamic acid (γ-PGA), which is loaded with quercetin (Qu)-modified Mg-Zn layered hydroxide salt (LHS) nanosheets (LHSQ) with anti-inflammatory, antimicrobial and pro-angiogenic bioactivities to combat the diabetic oral ulcers. These findings demonstrate that the LHSQ-loaded MN (LHSQ-MN) patches are capable of effectively penetrating the oral mucosa. In a rat model of diabetic oral ulcers, the application of LHSQ-MN patches is found to facilitate the establishment of regeneration sites, regulate the inflammatory microenvironment of damaged tissues, exhibit potent antibacterial effects, expedite the reconstitution of the mucosal epithelium, and accelerate ulcer healing through the promotion of angiogenesis. These outcomes highlight the potential of LHSQ-MN patches as a promising therapeutic strategy for the management of oral ulcers in diabetic patients.

Ferroptosis is a novel form of programmed cell death, distinguished from apoptosis, autophagy, and programmed necrosis and has received much attention since it was defined in 2012. Ferroptotic cells physiologically exhibit iron metabolism dysregulation, oxidative stress, and lipid peroxidation. Morphologically, they show plasma membrane disruption, cytoplasmic swelling, and mitochondrial condensation. Osteoporosis is taken more and more seriously as the proportion of the aging population continues to increase globally. Interestingly, ferroptosis has been demonstrated to be involved in the development and progression of osteoporosis in many extant studies. The review summarizes iron metabolism, lipid peroxidation, and the different regulatory signals in ferroptosis. Changes in signaling mechanisms within osteoblasts, osteoclasts, and osteocytes after ferroptosis occur are explained here. Studies showed ferroptosis play an important role in different osteoporosis models (diabetes osteoporosis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis). Inhibitors and EC (Exos) targeting ferroptosis could ameliorate bone loss in osteoporotic mice by protecting cells against lipid peroxidation. Shortly, we hope that more effective and appropriate clinical therapy means will be utilized in the treatment of osteoporosis.

CO2-responsive based separation membranes are attractive in the field of membrane separation, not only for their ability to modulate the pore size of the membrane in response to CO2 stimulation, but also for their ability to facilitate the removal of contaminants from the membrane surface. However, the introduction of CO2-responsive polymers by simple blending often results in membranes that are not responsive enough to last. In this study, we synthesized a hooked triblock copolymer and used it as an additive to prepare CO2-responsive PVDF membranes. The modified membrane combines the advantages of the PVDF material with the CO2 response of the triblock copolymer. It not only has good CO2 responsiveness, but also removes organic contaminants from the membrane surface well. The water flux of the hybrid membranes is 4 to 11 times higher than that of pure PVDF membranes, indicating that the triblock copolymer also has some porogenic ability. Surprisingly, the static contact angle on the membrane surface increased from 67 degrees to 86 degrees with the increase of the triblock copolymer content in the PVDF membrane. This suggests that modified PVDF membranes have some potential in the field of switchable oil-water separation.

OBJECTIVE:This study investigated the effect of neuromuscular electrical stimulation on the frontal ankle motor control in individuals with chronic ankle instability during drop landing. DESIGN:This was a randomized, controlled, double-blind trial. Thirty-six individuals with chronic ankle instability were randomly assigned to each group. Participants received 6-wk neuromuscular electrical stimulation intervention and sham stimulation in the neuromuscular electrical stimulation and control groups, respectively. Data were collected at week 0 and week 6 . A mixed-effects model and analysis of covariance were employed to investigate the between-group differences in continuous and discrete outcome variables at week 6 , with the outcome variables at week 0 as covariates. RESULTS:Compared to control group, neuromuscular electrical stimulation group exhibited a 2.66° (2.45, 2.86) reduction in frontal ankle inversion angle, a 47.41°/sec (-16.05, -78.77) decrease in peak ankle inversion angular velocity, and a 0.43 Nm/kg (0.18, 0.68) increase in peak ankle eversion moment during drop landing at week 6 . CONCLUSIONS:Applying 6-wk neuromuscular electrical stimulation to the fibularis longus resulted in decreased ankle inversion angle and ankle inversion angular velocity and increased peak ankle eversion moment during drop landing. Consequently, neuromuscular electrical stimulation could be considered an effective modality for individuals with chronic ankle instability to enhance the frontal ankle movement patterns and overall ankle motor control.

The ability of thermoelectric materials to generate electricity in response to local temperature gradients makes them a potentially promising solution for the regulation of cellular functions and reconstruction of tissues. Biocompatibility of implants is a crucial attribute for the successful integration of thermoelectric techniques in biomedical applications. This work focuses on the in vitro and in vivo evaluation of biocompatibility for 12 typical chalcogenide thermoelectrics, which are composed of biocompatible elements. Ag2Se, SnSe, Bi2Se3, Bi2Te2.88Se0.12 and Bi2Te3, each with a released ion concentration lower than 10 ppm in extracts, exhibited favorable biocompatibility, including cell viability, adhesion, and hemocompatibility, as observed in initial in vitro assessments. Moreover, in vivo biocompatibility assessment, achieved by hematological and histopathological analyses in the rat subcutaneous model, further substantiated the biocompatibility of Ag2Se, Bi2Se3, and Bi2Te3, with each possessing superior thermoelectric performance at room temperature. This work offers robust evidence to promote Ag2Se, Bi2Se3, and Bi2Te3 as potential thermoelectric biomaterials, establishing a foundation for their future applications in biomedicine.