This cross-sectional study aimed to investigate the association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and osteoporosis (OP) among US women. An analysis was conducted using data from 6149 women participating in the National Health and Nutrition Examination Survey (NHANES). Weighted multivariable logistic regression and restricted cubic spline models were applied to evaluate the relationship between NHHR and OP, with adjustments for sociodemographic, clinical, and metabolic covariates. After full adjustment, a significant U-shaped relationship was identified between NHHR and osteoporosis prevalence, with an inflection point at NHHR = 3.371. Below this threshold, each unit increase in NHHR was associated with a 29% reduction in OP risk (odds ratio = 0.71, 95% confidence intervals: 0.60-0.84, P < .001). No significant association was observed above this value. Inverse associations were particularly notable in women aged ≥65 years, non-Hispanic Whites, former smokers, and those with higher education or lower physical activity levels. Non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio demonstrates a nonlinear, threshold-dependent association with osteoporosis risk, supporting its potential role as a novel biomarker for OP in specific subpopulations. Further prospective studies are warranted to clarify causal mechanisms.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

The causal relationship between some lifestyles and rotator cuff injury is unclear. This study aims to elucidate the genetic causality between smoking initiation, alcohol intake frequency, and coffee consumption in relation to rotator cuff injury. We conducted a 2-sample Mendelian randomization (MR) analysis utilizing summary-level data from extensive genome-wide association studies. Single nucleotide polymorphisms achieving genome-wide significance ( P < 5 * 10 ‐8 ) were employed as instrumental variables for each exposure. The inverse variance weighted method served as the principal statistical technique, complemented by the weighted median, MR-Egger regression, and MR-PRESSO methods for sensitivity analyses, accommodating some of the assumptions inherent in IVs. The initiation of smoking was found to have a genetically predictive inverse association with rotator cuff injury incidence. The inverse variance weighted approach indicated a pooled odds ratio for rotator cuff injury of 0.70 (95% confidence interval 0.58–0.85; P = 3 * 10 ‐4 ) per standard deviation increase in smoking initiation rates. Similarly, coffee consumption demonstrated a negative genetic causality with rotator cuff injury, evidenced by an odds ratio of 0.46 (95% confidence interval 0.29–0.72; P = 8 * 10 ‐4 ). Conversely, alcohol consumption did not show a statistically significant causal relationship with rotator cuff injury incidence. The findings suggest a genetic predisposition that links smoking initiation and coffee consumption with a decreased risk of rotator cuff injury. Conversely, the genetic evidence to assert a causal relationship between alcohol intake and rotator cuff injury was found to be inconclusive.

Aseptic loosening resulting from periprosthetic osteolysis is still a common and serious complication of total joint arthroplasty, which represents the major cause of implant failure and revision surgery. Herein, a tantalum (Ta)/ polyetheretherketone (PEEK) composite (TPK) was fabricated and berbamine was grafted on the TPK surface for enhancing osseointegration and preventing periprosthetic osteolysis. The surface properties (e.g., roughness, hydrophilicity) and mechanical properties (e.g., compressive strength, modulus of elasticity) of TPKB are remarkably improved owing to incorporation of tantalum into PEEK, whereas grafting of berbamine displays no obvious change. TPKB remarkably facilitated osteoblasts differentiation of mouse bone mesenchymal stem cells (BMSCs) in vitro and boosted osseointegration in vivo owing to the presence of tantalum, whereas berbamine exhibited no obvious influences. Moreover, TPKB obviously prevented osteoclast differentiation of mouse bone marrow-derived mononuclear macrophages (BMDMs) in vitro and significantly maintained osseointegration in vivo, even with polyethylene debris, and thereby effective alleviating debris-induced periprosthetic osteolysis owing to the sustained release of berbamine. Collectively, berbamine grafted on TPKB played the critical role in treatment of osteoclast-related periprosthetic osteolysis. This study provides a promising strategy to develop an implant that could address the problem of aseptic loosening in dual directions of enhancing osseointegration and treat debris-induced periprosthetic osteolysis.

This study presents a pioneering approach utilizing hierarchically functionalized scaffolds to foster anisotropic osteochondral tissue regeneration, leveraging the integration of distinct yet interconnected layers. We developed 3D-printed polydopamine-modified polycaprolactone scaffolds, subsequently covered with a layer of electrospun polycaprolactone-gelatin fibers, and then functionalized with gelatin-bone morphogenetic protein-2 (BMP-2) following oxygen plasma surface treatments, creating a hierarchically organized multi-phasic architecture. This interconnected porous microstructure enabled controllable degradation while maintaining mechanical integrity and hydroxyapatite mineralization. In-vitro assessments showed superior support for rat bone marrow mesenchymal stem cells, enhancing adhesion, viability, and proliferation. Increased alkaline phosphatase activity and osteocalcin expression over 14 days indicated enhanced osteogenic performance, likely due to BMP-2 interaction with serum proteins, as supported by simulation studies, augmenting growth factor bioavailability. In-vivo investigations in rabbit critical-sized osteochondral defects at 4- and 12-weeks post-implantation demonstrated that the multi-phasic scaffolds notably promoted collagen types I and II secretion, neo-tissue formation, and integration with surrounding tissue, with significant results observed at 12 weeks, highlighting promising potential for osteochondral tissue engineering.

ObjectiveTo compare the clinical efficacy of the femoral neck system (FNS) alone versus FNS combined with an additional cannulated compression screw (CCS) for treating elderly patients (aged 65–75) with Garden I–III femoral neck fractures.MethodsThis retrospective study analyzed 126 patients treated between January 2020 and December 2022. Patients were divided into an FNS group (n = 60) and an FNS+CCS group (n = 66). Key outcomes included operative time, intraoperative blood loss, fluoroscopy frequency, fracture healing time, femoral neck shortening, complications, VAS pain scores, and Harris hip scores at final follow-up.ResultsThe two groups showed no significant differences in baseline characteristics. While intraoperative blood loss was comparable, the FNS+CCS group had significantly longer operative times and required more fluoroscopies. All patients were followed for an average of 14.1 months. The FNS+CCS group demonstrated a significantly shorter fracture healing time and a lower incidence of femoral neck shortening at final follow-up. Although VAS scores were similar between groups, the FNS+CCS group achieved significantly higher Harris hip scores. The incidence of complications did not differ significantly.ConclusionFor elderly patients with femoral neck fractures, FNS fixation augmented with a CCS offers significant advantages over FNS alone, including accelerated fracture healing and superior functional recovery of the hip joint, despite a longer operative time.

A rotator cuff tear (RCT) refers to a partial or complete rupture of the rotator cuff (the tendons of the supraspinatus, infraspinatus, teres minor, and subscapularis muscles). It is commonly caused by degenerative changes or trauma and manifests as shoulder pain, weakness, and limited range of motion.This study aimed to explore the correlation between inferior position of coracoid process and risk factors for rotator cuff injury. (1) Does the inferior position of the coracoid process increase the probability of risk factors leading to RCT? (2) Does a lower positioning of the coracoid process increase the probability of subcoracoid impact? (3) Does a lower positioning of the coracoid process correlate with the shape of the acromion? From May 2018 to Dec 2019, 93 patients (38 males and 55 females) with rotator cuff injuries were analyzed, with an average age of 57.7 ± 6.2 years. All patients received X-ray examination with Anterior-posterior view and supraspinatus outlet view to distinguish acromion morphology before surgery. MRI scan was used to assess the rotator cuff injury. Three-dimensional computerized tomography examination measured the position of coracoid process. The location of rotator cuff injury and the subcoracoacromial arch impingement were evaluated by arthroscopy. Pearson chi-square test was used for statistical analysis of the position of coracoid process. 76.3% (71/93) of the patients had rotator cuff tear (RCT) within 1.5 cm of the biceps tendon groove lateral, and the rates were higher in Type III/IV coracoids. Total 60 cases had subacromial impact, while 28 cases had subcoracoid impacts. Type III/IV coracoids had a higher probability of impact. The prevalence of Type III/IV coracoid processes was 22 (78.6%) in the 28 cases with type III acromion, which was significantly higher than that in cases with Type I/II acromion (P = 0.034). The inferior position of the coracoid process increases the probability of RCT, which may be related to the high incidence of type III acromion in such patients and the reduction of the subcoracoid gap. Level III, therapeutic study.

ObjectiveThis study aims to analyze the biomechanical characteristics of posterolateral plateau fractures fixed by a novel anatomical plate using finite element analysis.MethodsA three-dimensional digital model of the full length of right tibiofibula was obtained by CT scanning. A posterolateral tibial plateau fracture model was then created. The acquired fracture model was assembled with 4 groups of internal fixations: Group A, novel anatomical plate; Group B, straight buttress plate; Group C, oblique T-shaped locking plate; Group D, two lag screws. Axial loads of 500, 1,000 and 1,500 N perpendicular to the horizontal plane were used to simulate the stress on the lateral plateau of a 65 kg person standing, walking and fast running.ResultsVertical displacements of the posterolateral fragments in each of the four groups gradually increased under loads from 500 N to 1,500 N. The maximum displacement of the fracture fragment in four groups were all located on the lateral side of the proximal part, and the displacement gradually decreased from the proximal part to the distal end. The maximum displacement values under the axial load of 1,500 N was in the following order: novel anatomical plate (1.2365 mm) < oblique T-shaped locking plate (1.314 mm) < two lag screws (1.3747 mm) < straight buttress plate (1.3932 mm). As the axial load increased, the stress value of the different internal fixation models gradually increased. The stress behavior of the same internal fixation model under different loads was similar. The maximum stress value under the axial load of 1,500 N was in the following order: novel anatomical plate (114.63 MPa) < oblique T-shaped locking plate (277.17 MPa) < two lag screws (236.75 MPa) < straight buttress plate (136.2 MPa).ConclusionThe patients with posterolateral plateau fractures fixed with a novel anatomical plate in standing, walking and fast running can achieve satisfactory biomechanical results, which lays the foundation for future applications. At the same time, clinical fracture types are often diverse and accompanied by damage to the soft tissue. Therefore, the ideal surgical approach and appropriate internal fixation must be selected based on the patient's injury condition.

Aims In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA -damage -inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods An in vitro model for oxidative stress -induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth -generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel's mechanism in IVDD. Results A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle -punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress -induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD.

Objective:This study aimed to investigate the mechanical stability of a modified pedicle screw fixator and compare it with unilateral lumbopelvic fixation for treating sacroiliac joint disruption using finite element simulation technology. Methods:The digital model of a normal spine-pelvis-femur containing the main pelvic and lumbar ligaments was established based on computed tomography images. A sacroiliac joint disruption model was built and validated, which was stabilized with the models of a modified pedicle screw fixator or unilateral lumbopelvic fixation. A 400 N follower loading was applied to the lumbar vertebrae for the 2 fixation models to analyze displacement and stress distribution. In addition, the construct stiffness was calculated. Results:The peak amounts of sacral vertical displacement, horizontal displacement, posterior displacement, and overall displacement were 0.70 mm, 0.17 mm, 0.73 mm, and 0.88 mm, respectively, in the modified pedicle screw fixator model, which were less than those in the unilateral lumbopelvic fixation model (1.17 mm, 0.31 mm, 2.21 mm, and 2.29 mm, respectively). Compared with unilateral lumbopelvic fixation, the percentage decreases of the modified pedicle screw fixators were 40.2%, 45.2%, 67.0%, and 61.6%, respectively. The peak stress of the internal fixation and pelvis in the modified pedicle screw fixator model was 351.23 MPa and 39.91 MPa, which has 15.5% and 70.4% lower than in the unilateral lumbopelvic fixation model. The construct stiffness of the modified pedicle screw fixator (571 N/ mm) was 67% better than that of unilateral lumbopelvic fixation (342 N/mm). Conclusion:The finite element simulation results showed that the modified pedicle screw fixator model demonstrated smaller sacral displacement, fewer stresses on the internal fixation and bone, and higher construct stiffness compared with the unilateral lumbopelvic fixation model. Thus, the modified pedicle screw fixator may provide biomechanical advantages over unilateral lumbopelvic fixation in the treatment of sacroiliac joint disruption.

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.

Objective: This study aims to analyze the biomechanical characteristics of tile B2 pelvic fractures using finite element analysis when the superior ramus of the pubis was fixed by a plate or hollow screws in standing and sitting positions, respectively. Methods: A three-dimensional digital model of the tile B2 pelvic fracture was obtained by CT scanning the patient. The main ligament structure was then reconstructed based on the anatomical characteristics to create a finite element model of the tile B2 pelvic fracture. The posterior pelvic ring was fixed by sacroiliac joint screws, while the anterior ring injury of the superior ramus of the pubis was fixed by plates and hollow compression screws, respectively. The degrees of freedom of the bilateral acetabulum or two sides of the ischial tuberosity were constrained in the two models. A vertical load of 600 N was applied to the upper surface of the sacrum to measure the displacement and stress distribution of the pelvis in the standing and sitting positions. Results: The displacement distribution of both the healthy and the affected side of the pelvis was relatively uniform in both the plate group and the hollow screw group according to the finite element simulation results. The maximum displacement value in the sitting position was greater than the standing position, and the maximum displacement value of the hollow screw fixation was greater than that of the plate fixation. In the four groups of fixation models, the maximum displacement value of the pelvis in the hollow screw sitting position group was 1616.80 × 10−3 mm, which was greater than that of the other three groups, and in this group the total displacement value of the hollow screw in the anterior ring was 556.31 × 10−3 mm. The stress distribution of the pelvis in the various models was similar in the four groups of models, in which the maximum stress of the pelvis in the hollow screw sitting position group was the largest, which was 201.33 MPa, while the maximum stress in the standing position was 149.85 MPa greater than that in the sitting position of the hollow screw fixation. Conclusion: The anterior ring of patients with Tile B2 pelvic fractures fixed with hollow screws or plates in both standing and sitting positions can achieve satisfactory biomechanical results with significant safety margins for plates and screws.

ObjectiveThe study aimed to present the clinical results and complication rates of ring-pins with cable cerclage for treating the inferior pole of patella fracture.MethodA study that retrospectively reviewed consecutive patients of the displaced inferior pole of patella fracture (AO/OTA 34-A1) operated with a ring-pin tension band using cable cerclage between October 2015 and October 2017 was performed. The duration of surgery, motion range of the knee, function outcomes, and complications were recorded.ResultsThe average follow-up of 31 patients was 21 months. The mean operation time was 50 min. Fractures in all 31 patients healed at a mean duration of 8 weeks. There was no infection, no withdrawing of ring-pins, no implant breakage, and no loss of fracture reduction. The mean range of motion was 120°, and no patient complained of implant irritation at the final follow-up. The average Bostman score was 29.0 points, and 28 patients graded clinical outcomes excellent and 3 patients graded clinical outcomes good at the last follow-up.ConclusionsRing-pin combined with cable cerclage for treating the displaced inferior pole of patellar fracture is simple, and the postoperative internal fixation-related complication rate is low. It is a good choice for treating the displaced inferior pole of the patellar fracture.

Osteoporotic fractures are the most severe complications of osteoporosis, characterized by poor bone quality, difficult realignment and fixation, slow fracture healing, and a high risk of recurrence. Clinically managing these fractures is relatively challenging, and in the context of rapid aging, they pose significant social hazards. The rapid advancement of disciplines such as biophysics and biochemistry brings new opportunities for future medical diagnosis and treatment. However, there has been limited attention to precision diagnosis and treatment strategies for osteoporotic fractures both domestically and internationally. In response to this, the Chinese Medical Association Orthopaedic Branch Youth Osteoporosis Group, Chinese Geriatrics Society Geriatric Orthopaedics Committee, Chinese Medical Doctor Association Orthopaedic Physicians Branch Youth Committee Osteoporosis Group, and Shanghai Association of Integrated Traditional Chinese and Western Medicine Osteoporosis Professional Committee have collaborated to develop this consensus. It aims to elucidate emerging technologies that may play a pivotal role in both diagnosis and treatment, advocating for clinicians to embrace interdisciplinary approaches and incorporate these new technologies into their practice. Ultimately, the goal is to improve the prognosis and quality of life for elderly patients with osteoporotic fractures.

新形势、新环境下,创伤骨科医师面临伤情更加复杂、人口老龄化加剧的严峻挑战.随着数据处理能力的飞速发展、医工交叉的深入,人工智能的应用正逐步延伸至医学各相关领域,同样也是未来创伤骨科的发展重要方向,将为创伤骨科面临的问题提出新的解决途径.人工智能将在诊断、处理、教育与研究、系统分析等领域促进创伤骨科的发展.然而,人工智能在创伤骨科的应用离不开数据安全性、稳定性的影响,仍然面临一些问题.本文就人工智能的概念及在创伤骨科中的应用与挑战做一综述,旨在汲取国内外先进的人工智能理念及先进技术,以期提升其在创伤骨科的应用,为患者提供精准化、个性化的诊疗服务.

Early fracture fixation is the critical factor in fracture healing. Common internal fracture implants are made of metallic materials, which often affects the imaging quality of CT and MRI. Most patients will choose secondary surgery to remove the internal fixation implants, which causes secondary damage to them. The development of new degradable internal fracture implants has attracted more and more attention from orthopedic surgeons and researchers. Based on these problems, we improved the various properties of medical grade polycaprolactone (PCL) by adding poly(L-lactide) (PLLA). We produced PCL/PLLA strapping bands with different mass ratios by injection molding. We compared the mechanical properties, degradation properties, cell biocompatibility, bone marrow mesenchymal stem cells (BMSCs) adhesion, proliferation, osteogenic differentiation and fracture fixation effect of these strapping bands. The results showed that the tensile strength and yield force of the strapping bands increased with the increase of the content of PLLA. The addition of PLLA could significantly improve the mechanical strength in the early stage and accelerate the degradation rate of the strapping band. PCL/PLLA (80/20) strapping band had no significant cytotoxicity toward rBMSCs and could promote osteogenic differentiation of rBMSCs. The strapping band could ensure femoral fracture healing of beagles in 3 months and didn’t cause damage to the surrounding tissues and main organs. This study will provide some new insights into the biodegradable products of PCL/PLLA blends for internal fixation of fracture. Graphical Abstract We produced novel degradable PCL/PLLA strapping bands with different mass ratios by injection molding. We tested the biological safety of the prepared internal fixation strapping bands for fracture, such as cell experiment in vitro and animal experiment, and studied the degradation behavior in vitro. The strapping bands could ensure femoral fracture healing of beagles. This study will provide some new insights into the biodegradable products of PCL/PLLA blends for internal fixation of fracture. A Immunofluorescence staining of rBMSCs (live cells: green; dead cells: red). B Young’s modulus change curve during strapping bands degradation. C The implantation process of strapping bands. D Micro-CT images of the beagle’s fracture recovery after the operation.

Abstract Objective The pedicle screw construct and locking compression plate have been clinically investigated for the treatment of posterior pelvic ring injuries. However, few studies are available that evaluate the biomechanical performance of these two pelvic fixation techniques. The aim of this study was to compare the construct stability, model displacement and stress distribution of two implants with a finite element (FE) method. Methods A three-dimensional FE model of spine-pelvis-femur complex with ligaments was reconstructed from computed tomography images. The unstable posterior pelvic ring injury was created, which was fixed with the pedicle screw construct or locking compression plate. A follower load of 400 N was applied to the upper surface of the vertebrae to simulate upper body weight, while the ends of the proximal femurs were fixed. Results The construct stiffness of the pedicle screw model was 2 times that of the plate fixation. The maximum displacement of the pedicle screw model decreased by 51.2% compared with the plate fixation. The peek stresses of the implant and pelvis in the pedicle screw model decreased by 80.4% and 25% when compared with the plate model (44.57 MPa and 34.48 MPa in the pedicle screw model, and 227.47 MPa and 45.97 MPa in the plate model). Conclusions The study suggested that the pedicle screw construct could provide better fixation stability compared with locking compression plate, and serves as the recommended fixation method for the treatment of posterior pelvic ring injuries.

Excess osteoclast activity is found in many bone metabolic diseases, and inhibiting osteoclast differentiation has proven to be an effective strategy. Here, we revealed that osteoclast precursors (pre-OCs) were more susceptible to thioredoxin reductase 1 (TXNRD1) inhibitors than bone marrow-derived monocytes (BMDMs) during receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis. Mechanistically, we found that nuclear factor of activated T-cells 1 (NFATc1) upregulated solute carrier family 7 member 11 (SLC7A11) expression through transcriptional regulation during RANKL-induced osteoclastogenesis. During TXNRD1 inhibition, the rate of intracellular disulfide reduction is significantly reduced. Increased cystine transport leads to increased cystine accumulation, which leads to increased cellular disulfide stress and disulfidptosis. We further demonstrated that SLC7A11 inhibitors and treatments that prevent disulphide accumulation could rescue this type of cell death, but not the ferroptosis inhibitors (DFO, Ferro-1), the ROS scavengers (Trolox, Tempol), the apoptosis inhibitor (Z-VAD), the necroptosis inhibitor (Nec-1), or the autophagy inhibitor (CQ). An in vivo study indicated that TXNRD1 inhibitors increased bone cystine content, reduced the number of osteoclasts, and alleviated bone loss in an ovariectomized (OVX) mouse model. Together, our findings demonstrate that NFATc1-mediated upregulation of SLC7A11 induces targetable metabolic sensitivity to TXNRD1 inhibitors during osteoclast differentiation. Moreover, we innovatively suggest that TXNRD1 inhibitors, a classic drug for osteoclast-related diseases, selectively kill pre-OCs by inducing intracellular cystine accumulation and subsequent disulfidptosis.

The fabrication of cell-laden protein-based hydrogels (PBHs) for bioprinting necessitates careful consideration of numerous factors to ensure optimal structure and functionality. Bioprinting techniques, such as single-cell, multi-cell, and cell aggregate bioprinting, are employed to encapsulate cells within PBHs bioink, enabling the creation of scaffolds for cartilage and bone regeneration. During the fabrication process, it is imperative to account for biophysical and biochemical factors that influence cell behavior and protein structure within the PBHs. Precise control of crosslinking methods, hydrogel rheological properties, and printing parameters is also crucial to achieve desired scaffold properties without compromising cell viability and protein integrity. This review primarily focuses on the influence of biophysical factors, including composition, microstructure, biodegradation, and crosslinking, as well as biochemical factors, including chemical structure, growth factors, and signaling molecules, on protein structure and cell behavior. Additionally, key considerations for bioprinting PBHs and their impact on the successful regeneration of tissues are discussed. Furthermore, the review highlights current advancements, existing challenges, and promising prospects in the development of cell-laden PBHs for bioprinting applications and the regeneration of bone and cartilage.