Artemisinic acid attenuates osteoclast formation and titanium particle-induced osteolysis via inhibition of RANKL-induced ROS accumulation and MAPK and NF-κB signaling pathways.

Periprosthetic osteolysis (PPO) is the most common cause of joint arthroplasty failure. Its progression involves both biological and mechanical factors. Osteoclastogenesis induced by wear from debris-cell interactions, ultimately leading to excessive bone erosion, is considered the primary cause of PPO; therefore, targeting osteoclasts is a promising treatment approach. Currently available drugs have various side effects and limitations. Artemisinic acid (ArA) is a sesquiterpene isolated from the traditional herb Artemisia annua L. that has various pharmacological effects, such as antimalarial, anti-inflammatory, and antioxidant activities. Therefore, this study was aimed at investigating the effect of ArA on osteoclast formation and bone resorption function in vitro, as well as wear particle-induced osteolysis in vivo, and to explore its molecular mechanism of action. Here, we report that ArA inhibits RANKL-stimulated osteoclast formation and function. Mechanistically, ArA suppresses intracellular reactive oxygen species levels by activating the antioxidant response via nuclear factor erythroid-2-related factor 2 (Nrf2) pathway upregulation. It also inhibits the mitogen-activated kinases (MAPK) and nuclear factor-κB (NF-κB) pathways, as well as the transcription and expression of NFATc1 and c-Fos. In vivo experiments demonstrated that ArA reduces osteoclast formation and alleviates titanium particle-induced calvarial osteolysis. Collectively, our study highlights that ArA, with its osteoprotective and antioxidant effects, is a promising therapeutic agent for preventing and treating PPO and other osteoclast-mediated osteolytic diseases.

A New Method to Predict Postoperative Stem Anteversion in Total Hip Arthroplasty for Developmental Dysplasia of the Hip.

BACKGROUND: Preoperative evaluation of femoral anteversion to predict postoperative stem anteversion aids the selection of an appropriate prosthesis and optimizes the combined anteversion in total hip arthroplasty (THA) for developmental dysplasia of the hip (DDH). The conventional prediction methods are based on the femoral anteversion measurement at the location of the femoral head and/or neck. However, varied differences between femoral anteversion and postoperative stem anteversion were demonstrated. This study investigated the predictive role of a new method based on the principle of sagittal three-point fixation. METHODS: From January 2017 to December 2018, a total of 133 DDH hips that underwent THA were retrospectively analyzed. There were 76 Crowe type I, 27 type II, and 30 type III hips. The single-wedge stem was used in 49 hips, and the double-wedge stem was used in 84 hips. Preoperative native femoral anteversion at the femoral head-neck junction, anterior cortex anteversion at 2 levels of the lesser trochanter, posterior cortex anteversion at 5 levels of the femoral neck, and postoperative stem anteversion were measured using two-dimensional computed tomography. Predictive anteversion by the new method was calculated as the average anteversion formed by the anterior cortex at the lesser trochanter and the posterior cortex at the femoral neck. RESULTS: For hips with different neck heights, different Crowe types, different stem types, or different femoral anteversions, native femoral anteversion showed widely varied differences and correlations with stem anteversion, with differences ranging from -1.27 ± 8.33° to -13.67 ± 9.47° and correlations ranging from 0.122 (p = 0.705, no correlation) to 0.813. Predictive anteversion formed by the anterior cortex at the lesser trochanter proximal base and posterior cortex 10 mm above the lesser trochanter proximal base showed no significant difference with stem anteversion, with less varied differences (0.92 ± 7.52°) and good to excellent correlations (r = 0.826). CONCLUSION: Adopting our new method, predictive anteversion, measured as the average anteversion of the anterior cortex at the lesser trochanter proximal base and posterior cortex 10 mm above the lesser trochanter proximal base, predicted postoperative stem anteversion more reliably than native femoral anteversion.

Free vascularized fibula leads to hallux toe flexion deformity due to ischemic muscle contracture of flexor hallucis longus.

BACKGROUND: This study aimed to investigate the incidence of toe flexion deformity after fibular free flap transplantation and to analyze the etiology of the deformity. METHODS: Fifty patients underwent vascularized fibular free flap transplantation were retrospectively included. Statistical analysis examined correlations between deformity occurrence and resected fibula length and residual distal fibula length using the χ2 test. Doppler ultrasound and anatomical evaluations were conducted. RESULTS: Flexion deformity of the first toe was observed in all patients (100%), exacerbated by ankle dorsiflexion. χ2 test revealed no significant correlation between fibula length, distal residual fibula length, and flexion deformity. Doppler ultrasound revealed elevated echoes and blurred textures in the flexor hallucis longus post-fibular transplantation, while anatomical evaluation confirmed the peroneal artery as its primary nutrient supplier. CONCLUSION: This study reports a 100% incidence of toe flexion deformity post-transplantation. The deformity correlated strongly with ischemic contracture of the flexor hallucis longus.

TiO2 nanotube topography enhances osteogenesis through filamentous actin and XB130-protein-mediated mechanotransduction.

TiO2 nanotube topography, as nanomechanical stimulation, can significantly promote osteogenesis and improve the osteointegration on the interface of implants and bone tissue. However, the underlying mechanism has not been fully elucidated. XB130 is a member of the actin filament-associated protein family and is involved in the regulation of cytoskeleton and tyrosine kinase-mediated signalling as an adaptor protein. Whether XB130 is involved in TiO2 nanotubes-induced osteogenic differentiation and how it functions in mechano-biochemical signalling transduction remain to be elucidated. In this study, the role of XB130 on TiO2 nanotube-induced osteogenesis and mechanotransduction was systematically investigated. TiO2 nanotube topography was fabricated via anodic oxidation and characterized. The osteogenic effect was significantly accelerated by the TiO2 nanotube surface in vitro and vivo. XB130 was significantly upregulated during this process. Moreover, XB130 overexpression significantly promoted osteogenic differentiation, whereas its knockdown inhibited it. Filamentous actin depolymerization could change the expression and distribution of XB130, thus affecting osteogenic differentiation. Mechanistically, XB130 could interact with Src and result in the activation of the downstream PI3K/Akt/GSK-3ß/ß-catenin pathway, which accounts for the regulation of osteogenesis. This study for the first time showed that the enhanced osteogenic effect of TiO2 nanotubes could be partly due to the filamentous actin and XB130 mediated mechano-biochemical signalling transduction, which might provide a reference for guiding the design and modification of prostheses to promote bone regeneration and osseointegration. STATEMENT OF SIGNIFICANCE: TiO2 nanotubes topography can regulate cytoskeletal rearrangement and thus promote osteogenic differentiation of BMSCs. However, how filamentous actin converts mechanical stimulus into biochemical activity remains unclear. XB130 is a member of actin filament-associated protein family and involves in the regulation of tyrosine kinase-mediated signalling. Therefore, we hypothesised that XB130 might bridge the mechano-biochemical signalling transduction during TiO2 nanotubes-induced osteogenic differentiation. For the first time, this study shows that TiO2 nanotubes enhance osteogenesis through filamentous actin and XB130 mediated mechanotransduction, which provides new theoretical basis for guiding the design and modification of prostheses to promote bone regeneration and osseointegration.

Mechanical overloading leads to chondrocyte degeneration and senescence via Zmpste24-mediated nuclear membrane instability.

Patients with OA and varus knees are subject to abnormal mechanical environment and objective of this study was to investigate the molecular mechanisms underlying chondrocyte senescence caused by mechanical overloading and the role of Zmpste24-mediated nuclear membrane instability in varus knees. Finite element analysis showed that anteromedial region of tibial plateau experienced the most mechanical stress in an osteoarthritis patient with a varus knee. Immunohistochemistry exhibited lower Zmpste24 expression and higher expression of senescence marker p21 in the anteromedial region. Animal experiments and cell-stretch models also demonstrated an inverse relationship between Zmpste24 and mechanically induced senescence. Zmpste24 overexpression rescued cartilage degeneration and senescence in vitro by scavenging ROS. In conclusion, anteromedial tibial plateau is exposed to abnormal stress in varus knees, downregulation of Zmpste24, and nuclear membrane stability may explain increased senescence in this region. Zmpste24 and nuclear membrane stability are potential targets for treating osteoarthritis caused by abnormal alignment.

Aspirin prevents estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis and promoting osteogenesis.

BACKGROUND: Aspirin is a commonly used antipyretic, analgesic, and anti-inflammatory drug. Numerous researches have demonstrated that aspirin exerts multiple biological effects on bone metabolism. However, its spatiotemporal roles remain controversial according to the specific therapeutic doses used for different clinical conditions, and the detailed mechanisms have not been fully elucidated. Hence, in the present study, we aimed to identify the dual effects of different aspirin dosages on osteoclastic activity and osteoblastic bone formation in vitro and in vivo. METHODS: The effects of varying doses of aspirin on osteoclast and osteoblast differentiation were evaluated in vitro. The underlying molecular mechanisms were detected using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence techniques. An ovariectomized rat osteoporosis model was used to assess the bone-protective effects of aspirin in vivo. RESULTS: Aspirin dose-dependently suppressed RANKL-induced osteoclasts differentiation and bone resorption in vitro and reduced the expression of osteoclastic marker genes, including TRAP, cathepsin K, and CTR. Further molecular analysis revealed that aspirin impaired the RANKL-induced NF-κB and MAPK signaling pathways and prevented the nuclear translocation of the NF-κB p65 subunit. Low-dose aspirin promoted osteogenic differentiation, whereas these effects were attenuated when high-dose aspirin was administered. Both low and high doses of aspirin prevented bone loss in an ovariectomized rat osteoporosis model in vivo. CONCLUSION: Aspirin inhibits RANKL-induced osteoclastogenesis and promotes osteogenesis in a dual regulatory manner, thus preventing bone loss in vivo. These data indicate that aspirin has potential applications in the prevention and treatment of osteopenia.

CCL3 in the bone marrow microenvironment causes bone loss and bone marrow adiposity in aged mice.

The central physiological role of the bone marrow renders bone marrow stromal cells (BMSCs) particularly sensitive to aging. With bone aging, BMSCs acquire a differentiation potential bias in favor of adipogenesis over osteogenesis, and the underlying molecular mechanisms remain unclear. Herein, we investigated the factors underlying age-related changes in the bone marrow and their roles in BMSCs' differentiation. Antibody array revealed that CC chemokine ligand 3 (CCL3) accumulation occurred in the serum of naturally aged mice along with bone aging phenotypes, including bone loss, bone marrow adiposity, and imbalanced BMSC differentiation. In vivo Ccl3 deletion could rescue these phenotypes in aged mice. CCL3 improved the adipogenic differentiation potential of BMSCs, with a positive feedback loop between CCL3 and C/EBPα. CCL3 activated C/EBPα expression via STAT3, while C/EBPα activated CCL3 expression through direct promoter binding, facilitated by DNA hypomethylation. Moreover, CCL3 inhibited BMSCs' osteogenic differentiation potential by blocking ß-catenin activity mediated by ERK-activated Dickkopf-related protein 1 upregulation. Blocking CCL3 in vivo via neutralizing antibodies ameliorated trabecular bone loss and bone marrow adiposity in aged mice. This study provides insights regarding age-related bone loss and bone marrow adiposity pathogenesis and lays a foundation for the identification of new targets for senile osteoporosis treatment.

Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis.

BACKGROUND: The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation. METHODS: In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon. RESULTS: Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model. CONCLUSIONS: Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.

Use of a Gigli Saw as a Substitute Osteotomy Tool When Oscillating Saw Malfunctions Occur During Hip Arthroplasty.

OBJECTIVE: The oscillating saw has some inherent disadvantages, such as notch formation and blood splash. The objective is to introduce the Gigli saw as a substitute osteotomy tool when oscillating saw malfunctions occur during surgery. METHODS: During our retrospective study, 120 patients (120 hips) who underwent primary total hip arthroplasty (THA) because of femoral neck fracture, femoral head necrosis, developmental hip dysplasia (Crowe I), or primary osteoarthritis between October 2017 and April 2020 at our institute were included. Sixty patients (26 men and 34 women) with a mean age of 67.3 years (±15.1 years) underwent femoral neck osteotomy using a Gigli saw. The other 60 patients (32 men and 28 women) with a mean age of 64.4 years (±18.8 years) underwent femoral neck osteotomy using an oscillating saw. Intraoperative evaluations, including osteotomy time, osteotomy height, number of notch formations, and blood splash generation, were performed. Routine anteroposterior views of the pelvis and proximal femur were obtained for all patients after surgery. RESULTS: The mean osteotomy times were 26.60 ± 14.80 s and 31.80 ± 14.20 s with the oscillating saw and Gigli saw, respectively (t = 1.964, P = 0.0519). The mean osteotomy heights were 1.26 ± 0.22 cm and 1.20 ± 0.14 cm with the oscillating saw and Gigli saw, respectively (t = 1.782, P = 0.0773). The use of a Gigli saw did not result in bone notch formation or blood splash generation when multiple blood splashes were generated in the oscillating saw group. Postoperative radiographs showed no prostheses malposition in the Gigli saw and oscillating saw groups. CONCLUSION: The Gigli saw has various advantages and can be a substitute tool for femoral neck osteotomy during THA when oscillating saw malfunctions occur.

Analysis of related factors of long-term complications after vascularized fibular transplantation.

OBJECTIVES: Free fibula flap is the first choice for jaw reconstruction in head and neck oncology, but postoperative complications in donor site are ignored always. The main purpose of this study was to investigate the long-term complications and potential risk factors of donor site after vascularized fibular transplantation, and to explore the precautions of preparing vascularized fibular flap and the measures of preventing donor site complications. MATERIALS AND METHODS: Data were retrospectively collected on 31 patients who had undergone immediate mandibular reconstruction with a fibular flap after segmental mandibulectomy from 2013 to 2018 in Shanghai Ninth People's Hospital. Thirty-one patients (24 male, 7 female) were available for the long-term complications in donor site analysis from 25 to 96 months after surgery. The data were collected and analyzed, including age at time of operation, early postoperative complications, incidence of dorsiflexion weakness of hallux, donor site missing fibula length, proximal and distal stump fibula length, and subjective evaluation of foot function (AOFAS-hallux, AOFAS-ankle hindfoot, Enneking lower limb function score). In the single-factor analysis in this study, the correlation between related factors and long-term complications was statistically analyzed. For inter-group comparisons of quantitative data, if the normal distribution was satisfied, two independent sample t-tests were used; p < 0.05 was statistical significant. If the normal distribution was not satisfied, Wilcoxon rank-sum test was used, and p < 0.05 was considered statistically significant. For qualitative data, the Fisher exact probability method was compared between group differences, and p < 0.05 was statistically significant. RESULTS: The most commonly encountered complication in our series was dorsiflexion disorder, flexion deformity, numbness of the lateral side of the lower leg, and dorsum of the foot. Ten patients (32.26%) developed hallux flexion deformity after operation, 17 patients (54.84%) had hallux dorsiflexion dysfunction after operation, and 10 patients (32.26%) had numbness of the lateral side of the lower leg and dorsum of the foot. The incidence of hallux dorsiflexion dysfunction, thumb flexion deformity, and sensory disturbance was higher than that of other long-term complications in the donor area. The residual length of fibular distal was related to the dorsiflexion dysfunction and flexion deformity of hallux (p < 0.05). The early complications of donor site were correlated with the hallux dorsiflexion dysfunction (p < 0.05). CONCLUSIONS: The incidence of dorsiflexion disorder and flexion deformity is higher in patients after fibula transplantation. The less the residual length of fibular distal, the more obvious the long-term complications in the donor site, and the higher the incidence of dorsiflexion dysfunction and flexion deformity of hallux. CLINICAL RELEVANCE: The long-term complications of donor site after fibular transplantation seriously affect the quality of life of patients and provide clinical reference for further reducing the occurrence of donor site complications.

Fusion of multimodality image and point cloud for spatial surface registration for knee arthroplasty.

BACKGROUND: Image-guided computer-aided navigation system is an indispensable part of computer assisted orthopaedic surgery. However, the location and number of fiducial markers, the time required to localise fiducial markers in existing systems affect their effectiveness. METHOD: The study proposed that spatial surface registration between the point cloud on the surface of the fusion model based on preoperative knee MRI and CT images and the point cloud on the cartilage surface captured by intraoperative laser scanner could solve the above limitations. RESULTS: The experimental results show that the registration error of the method is less than 2 mm, but the total time from scanning the point cloud on patient's cartilage surface to registering it with the point cloud in preoperative image space is less than 2 min. CONCLUSION: The method achieves the registration accuracy similar to existing methods without selecting anatomical corresponding points, which is of great help to the clinic.

Application of a novel osteotomy instrumentation as a substitute tool in total hip arthroplasty.

BACKGROUND: Mechanical failure, power shortage, and inadvertent contamination of the oscillating saw occasionally occurs in actualizing femoral neck osteotomy during total hip arthroplasty (THA); however, no appropriate alternative solution is currently available. This study aimed to introduce a novel osteotomy instrumentation (fretsaw, jig, cable passer hook) as a substitute tool while the oscillating saw was unavailable during THA. METHODS: This study included 40 patients (40 hips) who underwent femoral neck osteotomy during primary THA using the new osteotomy instrumentation (n = 20) and the oscillating saw (n = 20). Clinical data and intraoperative findings of all patients were evaluated. RESULTS: The mean osteotomy time was 22.3 ± 3.1 s (range, 17-30 s) and 29.4 ± 3.7 s (range, 25-39 s) in the oscillating saw group and in the new osteotomy instrumentation group, respectively (P < 0.001). The Harris Hip Score (HHS) improved in both groups; the mean HSS was 82.3 ± 2.5 and 83.3 ± 3.5 in the oscillating saw group and new osteotomy instrumentation group at 6 months after surgery, respectively (P = 0.297). CONCLUSIONS: The original osteotomy instrumentation can be an ideal substitute tool for femoral neck osteotomy in THA, especially when the oscillating saw is unavailable or malfunctioning.

TiO2 Nanotubes Promote Osteogenic Differentiation Through Regulation of Yap and Piezo1.

Surface modification of titanium has been a hot topic to promote bone integration between implants and bone tissue. Titanium dioxide nanotubes fabricated on the surface of titanium by anodic oxidation have been a mature scheme that has shown to promote osteogenesis in vitro. However, mechanisms behind such a phenomenon remain elusive. In this study, we verified the enhanced osteogenesis of BMSCs on nanotopographic titanium in vitro and proved its effect in vivo by constructing a bone defect model in rats. In addition, the role of the mechanosensitive molecule Yap is studied in this research by the application of the Yap inhibitor verteporfin and knockdown/overexpression of Yap in MC3T3-E1 cells. Piezo1 is a mechanosensitive ion channel discovered in recent years and found to be elemental in bone metabolism. In our study, we preliminarily figured out the regulatory relationship between Yap and Piezo1 and proved Piezo1 as a downstream effector of Yap and nanotube-stimulated osteogenesis. In conclusion, this research proved that nanotopography promoted osteogenesis by increasing nuclear localization of Yap and activating the expression of Piezo1 downstream.

DNA-Based Daisy Chain Rotaxane Nanocomposite Hydrogels as Dual-Programmable Dynamic Scaffolds for Stem Cell Adhesion.

Interlocked DNA nanostructures perform programmable movements in nanoscales such as sliding, contraction, and expansion. However, utilizing nanoscaled interlocked movements to regulate the functions of larger length scaled matrix and developing their applications has not yet been reported. Herein we describe the assembly of DNA-based daisy chain rotaxane nanostructure (DNA-DCR) composed of two hollow DNA nanostructures as macrocycles, two interlocked axles and two triangular prism-shaped DNA structures as stoppers, in which three mechanical states─fixed extended state (FES), sliding state (SS), and fixed contracted state (FCS)─are characterized by using toehold-mediated strand displacement reaction (SDR). The DNA-DCRs are further used as nanocomposites and introduced into hydrogel matrix to produce interlocked hydrogels, which shows modulable stiffness by elongating the interlocked axles to regulate the hydrogel swelling with hybridization chain reaction (HCR) treatment. Then the DCR-hydrogels are employed as dynamic biointerfaces for human mesenchymal stem cells (hMSCs) adhesion studies. First, hMSCs showed lower cell density on bare DCR-hydrogel treated with HCR-initiated swelling for stiffness decreasing. Second, the cell adhesion ligand (RGD) modified DNA-DCRs are constructed for hydrogel functionalization. DCR(RGD) hydrogel endows the mobility of RGDs by switching the mechanical states of DNA-DCR. HMSCs showed increased cell density on DCRSS(RGD) hydrogel than on DCRFCS(RGD) hydrogel. Therefore, our DNA-DCR nanocomposite hydrogel exhibit dual-programmable performances including swelling adjustment and offering sliding for incorporated ligands, which can be both utilized as dynamic scaffolds for regulating the stem cell adhesion. The dual-programmable cross-scale regulation from interlocked DNA nanostructures to hydrogel matrix was achieved, demonstrating a new pathway of DNA-based materials.

Favorable osteogenic activity of iron doped in silicocarnotite bioceramic: In vitro and in vivo Studies.

BACKGROUND: Calcium phosphate silicate (Ca5(PO4)2SiO4 or CPS) is a promising bioceramic for bone grafting. Iron (Fe) is a trace element in the human body that has been reported to enhance the mechanical strength of CPS ceramics. However, the exact biofunctions of Fe, combined with another human trace element, viz. silicon (Si), in CPS and the optimal dose for Fe addition must be further investigated. METHODS: In vitro: the morphology, structure and cell adhesion were observed by SEM; the ability to promote osteogenic differentiation and mineralization was explored by ALP and alizarin red staining; the expression of osteogenic-specific genes and proteins was detected by PCR, WB and immunofluorescence. In vivo: Further exploration of bone regeneration capacity by establishing a skull defect model. RESULTS: In vitro, we observed increased content of adhesion-related proteins and osteogenic-related genes expression of Fe-CPS compared with CPS, as demonstrated by immunofluorescence and polymerase chain reaction experiments, respectively. In vivo micro-computed tomography images, histomorphology, and undecalcified bone slicing also showed improved osteogenic ability of Fe-CPS bioceramics. CONCLUSION: With the addition of Fe2O3, the new bone formation rate of the Fe-CPS scaffold after 12 weeks increased from 9.42% to 43.76%. Moreover, both in vitro and in vivo experimental outcomes indicated that Fe addition improved the CPS bioceramics in terms of their osteogenic ability by promoting the expression of osteogenic-related genes. Fe-CPS bioceramics can be employed as a novel material for bone tissue engineering on account of their outstanding new bone formation ability. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study suggests that Fe-CPS bioceramics can be employed as a novel material for bone tissue engineering on account of their outstanding new bone formation ability,which provides promising therapeutic implants and strategies for the treatment of large segmental bone defects.

Curcumin primed ADMSCs derived small extracellular vesicle exert enhanced protective effects on osteoarthritis by inhibiting oxidative stress and chondrocyte apoptosis.

Osteoarthritis (OA) is a common joint disease caused by progressive articular cartilage degeneration and destruction. Currently, there are no disease-modifying agents officially approved for OA patients. In this study, curcumin was loaded into adipose tissue-derived mesenchymal stem cells (ADMSCs)-derived small extracellular vesicle (ADMSCs-sEV) to synergistically exert chondro-protective effects in vitro and in vivo. We found curcumin primed ADMSCs derived sEV (sEV-CUR) exhibited an enhanced protective effect compared with free curcumin and ADMSCs-sEV in TBHP-induced chondrocytes. Moreover, our study demonstrated sEV-CUR more effectively down-regulated TBHP-induced oxidative stress and chondrocyte apoptosis in vitro. In OA mice model, our results indicated that sEV-CUR showed an improved cartilage protection, as biweekly intra-articular injection of sEV-CUR more efficaciously alleviated oxidative stress and chondrocyte apoptosis in OA cartilage. Overall, our findings showed sEV-CUR exhibited enhanced chondro-protective effects and holds great potential on the recovery of articular cartilage loss and destruction in OA patients.

Positive Correlation Between the Femur Neck Shaft and Anteversion Angles: A Retrospective Computed Tomography Analysis in Patients With Developmental Dysplasia of the Hip.

BACKGROUND: This study aimed to explore the anatomical correlation between the femoral neck shaft angle (NSA) and femoral anteversion angle (AA) in patients with developmental dysplasia of the hip based on the Crowe classification and provide a novel method to estimate the femoral AA on anteroposterior pelvic radiographs. METHODS: A total of 208 patients with dysplastic hips who underwent total hip arthroplasty at our institution were retrospectively included. Preoperative physiological AA and NSA were determined via 3-dimensional computed tomography. Linear regressions and Pearson's coefficients were calculated to assess the correlation between the femoral NSA and femoral AA. RESULTS: A total of 416 hips were divided into 5 subgroups: 99 normal, 143 type I, 71 type II, 63 type III, and 40 type IV hips following the Crowe classification. Dysplastic femurs had significantly higher AAs than normal hips (25.2° vs 31.4° vs 33.3° vs 35.5° vs 41.7°). Significant positive correlations between the AA and NSA were observed in normal (r = 0.635), type I (r = 0.700), type II (r = 0.612), and type III (r = 0.638) hips (P < .001); however, no meaningful correlation was observed in type IV hips (r = 0.218, P = .176). CONCLUSION: The NSA and AA correlated positively and significantly in the normal and dysplastic Crowe type I-III hips. The relationship between the NSA and AA indicates torsion of the proximal femur and offers an opportunity for straightforward estimation of AA based on NSA.

A novel efficient and precise technique for removing acetabular osteophytes in patients undergoing total hip arthroplasty: the SH-9Hospital acetabular edge file.

BACKGROUND: Total hip arthroplasty (THA) is frequently performed in patients with end-stage hip disease. Periacetabular osteophytes are common during THA; however, these osteophytes should be removed intraoperatively to avoid potential impingement between osteophytes and femoral prostheses and decrease dislocation risk. There are no current standard procedures or surgical technique criteria to remove these osteophytes. Osteophytes around the acetabulum are usually removed with an osteotome, yet this presents certain disadvantages. Hence, this study aimed to introduce a novel and more efficient technique than the aforementioned one, the SH-9Hospital acetabular edge file. METHODS: Fifty-four patients (54 hips) who underwent primary THA using osteotome and the SH-9Hospital acetabular edge file to remove periacetabular osteophytes intraoperatively were retrospectively studied. Clinical and radiographic data were obtained for all patients intra- and postoperatively. RESULTS: The mean osteophyte removal time was 274.6±102.7 s and 51.3±21.1 s in the osteotome and SH-9Hospital acetabular edge file groups, respectively. Intraoperative images and postoperative radiographs showed that acetabular osteophytes were removed thoroughly and precisely by the acetabular edge file and that there was no iatrogenic injury and prostheses malposition in both groups. CONCLUSIONS: The SH-9Hospital acetabular edge file was a novel, efficient, highly precise, and repeatable method for removing periacetabular osteophytes in patients undergoing total hip arthroplasty.

The effect of enhanced bone marrow in conjunction with 3D-printed PLA-HA in the repair of critical-sized bone defects in a rabbit model.

BACKGROUND: Traditionally, the iliac crest has been the most common harvesting site for autologous bone grafts; however, it has some limitations, including poor bone availability and donor-site morbidity. This study sought to explore the effect of enhanced bone marrow (eBM) in conjunction with three-dimensional (3D)-printed polylactide-hydroxyapatite (PLA-HA) scaffolds in the repair of critical-sized bone defects in a rabbit model. METHODS: First, 3D-printed PLA-HA scaffolds were fabricated and evaluated using micro-computed tomography (µCT) and scanning electron microscopy (SEM). Twenty-seven New Zealand white rabbits were randomly divided into 3 groups (n=9 per group), and the defects were treated using 3D-printed PLA-HA scaffolds (the PLA-HA group) or eBM in conjunction with 3D-printed PLA-HA scaffolds (the PLA-HA/eBM group), or were left untreated (the control group). Radiographic, µCT, and histological analyses were performed to evaluate bone regeneration in the different groups. RESULTS: The 3D-printed PLA-HA scaffolds were cylindrical, and had a mean pore size of 500±47.1 µm and 60%±3.5% porosity. At 4 and 8 weeks, the lane-sandhu X-ray score in the PLA-HA/eBM group was significantly higher than that in the PLA-HA group and the control group (P<0.01). At 8 weeks, the µCT analysis showed that the bone volume (BV) and bone volume/tissue volume (BV/TV) in the PLA-HA/eBM group were significantly higher than those in the PLA-HA group and the control group (P<0.01). Hematoxylin and eosin staining indicated that the new bone area in the PLA-HA/eBM group was significantly higher than that in the PLA-HA group and the control group (P<0.01). CONCLUSIONS: The group that was treated with eBM in conjunction with 3D-printed PLA-HA showed enhanced bone repair compared to the other 2 groups. PLA-HA/eBM scaffolds represent a promising way to treat critical-sized bone defects.