Efficacy of Autologous Adult Live-Cultured Osteoblast (AALCO) Implantation in Avascular Necrosis of the Femoral Head: A Mid-Term Outcome Analysis.

Introduction: Avascular Necrosis (AVN) of the femoral head, a condition characterized by the interruption of blood supply leading to bone tissue death, presents significant therapeutic challenges. Recent advancements in orthobiologics, including the use of Autologous Adult Live-Cultured Osteoblasts (AALCO), combined with core decompression, offer a novel approach for managing AVN. This study assesses the efficacy of this treatment modality in improving functional outcomes and hindering disease progression. Materials and methods: This retrospective observational study encompassed 30 patients treated between 2020 and 2023 for idiopathic AVN of the femoral head, grades I to III, who had not responded to conservative treatment. Patients were excluded based on specific criteria including age, secondary AVN causes, and certain health conditions. The treatment involved a two-stage surgical procedure under spinal anesthesia with OSSGROW® for AALCO generation. Post-operative care emphasized early mobilization, DVT prevention, and avoidance of NSAIDs. Outcome measures were evaluated using the Visual Analog Scale (VAS) for pain, modified Harris Hip Score, and annual MRI imaging for up to 36 months. Results: Among 26 patients (41 hips) completing the study, statistically significant improvements in pain and hip functionality were documented, alongside positive radiological signs of osteogenesis in the majority of cases. However, four instances required advancement to total hip replacement due to disease progression. Conclusion: The combination of core decompression and AALCO implantation shows promise as an effective treatment for AVN of the femoral head, with notable improvements in functional and radiological outcomes. This study supports the potential of orthobiologic approaches in AVN treatment, warranting further investigation through comprehensive randomized controlled trials.

Conversion Total Hip Arthroplasty After Failed Pedicled Peri-Hip Bone Flap Grafting: The Chinese Experience.

BACKGROUND: This study investigated the perioperative outcomes of patients undergoing conversion total hip arthroplasty (THA) after failed peri-hip bone flap grafting (PBFG) and compared them with those patients undergoing primary THA for osteonecrosis of the femoral head (ONFH). METHODS: From January 2010 to December 2021, 163 Chinese patients (163 hips) were treated by conversion THA after failed PBFG (containing 94 patients who had pedicled vascularized iliac bone flap grafting and 69 patients who had pedicled vascularized greater trochanter bone flap grafting), and 178 Chinese patients were treated by primary THA. The preoperative baseline data and perioperative indicators in both groups were compared. RESULTS: In the conversion group, patients had significantly greater blood loss, a longer length of stay, and greater changes in serum hemoglobin than those in the primary THA group (P < 0.05). The operative room time, transfusion volume, calculated blood loss, changes in serum hematocrit, and increased superficial infection (P > 0.05) in the conversion group were greater compared with the primary cohort; however, the difference was not statistically significant. The mean postoperative Harris Hip Scoring System (HHS) of the PBFG group at the one-month follow-up was 81, and the control group had an 82 score. Importantly, subgroup analysis of the PBFG group indicated that there was no significant difference between patients who had prior pedicled vascularized iliac bone flap grafting and pedicled vascularized greater trochanter bone flap grafting (P > 0.05), except for the operative room time (P = 0.032). CONCLUSION: Hip-sparing surgery of ONFH did not make THA more difficult or lead to more peri-operative complications, but increased blood loss and extended hospital stay from a prior PBFG are still notable problems in clinical practice. Thus, it is necessary for surgeons to focus attention on the improvement of the preoperative condition and prepare for any specific intraoperative challenges.

In situ metabolomic analysis of osteonecrosis of the femoral head (ONFH) using MALDI MSI.

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease characterized by disability and deformity. To better understand ONFH at molecular level and to explore the possibility of early diagnosis, instead of diagnosis based on macroscopic spatial characteristics, a matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) method was developed for ONFH disease for the first time. The most challenging step for ONFH MSI is to deal with human bone tissues which are much harder than the other biological samples studied by the reported MSI studies. In this work, the MSI sectioning method of hard bone tissues was established using tender acids and a series of test criteria. Small-molecule metabolites, such as lipids and amino acids, were detected in bone sections, realizing the in situ detection of spatial distribution of biometabolites. By comparing the distribution of metabolites from different regions of normal femoral head, ONFH bone tissue (ONBT), and adjacent ONFH bone tissue (ANBT), the whole process of femoral head from normal stage to necrosis was monitored and visualized at molecular level. Moreover, this developed MSI method was used for metabolomics study of ONFH. 72 differential metabolites were identified, suggesting that disturbances in energy metabolism and lipid metabolism affected the normal life activities of osteoblasts and osteoclasts. This study provides new perspectives for future pathological studies of ONFH.

Evaluation of the Tensor Fascia Lata Muscle Pedicle Bone Grafting Technique in the Management of Avascular Necrosis of the Femoral Head: An Observational Clinical Study.

BACKGROUND: Osteonecrosis of the hip is defined as necrosis of the bone tissue due to some form of vascular insult, subsequently leading to the collapse of the femoral head and secondary osteoarthritis, which leads to pain and impaired joint function. This disease is widely known to affect middle-aged groups; however, in the Indian population, even younger people are more commonly affected. The disease has a debilitating effect on the activities of daily living (ADL) and the productivity of individuals and has financial consequences. With the increased utilization of magnetic resonance imaging (MRI) in society, the disease is diagnosed in its early stages. Hip-preserving surgery like tensor fascia lata (TFL) muscle pedicle iliac bone grafting should be given a chance to preserve the native femoral head. METHODOLOGY: At a tertiary care teaching hospital in Gorakhpur, India, an observational clinical study was carried out. This study comprised 40 patients, ages 18-50 years, with femoral head osteonecrosis (stages II and III of the Ficat-Arlet staging system), who came to our institute's orthopedic outpatient department. Patients were treated with multiple drillings, curettage, and cheilectomy of the femoral head, in addition to TFL muscle pedicle bone grafting. The Harris hip score (HHS) was utilized to assess the clinical results, and the radiological assessment focused on signs of revascularization. RESULT: In our study, the most prevalent age group was 20-30 years (67.5%), with a male predominance (85%). Among our cohort of 40 patients, the HHS indicated excellent outcomes (90-100) in 14 cases (35%), good outcomes (80-89) in 19 cases (47.5%), fair outcomes (70-79) in six cases (15%), and poor outcomes (<70) in one case (2.5%), at the time of the final follow-up. The final follow-up period varied from one to 10 years. CONCLUSION: TFL muscle pedicle bone grafting procedure provides excellent clinical and radiological outcomes, especially in young patients in whom femoral head-preserving surgery is preferred over total hip arthroplasty. This procedure is effective in both early and advanced stages of femoral head osteonecrosis, provided there are no arthritic changes. It reduces symptoms and improves functional outcomes.

Open reduction and internal fixation of the proximal humerus with femoral head allograft augmentation "the French fry technique".

Fractures of the proximal humerus account for 4%-8% of injuries to the appendicular skeleton. Most are stable, minimally displaced osteoporotic fractures in the elderly, and are the result of low-energy falls. A large majority of these patients regain adequate shoulder function without operative intervention. Surgery is considered in approximately 20% of patients because they require improved shoulder function for their activities of daily living or because of the significant deformity of their fracture and the need to restore functional alignment, length, and rotation in active, higher demand individuals. However, fixation of these fractures can pose a challenge due to poor bone quality and displacing forces of the rotator cuff. This is especially true in 3-part and 4-part fractures. These factors lead to the high failure rates seen with early attempts at osteosynthesis. In the last 2 decades, locking plate technology has been an innovation in treating these complex fractures. Despite the improvements in torsional strength and rigidity, outcome studies on locking plate technology demonstrate equivocal results with complication rates as high as 20%-30% and a revision rate of 10%. Specifically, these complications include avascular necrosis, varus collapse, intra-articular screw penetration, and postoperative stiffness. Varus collapse occurs when the weak osteoporotic bone fails around the implant. In turn, fibular strut endosteal augmentation was introduced to provide additional support and decrease implant failure rates in displaced fractures with varus coronal malalignment and significant metaphyseal bone loss. Although clinically successful and biomechanically superior to plate-only constructs, a few concerns remain. In turn, we introduce a novel technique of creating individual cancellous femoral head allograft struts or "French fries" that provides structural support for the humeral head but does not have the potential problems of a cortical fibular strut.

Core Decompression with Bone Marrow Aspirate Concentrate Implantation in Osteonecrosis of the Femoral Head with a Minimum of 2-year Follow-up - A Pilot Study.

Introduction: Osteonecrosis of the femoral head (ONFH), resulting from impaired blood supply to the head of the femur, presents a significant challenge to clinicians due to its debilitating nature. Conservative treatment often offers insufficient pain relief and debilitating functional outcomes which necessitate alternative therapies. Bone marrow aspirate concentrate (BMAC), a potent orthobiologics and rich in mesenchymal stromal cells and growth factors, holds good promise as the minimally invasive procedure for ONFH. With the preceding research suggesting clinical and functional efficacy, we assessed the therapeutic effectiveness of BMAC in ONFH management in joint preservation. Materials and Methods: A prospective cohort study was conducted with 20 patients suffering from ONFH who failed to respond to 6 months of conservative treatment. A uniform surgical procedure was performed by a single surgeon, involving bone marrow extraction from the anterior iliac crest and subsequent processing into an 8-10 mL of BMAC concentrate. The BMAC was then injected into the implanted into the decompressed femoral head. The post-operative protocol comprised weight-bearing mobilization, physiotherapy, and a 4-week NSAID-free regimen. Outcome measures included pain scores, hip function, knee symptoms, sports activities, patient satisfaction, and recommendation of the procedure. Results: Of the 20 patients suffering from ONFH, primarily the left side, most of whom were at stage 2b, significant pain reduction and functional improvement were observed over 24 months. The mean pain score decreased from 9.00 to 3.55, while the hip function score increased from 46.12 to 88.60. However, some patients encountered complications such as symptom recurrence (5%), disease progression (10%), and persistent pain (5%). Conclusion: Core decompression with BMAC implantation emerges as a promising, effective, and safe treatment for ONFH with better costeffectiveness and minimal side effects, making it a feasible treatment alternative.

Case Report of a Delayed Rare Pipkin Type III Fracture in Adult Male Patient.

Introduction: Femoral head fractures are relatively rare compared to other hip pathologies. Despite being infrequent, these fractures can give rise to various complications, even after a successful surgical fixation. To categorize these fractures, Pipkin introduced a classification system, distinguishing them into four types. Among these, Type III (31C.3) fractures are associated with femoral neck fractures and are notably less common, often leading to unfavorable outcomes. Case Report: We present a case of a Type III Pipkin fracture in a 35-year-old male resulting from a road traffic accident. The patient underwent management with open reduction and internal fixation, utilizing headless compression screws and cancellous cannulated screws. Post-operative, the patient was instructed to remain non-weight bearing, and subsequent follow-ups were conducted to monitor for any potential complications. Conclusion: Femoral head fractures are recognized for their complexity, with outcomes becoming even more diverse when associated with neck fractures. Effective pre-operative planning, coupled with timely reduction and fixation, plays a pivotal role in the management of these fractures.

Freezing does not influence the microarchitectural parameters of the microstructure of the freshly harvested femoral head bone.

The femoral head is one of the most commonly used bones for allografts and biomechanical studies. However, there are few reports on the trabecular bone microarchitectural parameters of freshly harvested trabecular bones. To our knowledge, this is the first study to characterize the microstructure of femoral heads tested immediately after surgery and compare it with the microstructure obtained with conventional freezing. This study aims to investigate whether freezing at -80 °C for 6 weeks affects the trabecular microstructure of freshly harvested bone tissue. This study was divided into two groups: one with freshly harvested human femoral heads and the other with the same human femoral heads frozen at -80 °C for 6 weeks. Each femoral head was scanned using an X-ray microcomputed tomography scanner (µCT) to obtain the microarchitectural parameters, including the bone volume fraction (BV/TV), the mean trabecular thickness (Tb.th), the trabecular separation (Tb.sp), the degree of anisotropy (DA), and the connectivity density (Conn.D). There was no statistically significant difference between the fresh and the frozen groups for any of the parameters measured. This study shows that freezing at -80 °C for 6 weeks does not alter bone microstructure compared with freshly harvested femoral heads tested immediately after surgery.

[Analysis of influencing factors of early femoral head necrosis after femoral neck fracture and construction of nomogram prediction model].

OBJECTIVE: To explore the risk factors of early femoral head necrosis in patients with femoral neck fracture after operation, and to establish a nomogram prediction model. METHODS: A total of 167 patients with femoral neck fracture from January 2020 to April 2022 were selected and divided into necrosis group and non-necrosis group according to whether femoral head necrosis occurred in the early postoperative period. There were 21 males and 17 females in the necrosis group, aged from 33 to 72 years old, with an average of (53.49±10.96) years old, and the time from injury to operation ranged from 40 to 67 hours, with average time of(53.46±7.23) hours. There were 72 males and 57 females in the non-necrosis group, aged from 18 to 83 years, with an average of (52.78±12.55) years old, and the time from injury to operation was 18 to 65 hours, with an average time of(39.88±7.79) hours. The potential influencing factors, including patient gender, diabetes mellitus, hypertension, chronic liver disease, posterior inclination angle of the femoral head, operation mode, fracture displacement, fracture line location, preoperative braking traction, screw arrangement mode, reduction quality, age, body mass index(BMI), and injury to operation time were subjected to single factor analysis. Logistic multivariate regression analysis was conducted for factors with a significance level of P<0.05. RESULTS: The incidence of femoral head necrosis in 167 patients with femoral neck fracture was 22.76%. The following factors were identified as independent risk factors for early postoperative femoral head necrosis in patients with femoral neck fractures:coexisting diabetes[OR=5.139, 95%CI(1.405, 18.793), P=0.013], displaced fracture [OR=3.723, 95%CI(1.105, 12.541), P=0.034], preoperative immobilization[OR=3.444, 95%CI(1.038, 11.427), P=0.043], quality of reduction [OR=3.524, 95%CI(1.676, 7.411), P=0.001], and time from injury to surgery[OR=1.270, 95%CI(1.154, 1.399), P=0.000]. The Hosmer-Lemeshow goodness-of-fit test(χ2=3.951, P=0.862), the area under the receiver operator characteristic(ROC) curve was 0.944[P<0.001, 95%CI(0.903, 0.987)], with a sensitivity of 89.50%, the specificity was 88.40%, the maximum Youden index was 0.779, and the overall trend of the model correction curve was close to the ideal curve. Model regression equation was Z=1.637 × diabetes + 1.314× fracture displacement+1.237 × preoperative braking traction+1.260 × reduction quality + 0.239×injury to operation time-18.310. CONCLUSION: The occurrence of early femoral head necrosis in patients with femoral neck fracture postoperatively is affected by multiple factors. The risk early warning model established according to the factors has good predictive efficacy.

Case report: Imaging of septic arthritis in the hip joint of a calf treated with femoral head ostectomy.

A 24-day-old male Japanese Black calf presented with weight-bearing lameness in the left hind limb and a swollen pelvis. Ultrasonography revealed the accumulation of fluidity materials with a mixture of hyper- and hypo-echogenicity, enclosed by 5-10-mm-thick capsular structures. On the ventral-dorsal radiograph of the pelvis, irregular and radiolucent osseous changes were evident in the femoral head and acetabulum within the swollen hip joint, with soft-tissue density. Computed tomography (CT) confirmed the relationship between the bony and soft tissue lesions, which was suspected following ultrasonography and radiography, and provided additional findings, such as intra-articular accumulation of gas and the degree of osteolytic changes. Based on the imaging findings and cytology of the arthrocentesis specimen, the patient was diagnosed with hip arthritis and osteomyelitis of the femoral head. Additionally, the severity of the lesions supported our decision to perform a femoral head ostectomy. The postoperative radiographic and CT findings of the treated pelvis were helpful in evaluating the efficacy of this technique. Following treatment, the animal could walk and showed normal development, although it was three postoperative months before weight-bearing lameness improved. To the best of our knowledge, this is the first report to describe the combined use of ultrasonography, radiography, and CT in the diagnosis, preoperative planning, and evaluation of the postoperative effects of bovine hip arthritis. Additionally, this report details the therapeutic efficacy of femoral head ostectomy for bovine hip arthritis, a technique that has not been reported previously.

Concerns with alumina bipolar hemiarthroplasties compared to metal bipolar hemiarthroplasties when performed for nontraumatic osteonecrosis of the femoral head.

PURPOSE: A nationwide multicenter follow-up cohort study of hip replacement arthroplasties performed for nontraumatic osteonecrosis of the femoral head (ONFH) aimed to answer the following questions: What factors were associated with need for reoperation? Although many modifications were made in bipolar hemiarthroplasties (BPs) to improve their durability, could we find any evidence of their efficacy? METHODS: Excluding 58 infected hips and 43 ABS THAs with very poor survivorship, we analyzed 7393 arthroplasties; 6284 total hip arthroplasties (THAs), 886 BPs, 188 total resurfacing arthroplasties, and 35 hemi-resurfacing arthroplasties (hRSs). In the 886 BPs, 440 hips had a smooth small-diameter prosthetic neck (nBPs), 667 hips had a smooth neck (sBPs), 116 hips had highly cross-linked polyethylene in the outer head (hBPs), and 238 hips had an outer head whose outer surface was alumina ceramic (aBPs) (648 hips had an outer head whose outer surface was metal [mBPs]). Multivariate analyses using a Cox proportional-hazard model analyzed risk factors. RESULTS: Follow-up ranged from 0.1 to 27 (average, 6.9) years, during which 265 hips (3.6%) needed reoperation. Combined systemic steroid use and excessive alcohol consumption and lateral approach were associated with higher risks, aBPs were less durable than THAs or mBPs, and hRSs were inferior to the others. Regarding BPs, the following divisions did not influence their survivorship; nBP or not, sBP or not, and hBP or not. CONCLUSIONS: Factors associated with reoperation risk were identified as described above. The modifications made in BPs did not improve their durability, but aBPs made it worse. LEVEL OF CLINICAL EVIDENCE: Level III, therapeutic cohort study.

Factors influencing the survival status of the hip joint in post-collapse femoral head necrosis.

BACKGROUND: Despite hip function typically deteriorating in the post-collapse stage of osteonecrosis of the femoral head (ONFH), some patients can still demonstrate long-term favorable hip function, a state termed "survival with collapse". This study aims to identify the characteristics of patients suitable for "survival with collapse" in cases of ONFH. METHODS: This cross-sectional study included 65 patients (87 hips) diagnosed with post-collapse ONFH for ≥ 3 years (average 9.1 years, range 3-23 years). Hip function was assessed using the Harris Hip Score (HHS). Demographic, clinical, and radiographic data were compared between the favorable group (HHS > 80) and the poor group (HHS ≤ 80). Independent protective factors for hip function were identified by multivariate analysis and receiver operating characteristic (ROC) curve analysis was further applied to evaluate these factors' diagnostic efficacy. RESULTS: The favorable and poor groups included 46 and 41 hips, respectively. Significant differences were found in body mass index (BMI), Association Research Circulation Osseous (ARCO) stage, collapse degree, Japanese Investigation Committee (JIC) classification, necrotic size, and hip subluxation between the two groups (p < 0.05). Multivariate logistic regression identified collapse < 3 mm(OR:14.49, 95%CI: 3.52-59.68, p < 0.001), JIC types B (OR: 11.08, 95% CI: 1.07-115.12, p < 0.05) and C1(OR: 5.18, 95% CI: 1.47-18.20, p < 0.05) as independent protective factors for hip function, while BMI (OR: 0.76, 95% CI: 0.59-0.97, p = 0.029) was an independent risk factor. ROC curve analysis demonstrated that both collapse degree (AUC = 0.798, sensitivity = 91.3%, specificity = 68.3%, p < 0.0001) and JIC classification (AUC = 0.787, sensitivity = 80.4%, specificity = 73.2%, p < 0.0001) had satisfactory diagnostic value for hip function. Combining JIC classification and collapse degree (AUC = 0.868, sensitivity = 76.1%, specificity = 85.4%, p < 0.0001) significantly enhanced diagnostic efficacy compared to using either alone (p < 0.05). CONCLUSION: In ONFH, femoral head collapse does not necessarily determine a poor prognosis. Patients with mild collapse (< 3 mm) and preserved anterolateral wall are more likely to retain satisfactory hip function, making them candidates for "survival with collapse."

Three-dimensional analysis of age and sex differences in femoral head asphericity in asymptomatic hips in the United States.

BACKGROUND: The sphericity of the femoral head is a metric used to evaluate hip pathologies and is associated with the development of osteoarthritis and femoral-acetabular impingement. AIM: To analyze the three-dimensional asphericity of the femoral head of asymptomatic pediatric hips. We hypothesized that femoral head asphericity will vary significantly between male and female pediatric hips and increase with age in both sexes. METHODS: Computed tomography scans were obtained on 158 children and adolescents from a single institution in the United States (8-18 years; 50% male) without hip pain. Proximal femoral measurements including the femoral head diameter, femoral head volume, residual volume, asphericity index, and local diameter difference were used to evaluate femoral head sphericity. RESULTS: In both sexes, the residual volume increased by age (P < 0.05). Despite significantly smaller femoral head size in older ages (> 13 years) in females, there were no sex-differences in residual volume and aspherity index. There were no age-related changes in mean diameter difference in both sexes (P = 0.07) with no significant sex-differences across different age groups (P = 0.06). In contrast, there were significant increases in local aspherity (maximum diameter difference) across whole surface of the femoral head and all quadrants except the inferior regions in males (P = 0.03). There were no sex-differences in maximum diameter difference at any regions and age group (P > 0.05). Increased alpha angle was only correlated to increased mean diameter difference across overall surface of the femoral head (P = 0.024). CONCLUSION: There is a substantial localized asphericity in asymptomatic hips which increases with age in. While 2D measured alpha angle can capture overall asphericity of the femoral head, it may not be sensitive enough to represent regional asphericity patterns.

Femoral Neck Shaft Angle Measurement for Differentiating Femoral Head Stress Fracture from Avascular Necrosis.

OBJECTIVE: The study aimed to evaluate whether the measurement of Femoral Neck Shaft Angle (FNSA) can be helpful in differentiating femoral head Stress Fracture (SF) from Avascular Necrosis (AVN). METHODS: From September 2019 to April 2022, sixty-four patients [median age 32.0 years, interquartile range (IQR) 23.0-39.0 years] who underwent both hip radiograph and Magnetic Resonance Imaging (MRI) and diagnosed as femoral head SF or AVN were included in our retrospective study. Patients were divided into as having either femoral head SF (n = 34) or AVN (n = 30). The FNSA was measured in anteroposterior hip radiography. Continuous values were compared using the Mann-Whitney U test. The assessment of the predictive value of FNSA for femoral head SF was performed by Receiver Operating Characteristic (ROC) analysis. RESULTS: The FNSA was significantly higher in patients with SF (median 133.5°, IQR 128.0-136.7°) than those with AVN (median 127.5°, IQR 124.0-132.0°) (p = 0.001). In addition, the FNSA was significantly higher in SF femurs (median 134.8°, IQR 129.2-137.4°) than in contralateral normal femurs (median 127.1°, IQR 124.3-132.5°) in patients with unilateral femoral head SF (n = 30) (p < 0.001). In ROC analysis, the sensitivity, specificity, and Area Under the Curve (AUC) for predicting the femoral head SF were 77.3%, 63.3%, and 0.785 (95% confidence interval: 0.666-0.905), respectively, at a cutoff of 130.2°. CONCLUSION: Increased FNSA was associated with femoral head SF; thus, measurement of FNSA could be helpful for differentiating femoral head SF from AVN.

Changes of bone and articular cartilage in broilers with femoral head necrosis.

Femoral head necrosis (FHN) in broilers is a common leg disorder in intensive poultry farming, giving rise to poor animal health and welfare. Abnormal mechanical stress in the hip joint is a risk factor for FHN, and articular cartilage is attracting increasing attention as a cushion and lubrication structure for the joint. In the present study, broilers aged 3 to 4 wk with FHN were divided into femoral head separation (FHS) and femoral head separation with growth plate lacerations (FHSL) groups, with normal broilers as control. The features of the hip joint, bone, and cartilage were assessed in FHN progression using devices including computed tomography (CT), atomic force microscope (AFM), and transmission electron microscopy (TEM). Broilers with FHN demonstrated decreased bone mechanical properties, narrow joint space, and thickened femoral head stellate structures. Notably, abnormal cartilage morphology was observed in FHN-affected broilers, characterized by increased cartilage thickness and rough cartilage surfaces. In addition, as FHN developed, cartilage surface friction and friction coefficient dramatically increased, while cartilage modulus and stiffness decreased. The ultramicro-damage occurred in chondrocytes and the extracellular matrix (ECM) of cartilage. Cell disintegration, abnormal mitochondrial accumulation, and oxidative stress damage were observed in chondrocytes. A notable decline in cartilage collagen content was observed in ECM during the initial stages of FHN, accompanied by a pronounced reduction in collagen fiber diameter and proteoglycan content as FHN progressed. Furthermore, the noticeable loosening of the collagen fiber structure and the appearance of type I collagen were noted in cartilage. In conclusion, there was a progressive decrease in bone quality and multifaceted damage of cartilage in the femoral head, which was closely linked to the severity of FHN in broilers.

Mesenchymal stem cell-derived extracellular vesicles in joint diseases: Therapeutic effects and underlying mechanisms.

Joint diseases greatly impact the daily lives and occupational functioning of patients globally. However, conventional treatments for joint diseases have several limitations, such as unsatisfatory efficacy and side effects, necessitating the exploration of more efficacious therapeutic strategies. Mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have demonstrated high therapeutic efficacyin tissue repair and regeneration, with low immunogenicity and tumorigenicity. Recent studies have reported that EVs-based therapy has considerable therapeutic effects against joint diseases, including osteoarthritis, tendon and ligament injuries, femoral head osteonecrosis, and rheumatoid arthritis. Herein, we review the therapeutic potential of various types of MSC-EVs in the aforementioned joint diseases, summarise the mechanisms underlying specific biological effects of MSC-EVs, and discuss future prospects for basic research on MSC-EV-based therapeutic modalities and their clinical translation. In general, this review provides an in-depth understanding of the therapeutic effects of MSC-EVs in joint diseases, as well as the underlying mechanisms, which may be beneficial to the clinical translation of MSC-EV-based treatment. The translational potential of this article: MSC-EV-based cell-free therapy can effectively promote regeneration and tissue repair. When used to treat joint diseases, MSC-EVs have demonstrated desirable therapeutic effects in preclinical research. This review may supplement further research on MSC-EV-based treatment of joint diseases and its clinical translation.

Exploring of exosomes in pathogenesis, diagnosis and therapeutic of osteonecrosis of the femoral head: the mechanisms and signaling pathways.

Osteonecrosis of the femoral head (ONFH) is a refractory disease affecting young adults, resulting in severe hip pain, femoral head collapse, and disabling dysfunction. By far, the underlying mechanism of its pathology is unclear, and still lack of a mature and effective treatment. Exosomes, a regulator of cell-cell communication, their cargos may vary in response to different physiological or pathological conditions. To date, many studies have demonstrated that exosomes have the potential to become a diagnostic marker and therapeutic agent in many human diseases including ONFH. As a cell-free therapeutic agent, exosomes are becoming a promising tool within this field due to their crucial role in osteogenesis and angiogenesis in recent decades. Usually, exosomes from ONFH tissues could promote ONFH damage, while stem cells derived exosomes could delay diseases and repair femoral head necrosis. Herein, we describe the properties of exosomes, discuss its effect on pathogenesis, diagnosis, and treatment potential in ONFH, and examine the involvement of different signaling pathways. We also propose our suggestions for the future research of exosomes in ONFH field and hope to provide a potential therapeutic strategy for patients with ONFH.

Tanshinone IIA promotes osteogenic differentiation potential and suppresses adipogenic differentiation potential of bone marrow mesenchymal stem cells.

Tanshinone IIA (Tan IIA) may have therapeutic effects on avascular necrosis of the femoral head (ANFH) by targeting bone marrow mesenchymal stem cells (BMSCs). The effect and underlying mechanism of Tan IIA on adipogenesis and osteogenesis ability of BMSCs remain to be elucidated. In the present study BMSCs were treated with osteogenic or adipogenic differentiation medium with or without Tan IIA under hypoxic environment. Osteogenic differentiation potential was evaluated by alkaline phosphatase (ALP) measurement, alizarin red staining and reverse transcription­quantitative (RT­q) PCR of osteogenic marker genes. Adipogenic differentiation potential was evaluated with oil red staining and RT­qPCR of adipogenic marker genes. Detailed mechanism was explored by RNA­seq and small molecular treatment during osteogenesis and adipogenesis of BMSCs. ALP level, mineralized nodules and expression level of osteogenic marker genes significantly increased following Tan IIA treatment during osteogenic differentiation of BMSCs. Lipid droplet and expression levels of adipogenic marker genes significantly decreased following Tan IIA treatment during adipogenic differentiation of BMSCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of RNA­seq data indicated increased Akt and TGFß signaling following Tan IIA treatment. Further western blot assay confirmed that Tan IIA significantly activated Akt/cAMP response element­binding protein signaling and TGFß/Smad3 signaling. Application of Akti1/2 (an Akt inhibitor) significantly decreased the promotion effect of osteogenesis induced by Tan IIA, while the addition of SB431542 significantly reduced inhibition effect of adipogenesis caused by Tan IIA. Tan IIA could promote osteogenic differentiation potential of BMSCs by activating AKT signaling and suppress adipogenic differentiation potential of BMSCs by activating TGFß signaling.

CHRDL2 activates the PI3K/AKT pathway to ameliorate glucocorticoid-induced damages to bone microvascular endothelial cells (BMECs).

Steroid-induced avascular necrosis of the femoral head (ANFH) is characterized by the death of bone tissues, leading to the impairment of normal reparative processes within micro-fractures in the femoral head. Glucocorticoid (GCs)-induced bone microvascular endothelial cell (BMEC) damage has been reported to contribute to ANFH development. In this study, differentially expressed genes (DEGs) between necrosis of the femoral head (NFH) and normal samples were analyzed based on two sets of online expression profiles, GSE74089 and GSE26316. Chordin-like 2 (CHRDL2) was found to be dramatically downregulated in NFH samples. In GCs-stimulated BMECs, cellular damages were observed alongside CHRDL2 down-regulation. GCs-caused cell viability suppression, cell apoptosis promotion, tubule formation suppression, and cell migration suppression were partially abolished by CHRDL2 overexpression but amplified by CHRDL2 knockdown; consistent trends were observed in GCs-caused alterations in the protein levels of VEGFA, VEGFR2, and BMP-9 levels, and the ratios of Bax/Bcl-2 and cleaved-caspase3/Caspase3. GC stimulation significantly inhibited PI3K and Akt phosphorylation in BMECs, whereas the inhibitor effects of GCs on PI3K and Akt phosphorylation were partially attenuated by CHRDL2 overexpression but further amplified by CHRDL2 knockdown. Moreover, CHRDL2 overexpression caused improvement in GCs-induced damages to BMECs that were partially eliminated by PI3K inhibitor LY294002. In conclusion, CHRDL2 is down-regulated in NFH samples and GCs-stimulated BMECs. CHRDL2 overexpression could improve GCs-caused BMEC apoptosis and dysfunctions, possibly via the PI3K/Akt pathway.

Identification of steroid-induced osteonecrosis of the femoral head biomarkers based on immunization and animal experiments.

BACKGROUND: Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. METHOD: Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. RESULTS: Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. CONCLUSION: This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.