Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures.

Femoral head necrosis (FHN) is a serious complication after femoral neck fractures (FNF), often linked to sclerosis around screw paths. Our study aimed to uncover the proteomic and metabolomic underpinnings of FHN and sclerosis using integrated proteomics and metabolomics analyses. We identified differentially expressed proteins (DEPs) and metabolites (DEMs) among three groups: patients with FNF (Group A), sclerosis (Group B), and FHN (Group C). Using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we examined the roles of these proteins and metabolites. Our findings highlight the significant differences across the groups, with 218 DEPs and 44 DEMs identified between the sclerosis and FNF groups, 247 DEPs and 31 DEMs between the FHN and sclerosis groups, and a stark 682 DEPs and 94 DEMs between the FHN and FNF groups. Activities related to carbonate dehydratase and hydrolase were similar in the FHN and sclerosis groups, whereas extracellular region and lysosome were prevalent in the FHN and FNF groups. Our study also emphasized the involvement of the PI3K-Akt pathway in sclerosis and FHN. Moreover, the key metabolic pathways were implicated in glycerophospholipid metabolism and retrograde endocannabinoid signaling. Using western blotting, we confirmed the pivotal role of specific genes/proteins such as ITGB5, TNXB, CA II, and CA III in sclerosis and acid phosphatase 5 and cathepsin K in FHN. This comprehensive analyses elucidates the molecular mechanisms behind sclerosis and FHN and suggests potential biomarkers and therapeutic targets, paving the way for improved treatment strategies. Further validation of the findings is necessary to strengthen the robustness and reliability of the results.

Biomechanical properties of articular cartilage in different regions and sites of the knee joint: acquisition of osteochondral allografts.

Osteochondral allograft (OCA) transplantation involves grafting of natural hyaline cartilage and supporting subchondral bone into the cartilage defect area to restore its biomechanical and tissue structure. However, differences in biomechanical properties and donor-host matching may impair the integration of articular cartilage (AC). This study analyzed the biomechanical properties of the AC in different regions of different sites of the knee joint and provided a novel approach to OCA transplantation. Intact stifle joints from skeletally mature pigs were collected from a local abattoir less than 8 h after slaughter. OCAs were collected from different regions of the joints. The patella and the tibial plateau were divided into medial and lateral regions, while the trochlea and femoral condyle were divided into six regions. The OCAs were analyzed and compared for Young's modulus, the compressive modulus, and cartilage thickness. Young's modulus, cartilage thickness, and compressive modulus of OCA were significantly different in different regions of the joints. A negative correlation was observed between Young's modulus and the proportion of the subchondral bone (r = - 0.4241, P < 0.0001). Cartilage thickness was positively correlated with Young's modulus (r = 0.4473, P < 0.0001) and the compressive modulus (r = 0.3678, P < 0.0001). During OCA transplantation, OCAs should be transplanted in the same regions, or at the closest possible regions to maintain consistency of the biomechanical properties and cartilage thickness of the donor and recipient, to ensure smooth integration with the surrounding tissue. A 7 mm depth achieved a higher Young's modulus, and may represent the ideal length.

High-Speed Centrifugation Efficiently Removes Immunogenic Elements in Osteochondral Allografts.

OBJECTIVES: The current clinical pulse lavage technique for flushing fresh osteochondral allografts (OCAs) to remove immunogenic elements from the subchondral bone is ineffective. This study aimed to identify the optimal method for removing immunogenic elements from OCAs. METHODS: We examined five methods for the physical removal of immunogenic elements from OCAs from the femoral condyle of porcine knees. We distributed the OCAs randomly into the following seven groups: (1) control, (2) saline, (3) ultrasound, (4) vortex vibration (VV), (5) low-pulse lavage (LPL), (6) high-pulse lavage (HPL), and (7) high-speed centrifugation (HSC). OCAs were evaluated using weight measurement, micro-computed tomography (micro-CT), macroscopic and histological evaluation, DNA quantification, and chondrocyte activity testing. Additionally, the subchondral bone was zoned to assess the bone marrow and nucleated cell contents. One-way ANOVA and paired two-tailed Student's t-test are used for statistical analysis. RESULTS: Histological evaluation and DNA quantification showed no significant reduction in marrow elements compared to the control group after the OCAs were treated with saline, ultrasound, or VV treatments; however, there was a significant reduction in marrow elements after LPL, HPL, and HSC treatments. Furthermore, HSC more effectively reduced the marrow elements of OCAs in the middle and deep zones compared with LPL (p < 0.0001) and HPL (p < 0.0001). Macroscopic evaluation revealed a significant reduction in blood, lipid, and marrow elements in the subchondral bone after HSC. Micro-CT, histological analyses, and chondrocyte viability results showed that HSC did not damage the subchondral bone and cartilage; however, LPL and HPL may damage the subchondral bone. CONCLUSION: HSC may play an important role in decreasing immunogenicity and therefore potentially increasing the success of OCA transplantation.

Treatment of Articular Cartilage Defects: A Descriptive Analysis of Clinical Characteristics and Global Trends Reported from 2001 to 2020.

PURPOSE: To evaluate the clinical characteristics and global trends in the surgical treatment of articular cartilage defects. METHODS: Studies in English published between January 1, 2001 and December 31, 2020 were retrieved from MEDLINE, WOS, INSPEC, SCIELO, KJD, and RSCI on the "Web of Science." Patient data were extracted, including age, sex, defect location and laterality, duration of follow-up and symptoms, and body mass index (BMI). Data were further stratified according to the surgical method, lesion location, procedural type and geographical area, and time period. A comparative analysis was performed. RESULTS: Overall, 443 studies involving 26,854 patients (mean age, 35.25 years; men, 60.5%) were included. The mean lesion size and patient BMI were 3.51 cm2 and 25.61 kg/m2, respectively. Cartilage defects at the knees, talus, and hips affected 20,850 (77.64%), 3,983 (14.83%), and 1,425 (5.31%) patients, respectively. The numbers of patients who underwent autologous chondrocyte implantation, arthroscopic debridement/chondroplasty, osteochondral allograft (OCA), osteochondral autologous transplantation, and microfracture were 7,114 (26.49%), 5,056 (18.83%), 3,942 (14.68%), 3,766 (14.02%), and 2,835 (10.56%), respectively. European patients were the most numerous and youngest. North American patients had the largest defects. The number of patients increased from 305 in 2001 to 3,017 in 2020. In the last 5 years, the frequency of OCAs showed a greatly increasing trend. CONCLUSION: Clinical characteristics and global trends in the surgical treatment of articular cartilage defects were revealed. The choice of operation should be based on the patient characteristics and defect location, size, and shape, as well as the patient's preference.

Characteristics and Clinical Outcomes After Osteochondral Allograft Transplantation for Treating Articular Cartilage Defects: Systematic Review and Single-Arm Meta-analysis of Studies From 2001 to 2020.

Background: Osteochondral allograft transplantation (OCA) treats symptomatic focal cartilage defects with satisfactory clinical results. Purpose: To comprehensively analyze the characteristics and clinical outcomes of OCA for treating articular cartilage defects. Study Design: Systematic review; Level of evidence, 4. Methods: We searched Embase, PubMed, Cochrane Database, and Web of Science for studies published between January 1, 2001, and December 31, 2020, on OCA for treating articular cartilage defects. Publication information, patient data, osteochondral allograft storage details, and clinical outcomes were extracted to conduct a comprehensive summative analysis. Results: In total, 105 studies involving 5952 patients were included. The annual reported number of patients treated with OCA increased from 69 in 2001 to 1065 in 2020, peaking at 1504 cases in 2018. Most studies (90.1%) were performed in the United States. The mean age at surgery was 34.2 years, and 60.8% of patients were male and had a mean body mass index of 26.7 kg/m2. The mean lesion area was 5.05 cm2, the mean follow-up duration was 54.39 months, the mean graft size was 6.85 cm2, and the number of grafts per patient was 54.7. The failure rate after OCA was 18.8%, and 83.1% of patients reported satisfactory results. Allograft survival rates at 2, 5, 10, 15, 20, and 25 years were 94%, 87.9%, 80%, 73%, 55%, and 59.4%, respectively. OCA was mainly performed on the knee (88.9%). The most common diagnosis in the knee was osteochondritis dissecans (37.9%), and the most common defect location was the medial femoral condyle (52%). The most common concomitant procedures were high tibial osteotomy (28.4%) and meniscal allograft transplantation (24.7%). After OCA failure, 54.7% of patients underwent revision with primary total knee arthroplasty. Conclusion: The annual reported number of patients who underwent OCA showed a significant upward trend, especially from 2016 to 2020. Patients receiving OCA were predominantly young male adults with a high body mass index. OCA was more established for knee cartilage than an injury at other sites, and its best indication was osteochondritis dissecans. This analysis demonstrated satisfactory long-term postoperative outcomes.

Prevention of sclerosis around cannulated screw after treatment of femoral neck fractures with bioceramic nails: a finite element analysis.

PURPOSE: Conventional cannulated screws (CS) are the main treatment method for femoral neck fractures (FNF). However, the rate of femoral head necrosis remains high after FNF treatment. The study aimed to compare the biomechanical features of different internal fixation materials for the treatment of Pauwel type III FNF to explore new strategies for clinical management. METHODS: A new material was prepared by applying casting, freeze drying and sintering process. The independently developed calcium magnesium silicate ceramic powder and hydrogel solution were evenly mixed to obtain a high-viscosity bio-ink, and a bioceramic nail (BN) with high mechanical strength and high fracture toughness was successfully prepared. Four internal fixations were developed to establish the Pauwel type III FNF and healed fracture finite element models: A, three CSs; B, three BNs; C, two BNs and one CS; D, one BN and two CSs. Von Mises stress and displacement of the implants and femur were observed. RESULTS: The measured Mg content in ceramic powder was 2.08 wt%. The spectral data confirmed that the ceramic powder has high crystallinity, which coincides with the wollastonite-2 M (PDF# 27-0088). The maximum von Mises stresses for the four models were concentrated in the lower part of the fracture surface, at 318.42 Mpa, 103.52 MPa, 121.16 MPa, and 144.06 MPa in models A, B, C, and D, respectively. Moreover, the maximum Von-mises stresses of the implants of the four models were concentrated near the fracture end at 243.65 MPa (A) and 58.02 MPa (B), 102.18 MPa (C), and 144.06 MPa (D). The maximum displacements of the four models were 5.36 mm (A), 3.41 mm (B), 3.60 mm (C), and 3.71 mm (D). The displacements of the three models with BNs were similar and smaller than that of the triple CS fracture model. In the fracture healing models with and without three CSs, the greatest stress concentration was scattered among the lowest screw tail, femoral calcar region, and lateral femur shaft. The displacement and stress distributions in both models are generally consistent. The stress distribution and displacement of the three healed femoral models with BNs were essentially identical to the healing models with three CSs. The maximum von Mises stresses were 65.94 MPa (B), 64.61 MPa (C), and 66.99 MPa (D) while the maximum displacements of the three healed femoral models were 2.49 mm (B), 2.56 mm (C), and 2.49 mm (D), respectively. CONCLUSIONS: Bioceramic nails offer greater advantages than conventional canulated screws after femoral neck fractures. However, the combination of bioceramic nails and CSs is more clinically realistic; replacing all internal fixations with bioceramic nails after the healing of femoral neck fractures can solve the problem of sclerosis formation around CSs and improve bone reconstruction by their bioactivity.