Sea Cucumber-Inspired Aerogel for Ultrafast Hemostasis of Open Fracture.

The symptomatic management of hemorrhagic shock complicated by open fractures is a great challenge, because it is also complicated by complex wound bleeding, bacterial infection, and bone defects. Inspired by the water absorption and cross-sectional microstructure of sea cucumbers, in this study, a new sea cucumber-like aerogel (GCG) is proposed. Its aligned porous structure and composition can stop bleeding rapidly and effectively with a blood clotting index of 3.73 ± 1.8%. More importantly, the data of in vivo hemostasis test in an amputating rat tail hemostatic model (15.69 ± 2.45 s, 26.95 ± 8.43 mg) and liver puncture bleeding model (23.77 ± 2.68 s, 36.22 ± 16.92 mg) also indicate the excellent hemostatic performance of GCG. In addition, GCG also shows a significant inhibitory effect on S. aureus and E. coli, which can prevent the occurrence of postoperative osteomyelitis. Not only that, after filling in the bone defect, it is shown that this GCG aerogel completely degrades eight weeks after surgery and induces new bone ingrowth, achieving functional regeneration after hemostasis of an open fracture defect. Generally, because of its combination of hemostatic, antibacterial, and osteogenic activities, this new aerogel is a promising option for open fractures treatment.

Identification of key regulators responsible for dysregulated networks in osteoarthritis by large-scale expression analysis.

BACKGROUND: Osteoarthritis (OA) is a worldwide musculoskeletal disorder. However, disease-modifying therapies for OA are not available. Here, we aimed to characterize the molecular signatures of OA and to identify novel therapeutic targets and strategies to improve the treatment of OA. METHODS: We collected genome-wide transcriptome data performed on 132 OA and 74 normal human cartilage or synovium tissues from 7 independent datasets. Differential gene expression analysis and functional enrichment were performed to identify genes and pathways that were dysregulated in OA. The computational drug repurposing method was used to uncover drugs that could be repurposed to treat OA. RESULTS: We identified several pathways associated with the development of OA, such as extracellular matrix organization, inflammation, bone development, and ossification. By protein-protein interaction (PPI) network analysis, we prioritized several hub genes, such as JUN, CDKN1A, VEGFA, and FOXO3. Moreover, we repurposed several FDA-approved drugs, such as cardiac glycosides, that could be used in the treatment of OA. CONCLUSIONS: We proposed that the hub genes we identified would play a role in cartilage homeostasis and could be important diagnostic and therapeutic targets. Drugs such as cardiac glycosides provided new possibilities for the treatment of OA.

Natural Biomineralization-Inspired Magnesium Silicate Composite Coating Upregulates Osteogenesis, Enabling Strong Anterior Cruciate Ligament Graft-Bone Healing In Vivo.

Artificial ligaments prepared from polyethylene terephthalate (PET) are widely accepted for clinical anterior cruciate ligament (ACL) reconstruction to recover the native function of knee joints. However, due to the chemical inertness and hydrophobicity of PET, improving its bioactivity and promoting graft-bone integration are still great challenges. Inspired by the natural biomineralization process on the surface of a historical stone, in this study, a bioactive organic/inorganic composite coating that is composed of poly(allylamine hydrochloride) and chondroitin sulfate with magnesium silicate (MgSiO3) doping is developed for surface modification of PET (MSPC-PET). This composite coating promotes adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs) and its bioactive inorganic components (MgSiO3) could induce osteogenic differentiation of BMSCs. Furthermore, an in vivo experiment indicated that this composite coating might afford superior graft-bone integration between MSPC-PET and the host bone tunnel, and fibrous scar tissue formation was also inhibited. More importantly, a biomechanical analysis proved that there was a strong integration between the MSPC-PET graft and the bone tunnel, which will improve biomechanical properties for the restoration of ACL function. This study shows that this bioactive composite coating-modified PET graft for the ACL reconstruction can effectively achieve good integration of ACL artificial grafts and bone tunnels and prevent surgical failure.

An innovative three-dimensional method for identifying a proper femoral intramedullary entry point in total knee arthroplasty.

BACKGROUND:: Identification of the proper femoral intramedullary (IM) access point is an important determinant of final implant position in IM-guided total knee arthroplasty (TKA). The aim of this study was to identify the optimal entry point in Chinese participants using a new three-dimensional method. METHODS:: A series of computed tomography scans of 44 femurs in Chinese participants from October 2014 to October 2015 were imported into Mimics 17.0 software to identify the optimal entry point. The apex of the intercondylar notch (AIN) was used as the reference bony anatomical landmark to identify the proper entry point to insert the IM rod. The statistical significance was calculated on the basis of a 5% level (P < 0.05) using the Student's t-test. RESULTS:: For the males, the average ideal entry point was 1.49 mm medial and 13.39 mm anterior to the AIN. The values were 1.77 mm medial and 15.29 mm anterior to the AIN in females. A significant difference was present between males and females (13.39 ± 2.46 mm vs. 15.29 ± 3.44 mm, t = 2.124, P = 0.040). When using the recommended location as the entry point for the IM rod, the mean potential error differed significantly from the femoral trochlear groove (the potential error of IM in males in coronal plane: 0.93° ± 0.24° vs. 1.27° ± 0.32°, t = -4.166, P <0.001; the potential error of IM in males in sagittal plane: 1.40° ± 0.42° vs. 2.79° ± 0.70°, t = 7.155, P < 0.001; the potential error of IM in females in coronal plane: 0.73° ± 0.28° vs. 1.15° ± 0.35°, t = 3.940, P < 0.001; and the potential error of IM in females in sagittal plane: 1.48° ± 0.47° vs. 2.76° ± 0.83°, t =5.574, P < 0.001). A significant difference was present between the recommended point and the point 10 mm anterior to the origin of the posterior cruciate ligament (the potential error of IM in males in coronal plane: 0.93° ± 0.24° vs. 1.53° ± 0.43°, t = 5.948, P < 0.001; the potential error of IM in males in sagittal plane: 1.40° ± 0.42° vs. 2.15° ± 0.75°, t = 3.152, P = 0.003; the potential error of IM in females in coronal plane: 0.73° ± 0.28° vs. 1.28° ± 0.42°, t = -4.632, P < 0.001; and the potential error of IM in females in sagittal plane: 1.48° ± 0.47° vs. 2.40° ± 0.93°, t = 3.763, P = 0.001). CONCLUSIONS: The technique described here is an innovative method for swift, easy, and accurate access to the medullary canal during TKA, and it can optimize the position and orientation of the prosthetic components in knee arthroplasty.

Effect of glucocorticoids on miRNA expression spectrum of rat femoral head microcirculation endothelial cells.

The study profiled the differential miRNA expression from femoral head bone microvascular endothelial cells (BMECs) between model group and control group to explore the pathogenesis of steroid-induced osteonecrosis of femoral head (ONFH). Twenty 8-week-old Female Sprague-Dawley (SD) rats were randomly divided into control and model groups. Rats in model group received an intraperitoneal injection of 20-µg/kg lipopolysaccharide (LPS) at an interval of 24 h. Then, 24 h later, rats received three doses of 40-mg/kg methylprednisolone by intramuscular injection at intervals of 24 h. In control group, rats received the same volume of normal saline. After 4 weeks, the femoral heads were sectioned to confirm the establishment of the model. To replicate the animal model ex vivo, BMECs were isolated. Different miRNAs were screened using Agilent Gene Spring GX software, and real-time quantitative polymerase chain reaction (qPCR) was used to confirm the results of miRNA microarray analysis. The differentially expressed miRNA were assessed by bioinformatics analysis. Four differentially expressed miRNAs were identified (two upregulated: miR-132-3p, miR-335 and two down regulated: miR-466b-2-3p, let-7c-1-3p). qPCR results were consistent with the gene-chip results. Steroid-induced ONFH may cause miRNA changes in BMSCs. miR-132-3p and miR-335 may be important in steroid-induced ONFH.

Glycosaminoglycan Content of the Lateral Compartment Cartilage in Knees Conforming to the Indications for Oxford Medial Unicompartmental Knee Arthroplasty.

BACKGROUND: The quality of the lateral compartment cartilage is important to preoperative evaluation and prognostic prediction of unicompartmental knee arthroplasty (UKA). Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) enables noninvasive assessment of glycosaminoglycan (GAG) content in cartilage. This study aimed to determine the GAG content of the lateral compartment cartilage in knees scheduled to undergo Oxford medial UKA. METHODS: From December 2016 to May 2017, twenty patients (20 osteoarthritic knees) conforming to the indications for Oxford medial UKA were included as the osteoarthritis (OA) group, and 20 healthy volunteers (20 knees) paired by sex, knee side, age (±3 years), and body mass index (BMI) (±3 kg/m2) were included as the control group. The GAG contents of the weight-bearing femoral cartilage (wbFC), the posterior non-weight-bearing femoral cartilage (pFC), the lateral femoral cartilage (FC), and tibial cartilage (TC) were detected using dGEMRIC. The dGEMRIC indices (T1Gd) were calculated in the middle three consecutive slices of the lateral compartment. Paired t-tests were used to compare the T1Gd in each region of interest between the OA group and control group. RESULTS: The average age and BMI in the two groups were similar. In the OA group, T1Gd of FC and TC was 386.7 ± 50.7 ms and 429.6 ± 59.9 ms, respectively. In the control group, T1Gd of FC and TC was 397.5 ± 52.3 ms and 448.6 ± 62.5 ms, respectively. The respective T1Gd of wbFC and pFC was 380.0 ± 47.8 ms and 391.0 ± 66.3 ms in the OA group and 400.3 ± 51.5 ms and 393.6 ± 57.9 ms in the control group. Although the T1Gd of wbFC and TC tended to be lower in the OA group than the control group, there was no significant difference between groups in the T1Gd in any of the analyzed cartilage regions (P value of wbFC, pFC, FC, and TC was 0.236, 0.857, 0.465, and 0.324, respectively). CONCLUSIONS: The GAG content of the lateral compartment cartilage in knees conforming to indications for Oxford medial UKA is similar with those of age- and BMI-matched participants without OA.

Quantitative Evaluation of Joint Space Width in the Lateral Compartment after Medial Unicompartmental Knee Arthroplasty: Comparison of Three Radiographic Views.

Lateral compartment cartilage deterioration is the most common complication affecting medial unicompartmental knee arthroplasty (UKA) survivorship. The purpose of this study was to determine the best method of judging the degeneration of cartilage in the lateral compartment after medial UKA through analysis of different radiographic views. Forty-two participants were divided into two groups. Patients in Group A were followed for at least 10 months after undergoing a medial UKA (mean: 17.67 ± 7.65 months, range: 10-24 months), whereas those in Group B were evaluated 3 days after surgery. Joint space width in the lateral compartment of all patients was evaluated using three types of knee radiographs: weight-bearing anterior posterior (AP), supine AP, and supine valgus stress. No difference in joint space width in the lateral compartment after medial UKA was found for the three kinds of radiographs in Group A (F = 0.97, p = 0.39) and Group B (F = 1.499, p = 0.233). After evaluating the patients 3 days after surgery or following them for approximately 18 months after medial UKA, we determined that weight-bearing AP, supine AP, and supine valgus stress knee radiographs were comparable when used to assess residual cartilage thickness of the lateral compartment.