Histologic and biomechanical evaluation of the thoracolumbar fascia graft for massive rotator cuff tears in a rat model.

BACKGROUND: Fascial autografts, which are easily available grafts, have provided a promising option in patients with massive rotator cuff tears. However, no fascial autografts other than the fascia lata have been reported, and the exact healing process of the fascia-to-bone interface is not well understood. The objective of this study is to histologically and biomechanically evaluate the effect of the thoracolumbar fascia (TLF) on fascia-to-bone healing. METHODS: A total of 88 rats were used in this study. Eight rats were killed at the beginning to form an intact control group, and the other rats were divided randomly into 2 groups (40 rats per group): the TLF augmentation group (TLF group) and the repair group (R group). The right supraspinatus was detached, and a 3 × 5 mm defect of the supraspinatus was created. The TLF was used to augment the torn supraspinatus in the TLF group, whereas in the R group, the torn supraspinatus was repaired in only a transosseous manner. Histology and biomechanics were assessed at 1, 2, 4, 8, and 16 weeks postoperatively. RESULTS: The modified tendon maturation score of the TLF group was higher than that of the R group at 8 weeks (23.00 ± 0.71 vs. 24.40 ± 0.89, P = .025) and 16 weeks (24.60 ± 0.55 vs. 26.40 ± 0.55, P ≤ .001). The TLF group showed a rapid vascular reaction, and the peak value appeared at 1 week. Later, the capillary density decreased, and almost no angiogenesis was observed at 8 weeks postoperatively. Immunohistochemistry results demonstrated a significantly higher percentage of collagen I in the TLF group at 4, 8, and 16 weeks (24.78% ± 2.76% vs. 20.67% ± 2.11% at 4 weeks, P = .046; 25.46% ± 1.77% vs. 21.49% ± 2.33% at 8 weeks, P = .026; 34.77% ± 2.25% vs. 30.01% ± 3.17% at 16 weeks, P = .040) postoperatively. Biomechanical tests revealed that the ultimate failure force in the TLF group was significantly higher than that in the R group at the final evaluation (29.13 ± 2.49 N vs. 23.10 ± 3.47 N, P = .022). CONCLUSIONS: The TLF autograft can promote a faster biological healing process and a better fixation strength. It could be used as an alternative reinforcement or bridging patch when the fascia lata is not appropriate or available for superior capsule reconstruction (SCR).

Case-Specific Focal Sensor Design for Cardiac Electrical Impedance Tomography.

Electrical impedance tomography (EIT) is a non-invasive detection technology that uses the electrical response value at the boundary of an observation field to image the conductivity changes in an area. When EIT is applied to the thoracic cavity of the human body, the conductivity change caused by the heartbeat will be concentrated in a sub-region of the thoracic cavity, that is, the heart region. In order to improve the spatial resolution of the target region, two sensor optimization methods based on conformal mapping theory were proposed in this study. The effectiveness of the proposed method was verified by simulation and phantom experiment. The qualitative analysis and quantitative index evaluation of the reconstructed image showed that the optimized model could achieve higher imaging accuracy of the heart region compared with the standard sensor. The reconstruction results could effectively reflect the periodic diastolic and systolic movements of the heart and had a better ability to recognize the position of the heart in the thoracic cavity.

Aspirin inhibits adipogenesis of tendon stem cells and lipids accumulation in rat injury tendon through regulating PTEN/PI3K/AKT signalling.

Tendon injury repairs are big challenges in sports medicine, and fatty infiltration after tendon injury is very common and hampers tendon injury healing process. Tendon stem cells (TSCs), as precursors of tendon cells, have shown promising effect on injury tendon repair for their tenogenesis and tendon extracellular matrix formation. Adipocytes and lipids accumulation is a landmark event in pathological process of tendon injury, and this may induce tendon rupture in clinical practice. Based on this, it is important to inhibit TSCs adipogenesis and lipids infiltration to restore structure and function of injury tendon. Aspirin, as the representative of non-steroidal anti-inflammatory drugs (NSAIDs), has been widely used in tendon injury for its anti-inflammatory and analgesic actions, but effect of aspirin on TSCs adipogenesis and fatty infiltration is still unclear. Under adipogenesis conditions, TSCs were treated with concentration gradient of aspirin. Oil red O staining was performed to observe changes of lipids accumulation. Next, we used RNA sequencing to compare profile changes of gene expression between induction group and aspirin-treated group. Then, we verified the effect of filtrated signalling on TSCs adipogenesis. At last, we established rat tendon injury model and compared changes of biomechanical properties after aspirin treatment. The results showed that aspirin decreased lipids accumulation in injury tendon and inhibited TSCs adipogenesis. RNA sequencing filtrated PTEN/PI3K/AKT signalling as our target. After adding the signalling activators of VO-Ohpic and IGF-1, inhibited adipogenesis of TSCs was reversed. Still, aspirin promoted maximum loading, ultimate stress and breaking elongation of injury tendon. In conclusion, by down-regulating PTEN/PI3K/AKT signalling, aspirin inhibited adipogenesis of TSCs and fatty infiltration in injury tendon, promoted biomechanical properties and decreased rupture risk of injury tendon. All these provided new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy.

Interleukin-15 facilitates muscle regeneration through modulation of fibro/adipogenic progenitors.

BACKGROUND: Chronic muscle injury is characteristics of fatty infiltration and fibrosis. Recently, fibro/adipogenic progenitors (FAPs) were found to be indispensable for muscular regeneration while were also responsible for fibrosis and fatty infiltration in muscle injury. Many myokines have been proven to regulate the adipose or cell proliferation. Because the fate of FAPs is largely dependent on microenvironment and the regulation of myokines on FAPs is still unclear. We screened the potential myokines and found Interleukin-15 (IL-15) may regulate the fatty infiltration in muscle injury. In this study, we investigated how IL-15 regulated FAPs in muscle injury and the effect on muscle regeneration. METHODS: Cell proliferation assay, western blots, qRT-PCR, immunohistochemistry, flow cytometric analysis were performed to investigate the effect of IL-15 on proliferation and adipogensis of FAPs. Acute muscle injury was induced by injection of glycerol or cardiotoxin to analyze how IL-15 effected on FAPs in vivo and its function on fatty infiltration or muscle regeneration. RESULTS: We identified that the expression of IL-15 in injured muscle was negatively associated with fatty infiltration. IL-15 can stimulate the proliferation of FAPs and prevent the adipogenesis of FAPs in vitro and in vivo. The growth of FAPs caused by IL-15 was mediated through JAK-STAT pathway. In addition, desert hedgehog pathway may participate in IL-15 inhibiting adipogenesis of FAPs. Our study showed IL-15 can cause the fibrosis after muscle damage and promote the myofiber regeneration. Finally, the expression of IL-15 was positively associated with severity of fibrosis and number of FAPs in patients with chronic rotator cuff tear. CONCLUSIONS: These findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.

Safety and clinical efficacy of double posterolateral coaxial portals for endoscopic management of posterior ankle impingement syndrome.

Background: This study aims to analyze the safety and clinical efficacy of using double posterolateral coaxial portals for endoscopic treatment of posterior ankle impingement syndrome (PAIS), a procedure that has gained popularity in recent times. Methods: Six fresh foot samples were randomly selected to measure the distances of two posterolateral portals to the sural nerve in different positions (plantar flexion 10°, dorsiflexion 30°, and plantar flexion 30°) for safety evaluation. A prospective analysis was conducted on the clinical efficacy of the operative approach for endoscopic management of posterior ankle impingement syndrome, including evaluation of effectiveness and complications. Results: In this study, the mean distances of the first and second portals to the sural nerve were measured in different ankle positions. The distances were found to be 2.26 ± 0.22 cm and 1.59 ± 0.12 cm in the plantar flexion 10° position, 2.21 ± 0.21 cm and 1.55 ± 0.12 cm in the dorsiflexion 30° position, and 2.46 ± 0.29 cm and 1.73 ± 0.19 cm in the plantar flexion 30° position, demonstrating a significant safety margin from the nerve. A total of 38 patients underwent endoscopic treatment for posterior ankle impingement syndrome using double posterolateral coaxial portals between January 2012 and December 2017. This surgical approach provided access to the subtalar joint and posterior ankle region. The patients were followed up for an average of 38.2 months (24-72 months), with a satisfaction rate of 94.7%. There were no reported complications, and significant improvements were observed in both visual analogue scale (VAS) and The American Orthopedic Foot and Ankle Society Score (AOFAS) scores postoperatively. The VAS score decreased from 5.68 to 0.51 (P < 0.001), while the AOFAS score increased from 71.68 to 92.34 (P < 0.001), resulting in an excellent/good rate of 97.3%. Conclusion: The use of double posterolateral coaxial portals in the treatment of posterior ankle impingement syndrome offers several advantages, including improved safety, reduced risk of nerve injury, enhanced visualization of the posterior ankle and subtalar joint, favorable clinical outcomes, and minimal complications.

Copper modified cobalt-chromium particles for attenuating wear particle induced-inflammation and osteoclastogenesis.

The nature of aseptic prosthetic loosening mainly relates to the wear particles that induce inflammation and subsequent osteoclastogenesis. The ideal approach to impede wear particle-induced osteolysis should minimize inflammation and osteoclastogenesis. In this work, Co29Cr9W3Cu particles were used as a research model for the first time to explore the response of Co29Cr9W3Cu particles to inflammatory response and osteoclast activation in vitro and in vivo by using Co29Cr9W particles as the control group. In vitro studies showed that the Co29Cr9W3Cu particles could promote the generation of M2-phenotype macrophages and increase the expression level of anti-inflammatory factor IL-10, while inhibiting the formation of M1-phenotype macrophages and down-regulating the expression of inflammatory factors TNF-α, IL-6 and IL-1ß; More importantly, the Co29Cr9W3Cu particles reduced the expression of NF-κB and downstream osteoclast related-specific transcription marker genes, such as TRAP, NFATc1, and Cath-K; In vivo results indicated that the Co29Cr9W3Cu particles exposed to murine calvarial contributed to decreasing the amount of osteoclast and osteolysis area. These findings collectively demonstrated that Cu-bearing cobalt-chromium alloy may potentially delay the development of aseptic prosthetic loosening induced by wear particles, which is expected to provide evidence of Co29Cr9W3Cu alloy as an alternative material of joint implants with anti-wear associated osteolysis.

Silkworm spinning inspired 3D printing toward a high strength scaffold for bone regeneration.

Inspired by the silkworm spinning process for production of tough cocoons, a gradient printing-assembly technique with silk fibroin (SF) and hydroxyapatite (HA) to achieve high strength scaffolds for bone regeneration is developed. A coaxial extrude-nozzle is employed to provide gathered thickening and shearing for aligned assembly. The aligned SF-HA assembles into the compacted nanostructure, which performs a maximum compressive strength of 166 MPa and bending strength of 40 MPa. Scaffolds with various morphologies could be arbitrarily constructed via extruded 3D printing for the regeneration of cortical bone or cancellous bone. The hemolysis quantification of red blood cells (RBCs), proliferation and flow cytometry of bone marrow stem cells (BMSCs) have proved the excellent biocompatibility of the printed scaffolds. Osteogenic induced differentiation assay in vitro and surgical intervention for rat femoral defect repairing have verified the successful osteogenesis with high mechanical strength and remarkable stability in the physiological environment. The silkworm spinning inspired 3D printing offers a facile approach for the fabrication of implantable scaffolds with high strength and excellent biocompatibility, which is highly desired for the applications of bone tissue engineering.

Structural Engineering of Hollow Microflower-like CuS@C Hybrids as Versatile Electrochemical Sensing Platform for Highly Sensitive Hydrogen Peroxide and Hydrazine Detection.

Designing metal sulfides with unique configurations and exploring their electrochemical activities for hydrogen peroxide (H2O2) and hydrazine (N2H4) is challenging and desirable for various fields. Herein, hollow microflower-like CuS@C hybrids were successfully assembled and further exploited as a versatile electrochemical sensing platform for H2O2 reduction and N2H4 oxidation, of which the elaborate strategies make the perfect formation of hollow architecture, providing considerable electrocatalytic sites and fast charge transfer rate, while the appropriate introduction polydopamine-derived carbon skeleton facilitates the electronic conductivity and boosts structural robustness, thus generating wide linear range (0.05-14 and 0.01-10 mM), low detection limit (0.22 µM and 0.07 µM), and a rather low overpotential (-0.15 and -0.05 V) toward H2O2 and N2H4, as well as good selectivity, excellent reproducibility, and admirable long-term stability. It should be highlighted that the operating potentials can compare favorably with those of some reported H2O2 and N2H4 sensors based on noble metals. In addition, good recoveries and acceptable relative standard deviations (RSDs) attained in serum and water samples fully verify the accuracy and anti-interference capability of our proposed sensor systems. These results not only elucidate an effective structural nanoengineering strategy for electroanalytical science but also advance the rational utilization of H2O2 and N2H4 in practicability.

Femtosecond laser-induced periodic grooves and nanopore clusters make a synergistic effect on osteogenic differentiation.

Polyether-ether-ketone (PEEK) materials have good biocompatibility, excellent corrosion resistance, chemical stability and an elastic modulus close to that of natural bone. However, due to its biological inertness, PEEK may affect osteogenic differentiation and leads to osseointegration failure, though PEEK is expected to improve osseointegration. In this work, by changing the power of femtosecond laser, micro-grooves are made on the PEEK surface. As observed by scanning electron microscopy, the trench has a periodic structure, the micro shape is neat, and the trench is also covered with nanometer-level pore clusters. In the in vitro culture experiments, through the proliferation experiment of mouse bone marrow mesenchymalstem cells (mBMSCs), cell viability analysis and alkaline phosphatase activity analysis, it is proven that after femtosecond laser treatment of the PEEK surface, the micro-grooves on the surface and the nanopore clusters due to laser energy ablation can produce a synergistic effect, enhancing the osteogenic differentiation ability of cells, and improving the bone integration ability of PEEK materials.

[Three-dimensional printed Ti6Al4V-4Cu alloy promotes osteogenic gene expression through bone immune regulation].

OBJECTIVE: To investigate the effects of three-dimensional (3D) printed Ti6Al4V-4Cu alloy on inflammation and osteogenic gene expression in mouse bone marrow mesenchymal stem cells (BMSCs) and mouse mononuclear macrophage line RAW264.7. METHODS: Ti6Al4V and Ti6Al4V-4Cu alloys were prepared by selective laser melting, and the extracts of the two materials were prepared according to the biological evaluation standard of medical devices. The effects of two kinds of extracts on the proliferation of mouse BMSCs and mouse RAW264.7 cells were detected by cell counting kit 8 method. After co-cultured with mouse BMSCs for 3 days, the expression of osteogenesis- related genes [collagen type Ⅰ (Col-Ⅰ), alkaline phosphatase (ALP), Runx family transcription factor 2 (Runx-2), osteoprotegerin (OPG), and osteopontin (OPN)] were detected by real-time fluorescence quantitative PCR. After co-cultured with mouse RAW264.7 cells for 1 day, the expressions of inflammation-related genes [interleukin 4 (IL-4) and nitric oxide synthase 2 (iNOS)] were detected by real-time fluorescence quantitative PCR, and the supernatants of the two groups were collected to detect the secretion of vascular endothelial growth factor a (VEGF-a) and bone morphogenetic protein 2 (BMP-2) by ELISA. The osteogenic conditioned medium were prepared with the supernatants of the two groups and co-cultured with BMSCs for 3 days. The expressions of osteogenesis-related genes (Col-Ⅰ, ALP, Runx-2, OPG, and OPN) were detected by real-time fluorescence quantitative PCR. RESULTS: Compared with Ti6Al4V alloy extract, Ti6Al4V-4Cu alloy extract had no obvious effect on the proliferation of BMSCs and RAW264.7 cells, but it could promote the expression of OPG mRNA in BMSCs, reduce the expression of iNOS mRNA in RAW264.7 cells, and promote the expression of IL-4 mRNA. It could also promote the secretions of VEGF-a and BMP-2 in RAW264.7 cells. Ti6Al4V-4Cu osteogenic conditioned medium could promote the expressions of Col-Ⅰ, ALP, Runx-2, OPG, and OPN mRNAs in BMSCs. The differences were all significant ( P<0.05). CONCLUSION: 3D printed Ti6Al4V-4Cu alloy can promote RAW264.7 cells to secret VEGF-a and BMP-2 by releasing copper ions, thus promoting osteogenesis through bone immune regulation, which lays a theoretical foundation for the application of metal prosthesis.