Paradoxical Changes of Cutaneous Microcirculation and Sympathetic Fibers of Rat Hind Limbs after Sciatic Nerve Compression.

BACKGROUND: Recent studies show evidence that surgical nerve decompression could improve cutaneous blood flow (CBF), which might benefit ulcer healing. However, the change of CBF and sympathetic fibers after nerve compression is poorly understood. In the current study, a unilateral sciatic nerve compression model was created in Sprague-Dawley rats. METHODS: A laser Doppler imaging system was applied to assess the CBF of the regions below the ankles. Immunohistochemistry and transmission electron microscopy were used to investigate the histopathologic changes of sympathetic fibers in sciatic nerve samples. RESULTS: Laser Doppler imaging revealed decreased CBF of both the lesional limb and the contralesional limb, which occurred earlier in the lesional side, indicating an enhanced sympathetic tone on vasomotor function. Intraneural density of sympathetic fibers decreased on both sides and the ultrastructure of unmyelinated fibers of both sides degenerated in a nonsynchronized manner. CONCLUSIONS: The study revealed nonsynchronized reduced CBF of bilateral hind limbs with paradoxically degenerated and diminished sympathetic fibers in bilateral sciatic nerves after unilateral sciatic nerve compression. These results may validate the importance of and broaden the indications for surgical nerve decompression in preventing or treating foot ulcers.

Effect of different structures fabricated by additive manufacturing on bone ingrowth.

OBJECTIVE: To study the effects of different structures (solid/hollow) and pore diameters (300/600 µm) on bone ingrowth. METHODS: Porous titanium alloy scaffolds (3.2 * 10.5 mm) were printed using electron beam melting. The implants were divided into either Hollow or Solid Group. The upper half of each implant was printed with a pore diameter of 600 µm while the bottom half was printed with a pore diameter of 300 µm. Visualization of the structural morphology was done using Scanning Electron Microscope (SEM). Cell proliferation was evaluated with the cell counting kit-8 assay and live/dead staining assay. The different lateral femoral condyles of 15 New Zealand rabbits were implanted with different groups of scaffolds. The rabbits were randomly sacrificed at the 4th, 8th, and 12th week postoperatively. Bone mineral density (BMD) and bone volume fraction (BV/TV) evaluation was completed by quantitative Micro-Computed Tomography (Micro-CT). Tissue histology were stained with toluidine blue to observe bone ingrowth under an optical microscope, and the percentage of new bone area were calculated using Image Pro-Plus 6.0. RESULTS: SEM images showed a significant decrease in residual powder in the hollow implant and cell studies showed no obvious cytotoxicity for the Ti6Al4V scaffolds. Micro-CT reconstruction revealed high levels of new bone formation around the scaffolds. The trabeculae around the implants showed a gradual increase with each week, and new bone filled the scaffold pores gradually. BMD, BV/TV, and tissue histology revealed the 300 µm pore diameter is more conducive to bone ingrowth than the 600 µm (p < .05). CONCLUSION: Our study revealed that Ti6Al4V implants with hollow structure could reduce the residual metal powder and implants with 300 µm pore diameter were more effective on bone formation than a 600 µm.

Hypoxia Inducible Factor-1α Is a Regulator of Autophagy in Osteoarthritic Chondrocytes.

OBJECTIVE: To investigate the relationship between hypoxia inducible factor-1α (HIF-1α) and the autophagic response in osteoarthritic chondrocytes (OA), under inflammatory insult as represented by in vitro OA model. METHODS: Human chondrocyte cell line C28/I2 was cultured in both normoxic and hypoxic conditions and treated with interleukin-1ß (IL1ß) to emulate OA inflammatory insult in vitro. Cellular HIF-1α expression was silenced using siRNA transfection and cellular autophagic (P62/LC3II) response and OA chondrocyte damage (COL2A1/MMP13) related proteins were examined using western blotting. Cellular mitophagic (BNIP3/PINK1/Parkin) and apoptotic (Caspase/Cleaved Caspase 3) were also evaluated to assess mitophagy-mediated cell death due to HIF-1α silencing. RESULTS: Chondrocyte basal autophagy levels were higher in a HIF-1α elevated environment and was more resistant to IL1ß-induced inflammatory insult. Increase in autophagic proteins showed better chondrocyte repair, which resulted a lower level of reactive oxygen species production, and lesser damage to chondrocyte integrity. Silencing HIF-1α activates cellular PINK1/Parkin and BNIP3 mitophagic proteins, which leads to the activation of Caspase/Cleaved Caspase 3 apoptotic cascade. CONCLUSION: Our results show that chondrocyte autophagy is dependent on HIF-1α expression, showing the importance of HIF-1α in hypoxic chondrocyte function in OA. Dysregulation of HIF-1α expression results in the activation of mitophagy-mediated apoptosis.

Electrical Muscle Stimulation Accelerates Functional Recovery After Nerve Injury.

Electrical muscle stimulation has been demonstrated to facilitate nerve regeneration and functional recovery, but the underlying mechanism remains only partially understood. In this study, we investigated the positive effect of electrical muscle stimulation following nerve injury and its molecular mechanisms of autophagy regulation. The sciatic nerves of Sprague-Dawley rats were transected and immediately repaired. Gastrocnemius muscles were electrically stimulated using surface electrodes. Motor functional recovery was assessed by gait analysis, nerve conduction examination and histological appearance of the target muscle. Axon regeneration was investigated by morphometric analysis. Western blotting and immunofluorescence staining were used to detect the expression of molecular biological changes in distal nerve stump. Ultrastructural features of the nerve were evaluated by transmission electron microscope. We found that axon regeneration and motor functional recovery were improved by electrical muscle stimulation. The number of autophagosomes and the expression of autophagy marker LC3-Ⅱ in distal nerve stump were increased while the level of autophagy substrate protein P62 was decreased following electrical muscle stimulation. Blockage of the autophagy flux by chloroquine (CQ) diminished the positive effect of electrical muscle stimulation on nerve injury. These results illustrated that electrical muscle stimulation accelerates axon regeneration and functional recovery through promoting autophagy flux in distal nerve segments following nerve injury and immediate repair (IR) by a so far unknown mechanism.

Management strategies in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) also known as Landouzy-Dejerine disease, is an autosomal-dominant disorder of the skeletal muscles with the name according to the various muscle groups it affects: the face, shoulders and upper arms. It is the third most common genetic degenerative disorder of the skeletal muscles without specific patterns in all the affected individuals. At present there is no cure for the disease but numerous management strategies are available to improve the quality of life and prevent further degeneration of various muscle groups. This review aims to provide an insight on the management strategies for FSHD patients including both lifestyle and medical intervention.

Polyethylene on Cement Spacers: An Economic Approach to an Effective Infection Eradication in a Two-Stage Knee Revision Articulating Spacers.

Although two-stage revision surgery is generally considered as the gold standard treatment for periprosthetic joint infection (PJI) after total knee arthroplasty, the procedure is limited by the costs of commercially preformed spacers used for treatment. In this work, we aim to report a modified approach by which the cost of the spacer could be significantly reduced without compromising eradication of infection. Between 2010 and 2016, we performed a total of 11 two-stage revision arthroplasties using a surgically handmade spacer with a new polyethylene insert. Patients were aged 59 to 80 years old (mean 69.9 years), with a range of motion (ROM) between 20° and 65° on the affected knee (mean 46.4°) before the first-stage revision surgery. During the perioperative and postoperative period, functional and clinical evaluation of the patients were performed, including the determination of their articular ROM, Knee Society Knee Scores (KSKS), and Knee Society Function Scores (KSFS). All patients were followed up for an average of 2 years, ranging from 1 to 4 years. After the second-stage revision surgery, the mean ROM was increased by 46.8° (46.4°-93.2°) after the second-stage revision. KSKS and KSFS scores were recorded to increase by an average of 44.5° (range 40.4°-84.9°) and 46.9° (range 38.5°-85.4°), respectively. All 11 patients underwent a successful two-stage revision surgery, and no evidence of postsurgical infection was found during patient follow-up examination. Our results show that this personalized handmade antibiotic-loaded articulating spacer is cost-effective and efficacious.

Infection after total knee arthroplasty and its gold standard surgical treatment: Spacers used in two-stage revision arthroplasty.

Periprosthetic joint infection (PJI) is one of the most devastating postoperative complications of total knee arthroplasty (TKA). Treatment varies depending on the type of infection, but two-stage revision arthroplasty using an antibiotic spacer is considered to be the gold standard of treatment. Several types of spacers are available at the moment, each with different benefits and indications, and these spacers may be improved in the future. The primary goals of selecting a given spacer are to locally deliver antibiotics and to preserve soft tissue. Use of an appropriate spacer subsequently decreases the difficulty of the second revision, the operating time, and ultimately the risk of postoperative complications.

Sustained release vancomycin-coated titanium alloy using a novel electrostatic dry powder coating technique may be a potential strategy to reduce implant-related infection.

In order to tackle the implant-related infection, a novel way was developed in this study to coat vancomycin particles mixed with controlled release coating materials onto the surface of titanium alloy by using an electrostatic dry powder coating technique. To characterize this sustained release antibacterial coating, surface morphology, in vitro and in vivo drug release were sequentially evaluated. In vitro cytotoxicity was tested by Cell Counting Kit-8 (CCK-8) assay and cytological changes were observed by inverted microscope. The antibacterial properties against MRSA, including a bacterial growth inhibition assay and a colony-counting test by spread plate method were performed. Results indicated that the vancomycin-coated sample was biocompatible for Human osteoblast cell line MG-63 and displayed effective antibacterial ability against MRSA. The coating film was revealed uniform by scanning electron microscopy. Both the in vitro and in vivo drug release kinetics showed an initially high release rate, followed by an extended period of sustained drug release over 7 days. These results suggest that with good biocompatibility and antibacterial ability, the sustained release antibacterial coating of titanium alloy using our novel electrostatic dry powder coating process may provide a promising candidate for the treatment of orthopedic implant-related infection.