Lubricin Surface Modification Improves Tendon Gliding After Tendon Repair in a Canine Model In Vitro

Introduction: The role of friction as a source of adhesions has been recently investigated, with data suggesting that many strong repairs also have higher friction [1], and that this higher friction is associated with poorer results, at least in animal models [2]. Lubricin is a mucinous glycoprotein responsible for the boundary lubrication of articular cartilage [3,4]. Recent studies have identified lubricin on the surface of FDP tendon [5,6] suggesting that it may play a role in tendon lubrication. Tendon surface modification with gelatin and hyaluronic acid reduces the gliding resistance of both tendon graft and repaired tendon [7][8][9]. The purpose of this study was to investigate the effects of lubricin with or without hyaluronic acid (HA) on the gliding of repaired FDP tendon in a canine model in vitro. Materials and Methods: 32 flexor digitorum profundus (FDP) tendons from the 2nd -5th digits of forepaws from 4 adult mongrel dogs were used. The dogs were sacrificed for other IACUC approved projects. In each digit the proximal and middle phalanges, FDP tendon, flexor digitorum superficialis (FDS) tendon and FDS insertion, and proximal pulley were then harvested as a unit. The proximal interphalangeal joint was fixed in full extension. A complete laceration to the FDP tendon was made 6mm distal to the proximal pulley (analogous to the A2 pulley in humans) and repaired with a modified Pennington technique. After the gliding resistance of the repaired tendon was measured in vitro, the tendons were treated with one of four solutions (n=8 per group): Saline; 10% gelatin/1% HA/1% EDC (1-ethyl-3-(3-dimethylaminopropyl) carbdiimide hydrochloride) /1% NHS (Nhydroxysuccinimde) (cd-HA-gelatin); 10% gelatin/1% EDC/1% NHS + lubricin (cd-gelatin + lubricin); 10% gelatin/1% HA/1% EDC/1% NHS+ lubricin (cd-HA-gelatin + lubricin). Lubricin was purified from bovine synovial fluid [10]. After treatment, tendon gliding resistance was measured for 1000 cycles of simulated flexion/extension tendon motion. The average and peak gliding resistance over the flexion/extension cycle were calculated and compared to baseline. Treatment groups were compared using ANOVA. Following testing, the surface of the repaired tendon and its proximal pulley was also assessed qualitatively for surface smoothness by scanning electron microscopy. Results: The increase in average and peak gliding resistance in cd-HA-gelatin, cd-gelatin+lubricin, and cd-HA-gelatin+ lubricin tendons was significantly less than that of the saline control tendons after 1000 cycles (p<0.05) Discussion: In this study, the cd-HA-gelatin, cd-gelatin+lubricin and cd-HAgelatin+lubricin all improved the gliding resistance of the repaired flexor tendon compared to the saline controls. The two lubricin treated groups had the lowest gliding resistance throughout testing. The cd-HA-gelatin+lubricin tendons were significantly lower than the tendons treated with cd-HA-gelatin alone. While not significant, there was clearly a trend for improved results with cd-gelatin+lubricin, as well. The addition of lubricin to a tendon surface pre-treated with cd-gelatin and HA significantly reduces gliding resistance and maintains a qualitatively smooth tendon and pulley surface after 1000 cycles of simulated flexion/extension tendon motion compared to the carbodiimide derivatized hyaluronic acid (cd-HA-gelatin) preparation alone. These findings may have important implications for the development of tissue engineered tendon surfaces to improve the results after tendon repair

Characterization of Full-Length Enterovirus 71 Strains from Severe and Mild Disease Patients in Northeastern China

Human enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) has been a leading cause of childhood infection in China since 2008. Epidemic and molecular characteristics of HFMD have been examined in many areas of China, including the central and southern regions. However, clinical and genetic characterization of EV71 in the northeastern region of China is scarce. In this study, a series of analyses were performed on seven full-length EV71 sequences from HFMD patients who had either severe or mild disease. We have determined that these seven circulating EV71 viruses from Changchun, China are actually complex recombinant viruses involving multiple type A human enterovirus (HEV). Classified as EV71 subtype C4 (EV71 C4), these Changchun EV71 viruses contain genetic recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the structural protein region (P1) of these viruses resembled that of the prototype EV71 C1 strains. The non-structural protein domains (P2 and P3) showed a high degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5′UTR had unclassified recombination,while partial 3D region of these viruses showed a high degree of similarity to CA16. Phylogenetic analysis of full-length or partial sequences of isolates from severe or mild disease patients in Changchun always formed a single cluster in various phylogenetic analyses of different genomic regions, suggesting that all seven strains originated from one single common ancestor. There was no correlation between viral genomic sequence and virulence. Thus, we found that circulating recombinant forms of EV71 are prevalent among HFMD patients in Northeastern China. The existence of a unique cluster of EV71 related viruses in Northeast China has important implications for vaccine development that would address the increasing prevalence of HFMD

A Modified Sagittal Spine Postural Classification and Its Relationship to Deformities and Spinal Mobility in a Chinese Osteoporotic Population

BACKGROUND: Abnormal posture and spinal mobility have been demonstrated to cause functional impairment in the quality of life, especially in the postmenopausal osteoporotic population. Most of the literature studies focus on either thoracic kyphosis or lumbar lordosis, but not on the change of the entire spinal alignment. Very few articles reported the spinal alignment of Chinese people. The purpose of this study was threefold: to classify the spinal curvature based on the classification system defined by Satoh consisting of the entire spine alignment; to identify the change of trunk mobility; and to relate spinal curvature to balance disorder in a Chinese population. METHODOLOGY/PRINCIPAL FINDINGS: 450 osteoporotic volunteers were recruited for this study. Spinal range of motion and global curvature were evaluated noninvasively using the Spinal-Mouse® system and sagittal postural deformities were characterized. RESULTS: We found a new spine postural alignment consisting of an increased thoracic kyphosis and decreased lumbar lordosis which we classified as our modified round back. We did not find any of Satoh's type 5 classification in our population. Type 2 sagittal alignment was the most common spinal deformity (38.44%). In standing, thoracic kyphosis angles in types 2 (58.34°) and 3 (58.03°) were the largest and lumbar lordosis angles in types 4 (13.95°) and 5 (-8.61°) were the smallest. The range of flexion (ROF) and range of flexion-extension (ROFE) of types 2 and 3 were usually greater than types 4 and 5, with type 1 being the largest. CONCLUSIONS/SIGNIFICANCE: The present study classified and compared for the first time the mobility, curvature and balance in a Chinese population based on the entire spine alignment and found types 4 and 5 to present the worst balance and mobility. This study included a new spine postural alignment classification that should be considered in future population studies

Recent Advances in Ultrasound Diagnosis of Carpal Tunnel Syndrome

With the widespread use of high-resolution ultrasonography, ultrasonic examination has been shown to be useful as a diagnostic method for carpal tunnel syndrome. The main advantages of ultrasonography are that it is simple, quick, non-invasive, and economical. Another advantage is that tissue dynamics can be observed with real-time imaging. In recent reports, it has been shown that ultrasonic examination can provide similar diagnostic accuracy as nerve conduction study in the diagnosis of carpal tunnel syndrome. It has been expected that ultrasound demand in daily medical care will continue to increase. Ultrasonography in carpal tunnel syndrome shows an enlarged median nerve in proximal carpal tunnel, thickening of the flexor retinaculum, and edema around flexor tendons in cross-sectional images. In addition, with the introduction of new technologies such as ultrasonic elastography and speckle tracking, it has become possible to quantify dynamics and material property changes of nerves, tendons, and their surrounding structures. In this review, we describe recent advancements of carpal tunnel syndrome diagnosis based on ultrasound dynamic images, and discuss its pathology

The gliding characteristics of the flexor pollicis longus tendon in the carpal tunnel: potential implications for manual pipette users.

To understand the potential mechanism for hand and wrist complaints in pipette users, whose motion is characterized by repetitive thumb motion in certain wrist positions, the peak (PGR) and mean (MGR) gliding resistance of the flexor pollicis longus (FPL) tendon were measured in nine human cadaver wrists. The PGR with the wrist in 30° ulnar deviation and in the neutral position were significantly lower than the PGR with the wrist in 60° flexion. The MGR with the wrist in 30° ulnar deviation was significantly lower than the MGR with the wrist in 60° flexion, 60° extension, or 20° radial deviation with 40° extension. Based on these data, we believe that a manual pipette designed to be used in neutral to ulnar deviated wrist position could have ergonomic advantages

Apoptotic Body-Rich Media from Tenocytes Enhance Proliferation and Migration of Tenocytes and Bone Marrow Stromal Cells

The intrinsic healing following tendon injury is ideal, in which tendon progenitor cells proliferate and migrate to the injury site to directly bridge or regenerate tendon tissue. However, the mechanism determining why and how those cells are attracted to the injury site for tendon healing is not understood. Since the tenocytes near the injury site go through apoptosis or necrosis following injury, we hypothesized that secretions from injured tenocytes might have biological effects on cell proliferation and migration to enhance tendon healing. Tenocyte apoptosis was induced by 24 h cell starvation. Apoptotic body-rich media (T-ABRM) and apoptotic body-depleted media (T-ABDM) were collected from culture media after centrifuging. Tenocytes and bone marrow-derived stem cells (BMDSCs) were isolated and cultured with the following four media: (1) T-ABRM, (2) T-ABDM, (3) GDF-5, or (4) basal medium with 2% fetal calf serum (FCS). The cell activities and functions were evaluated. Both T-ABRM and T-ABDM treatments significantly stimulated the cell proliferation, migration, and extracellular matrix synthesis for both tenocytes and BMDSCs compared to the control groups (GDF-5 and basal medium). However, cell proliferation, migration, and extracellular matrix production of T-ABRM-treated cells were significantly higher than the T-ABDM, which indicates the apoptotic bodies are critical for cell activities. Our study revealed the possible mechanism of the intrinsic healing of the tendon in which apoptotic bodies, in the process of apoptosis, following tendon injury promote tenocyte and stromal cell proliferation, migration, and production. Future studies should analyze the components of the apoptotic bodies that play this role, and, thus, the targeting of therapeutics can be developed

A Canine Non-Weight-Bearing Model with Radial Neurectomy for Rotator Cuff Repair.

The major concern of using a large animal model to study rotator cuff repair is the high rate of repair retears. The purpose of this study was to test a non-weight-bearing (NWB) canine model for rotator cuff repair research.First, in the in vitro study, 18 shoulders were randomized to 3 groups. 1) Full-width transections repaired with modified Mason-Allen sutures using 3-0 polyglactin suture, 2) Group 1 repaired using number 2 (#2) polyester braid and long-chain polyethylene suture, and 3) Partial-width transections leaving the superior 2 mm infraspinatus tendon intact without repair. In the in vivo study of 6 dogs, the infraspinatus tendon was partially transected as the same as the in vitro group 3. A radial neurectomy was performed to prevent weight bearing. The operated limb was slung in a custom-made jacket for 6 weeks.In the in vitro study, mean ultimate tensile load and stiffness in Group 2 were significantly higher than Group 1 and 3 (p<0.05). In the in vivo study, gross inspection and histology showed that the preserved superior 2-mm portion of the infraspinatus tendon remained intact with normal structure.Based on the biomechanical and histological findings, this canine NWB model may be an appropriate and useful model for studies of rotator cuff repair