In Vivo Ultrasound Shear Wave Elastography Assessment of Acute Compartment Syndrome in a Turkey Model.

OBJECTIVE: The aim of the work described here was to evaluate the objectivity and reproducibility of non-invasive intra-compartment pressure (ICP) measurement using ultrasound shear wave elastography (SWE) in a turkey model in vivo and to determine the biological and histologic changes in acute compartment syndrome (ACS). METHODS: Twenty-four turkeys were randomly divided into four groups based on the duration and fasciotomy of ACS created by infusion of up to 50 mm Hg in the tibialis muscle: group 1, ACS 2 h; group 2, ACS 4 h; group 3, ACS 2 h + fasciotomy 2 h; group 4, ACS 4 h + fasciotomy 2 h. For each turkey, the contralateral limb was considered the control. Time-synchronized measures of SWE and ICP from each leg were collected. Then turkeys were euthanized for histology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) examination. RESULTS: All models created reproducible increases in ICP and SWE, which had a strong linear relationship (r = 0.802, p < 0.0001) during phase 1. SWE remained stable (50.86 ± 9.64 kPa) when ICP remained at 50.28 ± 2.17 mm Hg in phase 2. After fasciotomy, SWE declined stepwise and then normalized (r = 0.737, p < 0.0001). Histologically, the myofiber diameter of group 2 (82.31 ± 22.92 µm) and group 4 (90.90 ± 20.48 µm) decreased significantly (p < 0.01) compared with that of the control group (103.1 ± 20.39 µm); the interstitial space of all groups increased significantly (p < 0.01). Multifocal muscle damage revealed neutrophilic infiltration, degeneration, hemorrhage and necrosis, especially in group 4. Quantitative RT-PCR verified that interleukin-6 and heparin-binding EGF-like growth factor were significantly increased in group 4. CONCLUSION: SWE provided sensitive measurements correlating to ICP in a clinically relevant ACS animal model. Once ACS time was exceeded, progression to irreversible necrosis continued spontaneously, even after fasciotomy. SWE may help surgeons in the early detection, monitoring, prognosis and decision making on fasciotomy for ACS.

Carbodiimide-Derivatized Synovial Fluid for Tendon Graft Coating Improves Long-Term Functional Outcomes of Flexor Tendon Reconstruction.

BACKGROUND: Flexor digitorum profundus (FDP) tendon injury is common in hand trauma, and flexor tendon reconstruction is one of the most challenging procedures in hand surgery because of severe adhesion that exceeds 25% and hinders hand function. The surface properties of a graft from extrasynovial tendons are inferior to those of the native intrasynovial FDP tendons, which has been reported as one of the major causations. Improved surface gliding ability of the extrasynovial graft is needed. Thus, this study used carbodiimide-derivatized synovial fluid and gelatin (cd-SF-gel) to modify the surface of the graft, thus improving functional outcomes using a dog in vivo model. METHODS: Forty FDP tendons from the second and fifth digits of 20 adult women underwent reconstruction with a peroneus longus (PL) autograft after creation of a tendon repair failure model for 6 weeks. Graft tendons were either coated with cd-SF-gel ( n = 20) or not. Animals were euthanized 24 weeks after reconstruction, and digits were collected after the animals were euthanized for biomechanical and histologic analyses. RESULTS: Adhesion score (cd-SF-gel, 3.15 ± 1.53; control, 5 ± 1.26; P < 0.00017), normalized work of flexion (cd-SF-gel, 0.47 ± 0.28 N-mm/degree; control, 1.4 ± 1.45 N-mm/degree; P < 0.014), and distal interphalangeal joint motion (cd-SF-gel, 17.63 ± 6.77 degrees; control, 7.07 ± 12.99 degrees; P < 0.0015) in treated grafts all showed significant differences compared with nontreated grafts. However, there was no significant difference in repair conjunction strength between the two groups. CONCLUSION: Autograft tendon surface modification with cd-SF-gel improves tendon gliding ability, reduces adhesion formation, and enhances digit function without interfering with graft-host healing. CLINICAL RELEVANCE STATEMENT: The authors demonstrate a clinically relevant and translational technology by using the patient's own synovial fluid to "synovialize" an autologous extrasynovial tendon graft to improve functional outcomes following flexor tendon reconstruction.

KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction.

Progression of virtually all forms of chronic kidney disease (CKD) is associated with activation of pro-inflammatory and pro-fibrotic signaling pathways. Despite extensive research, progress in identifying therapeutic targets to arrest or slow progression of CKD has been limited by incomplete understanding of basic mechanisms underlying renal inflammation and fibrosis in CKD. Recent studies have identified Kruppel-like transcription factors that have been shown to play critical roles in renal development, homeostasis, and response to injury. Although KLF11 deficiency has been shown to increase collagen production in vitro and tissue fibrosis in other organs, no previous study has linked KLF11 to the development of CKD. We sought to test the hypothesis that KLF11 deficiency promotes CKD through upregulation of pro-inflammatory and pro-fibrogenic signaling pathways in murine unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis. We found that KLF11-deficiency exacerbates renal injury in the UUO model through activation of the TGF-ß/SMAD signaling pathway and through activation of several pro-inflammatory chemokine signaling pathways. Based on these considerations, we conclude that agents increase KLF11 expression may provide novel therapeutic targets to slow the progression of CKD.

Subsynovial connective tissue development in the rabbit carpal tunnel.

The carpal tunnel contains the digital flexor tendons and the median nerve, which are embedded in a unique network of fibrovascular interconnected subsynovial connective tissue (SSCT). Fibrous hypertrophy of the SSCT and subsequent adaptations in mechanical response are found in patients with carpal tunnel syndrome (CTS), but not much is known about the development of the SSCT. This observational study describes the morphological development of SSCT using histology and ultramicroscopy in an animal model at four time points between late-term fetuses through adulthood. A transition is seen between 3 days and 6 weeks post-partum from a dense solid SSCT matrix to a complex multilayered structure connected with collagenous fibrils. These preliminary data show a developmental pattern that matches an adaptive response of the SSCT to loading and motion. Understanding the anatomical development aids in recognizing the pathophysiology of CTS and supports research on new therapeutic approaches.

New transgenic NIS reporter rats for longitudinal tracking of fibrogenesis by high-resolution imaging.

Fibrogenesis is the underlying mechanism of wound healing and repair. Animal models that enable longitudinal monitoring of fibrogenesis are needed to improve traditional tissue analysis post-mortem. Here, we generated transgenic reporter rats expressing the sodium iodide symporter (NIS) driven by the rat collagen type-1 alpha-1 (Col1α1) promoter and demonstrated that fibrogenesis can be visualized over time using SPECT or PET imaging following activation of NIS expression by rotator cuff (RC) injury. Radiotracer uptake was first detected in and around the injury site day 3 following surgery, increasing through day 7-14, and declining by day 21, revealing for the first time, the kinetics of Col1α1 promoter activity in situ. Differences in the intensity and duration of NIS expression/collagen promoter activation between individual RC injured Col1α1-hNIS rats were evident. Dexamethasone treatment delayed time to peak NIS signals, showing that modulation of fibrogenesis by a steroid can be imaged with exquisite sensitivity and resolution in living animals. NIS reporter rats would facilitate studies in physiological wound repair and pathological processes such as fibrosis and the development of anti-fibrotic drugs.

Establishment of an in vivo turkey model for the study of flexor tendon repair.

Flexor tendon injuries are common and pose a clinical challenge for functional restoration. The purpose of our study was to assess the adequacy of the turkey as a large animal model for flexor tendon injuries in vivo. Twenty-four male turkeys underwent surgical flexor tendon cut and repair. Turkeys were allocated to five groups postoperatively: (1) foot casted in extension and sacrificed after 3 weeks; (2) foot casted in extension and sacrificed after 6 weeks; (3) foot casted in flexion and sacrificed after 3 weeks; (4) foot casted in flexion and sacrificed after 6 weeks; and (5) foot casted in flexion for 6 weeks and then free roaming allowed for an additional 3 weeks before sacrifice. After sacrifice, digits were collected and analyzed for adhesion formation, healing at the macrolevel and histologically, and biomechanical properties-including friction, work of flexion, stiffness, and strength of repair. All turkeys survived anesthesia and surgery. Tendon rupture occurred in all extension casts and in 11% of those casted in flexion. Friction and work of flexion were significantly higher in the repaired digit than the control digit. There was a correlation between duration of immobilization and repair strength. Histologically, the tendon healed with tenocytes migrating into the gap and producing collagen fibers. We have, for the first time, studied flexor tendon injury and repair using turkeys in terms of anesthesia, surgical procedures, postoperative care, and animal husbandry. The findings regarding functional and histological results from this novel avian model were comparable to the most commonly used mammal model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2497-2505, 2018.

Kinetic analysis of canine gait on the effect of failure tendon repair and tendon graft.

Kinetic analysis of canine gait has been extensively studied, including normal and abnormal gait. However, no research has looked into how flexor tendon injury and further treatment would affect the walking pattern comparing to the uninjured state. Therefore, this study was aimed to utilize a portable pressure walkway system, which has been commonly used for pedobarographic and kinetic analysis in the veterinary field, to examine the effect of a failed tendon repair and tendon graft reconstruction on canine digit kinetics during gait. 12 mixed breed (mongrel) hound-type female dogs were included in this study and 2nd and 5th digits were chosen to undergo flexor tendon repair and graft surgeries. Kinetic parameters from the surgery leg in stance phase were calculated. From the results, after tendon failure repair, decrease of weight bearing was seen in the affected digits and weight bearing was shifted to the metacarpal pad. After tendon graft reconstruction, weight bearing returned to the affected digits and metacarpal pads. Slight alteration in peak pressure and instant of peak force were identified, but it was estimated to have little influence on post-reconstruction gait. This study could serve as a reference in evaluating canine digit function in flexor tendon injury for future studies.