Multiscale molecular profiling of pathological bone resolves sexually dimorphic control of extracellular matrix composition.

Collagen assembly during development is essential for successful matrix mineralisation, which determines bone quality and mechanocompetence. However, the biochemical and structural perturbations that drive pathological skeletal collagen configuration remain unclear. Deletion of vascular endothelial growth factor (VEGF) in bone forming osteoblasts (OBs) induces sex-specific alterations in extracellular matrix (ECM) conformation and mineralisation coupled to vascular changes, which are augmented in males. Whether this phenotypic dimorphism arises as a result of the divergent control of ECM composition and its subsequent arrangement is unknown and is the focus of this study. Herein, we have used a murine osteocalcin-specific Vegf knockout (OcnVEGFKO) and performed ex vivo multiscale analysis at the tibiofibular junction of both sexes. Furthermore, we also deleted Vegf in vitro in OBs extracted from male and female mice in an attempt to link sex-specific matrix signatures to deviations in gene expression. Label-free and non-destructive polarisation-resolved second harmonic generation microscopy (p-SHG) revealed a reduction in collagen fibre number in males following the loss of VEGF, complemented by observable defects in matrix organisation by backscattered electron scanning electron microscopy. This was accompanied only in males by localised divergence in collagen orientation, determined by p-SHG anisotropy measurements, as a result of OcnVEGFKO. Raman spectroscopy confirmed the effect on collagen was linked to molecular dimorphic VEGF effects on collagen-specific proline and hydroxyproline, and collagen intra-stand stability, in addition to matrix carbonation and mineralisation. Vegf deletion in male and female murine OB cultures in vitro further highlighted divergence in genes regulating local ECM structure including Adamts2, Spp1, Mmp9 and Lama1 The current results demonstrate the utility of macromolecular imaging and spectroscopic modalities for the detection of collagen arrangement and ECM composition in pathological bone. Linking the sex-specific genetic regulators to matrix signatures could be important for treatment of dimorphic bone disorders which clinically manifest in both pathological nano and macro-level disorganisation

Development and validation of a model for quantifying glenohumeral ligament strains during function

Analysis of the function of glenohumeral ligaments (GHLs) during physical joint manipulations is hindered by an inability to adequately image these tissues during the movements. This restricts functional biomechanics studies only to the manoeuvres that may be replicated cadaverically. There is, however, a clinical imperative to be able to investigate complex manoeuvres that exacerbate symptoms but cannot be easily conducted physically in the laboratory. The aim of this study was to develop and validate an algorithm for a computer simulation model that allows the quantification of glenohumeral ligament lengths during function. Datasets of the humerus and scapula pair were segmented to provide individual surface meshes of the bones and insertion points of each glenohumeral ligament on both bones. An algorithm was developed in which the glenohumeral ligament attachment-to-attachment length was divided into two straight lines, plus an arc overlaying the spherical wrapping portions. The model was validated by simulating two classical cadaveric studies from the literature and comparing results. Predictions from the model were qualitatively similar to the results of the two cadaveric studies by a factor of 91.7% and 81.8%, respectively. Algorithm application will allow investigation of functional loading of the glenohumeral ligaments during simulated complex motions. This could then be used to provide diagnostic understanding and thus, inform surgical reconstruction

Rotator cuff-sparing approaches for glenohumeral joint access: an anatomic feasibility study

Background The deltopectoral approach for total shoulder arthroplasty can result in subscapularis dysfunction. In addition, glenoid wear is more prevalent posteriorly, a region difficult to access with this approach. We propose a posterior approach for access in total shoulder arthroplasty that uses the internervous interval between the infraspinatus and teres minor. This study compares this internervous posterior approach with other rotator cuff–sparing techniques, namely, the subscapularis-splitting and rotator interval approaches. Methods The 3 approaches were performed on 12 fresh frozen cadavers. The degree of circumferential access to the glenohumeral joint, the force exerted on the rotator cuff, the proximity of neurovascular structures, and the depth of the incisions were measured, and digital photographs of the approaches in different arm positions were analyzed. Results The posterior approach permits direct linear access to 60% of the humeral and 59% of the glenoid joint circumference compared with 39% and 42% for the subscapularis-splitting approach and 37% and 28% for the rotator interval approach. The mean force of retraction on the rotator cuff was 2.76 (standard deviation [SD], 1.10) N with the posterior approach, 2.72 (SD, 1.22) N with the rotator interval, and 4.75 (SD, 2.56) N with the subscapularis-splitting approach. From the digital photographs and depth measurements, the estimated volumetric access available for instrumentation during surgery was comparable for the 3 approaches. Conclusion The internervous posterior approach provides greater access to the shoulder joint while minimizing damage to the rotator cuff

A humeral coordinate system for in vivo 3-D kinematics of the Glenohumeral joint

The aim of this study was to define axes from clearly identifiable landmarks on the proximal aspect of the humerus and to compare these for reasonable best alternatives to the use of the humeral canal and elbow epicondylar axes to define a humeral coordinate frame (HCF). The elbow epicondylar axis (EC) and six different humeral canal axes (HC) based on varying lengths of humerus were quantified from 21 computed tomography (CT) scans of humeri. Six additional axes were defined using the proximal humerus only. These included a line from the center of a sphere fit on the humeral head to the 3D surface area centroid of the greater tubercle region, (GT). The inclinations of these axes relative to EC were calculated. GT was found to be the most closely aligned to EC (13.4° ± 6.8°). The inclinations of the other axes ranged from 36.3° to 86.8°. The HC axis orientation was found to be insensitive to humeral shaft lengths (variability, within average: 0.6°). This was chosen as one of two axes for the HCF. It was also the most inter-subject related axis to EC with inclination standard deviation of ±1.8°. EC was therefore predicted from this such that if the superior axis [1 0 0] of an image scan is maintained and the humerus rotated to make its quantified HC align superiorly in the direction [0.98 0.01 0.01], then its EC axis lies laterally in the direction [0 0 1]. This study demonstrates that it is possible with confidence to apply an orthogonal coordinate frame to the humerus based on proximal imaging data onl

The influence of full-thickness supraspinatus tears on abduction moments: the importance of the central tendon

Background: Detachment of the central tendon of the supraspinatus from its insertion is considered to be crucial to functional deficit. The aim of the present study was to assess the function of the supraspinatus in terms of abduction moments by introducing different tear configurations to assess the functional effect of the central tendon insertion. Methods: Ten fresh frozen shoulders from five cadavers were prepared for testing. A testing protocol was established to measure the abduction moment of the supraspinatus under physiological loading tailored to the anthropometrics of each specimen. Four conditions were tested: intact supraspinatus; complete detachment of portion of the supraspinatus tendon anterior to the main central tendon; detachment of the main central tendon; and detachment of the region of the supraspinatus posterior to the main central tendon. Results: There was a significant and large reduction in abduction moment when the central tendon was sectioned (p < 0.05). A smaller reduction in abduction moment was found when the regions anterior and posterior to the main central tendon were sectioned (p < 0.05). Conclusions: The central tendon is vital in the role of functional arm abduction through force transmission through the intact rotator cuff. Reinsertion of the central tendon in the correct anatomical location is desirable to optimize functional outcome of surgery

Assessment of non-adiabatic behaviour in thermoelastic stress analysis of composite sandwich panels

A modified Arcan fixture (MAF) is described. The is to characterize polymer foam materialswith respect to their mechanical properties at room and at elevated temperatures. The MAF enablesthe application of pure compression or high compression to shear bidirectional loading conditions thatis not possible with conventional Arcan fixtures. This paper focuses on the validation of the MAF setupat room temperature. The tensile and shear behaviour of a cross linked PVC foam material is studiedusing digital image correlation. Thermoelastic stress analysis is used to examine and validate theuniformity and symmetry of the stress fields obtained. To account for the inhomogeneity of the strainfield across the specimen cross sections, a "correction factor" for the measured "gauge section" surfacestrains has been determined using nonlinear finite element analysis (FEA). The measured mechanicalproperties are in excellent agreement with measurements conducted using conventional test methods

Treatment of Lymphangiomas in Children: An Update of Picibanil (OK-432) Sclerotherapy

Picibanil (OK-432) is a sclerosing agent derived from a low-virulence strain of Streptococcus pyogenes that induces regression of macrocystic lymphangiomas. This report describes a prospective, nonrandomized trial to evaluate the efficacy of Picibanil in the treatment of 13 affected children ranging in age from 1 to 94 months. On average, 4.1 fluoroscopically guided intracystic injections were performed per child, with an average total dose of 0.56 mg of Picibanil. As judged by physical examination and radiographic studies, 5 children (42%) showed a complete or substantial response, and 2 children (16%) showed an intermediate response. No response was seen in 5 children (42%), 2 of whom had massive craniofacial lymphangioma. Factors that contribute to failure with Picibanil sclerotherapy are the presence of a significant microcystic component to the lesion, massive craniofacial involvement, and previous surgical resection. Macrocystic lymphangiomas of the infratemporal fossa or cervical area have the best response to therapy