Lung on a chip: Co-culture of alveolar epithelial cells and bone marrow derived stromal stem cells in a microfluidic system

Background: Microfluidics system are novel tools to study cell-cell interactions in vitro. This project focuses on the development of a new microfluidic device to co-culture alveolar epithelial cells and mesenchymal stem cells to study cellular interactions involved in healing the injured alveolar epithelium. Methods: Microfluidic systems in polydimethylsiloxane were fabricated by soft lithography. The alveolar A549 epithelial cells were seeded and injury tests were made on the cells by perfusion with media containing H2O2 or bleomycin during 6 or 18hrs. Rat Bone marrow derived stromal cells (BMSC) were then introduced into the system and cell-cell interaction was studied over 24 hrs. Results: A successful co-culture of A549 alveolar epithelial cells and BMS was achieved in the microfluidic system. The seeded alveolar epithelial cells and BMSC adhered to the bottom surface of the microfluidic device and proliferated under constant perfusion. Epithelial injury to mimic mechanisms seen in idiopathic pulmonary fibrosis was induced in the microchannels by perfusing with H2O2 or bleomycin. Migration of BMSC towards the injured epithelium was observed as well as cell-cell interaction between the two cell types was also seen. Conclusion: We demonstrate a novel microfluidic device aimed at showing interactions between different cell types on the basis of a changing microenvironment. Also we were able to confirm interaction between injured alvolar epithelium and BMSC, and showed that BMSC try to heal the injured epitelium.

[Influence of chronic, structural changes of the muscle-tendon unit on the indication and technique of rotator cuff reconstruction]

Rotator cuff lesions are common and the incidence increases with age. After tendon rupture of the rotator cuff, the muscle-tendon unit retracts, which is accompanied by muscle fatty infiltration, atrophy, and interstitial fibrosis of the musculature, thus, fundamentally changing the muscle architecture. These changes are important prognostic factors for the operative rotator cuff reconstruction outcome. Selection of the correct time point for reconstruction as well as the optimal mechanical fixation technique are decisive for successful attachment at the tendon-to-bone insertion site. Thus, knowledge of the pathophysiological processes plays an important role. The goal of this article is to establish a relationship between currently existing evidence with respect to the preoperatively existing changes of the muscle-tendon unit and the choice of the time for the operation and the operative technique.

Cell-specific expression of human HGF by alveolar type II cells induces remodeling of septal wall tissue in the lung: a morphometric study

Hepatocyte growth factor (HGF) is involved in development and regeneration of the lungs. Human HGF, which was expressed specifically by alveolar epithelial type II cells after gene transfer, attenuated the bleomycin-induced pulmonary fibrosis in an animal model. As there are also regions that appear morphologically unaffected in fibrosis, the effects of this gene transfer to normal lungs is of interest. In vitro studies showed that HGF inhibits the formation of the basal lamina by cultured alveolar epithelial cells. Thus we hypothesized that, in the healthy lung, cell-specific expression of HGF induces a remodeling within septal walls. Electroporation of a plasmid of human HGF gene controlled by the surfactant protein C promoter was applied for targeted gene transfer. Using design-based stereology at light and electron microscopic level, structural alterations were analyzed and compared with a control group. HGF gene transfer increased the volume of distal air spaces, as well as the surface area of the alveolar epithelium. The volume of septal walls, as well as the number of alveoli, was unchanged. Volumes per lung of collagen and elastic fibers were unaltered, but a marked reduction of the volume of residual extracellular matrix (all components other than collagen and elastic fibers) and interstitial cells was found. A correlation between the volumes of residual extracellular matrix and distal air spaces, as well as total surface area of alveolar epithelium, could be established. Cell-specific expression of HGF leads to a remodeling of the connective tissue within the septal walls in the healthy lung, which is associated with more pronounced stretching of distal air spaces at a given hydrostatic pressure during instillation fixation.

Validation of a statistical shape model-based 2D/3D reconstruction method for determination of cup orientation after THA

The aim of this study was to validate the accuracy and reproducibility of a statistical shape model-based 2D/3D reconstruction method for determining cup orientation after total hip arthroplasty. With a statistical shape model, this method allows reconstructing a patient-specific 3D-model of the pelvis from a standard AP X-ray radiograph. Cup orientation (inclination and anteversion) is then calculated with respect to the anterior pelvic plane that is derived from the reconstructed model.

The effects of isoflurane minimum alveolar concentration on withdrawal reflex activity evoked by repeated transcutaneous electrical stimulation in ponies

The aim of this study was to quantify the effects of isoflurane at approximately the minimum alveolar concentration (peri-MAC) on the temporal summation (TS) of reflex activity in ponies. TS was evoked by repeated electrical stimulations applied at 5 Hz for 2 s on the digital nerve of the left forelimb of seven ponies. Surface electromyographic activity was recorded from the deltoid and common digital extensor muscles. TS thresholds and amplitude of response to stimulations of increasing intensities were assessed during anaesthesia at 0.85, 0.95 and 1.05 times the individual MAC, and after anaesthesia in standing animals. Under isoflurane anaesthesia, TS thresholds increased significantly in a concentration-dependent fashion and at each isoflurane MAC, the responses increased significantly for increasing stimulation intensities. A concentration-dependent depression of evoked reflexes with a reduction in the slopes of the stimulus-response function was observed for both muscles. The results demonstrated that with this model it is possible to describe and quantify the effects of anaesthetics on spinal sensory-motor processing in ponies.

Intraoperative template-molded bone flap reconstruction for patient-specific cranioplasty

Cranioplasty is a common neurosurgical procedure. Free-hand molding of polymethyl methacrylate (PMMA) cement into complex three-dimensional shapes is often time-consuming and may result in disappointing cosmetic outcomes. Computer-assisted patient-specific implants address these disadvantages but are associated with long production times and high costs. In this study, we evaluated the clinical, radiological, and cosmetic outcomes of a time-saving and inexpensive intraoperative method to mold custom-made implants for immediate single-stage or delayed cranioplasty. Data were collected from patients in whom cranioplasty became necessary after removal of bone flaps affected by intracranial infection, tumor invasion, or trauma. A PMMA replica was cast between a negative form of the patient's own bone flap and the original bone flap with exactly the same shape, thickness, and dimensions. Clinical and radiological follow-up was performed 2 months post-surgery. Patient satisfaction (Odom criteria) and cosmesis (visual analogue scale for cosmesis) were evaluated 1 to 3 years after cranioplasty. Twenty-seven patients underwent intraoperative template-molded patient-specific cranioplasty with PMMA. The indications for cranioplasty included bone flap infection (56%, n = 15), calvarian tumor resection (37%, n = 10), and defect after trauma (7%, n = 2). The mean duration of the molding procedure was 19 ± 7 min. Excellent radiological implant alignment was achieved in 94% of the cases. All (n = 23) but one patient rated the cosmetic outcome (mean 1.4 years after cranioplasty) as excellent (70%, n = 16) or good (26%, n = 6). Intraoperative cast-molded reconstructive cranioplasty is a feasible, accurate, fast, and cost-efficient technique that results in excellent cosmetic outcomes, even with large and complex skull defects.

Alveolar bone grafting in association with polyostotic fibrous dysplasia and bisphosphonate-induced abnormal bone turnover in a bilateral cleft lip and palate patient: a case report

A case is presented of extensive alveolar bone grafting in a patient with bilateral cleft lip and palate and polyostotic fibrous dysplasia. The patient previously underwent bisphosphonate therapy. Because of an abnormal and often decreased bone turnover caused by the fibrous dysplasia and the bisphosphonate therapy, bone grafting in such a patient poses several potential difficulties. In addition, the histomorphometric analysis of the bone grafts showed markedly decreased bone turnover. However, alveolar bone grafting using the iliac crest was performed successfully. Sufficient occlusion was achieved by postoperative low-loading orthodontic treatment.

The extended diep flap: extending the possibilities for breast reconstruction with tissue from the lower abdomen

The classical DIEP-flap is considered state-of-the-art in microsurgical autologous breast reconstruction. Some patients may require additional volume to match the contralateral breast. This quality control study prospectively evaluates the feasibility and outcome of a surgical technique, which pursues the volumetric augmentation of the DIEP-flap by harvesting of additional subscarpal fat tissue cranial to the classical flap border.

Three-dimensional surface reconstruction within noncontact diffuse optical tomography using structured light

A main field in biomedical optics research is diffuse optical tomography, where intensity variations of the transmitted light traversing through tissue are detected. Mathematical models and reconstruction algorithms based on finite element methods and Monte Carlo simulations describe the light transport inside the tissue and determine differences in absorption and scattering coefficients. Precise knowledge of the sample's surface shape and orientation is required to provide boundary conditions for these techniques. We propose an integrated method based on structured light three-dimensional (3-D) scanning that provides detailed surface information of the object, which is usable for volume mesh creation and allows the normalization of the intensity dispersion between surface and camera. The experimental setup is complemented by polarization difference imaging to avoid overlaying byproducts caused by inter-reflections and multiple scattering in semitransparent tissue.