The effect of time to post-operative weightbearing on functional and clinical outcomes in adults with a displaced intra-articular calcaneal fracture

Background: Post-operative weightbearing guidelines for displaced intra-articular calcaneal fractures (DIACF) have been pragmatically developed in the past, however hardly adapted to current health care insights. A period of six to nine weeks of non-weightbearing is usually recommended. It is unknown whether an earlier start of weightbearing is advisable. Objectives: The primary aim was to evaluate the effect of time to post-operative weightbearing on Böhler's angle. Secondary aims were to determine the effect on functional outcome (e.g., The American Orthopedic Foot and Ankle Society Sc

Development of a gut-on-a-chip model for high throughput disease modeling and drug discovery

A common bottleneck in any drug development process is finding sufficiently accurate models that capture key aspects of disease development and progression. Conventional drug screening models often rely on simple 2D culture systems that fail to recapitulate the complexity of the organ situation. In this study, we show the application of a robust high throughput 3D gut-on-a-chip model for investigating hallmarks of inflammatory bowel disease (IBD). Using the OrganoPlate platform, we subjected enterocyte-like cells to an immune-relevant inflammatory trigger in order to recapitulate key events of IBD and to further investigate the suitability of this model for compound discovery and target validation activities. The induction of inflammatory conditions caused a loss of barrier function of the intestinal epithelium and its activation by increased cytokine production, two events observed in IBD physiopathology. More importantly, anti-inflammatory compound exposure prevented the loss of barrier function and the increased cytokine release. Furthermore, knockdown of key inflammatory regulators RELA and MYD88 through on-chip adenoviral shRNA transduction alleviated IBD phenotype by decreasing cytokine production. In summary, we demonstrate the routine use of a gut-on-a-chip platform for disease-specific aspects modeling. The approach can be used for larger scale disease modeling, target validation and drug discovery purpose