Tendinitis Relief: Three Dimensional Modeling of Cold Therapy for the Treatment of Supraspinatus Tendinitis

Shoulder bursitis and supraspinatus tendinitis are common conditions that result from the inflammation of the supraspinatus tendon. These cause pressure to be placed more heavily on the anterior bursa sac, along with the surrounding bones and nerves. A common treatment is conductive cooling on the affected region, generally in the form of a cold pack. However, if the cold pack is left on for too short of a time period, the cooling may not reach the tendon. The tendinitis would not be adequately treated in this case, as the inflammation could not be reduced if the tendon is not cooled to a temperature close to that of the rest of the body. If it is left on for too long, the patient may be subject to significant pain and the surrounding healthy tissue may be permanently damaged. Therefore, our goal is to identify the ideal treatment time for treating supraspinatus tendon inflammation. We created a three-dimensional model of the shoulder using COMSOL, with components integrated from Autodesk™ Computer aided design software and Google Sketch-Up. The implementation of our model into COMSOL allowed us to simulate the effects of this type of cold therapy on a human shoulder. A number of major parameter simplifications were required for adequate implementation into our model. Such simplifications included the grouping of the skin and muscle components, approximation of the humerus to a cylinder and a sphere, and grouping of the bursa sac and supraspinatus tendon into one domain because the two structures were too close together to be included in the model individually. We researched relevant literature to obtain property values for the bone and tissue components of our model. We used our best judgment to approximate the property values for parts of the geometry that were simplified, such as the tendon, muscle, and skin. In order to counteract any inaccuracy that could have resulted from imprecise averaged values, we performed sensitivity analysis to determine how tendon temperature varied with changes in the various material properties. This analysis supported our approximations. To further validate our model, we compared our results with previous research. The results of their study provided us with a guideline as to how much the muscle region should cool in a certain time period. Within that time period, our muscle tissue cooled by the expected amount, which validated our model. We decided that a 3-dimensional analysis of the supraspinatus tendon was necessary because the shoulder is asymmetric, so a 2-dimensional model would not be capable of capturing the necessary complexity. We determined that the standard suggested practice of treating an injury for a maximum of 20 minutes was not applicable for injuries that are as deep as the supraspinatus tendon. In this amount of time, the tendon’s temperature decreased by 3.05 Kelvin, when it needed to decrease by 7 K to be measured as successful cooling. We identified the ideal cold treatment time to be 96 minutes, using COMSOL to determine the point at which the supraspinatus tendon cooled within 1 K of body temperature. Further analysis indicated that the suprascapular nerve would not reach the threshold for cold pain of 288 K. However, other areas closer to the surface would reach temperatures well below this threshold. The cooling of the nerves running through this region could lead to significant pain. Literature shows that cooling for more than an hour could lead to permanent tissue damage, so 96 minutes of continuous cold treatment is not recommended. While our assumptions limit the clinical significance of this study, our results indicated that the use of cold therapy for only 20 minutes is ineffective because it does not reduce the temperature of the tendon enough to reduce inflammation. Cold treatment would likely be improved by the addition of anti-inflammatory drugs, in an attempt to combat the inflammation in two ways. We would recommend that further studies utilize unique heat transfer properties for the structures present in the shoulder instead of grouping them as one. This would bring the study closer to a clinically significant stage. In addition, further analysis of the likelihood of the pain response could be included by the addition of nerves to the model. Our model could also be used to test other cold or heat therapy technologies and their probable pervasiveness in the human shoulder, specifically the glenoid and sub-acromial regions

Tubular β-catenin and FoxO3 interactions protect in chronic kidney disease

The Wnt/β-catenin signaling pathway plays an important role in renal development and is reexpressed in the injured kidney and other organs. β-Catenin signaling is protective in acute kidney injury (AKI) through actions on the proximal tubule, but the current dogma is that Wnt/β-catenin signaling promotes fibrosis and development of chronic kidney disease (CKD). As the role of proximal tubular β-catenin signaling in CKD remains unclear, we genetically stabilized (i.e., activated) β-catenin specifically in murine proximal tubules. Mice with increased tubular β-catenin signaling were protected in 2 murine models of AKI to CKD progression. Oxidative stress, a common feature of CKD, reduced the conventional T cell factor/lymphoid enhancer factor–dependent β-catenin signaling and augmented FoxO3-dependent activity in proximal tubule cells in vitro and in vivo. The protective effect of proximal tubular β-catenin in renal injury required the presence of FoxO3 in vivo. Furthermore, we identified cystathionine γ-lyase as a potentially novel transcriptional target of β-catenin/FoxO3 interactions in the proximal tubule. Thus, our studies overturned the conventional dogma about β-catenin signaling and CKD by showing a protective effect of proximal tubule β-catenin in CKD and identified a potentially new transcriptional target of β-catenin/FoxO3 signaling that has therapeutic potential for CKD

Robotic fluidic coupling and interrogation of multiple vascularized organ chips

Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ???interrogator??? that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood???brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling