Mechanoscopy: A Novel Device and Procedure for in vivo Detection of Chronic Colitis in Mice.

BACKGROUND: Gut stiffening caused by fibrosis plays a critical role in the progression of inflammatory bowel disease (IBD) and colon cancer. Previous studies have characterized the biomechanical response of healthy and pathological gut, with most measurements obtained ex vivo. METHODS: Here, we developed a device and accompanying procedure for in vivo quantification of gut stiffness, termed mechanoscopy. Mechanoscopy includes a flexible balloon catheter, pressure sensor, syringe pump, and control system. The control system activates the balloon catheter and performs automated measurements of the gut stress-strain biomechanical response. RESULTS: A gut stiffness index (GSI) is identified based on the slope of the obtained stress-strain response. Using a colitis mouse model, we demonstrated that GSI positively correlates with the extent of gut fibrosis, the severity of mucosal damage, and the infiltration of immune cells. Furthermore, a critical strain value is suggested, and GSI efficiently detects pathological gut fibrotic stiffening when the strain exceeds this value. CONCLUSIONS: Based on these results, we envision that mechanoscopy and GSI will facilitate the clinical diagnosis of IBD.

Here, we present a novel procedure/device, termed mechanoscopy, which we have demonstrated to accurately detect and differentiate between fibrosis and inflammation in rodent models of colitis. Thus, mechanoscopy offers a translationally relevant approach for ultrasensitive and minimally invasive IBD diagnosis.

Intrinsic coating morphology modulates acute drug transfer in drug-coated balloon therapy.

The hallmark of drug-coated balloon (DCB) therapy for the treatment of peripheral vascular disease is that it allows for reopening of the narrowed lumen and local drug delivery without the need for a permanent indwelling metal implant such as a stent. Current DCB designs rely on transferring drugs such as paclitaxel to the arterial vessel using a variety of biocompatible excipients coated on the balloons. Inherent procedural challenges, along with limited understanding of the interactions between the coating and the artery, interactions between the coating and the balloon as well as site-specific differences, have led to DCB designs with poor drug delivery efficiency. Our study is focused on two clinically significant DCB excipients, urea and shellac, and uses uniaxial mechanical testing, scanning electron microscopy (SEM), and biophysical modeling based on classic Hertz theory to elucidate how coating microstructure governs the transmission of forces at the coating-artery interface. SEM revealed shellac-based coatings to contain spherical-shaped microstructural elements whereas urea-based coatings contained conical-shaped microstructural elements. Our model based on Hertz theory showed that the interactions between these intrinsic coating elements with the arterial wall were fundamentally different, even when the same external force was applied by the balloon on the arterial wall. Using two orthogonal cell-based assays, our study also found differential viability when endothelial cells were exposed to titrated concentrations of urea and shellac, further highlighting the need to maximize coating transfer efficiency in the context of DCB therapies. Our results underscore the significance of the excipient in DCB design and suggest that coating microstructure modulates acute drug transfer during device deployment.