Mechanobiology of gastric needle insertions: a combined experimental and numerical study.

Abstract

The rising use of biologic drugs has increased the demand for alternative gastric administration methods. Inception of devices engineered to insert medication into the mucosal lining overcomes limitations of traditional administration methods. Mechanical forces from such microneedle insertions can affect tissue and cellular behavior, particularly mechanotransduction markers. This study investigates the effects of needle insertion in gastric tissue to inform the design of alternative drug delivery devices. Experimental and computational approaches were utilized, using tension and radial compression tests on porcine gastric tissue to inform a finite element analysis (FEA) model. This model was validated with atomic force microscopy (AFM)-based micro-indentation to examine stiffness variations near the insertion site, and yes-associated-protein-1 (YAP-1) expression was analyzed to assess cellular mechanotransduction. AFM results revealed a distance-dependent decrease in tissue stiffness from the insertion site (p < 0.05), with significant differences in needle geometry (p < 0.05). The FEA model correlated well with AFM findings, confirming its validity for further cellular simulations. Mechanical stresses from needle insertion were shown to propagate through the tissue, affecting both cytoplasmic and nuclear stress distributions and altering nuclear morphology near the insertion site. The blunt needle produced a higher localized stress field compared to the sharp needle. Additionally, YAP-1 expression was lower in the injected samples than in control samples showing distance-dependent responses observed. This study demonstrates a validated model linking tissue mechanics and cellular responses, highlighting how needle geometry impacts gastric tissue mechanics and mechanotransduction, providing insights essential for designing gastric drug delivery devices.