Abstract

Subcutaneous injection, which is a preferred delivery method for many drugs, causes deformation, damage, and fracture of the subcutaneous tissue. Yet, experimental data and constitutive modeling of these dissipation mechanisms in subcutaneous tissue remain limited. Here we show that subcutaneous tissue from the belly and breast anatomical regions in the swine show nonlinear stress-strain response with the characteristic J-shaped behavior of collagenous tissue. Additionally, subcutaneous tissue experiences damage, defined as a decrease in the strain energy capacity, as a function of the previously experienced maximum deformation. The elastic and damage response of the tissue are accurately described by a microstructure-driven constitutive model that relies on the convolution of a neo-Hookean material of individual fibers with a fiber orientation distribution and a fiber recruitment distribution. The model fit revealed that subcutaneous tissue can be treated as initially isotropic, and that changes in the fiber recruitment distribution with loading are enough to explain the dissipation of energy due to damage. When tested until failure, subcutaneous tissue that has undergone damage fails at the same peak stress as virgin samples, but at a much larger stretch, overall increasing the tissue toughness. Together with a finite element implementation, these data and constitutive model may enable improved drug delivery strategies and other applications for which subcutaneous tissue biomechanics are relevant.

Full Text
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