Ex vivo Tissue Provides Insight into Bleb Dynamics During Large-Volume Subcutaneous Injection

Large-volume subcutaneous injections can create visible protrusions called blebs, whose size and shape affect drug absorption and patient comfort. In vivo pig studies have documented how the bleb dimensions and tissue pressure vary with injection volume, flow rate, and fluid viscosities. However, its underlying mechanics remain unclear due to limited temporal and spatial measurements. This study evaluates whether ex vivo tissue can serve as an inexpensive and practical surrogate to study tissue deformation and uses this model to investigate the roles of fluid properties and vascular perfusion during large-volume injections.

We performed subcutaneous injections into store-bought pork belly tissue, replicating the injectate conditions from previous in vivo studies. Using a depth camera and pressure sensor, we continuously measure the bleb surface profile and in-line pressure. These measurements are converted into height, area, and tissue pressure at different injection volumes and are compared directly with previously published in vivo data.

Bleb height and area increased monotonically with injected volume but were independent of viscosity and flow rate. Tissue pressure rose initially and then plateaued, even as bleb dimensions continued to grow. These trends closely mirrored in vivo findings.

Ex vivo tissue mimics bleb shape and tissue pressures of in vivo subcutaneous injections, indicating that in vivo systemic factors are negligible over typical injection timescales. These results validate the use of ex vivo surrogates for studying bleb formation and challenge assumptions in current poroelastic models, which fail to capture the observed decoupling between tissue pressure and bleb growth.