<p>Injection to the subcutaneous (SC) tissue is one of the preferred methods for drug delivery of pharmaceuticals, from small molecules to monoclonal antibodies. Delivery to SC has become widely popular in part thanks to the low cost, ease of use, and effectiveness of drug delivery through the use of auto-injector devices. However, injection physiology, from initial plume formation to the eventual uptake of the drug in the lymphatics, is highly dependent on SC mechanics, poroelastic properties in particular. Yet, the poroelastic properties of SC have been understudied. In this thesis, I present a two-pronged approach to understanding the poroelastic properties of SC. Experimentally, mechanical and fluid transport properties of SC were measured with confined compression experiments and compared against gelatin hydrogels used as SC-phantoms. It was found that SC tissue is a highly non-linear material that has viscoelastic and porohyperelastic dissipation mechanisms. Gelatin hydrogels showed a similar, albeit more linear response, suggesting a micromechanical mechanism may underline the nonlinear behavior. The second part of the thesis focuses on the multiscale modeling of SC to gain a fundamental understanding of how geometry and material properties of the microstructure drive the macroscale response. SC is composed of adipocytes (fat cells) embedded in a collagen network. The geometry can be characterized with Voroni-like tessellations. Adipocytes are fluid-packed, highly deformable and capable of volume change through fluid transport. Collagen is highly nonlinear and nearly incompressible. Representative volume element (RVE) simulations with different Voroni tesselations shows that the different materials, coupled with the geometry of the packing, can contribute to different material response under the different kinds of loading. Further investigation of the effect of geometry showed that cell packing density nonlinearly contributes to the macroscale response. The RVE models can be homogenized to obtain macroscale models useful in large scale finite element simulations of injection physiology. Two types of homogenization were explored: fitting to analytical constitutive models, namely the Blatz-Ko material model, or use of Gaussian process surrogates, a data-driven non-parametric approach to interpolate the macroscale response.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/23704215 |
| Date | 18 July 2023 |
| Creators | Jacques Barsimantov Mandel (16611876) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/MULTISCALE_MODELING_AND_CHARACTERIZATION_OF_THE_POROELASTIC_MECHANICS_OF_SUBCUTANEOUS_TISSUE/23704215 |
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