Research Information System
Presentation, pp.126, 2025
Nanomedicine involves therapeutic and diagnostic agents formulated as nanoparticles (NPs) that can be designed in various sizes, shapes and functionalities. Despite the major promise of nanomedicine for targeted drug therapies and vaccination technologies, its clinical translation remains limited by challenges in efficient delivery to the target tissues. In particular, the extracellular matrix (ECM), primarily composed of collagen along with other proteins, is a heterogeneous, porous, nanofibrous network that poses a significant barrier for NP delivery due to complex particle-fluid-structure interactions hindering advective and diffusive transport of fluids and NPs. Applications in drug delivery, tissue engineering, and disease modeling e.g. via in vitro microphysiological systems, are currently limited by the lack of a clear understanding of the transport characteristics of NPs in the tissue ECM. In this study, we consider microstructure-level modeling of fluid and NP transport in collagen hydrogels as in vitro ECM mimics to investigate the effects of ECM density, structural anisotropy and NP size on transport characteristics. Finite element method (FEM) simulations in COMSOL Multiphysics are combined with Brownian dynamics modeling in MATLAB to predict fluid and nanoparticle transport within collagen hydrogels. Key transport coefficients, including permeability and effective diffusivity, are evaluated for varying collagen concentrations (1.5 mg/mL to 6 mg/mL), fiber orientations (parallel, transverse, or random), and nanoparticle diameters (50 nm to 400 nm). In addition, permeability and effective diffusivity for selected conditions are experimentally measured for collagen hydrogels in bulk and microfluidic perfusion assays using fluorescence recovery after photobleaching (FRAP) and timelapse microscopy analysis. The predictions of the computational models are found to be in good agreement with the experimental measurements. These findings contribute to a deeper understanding of NP transport mechanisms, paving the way for improved nanomedicine design and delivery strategies.