Particle Trapping Mechanisms in Biological Hydrogels

Understanding particle transport in hydrogels is an important step for the development of advanced drug delivery techniques. A large body of experimental research has shown that besides excluded volume effects and hydrodynamics, other nonsteric particle-gel interactions can also determine particle mobility in hydrogels. In this thesis, we aim to systematically investigate the effect of long-ranged repulsive or attractive particle-gel interactions on the particle mobility and to determine general particle diffusion mechanisms in hydrogels. For this, we present general models to simulate diffusion of particles in gels with different particle-gel interactions. First, we introduce a model for the diffusion of particles smaller than the mesh size in hydrogels with electrostatic particle-gel interactions. The gel is comprised of a spatially ordered, cubic symmetric fiber lattice. The diffusive behavior is highly charge asymmetric: Particles are slowed down more strongly by attractive than by repulsive electrostatic interactions. Furthermore, the particle mobility is highly sensitive to the ionic strength, particularly for electrostatic attraction, in agreement with experimental data. Second, we examine the effect of spatial disorder of the polymer lattice on the particle diffusive behavior. The effect of spatial disorder is linked to the presence of long-ranged particle-gel interactions. For repulsive interactions, an intermediate degree of disorder minimizes the particle mobility inside the gel but for high degrees of disorder, the diffusivity increases again. For attractive interactions, disorder slows down diffusion since particles are immobilized in regions with locally increased fiber density. A comparison between simulations with spatially disordered gels and published experimental data reveals qualitative agreement. Third, we extend our model to simulate the diffusion of particles in heterogeneous gels with mixed electrostatically attractive and repulsive interaction sites, as relevant for biological hydrogels. ...