Nanoagents in 3-dimensional biopolymer hydrogels

This research project ended with the first funding period.

Biopolymers constitute 3-dimensional scaffolds around cells and pose a significant diffusion barrier towards molecules and nanoparticles. The successful penetration of molecules through these barriers can affect the cell behavior in many ways, ranging from altered metabolism, stimulated cell proliferation and migration to induced cell death.
Such a biopolymer based diffusion barrier system is the basal lamina, an extracellular matrix system that constitutes a barrier between the blood stream and the connective tissue. The basal lamina also plays a key role in angiogenesis, cell differentiation and tumour growth, whereas the connective tissue has mainly mechanical function and regulates the communication between embedded cells. These extracellular biopolymers can be reconstituted into hydrogels, where their properties can be studied under well-defined conditions. However, the diffusion behavior of nanoparticles in biopolymer based hydrogel environments and their influence on cell behavior such as cell viability, proliferation and migration is to date not well understood.
An important example for cells that might be affected by nanoagents is given by leukocytes. To fulfil their role in the immune defense, leukocytes migrate between the blood stream and the connective tissue. The presence of nanoagents, however, might either enhance or hamper the migration activity of those cells.
In this project we aimed at creating artificial, 3-dimensional hydrogel environments for the systematic study of nanoparticles and their interaction with both the hydrogel components and living cells. We planned to

1. compare the diffusion behavior of variaus, nanoagents, i.e. DNA-based containers (A06 Liedl), porous nanoparticles (B05 Bein), nucleic acid/PEI complexes (B04 Wagner) and functionalized liposomes (my own group) in a 3D model of the basal lamina and the connective tissue.
2. study the formation of gradients of nanoparticles in reconstituted 3D hydrogels
3. evaluate the influence of nanoparticles on the viability of leukocytes and
4. quantify the ability of leukocytes to migrate into 3D hydrogels in the presence of nanoparticles.

Our systematic approach allowed us to make predictions for more complex in vivo situations which we compared with experimental results from project B10 (Krombach/Rehberg).