Abstract
AbstractSummary: To ultimately assess the ability of macromolecular medicines e.g. liposomes, non viral gene delivery systems, to penetrate one of the least studied physiological barriers, the extracellular matrix (ECM), composite networks made of different ECM components i.e. type I collagen, hyaluronic acid and a proteoglycan, decorin, were prepared. These composite networks were characterized by rheology, Confocal Reflection Microscopy, Fluorescence Recovery After Photobleaching and Transmission Electron Microscopy. While being at the low end of its physiological concentration, collagen appears to be the backbone of the composite networks as it provides the elastic modulus. On the other hand, 15 kDa and 1.1 MDa hyaluronic acid, when present at physiological levels interpenetrate the collagen network. When approaching their overlap concentration, hyaluronic acid chains lead to an increase of the population of collagen fibrils. Finally, while decorin increased the population of fibrils in pure collagen networks, its role in presence of hyaluronic acid remains unclear as it does not alter the diameter of fibrils nor their population.
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