ABSTRACT
Mucin glycoproteins are key components of native mucus which serves as an initial barrier in the human body against microbial attack. Mucins are able to prevent bacterial adhesion and can trap viruses. However, the weak mechanical properties of mucin solutions have so far prevented their application in a physiological environment. Here, methylcellulose biopolymers are used as mechanical adjuvants to overcome this limitation and generate a thermoresponsive mucin/methylcellulose hybrid system. The hybrid material developed combines the selective permeability properties brought about by mucins with the thermal autogelation properties of methylcellulose. As a consequence, triggered by contact with body-warm surfaces, the hybrid material rapidly forms a gel at physiological conditions, and this external temperature stimulus can also be harnessed to stimulate drug release from incorporated thermosensitive liposomes. Finally, the hybrid gel selectively retards the release of embedded molecules which can be used to further control and prolong drug release from the material.
Subject(s)
Hydrogels/chemistry , Liposomes/chemistry , Metal Nanoparticles/chemistry , Methylcellulose/chemistry , Mucins/chemistry , Animals , Cell Line, Tumor , Delayed-Action Preparations , Drug Liberation , Humans , Hydrogels/pharmacology , Interleukin-8/metabolism , Liposomes/pharmacology , Methylcellulose/pharmacology , Mice , Models, Biological , Mucins/pharmacology , NIH 3T3 Cells , Rheology , Silver/chemistry , Temperature , Viscosity , Wound Healing/drug effectsABSTRACT
The migration of cells within a three-dimensional extracellular matrix (ECM) depends sensitively on the biochemical and biophysical properties of the matrix. An example for a biological ECM is given by reconstituted basal lamina gels purified from the Engelbreth-Holm-Swarm sarcoma of mice. Here, we compare four different commercial variants of this ECM, which have all been purified according to the same protocol. Nevertheless, in those gels, we detect strong differences in the migration behavior of leukocyte cells as well as in the Brownian motion of nanoparticles. We show that these differences correlate with the mechanical properties and the microarchitecture of the gels which in turn arise from small variations in their biochemical composition.
