Control of particle uptake kinetics from particulate mesoporous silica films by cells through covalent linking of particles to the substrate - towards sequential drug delivery for tissue engineering applications.

Abstract

A sequential release of biological cues is of high interest in tissue engineering applications, as both the proliferation and the differentiation of stem cells can be drugged. In previous studies we have shown that particulate films of mesoporous silica particles can be successfully applied for influencing stem cell fates through intracellular drug delivery after particle internalisation by the cells. In this study, we develop this concept towards an enhanced control of the particle uptake kinetics through either adsorption or covalent linking of the mesoporous silica particles to the substrate. Microscopy glass slides were initially functionalized by an aminosilane to which a thin layer of hyaluronic acid was covalently attached through an amide bond. A sub-monolayer of amino-functionalized mesoporous silica nanoparticles with a diameter of 400 nm were then adsorbed to the hyaluronic acid-functionalized surface by adsorption under high-shear conditions. Subsequently, the adsorbed particles were covalently linked to the hyaluronic acid through an amide bond. Corresponding films without the covalent coupling step were used as the control. Muscle stem cells attach and proliferate nicely on all films, and do internalize particles in all cases. However, the kinetics of particle internalization was clearly delayed for the covalently attached particles in comparison to physisorbed particles. Thus, the results imply that tuning of the particle-substrate interactions through linking chemistries is a promising means of achieving sequential particle-mediated drug release from films and that corresponding chemistries should also be applicable for 3D scaffold systems.