Development of dual-responsive chitosan-collagen scaffolds for pulsatile release of bioactive molecules

Advancement in polymer science and engineering has led to the development of new polymeric systems for well-controlled delivery of therapeutic agents. In this work, thermo and pH responsive chitosan-collagen (CHT-CLG) scaffolds were prepared using a non-residue strategy. CHT-CLG scaffolds (pH sensitive) were produced by freeze drying method, cross-linked with glutaraldehyde, and coated with poly(N,N′-diethylacrylamide) (PDEAAm) in supercritical media to confer the thermoresponsive behavior. This green and integrated process generated a wide range of porous structures with different mechanical properties, reversible swelling ability and controlled biodegradability, depending on the scaffold composition and cross-linking degree. Microarchitectural analysis by scanning electron microscopy and mercury intrusion porosimetry demonstrated that the coating of the pores inner surface was efficiently achieved without compromising the porosity. The ability of these dual sensitive structures to control the release of a low molecular weight drug (ibuprofen, Ibu) and a model protein (BSA) was investigated. Additionally, a mathematical model was adjusted to the experimental release profiles in order to quantitatively describe the drug release and elucidate the underlying drug release mechanisms. The tunable morphological and mechanical properties together with the well-controlled pulsatile release of bioactive molecules make these structures attractive ON-OFF systems in biomedical and pharmaceutical fields.