In the tissue engineering (TE) field, the concept of producing multifunctional scaffolds, capable not only
of acting as templates for cell transplantation but also of delivering bioactive agents in a controlled
manner, is an emerging strategy aimed to enhance tissue regeneration. In this work, a complex hybrid
release system consisting in a three-dimensional (3D) structure based on poly(d,l-lactic acid) (PDLLA)
impregnated with chitosan/chondroitin sulfate nanoparticles (NPs) was developed. The scaffolds were
prepared by supercritical fluid foaming at 200 bar and 35 "C, and were then characterized by scanning
electron microscopy (SEM) and micro-CT. SEM also allowed to assess the distribution of the NPs within
the structure, showing that the particles could be found in different areas of the scaffold, indicating a
homogeneous distribution within the 3D structure. Water uptake and weight loss measurements were
also carried out and the results obtained demonstrated that weight loss was not significantly enhanced
although the entrapment of the NPs in the 3D structure clearly enhances the swelling of the structure.
Moreover, the hybrid porous biomaterial displayed adequate mechanical properties for cell adhesion and
support. The possibility of using this scaffold as a multifunctional material was further evaluated by the
incorporation of a model protein, bovine serum albumin (BSA), either directly into the PDLLA foam or
in the NPs that were eventually included in the scaffold. The obtained results show that it is possible to
achieve different release kinetics, suggesting that this system is a promising candidate for dual protein
delivery system for TE applications.