Design of bioactive and biomimetic scaffolds based on chitosan-alginate polyelectrolyte complexes for tissue engineering

Abstract

The replacement and regeneration of biological tissues by fabricating three-dimensional functionalized constructs that can improve material interaction with cells is an important challenge of tissue engineering. In this study, bioactive and biomimetic scaffolds based on chitosan-alginate polyelectrolyte complexes (PECs) were fabricated by freeze-drying method and then crosslinked with CaCl₂. Various chitosan-alginate (CS-AL) molar ratios were used to obtain PECs with different structural and mechanical properties. The CS₁-AL_2.3 scaffold showed to possess the best mechanical properties (8 MPa) and good pore morphology with an average size of 100-150 μm. After the crosslinking process, a less porous structure but with higher elastic modulus (30 MPa) was obtained. To make matrix bioactive and biomimetic, the CS₁-AL_2.3 system was first functionalized with 3,4-dihydroxyhydrocinnamic acid (HCAF) and then with PySO₃ or Heparin to introduce groups/molecules mimicking the extracellular matrix. While the antioxidant properties of the scaffolds containing HCAF improved by 3 orders of magnitude, compared to the non-functionalized matrix, the introduction of sulfonic groups into the bioactive scaffold made the structure more porous and hydrophilic with respect to the heparinized one also favoring the penetration and proliferation of fibroblasts into the scaffold. These results indicate the potential of these novel systems for tissue engineering.

Keywords: 3,4-Dihydroxyhydrocinnamic acid; Bioactive and biomimetic scaffolds; Chitosan; Heparin; Polyelectrolyte complexes; Sodium alginate.