Development of ternary multilayer systems from polysaccharides and metal ions for tissue engineering applications

Abstract

Surface modification at the micro- and nanoscale enables precise control of cell behaviour. In this study, polyelectrolyte multilayers (PEMs) composed of chitosan with alginate or hyaluronic acid were fabricated using the layer-by-layer technique and doped with biologically relevant metal ions (Ca²⁺, Co²⁺, Cu²⁺, Fe³⁺). Metal ions binding to multilayers through coordination with functional groups of polysaccharides modulated their physicochemical properties and the bioactivity toward multipotent murine C3H10T1/2 embryonic fibroblasts. Surface characterization revealed metal-ion-dependent changes in wettability, surface potential, and mechanical properties. Metal ion content in PEM is quantified by inductively coupled plasma mass spectrometry (ICP-MS), showing the highest concentration of Fe3+, followed by Ca 2+, Cu²⁺ and Co²⁺. Notably, Cu2+ and Fe3+ doped PEMs enhanced cell adhesion, spreading, and proliferation. These findings demonstrate that metal ions doped PEMs are promising cytokine-free bioactive coatings for implants and scaffolds, with potential promote regeneration of bone and connective-type tissues.