Effect of metal ions on the physical properties of multilayers from hyaluronan and chitosan, and the adhesion, growth and adipogenic differentiation of multipotent mouse fibroblasts

[EN] Polyelectrolyte multilayers (PEMs) consisting of the polysaccharides hyaluronic acid (HA) as the polyanion and chitosan (Chi) as the polycation were prepared with layer-by-layer technique (LbL). The [Chi/HA](5) multilayers were exposed to solutions of metal ions (Ca2+, Co2+, Cu2+ and Fe3+). Binding of metal ions to [Chi/HA](5) multilayers by the formation of complexes with functional groups of polysaccharides modulates their physical properties and the bioactivity of PEMs with regard to the adhesion and function of multipotent murine C3H10T1/2 embryonic fibroblasts. Characterization of multilayer formation and surface properties using different analytical methods demonstrates changes in the wetting, surface potential and mechanical properties of multilayers depending on the concentration and type of metal ion. Most interestingly, it is observed that Fe3+ metal ions greatly promote adhesion and spreading of C3H10T1/2 cells on the low adhesive [Chi/HA](5) PEM system. The application of intermediate concentrations of Cu2+, Ca2+ and Co2+ as well as low concentrations of Fe3+ to PEMs also results in increased cell spreading. Moreover, it can be shown that complex formation of PEMs with Cu2+ and Fe3+ ions leads to increased metabolic activity in cells after 24 h and induces cell differentiation towards adipocytes in the absence of any additional adipogenic media supplements. Overall, complex formation of [Chi/HA](5) PEM with metal ions like Cu2+ and Fe3+ represents an interesting and cheap alternative to the use of growth factors for making cell-adhesive coatings and guiding stem cell differentiation on implants and scaffolds to regenerate connective-type of tissues.This work was part of the High-Performance Center Chemical and Biosystems Technology Halle/Leipzig, supported by the European Regional Development Fund (ERDF), and a grant to HK from the Martin Luther University Halle-Wittenberg for female PhD students. The work was further supported by the Fraunhofer Internal Programs under Grant No. Attract 069-608203 (CEHS). TG acknowledges the kind support by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers ``Digital biodesign and personalized healthcare'' 075-15-2020926. GGF acknowledges funding by the State Research Agency. Ministry of Science and Innovation of Spain, grant PID2019106000RB-C21/AEI/10.13039/501100011033 project. We are grateful for the kind support by Christian Willems for the help in formatting and proof reading the manuscript.Kindi, H.; Menzel, M.; Heilmann, A.; Schmelzer, CEH.; Herzberg, M.; Fuhrmann, B.; Gallego-Ferrer, G.... (2021). Effect of metal ions on the physical properties of multilayers from hyaluronan and chitosan, and the adhesion, growth and adipogenic differentiation of multipotent mouse fibroblasts. Soft Matter. 17(36):8394-8410. https://doi.org/10.1039/d1sm00405k83948410173

Carbonyl Iron Foam Surfaces Modified with Poly (L-Lysine) As Smart Surface for Bone Implant

This article presents the surface modification of iron Fe (110) surfaces with Poly-L-Lysine (PLL) with the aim of preparing carbonyl iron bone implants which are less corrosive and more compatible with fibroblast cells. The cytocompatibility of modified surfaces with commercially available α-PLL and electrodeposited ε-PLL was compared by combination of DFT computational simulations with experimental electrochemical and cell adhesion studies to obtain “smart” surface application. Experimental study of fibroblasts adhesion showed better viability of cells on ε-PLL than on α-PLL after modification of Fe surfaces as “smart” surfaces to obtain a different hydrophobicity. The porosity of Fe (110) prevented direct measurements of contact angle and therefore surface hydrophobicity was simulated with calculation of adsorption energies for Fe with both α-/ε- PLL structures. This technique was also employed to calculate the interaction of O-H bonds at the surface. The corrosion potential of Fe (110) with superficially modified ε-PLL was shifted by 0.088V compared to the bare iron surface, thus indicating a stronger resistance to corrosion. The results suggest that modification of Fe surface with ε-PLL has a more pronounced effect on cellular growth on this implant and that the slightly hydrophobic character of ε-PLL leads to better cell adhesion ability

Metal Ion Doping of Alginate-Based Surface Coatings Induces Adipogenesis of Stem Cells

[EN] Metal ions are important effectors of protein and cell functions. Here, polyelectrolyte multilayers (PEMs) made of chitosan (Chi) and alginate (Alg) were doped with different metal ions (Ca2+, Co2+, Cu2+, and Fe3+), which can form bonds with their functional groups. Ca2+ and Fe3+ ions can be deposited in PEM at higher quantities resulting in more positive zeta potentials and also higher water contact angles in the case of Fe3+. An interesting finding was that the exposure of PEM to metal ions decreases the elastic modulus of PEM. Fourier transformed infrared (FTIR) spectroscopy of multilayers provides evidence of interaction of metal ions with the carboxylic groups of Alg but not for hydroxyl and amino groups. The observed changes in wetting and surface potential are partly related to the increased adhesion and proliferation of multipotent C3H10T1/2 fibroblasts in contrast to plain nonadhesive [Chi/Alg] multilayers. Specifically, PEMs doped with Cu2+ and Fe3+ ions greatly promote cell attachment and adipogenic differentiation, which indicates that changes in not only surface properties but also the bioactivity of metal ions play an important role. In conclusion, metal ion-doped multilayer coatings made of alginate and chitosan can promote the differentiation of multipotent cells on implants without the use of other morphogens like growth factors.This work was partly funded by the International Graduate School AGRIPOLY supported by the European Regional Development Fund (ERDF) and the Federal State Saxony-Anhalt and a grant to H.K. from Martin Luther University Halle-Wittenberg for female PhD students. This work was further supported by the Fraunhofer Internal Programs without Grant Attract 069608203 (CEHS) . G.G.F. acknowledges funding by the State Research Agency of the Ministry of Science and Innovation of Spain, PID2019-106000RB-C21/AEI/10.13039/501100011033 project.Kindi, H.; Willems, C.; Zhao, M.; Menzel, M.; Schmelzer, C.; Herzberg, M.; Fuhrmann, B.... (2022). Metal Ion Doping of Alginate-Based Surface Coatings Induces Adipogenesis of Stem Cells. ACS Biomaterials Science & Engineering. 8(10):4327-4340. https://doi.org/10.1021/acsbiomaterials.2c004444327434081