Self-assembled phosphate-polyamine networks as biocompatible supramolecular platforms to modulate cell adhesion.

The modulation of cell adhesion via biologically inspired materials plays a key role in the development of realistic platforms to envisage not only mechanistic descriptions of many physiological and pathological processes but also new biointerfacial designs compatible with the requirements of biomedical devices. In this work, we show that the cell adhesion and proliferation of three different cell lines can be easily manipulated by using a novel biologically inspired supramolecular coating generated via dip coating of the working substrates in an aqueous solution of polyallylamine in the presence of phosphate anions-a simple one-step modification procedure. Our results reveal that selective cell adhesion can be controlled by varying the deposition time of the coating. Cell proliferation experiments showed a cell type-dependent quasi-exponential growth demonstrating the nontoxic properties of the supramolecular platform. After reaching a certain surface coverage, the supramolecular films based on phosphate-polyamine networks displayed antiadhesive activity towards cells, irrespective of the cell type. However and most interestingly, these antiadherent substrates developed strong adhesive properties after thermal annealing at 37 °C for 3 days. These results were interpreted based on the changes in the coating hydrophilicity, topography and stiffness, with the latter being assessed by atomic force microscopy imaging and indentation experiments. The reported approach is simple, robust and flexible, and would offer opportunities for the development of tunable, biocompatible interfacial architectures to control cell attachment for various biomedical applications.

Tailored polyelectrolyte thin film multilayers to modulate cell adhesion.

The layer-by-layer assembly of polyelectrolyte multilayers (PEMs) from natural or synthetic polyelectrolytes constitutes a very versatile and simple strategy to modify surfaces and modulate cell behavior. PEMs assembled from natural polyelectrolytes are very appealing for biological and medical applications due to their high biocompatibility. However, PEMs from natural polyelectrolytes display poor cell adhesion as they are soft materials with an elasticity modulus of a few kilopascal. In this report, the authors present results on the modulation of cell adhesion of different immortalized cell lines by PEMs. Two strategies are employed to vary cell adhesion: (1) a heterogeneous polyelectrolyte multilayer is assembled employing a rigid bottom block including a synthetic polyelectrolyte with a soft upper block of natural polyelectrolytes and (2) polyelectrolyte multilayers from natural polyelectrolytes are thermally annealed after assembly. The physicochemical characteristics of the PEMs change upon thermal treatment. Depending on the composition of the polyelectrolyte multilayer, cell adhesion may be enhanced or reduced. Based on the impact on PEM properties and cell adhesion caused by thermal annealing, a temperature gradient is applied to a PEM of poly-l-lysine/alginate to induce a spatial variation of PEM properties, resulting in a gradient in cell adhesion. The strategies shown here can be employed as simple alternatives to tailor PEM properties by means of fully biocompatible procedures.

Enhanced antiadhesive properties of chitosan/hyaluronic acid polyelectrolyte multilayers driven by thermal annealing: Low adherence for mammalian cells and selective decrease in adhesion for Gram-positive bacteria.

The development of antifouling coatings with restricted cell and bacteria adherence is fundamental for many biomedical applications. A strategy for the fabrication of antifouling coatings based on the layer-by-layer assembly and thermal annealing is presented. Polyelectrolyte multilayers (PEMs) assembled from chitosan and hyaluronic acid were thermally annealed in an oven at 37°C for 72h. The effect of annealing on the PEM properties and topography was studied by atomic force microscopy, ζ-potential, circular dichroism and contact angle measurements. Cell adherence on PEMs before and after annealing was evaluated by measuring the cell spreading area and aspect ratio for the A549 epithelial, BHK kidney fibroblast, C2C12 myoblast and MC-3T3-E1 osteoblast cell lines. Chitosan/hyaluronic acid PEMs show a low cell adherence that decreases with the thermal annealing, as observed from the reduction in the average cell spreading area and more rounded cell morphology. The adhesion of S. aureus (Gram-positive) and E. coli (Gram-negative) bacteria strains was quantified by optical microscopy, counting the number of colony-forming units and measuring the light scattering of bacteria suspension after detachment from the PEM surface. A 20% decrease in bacteria adhesion was selectively observed in the S. aureus strain after annealing. The changes in mammalian cell and bacteria adhesion correlate with the changes in topography of the chitosan/hyaluronic PEMs from a rough fibrillar 3D structure to a smoother and planar surface after thermal annealing.

Polyelectrolytes Multilayers to Modulate Cell Adhesion: A Study of the Influence of Film Composition and Polyelectrolyte Interdigitation on the Adhesion of the A549 Cell Line.

Polyelectrolyte multilayers (PEMs) with different polycation/polyanion pairs are fabricated by the layer-by-layer technique employing synthetic, natural, and both types of polyelectrolytes. The impact of the chemical composition of PEMs on cell adhesion is assessed by studying cell shape, spreading area, focal contacts, and cell proliferation for the A549 cell line. Cells exhibit good adhesion on PEMs containing natural polycations and poly(sodium 4-styrenesulfonate) (PSS) as polyanion, but limited adhesion is observed on PEMs fabricated from both natural polyelectrolytes. PEMs are then assembled, depositing a block of natural polyelectrolytes on top of a stiffer block with PSS as polyanion. Cell adhesion is enhanced on top of the diblock PEMs compared to purely natural PEMs. This fact could be explained by the interdigitation between polyelectrolytes from the two blocks. Diblock PEM assembly provides a simple means to tune cell adhesion on biocompatible PEMs.