Bioactive Topographies: Shaping Cell Behavior with Thermally Patterned Poly(ε-caprolactone)

The interface between biomaterials and biological systems critically governs the cellular fate and function. This study presents a straightforward methodology for engineering cell-material interfaces on semicrystalline poly(epsilon-caprolactone) (PCL) films. Our approach leverages thermomechanical treatments to precisely control the surface presentation of cell-adhesive arginine-glycine-aspartic acid (RGD) peptides. By employing a solvent casting technique, followed by controlled thermal annealing, we successfully fabricated PCL films exhibiting a range of crystallinity levels. This variation in crystallinity allowed for the fine-tuned modulation of RGD peptide density across the PCL surfaces, spanning from 25 to 70 nmol/cm2, achieved through consistent aminolysis reaction conditions. Subsequent application of uniaxial stretching induced anisotropic reorientation of these peptides, effectively generating surfaces with defined biochemical patterns capable of directing cellular adhesion, morphology, and orientation. Our results reveal that the surface density of RGD peptides exerts a significant influence on cell behavior measured through the focal adhesion assembly, which is crucial for cell-material interaction and signaling. Furthermore, the peptide density and orientation significantly impacted the cell migration directionality. Through quantitative analysis of cell trajectories obtained via time-lapse microscopy, we demonstrated the ability of these patterned biochemical signals to effectively guide cellular motility along predetermined paths. These findings emphasize the importance of ligand spacing and the synergistic interplay between biochemical and topographical cues in cell-material interactions. Importantly, the developed method is straightforward and highly reproducible with the flexibility to reset and redefine the surface patterns. While primarily conceived as a fundamental approach, it holds potential for scalability and industrial translation thanks to the relatively simple processing of PCL compared to other biopolymers.