Gradient polymers for tissue engineering

With increasing life expectancy, there is an constant demand for finding solutions to restore damaged or diseased tissues and organs. Regenerative medicine holds the promise to create continuous body-part replacements through the combination of cells, biological factors, and synthetic scaffolds. However, a better control over cell-material interactions needs to be achieved to fabricate better performing and long-lasting supports for tissue engineering (TE). In the human body chemical and physical gradients regulate cell migration and differentiation. It is thus crucial to control these processes in 3D artificial scaffolds used in regenerative medicine. In order to accomplish this, the modification of biomaterials’ interfaces represent a potentially successful approach. This includes the fabrication of synthetic extra-cellular matrices (ECMs) presenting interfacial gradients which can regulate the behavior of adhering cells. Inspired by these approaches I fabricated chemical gradients on polymer substrates in order to determine cell response on both 2D and 3D supports. A specific focus is placed on polymer brush coatings with controllable properties (adhesion, flexibility, bioactivity) synthesized by surface-initiated atom transfer radical polymerization (SI-ATRP). By this method poly(N-isopropyl acrylamide) (PNIPAM) and functionalizable poly(oligo(ethylene glycol) methacrylate (POEGMA) brushes were “grafted-from” 2D and 3D poly(ε-caprolactone) (PCL) supports. These thermoresponsive PNIPAM layers were applied to thermally control cellular adhesion while POEGMA-coated supports were used to vary the bioactivity of the coating via conjugated with fibronectin (FN) and growth factors. The peculiar physical properties of POEGMA brushes such as wettability and high functionality were exploited to obtain multi-dimensional surface gradients of (bio)chemical signals for spatially controlling cell behavior