Surface modification of polycaprolactone with sulfated alginate for enhanced binding of a heparin-binding protein

Surface modification of poly(ε-caprolactone) (PCL) to facilitate interactions with high pI proteins is a strategy used to enhance 3D PCL scaffolds for tissue engineering applications. The approach of the current study was to firstly optimise the surface modification on 2D films and then apply to 3D scaffolds. Melt-pressed PCL films were grafted with 2-aminoethyl methacrylate via gamma radiation induced grafting to introduce amine functional groups to the substrate surfaces. The effect of different grafting conditions including monomer concentration, radiation dose, solvent and solution pH on the degree of grafting was evaluated using contact angle measurements and X-ray photoelectron spectroscopy. The optimised grafting conditions ensured the grafts had a hydrodynamic radius of <5 nm to allow clearance from the body after degradation of the PCL material. Solution binding studies of the polymers alginate, sulfated alginate (S-Alg), and heparin with the high pI heparin binding protein, lactoferrin (LF) confirmed that S-Alg is an effective heparin mimetic. This biopolymer was selected for conjugation to the amine-grafted PCL films through carbodiimide chemistry and time-of-flight secondary ion mass spectrometry was used to verify amide coupling. The stability of the surface layer was evaluated in vitro in buffer solution to determine that the unaltered and functional lifetime of the surface layer was at least 21 days. Binding of LF to the S-Alg modified surface was confirmed. The optimised amine grafting and S-Alg conjugation conditions were applied to 3D-printed medical-grade PCL scaffolds to demonstrate the potential clinical translation of this work.