Permanent Hydrophilization and Generic Bioactivation of Melt Electrowritten Scaffolds

Melt electrowriting (MEW) is an emerging additive manufacturing technology that direct-writes low-micron diameter fibers into 3D scaffolds with high porosities. Often, the polymers currently used for MEW are hydrophobic thermoplastics that induce unspecific protein adsorption and subsequent uncontrolled cell adhesion. Here are developed a coating strategy for MEW scaffolds based on six-arm star-shaped NCO-poly(ethylene oxide-stat-propylene oxide) (sP(EO-stat-PO)). This permanently hydrophilizes the PCL through the formation of a hydrogel coating and minimizes unspecific interactions with proteins and cells. It also provides the option of simultaneous covalent attachment of bioactive molecules through reaction with isocyanates before these are hydrolyzed. Furthermore, a photoactivatable chemical functionalization is introduced that is not dependent on the time-limited window of isocyanate chemistry. For this, photo-leucine is covalently immobilized into the sP(EO-stat-PO) layer, resulting in a photoactivatable scaffold that enables the binding of sterically demanding molecules at any timepoint after scaffold preparation and coating and is decoupled from the isocyanate chemistry. A successful biofunctionalization of MEW scaffolds via this strategy is demonstrated with streptavidin and collagen as examples. This hydrogel coating system is a generic one that introduces flexible specific and multiple surface functionalization, potentially for a spectrum of polymers made from different manufacturing processes.