A Supramolecular Platform for the Introduction of Fc-Fusion Bioactive Proteins on Biomaterial Surfaces

: Putti M, de Jong SMJ, Stassen OMJA, Sahlgren CM, Dankers PYW

Publisher: AMER CHEMICAL SOC

: Washington

: 2019

: ACS Applied Polymer Materials

: ACS APPLIED POLYMER MATERIALS

: ACS APPL POLYM MATER

: 1

: 8

: 2044

: 2054

: 21

DOI: https://doi.org/10.1021/acsapm.9b00334

Bioorthogonal chemistry is an excellent method for functionalization of biomaterials with bioactive molecules, as it allows for decoupling of material processing and bioactivation. Here, we report on a modular system created by means of tetrazine/trans-cyclooctene (Tz/TCO) click chemistry undergoing an inverse electron demand Diels-Alder cycloaddition. A reactive supramolecular surface based on ureido-pyrimidinones (UPy) is generated via a UPy-Tz additive, in order to introduce a versatile TCO-protein G conjugate for immobilization of Fc-fusion proteins. As a model bioactive protein, we introduced FcJagged1, a Notch ligand, to induce Notch signaling activity on the material. Interestingly, HEK293 FLN1 cells expressing the Notch1 receptor were repelled by films modified with TCO-protein G but adhered and spread on functionalized electrospun meshes. This indicates that the material processing method influences the biocompatibility of the postmodification. Notch signaling activity was upregulated 5.6-fold with respect to inactive controls on electrospun materials modified with TCO-protein G/Fc-Jagged1. Furthermore, downstream effects of Notch signaling were detected on the gene level in vascular smooth muscle cells expressing the Notch3 receptor. Taken together, our results demonstrate the successful use of a modular supramolecular system for the postprocessing modification of solid materials with functional proteins.