Core-Shell Microfibers via Bioorthogonal Layer-by-Layer Assembly

摘要

A new technique is described for the construction of core-shell microfibers for biomedical applications. Fibrous scaffolds were fabricated by electrospinning, followed by covalent layer-by-layer deposition based on the rapid bioorthogonal reaction between s-tetrazines (Tz) and trans-cyclooctenes (TCOs). Electro-spun poly(e-caprolactone) (PCL) scaffolds were subjected to surface modifications to install tetrazine groups. The scaffolds were iteratively submerged in aqueous solutions of TCO-modified hyaluronic acid (HA-TCO) and tetrazine-modified hyaluronic acid (HA-Tz), resulting in the controlled growth of a cross-linked HA gel around individual microfibers. Integrin-binding motifs were covalently attached to the surface of the microfibers using TCO-conjugated RGD peptide. The scaffolds fostered the attachment and growth of primary porcine vocal fold fibroblasts without a significant induction of the myofibroblast phenotype. Stimulation with transforming growth factor beta (TGF-beta) moderately enhanced fibroblast activation, and inhibition of the Rho/ROCK signaling pathway using Y27632 further decreased the expression of myofibroblastic markers. The bioorthogonally assembled scaffolds with a stiff PCL core and a soft HA shell may find application as therapeutic implants for the treatment of vocal fold scarring.