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

• Published in: ACS macro letters Vol. 9; no. 9; pp. 1369 - 1375
• Main Authors: Ravikrishnan, Anitha, Zhang, He, Fox, Joseph M, Jia, Xinqiao
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15-09-2020
• ISSN: 2161-1653; 2161-1653
• DOI: 10.1021/acsmacrolett.0c00515

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). Electrospun poly­(ε-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-β) 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.