Hierarchical Shish–Kebab Structures Functionalizing Nanofibers for Controlled Drug Release and Improved Antithrombogenicity

The functionalization of the fibrous scaffolds including drug loading and release is of significance in tissue engineering and regenerative medicine. Our previous results have shown that the shish–kebab structure-modified fibrous scaffold shows a completely different microenvironment that mimics the topography of the collagen fibers, which interestingly facilitates the cell adhesion and migration. However, the functionalization of the unique structure needs to be further investigated. In this study, we modified the heparin-loaded fiber with a shish–kebab structure and tuned the kebab structure as the barrier for the sustained release of heparin. The introduction of the kebab structure increases the diffusion energy barrier by extending the diffusion distance. Moreover, the discontinued surface topography of the shish–kebab structure altered the surface chemistry from hydrophobic for the original poly­(ε-caprolactone) (PCL) nanofibers to hydrophilic for the PCL nanofibers with the shish–kebab structure, which might have inhibited the activation of fibrinogen and thus improved the anticoagulant ability. This synergistic effect of heparin and the kebab structure significantly promotes the endothelial cell affinity and antithrombogenicity. This method might be a viable and versatile drug delivery strategy in vascular tissue engineering.