Bioabsorbable Stent-Covering with Sustained Anticoagulant Activity Fabricated via Alternate Layer-by-Layer Self-Assembly of Heparin and Silk Fibroin

Abstract

For severe local vasculopathy, covered stents are considered the major medical devices in interventional therapy due to their function to isolate lesions and deliver drugs. However, commercial stent-coverings have unsatisfactory drug-loading capacity and lack bioactivity. Silk fibroin (SF) possesses excellent biocompatibility, biodegradability, and endothelialization ability. In this study, we developed a bioabsorbable SF stent-covering loaded with heparin (Hep) via layer-by-layer self-assembly. Hep was embedded in the stent-covering via interfacial adsorption (Hep-SF) or direct blending with SF (Hep/SF). For interfacial adsorption, the Hep loading capacity increased with adsorption time and Hep concentration, reaching up to 589 μg/cm². All Hep-modified SF stent-coverings were nonhemolytic. After Hep modification, the recalculation time of the Hep-SF stent-covering was significantly prolonged (>2 h), platelet adhesion to its surface was reduced, and no obvious clots formed. Compared to the Hep/SF stent-coverings, the release quantity of Hep from the Hep-SF stent-covering was higher at each time point, regardless of diffusion or enzymatic degradation, but its diffusion release rate was lower than that of the high-dosage Hep/SF stent-covering, suggesting that the Hep-SF stent-covering had more sustained Hep release. Moreover, the released Hep maintained a high anticoagulant activity to significantly prolong activated partial thromboplastin time and thrombin time after long-time diffusion or enzymatic degradation. The results indicated that the Hep-SF stent-covering developed in this study not only had a high loading capacity for anticoagulant drugs (on-demand adjustable) but also could achieve effective and sustained anticoagulant function until the SF material was completely degraded.