Chemical surface modification of poly(ε-caprolactone) for accelerated wound healing after implantation of vascular devices

Abstract

Surface modification of vascular implants, like stents, using polymer coatings is an often employed and efficient method. Prevalent, a biodegradable polymer is applied as coating, which additionally functions as local drug delivery system. Handicap of nearly all body foreign polymeric surfaces are inflammatory response, granulation and low reendothelialization. To improve wound healing we modified the surface of the often used biodegradable polyester poly(ε- caprolactone) (PCL). Therefore, we activated the surface by means of wet chemical and plasma chemical methods to create terminal amino groups. These groups were used to bind acetylsalicylic acid (ASS) as model drug to reduce inflammatory reactions. This surface loading functions as an additionally drug reservoir beside a possible incorporated bulk drug. Furthermore, the Vascular Endothelial Growth Factor (VEGF) was coupled to the activated surface to enhance a fast reendothelialization of implants which reduces risk of thrombosis, chronic inflammatory body response and granulation. The surface activation and modifications were analyzed by FTIR-ATR-spectroscopy and contact angle measurements. Additionally, amino groups were detected by fluorescence measurements after the reaction of the amino functionalized surfaces with 4-chloro-7-nitrobenzo-2-oxa-1,3- diazole (NBD-CL). The release of surface bonded ASS was analyzed by HPLC. Coupled VEGF was analyzed by using an indirect ELISA.

ASS shows a short and completely burst release within 4 hours. Bis(sulfosuccinimidyl)suberate (BS³) and glutardialdehyde (GDA) were the best linkers for VEGF surface coupling. Consequently, the presented chemical modification turned out to be a promising method to modify also other polymers for enhancing the performance of the foreign surface material to the body materials.