Surface functionalization of poly(ε‐caprolactone) improves its biocompatibility as scaffold material for bioartificial vessel prostheses

Abstract

Within this study, chemically modified polymer surfaces were to be developed, which should enhance the subsequent immobilization of various bioactive substances. To improve the hemocompatibility and endothelialization of poly(ε-caprolactone) (PCL) intended as scaffold material for bioartificial vessel prostheses, terminal amino groups via ammonia (NH₃) plasma, oxygen (O₂) plasma/aminopropyltriethoxysilane (APTES), and 4,4'-methylenebis(phenyl isocyanate) (MDI)/water were provided. Then, immobilization of the anti-inflammatory and antithrombogenic model drug acetylsalicylic acid (ASA) and vascular endothelial growth factor (VEGF) were performed by employing N,N-disuccinimidyl carbonate (DSC) as crosslinker. Contact angle and fluorescence measurements, X-ray photoelectron spectroscopy and infrared spectroscopy confirmed the surface modification. Here the highest functionalization was observed for the O₂ plasma/APTES modification. Furthermore, biocompatibility studies demonstrated that the surface reactions have no negative influence, neither on the viability of L929 mouse fibroblasts, nor on primary or secondary hemostasis. Release studies showed that the immobilization of ASA and VEGF on the modified PCL surface via DSC is greatly improved compared to the adsorption-only reference. The advantage of DSC is that it immobilizes both bioactive substances via non-hydrolyzable and/or hydrolyzable covalent bonding. The highest ASA loading and cumulative release was detected using NH₃ plasma-activated PCL samples. For VEGF, the O₂ plasma/APTES-modified PCL samples were most efficient with regard to loading and cumulative release. In conclusion, both modifications are promising methods to optimize PCL as scaffold material for bioartificial vessel prostheses.

Surface functionalization of poly(ε-caprolactone) and poly(3-hydroxybutyrate) with VEGF

“…In this context, the biodegradable polymers PCL and P(3HB) play an important role for drug delivery systems. In former investigations we already described promising results of amino group modified PCL surfaces [2].…”

“…In particular, relative viability of L929 cells on PCL was similar on both plasma-chemical modified surfaces compared to untreated PCL, with nearly similar cell viabilities of 98% and 107% for CO 2 and O 2 plasma-chemical modified surfaces, respectively. In contrast, on P(3HB), cell viability of L929 cells was slightly enhanced on the CO 2 and significantly decreased on the O 2 plasma-chemical modified surfaces with 114% and 76% in comparison to the untreated P(3HB) surface.…”

“…The immobilized VEGF was calculated by a sandwich-avidin-biotin complex (ABC)-ELISA to convert the PAP-ELISA signal. VEGF loading was determined via ELISA using PAP for signal amplification according to Wulf et al [2]. In order to eliminate positive immobilization results by unspecific VEGF adhesion and to measure only covalently bounded VEGF, we optimized the washing procedures for PCL and P(3HB) surfaces.…”

“…In this context, biodegradable polymers such as poly(ε-caprolactone) (PCL) and poly (3-hydroxybutyrate) [P(3HB)] are approved and promising candidates as implant materials regarding the immobilization and controlled release of biomolecules. For instance, synthetic degradable PCL and P(3HB) are widely used in the biomedical field, such as material for sutures, wound dressings, drug delivery devices and scaffolds for tissue engineering, especially in the development of scaffolds for tissue-engineered vessel grafts or prostheses [1], [2], [3], [4].…”

Enhanced Endothelialization of PCL Through Chemical Activation, Protein Precoating and VEGF Stimulation

“…The formation of an intact endothelium at the vesselstent interface straight after implantation is of key importance for preventing thrombosis as well as restenosis. Therefore we attempted to improve endothelialisation of poly(ε-caprolactone), a polymer often used in artificial vessel development [2,3], via three different strategies: 1. chemical surface activation, 2. precoating with proteins of the extracellular matrix, and 3. stimulation of endothelial growth with specific growth factor. In order to provide insights into the materials' feasibility for use in cardiovascular stents, we are using primary human umbilical vein endothelial cells (HUVECs) in vitro to test surface-functionalized polymers for both their biocompatibility and cell stimulatory potential.…”