Surface Engineering of Polycaprolactone by Biomacromolecules and their Blood Compatibility

Abstract

Improving blood compatibility of biodegradable polymers is an area of intensive research in blood contacting devices. In this study, curdlan sulphate and heparin-modified poly (caprolactone) (PCL) hybrids were developed by physically entrapping these molecules on the PCL surface. This modification technique was performed by reversible gelation of the PCL surface region following exposure to a solvent and nonsolvent mixture. The presence of these biomacromolecules on the PCL surface was verified by atomic force microscopy (AFM) and scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDAX) analysis, while wettability of the films was investigated by dynamic contact angle measurements. The blood compatibilities of the surface-modified films were examined using in vitro platelet and leukocyte adhesion and thrombus formation. Mouse RAW 264.7 macrophage cells were used to assess the cell adhesion and inflammatory response to the modified surface by quantifying mRNA expression levels of proinflammatory cytokines namely TNF-α and IL-1β using real-time polymerase chain reaction (RT-PCR). A lower platelet and leukocyte adhesion and activation was observed on the modified films incubated with whole human blood for 2 h. The thrombus formation on the PCL was significantly decreased upon immobilization of both curdlan sulphate (39%, *p<0.05) and heparin (28%, *p<0.01) when compared to bare PCL (80%). All of these results revealed that improved blood compatibility was obtained by surface entrapment of both curdlan sulphate (CURS) and heparin (HEP) onto PCL films. Both PCL-CURS and PCL-HEP films reduced RAW 264.7 macrophage cell adhesion (*p<0.05) with respect to the base unmodified PCL. The cellular inflammatory response was suppressed on the modified substrates. The mRNA expression levels of proinflammmatory cytokines (TNF-α and IL-1β) were upregulated on bare PCL, while it was significantly lower on PCL-CURS and PCL-HEP substrates (**p<0.001). Thus, this biomacromolecule entrapment process can be applied on PCL in order to achieve improved blood compatibility and reduced inflammatory host response for its future blood contacting applications.