Intrinsic Vascularization of Recombinant eADF4(C16) Spider Silk Matrices in the Arteriovenous Loop Model.

Abstract

The surgically induced angiogenesis by means of arteriovenous (AV) loops represents a powerful method to significantly enhance vascularization of biomaterials. Regarding tissue engineering applications, spider silk is a promising biomaterial with a good biocompatibility and slow biodegradation. This study aims at investigating vascularization as well as de novo tissue formation of fibrous matrices made of electro-spun (ES) or wet-spun (WS) engineered ADF4(C16) spider silks in the rat AV loop model. Either ES or WS spider silk fibrous matrices were filled into Teflon chambers. Intrinsic vascularization was induced by means of an AV loop. After 4 weeks of vascularization, de novo tissue formation and biocompatibility were analyzed. Regardless of their significantly differing fiber diameters, both ES and WS eADF4(C16) fiber matrices displayed a good biocompatibility and initiated de novo tissue formation as well as vessel formation. Both matrices demonstrated partial vascularization originating from the AV loop, with more vessels in spider silk matrices with lower fiber diameters. We were able to demonstrate intrinsic vascularization of spider silk fibrous matrices by means of the AV loop. Moreover, our study indicates that the adjustment of the fiber diameter of engineered spider silks enables new possibilities to optimize vascularization. Impact Statement Spider silk is a promising biomaterial demonstrating excellent biocompatibility and biodegradation. Biotechnology allows the high-volume production of recombinant spider silk proteins, such as eADF4(C16), with the required purity for biomedical applications. In this study, eADF4(C16) fibrous matrices were produced by either electro- or wet-spinning, resulting in different fiber diameters. Forming an arteriovenous fistula, surgical vascularization of the scaffolds was induced. After 4 weeks, both silks demonstrated a good biocompatibility and tissue formation. The thinner electro-spun fibers displayed a faster biodegradation and vascularization, indicating that the adjustment of the fiber diameter is a valuable tool to fine-tune vascularization and biodegradation.