Biocompatibility Assessment of a New Biodegradable Vascular Graft via In Vitro Co-culture Approaches and In Vivo Model.

Marjan Enayati,Barbara Messner,Christian Grasl,Helga Bergmeister,Christoph Kaun,Bruno K Podesser,Magdalena Eilenberg,Ingrid Walter,Johann Wojta,Heinrich Schima,Peter Riedl,Robert Liska

doi:10.1007/s10439-016-1601-y

Abstract

Following the implantation of biodegradable vascular grafts, macrophages and fibroblasts are the major two cell types recruited to the host-biomaterial interface. In-vitro biocompatibility assessment usually involves one cell type, predominantly macrophages. In this study, macrophage and fibroblast mono- and co-cultures, in paracrine and juxtacrine settings, were used to evaluate a new biodegradable thermoplastic polyurethane (TPU) vascular graft. Expanded-polytetrafluoroethylene (ePTFE) grafts served as controls. Pro/anti-inflammatory gene expression of macrophages and cytokines was assessed in vitro and compared to those of an in vivo rat model. Host cell infiltration and the type of proliferated cells was further studied in vivo. TPU grafts revealed superior support in cell attachment, infiltration and proliferation compared with ePTFE grafts. Expression of pro-inflammatory TNF-α/IL-1α cytokines was significantly higher in ePTFE, whereas the level of IL-10 was higher in TPU. Initial high expression of pro-inflammatory CCR7 macrophages was noted in TPU, however there was a clear transition from CCR7 to anti-inflammatory CD163 expression in vitro and in vivo only in TPU, confirming superior cell-biomaterial response. The co-culture models, especially the paracrine model, revealed higher fidelity to the immunomodulatory/biocompatibility behavior of degradable TPU grafts in vivo. This study established an exciting approach developing a co-culture model as a tool for biocompatibility evaluation of degradable biomaterials.Electronic supplementary materialThe online version of this article (doi:10.1007/s10439-016-1601-y) contains supplementary material, which is available to authorized users.

Highlights

Despite considerable research in the field of small diameter vascular graft (SDVG) replacement, there is still no ideal alternative to autografts up to now
Amplicon Size attached to the thermoplastic polyurethane polymer (TPU) grafts and no significant changes in morphology were apparent compared to the graftfree cultures (Figs. 1d–1i)
The morphology of macrophages and fibroblasts did not change in the cocultures, suggesting that these two cell types had no obvious effect on the structure of one-another

Summary

Introduction

Despite considerable research in the field of small diameter vascular graft (SDVG) replacement, there is still no ideal alternative to autografts up to now. Numerous problems are associated to synthetic SDVGs such as, thrombogenicity and intimal hyperplasia.[11]. Developing new generations of such conduits has become a major focus of scientists. One new approach is designing cell-free degradable vascular grafts, which promote remodeling via fast host cell infiltration. Permanent presence of the foreign material in the host tissue will be avoided in these grafts.[22]. In our previous study a new biodegradable thermoplastic polyurethane polymer (TPU) with ultimate mechanical and functional behavior was synthesized and characterized.[4] the inflammatory potential of the graft, which may evoke acute/chronic inflammatory responses at the site of implantation, still needs to be fully characterized

Methods

Results

Discussion

Conclusion