Beneficial use of fibroblast growth factor 2 and RGTA, a new family of heparan mimics, for endothelialization of PET prostheses

Abstract

We have studied the endothelialization of polyethylene terephtalate (PET) prostheses coated with collagen by adult human saphenous endothelial cells (EC) under various in vitro conditions. Collagenous PET was impregnated either by Fibroblast Growth Factor 2 (FGF2), heparin, a synthetic heparan sulfate mimic named RGTA 11 (for ReGeneraTing Agent), or combinations of these products. RGTA 11 belongs to a new family of drugs, which have been previously described as stabilizer and protector of heparin binding growth factors (HBGF), and to act in vivo as to stimulate wounded tissue repair. As endothelialization of prosthesis can be obtained in vivo after EC seeding and/or by transanastomotic, as well as by transprosthetic EC migrations, we have designed in vitro models to study the growth of EC seeded on PET, the EC colonization of an acellular area on PET, and the migration of EC from a collagen gel through the prosthesis. The combinations of either RGTA11 or heparin with FGF2 enhanced after a week by 5-fold the growth of seeded EC compared to RGTA or heparin alone and by 3-fold compared to FGF2 alone (p < 0.05). More than 80% of the colonization of an acellular area was achieved within 6 days when FGF2 was combined with RGTA11 or heparin. In contrast, colonization was only of 20% promoted in presence of FGF2 alone and not promoted in the presence of RGTA or heparin alone (p < 0.05). In addition, transprosthetic migration of EC and endothelialization of the luminal side were observed only when gel contained RGTA11 or heparin in combination with FGF2. The present work did strongly indicate that RGTA11 could be used in vivo as to improve endothelialization and should be the focus of continued investigation.