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

We have studied the endothelialization of polyethylene terephtalate (PET) p rostheses coated with collagen by adult human saphenous endothelial cells ( EC) under various in vitro conditions. Collagenous PET was impregnated eith er by Fibroblast Growth Factor 2 (FGF2), heparin, a synthetic heparan sulfa te mimic named RGTA 11 (for ReGenera Ting Agent), or combinations of these products. RGTA 11 belongs to a new family of drugs, which have been previou sly described as stabilizer and protector of heparin binding growth factors (HBGF), and to act in vivo as to stimulate wounded tissue repair, As endot helialization 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 co lonization of an acellular area on PET, and the migration of EC from a coll agen gel through the prosthesis. The combinations of either RGTA11 or hepar in with FGF2 enhanced after a week by 5-fold the growth of seeded EC compar ed 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 ed wi thin 6 days when FGF2 was combined with RGTA ii or heparin. In contrast, co lonization was only of 20% promoted in presence of FGF2 alone and not promo ted in the presence of RGTA or heparin alone (p < 0.05). In addition, trans prosthetic 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 inves tigation. (C) 2001 John Wiley & Sons. Inc. J Biomed Mater Res (Appl Biomate r) 58: 1-9. 2001.