Engineering of vascular ingrowth matrices: Are protein domains an alternative to peptides?

Abstract

Anastomotic intimal hyperplasia and surface thrombogenicity are the main reasons for the high failure rate of prosthetic small-diameter vascular grafts. While anastomotic intimal hyperplasia is a multifactorial event, ongoing surface thrombogenicity is primarily caused by the lack of an endothelium, even after years of clinical implantation. After decades of poorly performing synthetic artery-grafts, tissue engineering has emerged as a promising approach to generate biologically functional bio-synthetic hybrid grafts mimicking native arteries regarding the presence of an endothelial lining on the blood surface. "In vitro endothelialization" represented the first generation of such tissue-engineered vascular grafts, utilising cell culture techniques for the creation of a confluent autologous endothelium on ePTFE grafts. The clinical long-term results with this method in almost 200 patients are highly encouraging, showing patencies equal to vein grafts. Since "in vitro endothelialization" requires cell culture facilities, it will always be confined to large centres. Therefore, research of the 1990s turned to the development of spontaneously endothelializing implants, to make tissue-engineered grafts amenable to the entire vascular-surgical community. Apart from scaffold designs allowing transmural ingrowth, biological signalling through a facilitating ingrowth matrix holds a key to spontaneous endothelialization. In biological signalling, the increasingly deeper understanding of bio-active molecules and the discovery of domains and peptide sequences during the 1980s created the expectation in the 1990s that peptide signalling may be all that is needed. This present review highlights the possible problems associated with such a reductionist approach. Using the fibronectin molecule, we demonstrated that domains may be more suitable modules in tissue engineering than peptide sequences.

The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model

“…It was known that neointimal hyperplasia is the main stage in the pathogenesis of restenosis development after vascular injury (1)(2)(3). It is also the main cause of late graft occlusions after vascular surgery (1-3).…”

“…The main reason for early failure of small diameter grafts used in vascular surgery is thrombotic occlusion, whereas the main reason for late failure is neointimal hyperplasia (1)(2)(3). Therapeutic interventions such as balloon angioplasty, stenting and surgical vascular anastomosis results in arterial injury.…”

The selective modulation of endothelial cell mobility on RGD peptide containing surfaces by YIGSR peptides

“…It is, therefore, reasonable to assume that combinations of these bioactive peptides will be needed to confer increased biological activity to biomaterials [21]. We have investigated the effect of the 67 kDa LBP ligand, YIGSR [12] and the PHSRN motif from fibronectin domain FIII-9 [22] on the migration of the major vascular cells (MVEC and HVSMC) on surfaces modified with the potent cell binding RGD peptide [11].…”

Effect of Tadalafil on Neointimal Hyperplasia in a Rabbit Carotid Artery Anastomosis Model

“…Neointimal hyperplasia is a main factor in the pathogenesis of restenosis, which occurs following arteriosclerosis, vascular damage and angioplasty, and of the late-term graft failure in vascular surgery. [1][2][3][4] Neointimal hyperplasia is developed in three steps: destruction of extracellular matrix (ESM), proliferation of vascular smooth muscle cells (VSMC), and their migration from media to intima.…”