Improved endothelialization and reduced thrombosis by coating a synthetic vascular graft with fibronectin and stem cell homing factor SDF-1α.

Failure of synthetic small-diameter vascular grafts is determined mainly by the lack of endothelial cells, as these cells inhibit thrombosis and intimal hyperplasia. Coating of graft material with homing factors for circulating stem cells has the potential to improve endogenous endothelialization of these grafts and to reduce graft failure. Synthetic knitted polyester grafts (6mm diameter) were coated with FN and SDF-1α before surgical interposition in the carotid artery of sheep. Similar uncoated vascular grafts were implanted in the contralateral side as internal controls. To study the early attraction of stem cells, grafts were implanted in a first series of nine sheep and explanted after 1 or 3 days. In coated grafts, four times higher fractions of CD34(+) and three to four times higher fractions of CD117(+) cells adhering to the vessel walls were found than in control grafts (P<0.05). When such coated and non-coated grafts were implanted in 12 other sheep and explanted after 3 months, all coated grafts were patent, while one control graft was occluded. EcNOS staining revealed that FN-SDF-1α coating significantly increased coverage with endothelial cells from 27 ± 4% of the graft to 48 ± 4% compared with the controls (P=0.001). This was associated with a significant reduction of intimal hyperplasia (average thickness 1.03 ± 0.09 mm in controls vs. 0.69 ± 0.04 mm in coated grafts; P=0.009) and significantly less adhesion of thrombotic material in the middle part of the graft (P=0.029). FN-SDF-1α coating of synthetic small-caliber vascular grafts stimulated the attraction of stem cells and was associated with improved endothelialization and reduced intimal hyperplasia and thrombosis.

Cyclically stretching developing tissue in vivo enhances mechanical strength and organization of vascular grafts.

Tissue-engineered vascular grafts must have qualities that rival native vasculature, specifically the ability to remodel, the expression of functional endothelial components and a dynamic and functional extracellular matrix (ECM) that resists the forces of the arterial circulation. We have developed a device that when inserted into the peritoneal cavity, attracts cells around a tubular scaffold to generate autologous arterial grafts. The device is capable of cyclically stretching (by means of a pulsatile pump) developing tissue to increase the mechanical strength of the graft. Pulsed (n=8) and unpulsed (n=8) devices were implanted for 10 days in Lovenaar sheep (n=8). Pulsation occurred for a period of 5-8 days before harvest. Thick unadhered autologous tissue with cells residing in a collagen ECM was produced in all devices. Collagen organization was greater in the circumferential direction of pulsed tissue. Immunohistochemical labelling revealed the hematopoietic origin of >90% cells and a significantly higher coexpression with vimentin in pulsed tissue. F-actin expression, mechanical failure strength and strain were also significantly increased by pulsation. Moreover, tissue could be grafted as carotid artery patches. This paper shows that unadhered tissue tubes with increased mechanical strength and differentiation in response to pulsation can be produced with every implant after a period of 10 days. However, these tissue tubes require a more fine-tuned exposure to pulsation to be suitable for use as vascular grafts.