Mechanisms of healing in synthetic grafts

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In previous baboon studies we have shown that porous (60 μm mean internodal distance) polytetrafluoroethylene (PTFE) grafts heal by ingrowth of endothelium and smooth muscle cells from the adjacent artery and from capillaries penetrating through the interstices of the graft. However, porous grafts (principally made of Dacron) in humans do not heal. This has been attributed to a wound healing deficiency in humans; however, it might be due to an inhibitory effect of the Dacron itself. To examine the latter possibility, we undertook this study to compare the healing of 4 mm internal diameter porous Dacron grafts (USCI, Sauvage Filamentous Knitted) with that of Gore-Tex 60 μm PTFE grafts in baboons (the latter graft not available for clinical use). The grafts were harvested at 2, 4, and 12 weeks and assessed for (1) percentage of endothelial coverage, (2) endothelial cell (EC) proliferation (thymidine labeling index), (3) intimal area, and (4) smooth muscle cell (SMC) proliferation (thymidine labeling index). The PTFE grafts at all three time points were fully covered, whereas only one of five Dacron grafts was completely covered at 12 weeks. The intima of the PTFE grafts consisted of ECs and SMCs, whereas that of the Dacron grafts contained ECs and SMCs as well as focal accumulations of thrombus. The intimal cross-sectional areas in the Dacron grafts (3.0 ± 1.2 mm2) were significantly greater than in the PTFE grafts (0.8 ± 0.6 mm2) at 4 weeks; there was no difference at 12 weeks (Dacron, 2.6 ± 2.3 mm2 and PTFE, 3.0 ± 2.5 mm2). SMCs in the intima of the Dacron and PTFE grafts were actively proliferating at 4 weeks but returned to normal levels at 12 weeks. ECs continued to proliferate even at 12 weeks in both Dacron and PTFE grafts, suggesting continued denudation and replacement. Although both USCI Dacron and porous PTFE grafts heal by proliferation of cells derived from invading capillaries, nevertheless endothelial coverage in some Dacron grafts is incomplete even as late as 12 weeks. This result suggests that the failure of Dacron grafts in humans to develop an endothelial lining might be attributable in part to the graft material itself.