Prevention of anastomotic intimal hyperplasia (AIH) requires inhibition of the migration of smooth muscle cells (SMCs) and promotion of endothelial cell (ECs) growth from the native arterial wall. We investigated the effect of coacervated alpha-elastin on migration of SMCs and ECs in vitro. SMCs and ECs were prepared from porcine aortic media and endothelium. Coacervated alpha-elastin was coated and cross-linked around the perimeter of each 1 cm diameter center of a well in a 12 well plate. SMCs and ECs were placed and cultured within the center of each well. The migration of SMCs and ECs on coacervated alpha-elastin was assayed on the second, third (10 mg/ml), or fourth day (0.1, 1.0, 10.0 mg/ml) of cultivation by measuring the area of migration from the 1 cm diameter center. Coacervated alpha-elastin was then coated and cross-linked on a Dacron graft using 1% glycerol polyglycidyl ether (GPGE) and examined with scanning electron microscopy to determine the feasibility of graft coating. SMC migration was significantly inhibited dose dependently over time (p < 0.005), e.g., 0.1 mg/ml (45.4% +/- 2.7%: % of MES [pH 5] and 1% GPGE without alpha-elastin), 1.0 mg/ml (32.0% +/- 1.4%), 10.0 mg/ml (8.3% +/- 2.9%). EC migration (90.7% +/- 6.2%: p = ns) was not inhibited by 0.1 mg/ml of coacervated alpha-elastin. Cross-linked coacervated alpha-elastin was coated on a dacron graft uniformly. Incorporation of coacervated alpha-elastin into the structure of arterial prostheses offers the possibility of inhibition of SMC hyperplasia without inhibition of EC formation.

Anastomosis, Surgical↗

PubMedDate not supplied

Enhanced neointima formation and attachment on the high-porosity inner surface of modified PTFE vascular grafts.

Highly porous PTFE arterial prostheses form endothelium more extensively than the low-porosity grafts in clinical use, but are subject to seroma formation. PTFE vascular grafts were modified to produce a highly porous inner layer (inner layer 60 or 90 microns, outer layer 20 microns). The effect of this modified, composite design on the histology of graft healing was investigated. Twenty-five modified and 25 control grafts, each 4 mm in diameter by 5 cm in length, were implanted into carotid and femoral arteries of dogs. No late seroma formation was observed. After 12 and 18 weeks, the neointima of the grafts was examined by light microscopy and scanning electron microscopy. At 2- and 4-mm distances from the proximal and distal anastomoses, intimal thickness of the control grafts was 238.7 and 96.1 microns, respectively; for the modified grafts it was 236.2 and 202.8 microns at 18 weeks. Thus, the neotinima of modified grafts was thicker than that of control grafts when measured at 4 mm from the anastomoses. Neointimal coverage was less extensive in the control grafts than in modified grafts (26.8 +/- 6.1% vs. 58.8 +/- 13.2%; p < .05). Smooth muscle cells were seen on light-microscopy to penetrate the highly porous inner layer; on scanning electron microscopy, the PTFE fibrils appeared to anchor the neointima of the modified graft. The results suggest that modified PTFE grafts with an inner surface of 60 or 90 microns internodal distance have enhanced formation and anchoring of neointima while remaining impervious to blood.

Animals↗