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Updated: Mar 17, 2026
Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency
Published on: January 15, 2017
Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia in a Swine Model of Arteriovenous Bypass
Robert N Goldstone1, Michael C McCormack1, Saiqa I Khan1
1Division of Plastic and Reconstructive Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA.
Insights
Photochemical tissue passivation (PTP) strengthens vein grafts, significantly reducing intimal hyperplasia (IH) and medial hypertrophy. This innovative treatment inhibits smooth muscle cell proliferation and migration, improving graft patency for cardiovascular and peripheral artery disease.
Area of Science:
- Biomaterials Science
- Vascular Surgery
- Regenerative Medicine
Background:
- Coronary artery disease and lower extremity ischemia treatments rely on bypass grafting.
- Venous graft patency is limited by intimal hyperplasia (IH) due to venous injury.
- Smooth muscle cell (SMC) proliferation and migration contribute to IH development.
Purpose of the Study:
- To investigate if photochemical tissue passivation (PTP) treatment of vein grafts can inhibit IH.
- To assess PTP's effect on SMC proliferation and migration in vein grafts.
Main Methods:
- Porcine veins underwent PTP at varying fluences (up to 120 J/cm²).
- Tensiometry measured vessel stiffness; PTP at 90 J/cm² significantly increased Young's modulus.
- Vein grafts (PTP-treated vs. untreated) were implanted in pigs, with analysis at 4 weeks for IH, medial hypertrophy, and cell proliferation (PCNA) and differentiation (SMA).
Main Results:
- PTP treatment at 90 J/cm² increased vein graft stiffness (10-fold greater Young's modulus).
- PTP reduced IH by 66% and medial hypertrophy by 49% in grafts.
- PTP decreased alpha-smooth muscle actin (SMA)-positive cells and proliferating cell nuclear antigen (PCNA)-positive cells (18% in controls vs. 5% in PTP-treated grafts).
Conclusions:
- PTP strengthens vein grafts, making them more resistant to injury.
- PTP effectively reduces smooth muscle cell proliferation and migration.
- PTP inhibits intimal hyperplasia development, offering a promising strategy for improving bypass graft patency.
Background:
Bypass grafting remains the standard of care for coronary artery disease and severe lower extremity ischemia. Efficacy is limited by poor long-term venous graft patency secondary to intimal hyperplasia (IH) caused by venous injury upon exposure to arterial pressure. We investigate whether photochemical tissue passivation (PTP) treatment of vein grafts modulates smooth muscle cell (SMC) proliferation and migration, and inhibits development of IH.
Methods And Results:
PTP was performed at increasing fluences up to 120 J/cm(2) on porcine veins. Tensiometry performed to assess vessel elasticity/stiffness showed increased stiffness with increasing fluence until plateauing at 90 J/cm(2) (median, interquartile range [IQR]). At 90 J/cm(2), PTP-treated vessels had a 10-fold greater Young's modulus than untreated controls (954 [IQR, 2217] vs 99 kPa [IQR, 63]; P=0.03). Each pig received a PTP-treated and untreated carotid artery venous interposition graft. At 4-weeks, intimal/medial areas were assessed. PTP reduced the degree of IH by 66% and medial hypertrophy by 49%. Intimal area was 3.91 (IQR, 1.2) and 1.3 mm(2) (IQR, 0.97; P≤0.001) in untreated and PTP-treated grafts, respectively. Medial area was 9.2 (IQR, 3.2) and 4.7 mm(2) (IQR, 2.0; P≤0.001) in untreated and PTP-treated grafts, respectively. Immunohistochemistry was performed to assess alpha-smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA). Objectively, there were less SMA-positive cells within the intima/media of PTP-treated vessels than controls. There was an increase in PCNA-positive cells within control vein grafts (18% [IQR, 5.3]) versus PTP-treated vein grafts (5% [IQR, 0.9]; P=0.02).
Conclusions:
By strengthening vein grafts, PTP decreases SMC proliferation and migration, thereby reducing IH.
