Inhibiting intimal hyperplasia in prosthetic vascular grafts via immobilized all-trans retinoic acid

JOURNAL OF CONTROLLED RELEASE

卷:274

Article

Gregory, Elaine K.^1,3  Webb, Antonio⁴  Vercammen, Janet M.^1,3  Kelly, Megan E.^1,3  Akar, Banu²  van Lith, Robert^2,3  Bahnson, Edward M.⁵  Jiang, Wulin^1,3  Ameer, Guillermo A.^1,2,3  Kibbe, Melina R.^1,3,5 

[1] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA

[2] Northwestern Univ, McCormick Sch Engn, Dept Biomed Engn, Evanston, IL 60201 USA

[3] Northwestern Univ, Simpson Querrey Inst BioNanotechnol, Chicago, IL 60611 USA

[4] Univ Florida, Gainesville, FL 32611 USA

[5] Univ North Carolina Chapel Hill, Dept Surg, Chapel Hill, NC 27599 USA

关键词: Peripheral vascular disease;    Restenosis;    Intimal hyperplasia;    atRA, endothelium;    Nitric oxide;   

DOI  :  10.1016/j.jconrel.2018.01.020

来源: Elsevier

【 摘 要 】

Peripheral arterial disease is a leading cause of morbidity and mortality. The most commonly utilized prosthetic material for peripheral bypass grafting is expanded polytetrafluoroethylene (ePTFE) yet it continues to exhibit poor performance from restenosis due to neointimal hyperplasia, especially in femoral distal bypass procedures. Recently, we demonstrated that periadventitial delivery of all-trans retinoic acid (atRA) immobilized throughout porous poly(1,8 octamethylene citrate) (POC) membranes inhibited neointimal formation in a rat arterial injury model. Thus, the objective of this study was to investigate whether atRA immobilized throughout the lumen of ePTFE vascular grafts would inhibit intimal formation following arterial bypass grafting. Utilizing standard ePTFE, two types of atRA-containing ePTFE vascular grafts were fabricated and evaluated: grafts whereby all-trans retinoic acid was directly immobilized on ePTFE (atRA-ePTFE) and grafts where all-trans retinoic acid was immobilized onto ePTFE grafts coated with POC (atRA-POC-ePTFE). All grafts were characterized by SEM, HPLC, and FTIR and physical characteristics were evaluated in vitro. Modification of these grafts, did not significantly alter their physical characteristics or biocompatibility, and resulted in inhibition of intimal formation in a rat aortic bypass model, with atRA-POC-ePTFE inhibiting intimal formation at both the proximal and distal graft sections. In addition, treatment with atRA-POC-ePTFE resulted in increased graft endothelialization and decreased inflammation when compared to the other treatment groups. This work further confirms the biocompatibility and efficacy of locally delivered atRA to inhibit intimal formation in a bypass setting. Thus, atRA-POC-ePTFE grafts have the potential to improve patency rates in small diameter bypass grafts and warrant further investigation.

【 授权许可】

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