Inhibiting intimal hyperplasia in prosthetic vascular grafts via immobilized all-trans retinoic acid
| Autor: | Melina R. Kibbe, Wulin Jiang, Edward Moreira Bahnson, Guillermo A. Ameer, Janet M. Vercammen, Megan E. Kelly, Banu Akar, Elaine K. Gregory, Antonio R. Webb, Robert van Lith |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Neointima Pathology medicine.medical_specialty Intimal hyperplasia Retinoic acid Pharmaceutical Science Lumen (anatomy) Tretinoin 02 engineering and technology 030204 cardiovascular system & hematology Article Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Restenosis Blood vessel prosthesis medicine Animals Humans Polytetrafluoroethylene Neointimal hyperplasia Hyperplasia Chemistry 021001 nanoscience & nanotechnology medicine.disease Blood Vessel Prosthesis Tunica Intima 0210 nano-technology medicine.drug |
| Zdroj: | Journal of Controlled Release. 274:69-80 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2018.01.020 |
| Popis: | 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 chararcteristics 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. |
| Databáze: | OpenAIRE |
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