title: Development of a total atherosclerotic occlusion with cell-mediated calcium deposits in a rabbit femoral artery using tissue-engineering scaffolds.
abstract: This study sought to establish a chronic total occlusion (CTO) model with cell-mediated calcium deposits in rabbit femoral arteries. CTO is the most severe case in atherosclerosis and contains calcium deposits. Previous animal models of CTO do not mimic the gradual occlusion of arteries or have calcium in physiological form. In the present study we tested the strategy of placing tissue-engineering scaffolds preloaded with cells in arteries to develop a novel CTO model. Primary human osteoblasts (HOBs) were first cultured in vitro on polycaprolactone (PCL) scaffolds with 5 ng TGFβ1 loading for 28 days for precalcification. The HOB-PCL construct was then implanted into a rabbit femoral artery for an additional 3, 10 or 28 days. At the time of sacrifice, angiograms and gross histology of arteries were captured to examine the occlusion of arteries. Fluorescent staining of calcium and EDS detection of calcium were used to evaluate the presence and distribution of calcium inside arteries. Rabbit femoral arteries were totally occluded over 28 days. Calcium was presented at CTO sites at 3, 10 and 28 days, with the day 10 specimens showing the maximum calcium. Chronic inflammatory response and recanalization were observed in day 28 CTO sites. A novel CTO model with cell-mediated calcium has been successfully established in a rabbit femoral artery. This model can be used to develop new devices and therapies to treat severe atherosclerotic occlusion.
authors.affiliation: Janey Briscoe Center for Cardiovascular Research, Janey and Dolph Briscoe Division of Cardiology, Department of Medicine, University of Texas Health Science Center at San Antonio, TX, USA. beilizhu@yahoo.com
authors.forename: Beili
authors.initials: B
authors.lastname: Zhu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Bailey
authors.forename: James
authors.initials: J
authors.lastname: Elliott
authors.forename: Xiankai
authors.initials: X
authors.lastname: Li
authors.forename: G Patricia
authors.initials: GP
authors.lastname: Escobar
authors.forename: Eva M
authors.initials: EM
authors.lastname: Rodriguez
authors.forename: C Mauli
authors.initials: CM
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000473:pathology*; D050197:Atherosclerosis / Q000150:complications / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D005453:Fluorescence; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D011091:Polyesters; D011817:Rabbits; D011859:Radiography; D013052:Spectrometry, X-Ray Emission; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D011091:Polyesters; D053773:Transforming Growth Factor beta1; C016240:polycaprolactone; D002118:Calcium