Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

Abstract

There is a need for off-the-shelf, small-diameter vascular grafts that are safe and exhibit high long-term patency. Decellularized tissues can potentially be used as vascular grafts; however, thrombogenic and unpredictable remodeling properties such as intimal hyperplasia and calcification are concerns that hinder their clinical use. The objective of this study was to investigate the long-term function and remodeling of extracellular matrix (ECM)-based vascular grafts composited with antioxidant poly(1, 8-octamethylenecitrate-co-cysteine) (POCC) with or without immobilized heparin. Rat aortas were decellularized to create the following vascular grafts: 1) ECM hybridized with POCC (Poly-ECM), 2) Poly-ECM subsequently functionalized with heparin (Poly-ECM-Hep), and 3) non-modified vascular ECM. Grafts were evaluated as interposition grafts in the abdominal aorta of adult rats at three months. All grafts displayed antioxidant activity, were patent, and exhibited minimal intramural cell infiltration with varying degrees of calcification. Areas of calcification co-localized with osteochondrogenic differentiation of vascular smooth muscle cells, lipid peroxidation, oxidized DNA damage, and cell apoptosis, suggesting an important role for oxidative stress in the calcification of grafts. The extent of calcification within grafts was inversely proportional to their antioxidant activity: Poly-ECM-Hep>ECM>Poly-ECM. The incorporation of antioxidants into vascular grafts may be a viable strategy to inhibit degenerative changes.

Injectable muscle-adhesive antioxidant conductive photothermal bioactive nanomatrix for efficiently promoting full-thickness skeletal muscle regeneration

“…Our group also reported a series of citric acid-based hybrid polymers and demonstrated their promising biomedical applications in bioimaging, drug delivery/obesity therapy and skin regeneration [ [26] , [27] , [28] , [29] , [30] ]. Recent studies exhibited that citric acid-based polymers could efficiently improve the angiogenesis which was the vital step during the tissue formation [ 31 ]. Therefore, it was very promising to design citric acid-based biomaterials matrix with multifunctional properties for enhanced skeletal muscle regeneration.…”

Sterilization and disinfection methods for decellularized matrix materials: Review, consideration and proposal

“…Applications : Alcohol is commonly used in disinfection of skin and precision instruments, etc. There are many reports on the use of alcohol to disinfect dECM, which are mainly derived from pericardium [ 11 ], valve [ 123 , 124 ], blood vessel [ 12 , 121 , 125 , 126 ], liver [ [127] , [128] , [129] ], pancreas [ 130 ], trachea [ 131 ], bladder [ 130 , [132] , [133] , [134] , [135] ], kidney [ 48 , 136 ], bone [ 137 , 138 ], tendon [ [139] , [140] , [141] ] and nerve [ 142 ].…”

Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification

“…Poly(1,8-octamethylene citrate) (POC), an elastomer constructed as a biodegradable material, has been shown previously to decrease ROS production in neighboring tissues when coated onto vascular grafts 84 . Its derivative, POCC, when coated, was also found to attenuate local oxidized DNA and lipid damages, accompanied by a reduction in graft calcification 54 .…”

“…Multiple non-natural chemicals/medications also exhibit antioxidant properties and are effective against VC. We identified 19 types of such candidates with potential therapeutic effects against VC: acetylcysteine 33 , alendronate 49 , BMP inhibitor 39 , dimethyl fumarate 47 , farnesyltransferase inhibitor 41 , gemigliptin 57 , growth hormone-releasing hormone (GHRH) receptor agonist 58 , metformin 42 , pentoxifylline 64 , pravastatin 33 , pyrrolidine dithiocarbamate (PDTC) 34 , simvastatin 32 , sodium hydrosulfide 53 , sodium selenite 37,45 , STS 36,43,44 , Tempol 40 , TRAM-34 46 , topical poly(1,8-octamethylene-citrate-co-cysteine) (POCC) 54 , and hydrogen peroxide 51 . Among these, 11 (57.9%) were medications with specific clinical indications, while 8 (42.1%) were non-medicinal chemicals.…”