title: Engineering biodegradable polyester elastomers with antioxidant properties to attenuate oxidative stress in tissues.
abstract: Oxidative stress plays an important role in the limited biological compatibility of many biomaterials due to inflammation, as well as in various pathologies including atherosclerosis and restenosis as a result of vascular interventions. Engineering antioxidant properties into a material is therefore a potential avenue to improve the biocompatibility of materials, as well as to locally attenuate oxidative stress-related pathologies. Moreover, biodegradable polymers that have antioxidant properties built into their backbone structure have high relative antioxidant content and may provide prolonged, continuous attenuation of oxidative stress while the polymer or its degradation products are present. In this report, we describe the synthesis of poly(1,8-octanediol-co-citrate-co-ascorbate) (POCA), a citric-acid based biodegradable elastomer with native, intrinsic antioxidant properties. The in vitro antioxidant activity of POCA as well as its effects on vascular cells in vitro and in vivo were studied. Antioxidant properties investigated included scavenging of free radicals, iron chelation and the inhibition of lipid peroxidation. POCA reduced reactive oxygen species generation in cells after an oxidative challenge and protected cells from oxidative stress-induced cell death. Importantly, POCA antioxidant properties remained present upon degradation. Vascular cells cultured on POCA showed high viability, and POCA selectively inhibited smooth muscle cell proliferation, while supporting endothelial cell proliferation. Finally, preliminary data on POCA-coated ePTFE grafts showed reduced intimal hyperplasia when compared to standard ePTFE grafts. This biodegradable, intrinsically antioxidant polymer may be useful for tissue engineering application where oxidative stress is a concern.
authors: Biomedical Engineering Department, Northwestern University, Evanston IL 60208, USA.
authors: Robert
authors: R
authors: van Lith
authors: Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA; Institute for BioNanotechnology in Medicine, Northwestern University, Chicago IL 60611, USA.
authors: Elaine K
authors: EK
authors: Gregory
authors: Biomedical Engineering Department, Northwestern University, Evanston IL 60208, USA.
authors: Jian
authors: J
authors: Yang
authors: Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA; Institute for BioNanotechnology in Medicine, Northwestern University, Chicago IL 60611, USA.
authors: Melina R
authors: MR
authors: Kibbe
authors: Biomedical Engineering Department, Northwestern University, Evanston IL 60208, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA; Chemistry of Life Processes Institute, Northwestern University, Evanston IL 60208, USA; Institute for BioNanotechnology in Medicine, Northwestern University, Chicago IL 60611, USA. Electronic address: g-ameer@northwestern.edu.
authors: Guillermo A
authors: GA
authors: Ameer
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D001011:Aorta / Q000473:pathology; D001672:Biocompatible Materials / Q000737:chemistry*; D049109:Cell Proliferation; D002470:Cell Survival; D002614:Chelating Agents / Q000737:chemistry; D019343:Citric Acid / Q000737:chemistry; D020724:Elastomers; D005609:Free Radicals; D006168:Guinea Pigs; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D007501:Iron / Q000737:chemistry; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013718:Tensile Strength
chemical_list: D000975:Antioxidants; D001672:Biocompatible Materials; D002614:Chelating Agents; D020724:Elastomers; D005609:Free Radicals; D011091:Polyesters; D011108:Polymers; D017382:Reactive Oxygen Species; D019343:Citric Acid; D007501:Iron; D010100:Oxygen
keywords: Antioxidant; Ascorbic acid; Biodegradable; Citric acid; Elastomer; Oxidative stress