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.

A polymer–extracellular matrix composite with improved thromboresistance and recellularization properties

“…Lastly, POC has also been shown to have significant antioxidant activity,[28] which may contribute to its observed anti-inflammatory properties. [29] Therefore, the use of POC on the ECM of decellularized tissues or organs could potentially decrease inflammatory responses in vivo by masking any residual antigen and/or attenuate oxidative stress in tissues.…”

Enabling non-invasive assessment of an engineered endothelium on ePTFE vascular grafts without increasing oxidative stress

“…[17] The prepolymer was firstly dissolved in absolute ethanol at 10 wt% and added to tissue culture muti-well plates (Corning®, Lowell, MA) at 10 mg/cm 2 , or perfused through 5 mm diameter ePTFE vascular grafts (Vascutek, Somerset, NJ) using a syringe pump set at 1 mL/min flow rate. After ethanol evaporation, the plates or grafts with POC prepolymer were post-polymerized at 80°C for 4 days.…”

Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

“…[19] Briefly, all three types of grafts (n=3 per group) were weighed and incubated in a solution of ABTS (7 mM) and sodium persulfate (2.45 mM) at 37 °C. At each time point (days 0, 3, 6 and 9), ABTS solution was sampled, diluted with MQ water 1:10 and the absorbance measured at 734 nm.…”

“…inflammation, apoptosis, and calcification) caused by oxidative stress. We previously reported the synthesis of antioxidant, citric based polymers[18, 19] and the preparation of antioxidant, citric acid-based polymer-ECM composite vascular grafts whereby the polymer coating was functionalized with heparin to enhance graft thromboresistance. [8, 9] When compared to vascular ECM grafts, the polymer-ECM composite grafts exhibited reduced neointimal hyperplasia after one month of implantation in the abdominal aorta of Sprague Dawley rats.…”