First-Ever Inherently Antioxidant Biodegradable Biomaterial Developed

Vascular grafts, particularly ones composed of artificial materials like Teflon or poly-tetrafluoroethylene  (ePTFE), have long been fraught with limitations. Perhaps until now, that is.

Researchers at Northwestern University’s college of engineering have announced a new polymer that may improve the success of synthetic vascular grafts by reducing one of the key contributors to failure: oxidative stress.

Blood vessels involved in vascular grafting and other vascular interventions are often subject to atherosclerosis and restenosis, or a closing off of the grafted vessel over time. Eventually this leads to a failure of the graft or vessel, and the patient is back where they started. Both of these conditions have been associated with oxidative stress that develops during the healing cycle. When a synthetic graft is implanted, this is further complicated by the body’s natural inflammatory response to implanted materials, which in itself can contribute to oxidative stress. 

Reducing oxidative stress was the focus of the Northwestern team’s research, and they came up with a novel approach: make antioxidants part of the material you are implanting. If antioxidants are released by your implant, then perhaps it can reduce oxidative stresses in the local areas where it is implanted. This, in turn, may increase biocompatibility and reduce the types of complications previously seen with grafting procedures.

“In the past, people have added antioxidant vitamins to a polymer and blended it in. That can affect the mechanical properties of the material and limit how much antioxidant you can add, so it doesn’t work well. What we’re doing is different. We’re building a material that is already inherently, intrinsically antioxidant,” said Professor Guillermo Ameer, a researcher in the department of biomedical engineering at Northwestern’s McCormick School of Engineering and Applied Science and professor of surgery at the Feinberg School of Medicine, in a press release published recently by the school.

Specifically, Ameer and his team are using a newly synthesized material that contains antioxidants in its very structure. This material is called poly (1,8-octanediol-co-citrate-co-ascorbate) (POCA), a flexible elastomeric plastic that is partially made from citric acid and ascorbate. Ascorbate is also better known as vitamin C, a potent anti-oxidant. Like most degradable polymers, POCA releases degradation products. Unlike most degradable polymers, however, POCA releases degradation products that reduce oxidative stresses and appear to be beneficial.

In vitro testing from Ameer’s study showed that antioxidants were being released into the culture medium. Antioxidant activity was even present after the polymer had completely degraded. When cultured with endothelial cells, the cells that line the interior of blood vessels, there were no apparent negative effects, and the cells were able to grow on the POCA material. When these same cells were exposed to added oxidative stress, the polymer and its degradation products reduced the oxidative cell death that would normally be seen.

In vivo POCA also led to some interesting outcomes when coated on an expanded ePTFE graft. This preliminary testing led to decreased intimal hyperplasia when compared to an uncoated ePTFE graft. Intimal hyperplasia in many cases is associated with restenosis of vessels that have been repaired.

According to the press release, Ameer also believes the new biomaterial may find applications outside of vascular grafting, such as in creating scaffolds for tissue engineering, coating and manufacturing safer medical devices, promoting healing in regenerative medicine, and protecting cells, genes, and viruses during drug delivery.