Insights into the mechanisms that trigger excessive healing around heart stents could inform development of new stent materials

A study by UK researchers provides insights into how the body reacts to the metal stents used to wedge open blocked blood vessels in heart patients. The research could aid the creation of materials designed to reduce the risk of complications associated with stents.

In an angioplasty, a stent is inserted into a blood vessel to widen it, with the aim of improving blood flow. In around a quarter of cases, however, healing of the surrounding tissue leads to a new blockage - a complication known as in-stent restenosis (ISR). Although medicated stents reduce the risk of ISR, they are expensive and may increase the likelihood of a clot forming on the stent, and of heart attack.

An ideal alternative would be a material or stent coating that triggered a less vigorous healing response. But first scientists need to understand more about the complex processes that lead to ISR. Matteo Santin and colleagues at the University of Brighton studied the effects of stainless steel stents on human cells, comparing them to the effects of fibrin and collagen gels, which mimicked substrates in clots and damaged blood vessels respectively.

cells-405

Source: © J. R. Soc. Interface

Smooth muscle cells adhering to tissue culture plastic, collagen gel and stainless steel

’We tried to understand why stainless steel upsets this healing process and all our evidence shows that the interaction of the cells with the metal surface leads to excessive proliferation of the smooth muscle cells,’ says Santin. Their work builds on previous studies indicating that the metal surface activates inflammatory cells to produce signals that stimulate cell growth. 

’It has long been known that the phenotype of smooth muscle cells is much dependent on the underlying substrate and that the stent material has adverse effects during the healing response,’ says Vicente Andr?s, a vascular biologist at the Spanish National Centre for Cardiovascular Research in Madrid, Spain. ’The studies by Guildford et al  are of obvious interest, however more work is needed to conclusively demonstrate effects on cell proliferation.’ 

Meanwhile, Santin’s team has been working on making stent surfaces more biocompatible. They have already applied for a patent for a dendrimeric polymer that Santin describes like a ’nano-tree’ - the root sticks to the metal surface, while the branches selectively interact with molecules involved in cell behaviour. An ultra-fine layer of the polymer shouldn’t crack like existing coatings upon expansion of the stent, crucial because loose pieces are a potential cause of clots. 

Hayley Birch