One additive, less stress

Additives are chemical substances that are used to provide colour to plastics, improve their performance by helping to make them resistant to UV, microbes, corrosion and much more. However, these substances are not all harmless. This young start-up has now developed multifunctional additive technology that eliminates or reduces toxicity without making any compromise on performance. Sustainable Plastics talked to Kumar Challa, president, CSO & co-founder, to find out more.

The company’s name is a reference to how it got started, said Kumar Challa. “We started as a blood bag company, and initially, our technology was developed to increase the shelf life and health of the blood stored in blood bags, with the ultimate aim of creating a non-toxic blood bag. That's how we began.”

Xheme was founded in 2019, in Newton, Massachusetts by Challa together with three other partners - Pamela Burton, Jonathan Plaut, and Venugopal Nambula. As a nanotechnology scientist working in academia, Challa had been collaborating with researchers at various institutions on the design and application of new nanomaterials. During one such project, they discovered that they had stumbled on a material that lengthened the life span of red blood cells. After conducting a series of biological tests, they realised the potential of the finding and decided to file for a patent. Then came the decision to start a company.

“The intention was to develop a next-generation blood bag, in which blood could be stored for a longer period. At that time, we thought that that was the main pain point in the industry. It was only later that we realised that the real pain point is the toxic plasticiser that goes into producing the current blood bag,” explained Challa.

Switching focus
Today, blood bags are made from plasticised PVC. First introduced by Carl Walter over 40 years ago to replace the more fragile glass containers used until then, it remains the material of choice because of its favourable properties. Next to being cost-effective, plasticised PVC offers the necessary permeability to oxygen for the blood platelets to survive, yet without being too permeable to water; it can be sterilised with steam prior to use; is strong yet flexible, and is translucent, allowing the contents to be visually monitored.

However, plasticised PVC comes with one big disadvantage: the plasticisers used are toxic substances. Moreover, because these plasticisers are not chemically bound to the polymer, they can – and do - leach out of the material. Today, PVC plasticised with di(2-ethylhexyl) phthalate – DEHP -  is the most common material used to produce blood bags and soft PVC can contain as much as 40 percent by weight of DEHP plasticisers. 
Concerns about its toxicity have led the European Union to ban the use of DEHP in blood storage bags, with the sunset date for commercialisation of bags containing DEHP set for 27 May 2025.
Somewhat paradoxically, DEHP also interacts with the red blood cell membrane, actually reducing the breakdown of the red blood cells and extending their life. Replacing DEHP with alternatives such as DEHT and DINCH is therefore not as straightforward as it may seem: these alternative plasticisers have been found to increase the breakdown of red blood cells, which could lead to a shorter shelf life for stored blood and even to shortages in the blood supply.
With this background in mind, the new additive developed by Xheme, called XMA, could be a potential game changer. According to Challa, Xheme’s technology, which uses its XMA additive together with another non-toxic plasticiser, would allow the ‘toxic plasticiser to be replaced by a benign plasticiser’, that meets or exceeds the 42-day global storage standard for red blood cells.

“We even envision that, at a certain point, we will no longer have to use PVC at all. This is one of the directions we are now working in,” said Challa.  “At the same time, we realised we could also do far more with our additive for the wider plastics industry. Our additive offers converters the choice of reducing the number of additives needed to produce their products while maintaining performance. This additive has amazing unique properties. We can fine-tune these and programme the chemistry to take on all types of challenges related to plastic films.”

Moreover, he added, at the end of life, many of these plastic films are not recyclable. “We realised we could change that: we could design plastic films that were nontoxic, both for humans and the environment, but at the same time, made no concessions to performance – and ensure that at the end of life, they could be disposed of sustainably. That is our vision We still have a long way to go, but we have the building blocks to demonstrate that that vision is attainable.”

‘Like a sponge’
To make it easier to understand how Xheme’s XMA multifunctional additive works, ‘imagine a sponge made up of bi-metallic oxide nanoporous structures’, said Challa. ‘It has the ability to scavenge free radicals and can actually capture peroxide and decompose this into oxygen and water. It can also absorb UV radiation under certain conditions and has been found to have antimicrobial properties. As well, because it can capture the oxygenated radicals, it can also function as an anticorrosive.”
This also explains why it can extend the life span of stored red blood cells. Red blood cells are particularly susceptible to oxidative stress. As XMA absorbs the oxygenated radicals, it eliminates oxidative stress.
In short, XMA offers different functionalities under different conditions, and Xheme’s goal is to continue to add to these functionalities.

Beyond blood bags
Having established the multifunctionality of its XMA additive, Xheme is looking to create nanocomposite plastic films  for different applications ‘able to perform at the highest level’, said Challa, ‘without compromising on either human or eco toxicity’.
One example is the company’s realisation that the way the additive affected red blood cells meant that it could work the same magic for other cells as well -  such as cell culture media for bioprocessing. Cell culture media are an important factor in the success of cell-based biomanufacturing, such as for the production on pharmaceuticals, and a significant cost consideration.
Challa: “So, we asked ourselves, what about microalgae cells? Can we increase the viability of micro algae cells, make them grow better, make them happy?”
Microalgae can be grown in plastic bioreactors, he explained. Throughout their growth they very effectively absorb carbon dioxide and convert that into useful chemicals and biofuels. Typically, however, a considerable portion of the yield is lost during bioprocessing. A nanocomposite film grade incorporating Xheme’s XMA additive could increase performance by reducing that loss, which would also save the number of man hours spent working with the bioreactor. 
The further exploration of this concept led Xheme to direct its efforts towards developing and bringing three separate products to the market. The first, obviously, is the new generation of blood bags. The second is the polyethylene bioprocessing bag  - which basically involves taking cells, and using these cells to make pharmaceuticals – proteins, antibodies, antiviral drugs, etc., according to Challa. There are two types of bio reactors, he continued. “One is a traditional stainless-steel reactor. The other one is a single-use, disposable plastic reactor. The stainless-steel reactor needs to be thoroughly cleaned after the drug is manufactured before another batch can be produced. It takes several man hours to clean. We are working on launching a nanocomposite bioprocessing bag to market that can increase the yield of the drug produced while decreasing the manhours needed to double production.”

The third case study relates to industrial applications for plastics companies. “Of the three we are now focusing more and more on the bioprocessing plastic bags, where our proof-of-concept results are irrefutable,” Challa added.
He characterises the bioprocessing bags currently on the market as passive – ‘housing for the cells’. By contrast, Xheme’s bags actively remove oxidative stress and therefore actively enable increased production.
Pricewise, little is expected to change, as the production process remains the same. “For blood bags, price is an issue – we could not add even a penny to the price,” he said. Xheme has shown that blood bags formulated with XMA could not only be manufactured, but that they could be manufactured without changing the established industry standards for either manufacturing or storing red blood. Moreover, only around 2% of XMA additive needs to be incorporated into the film for it to work.
The situation was slightly different for the bioprocessing bags, Challa noted. “There price is far less of an issue.” Xheme is currently producing the nanocomposite films for the bags at pilot scale but is hoping to validate the technology on a larger scale within the next few months.

Looking ahead
Coming back to the blood bags, Challa noted that there were some interesting developments expected over the coming months. Xheme collaborates on its blood bag research with partners such as Vitalant Research Institute and the Canadian Blood Services, who do all the blood biology work and with film manufacturing company Transcendia. The partnership with industry is ‘very important for our success’, Challa emphasised.
The data on the new bags look very promising: studies conducted by Challa and  by Tamir Kanias, an associate investigator at the Vitalant Research Institute, were recently completed demonstrating that combining XMA with DEHT plasticized PVC produces a blood bag that meets the established 42-day blood shelf-life benchmark - a marked improvement compared to PVC plasticised with DEHT only. The two scientists moreover observed a 20-25% reduction in red blood cell death,  with no evidence of significant leaching of XMA when tested in salt water for up to 50 days. The combined XMA-DEHT-PVC formula also demonstrated the additive’s antimicrobial properties. Xheme is currently running field tests in cooperation with one of North America’s largest blood banks and the Canadian Blood Services, as well.

In addition, the company has been working with Renolit, a Germany-headquartered manufacturer of plastic films and other plastic products for various markets, including the medical & pharmaceutical sector, for the past three years on the development of a blood bag without DEHP. 
“Renolit supplied the PVC pellets required to produce the proof-of-concept non-toxic blood bag for which we now have the results. The next step is to replace the PVC completely with a different biocompatible polymer, enabling us to bring a completely non-toxic blood bag to the market. We are doing a pilot run of the new bags later this fall and are looking at three potential other polymers, one of which is EVA,” Challa said. “But in the end, it is our additive that creates the effect of reducing oxidative stress – whether incorporated into polyethylene, EVA or something else, the function will remain the same, allowing us to finally phase out the use of plasticised PVC in packaging and medical equipment.”