Scientists optimize detection of biomaterials and identify ‘winning’ formulations

Rice University bioengineer Omid Veiseh and colleagues identified novel biomaterial formulations that could help turn the page in the treatment of type 1 diabetes, opening the door to a more sustainable, long-term, and self-regulated way of managing the illness.

To do this, they developed a new detection technique that involves labeling each biomaterial formulation in a library of hundreds with a unique “barcode” before implanting them into living subjects.

According to the study in Nature Biomedical Engineering, using one of the alginate formulations to encapsulate human insulin-secreting islet cells, provided long-term control of blood sugar in diabetic mice. Catheters coated with two other high-performance materials did not clog.

“This work was motivated by a great unmet need,” said Veiseh, a Rice assistant professor of bioengineering and a fellow at the Texas Institute for Cancer Research and Prevention. “In patients with type 1 diabetes, the body’s immune system attacks the insulin-producing cells of the pancreas. As those cells die, the patient loses the ability to regulate blood glucose.”

For decades, scientists worked to achieve what Veiseh called a “‘holy grail’ goal of housing islet cells within a porous matrix made of a protective material that would allow the cells to access oxygen and nutrients without being knocked around.” by the host’s immune system.

However, materials with optimal biocompatibility were very difficult to find, due in part to selection limitations. On the one hand, the response of the immune system to a certain implanted biomaterial can only be evaluated in a living host.

“The problem is that the immune response needs to be investigated inside the body of these diabetic mice, not in a test tube,” said Boram Kim, a graduate student in Veiseh’s lab and co-senior author of the study. “That means if you want to test these hundreds of alginate molecules, then you need to have hundreds of animal test subjects. Our idea was to detect hundreds of biomaterials at the same time, in the same test subject.”

On the other hand, different biomaterial formulations look the same, making it impossible to identify high-performance ones in the absence of some telltale trait. This made testing more than one biomaterial per host unfeasible.

“They are different materials but they look the same,” Veiseh said. “And once they’re implanted into a test subject’s body and then removed, we can’t distinguish between the materials and we wouldn’t be able to identify which material formulation worked best.”

To overcome these limitations, Veiseh and his colleagues devised a way to label each alginate formulation with a unique “barcode” that allowed them to identify the ones that worked best.

“We matched each modified biomaterial to human umbilical vein endothelial cells (HUVECs) from a different donor,” Kim said.

“HUVEC cells, because they come from single donors, act like a barcode that lets us know which material was used initially,” Veiseh added. “The winners are the ones with living cells. Once we found them, we sequenced the genome of those cells and found out what material was combined with it. That’s how we found the big hits.”

Trials are underway for the use of stem cell-derived islet cells in diabetic patients. However, current islet treatments require immunosuppression, making them a difficult way to treat type 1 diabetes.

“Currently, to use implanted islet cells in diabetic patients, you have to suppress the entire immune system, just as if you were trying to do an organ transplant,” Veiseh said. “That comes with a lot of complications for the patient.

“They can develop cancer, they can’t fight infections, so for the vast majority of patients, it’s better to do self-injecting insulin therapy. With this biomaterial encapsulation strategy, immunosuppression is not needed.”

Placing real HUVEC cells inside the biomaterial capsules increased the likelihood that the host’s immune system would detect a foreign presence. This makes the experiment more robust than just testing the immune response to the biomaterials alone.

“We wanted to test a library of these materials, with the selection pressure of having cells inside the beads making it more difficult for the immune system to miss the material,” Veiseh said. “All of the islet cell manufacturers are very interested in being able to get rid of immunosuppression and instead use these alginate hydrogel matrices to protect the implanted cells.”

The new high-throughput “barcode” approach can be implemented to detect other medical applications using fewer live test subjects.

“That actually feeds into a lot of other projects in my lab where we’re doing cell-based bioproduction for other disease indications,” Veiseh said. “The same modifications can be applied to all types of materials entering the body. This is not limited to just cell transplantation. The technology we developed can be combined with many different device concepts.

“For example, some diabetic patients use automated pump systems to self-administer insulin. The catheters in these pump systems need to be replaced every few days because they clog. We were able to show that coating the catheters with these new materials prevented clogging.”

“With this new cell-based barcoding technology, biomaterials research has just received an unprecedented boost that will speed translation into clinically applicable products and make them more affordable,” said Dr. José Oberholzer, transplant surgeon and bioengineer from the University of Virginia. .

“This is a true paradigm shift. With this method, we can now screen hundreds of biomaterials at a time and select those that are not rejected by the human body. We can protect cell grafts from immune system attacks, without the need for immunosuppressants.” medications,” Oberholzer added.

Former Rice professor of bioengineering and current NuProbe US CEO David Zhang noted that “high-throughput DNA sequencing has revolutionized many biomedical fields.”

“I am pleased to be working with Omid to enable the development of improved biomaterials using my team’s expertise in DNA sequencing,” added Zhang, who was a co-investigator on the grant. “These improved biomaterials may enable durable implanted cell therapies to function as living drug factories and may have a positive disruptive impact on patients with a variety of chronic diseases.”

The National Institutes of Health (R01 DK120459), JDRF (3-SRA-2021-1023-SB), the National Science Foundation (CBET1626418), the Rice University Academy Grant, and the Rice Computer Sharing Authority supported the investigation.