Northwestern University researchers have developed a new antioxidant biomaterial that could potentially offer relief to people with severe chronic pancreatitis. The current treatment for this condition involves removing the pancreas, resulting in the loss of insulin-producing cells known as islets. While surgeons have been transplanting islets to the liver to preserve insulin responses, this method has not been very successful. A new approach involves using a synthetic gel to transplant islets to the omentum, which has shown promise in both small and large animal studies. This new strategy has resulted in more islets surviving transplantation and forming blood vessels within the omentum.
The article will be published in the journal Science Advances on June 7. Prior to removing the pancreas from patients suffering from severe and painful chronic pancreatitis, surgeons extract clusters of insulin-producing tissue, known as islets, and transplant them into the liver’s blood vessels. The aim of the transplant is to maintain the patient’s ability to regulate their own blood glucose levels without the need for insulin injections. Unfortunately, this process unintentionally results in the destruction of 50-80% of islets, and one-third of patients develop diabetes after the surgery. After three years, 70% of patients remain diabetic.patients from needing insulin injections and reduced the side effects commonly associated with the treatment. The researchers discovered that by transplanting islets from the pancreas to the omentum instead of the liver, and utilizing an antioxidant and anti-inflammatory biomaterial to support the islets, they were able to create a healthier environment for the insulin-producing cells. This biomaterial transformed from a liquid to a gel at body temperature, providing a more stable and supportive structure for the islets. In both mouse and non-human primate studies, the gel effectively prevented the need for insulin injections and minimized the associated side effects such as weight gain, hypoglycemia, and fatigue.The study, led by Northwestern’s Guillermo A. Ameer, found that a synthetic antioxidant gel could enhance the survival and function of transplanted islets by reducing oxidative stress and inflammation. This is the first instance of such a gel being used for this purpose. Ameer noted that while islet transplantation has shown improvement, long-term outcomes are still not great, and there is a need for alternative solutions. The team engineered a state-of-the-art synthetic material that creates a supportive microenvironment for islet function. In animal testing, this material was successful in maximizing islet function.The article discusses a new approach to treating chronic pancreatitis and diabetes. The researchers were able to restore normal blood sugar levels and reduce the amount of insulin needed by the animals. Jacqueline Burke, a research assistant professor of biomedical engineering at Northwestern, expressed hope that this approach would eliminate the need for patients to choose between living with the physical pain of chronic pancreatitis or dealing with the complications of diabetes. Ameer, an expert in regenerative engineering, is the Daniel Hale Williams Professor of Biomedical Engineering at Northwestern’s McCormick School of Engineering and a Professor of Surgery at Northwestern.stern University Feinberg School of Medicine and founding director of the Center for Advanced Regenerative Engineering.
‘Compromised quality of life’
Patients who have lost their pancreas face challenges such as managing blood-sugar levels. They struggle to maintain glycemic control without the help of islets, which secrete insulin in response to glucose. This can lead to a lifelong battle of closely monitoring blood-sugar levels and frequently injecting insulin.
“Living without functioning islets places a great burden on patients,” Burke said. “They must learn to count carbs, dose insulin at the appro rnrnPatients with diabetes spend a lot of time and mental energy on managing their blood glucose levels. Even with careful management, using insulin therapy is not as effective as the body’s own islets for controlling glucose. If blood glucose levels are not well-controlled, patients can develop complications like blindness and amputation. The goal of the biomaterial being developed is to preserve the islets so that patients can live a normal life without diabetes.
Dr. Ameer stated, “It significantly impacts their quality of life. Instead of having to take multiple insulin injections, we would like to collect and preserve as many islets as possible.” However, the current standard of care for diabetes management falls short.The care of islets after removal from the pancreas and transplantation into the liver through portal vein infusion often results in poor outcomes. This is due to the common complications of the procedure, including an inflammatory response from islets in direct contact with blood flow, a high rate of islet death, and the potential for dangerous clots in the liver from the transplanted islets. As a result, medical professionals and researchers have been exploring alternative transplantation sites. Previous clinical studies have shown researchers transplanting islets into alternative sites.The researchers sought to relocate the islets to the omentum instead of the liver to bypass clotting issues. To anchor the islets on the omentum, doctors utilized plasma from the patients’ own blood to create a biologic gel. While the omentum seemed to be a better site for transplantation than the liver, there were still several problems, such as clots and inflammation.
“The research and medical communities have shown a lot of interest in finding an alternative site for islet transplantation,” Ameer explained. “The results of the omentum study were promising, but the outcomes were inconsistent. We believe this is due to the use of the patients’ blood and the additional component.”It is necessary to make the biologic gel in a way that can cause differences in results for patients.”
A citrate solution
To safeguard the islets and enhance results, Ameer looked to the citrate-based biomaterials platform with natural antioxidant properties that he had developed in his lab. These biomaterials, which are used in products approved by the U.S. Food and Drug Administration for musculoskeletal surgeries, have shown the ability to manage the body’s inflammatory reactions. Ameer wanted to see if a modified version of these biomaterials with biodegradable and temperature-sensitive phase-changing properties would offerThis gel made from citrate is a better option than a biologic gel obtained from blood. In cell cultures, both mouse and human islets stored within the citrate-based gel stayed alive for a longer time than islets in other solutions. When exposed to glucose, the islets released insulin, showing normal functionality. The gel was also tested in small and large animal models. It is liquid at room temperature and turns into a gel at body temperature, making it easy to apply and stay in place.
In the animal studies, the gel effectively secured the islets onto the omentum of the animals. Compared to the current gel used for islet transplantation, this citrate-based gel showed superior results.
When researchers implanted the new material containing islets into diabetic mice, they found that more islets survived and the animals eventually restored normal blood glucose levels. Dr. Ameer attributes the success of the new material to its biocompatibility and antioxidant properties.
Dr. Ameer explained, “Islets are very sensitive to oxygen and can be affected by both too little and too much oxygen. The material’s natural antioxidant properties help protect the cells, which is something that plasma from the patient’s own blood cannot provide.”
Integration with tissues
After approximately three months, the body absorbed 80-90% of the biocompatible gel. However, by this point, the gel was no longer necessary.
Ameer expressed his fascination with the fact that the islets were able to regenerate blood vessels. He explained that the body created a new network of blood vessels to reconnect the islets with the body, which is a significant breakthrough because the blood vessels are essential for keeping the islets alive and healthy. Additionally, Ameer mentioned that the gel is absorbed into the surrounding tissue, leaving minimal evidence behind.
His next step is to conduct tests of the hydrogel in animal models over an extended period of time. He also emphasized that the new hydrogel could be used for various cell replacement therapies, such as stem cell-derived beta cells for diabetes treatment.
The study titled “Phase-changing citrate mThe study, titled “Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum,” received funding from the U.S. Department of Defense and the National Science Foundation.