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DAMPening the effects of trauma-induced inflammation

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Science Translational Medicine  11 Jan 2017:
Vol. 9, Issue 372, eaal4992
DOI: 10.1126/scitranslmed.aal4992

Abstract

Amine-containing polymers immobilized on mesh and placed at trauma sites scavenge biomolecules that initiate a damaging immune response.

When a patient experiences a traumatic injury, medical care begins with a primary survey to assess for major problems that affect breathing ability, blood circulation, and neurological function. Although it is absolutely necessary to stabilize these high-order biological functions first, managing trauma at the molecular level can be very important for limiting traumatic damage and ensuring patient survival. When cells and their associated extracellular matrix are damaged, they release molecules called damage-associated molecular patterns (DAMPs), which can be recognized by toll-like receptors (TLRs) on immune cells, triggering a cascade of inflammation. Under normal conditions, localized inflammation allows for management of the damage and sometimes tissue regeneration, but trauma often produces very high amounts of systemic DAMPs, which can result in harmful posttraumatic conditions such as blood clots and organ damage. To address this, Lee et al. designed a biomaterial that can be placed into the trauma site to limit the deleterious effects of DAMPs.

DAMPs are mostly comprised of anionic biomolecules such as RNA and DNA, and cationic amine-containing polymers can readily complex with these molecules. Lee et al. postulated that if these polymers were immobilized onto electrospun microfiber meshes placed into the trauma site, they would act as DAMP sponges, limiting their capacity to cause damage. These biomolecule-scavenging biomaterials were found to isolate DAMPs without being cytotoxic to mammalian cells, and the immobilized polymers were even more effective than free polymers. The authors also demonstrated the capacity of these materials to counteract proinflammatory DAMP activity in trauma patient serum samples and clotting activity induced by cellular damage in mouse samples. When hearts were infused with DAMP solution and implanted ectopically into mice, those grafts given the solution pretreated with immobilizing polymer showed no organ damage, unlike those given untreated solution. Although further studies are needed to test the capacity of these materials to work in vivo and in higher-order animals, Lee et al. provide considerable evidence that immobilized amine-containing polymers can prevent localized and systemic damage caused by trauma-induced biomolecule release.

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