Functionalized microfiber mesh for inflammation and thrombosis prevention

Unmet Need

Trauma is a significant global health issue responsible for approximately 10% of deaths and over 15% of disabilities worldwide according to the World Health Organization. In addition to physical injuries, trauma-induced inflammation plays a crucial role in adverse outcomes experienced by these patients. The inflammatory cascade begins when injured cells release damage-associated molecular patterns (DAMPs) into their surrounding environment. Examples of DAMPs include cytoplasmic elements such as S100 and heat-shock proteins, mitochondrial components like mitochondrial DNA and reactive oxygen species, and nuclear elements such as DNA, RNA, and histones. DAMPs are recognized by immune cells, triggering an inflammatory cascade often through binding toll-like receptors (TLRs) or other pattern recognition receptors (PRRs). While substantial blood loss accounts for about one-third of trauma-related deaths, the remainder of patients often succumb to consequences of trauma-induced inflammation. The abundance of DAMPs overwhelms the body and leads to complications such as blood clots, organ damage, and immunosuppression, which can lead to multi-organ failure and sepsis. Current management of trauma-induced inflammation focuses on symptomatic treatments, including anti-inflammatory medications and prophylactic antibiotics to alleviate the symptoms rather than addressing the root cause of the inflammation — DAMPs. There is a need for the development of effective treatment strategies that directly target the molecular mechanism of trauma-induced inflammation. Addressing this gap is critical to improve patient outcomes, reduce mortality rate, and decrease disabilities associated with trauma.

Technology

Duke inventors have developed a treatment method for trauma-induced inflammation. This is intended to be used in trauma centers and critical care environments to sequester DAMPs from biological samples, thereby preventing trauma-induced inflammation. Specifically, this treatment uses poly(styrene-alt-maleic anhydride) (PSMA) / polystyrene microfiber meshes that are functionalized with nucleic acid binding polymers (NABPs) such as polyethyleneimine (PEI) and PAMAM-G3. The functionalized meshes have been shown to inhibit both nucleic acid and certain non-nucleic acid TLR ligands with minimal cytotoxicity. This has been demonstrated both in cell culture and in animal models of DAMP-induced thrombosis. In cell culture, functionalized meshes were shown to neutralize both nucleic acid and non-nucleic acid DAMPs preventing TLR stimulation and coagulation. In animal models, hearts treated with DAMP solutions that were pretreated with the NABP-functionalized mesh showed significant capture and removal of DAMPs. This pretreatment prevented the development of thrombosis and organ damage, in contrast to the untreated samples. These results suggest a method that may significantly improve outcomes of patients experiencing trauma-induced inflammation.

Other Applications

This technology could also be useful in organ transplantation, autoimmune diseases, cardiovascular diseases, radiation exposure, and cancer, where DAMPs also play a significant role in inflammation and disease progression.

Advantages

• This therapeutic approach targets DAMPs, the root cause of trauma-induced inflammation
• In vivo data suggests this therapeutic approach may reduce morbidity
• Various potential uses — this technology is not disease specific