Inhibits the Activation of Pro-Inflammatory Macrophages, Delivering a Therapeutically Effective Amount of DGEA to the Inflammation Site
This hydrogel composition inhibits the activation of pro-inflammatory macrophages, treating diseases and disorders associated with excessive or sustained inflammation. Inflammation is the body’s defense mechanism in response to trauma, injury, or microbial invasion. The classic signs of acute inflammation include pain, heat, redness, swelling, and loss of function. In some situations, inflammation lingers beyond an acute response, leading to chronic inflammatory disorders, such as cardiovascular and pulmonary diseases, osteoarthritis, cataracts, cancer, and diabetes. Globally, 3 out of 5 people die due to chronic inflammatory morbidities. Hence, there is a need to control inflammation by manipulating the immune response.
Macrophages are immune cells integral to promoting wound healing and resolution of inflammation. These cells change their functions in response to environmental cues, thereby acquiring various phenotypes, a process called macrophage polarization. Activated macrophages (M1) are characteristic of a pro-inflammatory phenotype, and an excess of M1 macrophages is a marker of a disproportionate inflammatory response. Extracellular matrix (ECM) proteins, such as collagen, also inform macrophage polarization. Some current therapies use ECM-derived peptides to alter cellular responses via integrin receptor interactions. Specifically, integrin α2β1 is a cell-membrane receptor that plays a pivotal role in macrophage polarization, and previous studies have shown that binding via integrin α2β1 drastically increases M1 markers.
Researchers at the University of Florida have developed a hydrogel comprising DGEA, a collagen-derived peptide, blocking the binding sites of the α2β1 integrin, to address various chronic inflammatory diseases. Through this interaction, DGEA can impair the activation of pro-inflammatory M1 macrophages and deliver a therapeutically effective amount of DGEA to the site of inflammation. The clinical application would be first for topical treatment of chronic wounds such as diabetic ulcers, and next for internal inflammation-related disorders.
Application
Hydrogel comprising DGEA, an extracellular matrix-derived tetrapeptide that blocks the binding site of the α2β1 integrin, inhibiting activation of pro-inflammatory macrophages and targeting inflammation
Advantages
- Compositions, including DGEA, can impair pro-inflammatory macrophage activation, allowing for the treatment of inflammatory disorders by manipulating the immune response
- This hydrogel could treat inflammation of any organ, enabling a broad range of therapeutic applications
- DGEA corresponds to a peptide sequence in collagen, a vital component of the extracellular matrix (ECM) involved in wound healing, making it a great candidate drug to promote wound healing
- The composition can treat inflammation in healthy and immunocompromised patients, treating patients who may not qualify for traditional therapies
- Administration routes can be local and systemic, enabling better dosage designs depending on patients’ and disease requirements
Technology
This hydrogel composition aims to treat inflammatory diseases by modulating pro-inflammatory macrophage activation. Upon an inflammatory stimulus during the wound-healing cascade, macrophages release cytokines to initiate inflammation. However, an unbalanced production of inflammatory cytokines causes an excess of activated pro-inflammatory (M1) macrophages. This dysregulation at a site of inflammation or wound healing can lead to developing chronic inflammatory disorders. Integrin α2β1 is a protein that plays a significant role in macrophage polarization and activation of pro-inflammatory macrophages. This biofunctional hydrogel comprises an extracellular matrix-derived peptide, DGEA, corresponding to the minimal recognition sequence for α2β1. DGEA can bind to and block α2β1 binding sites, impairing its ability to promote macrophage polarization and reducing the M1 macrophages. Hence, this composition can serve as a biomaterial tool to address chronic inflammatory diseases by inhibiting pro-inflammatory macrophage activation.
Brochure
