Macrophages are central players in disease progression but also have a decisive role in wound healing/muscle regeneration. In this project, I would like to explore the delivery aspect of macrophage activation. Skeletal muscle is the most abundant tissue in the body and has the capacity to regenerate during normal instances of strain or injury. However, this capacity for muscle generation is lost or impaired in cases of myopathic disease (i.e. multiple sclerosis, Duchenne Muscular Dystrophy), aging, cardiovascular disease, and extreme injury.
Muscle regeneration is characterized by a precise choreography of immune cells that remove of apoptotic cells and driving proliferation of new one. In particular, monocytes are recruited to the site of injury in a subpopulation specific manner. Phagocytic, pro-inflammatory (M1) macrophages appearing in early stages followed by anti-inflammatory (M2) wound healing macrophages in late stages.Changes in this cascade can impact the outcome of muscle regeneration leading to chronic inflammation and scarring.Current muscle regeneration drug delivery studies are done using intramuscular injection of ex vivo activated macrophages, intramuscular injection of cytokines that stimulate macrophage activity, and the use of implantable biomaterials to control cell recruitment and drug release. However, with these models there is still a need to regulate the spatiotemporal recruitment and activation phenotype of macrophage.