Age and sex differences in the immune response to synthetic materials

Project Summary The WHO estimates that 1 in 6 people will be 60 years or older by 2030. A hallmark of aging is the immunological changes that increase susceptibility of this population to inflammatory agerelated diseases, hinder response to infections and vaccines, and lower regenerative capacity. Synthetic biomaterials are used in multiple ways including drug delivery, vaccines, prosthetics, and scaffolds in tissue engineering to promote tissue regeneration. Implanting a biomaterial creates an injury and initiates the immune-driven development of a foreign body reaction. Immune-tissue engineering solutions must be designed to modulate the local microenvironment while overcoming the FBR. With an aging population there is a critical need to understand the age-specific immune-material interactions to rationally design biomaterial solutions for tissue engineering. The goal is to identify key material design criteria that effectively modulate aged immune cells. The overarching hypothesis is that the aged immune dysregulation towards an effector state compounds the adverse reaction to synthetic materials and prevents scaffolds from functioning as designed. My proposed research for the R00 focuses on designing materials for the aged immune system to reduce fibrosis and promote tissue regeneration. The goal of the R00 is split into 3 aims to understand how we can optimally design materials to promote a desired immune response in aged cells accounting for biologic sex targeting the innate (Aim 1) and adaptive (Aim 2) immune system and how both arms of the immune system (Aim 3) can be used to promote regeneration.