Control of innate immune response by biomaterial surface topography, energy, and stiffness

As the focus of implantable biomaterials has shifted from bioinert implants to bioactive designs, recent research has highlighted the complex interactions between cell physiologic systems and material properties, particularly physical cues. From the cells known to interact with implanted biomaterials, the response of the immune system has been a critical target of study recently. Here, we review studies characterizing the response of innate immune cells to various material cues, particularly of those at the surface of implanted materials.The innate immune system consists of cell types with various roles in inflammation. Neutrophils and macrophages serve both phagocytic and signaling roles, especially early in the inflammatory phase of biomaterial implantation. These cell types ultimately dictate the outcome of implants as chronic inflammation, fibrosis, or integration. Other cell types like dendritic cells, mast cells, natural killer cells, and innate lymphoid cells may also serve an immunomodulatory role in the biomaterial context. This review highlights recent advances in our understanding of the role of innate immunity in the response to implantable biomaterials as well as key mechanobiological findings in innate immune cells underpinning these advances. STATEMENT OF SIGNIFICANCE: This review highlights recent advances in the understanding of the role of innate immunity in the response to implantable biomaterials, especially in neutrophils and macrophages, as well as key mechanobiological findings in innate immune cells underpinning these advances. Here we discuss how physicochemical properties of biomaterials control innate immune cell behavior.