Innate Immunity and Biomaterials at the Nexus: Friends or Foes

Abstract

Biomaterial implants are an established part of medical practice, encompassing a broad range of devices that widely differ in function and structural composition. However, one common property amongst biomaterials is the induction of the foreign body response: an acute sterile inflammatory reaction which overlaps with tissue vascularisation and remodelling and ultimately fibrotic encapsulation of the biomaterial to prevent further interaction with host tissue. Severity and clinical manifestation of the biomaterial-induced foreign body response are different for each biomaterial, with cases of incompatibility often associated with loss of function. However, unravelling the mechanisms that progress to the formation of the fibrotic capsule highlights the tightly intertwined nature of immunological responses to a seemingly noncanonical “antigen.” In this review, we detail the pathways associated with the foreign body response and describe possible mechanisms of immune involvement that can be targeted. We also discuss methods of modulating the immune response by altering the physiochemical surface properties of the biomaterial prior to implantation. Developments in these areas are reliant on reproducible and effective animal models and may allow a “combined” immunomodulatory approach of adapting surface properties of biomaterials, as well as treating key immune pathways to ultimately reduce the negative consequences of biomaterial implantation.

Biologic Scaffolds

“…The host response following implantation of any biomaterial, including ECM materials, begins with the Vroman effect, 11 followed by activation of the innate immune system, including dendritic cells, neutrophils, and macrophages, among others Christo et al 2015). Depending on the implanted material, activation of the adaptive immune system, which involves lymphocytes (T and B cells), also occurs (Franz et al 2011;Mora-Solano and Collier 2014).…”

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

“…Until now, all biomaterials meant for use in humans trigger a tissue response when they come in contact with either healthy or sick tissue [15][16][17]. However, this response is triggered by physical contact between the tissue and the biomaterial which is implanted in an organ or tissue.…”

Polymer scaffold architecture is a key determinant in mast cell inflammatory and angiogenic responses

“…A critical variable dictating the fate of an implanted biomaterial is its initial interactions with the innate immune system. If the scaffold elicits an inflammatory response by cells such as macrophages, mast cells, dendritic cells, or neutrophils, the result can be fibrotic encapsulation and implant failure . In this study, we sought to determine if changing electrospun scaffold architecture could alter the response of mast cells, a key sentinel cell of innate immunity.…”

“…Macrophages will fuse to form multinucleated foreign body giant cells (FBGCs) when met with a material they cannot infiltrate nor engulf, such as a dense scaffold with small pore size. In this scenario, FBGCs release highly inflammatory reactive oxygen species in an attempt to break down the material . This relationship between implant architecture and inflammation prompted the goal to create scaffolds with sub‐micron fiber diameters and increased pore size.…”

“…Biomaterial design can alter this outcome, but the mechanisms by which polymer architecture alters immunity has yet to be fully determined. Innate immune cells are understood to determine the fate of implanted biomaterials . While there has been considerable attention given to macrophages and neutrophils, much less is known about mast cell–biomaterial interactions.…”