Effects of age-related shifts in cellular function and local microenvironment upon the innate immune response to implants

Abstract

The host macrophage response is now well recognized as a predictor of the success or failure of biomaterial implants following placement. More specifically, shifts from an “M1” pro-inflammatory towards a more “M2-like” anti-inflammatory macrophage polarization profile have been shown to result in enhanced material integration and/or tissue regeneration downstream. As a result, a number of biomaterials-based approaches to controlling macrophage polarization have been developed. However, the ability to promote such activity is predicated upon an in-depth, context-dependent understanding of the host response to biomaterials. Recent work has shown the impacts of both tissue location and tissue status (i.e. underlying pathology) upon the host innate immune response to implants, representing a departure from a focus upon implant material composition and form. Thus, the ideas of “biocompatibility,” the host macrophage reaction, and ideal material requirements and modification strategies may need to be revisited on a patient, tissue, and disease basis. Immunosenescence, dysregulation of macrophage function, and delayed resolution of immune responses in aged individuals have all been demonstrated, suggesting that the host response to biomaterials in aged individuals should differ from that in younger individuals. However, despite the increasing usage of implantable medical devices in aged patients, few studies examining the effects of aging upon the host response to biomaterials and the implications of this response for long-term integration and function have been performed. The objective of the present manuscript is to review the putative effects of aging upon the host response to implanted materials and to advance the hypothesis that age-related changes in the local microenvrionement, with emphasis on the extracellular matrix, play a previously unrecognized role in determining the host response to implants.

<p>Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO₂ Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy</p>

“…This polarization shift has been widely reported to promote satisfied tissue repair and bone integration around the implant. 58 To further investigate the relationship between Ag + ions concentration and its immunoregulatory function, we cultured macrophages with medium containing different concentrations of AgNPs (0~2.0 ppm) ( Figure S1D-F). Compared with the control group, macrophages expressed more Arginase1 and fewer iNOS when the concentration of AgNPs ≤ 0.20 ppm, which indicated the trend of M2 polarization instead of M1 polarization.…”

Macrophages in the Aging Liver and Age-Related Liver Disease

“…Infiltrating macrophages can be derived from either classical (CD14 + CD16 − human, Ly6C hi mouse) or non-classical (CD14 + CD16 + human, Ly6C lo mouse) monocytes, which extravasate into tissue sites under chemokine concentration gradient guidance ( 17 , 23 ). Following extravasation, monocytes differentiate into macrophages whose functionality are largely based on the integration of the various signaling molecules present in the local microenvironment ( 24 , 25 ).…”

Xenogeneic bone matrix immune risk assessment using GGTA1 knockout mice

“…Biomaterials derived from mammalian extracellular matrix (ECM) have been widely used in surgical wound repair, tissue reconstruction and tissue engineering due to their good biocompatibility [1,2]. However, the immune risk caused by animal derived biomaterials or xenogeneic organs directly affected the safety and effectiveness of these materials and limited their applications [1,3,4]. Immune reactions between the antigen on xenografts and the antibody in humans may lead to immune mediated tissue degeneration and dystrophic calcification [5].…”