Distinct macrophage populations and phenotypes associated with IL-4 mediated immunomodulation at the host implant interface.

The host macrophage response to implants has shown to be affected by tissue location and physio-pathological conditions of the patient. Success in immunomodulatory strategies is thus predicated on the proper understanding of the macrophage populations participating on each one of these contexts. The present study uses an in vivo implantation model to analyze how immunomodulation via an IL-4 eluting implant affects distinct macrophage populations at the tissue-implant interface and how this may affect downstream regenerative processes. Populations identified as F4/80+, CD68+ and CD11b+ macrophages at the peri-implant space showed distinct susceptibility to polarize towards an M2-like phenotype under the effects of delivered IL-4. Also, the presence of the coating resulted in a significant reduction in F4/80+ macrophages, while other populations remained unchanged. These results suggests that the F4/80+ macrophage population may be predominant in the early stages of the host response at the surface of these implants, in contrast to CD11b+ macrophage populations which were either fewer in number or located more distant from the implant surface. Gene expression assays showed increased proteolytic activity and diminished matrix deposition as possible mechanisms explaining the decreased fibrotic capsule deposition and improved peri-implant tissue quality shown in previous studies using IL-4 eluting coatings. The pattern of M2-like gene expression promoted by IL-4 was correlated with glycosaminoglycan production within the site of implantation at early stages of the host response, suggesting a significant role in this response. These findings demonstrate that immunomodulatory strategies can be utilized to design and implement targeted delivery for improving biomaterial performance.

Effects of aging upon the host response to implants.

Macrophage polarization during the host response is now a well-accepted predictor of outcomes following material implantation. Immunosenescence, dysregulation of macrophage function, and delayed resolution of immune responses in aged individuals have all been demonstrated, suggesting that host responses to materials in aged individuals should differ from those in younger individuals. However, few studies examining the effects of aging upon the host response have been performed. The present work sought to elucidate the impacts of aging upon the host response to polypropylene mesh implanted into 8-week-old and 18-month-old mice. The results showed that there are significant differences in macrophage surface marker expression, migration, and polarization during the early host macrophage response and delayed resolution of the host response in 18-month-old versus 8-week-old mice. These differences could not be attributed to cell-intrinsic defects alone, suggesting that the host macrophage response to implants is likely also dictated to a significant degree by the local tissue microenvironment. These results raise important questions about the design and testing of materials and devices often intended to treat aged individuals and suggest that an improved understanding of patient- and context-dependent macrophage responses has the potential to improve outcomes in aged individuals. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1281-1292, 2017.