Chronic inflammatory responses to microgel-based implant coatings

Abstract

Inflammatory responses to implanted biomedical devices elicit a foreign body fibrotic reaction that limits device integration and performance in various biomedical applications. We examined chronic inflammatory responses to microgel conformal coatings consisting of thin films of poly(N-isopropylacrylamide) hydrogel microparticles cross-linked with poly(ethylene glycol) diacrylate deposited on poly(ethylene terephthalate) (PET). Unmodified and microgel-coated PET disks were implanted subcutaneously in rats for 4 weeks and explants were analyzed by histology and immunohistochemistry. Microgel coatings reduced chronic inflammation and resulted in a more mature/organized fibrous capsule. Microgel-coated samples exhibited 22% thinner fibrous capsules that contained 40% fewer cells compared to unmodified PET disks. Furthermore, microgel-coated samples contained significantly higher levels of macrophages (80%) than unmodified PET controls. These results demonstrate that microgel coatings reduce chronic inflammation to implanted biomaterials. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Figure 1

Microgel coatings reduce chronic inflammation associated with materials implanted subcutaneously in the rat dorsum for 4 wk. Explants were evaluated for fibrous encapsulation by staining collagen (pink), elastin (black), and nuclei (black). Representative images for unmodified PET (a) and microgel-coated PET (b) disks, and the original implant location is designated. Black arrows indicate capsule measurements. Microgel coatings reduced fibrous capsule thickness by 22% compared to unmodified PET controls as quantified in (c), * p < 0.04. The density of capsule-associated cells was also significantly reduced in microgel-coated samples (* p < 5.6×10⁻³) compared to unmodified PET controls as quantified in (d). Data is represented as the average value ± standard error of the mean using n = 4–7 samples per treatment group. Scale bar is 50 μm.

Figure 2

Inflammatory cell profiles associated with biomaterials implanted subcutaneously in the rat dorsum for 4 wk. Explant sections were stained via immunohistochemical methods for macrophage marker CD68 (pink) and counter-stained with hematoxylin to label nuclei (blue). Representative images for unmodified PET (a) and microgel-coated PET (b) disks, and the original implant location is designated. Total CD68+ cells were quantified in (c), but no statistical differences were found between treatment groups. (d) When normalized to total capsule-associated cells (from Fig. 1d), unmodified PET controls contained proportionately fewer CD68+ cells than microgel-coated PET (* p < 0.02). Multinucleated CD68+ cells (FBGCs) at the cell-implant interface were also quantified (e), but no statistical differences were found between treatment groups. FBGCs are designated by black arrows. Data is represented as the average value ± standard error of the mean using n = 4–7 samples per treatment group. Scale bar is 50 μm.