Spatiotemporal histological changes observed in mouse subcutaneous tissues during the foreign body reaction to silicone

Abstract

We investigated spatiotemporal changes in host tissues during foreign body reactions. Silicone tube was subcutaneously embedded into ICR mice, and tissue surrounding silicone (TSS) was observed at 2, 7, 14, 21, 28, 43, and 70 days (D) postsurgery. The thin layer (TL) and loose connective tissues (LCTs) (inside and outside the TSS) developed until D21 and densified afterward. Neutrophils infiltrated the TSS until D14 and formed neutrophil extracellular traps (NETs) in the TL during D7‐21. In the LCTs, mast cell counts increased until D21, and macrophage numbers peaked at D14. Several macrophages showed LYVE‐1 expression, supporting a tissue‐remodeling role. Developmental indices of collagen fibers (CFs) and reticular fibers (RFs) increased during D2‐21. NETs, but not neutrophils, were detected after D28. Mast cell numbers peaked at D43 and were maintained until D70. Myofibroblasts consistently localized to the TL from D14. During D21‐28, the area of connective tissue (CNT), and CFs and RFs decreased and increased, respectively, and both remained constant during D28‐70. The CF density remained constant from D21 and increased at D70. Thus, TSS showed two phases: inflammation and CNT development (D2‐21), and inflammation convergence and CNT stabilization (D28‐70). These results provide insights into foreign body reactions in clinical cases.

Micrococcal Nuclease stimulates Staphylococcus aureus Biofilm Formation in a Murine Implant Infection Model

“…The foreign body reaction is a process where an implant evokes an inflammatory reaction which recruits neutrophils, macrophages, and other immunomodulatory cells to the implant site often resulting in the enclosure of the biomaterial in fibrous tissue ( Anderson et al., 2008 ). The early stages of the foreign body reaction are marked by the transient presence of neutrophils and extensive production of neutrophil extracellular traps by activated neutrophils around these biomaterial implants ( Jhunjhunwala et al., 2015 ; Vitkov et al., 2015 ; Oe et al., 2021 ). Neutrophil extracellular traps are composed of DNA fibers and antimicrobial peptides such as citrullinated histones, myeloperoxidase, neutrophil elastase and cathepsin ( Brinkmann et al., 2004 ; Wang et al., 2009 ).…”

Modified foreign body reaction to silicone imbedded in subcutaneous tissues by different mouse systemic immune conditions

“…Surgeries were performed according to a previous study 3 . At 8 weeks of age, mice were anesthetized by intraperitoneal injection of a mixture of medetomidine (0.3 mg/kg), midazolam (4 mg/kg), and butorphanol (5 mg/kg).…”

“…The ST was easily retrieved because it was weakly attached to the subcutaneous tissues, as described previously 3 . D7 and D14 were considered as the reaction phases in the previous study 3 . D35 was selected as the stability phase.…”

“…Immunohistochemistry for CD3, B220, Gr‐1, CD31, CD68, and CD204 was performed to detect T cells, B cells, granulocytes, vascular endothelial cells, M1‐type macrophages, and M2‐type macrophages as previously described 3 . The paraffin sections were deparaffinized, and antigen retrieval was performed.…”

“…During FBR, immune cells, especially macrophages, play crucial roles in both inflammation and fibrosis 1 . In a previous study, FBRs to silicone tubes (STs) subcutaneously embedded in the back skin of ICR mice were divided into two main stages 3 . Briefly, the early stage of FBR mainly proceeded to an innate immune response characterized by infiltration of neutrophils and macrophages around the ST.…”