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Beyond its actions on the nervous system, amitriptyline (AM) has been shown to lower inflammatory, angiogenic, and fibrogenic markers in a few pathological conditions in human and in experimental animal models. However, its effects on foreign body reaction (FBR), a complex adverse healing process, after biomedical material implantation are not known. We have evaluated the effects of AM on the angiogenic and fibrogenic components on a model of implant‐induced FBR. Sponge disks were implanted subcutaneously in C57BL/6 mice, that were treated daily with oral administration of AM (5 mg/kg) for seven consecutive days in two protocols: treatment was started on the day of surgery and the implants were removed on the seventh day after implantation and treatment started 7 days after implantation and the implants removed 14 after implantation. None of the angiogenic (vessels, Vascular endothelial growth factor (VEGF), and interleukin‐1β (IL‐1β) or fibrogenic parameters (collagen, TGF‐β, and fibrous capsule) and giant cell numbers analyzed were attenuated by AM in 7‐day‐old implants. However, AM was able to downregulate angiogenesis and FBR in 14‐day‐old implants. The effects of AM described here expands its range of actions as a potential agent capable of attenuating fibroproliferative processes that may impair functionality of implantable devices. [ABSTRACT FROM AUTHOR]

Sodium butyrate (NaBu), a histone deacetylase inhibitor, has shown to exert beneficial actions attenuating inflammation in a number of intestinal and extra-intestinal diseases. However, the effects of NaBu on persistent inflammatory processes as in a response to implantation of foreign material have not been investigated. Synthetic matrix of polyether-polyurethane sponge was implanted in mice's subcutaneous layer of the dorsal region, and the animals were treated daily with oral administration of NaBu (100 mg/kg). After 7 days, the implants were removed and processed for assessment of inflammatory markers. Butyrate treatment caused a significant attenuation of neutrophil and macrophage infiltration in implants, which was reflected by the reduction of myeloperoxidase and N-acetyl-β-D-glucosaminidase activities, respectively. Similar reduction was observed in intra-implants nitrite levels of NaBu-treated mice. NaBu treatment was also able to decrease mast cell recruitment/activation and the levels of CXCL1, CCL2, IL-6, TNF-ɑ, and TGF-β1 in the implants but did not alter the levels of IL-10. In addition, NaBu administration decreased the concentration of proteins p65 and p50 in the nucleus as compared with the cytoplasm by western blot analysis. This result suggests that treatment with NaBu inhibited the NF-κB pathway. The circulating levels of TNF-ɑ and TGF-β1 were also attenuated by NaBu. Persistent inflammation at sites of implanted devices very often impairs their functionality; therefore, our findings suggest that NaBu holds potential therapeutic value to control this adverse response to biomedical implants. [ABSTRACT FROM AUTHOR]

Objective: Obesity is a highly prevalent multifactorial metabolic condition in which the need for functional bioengineered substitutes (e.g., scaffolds for tissue engineering) is likely to occur. However, the adverse foreign body response (FBR) that invariably takes place adjacent to implant devices impairing their function is poorly characterized in this condition. This study investigated the influence of obesity on the host response to a synthetic matrix implanted subcutaneously in high-fat-fed obese mice.Methods: Histological analysis of 14-day-old implants was performed to identify collagen deposition, capsule thickness, fibroblast-like cells, foreign body giant cells, and mast cells. In addition, transforming growth factor β1 (TGF-β1) levels in the implants and serum were determined.Results: All fibrogenic markers (and TGF-β1 levels) increased in the implants of obese mice compared with their nonobese counterparts. Particularly relevant was the fibrous capsule thickness in implants of obese mice (234.2 ± 22.1 µm vs. 109.2 ± 13.4 µm in implants of nonobese animals).Conclusions: The study results showing that obesity upregulates the main features of the FBR induced by subcutaneous implants in mice may be relevant in understanding biomaterial integration and performance in this condition. This is crucial to the development of strategies to maintain the integrity and function of implantable devices. [ABSTRACT FROM AUTHOR]