Androgen administration and macrophage behavior in the tissue-implant response - biomed 2011

Macrophages are a critical component in the biocompatibility and function of implantable ceramic materials used in drug delivery applications. As part of the chronic inflammatory response, these cells surround the implant, establishing the tissue-implant interface and produce cytokines critical for recruitment of other complementary cells involved in the response. The purpose of this study was to evaluate the effect of androgens on behavior of the macrophage by further quantifying their presence in the fibrous tissue capsule of calcium phosphate (TCP) ceramic drug delivery systems with respect to their cytokine activity and release profile of the implant. Sixteen animals in four experimental groups were implanted with one TCP bioceramic each. Group I animals were implanted with a sham TCP ceramic not containing a steroid hormone (control group). Group II animals received the testosterone loaded TCP ceramic. Group III animals were implanted with the dihydrotestosterone loaded ceramic. Group IV animals received the androstenedione ceramic. At 90 days post-implantation, the animals were euthanized. The implants and fibrous tissue capsules were then extracted. Determination of macrophage populations and their behavior was conducted microscopically following H&E and IHC staining of antibodies to IL-1, IL-2, IL-6, and TNF- positive cells. All three of the hormones administered in this study, particularly androstenedione, significantly affect macrophage migration to the implant interface and surrounding fibrous tissue capsule when compared to the control group. In addition, these hormones limit the expression of cytokines severely limiting recruitment of other cells involved in the tissue-implant response.