Inflammation around an implant is like an orchestra rehearsal, where the conductor is the material itself and the musicians are immune cells. The score is the same, but it sounds different depending on who is sitting at the stands: young or old, male or female.
Scientists took mice of two ages, 2 and 18 months (roughly like 20 and 70 years in humans), and implanted particles of two common polymers into their thigh muscles: polycaprolactone and polyethylene. After six weeks, they read all the active genes in the tissue around the implant, measured scar thickness, and counted immune cells. It turned out that sex changes the score more strongly than age: between males and females of the same age, more than 3000 genes differed, while between young and old mice of the same sex, fewer than 200 did.
The difference between the sexes also showed up in the composition of immune cells. In old males, the proportion of CD8+ T cells, which usually attack infected cells, grew in the tissue around the implant, while in females it was CD4+ T cells, which help other immune cells. Macrophages, the main "cleaners" and regulators of inflammation, carried more of the marker CD86, linked to aggressive inflammation, in females, and more of CD206, which indicates healing and tissue remodeling, in males.
This study was the first to compare age and sex in a single fibrosis model with two different implants. It shows that you cannot predict the body's response to a material from gene activity alone: you also need to look at proteins, cells, and the scar itself. Moreover, the picture depends on the specific polymer.
In practice, this means that preclinical testing of biomaterials should include both sexes and different age groups. If a material is tested only on young males, as is often done, you can miss the specifics of the female body or of older age. As a result, an implant that is safe for some will turn out to be problematic for others. The orchestra is one, but the score must be written with all the musicians in mind.
The difference in gene expression between the sexes at a single age exceeded 3000 genes, whereas between ages within one sex there were fewer than 200 differences. This shows how much more strongly sex influences the transcriptome than age does in this model.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.