Preclinical Analysis of Sex-Specific Differences in the Angiogenic and Inflammatory Tissue Response to Surgical...

Surgical sutures are widely used biomaterials in clinical practice. Like all other biomaterials, they induce a foreign body response after implantation that involves inflammation and angiogenesis. Although it is well known that these processes differ in males and females, sex-specific differences in the tissue response to sutures have not been investigated so far. To do this in the present study, polypropylene sutures were implanted into the dorsal skinfold chamber and subcutaneous flank tissue of male and female mice to assess their acute and chronic effects on the local tissue microenvironment using intravital fluorescence microscopy and immunohistochemistry over 14 and 28 days, respectively. Microhemodynamic parameters and the numbers of rolling and adherent leukocytes in venules next to the implants were comparable in male and female mice. Immunohistochemical analyses on day 14 revealed a stronger neutrophilic (myeloperoxidase (MPO)⁺ cells: 526 ± 29 mm^-2) and macrophage (CD86⁺ cells: 188 ± 21 mm^-2; CD163⁺ cells: 269 ± 25 mm^-2) response, as well as reduced T-cell activation (CD3⁺ cells: 31 ± 4 mm^-2) in females when compared to males (MPO⁺ cells: 221 ± 25 mm^-2; CD86⁺ cells: 120 ± 15 mm^-2; CD163⁺ cells: 101 ± 19 mm^-2; CD3⁺ cells: 62 ± 13 mm^-2), while microvessel density and collagen deposition in the forming granulation tissue around the implants did not differ between sexes. In the flank model, there were no detectable sex-specific differences in the chronic foreign body response. These findings demonstrate that polypropylene sutures provoke a stronger early activation of the innate immune system in females, whereas the chronic foreign body response to the implants is comparable in both sexes.