FOreign body Reaction to bioMaterials and the Effect of Disease; inFORMED-trial

Foreign body reaction to biomaterials like meshes for hernia repair should be
minimal. A mesh should successfully integrate in the body without causing
massive inflammation and/ or fibrosis. Before a mesh can be used in the clinic,
it is necessary to examine its effect on inflammation and fibrosis. For this,
cell culture and animal experiments are used. In previous studies we have shown
that culturing monocytes isolated from healthy donors on different meshes leads
to a mesh specific reaction and that even in an in vitro model for
contamination, meshes still elicit specific reactions in macrophages.

These two culture models are set-up with cells of healthy donors. It is known
from the clinic however that certain groups of patients have increased risk for
adverse outcomes after implantation of a mesh, such as obese, diabetic, smoking
or old patients and patients with an aortic aneurysm. Age and disease affect
the behavior of cells involved in wound healing and reaction to meshes.

Obesity for instance induces a phenotypic switch in adipose tissue macrophage
polarization, from M2 (macrophages type 2, anti-inflammatory) to M1
(macrophages type 1, pro-inflammatory) activation and obese subjects have more
total fibrosis in white adipose tissue and have more fibrosis around adipocytes
than lean subjects. In addition, recently it was found that macrophages from
obese patients have less differentiation capacity towards an anti-inflammatory
M2 phenotype.

The set-up culture models do not take these diseases into account and it is
expected that cells from obese patients or patients with an aortic aneurysm
will behave differently from cells from healthy subjects in their reaction to
meshes. Therefore, we propose to use macrophages in our earlier set-up models.

The aim if this study is to investigate how disease affects the foreign body
reaction and how cells from patients at risk for adverse outcomes respond to
meshes in vitro. This knowledge can be used to choose the best performing
meshes to be used in specific patient groups. This might eventually lead to a
model that can be used to test several meshes using the patient*s own cells
prior to implantation of a mesh.

Primary Objective:
Examine the effect of disease on the responses to meshes

Secondary Objective(s):
- Compare the acute reaction of macrophages from patients at risk of adverse
outcome (obese or aortic aneurysm) after implantation of meshes with the
reaction of macrophages from healthy donors to meshes.

prospective study

In every group we will include 20 patients.
- 20 patients with BMI >30
- 20 patients with an aortic aneurysm >3cm (BMI between 18-27kg/m2)
- 40 volunteers, control

There is no serious extra risk for patients that are participating is this
trial.