Evaluating the Nature of Immune Responses to Implanted Polypropylene Mesh
The TissueFAXS PLUS is a modular upright fluorescence and brightfield system for the scanning and analysis of tissue sections, cytospins, smears, and tissue microarrays on slides1. It is a versatile whole slide imaging system that can provide a range of capabilities, including brightfield scanning, widefield fluorescence, confocal, and multispectral microscopy. Furthermore, an inbuilt image analysis software completes the package.
The system has recently been used to investigate the type of immune reactions that occur at the site of implanted polypropylene meshes.
Surgical mesh is used in a range of tissue repair procedures to stabilize and strengthen soft tissue defects or to support prolapsed organs and viscera. One of their most common applications is hernia repair. The mesh serves to mechanically strengthen the weakened area while simultaneously providing a scaffold to support the growth of new tissue, which expands through pores in the mesh and eventually surrounds it.
Historically, hernia surgery required tissue at the edges of the torn or weakened area to be stitched together. These stitches were frequently subjected to considerable strain and, consequently, hernia repair commonly failed. The introduction of meshes has resulted in considerably fewer hernia recurrences.
The first meshes to be used were made from polypropylene, and this continues to be the most common type of mesh used in hernia and pelvic organ prolapse repairs. However, since polypropylene is not a product that occurs naturally in the body, it is identified as being foreign and the body raises an immune response in an attempt to remove it and minimize the potential threat. Although measures are taken to control immune responses to polypropylene mesh implants, implant rejection is an ongoing concern with hernia repair.
Immune Response to Implants
Immune cells migrate to the site of the implant, causing inflammation and the formation of a fibrous capsule (known as a foreign body granuloma) that encapsulates the mesh to isolate it from the rest of the body2. This granulomatous inflammation in response to a foreign body is typically considered to be due to activation of the innate immune system, and so dominated by macrophages that collect at the mesh surface3,4.
The adaptive immune response, which is more specific but takes longer to initiate, involves the release of B-lymphocytes and T-lymphocytes5. Since lymphocytes have been detected in the foreign body granuloma that develops at the site of the mesh implant, there is the possibility that adaptive immunity may play a role in the foreign body reaction6,7. The role of the adaptive immune system at the site of mesh implants, however, remains uncertain.
Evaluation of Immune Response to Polypropylene Mesh
A recent study investigated the foreign body reaction to seven polypropylene meshes that had been removed from patients due to hernia recurrence8. The meshes had been in situ in the abdomen for a median duration of one year.
Each mesh was viewed by immunofluorescence microscopy using a TissueGnostics TissueFAXS PLUS and StrataQuest analysis software to determine which immune cells were present. A pronounced foreign body reaction was apparent on all the specimens, and this was restricted to the vicinity of the mesh fibers where there was dense cellular infiltrates of mononuclear cells.
In addition to macrophages from the innate immune system, T-helper cells and regulatory T-cells of the adaptive immune response were also present. Furthermore, significant clustering of the adaptive immune cells was observed at the mesh fibers. The density of the different classes of immune cells was determined in circles of 1 mm2 across the mesh fibers as well as in the surrounding tissue at an increasing distance from the site of the implant. There was a high proportion of innate immune cells in the foreign body granuloma, as expected for immune responses against foreign structures “invading” the body. However, also adaptive immune cells were frequently observed at a higher abundance than expected. In particular, the proportions of T cells present were similar to those observed for macrophages. In addition, B-cells were found to be clustered around blood vessels serving the tissues surrounding the mesh. The concentration of both innate and adaptive immune cells decreased significantly with increasing distance from the mesh fibers.
This latest research thus supports previous hypotheses that both innate and adaptive immune cells participate in the chronic foreign body response to implanted polypropylene meshes. The predominant immune cells involved in this response are T cells and macrophages.
This new finding may help physicians control foreign body granuloma formation at the site of hernia repair, which in turn could reduce the risk of rejection and patient morbidity from chronic inflammation at the repair site and promote speedy healing.
References and Further Reading
1. TissueGnostics. Upright Brightfield & Fluorescence Cytometers.
2. Krzyszczyk P, Schloss R, Palmer A, et al. Front Physiol. 2018;9:419.
3. Klosterhalfen B, Junge K, Klinge U. Expert Rev Med Devices 2005;2:103–117.
4. Pagán AJ, Ramakrishnan L. Annu Rev Immunol. 2018;36:639-665.
5. Netea MG, Schlitzer A, Placek K et al. Cell Host Microbe 2019;25:13–26.
6. Klinge U, Dietz U, Fet N, Klosterhalfen B. Hernia 2014;18:571–578.
7. Tennyson L, Rytel M, Palcsey S et al. Am J Obstet Gynecol 2019;220:187.e1-187.
8. Dievernich, A., Achenbach, P., Davies, L. et al. Hernia (2021)