Animal experimental research assessing urogynecologic surgical mesh implants: Outcome measures describing the host response, a systematic review and meta‐analysis

Abstract

Aim Before the introduction of new biomaterials for prolapse surgery, animal studies on the host response are required. Unfortunately, large variation in study design hampers obtaining an overview of the safety and efficacy, and translation to clinical practice. Our aim is to systematically review the literature on all outcome measures describing the host response in animal studies assessing the biocompatibility of urogynecologic surgical mesh implants for prolapse surgery. Furthermore, by meta‐analysis, we aim to assess the effect of implantation and compare this to control animals receiving sham surgery or native tissue repair. Methods We performed a systematic search from inception to August 2020. Since this is an explorative study we included original, controlled, and noncontrolled animal studies describing any host response to the implant. Quantitative outcome measures reported ≥10 times in ≥2 articles were eligible for meta‐analysis. Results Fifty articles were included in the qualitative synthesis and 36 articles were eligible for meta‐analysis. In total, 154 outcome measures were defined and classified into (1) histomorphology, (2) biomechanics and, (3) macroscopic morphology. Animals with vaginal implants demonstrated significantly increased M1 and M2 macrophages, MMP‐2, neovascularization, TNF‐α, and stiffness, and lower vaginal contractility compared to control animals. Conclusion The host response significantly differs in animals after vaginal mesh implantation compared to control animals, both pro‐ and anti‐inflammatory. However, we observed a paucity in the uniformity of reported outcomes. For future animal studies, we propose the development of a core outcome set, which ideally predicts the host response in women.

The impact of bacterial contamination on the host response towards fully absorbable poly-4-hydroxybutyrate and nonabsorbable polypropylene pelvic floor implants

“…Extensive histological analysis revealed higher levels of inflammatory cell infiltration, vascularization, and FBGC formation in mice with a biomaterial as compared to sham mice, confirming previous observations [ [42] , [43] , [44] , [45] , [46] ]. It is known that denser implants with smaller pores induce a more pronounced or prolonged inflammatory response as compared to lighter implants with larger pores [ 47 ].…”

“…Thirdly, we used relatively high doses and a monoculture of S. aureus bacteria whereas the vaginal flora in women is multimicrobial and also contains non-pathogenic commensals. And finally, the host response is also dependent on the site of implantation because this response has been shown to significantly differ in the vagina as compared to the abdomen [ 46 ], so this should be taken into account when interpreting these results.…”

Vaginal changes after ovariectomy in ewes -- a large animal model for Genitourinary Syndrome of Menopause

“…Furthermore, our research group has extensive experience with the evaluation of physiologic changes in the vagina and pelvic floor, including a variety of outcome measures and innovative technologies. [22][23][24][25][26][27] Also for this study, we devised an innovative way to determine the mean epithelial thickness of the vaginal wall, which provided a solid and representative value for our primary outcome. In addition, the 4-point grading scale, used for histology assessment, was determined from the data available from this study.…”

Role of Fibroblasts and Myofibroblasts on the Pathogenesis and Treatment of Pelvic Organ Prolapse

“…Even though implants are initially designed to surgically correct POP and provide mechanical support to the pelvic tissues, ideally they should induce a foreign body response that results in the development of new connective tissue that is mechanically self-sufficient to support descending organs [ 18 , 26 ]. Animal studies in which vaginal implant surgeries were performed indicated that healing response, vascularization, and collagen metabolism are increased, and consequently increase the mechanical properties of the tissue as compared to NTR [ 27 ].…”