Introduction and Hypothesis <p>Mesh-augmented surgery in urogynecology involves the use of surgical mesh to support and reinforce weakened pelvic tissue. Although it can be effective, there are potential complications, including mesh extrusion and dyspareunia related to excessive inflammatory response. One possible approach to preventing excessive inflammation and promoting mesh–tissue integration is to utilize a mesh sandwiched between two layers of platelet-rich plasma-decellularized amnion scaffold (PRP-DAS).</p> Methods <p>This experimental study was performed on 24 menopausal rabbit models. The treatment group consisted of a polypropylene (PP) mesh coated with PRP-DAS on both sides, whereas the control group included a PP mesh without PRP-DAS. Mesh–tissue integration was evaluated through macroscopic, histological, and immunohistochemical analyses. Macroscopic assessment focused on mesh extrusion and contraction, whereas histology and immunohistochemistry were done by assessing inflammatory response (inflammatory infiltrates [ININ] and interleukin-17 [IL-17] expression), neovascularization (angiogenesis score and cluster of differentiation 31/CD31 expression) and collagen deposition using image J on days 14, 28, and 90 following mesh implantation. Data were analyzed using one-way ANOVA followed by Tukey post hoc test.</p> Results <p>Results demonstrated that no mesh extrusion was found in either group; however, mesh contraction was significantly lower in the PRP-DAS group than in controls. On days 28 and 90, ININ was significantly lower (<i>p</i> &lt; 0.01; <i>p</i> = 0.011) and IL-17 expression was markedly elevated (<i>p</i> &lt; 0.01) in the PRP-DAS group compared with the controls. Moreover, collagen deposition was significantly higher (<i>p</i> &lt; 0.01) in the PRP-DAS group by day 90.</p> Conclusion <p>The PRP-DAS sandwich prevents excessive inflammatory response and enhanced mesh–tissue integration in the menopausal rabbit model.</p>