Liangpeng Ge,1–5,* Qingtao Li,2,3,* Junzi Jiang,2,3 Xiaoyan You,1 Zuohua Liu,1 Wen Zhong,6 Yong Huang,1 Malcolm MQ Xing2,31Chongqing Academy of Animal Sciences, Chongqing, People’s Republic of China; 2Department of Mechanical and Manufacturing Engineering, Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada; 3Manitoba Institute of Child Health, Winnipeg, MB, Canada; 4Key Laboratory of Pig Industry Sciences, Ministry of Agriculture,Chongqing, People’s Republic of China; 5Chongqing Key Laboratory of Pig Industry Sciences, Chongqing, People’s Republic of China; 6Department of Textile Sciences, Faculty of Human Ecology, University of Manitoba, Winnipeg, MB, Canada*These authors contributed equally to this workAbstract: Pelvic organ prolapse (POP) is a serious health issue affecting many adult women. Complications of POP include pelvic pressure, pelvic pain, and problems in emptying their bowels or bladder. Sometimes, POP may even cause urinary outflow obstruction and lead to bladder or kidney infections. Currently, synthetic and naturally derived materials have been chosen for treatment of POP to reduce the high recurrence rates after surgical interventions. However, existing materials for POP treatment cannot meet the clinical requirements in terms of biocompatibility, mechanics, and minimal risk of rejection. Especially, erosion in synthetic polymers and rapid degradation in natural polymers limit their further applications in clinics. To address these concerns, we report a novel POP replacement using core–sheath polystyrene/gelatin electrospun nanofiber mesh. The outside gelatin sheath provides a hydrophilic surface and implantable integrity between host and guest, while the inner PS core offers the necessary mechanical support. The composite mesh shows graft accommodation in pelvic submucosa after implantation in vivo, as shown in hematoxylin–eosin staining and T helper cell phenotype and macrophage phenotype stainings. Qualitative analysis of inducible nitric oxide synthase, arginase, interferon-γ, and interleukin-10 gene expressions also indicates that the implanted composite mesh switches to accommodation mode 2 weeks postimplantation. Thus, these novel core–sheath polystyrene/gelatin nanofibrous membranes are promising in pelvic reconstruction.Keywords: core-sheath nanofibrous patch, polystyrene, gelatin, pelvic reconstruction