Electrospun nanofiber mesh with connective tissue growth factor and mesenchymal stem cells for pelvic floor repair: Long-term study.

Pelvic organ prolapse (POP) affects many women, with an estimated lifetime risk of surgical intervention of 18.7%. There is a need for alternative approaches as the use of synthetic nondegradable mesh was stopped due to severe adverse events, and as current methods for pelvic floor repair have high POP recurrence rates. Thus, we hypothesized that electrospun degradable meshes with stem cells and growth factor were safe and durable for the long term in elderly rats. In an abdominal repair model, electrospun polycaprolactone (PCL) meshes coated with connective tissue growth factor (CTGF)/PEG-fibrinogen (PF) and rat mesenchymal stem cells were implanted in elderly female rats and removed after in average 53 weeks (53-week group). Collagen amount and production were quantified by qPCR and Western blotting. Moreover, histological appearance and biomechanical properties were evaluated. Results were compared with previous results of young rats with identical mesh implanted for 24 weeks (24-week group). The 53-week group differed from the 24-week group in terms of (1) reduced collagen III, (2) strong reduction in foreign body response, and (3) altered histological appearance. We found comparable biomechanical properties, aside from higher, not significant, mean tissue stiffness in the 53-week group. Lastly, we identified mesh components 53 weeks after implantation. This study provides new insights into future POP repair in postmenopausal women by showing how CTGF/PF-coated electrospun PCL meshes with stem cells exhibit sufficient support, biocompatibility, and no mesh-related complications long term in an abdominal repair model in elderly rats.

Electrospun nanofiber mesh with fibroblast growth factor and stem cells for pelvic floor repair.

Surgical outcome following pelvic organ prolapse (POP) repair needs improvement. We suggest a new approach based on a tissue-engineering strategy. In vivo, the regenerative potential of an electrospun biodegradable polycaprolactone (PCL) mesh was studied. Six different biodegradable PCL meshes were evaluated in a full-thickness abdominal wall defect model in 84 rats. The rats were assigned into three groups: (1) hollow fiber PCL meshes delivering two dosages of basic fibroblast growth factor (bFGF), (2) solid fiber PCL meshes with and without bFGF, and (3) solid fiber PCL meshes delivering connective tissue growth factor (CTGF) and rat mesenchymal stem cells (rMSC). After 8 and 24 weeks, we performed a histological evaluation, quantitative analysis of protein content, and the gene expression of collagen-I and collagen-III, and an assessment of the biomechanical properties of the explanted meshes. Multiple complications were observed except from the solid PCL-CTGF mesh delivering rMSC. Hollow PCL meshes were completely degraded after 24 weeks resulting in herniation of the mesh area, whereas the solid fiber meshes were intact and provided biomechanical reinforcement to the weakened abdominal wall. The solid PCL-CTGF mesh delivering rMSC demonstrated improved biomechanical properties after 8 and 24 weeks compared to muscle fascia. These meshes enhanced biomechanical and biochemical properties, demonstrating a great potential of combining tissue engineering with stem cells as a new therapeutic strategy for POP repair. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:48-55, 2020.