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

Abstract

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.

Keywords: biodegradable mesh; connective tissue growth factor; mesenchymal stem cells; pelvic floor repair; pelvic organ prolapse; tissue engineering.

FIGURE 1

Collagen I and collagen III. mRNA expression of collagen I (A) and collagen III (B) relative to GAPDH expression, and protein amounts of collagen I (C) and collagen III (D) as ratio of total protein. *p < .05. Data on the 24‐week group is from the study by Hansen et al.

FIGURE 2

Histological assessment. (A,B) From the 53‐week group showing; (A) HE stain; foreign body giant cells (FBGCs) marked with arrows, blood vessels marked with ‘V’, and (B) MT stain; estimated percentage of collagen shown. (C) Amount of FBGCs evaluated as an average amount at ×200 magnification. (D) Degree of vascularization evaluated as average amount of blood vessels at ×200 magnification. (E) Collagen content evaluated as percentage of collagen. ****p < .0001. Evaluated specimens of the 24‐week group is from the study by Hansen et al.

FIGURE 3

Main histological categories; high foreign body giant cell (FBGC) response, low FBGC response, high vascularization and abscess formation, and their appearance in the two groups. Images of high FBGC response and abscess formation from the 24‐week group, and images of low FBGC response and high vascularization from the 53‐week group. Evaluated specimens of the 24‐week group is from the study by Hansen et al.

FIGURE 4

Evaluation of mesh remnants. Representative images of thick and thin cell dense and cell poor areas, mesh fibers in cell dense area, and dissolved mesh. All images from the 53‐weeks specimens

FIGURE 5

(A) Stress–strain curves. (B) Ultimate tensile strength (UTS). (C) Strain at UTS. (D) Young's modulus. *p < .05; **p < .01; ****p < .0001. Data on the 24‐week group is from the study by Hansen et al.