Pelvic organ prolapses (POP) is a serious gynecologic disease. Use of vaginal mesh implantation in order to provide effective support for the pelvic floor and increase muscle contraction of the pelvic organ is a common treatment method for POP, but body inflammatory responses and potential risks of mesh leakage faced this method with challenges. Recently, implantation of mesenchymal stem cells (MSCs)-loaded scaffolds in order to provide effective support for pelvic floor and induce pelvic floor muscle regeneration has been noticed [1]. In this study, we intended to design and development of biodegradable collagen (COL)/polyvinyl alcohol (PVA) nanofibrous scaffolds to human MSCs delivery for POP treatment. This study examined design parameters of pelvic floor repair scaffolds including chemical structure, mechanical properties, morphology, swelling capacity, biodegradability and biocompatibility.

Aqueous solutions of COL and PVA were prepared and mixed with volumetric ratios of COL to PVA  0, 30/70, 50/50 and subjected to electrospinning. Prepared scaffolds were cross-linked with glutaraldehyde (GA) in order to improved mechanical properties and increased chemical stability. Chemical structure, tensile strength, biodegradation and swelling ratio of nanofibers were studied and effects of varying the ratio of COL to PVA and GA cross-linking on their physicochemical properties investigated. Human adipose derived stem cells (ADSCs) were used to measure the cytotoxicity of prepared scaffolds using MTT assay in 24, 48 and 72 hrs. Based on the analyses conducted, COL/PVA 50/50 was selected for additional tests including in vitro and in vivo analysis.

Scanning electron microscopy (SEM) images showed that all synthesized scaffolds had a completely porous structure with high interconnectivity. ImageJ analysis of SEM images showed that COL/PVA: 0, 30/70, 50/50 had mean pore size of 40.72, 60.504, 87.28 µm2 respectively. Water contact angel value of uncross-linked COL/PVA 50/50 and cross-linked COL/PVA 50/50 were 95.102 0 and 68.226 0 respectively. Swelling and biodegradation ratio in all scaffold groups increased over time. There was no significant difference in swelling capacity of different groups after 72 hrs. The lowest degradation percentage belonged to COL/PVA 50/50, which had lost 61.6% of its initial weight after 21 days of exposure to biological environment. After GA treatment, young modulus of all prepared scaffolds increased more than 10 times and in COL/PVA 50/50 went from 1.21 MPa to 11.10 MPa. According to MTT results, COL/PVA 50/50 had maximum cell viability percentage after 72 hrs. SEM images of ADSCs loaded COL/PVA 50/50 demonstrated ADSCs well penetrated to scaffold pores and elongated along the nanofibers.

COL/PVA 50/50 nanofibrous scaffolds could act as a mechanical support for pelvic floor muscle and provide a suitable platform for transfer of ADSCs with their porous structure. RGD motifs of COL as cell adhesion sequences enhanced biocompatibility of COL/PVA scaffolds. Also, increasing surface hydrophilicity and chemical stability of scaffolds after GA treatment are very effective in improving cell-scaffold interactions. According to previous studies results, young's modulus of 10 MPa could be suitable for pelvic repair scaffolds [2]. In addition, scaffolds complete degradation after in vivo application can minimize vaginal meshes surgical removal potential risks [3]. Use of this method for POP treatment required further analysis and in vivo study on POP induced rat models are being completed.

In this study, a biodegradable nanofibrous scaffold was designed and developed for POP treatment. Results of reviews showed COL/PVA 50/50 nanofibrous scaffolds had good hydrophilicity, suitable biodegradation time, biomechanical properties and biocompatibility for pelvic floor regeneration. Generally, these scaffolds showed promising potential for POP treatment.

Composite electrospun scaffold containing decellularized amniotic matrix for pelvic organ prolapse
Comparison of candidate scaffolds for tissue engineering for stress urinary incontinence and pelvic organ prolapse repair
Galvanic Cell-Stimulated Mesenchymal Stem Cell Mesh for Enhanced Pelvic Organ Prolapse Treatment