Electrospun Nanofibers with Core–Shell Structure for Treatment of Bladder Regeneration

Abstract

Hyaluronic acid (HA) is an important component of the extracellular matrix (ECM), and electrospun scaffolds have the three-dimensional porous network structure characteristics similar to those of the autologous ECM. However, scaffold fabrication of water-dissolved HA without surfactant by electrospinning is difficult. This study reports the fabrication of HA-coated biomimetic nanofiber scaffolds through coaxial electrospinning of poly(l-lactide)/poly(e-caprolactone) (PLCL) and HA to modulate proliferation and migration of smooth muscle cells (SMCs) for bladder regeneration. The nanofibers were verified by scanning and transmission electron microscopy, attenuated total reflection Fourier transform infrared spectroscopy. Contact angle and swelling were measured to determine hydrophilicity of the nanofiber scaffolds. SMCs were seeded onto the PLCL/HA and PLCL scaffolds for the in vitro study. For the in vivo study, 36 rats were divided into the PLCL/HA, PLCL, cystotomy controls, and sham surgery groups, 8 rats per group. The 40–50% supratrigonal cystectomy was performed and replaced with or without domed scaffolds. The rats were followed for 4 and 10 weeks. After the follow-up, urodynamic test was performed to check the functions of bladder. The defect area was excised for histological examination. Highly uniform PLCL/HA nanofibers had the core–shell structures. The HA coating on the PLCL nanofibers endowed the nanofibrous mats with increased anisotropic wettability and swelling. The PLCL/HA nanofibers significantly promoted SMC proliferation and migration. In vivo implantation in a rat bladder augmentation model demonstrated that the bladder walls made of PLCL/HA nanofiber scaffolds integrated with host tissue and stimulated the formation of bladder smooth muscle layers that expressed contractile protein alpha-smooth muscle actin. In addition, bladder capacity was significantly improved. These findings show that the bilayer PLCL/HA nanofiber domed mesh is a promising scaffold with good cytocompatibility and can promote smooth muscle tissue proliferation for bladder regeneration.

Impact Statement

The extracellular matrix (ECM)-inspired electrospinning scaffolds have a good cytocompatibility. Hyaluronic acid (HA) is one of the main components in the bladder ECM, but it is hard to be made by electrospinning alone. In this study, it is shown that coaxial electrospinning can fabricate poly(l-lactide)/poly(e-caprolactone) (PLCL)/HA nanofibers with the core–shell structure. The HA coating nanofibers have more hydrophilicity, which can promote cell proliferation and migration by filopodial outgrowth. We also fabricated domed PLCL/HA nanofiber scaffolds used in bladder regeneration by improving bladder capacity and facilitating smooth muscle proliferation.