Surface-Conjugated Galactose on Electrospun Polycaprolactone Nanofibers: An Innovative Scaffold for Uterine Tissue Engineering.

Abstract

The uterus, a vital organ in the female reproductive system, nurtures and supports developing embryos until maturity. This study focuses on addressing uterine related problems by creating a nanofibrous scaffold to regenerate uterine myometrial tissue, closely resembling the native extracellular matrix (ECM) for enhanced efficacy. To achieve this, we utilized polycaprolactone (PCL) as a biomaterial and employed an electrospinning technique to generate PCL nanofibers in both random and aligned orientations. Due to the inherent hydrophobic nature of PCL nanofibers, a two-step wet chemistry surface modification technique is used, involving the conjugation of galactose onto them. Galactose, a lectin-binding sugar, was chosen to enhance the scaffold's hydrophilicity, thereby improving cell adhesion and fostering l-selectin-based interactions between the scaffold and uterine cells. These interactions, in turn, activated uterine fibroblasts, leading to ECM remodeling. The optimized electrospinning process successfully generated random and aligned nanofibers. Subsequent surface modification was carried out, and the modified scaffold was subjected to various physicochemical characterization, such as the ninhydrin assay, enzyme-linked lectin assay techniques that revealed successful galactose conjugation, and mechanical characterization to assess any changes in material bulk properties resulting from the modification. The tensile strength of random galactose-modified PCL fibers reached 0.041 ± 0.01 MPa, outperforming random unmodified PCL fibers (0.026 ± 0.01 MPa), aligned unmodified PCL fibers (0.011 ± 0.001 MPa), and aligned modified PCL fibers (0.016 ± 0.002 MPa). Cytocompatibility studies with human uterine fibroblast cells showed enhanced viability and proliferation on the modified scaffolds. Initial pilot studies were attempted in the current study involving subcutaneous implantation in the dorsal area of Wistar rats to assess biocompatibility and tissue response before proceeding to intrauterine implantation indicated that the modification did not induce adverse inflammation in vivo. In conclusion, our study introduces a surface-modified PCL nanofibrous material for myometrial tissue engineering, offering promise in addressing myometrial damage and advancing uterine health and reproductive well-being.