Engineering Nanofiber Morphology in Electrospun Poly(Oligoethylene Glycol Methacrylate)-Based Tissue Scaffolds

Abstract

Soft tissue engineering has become increasingly relevant in efforts to create complex, functional tissues for tissue replacement in tissue engineering applications or for the development of more complex tissue models for drug screening or fundamental research. Tissue engineering of micro- and nano-scale structures has been explored through a number of biofabrication techniques but most successfully on the nano-scale through electrospinning. Electrospun nanofibers represent one of the most similar structures to natural extracellular matrix (ECM), while electrospinning of hydrogel nanofibers is particularly relevant given that such nanofibers support the high water content environment required by cells to survive. Herein, a reactive cell electrospinning process is demonstrated based on dynamic hydrazone-crosslinked poly(oligoethylene glycol methacrylate (POEGMA) hydrogel nanofibers that can be electrospun from an aqueous solution, allowing for the generation of cell-loaded hydrogel nanofibers in a single fabrication/cell-seeding step. Using the proper collectors, the fabrication of aligned and/or multi-layered scaffolds is demonstrated without the risk of layer delamination due to the dynamic crosslinking of POEGMA hydrogels. Co-electrospun NIH 3T3 fibroblasts and Psi2 12S6 epithelial cells were found to proliferate over 14 days within the networks, while electrospun C2C12 myoblasts were found to align along the direction of aligned fibers. POEGMA hydrogels provide a suitable environment for cells and can be expanded to multi-layer, multi-cellular networks with tunable micro-architectures to better mimic more complex aligned (e.g. muscle) and/or multi-layer (e.g. smooth muscle vasculature, esophageal) tissues.