
We chose poly(3-hydroxybutyrate- co-3-hydroxyhexanoate) (PHBH), a biocompatible and flexible polyester, as the matrix fiber. Alginate can easily form a hydrogel in the presence of divalent cations such as calcium, while cross-linked alginic acid can be chelated by ethylenediaminetetraacetic acid (EDTA) for easy dissolution. Alginate hydrogel has been extensively investigated for biomedical applications such as cell scaffolding and drug release. Electrospun nanofibers with high orientation were deposited on the surface of hydrogel beads of alginate, a natural hydrophilic and anionic polysaccharide commonly obtained from brown algae that exhibits good biocompatibility and biodegradability. We have focused on electrospinning as a promising technique to fabricate geometrically controlled nanofibers. Our model cyst is a controlled nano-structure, the “nanofiber-mâché ball”-a hollow nanofiber sphere made of biodegradable polyester. The approach introduced in this study was inspired by the fabrication of papier-mâché dolls from balloons and paper.

However, cell aggregates prepared by these methods are cell-filled structures it has been impossible to form a hollow structure such as a cyst. Previously reported methods of preparing three-dimensional (3D) cellular structures include the hanging drop method, the formation of spheroids by cell non-adhesive multi-plate or micropatterned-substrate methods, and the use of cell sheets, bioprinting, and hydrogels for forming 3D cell aggregates. Most investigations of cyst biology have involved in vivo experimental models elucidating cellular behaviors in the cyst in vitro has proved difficult. Treatment of malignancies is difficult, especially if the brain stem is extensively involved in the cyst. For example, an intracranial epidermoid cyst sometimes undergoes a malignant transformation into an intracranial squamous-cell carcinoma, which has a poor prognosis. Cysts occur in every kind of tissue they are usually harmless and heal spontaneously, but occasionally transform into malignant tumors. The novel nanofiber-mâché technique, using a millimeter-sized hollow fibrous scaffold, is excellently suited to investigating cyst physiology.Ĭysts are spherical sac-like multicellular structures with fluid and semisolid matter inside. This structure helped to form an adepithelial layer on the inner surface. Circumferentially aligned fibers on the internal interface between the duct and hollow ball inhibited cells from migrating out of the interior, similar to a fish bottle trap. This resulted in a concentration gradient that induced oriented migration, in which seeded cells adhered randomly to the inner surface, formed a highly oriented structure, and then secreted a dense web of collagen fibrils. Two ducts located on opposite sides provided a route to exchange nutrients and waste. A ball with approximately 230 mm 3 inner volume provided a fibrous geometry mimicking the topography of the extracellular matrix. For this purpose, we designed a hollow nanofiber sphere, the “nanofiber-mâché ball.” This hollow structure was fabricated by electrospinning nanofiber onto alginate hydrogel beads followed by dissolving the beads. The occasional malignant transformation of intracranial epidermoid cysts into squamous cell carcinomas remains poorly understood the development of an in vitro cyst model is urgently needed.
