Electrospun cornea scaffold

Infections and injuries to the cornea may require cornea transplant. However, the lack of donor cornea has prompted researchers to look into constructing implants for cornea treatment. Electrospun scaffolds have shown great promises in various regenerative scaffolds. The ability control nanofibers arrangement has made it an attractive option to replicate ordered extracellular matrix (ECM) such as cornea.

Researchers have shown that several types of corneal cells grew well on electrospun scaffolds. Deshpande et al (2010) were able to culture limbal epithelial cells on electrospun poly(lactide-co-glycolide) scaffold for the purpose of delivering the cell to the cornea. Human keratocytes (HKs) and human corneal epithelial cells (HCECs) have been found to grow well on electrospun polyvinyl acetate (PVA)/collagen (PVA-COL) scaffolds. Wu et al (2018) showed that HKs grew in the same orientation as aligned electrospun PVA-COL fibers. On random organized electrospun PVA-COL fibers, no cell orientation was observed. HCECs did not show any orientation on both aligned and random nanofibers.

A challenge for cornea scaffold is that it should demonstrate a high degree of optical transparency, either at implantation or following recovery. Electrospun randomly organized fibers generally exhibit low level of transparency. A significantly higher level of transparency can be achieved when the fiber is organized [Wu et al 2018]. Comparison of the transparency using spectrum analysis showed that aligned-oriented nanofibrous mat has a transparency that is twice higher than randomly oriented nanofibrous mat [Kim et al 2018]. To enhance the transparency of electrospun aligned nanofibers, Kong et al (2017) used laser to create perforations of diameters in the range of 100 to 200 µm at intervals of 50 to 100 µm on the membrane. This perforated electrospun poly (lactic-co-glycolide) (PLGA) membrane was sandwiched between collagen gels and compressed to give a hybrid construct. This hybrid construct was found to exhibit an optical transmittance of 63% and this was increased to 72% after 7 days of immersion in PBS solution.

Transparency due to fiber organization is not restricted to just parallel aligned fibers. Electrospinning may also be used to produce fibers that are radiating from a center. Kim et al (2018) used a non-conducting hemispherical device with a conducting pin in the middle and a wire that forms a ring at the base of the hemispherical device. This setup encourages the formation of a three-dimensional (3D) scaffold with electrospun fibers radiating from the center to the circular wire at the base. Due to the fiber organization, this scaffold was found to exhibit high transparency which is similar to native cornea in the visible wavelength when wetted in PBS. In clinical application of cornea repair scaffold, mechanical resistance against suture pullout is an important consideration on top of optical transparency. Stafiej et al (2018) seek to construct such a scaffold by using electrospun polycaprolactone (PCL) fibers reinforced alginate hydrogel. Using both randomly and cross-aligned electrospun PCL fibers as reinforcement, they found that randomly oriented fibers provided greater mechanical pullout strength compared to aligned fibers with thicker membrane providing more mechanical support. A membrane thickness of 20-30 µm showed mechanical resistance similar to amniotic membrane, the clinical gold standard. PCL/alginate composite hydrogel with PCL nanofiber membrane of thickness up to 30 µm show transparencies over 50% at 400 nm.

(A) Electrospinning setup of the fabrication of 3D radially oriented nanofibrous scaffolds, (B) copper wires, and metal pin in the hemispherical device designed to be electrically connected to each other [Kim et al 2018].

In cornea treatment, researchers have also looked into other areas where electrospun scaffold may play a part. Ortega et al (2013) investigated the use of constructed electrospun niches to house limbal stem cell which plays an important role in cornea regeneration. To construct this artificial niches, electrospinning was used in combination with microfabrication. Microstereolithography via a layer-by-layer photocuring was used to create a template which electrospun poly(lactic-co-glycolic acid) 50:50 was deposited. The template was in the form of a ring with micro-pockets on its circumstance. The deposited electrospun membrane which took on the shape of the underlying template was peeled off the template as the final scaffold. Mirzaeei et al (2018) electrospun fibrous meshes of chitosan/polyvinyl pyrrolidone (PVP), chitosan/PVP/polyvinyl alcohol (PVA) and zein/Eudragit loaded with triamcinolone acetonide for the purpose of ocular delivery. Of these, chitosan/PVP electrospun fibers showed a sustained release up to 4 days while zein/Eudragit fibers released 77% of the drugs within this period. Investigation into the release kinetics of electrospun fibrous meshes of triamcinolone acetonide loaded chitosan/polyvinyl pyrrolidone (PVP) electrospun nanofibers showed the preferred Zero-order kinetic with constant release rate and independent drug concentration while other polymer combinations adhere to Higuchi model.

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