Electrical Signal Initiates Kinetic Assembly of Collagen to Construct Optically Transparent and Geometry Customized Artificial Cornea Substitutes

Corneal transplantation is an effective treatment for reconstructing injured corneas but is very limited due to insufficient donors, which has led to a growing demand for development of artificial corneal substitutes (ACSs). Collagen is a potential building block for ACS fabrication, whereas technically there are limited capabilities to control the collagen assembly for creating highly transparent collagen ACSs. Here, we report an electro-assembly technique to kinetically control collagen assembly on the nanoscale that allows the yielding collagen ACSs with structure determined superior optics. Structurally, the kinetically electro-assembled collagen (KEA-Col) is composed of partially aligned microfibrils (∼10 nm in diameter) with compacted lamellar organization. Optical analysis reveals that such microstructure is directly responsible for its optimal light transmittance by reducing light scattering. Moreover, this method allows the creation of complex three-dimensional geometries and thus is convenient to customize collagen ACSs with specific curvatures to meet refractive power requirements. Available properties (e.g., optics and mechanics) of cross-linked KEA-Cols were studied to meet the clinical requirement as ACSs, and in vitro tests further proved their beneficial characteristics of cell growth and migration. An in vivo study established a rabbit lamellar keratectomy corneal wound model and demonstrated the customized collagen ACSs can adapt to the defective cornea and support epithelial healing as well as stroma integration and reconstruction with lower immunoreaction compared with commercial xenografts, which suggests its promising application prospects. More broadly, this work illustrates the potential for enlisting electrical signals to mediate collagen's assembly and microstructure organization for specific structural functionalization for regenerative medicine.