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 electroassembled 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.

Collagen is a biological building block that is hierarchically assembled into diverse morphological structures that, in some cases, is dynamically adaptive in response to external cues and in other cases forms static terminal structures. Technically, there is limited capabilities to guide the emergence of collagen’s hierarchical organization to recapitulate the richness of biological structure and function. Here, we report an electro-assembly pathway to create a dynamically adaptive intermediate molten fibril state for collagen. Structurally, this intermediate state is composed of partially aligned and reversibly associating fibrils with limited hierarchical structure. These molten fibrils can be reversibly reconfigured to offer dynamic properties such as stimuli-stiffening, stimuli-contracting, self-healing, and self-shaping. Also, molten fibrils can be guided to further assemble to recapitulate the characteristic hierarchical structural features of native collagen (e.g., aligned fibers with D-banding). We envision that the electro-assembly of collagen fibrils will provide previously unidentified opportunities for tailored collagen-based biomedical materials.