According to its developers, the nanoadhesive is based on tetrahedral framework nucleic acids mixed with functionalized polycationic recombinant proteins — a composition that minimizes the risks of tissue necrosis and inflammation common among polymeric adhesives. It is also reportedly capable of inhibiting bacterial growth and promoting tissue repair.

DNA-protein hybrid cage-like nanoadhesive for corneal transplantation. Source: Jing Zhao and Feng Zhang from Eye & ENT Hospital of Fudan University

The development of such a material is necessary in current ophthalmology practices to potentially avoid traumatic suturing surgery. While current varieties of polymeric adhesives for repairing human tissue have been developed, their use in ocular tissue adhesion — particularly in corneal transplantation — is still limited to the preclinical stage.

This is because polymeric adhesives create connections with wound tissue via covalent bonding, which leads to chemical damage to cells and extracellular matrix. Moreso, the physical barrier produced through monomer crosslinking also prevents the cell migration process and also restricts cell-substrate attachment.

Because the cornea is an avascular, low-cell-density tissue that relies on aqueous humor circulation to maintain metabolism, the side effects of polymeric adhesives will be exacerbated in the application of corneal tissue repair, thereby potentially resulting in issues like delayed wound healing, inflammation, neovascularization and necrosis.

As such, the researchers developed a method to construct the nanoadhesive using tetrahedral framework nucleic acids and functionalized polycationic recombinant proteins (K72). In this adhesive system, a rigid tetrahedral nucleic acid framework was incorporated as a substitute for traditional inorganic nanoparticles, thereby enhancing biocompatibility.

Additionally, this negatively charged 3D DNA supramolecular framework clears the way for the adsorption of polycationic protein K72 onto its surface, ultimately assembling into a cage-like nanostructure with a highly positively charged surface. This structure adheres efficiently to the cornea, providing an adhesive strength of 2.3 kPa — roughly an order of magnitude stronger than DNA-protein micelles lacking the tetrahedral framework.

During in vitro tests, the nanoadhesive demonstrated ideal cell compatibility. Further, no inhibition of cell activity was observed at 50 μg/mL while the assembled K72 demonstrated antibacterial performance approximately 20 times greater than free K72. Likewise, during animal studies, the nanoadhesive prevented wound infection and vascularization without causing necrosis in the transplanted corneal lenticule, subsequently enhancing the corneal repair process.