Promising alternative: A versatile biomacromolecules-based cage-like nanoadhesive as an optimized strategy to polymer-based adhesives for corneal transplantation

A research team from the Eye & ENT Hospital of Fudan University, China, has developed a novel biocompatible nanoadhesive for corneal transplantation. The nanoadhesive is based on tetrahedral framework nucleic acids combined with functionalized polycationic recombinant proteins. This unique composition minimizes the risks of tissue necrosis and inflammation associated with polymeric adhesives while inhibiting bacterial growth and promoting tissue repair. This work demonstrates an efficient strategy to break through the bottleneck of current ophthalmic adhesives.

Developing safe and efficient tissue adhesives is urgently required in current ophthalmology practices to avoid the traumatic suturing surgery. Although a variety of polymeric adhesives have been used to repair human tissue, their application in ocular tissue adhesion, especially in corneal transplantation, is still restricted to the preclinical stage. Polymeric adhesives form connections with wound tissue through covalent bonding, leading to chemical damage to cells and extracellular matrix. Meanwhile, the generated physical barrier through monomer crosslinking also inhibit cell migration process and restrict cell-substrate attachment. As the cornea is an avascular, low-cell-density tissue that relies on aqueous humor circulation to maintain metabolism, these side effects of polymeric adhesives will be amplified in the application in corneal tissue repairing, leading to the problems such as delayed wound healing, inflammation, neovascularization, and even necrosis.

The Solution: The researchers reported a novel strategy to construct nanoadhesive by tetrahedral framework nucleic acids and functionalized polycationic recombinant proteins (K72). In the adhesive system, a rigid tetrahedral nucleic acid framework is introduced to replace traditional inorganic nanoparticles to improve biocompatibility. Moreover, this negatively charged 3D DNA supramolecular framework can guide the adsorption of polycationic protein K72 on its surface, and finally assemble into a cage-like nanostructure with a positively supercharged surface, which can be efficiently adsorbed on the cornea and provide adhesive strength of 2.3kPa, which is about one order of magnitude stronger than DNA-protein micelle without a tetrahedral framework. In vitro tests, the nanoadhesive demonstrates excellent cell compatibility. No inhibition of cell activity can be observed at 50μg/mL. The assembled K72 demonstrated antibacterial performance 20 times greater than free K72. Animal studies confirmed that the nanoadhesive effectively prevents wound infection and vascularization without causing necrosis in the transplanted corneal lenticule, enhancing the corneal repair process.

The Future: Since nanoadhesives have significantly weaker adhesive strengths than polymeric adhesives, their biological and medical applications have long been underestimated. This work demonstrates the huge potential of nanoadhesives in repairing delicate biological tissues. The nanoadhesives can circumvent the inherent problems of polymeric adhesives, such as barrier effects and chemical toxicity on delicate tissues, which pose various obstacles and risks during tissue repair and regeneration. Furthermore, the methodological exploration of nanoadhesives constructed based on pure biological macromolecules reported in the study also provides ideas for the subsequent expansion of the diversity of medical nanoadhesives.

The Impact: This work establishes a novel adhesive system constructed by purely biomacromolecules, DNA-protein hybrid nanoadhesives, for corneal transplantation. This first practice in ophthalmic surgery opens new frontier for medical applications of nanoadhesives.

The research has been recently published in the online edition of Materials Futures, a prominent international journal in the field of interdisciplinary materials science research.

Reference:
Jing Zhao, Feng Zhang, Zhe Zhang, Zhenhua Li, Yanze Yu, Bingqing Sun, Binghong Yu, Yong Ma, Xuan Ding, Liyin Wang, Lifei Zheng, Wenguo Cui, Xingtao Zhou. Supercharged Nanoadhesive through Co-assembly of Recombinant Protein and Tetrahedral DNA for Corneal Transplantation[J]. Materials Futures. DOI: 10.1088/2752-5724/adac80

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