Preparation and Evaluation of Bacterial Nanocellulose/Hyaluronic Acid Composite Artificial Cornea for Application of Corneal Transplantation

The treatment for corneal damage requires donor corneal transplantation, but there is a serious scarcity of donor corneas worldwide. In this study, we aimed to design a new artificial cornea with good cytocompatibility, excellent optical properties and suture resistance, and great moisturizing properties. A new bacterial nanocellulose (BNC) membrane with anisotropic mechanical properties and high light transmission was produced in a horizontal rotary drum reactor. However, as a potential material for artificial keratoplasty, the transparency and mechanical properties of the new BNC membrane were not satisfactory. Thus, hyaluronic acid (HA) was introduced in the BNC to synthesize the BNC/HA composite membrane by using 1,4-butanediol diglycidyl ether (BDDE) as the chemical cross-linking agent. The micro-morphology, light transmittance, mechanical properties, water content, moisture retention ability, and cytocompatibility of the composite membranes were further evaluated. HA was fixed in the BNC network by the ether bond, and the composite membrane was found to have excellent light transmittance (up to 95.96%). The composite membrane showed excellent mechanical properties, for instance, its tensile strength exceeded the human normal intraocular pressure (IOP) (1.33-2.80 kPa), the maximum burst pressure was about 130 kPa, 46-97 times that of the normal IOP, and its suture force was close to that of the human amniotic membrane (0.1 N). Based on the three-dimensional network scaffold of BNC and the high water absorption characteristics of HA, the artificial cornea had high water content and high moisture retention ability. The rabbit corneal stromal cells cultured in vitro showed that the artificial cornea substitute had excellent cytocompatibility. BDDE is the most frequently used cross-linker in most HA products in the current cosmetic medicine industry owing to its long-term safety records for over 15 years. Therefore, the BNC/HA composite hydrogel cross-linked with BDDE has great potential in artificial keratoplasty or ocular surface repair.