Development of an <i> in-situ</i> Printing System with Human Platelet Lysate Based Bioink to Treat Corneal Perforation

Abstract

Purpose: Corneal perforation is a clinical emergency. Tissue glue to seal the perforation, and supplementary topical medication represents existing standard treatment. Previously, our group developed a transparent bioink that showed good cell compatibility and accelerated corneal epithelial cells healing in-vitro. This study aims to develop a novel treatment method for corneal perforation using this bioink. Methods: Rheometry was used to measure bioink behaviour at room and corneal surface temperatures. Bioink adhesiveness to porcine skin and burst pressure limit were also measured. Based on rheological behaviour, a hand-held biopen was developed to extrude the bioink onto the cornea. An animal trial (5 New Zealand white rabbits) to compare bioink and cyanoacrylate glue (control group) impact on a 2mm perforation was conducted to evaluate safety and efficacy. Results: Bioink has higher adhesiveness compared to commercial fibrin glue and can withstand burst pressure approximately 6.4x higher than routine intraocular pressure. Bioink-treated rabbits had lower pain score and faster recovery, despite generating similar scar-forming structure after healing compared to controls. No secondary corneal ulcer was generated in rabbits treated with bioink. Conclusions: This study reports a novel in-situ printing system capable of delivering a transparent bioink to the cornea and successfully treating small corneal perforations. Bioink-treated rabbits recovered faster to completely healed perforation and required no additional analgesia. Both groups showed scarred corneal tissue after healing, however no infection and inflammation was observed 3 weeks. The delivery system was easy to use and may represent an alternative treatment for corneal perforation. Funding Information: We acknowledge the funding support from Australian Research Council (ARC) Centre of Excellence Scheme (CE140100012), Sydney Eye Hospital Foundation and NSW Medical Device Fund. The hPL used within the study was a gift from Australia Red Cross. Declaration of Interests: J. You (P), iFix Medical (I,F); H. Frazer (P); S. Sayyar, None; Z. Chen, None; X. Liu, None; A. Taylor, None; B. Filippi, None; S. Beirne, None; I. Wise, None; C. Hodge, None; G. Wallace, None; G. Sutton (P), iFix Medical (I). Ethics Approval Statement: Human corneas not meeting transplantation quality requirements were obtained from New South Wales Organ & Tissue Donation Service (Human Research Ethics Committee approval 14/275). The trial was conducted at the University of Sydney Charles Perkins Centre Laboratory Animal House Facility with Animal Ethics Committee approval (AEC: 2018/1317).