Performance of collagen-based corneal implant with anti-infective capability in rabbit model of infectious keratitis

Event Abstract Back to Event Performance of collagen-based corneal implant with anti-infective capability in rabbit model of infectious keratitis Andri Riau1, 2*, Debasish Mondal2*, Thet Tun Aung3*, Roger W. Beuerman3*, Bo Liedberg1, 4*, Subbu S. Venkatraman1* and Jodhbir S. Mehta1, 2, 5, 6* 1 Nanyang Technological University, School of Materials Science and Engineering, Singapore 2 Singapore Eye Research Institute, Tissue Engineering and Stem Cell Group, Singapore 3 Singapore Eye Research Institute, Anti-infective Research Group, Singapore 4 Nanyang Technological University, Center for Biomimetic Sensor Science, Singapore 5 Singapore National Eye Center, Singapore 6 Duke-NUS Graduate Medical School, Singapore Introduction: Bacterial infection after implantation of a corneal implant is a serious complication and an economic burden. Conventional antibiotic prophylaxis, such as topical vancomycin application, is limited by low bioavailability, high dosing requirement and poor patient compliance[1],[2]. An ideal solution to overcome these issues is an antibiotic-eluting implant that sustains the local antibiotic delivery. In this study, we incorporated vancomycin in collagen hydrogel (VH) to create an artificial cornea with anti-infective capability. Materials and methods: Vancomycin was loaded in 15%(w/v) bovine collagen type I collagen hydrogels with 0.2 mm thickness and 5 mm diameter. Release profile of the VH and minimum inhibitory concentration (MIC) of the drug released in the PBS medium against Staphylococcus aureus on day 1, 3, 5, 7 and 10 were first assessed. Clear medium in wells indicated complete inhibition of vancomycin against S. aureus at respective drug concentration. The VH was then implanted intrastromally following femtosecond laser-assisted small incision lenticule extraction in rabbits. In vivo biocompatibility of the implants was followed up to 1 month post-implantation using an in vivo confocal microscope (n=3). In a separate group of rabbits (n=3), 50 μl of 108 CFU/ml S. aureus inoculate was injected intrastromally on day 2 post-implantation and the performance of the implants was followed up for 3 further days. Blank hydrogel (BH) was implanted in contralateral eyes for comparison. Follow-up observations were performed by slit lamp photography and optical coherence tomography. After the rabbits were sacrificed and corneas were dissected, bacterial quantification and immunohistochemistry of inflammatory markers, CD18, were carried out. Results and discussion: In vitro, the drug could be released for up to 7 days with concentrations better than theoretical MIC of vancomycin against S. aureus (2 μg/ml) (Figure 1A and B)[3], except the day 7 eluent, which had a reduced MIC (4 μg/ml) (Figure 1C). The VH was biocompatible, showing no significant difference (p>0.05) in epithelial, keratocyte, and endothelial cell morphology (Figure 2A) and density (Figure 2B) compared to non-operated corneas after 1 month post-implantation. On day 3 post-infection (5 days post-implantation), the VH-implanted corneas appeared clear and non-edematous compared to the BH-implanted corneas, which were hazy, edematous, and had excessive inflammation (Figure 3A and B). The post-infected corneas were significantly thicker in corneas with BH (713±73 μm) than those with VH (537±56 μm) (p=0.029). Immunohistochemistry further demonstrated a significant reduction in CD18-positive cells in VH-implanted corneas (49±9 cells/unit area) compared to BH-implanted corneas (523±15 cells/unit area) (p<0.001). In addition, there was a log 2.5 reduction in S. aureus in corneas implanted with VH compared to those implanted with BH (p=0.016). Summary: This study demonstrated the efficacy of localized vancomycin delivery from a collagen-based corneal implant in preventing implantable device-associated S. aureus infections in vivo. This study was supported by Singapore National Medical Research Council funded Translational and Clinical Research (TCR) Flagship Programme (NMRC/TCR/008-SERI/2013).References:[1] Sasaki H, Ichikawa M, Yamamura K, Nishida K, Nakamura J. Ocular membrane permeability of hydrophilic drugs for ocular peptide delivery. J Pharm Pharmacol 1997;49:135-9.[2] Chew HF, Ayres BD, Hammersmith KM, Rapuano CJ, Laibson PR, Myers JS, Jin YP, Cohen EJ. Boston keratoprosthesis outcomes and complications. Cornea 2009;28:989-96.[3] Tenover FC, Moellering RC Jr. The rationale for revising the Clinical and Laboratory Standards Institute vancomycin minimal inhibitory concentration interpretive criteria for Staphylococcus aureus. Clin Infect Dis 2007;44:1208-15. Keywords: in vivo, Drug delivery, Implant, Biocompatibility Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: General Session Oral Topic: Biomaterials for therapeutic delivery Citation: Riau A, Mondal D, Aung T, Beuerman RW, Liedberg B, Venkatraman SS and Mehta JS (2016). Performance of collagen-based corneal implant with anti-infective capability in rabbit model of infectious keratitis. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01668 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. 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Received: 27 Mar 2016; Published Online: 30 Mar 2016. * Correspondence: Dr. Andri Riau, Nanyang Technological University, School of Materials Science and Engineering, Singapore, Singapore, Email1 Dr. Debasish Mondal, Singapore Eye Research Institute, Tissue Engineering and Stem Cell Group, Singapore, Singapore, debasishmondal.ntu@gmail.com Dr. Thet Tun Aung, Singapore Eye Research Institute, Anti-infective Research Group, Singapore, Singapore, thet.tun.aung@seri.com.sg Dr. Roger W Beuerman, Singapore Eye Research Institute, Anti-infective Research Group, Singapore, Singapore, rwbeuerman@gmail.com Dr. Bo Liedberg, Nanyang Technological University, School of Materials Science and Engineering, Singapore, Singapore, bliedberg@ntu.edu.sg Dr. Subbu S Venkatraman, Nanyang Technological University, School of Materials Science and Engineering, Singapore, Singapore, subbu@Nus.edu.sg Dr. Jodhbir S Mehta, Nanyang Technological University, School of Materials Science and Engineering, Singapore, Singapore, jodmehta@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Andri Riau Debasish Mondal Thet Tun Aung Roger W Beuerman Bo Liedberg Subbu S Venkatraman Jodhbir S Mehta Google Andri Riau Debasish Mondal Thet Tun Aung Roger W Beuerman Bo Liedberg Subbu S Venkatraman Jodhbir S Mehta Google Scholar Andri Riau Debasish Mondal Thet Tun Aung Roger W Beuerman Bo Liedberg Subbu S Venkatraman Jodhbir S Mehta PubMed Andri Riau Debasish Mondal Thet Tun Aung Roger W Beuerman Bo Liedberg Subbu S Venkatraman Jodhbir S Mehta Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.