School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore; Center for Cellular & Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, USA.
Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore.
Acta Biomater. 2019 Aug;94:585-596. doi: 10.1016/j.actbio.2019.05.053. Epub 2019 May 24.
An artificial cornea or keratoprosthesis requires high mechanical strength, good biocompatibility, and sufficient wear and corrosion resistance to withstand the hostile environment. We report a reduced graphene oxide-reinforced titania-based composite for this application. Graphene oxide nanoparticles (GO) and liquid crystalline graphene oxide (LCGO) were the graphene precursors and mixed with titanium dioxide (TiO) powder. The composites reinforced with reduced GO or LCGO were produced through spark plasma sintering (SPS). The mechanical properties (Young's modulus and hardness), wear behaviour and corrosion resistance were studied using nanoindentation, anoidic polarization, long-term corrosion assay in artificial tear fluid and tribology assay in corroboration with atomic force microscopy and scanning electron microscopy. Biocompatibility was assessed by human corneal stromal cell attachment, survival and proliferation, and DNA damages. Sintered composites were implanted into rabbit corneas to assess for in vivo stability and host tissue responses. We showed that reduced graphene/TiO hybrids were safe and biocompatible. In particular, the 1% reduced LCGO/TiO (1rLCGO/TiO) composite was mechanically strong, chemically stable, and showed better wear and corrosion resistance than pure titania and other combinations of graphene-reinforced titania. Hence the 1rLCGO/ TiO bioceramics can be a potential skirt biomaterial for keratoprosthesis to treat end-stage corneal blindness. STATEMENT OF SIGNIFICANCE: The osteo-odonto-keratoprosthesis (OOKP) is an artificial cornea procedure used to restore vision in end-stage corneal diseases, however it is contraindicated in young subjects, patients with advanced imflammatory diseases and posterior segment complications. Hence, there is a need of an improved keratoprosthesisskirt material with high mechanical and chemical stability, wear resistance and tissue integration ability. Our study characterized a reduced graphene oxide-reinforced titania-based biomaterial, which demonstrated strong mechanical strength, wear and corrosion resistance, and was safe and biocompatible to human corneal stromal cells. In vivo implantation to rabbit corneas did not cause any immune and inflammation outcomes. In conclusion, this invention is a potential keratoprosthesis skirt biomaterial to withstand the hostile environment in treating end-stage corneal blindness.
一种人工角膜或角膜假体需要具有高机械强度、良好的生物相容性和足够的耐磨性和耐腐蚀性，以承受恶劣的环境。我们报告了一种用于此应用的还原氧化石墨烯增强的基于二氧化钛的复合材料。氧化石墨烯纳米粒子（GO）和液晶氧化石墨烯（LCGO）是石墨烯前体，并与二氧化钛（TiO）粉末混合。通过火花等离子体烧结（SPS）生产了用还原氧化石墨烯或 LCGO 增强的复合材料。使用纳米压痕、阳极极化、在人工泪液中的长期腐蚀试验和原子力显微镜和扫描电子显微镜协同作用下的摩擦学试验研究了机械性能（杨氏模量和硬度）、耐磨性和耐腐蚀性。通过人角膜基质细胞附着、存活和增殖以及 DNA 损伤评估了生物相容性。将烧结复合材料植入兔角膜中以评估体内稳定性和宿主组织反应。我们表明，还原氧化石墨烯/TiO 杂化物是安全且生物相容的。特别是，1%还原的 LCGO/TiO（1rLCGO/TiO）复合材料具有机械强度高、化学稳定性好，并且在耐磨性和耐腐蚀性方面优于纯二氧化钛和其他氧化石墨烯增强的二氧化钛复合材料。因此，1rLCGO/TiO 生物陶瓷可以作为治疗终末期角膜盲的角膜假体的潜在生物材料。
骨牙角膜假体（OOKP）是一种用于治疗终末期角膜疾病的人工角膜手术，但它不适合年轻患者、患有晚期炎症性疾病和后节并发症的患者。因此，需要一种具有高机械和化学稳定性、耐磨性和组织整合能力的改良的角膜假体裙边材料。我们的研究描述了一种还原氧化石墨烯增强的基于二氧化钛的生物材料，该材料具有很强的机械强度、耐磨性和耐腐蚀性，对人角膜基质细胞安全且生物相容。将其植入兔角膜后不会引起任何免疫和炎症反应。总之，本发明是一种潜在的角膜假体裙边生物材料，可用于治疗终末期角膜盲，以承受恶劣的环境。
