Biomimetic bone-like composites as osteo-odonto-keratoprosthesis skirt substitutes

Abstract

Osteo-odonto-keratoprostheses, incorporating dental laminate material as an anchoring skirt around a central poly(methyl methacrylate) (PMMA) optic, have been used to replace the cornea for many years. However, there are many intricacies associated with the use of autologous dental laminate material, surgical complexity and skirt erosion. Tissue engineering approaches to bone replacement may offer suitable alternatives in osteo-odonto-keratoprosthesis (OOKP) surgery. In this study, a hydrogel polymer composite was investigated as a synthetic substitute for the OOKP skirt. A novel high strength interpenetrating network (IPN) hydrogel composite with nano-crystalline hydroxyapatite (nHAp) coated poly (lactic-co-glycolic acid) PLGA microspheres was created to mimic the alveo-dental lamina by employing agarose and poly(ethylene glycol) diacrylate (PEGDA) polymers. The incorporation of nHAp coated PLGA microspheres into the hybrid IPN network provide a micro-environment similar to that of skeletal tissues and improve cellular response. Agarose was used as a first network to encapsulate keratocytes/3T3 fibroblasts and PEGDA (6000 Da) was used as a second network with varying concentrations (20 and 40 wt %) to produce a strong and biocompatible scaffold. An increased concentration of either agarose or PEG-DA and incorporation of nHAp coated PLGA microspheres led to an increase in the elastic modulus. The IPN hydrogel combinations supported the adhesion and proliferation of both fibroblast and ocular human keratocyte cell types during in in-vitro testing. The cells endured the encapsulation process into the IPN and remained viable at 1 week post-encapsulation in the presence of nHAp coated microspheres. The material did not induce significant production of inflammatory cytokine IL-6 in comparison to a positive control ( p < 0.05) indicating non-inflammatory potential. The nHAp encapsulated composite IPN hydrogels are mechanically strong, cell supportive, non-inflammatory materials supporting their development as OOKP skirt substitutes using a new approach to dental laminate biomimicry in the OOKP skirt material.