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.

Artificial Cornea: Past, Current, and Future Directions

“…They also added poly(ethylene glycol) diacrylate (PEGDA) polymers and agarose to improve the mechanical strength of the hydrogels. This study suggested the PEGDA-agarose based IPN can be used in the future to replace the OOKP lamina ( 89 ).…”

“…To decrease laminar resorption, and simplify the surgical procedure, decrease costs, and avoid oral trauma, skirts made of synthetic materials similar to the osteo-odonto-acrylic lamina have been introduced. Avadhanam et al incorporated nano-crystalline hydroxyapatite (nHAp) coated poly (lactic-co-glycolic acid) PLGA microspheres with a high strength interpenetrating network (IPN) hydrogel to mimic the odonto-acrylic lamina microenvironment ( 89 ). They also added poly(ethylene glycol) diacrylate (PEGDA) polymers and agarose to improve the mechanical strength of the hydrogels.…”

Dexamethasone release pattern via a three-dimensional system for effective bone regeneration

“…Utilizing a mineralized microenvironment is another strategy that needs further research since the osteoblastic cells could recognize hydroxyapatite as their own substance which helps in increasing cell attachment, proliferation, and differentiation [75,76]. Hydroxyapatite would stimulate the cells to adhere [76], while the modified hydrogels would have an enhanced loading efficiency for DEX.…”

A comprehensive review on the COVID-19 vaccine and drug delivery applications of interpenetrating polymer networks

“…Other than drug delivery, the scientific community has also reported widespread applications of interpenetrating polymer networks as wound dressing formulations [ 4 – 6 ], for tissue engineering to design artificial scaffolds [ 7 , 8 ] and injectable supports [ 9 ] and bone graft substitutes [ 10 ], etc. Incorporating natural and/or biopolymers even of synthetic origin is believed to offer a sustainable approach to IPN synthesis owing to the low toxicity profiles of such polymer subunits.…”

“…[ 3 ]. Irradiation with high-energy gamma ( gamma ) and beta ( beta ) rays is recommended for polymer networks because it increases the mechanical stability of the polymers [ 10 ].…”