Fabrication And Functional Characterization Of A Tough Sphere-templated Hydrogel Scaffold For The Skirt Of Artificial Cornea

Purpose:To developed a tough, intelligent scaffold based on poly (acrylic acid) and poly (N-isopropyl acrylamide) with controllable, uniform, and interconnected porous structure as the skirt of artificial cornea.Methods:The poly (acrylic acid)(PAAc)/poly (N-isopropyl acrylamide)(PNIAPM) double network hydrogels was synthetized using double network polymerization techniques by the synthesis of the second network (PNIPAM) within the first network (PAAc) rigid skeleton. And then the PAAc/PNIPAM-based scaffold was fabricated using the sphere-templating scaffold fabrication techniques by the UV polymerization of the PAAc/PNIPAM double network hydrogel after infiltating through a PMMA microspheres template. The morphology of the PAAc/PNIPAM-based scaffold was analysised using the scanning electron microscopy. The mechanical properties of the PAAc/PNIPAM hydrogels and their porous scaffolds were characterized by fracture stress and strain, Young’s modulus and toughness got from a tensile stress-strain measurements using an Instron materials testing system at37℃in water. The dual temperature/pH sensitivities were explored by swelling studies in functions of temperature and pH of swelling medium. The biocompatibility of the PAAc/PNIPAM-based scaffold was evaluated using indirect cytotoxicity, endotoxicity, and cytocompatibility tests on NIH-3T3cells respectively. And the capability of biointegration of the PAAc/PNIPAM-based scaffold was demonstrated by being implanted subconjunctivally on a rabbit model.Results:In the study, a tough, intelligent precision porous hydrogel scaffold with good biocompatibility and the capability to encourage cellular integration, was developed by combining sphere-templating scaffold fabrication and double network polymerization techniques. A mechanical assessment showed the toughness of the hydrogel and scaffold to be up to～1.4x107Jm-3and～1.5×106Jm-3respectively, as compared with104-105Jm-3for most synthetic hydrogels and meet the requirements of some human tissues such as cornea, skin, blood vessel and tendon. The swelling study demonstrated the scaffold possessing both thermosensitivity and pH-sensitivity properties. In vitro cell testing demonstrated the scaffold matrices provided a biocompatible surface area promoting NIH-3T3cell adhesion, proliferation and infiltration. An in vivo rabbit study showed the scaffolds promoting strong cellular integration by allowing cells to migrate into the porous structure from the surrounding tissues.Conclusions:In addition to enhanced mechanical properties and dual temperature/pH sensitivities, the sphere-templated PAAc/PNIPAM-based hydrogel scaffold showed good biocompatibility and strong cellular integration capability making it potentially valuable as the skirt of the artficial cornea.