Fabrication and In Vivo Assessment of Oxidatively Responsive PolyHIPE Scaffolds for Use in Diabetic Orthopedic Applications.

Abstract

Achieving surgical success in orthopedic patients with metabolic disease remains a substantial challenge. Diabetic patients exhibit a unique tissue microenvironment consisting of high levels of reactive oxygen species (ROS), which promotes osteoclastic activity and leads to decreased bone healing. Alternative solutions, such as synthetic grafts, incorporating progenitor cells or growth factors, can be costly and have processing constraints. Previously, the potential for thiol-methacrylate networks to sequester ROS while possessing tunable mechanical properties and degradation rates has been demonstrated. In this study, the ability to fabricate thiol-methacrylate interconnected porous scaffolds using emulsion templating to create monoliths with an average porosity of 97.0% is reported. The average pore sizes of the scaffolds range from 27 to 656µm. The scaffolds can sequester pathologic levels of ROS via hydrogen peroxide consumption and are not impacted by sterilization. Subcutaneous implantation shows no signs of acute toxicity. Finally, in a 6-week bilateral calvarial defect model in Zucker diabetic fatty rats, ROS scaffolds increase new bone volume by 66% over sham defects. Histologic analysis identifies woven bone infiltration throughout the scaffold and neovascularization. Overall, this study suggests that porous thiol-methacrylate scaffolds may improve healing for bone grafting applications where high levels of ROS hinder bone growth.