Graphene Oxide/Chitosan/Hydroxyapatite Composite Membranes Enhance Osteoblast Adhesion and Guided Bone Regeneration

Abstract
Two-dimensional materials provide a secluded space for bone formation and preserve the growth of surrounding tissues, thus playing a crucial role in guided bone regeneration (GBR). Graphene oxide (GO) has been widely employed in GBR due to its good mechanical and hydrophilic properties. A single GO membrane, however, does not provide a friendly environment for osteogenic cell adhesion. With their adjustable mechanical properties and excellent biocompatibility, composite membranes can simulate the multicomponent structure of an extracellular matrix for cell adhesion. To obtain two-dimensional membranes with appropriate mechanical strength and sufficient biocompatibility, GO-based composite membranes simultaneously containing chitosan (CS) and hydroxyapatite (HAP) were first prepared using one-step vacuum filtration and a biomimetic mineralization method. CS and HAP improved the mechanical strength and surface hydrophilicity of the membranes. In addition, moderate addition of HAP enhanced the adhesion, differentiation, and mineralization of osteoblasts. The prepared composite membranes were then implanted into a calvarial defect model to evaluate their osteogenic induction effects in vivo. Microcomputed tomography observation and histological analysis indicate that GO/CS/HAP composite membranes can accelerate bone regeneration without the contribution of endogenous cytokines. GO/CS/HAP composite membranes with unique biomimetic porous structures, superior mechanical properties, and excellent bone regeneration capacity are potential materials for application in GBR.
Funding Information
  • Natural Science Foundation of Hebei Province (B2019201333, B2019201449, B2020201020, H2019201466)
  • National Natural Science Foundation of China (21471044, 21807023, 31971304)
  • Medical Discipline Project of Hebei University (2020A03)
  • Post-graduate,s Innovation Fund Project of Hebei University (hbu2020ss012)
  • Priority Strategy Project of Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education (ts2019006, ts2020003)
  • Science and Technology Project of Hebei Education Department (ZD2020150)
  • Science Foundation for Distinguished Young Scholars of Hebei Province (B2021201045)