Hierarchically Porous Hydroxyapatite Hybrid Scaffold Incorporated with Reduced Graphene Oxide for Rapid Bone Ingrowth and Repair

Abstract

Hydroxyapatite (HA), the traditional bone tissue replacement material was widely used in the clinical treatment of bone defects because of its excellent biocompatibility. However, the processing difficulty and poor osteoinductive ability greatly limit the application of HA. Although many strategies have been reported to improve the machinability and osteointegration ability, the performance including mechanical strength, porosity, cell adhesion, etc. of material still can not meet the requirements. In this work, a soft template method was developed and a porous scaffold with hierarchical pore structure, nano surface morphology, suitable porosity and pore size, and good biomechanical strength was successfully prepared. The hierarchical pore structure is beneficial for cell adhesion, fluid transfer, and cell ingrowth. Moreover, the loaded reduced graphene oxide (rGO) can improve the adhesion and promote the proliferation and spontaneous osteogenic differentiation bone marrow mesenchymal stem cells. The scaffold is then crushed, degraded and wrapped by the newly formed bone and the newly formed bone gradually replaces the scaffold. The degradation rate of the scaffold well matches the rate of the new bone formation. The hierarchical porous HA/rGO composite scaffolds can greatly accelerate the bone ingrowth in the scaffold and bone repair in critical bone defects, thus providing a clinical potential candidate for large segment bone tissue engineering.

Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

“…Thus, biomaterial scaffolds having 3D hierarchical structures with porous nanostructures are the most promising bone substitutes. 28 The defined structure, as a kind of mechanical cue, can influence cell behaviors and control some of their key features at the molecular and cellular levels. 7,12 When fabricating bone substitute scaffolds, we need to consider the impact of physical cues such as internal porosity, 7 pore structure, surface roughness, compressive moduli, 29 and the alignment of ECM and bone cells.…”

“…110 Usually, scaffolds must be post-processed after their initial fabrication to develop a porous structure. Lyophilization, 1 sintering, 28 gas foaming, 111 and phase separation 109 are commonly used techniques for pore formation. Pore parameters such as size, porosity, 7 and interconnectivity 109 crucially influence cell behaviors.…”

“…113 In the same way, Zhou et al successfully fabricated a hierarchical interconnected pore structure with suitable porosity and pore size that enabled stem cells to proliferate and differentiate more actively, and to rapidly grow into the scaffold during the osteogenesis. 28 Besides, the pore structure and size could affect cell shape and spreading of macrophages, modulate autophagy activation, subsequently suppress inflammatory and promote osteogenesis. 116…”

Graphenic Materials for Biomedical Applications

“…The addition of rGO promotes adhesion and proliferation, as well as the spontaneous osteogenic differentiation of mesenchymal stem cells derived from bone marrow. Therefore, this porous hydroxyapatite/rGO composite scaffold is capable of promoting bone growth in scaffolding and repairing severe bone defects [86].…”

Facile optimization of hierarchical topography and chemistry on magnetically active graphene oxide nanosheets

“…Optimization of necessary topography and chemistry in two dimensional (2D) graphene oxide (GO) nanosheets remains instrumental for achieving diverse and important properties in synthesized materials having impactful signicance in practical settings. [1][2][3][4][5] Inspired by these diverse and rational uses of GO-nanosheets, here, a facile and robust chemical approach has been unprecedentedly introduced for optimizing both the hierarchical topography and desired chemistry in the available space (in the order of mm) of 2D GO nanosheets. Interestingly, the co-optimization of appropriate hierarchical topography and low surface energy chemistry on macro-scale (porous/featureless) objects (that are visible with the naked eye) is imperative for achieving bioinspired extreme liquid wettability.…”