Three-dimensional (3D), macroporous, elastic, and biodegradable nanocomposite scaffold for in situ bone regeneration: Toward structural, biophysical, and biochemical cues integration

Although bone tissue with remarkable healing capabilities, the rapid and successful bone regeneration continues to present a challenge because that the influence factors for bone healing are multifaceted, especially for massive bone defects. From a cell/material interactions point of view, integrating multiple cues into one biomaterial is considered as a promising approach in the clinical treatment of bone defects thanks to the provided multiple stimuli. Herein, 3D macroporously elastic biodegradable nanocomposite bone scaffolds (PCSG) were successfully developed based on poly(citrate-siloxane) (PCS) hybrid elastomer and reduced graphene oxide (rGO). The PCSG scaffolds combine with structure (3D, largely open and interconnected pore architecture, high porosity), biophysics (high mechanical properties, roughness surface, piezoelectricity property), and biochemistry cues (silica cross-linked network, Si ions release). Experiments demonstrate that the structurally, biophysically, and biochemically biomimetic properties of PCSG scaffolds are beneficial for triggering cell adhesion, proliferation, matrix mineralization, osteogenic differentiation of osteoblasts (MC3T3-E1) in vitro and significantly promoting in situ bone regeneration in a calvarial bone defect model. The effective and simple strategy of multiple cues integration could pave a universally applicable way in development of bone tissue engineering biomaterials with good osteoinductivity and osteoconductivity for large defects repair, and the reported PCSG scaffolds demonstrate the potential clinic application in fields of bone regeneration and 3D culture of cells.