Physical stimulations such as magnetic, electric and mechanical stimulation could enhance cell activity and promote bone formation in bone repair process via activating signal pathways, modulating ion channels, regulating bone-related gene expressions, etc. In this paper, bioeffects of physical stimulations on cell activity, tissue growth and bone healing were systematically summarized, which especially focused on their osteogenesis-inducing mechanisms. Detailedly, magnetic stimulation could produce Hall effect which improved the permeability of cell membrane and promoted the migration of ions, especially accelerating the extracellular calcium ions to pass through cell membrane. Electric stimulation could induce inverse piezoelectric effect which generated electric signals, accordingly up-regulating intracellular calcium levels and growth factor synthesis. And mechanical stimulation could produce mechanical signals which were converted into corresponding biochemical signals, thus activating various signaling pathways on cell membrane and inducing a series of gene expressions. Besides, the equipments of physical stimulation system were discussed. The opportunities and challenges of physical stimulations were also presented from the perspective of bone repair.

A custom-designed three-dimensional additive manufacturing device was developed to fabricate scaffolds for intervertebral disk (IVD) regeneration. This technique integrated a computer with a device capable of 3D movement allowing for precise motion and control over the polymer scaffold resolution. IVD scaffold structures were designed using computer-aided design to resemble the natural IVD structure. Degradable polyurethane (PU) was used as an elastic scaffold construct to mimic the elastic nature of the native IVD tissue and was deposited at a controlled rate using ultra-fine micropipettes connected to a syringe pump. The elastic PU was extruded directly onto a collecting substrate placed on a freezing stage. The three-dimensional movement of the computer-controlled device combined with the freezing stage enabled precise control of polymer deposition using extrusion. The addition of the freezing stage increased the polymer solution viscosity and hardened the polymer solution as it was extruded out of the micropipette tip. This technique created scaffolds with excellent control over macro- and micro-structure to influence cell behavior, specifically for cell adhesion, proliferation, and alignment. Concentric lamellae were printed at a high resolution to mimic the native shape and structure of the IVD. Seeded cells aligned along the concentric lamellae and acquired cell morphology similar to native tissue in the outer portion of the IVD. The fabricated scaffolds exhibited elastic behavior during compressive and shear testing, proving that the scaffolds could support loads with proper fatigue resistance without permanent deformation. Additionally, the mechanical properties of the scaffolds were comparable to those of native IVD tissue.

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