Inhibitory Modulation of Osteoclastogenesis by the Shape Recovery Forces
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Graphical Abstract
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Abstract
In bone, osteoclasts are the primary type of cells responsible for bone resorption. Osteoclasts are mechanosensitive. This paper proposed to apply the shape recovery stress, generated from shape recovery polymers (SMPs), for the in situ modulation of osteoclastogenesis. Three-dimensional PLA/PCL constructs with different mass ratios of poly(lactic acid) (PLA) and polycaprolactone (PCL) at 7∶3, 5∶5, 3∶7 and pure PLA were firstly prepared by thermally induced phase separation (TIPS). The morphology, composition and thermal properties of these constructs were characterized. Then, the selected PLA/PCL (5:5) construct was shape programmed by hot-pressing to the deformation ratios of 0, 50% and 75% at 45 ℃ and shape-fixed at the cooling temperature of 4 ℃, and their shape memory properties were characterized. Finally, the in vitro proof-of-concept experiment was carried out to examine the effect of shape recovery stress on the inhibition of osteoclastogenesis in RAW264.7 macrophages. The shape recovery temperature of the PLA/PCL (5∶5) formulation was found to be close to the human body temperature, thus rendering it a suitable candidate for the fabrication of 3D scaffolds. The shape recovery stress was associated to the shape programming strain. The shape recovery stress generated by the 75% group was 1.7 times that of the 50% group. The in situ applied shape recovery stress effectively inhibited the fusion of macrophages and osteoclastogenesis by suppressing the cells to express relevant markers, and its inhibitory effect on formation of osteoclasts was related to the magnitude of the shape recovery forces applied.
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