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    形状回复力对抑制破骨细胞形成的调控作用

    Inhibitory Modulation of Osteoclastogenesis by the Shape Recovery Forces

    • 摘要: 破骨细胞是骨吸收的主要功能细胞,具有力学敏感性。本研究旨在利用形状记忆聚合物(SMPs)的形状回复力原位调控破骨细胞的形成。首先将纯聚乳酸(PLA)、不同质量比(7∶3、5∶5、3∶7)的PLA和聚己内酯(PCL)通过热致相分离法(TIPS)制备PLA/PCL 3D支架,并表征其形貌、结构、热性能;然后,将筛选的PLA/PCL(5∶5)支架在45 ℃下压缩塑形(压缩比分别为0、50%、75%)和4 ℃下冷却固定,并表征形状记忆性能;最后,通过基于RAW264.7巨噬细胞的破骨分化实验验证了形状回复力对抑制破骨细胞形成的调控作用。结果表明:PLA/PCL(5∶5)材料体系的形状回复温度接近人体体温,适合制备3D支架;形状回复力与塑形应变相关,压缩比75%组的支架产生的形状回复力为50%组的1.7倍;形状回复力可抑制巨噬细胞的融合分化及相关功能表达,对破骨细胞形成的抑制作用与回复力大小有关。

       

      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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