Spatial Distribution of Biomaterial Microenvironment pH and Its Modulatory Effect on Osteoclasts at the Early Stage of Bone Defect Regeneration
Spatial Distribution of Biomaterial Microenvironment pH and Its Modulatory Effect on Osteoclasts at the Early Stage of Bone Defect Regeneration
复制标题
骨缺损再生早期生物材料微环境pH的空间分布及其对破骨细胞的调节作用
DOI：
10.1021/acsami.8b20580
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发表时间：
2019-03-06
影响因子：
9.5
通讯作者：
Pan, Haobo
中科院分区：
文献类型：
--
作者：
Liu, Wenlong;Dan, Xiuli;Pan, Haobo
人们普遍认为，生物可降解材料极大地影响了细胞所在的附近微环境;然而，由于技术瓶颈，很少讨论界面性质的范围。本研究的目的是描绘生物材料的微环境边界相关联的界面H+分布与周围的细胞行为。使用废用相关的骨质疏松小鼠模型，我们证实，异常激活的破骨细胞可以抑制在相对碱性条件下。破骨细胞的分化和磷灰石再吸收能力被“关闭”时，培养在滴定的材料提取物的pH值高于7.8。为了产生一个本地化的碱性微环境，制造了一系列的硼硅酸盐和他们的界面H+分布监测时空采用非侵入性的微测试技术。通过将界面H+分布与破骨细胞“开关”行为相关联，发现测试材料的微环境边界为400 +/- 50 μ m，这比普遍接受的值300 μ m更宽。此外，植入具有较高界面pH值和较宽有效范围的材料的骨质疏松小鼠具有较低的破骨细胞活性和较厚的新骨。综上所述，可降解生物材料的有效质子微环境边界被描绘，并且弱碱性微环境被证明可能通过抑制异常活化的破骨细胞来促进骨质疏松骨的再生。
It is generally accepted that biodegradable materials greatly influence the nearby microenvironment where cells reside; however, the range of interfacial properties has seldom been discussed due to technical bottlenecks. This study aims to depict biomaterial microenvironment boundaries by correlating interfacial H+ distribution with surrounding cell behaviors. Using a disuse-related osteoporotic mouse model, we confirmed that the abnormal activated osteoclasts could be suppressed under relatively alkaline conditions. The differentiation and apatite-resorption capability of osteoclasts were "switched off" when cultured in titrated material extracts with pH values higher than 7.8. To generate a localized alkaline microenvironment, a series of borosilicates were fabricated and their interfacial H+ distributions were monitored spatiotemporally by employing noninvasive microtest technology. By correlating interfacial H+ distribution with osteoclast "switch on/off" behavior, the microenvironment boundary of the tested material was found to be 400 +/- 50 mu m, which is broader than the generally accepted value, 300 mu m. Furthermore, osteoporotic mice implanted with materials with higher interfacial pH values and boarder effective ranges had lower osteoclast activities and a thicker new bone. To conclude, effective proton microenvironment boundaries of degradable biomaterials were depicted and a weak alkaline microenvironment was shown to promote regeneration of osteoporotic bones possibly by suppressing abnormal activated osteoclasts.