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Spatial Distribution of Biomaterial Microenvironment pH and Its Modulatory Effect on Osteoclasts at the Early Stage of Bone Defect Regeneration
- Liu, Wenlong, Dan, Xiuli, Lu, William W., Zhao, Xiaoli, Ruan, Changshun, Wang, Ting, Cui, Xu, Zhai, Xinyun, Ma, Yufei, Wang, Deping, Huang, Wenhai, Pan, Haobo
- ACS applied materials & interfaces 2019 v.11 no.9 pp. 9557-9572
- animal models, biocompatible materials, biodegradability, bones, mice, osteoclasts, pH, protons
- 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 μm, which is broader than the generally accepted value, 300 μm. 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.