Spatial Distribution of Biomaterial Microenvironment pH and Its Modulatory Effect on Osteoclasts at the Early Stage of Bone Defect Regeneration

Wenlong Liu, Xiuli Dan, William W. Lu, Xiaoli Zhao, Changshun Ruan, Ting Wang, Xu Cui, Xinyun Zhai, Yufei Ma, Deping Wang, Wenhai Huang, Haobo Pan

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)9557-9572
Number of pages16
JournalACS Applied Materials and Interfaces
Issue number9
StatePublished - Mar 6 2019
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (Nos 81672227, 31870956); the Strategic Priority Research Program A of the Chinese Academy of Sciences (XDA16021000); the Highlight Research of Frontier Science, the Chinese Academy of Sciences (No. QYZDB-SSW-JSC030); the Shenzhen Science and Technology Research Funding (Nos JCYJ20170413162104773, CXZZ20150401152251209, JSGG20151030140325149, JSGG20150331154931068, and CXZZ20140417113430716); the Youth Innovation Promotion Association of the CAS; Shenzhen Peacock Program (No. 110811003586331); and partially from the Hong Kong General Research Fund.

Publisher Copyright:
© 2019 American Chemical Society.


  • biodegradable material
  • bone regeneration
  • interfacial pH
  • microenvironment boundary
  • osteoclast


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