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

ACS Appl Mater Interfaces. 2019 Mar 6;11(9):9557-9572. doi: 10.1021/acsami.8b20580. Epub 2019 Feb 19.

Abstract

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.

Keywords: biodegradable material; bone regeneration; interfacial pH; microenvironment boundary; osteoclast.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / pharmacology
  • Bone Diseases / metabolism
  • Bone Diseases / pathology
  • Bone Regeneration* / drug effects
  • Cell Differentiation / drug effects
  • Culture Media / chemistry*
  • Disease Models, Animal
  • Durapatite / chemistry
  • Female
  • Hydrogen-Ion Concentration
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Osteoclasts / cytology
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Biocompatible Materials
  • Culture Media
  • Durapatite
  • Matrix Metalloproteinase 9