BMP2-Mediated Silica Deposition: An Effective Strategy for Bone Mineralization

ACS Biomater Sci Eng. 2023 Apr 10;9(4):1823-1833. doi: 10.1021/acsbiomaterials.1c01095. Epub 2022 Jan 28.

Abstract

The combined use of an osteogenic factor, such as bone morphogenetic protein 2 (BMP2), with a bone scaffold was quite functional for the reconstruction of bone defects. Although many studies using BMP2 have been done, there is still a need to develop an efficient way to apply BMP2 in the bone scaffold. Here, we reported an interesting fact that BMP2 has a silica deposition ability in the presence of silicic acid and proposed that such an ability of BMP2 can effectively immobilize and transport itself by a kind of coprecipitation of BMP2 with a silica matrix. The presence of BMP2 in the resulting silica was proved by SEM and EDS and was visualized by FITC-labeled BMP2. The delivery efficacy of BMP2 of silica-entrapped BMP2 on osteoblast differentiation and mineralization using MC3T3 E1 preosteoblast cells was evaluated in vitro. The coprecipitated BMP2 with silica exhibited osteogenesis at a low concentration that was insufficient to give an osteoinductive signal as the free form. Expectedly, the silica-entrapped BMP2 exhibited thermal stability over free BMP2. When applied to bone graft substitution, e.g., hydroxyapatite granules (HA), silica-entrapped BMP 2 laden HA (BMP2@Si/HA) showed sustained BMP2 release, whereas free BMP2 adsorbed HA by a simple dipping method (BMP2/HA) displayed a burst release of BMP2 at an initial time. In the rat critical-size calvarial defect model, BMP2@Si/HA showed better bone regeneration than BMP2/HA by about 10%. The BMP2/silica hybrid deposited on a carrier surface via BMP2-mediated silica precipitation demonstrated an increase in the loading efficiency, a decrease in the burst release of BMP2, and an increase in bone regeneration. Taken together, the coprecipitated BMP2 with a silica matrix has the advantages of not only being able to immobilize BMP2 efficiently without compromising its function but also serving as a stable carrier for BMP2 delivery.

Keywords: BMP2; bioinspired silicification; bone regeneration; bone scaffold; silica hybrid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Morphogenetic Protein 2 / pharmacology
  • Calcification, Physiologic*
  • Osteogenesis
  • Rats
  • Silicon Dioxide / pharmacology
  • Tissue Scaffolds*

Substances

  • Bone Morphogenetic Protein 2
  • Silicon Dioxide