Hydroxyapatite microbeads containing BMP-2 and quercetin fabricated via electrostatic spraying to encourage bone regeneration

Biomed Eng Online. 2023 Feb 18;22(1):15. doi: 10.1186/s12938-023-01078-y.

Abstract

Background: Hydroxyapatite (HAp) possesses osteoconductive properties, and its granular form can serve as an effective drug delivery vehicle for bone regeneration. Quercetin (Qct), a plant-derived bioflavonoid, is known to promote bone regeneration; however, its comparative and synergistic effects with the commonly used bone morphogenetic protein-2 (BMP-2) have not been investigated.

Methods: We examined the characteristics of newly formed HAp microbeads using an electrostatic spraying method and analyzed the in vitro release pattern and osteogenic potential of ceramic granules containing Qct, BMP-2, and both. In addition, HAp microbeads were transplanted into a rat critical-sized calvarial defect and the osteogenic capacity was assessed in vivo.

Results: The manufactured beads had a microscale size of less than 200 μm, a narrow size distribution, and a rough surface. The alkaline phosphatase (ALP) activity of osteoblast-like cells cultured with the BMP-2-and-Qct-loaded HAp was significantly higher than that of either Qct- or BMP-2-loaded HAp groups. The mRNA levels of osteogenic marker genes such as ALP and runt-related transcription factor 2 were found to be upregulated in the HAp/BMP-2/Qct group compared to the other groups. In micro-computed tomographic analysis, the amount of newly formed bone and bone surface area within the defect was significantly higher in the HAp/BMP-2/Qct group, followed by the HAp/BMP-2 and HAp/Qct groups, which is consistent with the histomorphometrical results.

Conclusions: These results imply that electrostatic spraying can be an efficient strategy to produce homogenous ceramic granules and that the BMP-2-and-Qct-loaded HAp microbeads can serve as effective implants for bone defect healing.

Keywords: Bone morphogenetic protein-2; Bone regeneration; Electrostatic spraying; Hydroxyapatite microbeads; Quercetin.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Regeneration
  • Durapatite* / pharmacology
  • Microspheres
  • Osteogenesis
  • Quercetin* / pharmacology
  • Rats
  • Static Electricity

Substances

  • Durapatite
  • Quercetin
  • Bone Morphogenetic Protein 2