Acceleration of bone union by in situ-formed hydrogel containing bone morphogenetic protein-2 in a mouse refractory fracture model

J Orthop Surg Res. 2020 Sep 18;15(1):426. doi: 10.1186/s13018-020-01953-7.

Abstract

Background: An enzymatic crosslinking strategy using hydrogen peroxide and horseradish peroxidase is receiving increasing attention for application with in situ-formed hydrogels (IFHs). Several studies have reported the application of IFHs in cell delivery and tissue engineering. IFHs may also be ideal carrier materials for bone repair, although their potential as a carrier for bone morphogenetic protein (BMP)-2 has yet to be examined. Here, we examined the effect of an IFH made of hyaluronic acid (IFH-HA) containing BMP-2 in promoting osteogenesis in a mouse refractory fracture model.

Methods: Immediately following a fracture procedure, animals either received no treatment (control) or an injection of IFH-HA/PBS or IFH-HA containing 2 μg BMP-2 (IFH-HA/BMP-2) into the fracture site (n = 16, each treatment).

Results: Fracture sites injected with IFH-HA/BMP-2 showed significantly greater bone volume, bone mineral content, and bone union compared with sites receiving no treatment or treated with IFH-HA/PBS alone (each n = 10). Gene expression levels of osteogenic markers, Alpl, Bglap, and Osx, were significantly raised in the IFH-HA/BMP-2 group compared to the IFH-HA/PBS and control groups (each n = 6).

Conclusion: IFH-HA/BMP-2 may contribute to the treatment of refractory fractures.

Keywords: Bone morphogenetic protein; Hyaluronic acid; In situ-formed hydrogels; Refractory fracture.

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Density
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Disease Models, Animal
  • Femoral Fractures / drug therapy*
  • Femoral Fractures / genetics
  • Femoral Fractures / pathology
  • Femoral Fractures / physiopathology*
  • Femur / metabolism*
  • Femur / pathology*
  • Femur / physiopathology
  • Gene Expression / drug effects
  • Hydrogels / administration & dosage*
  • Injections, Intralesional
  • Mice, Inbred C57BL
  • Organ Size
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Sp7 Transcription Factor / genetics
  • Sp7 Transcription Factor / metabolism

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Hydrogels
  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • ALPL protein, mouse
  • Alkaline Phosphatase

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