The Cocktail Effect of BMP-2 and TGF-β1 Loaded in Visible Light-Cured Glycol Chitosan Hydrogels for the Enhancement of Bone Formation in a Rat Tibial Defect Model

Mar Drugs. 2018 Sep 25;16(10):351. doi: 10.3390/md16100351.

Abstract

Bone tissue engineering scaffolds offer the merits of minimal invasion as well as localized and controlled biomolecule release to targeted sites. In this study, we prepared injectable hydrogel systems based on visible light-cured glycol chitosan (GC) hydrogels containing bone morphogenetic protein-2 (BMP-2) and/or transforming growth factor-beta1 (TGF-β1) as scaffolds for bone formation in vitro and in vivo. The hydrogels were characterized by storage modulus, scanning electron microscopy (SEM) and swelling ratio analyses. The developed hydrogel systems showed controlled releases of growth factors in a sustained manner for 30 days. In vitro and in vivo studies revealed that growth factor-loaded GC hydrogels have no cytotoxicity against MC3T3-E1 osteoblast cell line, improved mRNA expressions of alkaline phosphatase (ALP), type I collagen (COL 1) and osteocalcin (OCN), and increased bone volume (BV) and bone mineral density (BMD) in tibia defect sites. Moreover, GC hydrogel containing BMP-2 (10 ng) and TGF-β1 (10 ng) (GC/BMP-2/TGF-β1-10 ng) showed greater bone formation abilities than that containing BMP-2 (5 ng) and TGF-β1 (5 ng) (GC/BMP-2/TGF-β1-5 ng) in vitro and in vivo. Consequently, the injectable GC/BMP-2/TGF-β1-10 ng hydrogel may have clinical potential for dental or orthopedic applications.

Keywords: bone formation; bone morphogenetic protein-2; in vitro and in vivo; injectable hydrogel system; transforming growth factor-beta1; visible light-cured glycol chitosan.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone Morphogenetic Protein 2 / therapeutic use
  • Cell Differentiation / drug effects
  • Cell Line
  • Chitosan / chemistry
  • Delayed-Action Preparations
  • Disease Models, Animal
  • Drug Liberation
  • Drug Synergism
  • Humans
  • Hydrogels / chemistry
  • Light
  • Male
  • Osteoblasts
  • Osteogenesis / drug effects*
  • Rats
  • Rats, Wistar
  • Tibia / diagnostic imaging
  • Tibia / injuries
  • Tissue Scaffolds / chemistry*
  • Transforming Growth Factor beta1 / pharmacology*
  • Transforming Growth Factor beta1 / therapeutic use
  • Treatment Outcome
  • Wounds and Injuries / diagnostic imaging
  • Wounds and Injuries / therapy*
  • X-Ray Microtomography

Substances

  • Bone Morphogenetic Protein 2
  • Delayed-Action Preparations
  • Hydrogels
  • Transforming Growth Factor beta1
  • glycol-chitosan
  • Chitosan