Injectable angiogenic and osteogenic carrageenan nanocomposite hydrogel for bone tissue engineering

Int J Biol Macromol. 2019 Feb 1:122:320-328. doi: 10.1016/j.ijbiomac.2018.10.182. Epub 2018 Oct 26.

Abstract

Functional biomaterials that couple angiogenesis and osteogenesis processes are vital for bone tissue engineering and bone remodeling. Herein we developed an injectable carrageenan nanocomposite hydrogel incorporated with whitlockite nanoparticles and an angiogenic drug, dimethyloxallylglycine. Synthesized whitlockite nanoparticles and nanocomposite hydrogels were characterized using SEM, TEM, EDS and FTIR. Developed hydrogels were injectable, mechanically stable, cytocompatible and has better protein adsorption. Incorporation of dimethyloxallylglycine resulted in initial burst release followed by sustained release for 7 days. Human umbilical vein endothelial cells exposed to dimethyloxallylglycine incorporated nanocomposite hydrogel showed enhanced cell migration and capillary tube-like structure formation. Osteogenic differentiation in rat adipose derived mesenchymal stem cells after 7 and 14 days revealed increased levels of alkaline phosphatase activity in vitro. Furthermore, cells exposed to nanocomposite hydrogel revealed enhanced protein expressions of RUNX2, COL and OPN. Overall, these results suggest that incorporation of whitlockite and dimethyloxallylglycine in carrageenan hydrogel promoted osteogenesis and angiogenesis in vitro.

Keywords: Angiogenesis; Carrageenan hydrogel; Dimethyloxallylglycine; Osteogenesis; Whitlockite nanoparticles.

MeSH terms

  • Bone and Bones / cytology
  • Bone and Bones / drug effects*
  • Bone and Bones / physiology
  • Carrageenan / administration & dosage*
  • Carrageenan / chemistry
  • Carrageenan / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Hydrogels / chemistry*
  • Injections
  • Nanocomposites*
  • Neovascularization, Physiologic / drug effects*
  • Osteogenesis / drug effects*
  • Tissue Engineering

Substances

  • Hydrogels
  • Carrageenan