Modularly engineered alginate bioconjugate hydrogel as biocompatible injectable scaffold for in situ biomineralization

Carbohydr Polym. 2020 Apr 1:233:115832. doi: 10.1016/j.carbpol.2020.115832. Epub 2020 Jan 7.

Abstract

In the present study, a type of bioconjugate was synthesized by post modification of alginate by conjugating temperature-responsive poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) and O-phosphorylethanolamine as phosphorylation functional groups. Freely flowing bioconjugate sols at low temperature can transform to stable viscoelastic gels at the physiological temperature (37 °C). Subcutaneous administration of temperature-responsive bioconjugate sols into the dorsal region of Sprague-Dawley rats formed in situ hydrogel. in situ formation of bioconjugate gels in stimulated body fluids at 37 °C showed nucleation and hydroxyapatite mineral growth. Furthermore, hydroxyapatite growth was also found in in vivo gels, which suggested the potential of alginate-based bioconjugate gels as a scaffold for bone engineering. Bone morphogenetic protein 2 (BMP-2)-loaded bioconjugate formed stable gel in vivo, and demonstrated sustained release. BMP-2-loaded bioconjugates exhibited in situ biomineralization in vivo. These results imply that the in situ formation of injectable biomimetic materials has potential for bone tissue engineering applications.

Keywords: Alginate; BMP-2; Biomineralization; Bone repair; Controlled release; Temperature-responsive.

MeSH terms

  • Alginates / chemical synthesis
  • Alginates / pharmacology*
  • Alginates / toxicity
  • Animals
  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / pharmacology*
  • Biocompatible Materials / toxicity
  • Biomineralization / drug effects*
  • Bone Morphogenetic Protein 2 / pharmacology
  • Drug Delivery Systems
  • Durapatite / metabolism
  • Ethanolamines / chemistry
  • HEK293 Cells
  • Humans
  • Hydrogels / chemical synthesis
  • Hydrogels / pharmacology*
  • Hydrogels / toxicity
  • Male
  • Phase Transition
  • Polyesters / chemical synthesis
  • Polyesters / pharmacology*
  • Polyesters / toxicity
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / pharmacology*
  • Polyethylene Glycols / toxicity
  • Rats, Sprague-Dawley
  • Tissue Engineering / methods

Substances

  • Alginates
  • BMP2 protein, human
  • Biocompatible Materials
  • Bone Morphogenetic Protein 2
  • Ethanolamines
  • Hydrogels
  • Polyesters
  • Polyethylene Glycols
  • phosphorylethanolamine
  • Durapatite