Bone regeneration in osteoporosis by delivery BMP-2 and PRGF from tetronic-alginate composite thermogel

Int J Pharm. 2018 May 30;543(1-2):160-168. doi: 10.1016/j.ijpharm.2018.03.034. Epub 2018 Mar 19.

Abstract

As the life expectancy of the world population increases, osteoporotic (OP) fracture risk increase. Therefore in the present study a novel injectable thermo-responsive hydrogel loaded with microspheres of 17β-estradiol, microspheres of bone morphogenetic protein-2 (BMP-2) and plasma rich in growth factors (PRGF) was applied locally to regenerate a calvaria critical bone defect in OP female rats. Three systems were characterized: Tetronic® 1307 (T-1307) reinforced with alginate (T-A), T-A with PRGF and T-A-PRGF with microspheres. The addition of the microspheres increased the viscosity but the temperature for the maximum viscosity did not change (22-24 °C). The drugs were released during 6 weeks in one fast phase (three days) followed by a long slow phase. In vivo evaluation was made in non-OP and OP rats treated with T-A, T-A with microspheres of 17β-estradiol (T-A-βE), T-A-βE prepared with PRGF (T-A-PRGF-βE), T-A-βE with microspheres of BMP-2 (T-A-βE-BMP-2) and the combination of the three (T-A-PRGF-βE-BMP). After 12 weeks, histological and histomorphometric analyzes showed a synergic effect due to the addition of BMP-2 to the T-A-βE formulation. The PRGF did not increased the bone repair. The new bone filling the OP defect was less mineralized than in the non-OP groups.

Keywords: BMP-estradiol; Hydrogel; Osteoporosis; Sustained release; Tetronic-alginate.

MeSH terms

  • Alginates / administration & dosage*
  • Animals
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Regeneration / drug effects*
  • Collagen Type I / metabolism
  • Estradiol / administration & dosage*
  • Female
  • Glucuronic Acid / administration & dosage
  • Hexuronic Acids / administration & dosage
  • Hydrogels / administration & dosage*
  • Intercellular Signaling Peptides and Proteins / administration & dosage*
  • Microspheres
  • Osteoporosis / drug therapy*
  • Osteoporosis / metabolism
  • Polyamines / administration & dosage*
  • Rats, Sprague-Dawley

Substances

  • Alginates
  • Bone Morphogenetic Protein 2
  • Collagen Type I
  • Hexuronic Acids
  • Hydrogels
  • Intercellular Signaling Peptides and Proteins
  • Polyamines
  • Tetronic 1307
  • Estradiol
  • Glucuronic Acid