Endocultivation: continuous application of rhBMP-2 via mini-osmotic pumps to induce bone formation at extraskeletal sites

Int J Oral Maxillofac Surg. 2017 May;46(5):655-661. doi: 10.1016/j.ijom.2017.01.010. Epub 2017 Feb 10.

Abstract

The continuous presence of recombinant human bone morphogenetic protein 2 (rhBMP-2) inside a scaffold may be crucial to the outcome in bone tissue engineering. This study investigated whether the release of the growth factor rhBMP-2 via different continuous application schemes influences histomorphological aspects of the hard and soft tissues induced. Three-dimensionally printed hydroxyapatite scaffolds were implanted into one latissimus dorsi muscle of 42 female Lewis rats. Simultaneously implanted mini-osmotic pumps were used to provide a continuous application of rhBMP-2 over 1, 2, or 4 weeks (total dose 200μg). A reference group received rhBMP-2 at the time of implantation only, and a control group received only block implantation. Bone density and histological examinations were performed after 8 weeks. No significant difference in bone density was found between the groups; however, the blood vessel count differed significantly between the groups receiving continuous treatments and both the control group and simultaneous rhBMP-2 treatment group (P<0.0001). Soft tissue types were distributed differently among the study groups. RhBMP-2 application via mini-osmotic pumps is as suitable for inducing bone formation as a single application at the time of implantation. The time interval over which rhBMP-2 was administered had no impact on the amount of new bone formation, probably due to the study duration and low local concentrations of growth factor.

Keywords: bone density; endocultivation; heterotopic bone induction; rhBMP-2; soft tissue.

MeSH terms

  • Animals
  • Biological Availability
  • Bone Density
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Drug Delivery Systems*
  • Durapatite / pharmacology
  • Female
  • Models, Animal
  • Osmosis
  • Osteogenesis / drug effects*
  • Rats
  • Rats, Inbred Lew
  • Recombinant Proteins / pharmacology
  • Tissue Engineering / methods*
  • Tissue Scaffolds
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Bone Morphogenetic Protein 2
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Durapatite