Analysis of hydrolyzable polyethylene glycol hydrogels and deproteinized bone mineral as delivery systems for glycosylated and non-glycosylated bone morphogenetic protein-2

Acta Biomater. 2012 Jan;8(1):116-23. doi: 10.1016/j.actbio.2011.08.002. Epub 2011 Aug 12.

Abstract

Bone morphogenetic proteins (BMP), in particular BMP-2, are the growth factors primarily responsible for osteoinduction. A knowledge of interactions between bone substitute materials and growth factor variants is crucial to designing bone substitutes with an ideal release profile. Here we compare glycosylated and non-glycosylated recombinant human bone morphogenetic protein-2 (rhBMP-2) either incorporated into a hydrolyzable polyethylene glycol (PEG) hydrogel developed as a slow release system or adsorbed to a deproteinized bovine bone matrix (DBBM), a clinically well-established bone substitute material. rhBMP-2 loaded materials were immersed in cell culture medium and rhBMP-2 concentration profiles in the supernatant were determined by an enzyme-linked immunosorbent assay. The corresponding biological activities were assessed in vitro by alkaline phosphatase activity assay. We show a strong affinity of rhBMP-2 for DBBM and reduced biological activity after its release from PEG hydrogels. Glycosylated rhBMP-2 was significantly less affected by the hydrogel and interacted significantly more strongly with DBBM than non-glycosylated rhBMP-2. We therefore question the combination of PEG hydrogels with DBBM as a rhBMP-2 delivery system over DBBM alone, since rhBMP-2 released from the hydrogel will be trapped by DBBM. Moreover, our results suggest that glycosylated rhBMP-2 is favorable in combination with PEG hydrogels, since its activity is better preserved, whereas in combination with DBBM non-glycosylated rhBMP-2 is favorable, benefiting from an initially higher concentration of free rhBMP-2.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism*
  • Bone and Bones / chemistry*
  • Cattle
  • Cell Line
  • Cell Survival
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Drug Delivery Systems*
  • Glycosylation
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / metabolism*
  • Hydrolysis
  • Materials Testing
  • Mice
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / metabolism*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Bone Morphogenetic Protein 2
  • Drug Carriers
  • Hydrogels
  • Recombinant Proteins
  • Polyethylene Glycols