Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates

J Mater Sci Mater Med. 2013 May;24(5):1201-9. doi: 10.1007/s10856-013-4877-6. Epub 2013 Feb 8.

Abstract

The possibility to affect bone formation by using crushed versus solid hydrogels as carriers for bone morphogenetic protein 2 (BMP-2) was studied. Hydrogels, based on chemical crosslinking between hyaluronic acid and poly(vinyl alcohol) derivatives, were loaded with BMP-2 and hydroxyapatite. Crushed and solid forms of the gels were analyzed both in vitro via a release study using ¹²⁵I radioactive labeling of BMP-2, and in vivo in a subcutaneous ectopic bone model in rats. Dramatically different morphologies were observed for the ectopic bone formed in vivo in the two types of gels, even though virtually identical release profiles were observed in vitro. Solid hydrogels induced formation of a dense bone shell around non-degraded hydrogel, while crushed hydrogels demonstrated a uniform bone formation throughout the entire sample. These results suggest that by crushing the hydrogel, the construct's three-dimensional network becomes disrupted. This could expose unreacted functional groups, making the fragment's surfaces reactive and enable limited chemical fusion between the crushed hydrogel fragments, leading to similar in vitro release profiles. However, in vivo these interactions could be broken by enzymatic activity, creating a macroporous structure that allows easier cell infiltration, thus, facilitating bone formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density / drug effects
  • Bone Morphogenetic Protein 2 / pharmacokinetics
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Choristoma / chemically induced
  • Choristoma / pathology
  • Drug Implants / chemistry
  • Drug Implants / pharmacokinetics
  • Drug Implants / pharmacology
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacokinetics
  • Hyaluronic Acid / pharmacology*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacokinetics
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology*
  • Male
  • Organ Size / drug effects
  • Osteogenesis / drug effects*
  • Porosity
  • Rats
  • Rats, Sprague-Dawley
  • Skin Diseases / chemically induced
  • Skin Diseases / pathology
  • Surface Properties

Substances

  • Bone Morphogenetic Protein 2
  • Drug Implants
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Hyaluronic Acid