The effect of a slow mode of BMP-2 delivery on the inflammatory response provoked by bone-defect-filling polymeric scaffolds

Biomaterials. 2010 Oct;31(29):7485-93. doi: 10.1016/j.biomaterials.2010.06.037.

Abstract

We investigated the inflammatory response to, and the osteoinductive efficacies of, four polymers (collagen, Ethisorb, PLGA and Polyactive) that bore either an adsorbed (fast-release kinetics) or a calcium-phosphate-coating-incorporated (slow-release kinetics) depot of BMP-2. Titanium-plate-supported discs of each polymer (n = 6 per group) were implanted at an ectopic (subcutaneous) ossification site in rats (n = 48). Five weeks later, they were retrieved for a histomorphometric analysis of the volumes of ectopic bone and foreign-body giant cells (a gauge of inflammatory reactivity), and the degree of polymer degradation. For each polymer, the osteoinductive efficacy of BMP-2 was higher when it was incorporated into a coating than when it was directly adsorbed onto the material. This mode of BMP-2 carriage was consistently associated with an attenuation of the inflammatory response. For coated materials, the volume density of foreign-body giant cells was inversely correlated with the volume density of bone (r(2) = 0.96), and the volume density of bone was directly proportional to the surface-area density of the polymer (r(2) = 0.97). Following coating degradation, other competitive factors, such as the biocompatibility and the biodegradability of the polymer itself, came into play.

Publication types

  • 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 / pharmacology*
  • Bone and Bones / drug effects
  • Bone and Bones / immunology*
  • Collagen / adverse effects
  • Collagen / chemistry
  • Giant Cells, Foreign-Body / drug effects
  • Giant Cells, Foreign-Body / metabolism
  • Lactic Acid / adverse effects
  • Lactic Acid / chemistry
  • Osteogenesis / drug effects
  • Polyesters / adverse effects
  • Polyesters / chemistry
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / chemistry
  • Polyglycolic Acid / adverse effects
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / adverse effects*
  • Polymers / chemistry
  • Rats
  • Tissue Scaffolds / adverse effects*
  • Tissue Scaffolds / chemistry*

Substances

  • Bone Morphogenetic Protein 2
  • Ethisorb
  • Polyesters
  • Polymers
  • polyethylene oxide-polybutylene terephthalate copolymer
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethylene Glycols
  • Collagen