Development of Collagen-Hydroxyapatite Scaffolds Incorporating PLGA and Alginate Microparticles for the Controlled Delivery of rhBMP-2 for Bone Tissue Engineering

J Control Release. 2015 Jan 28;198:71-9. doi: 10.1016/j.jconrel.2014.11.021. Epub 2014 Dec 4.

Abstract

The spatiotemporally controlled delivery of the pro-osteogenic factor rhBMP-2 would overcome most of the severe secondary effects linked to the products delivering this protein for bone regeneration. With this in mind, the aim of the present work was to develop a controlled rhBMP-2 release system using collagen-hydroxyapatite (CHA) scaffolds, which had been previously optimized for bone regeneration, as delivery platforms to produce a device with enhanced capacity for bone repair. Spray-drying and emulsion techniques were used to encapsulate bioactive rhBMP-2 in alginate and PLGA microparticles, with a high encapsulation efficiency. After incorporation of these microparticles into the scaffolds, rhBMP-2 was delivered in a sustained fashion for up to 28days. When tested in vitro with osteoblasts, these eluting materials showed an enhanced pro-osteogenic effect. From these results, an optimal rhBMP-2 eluting scaffold composition was selected and implanted in critical-sized calvarial defects in a rat model, where it demonstrated an excellent healing capacity in vivo. These platforms have an immense potential in the field of tissue regeneration; by tuning the specific therapeutic molecule to the tissue of interest and by utilizing different collagen-based scaffolds, similar systems can be developed for enhancing the healing of a diverse range of tissues and organs.

Keywords: Bone tissue engineering; Calcium alginate; Collagen based scaffolds; Microparticles; PLGA; rhBMP-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry
  • Animals
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Regeneration / drug effects*
  • Bone and Bones
  • Cell Line
  • Collagen / chemistry*
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Durapatite / chemistry*
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Lactic Acid / chemistry
  • Male
  • Mice
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats, Wistar
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Tissue Engineering
  • Tissue Scaffolds*

Substances

  • Alginates
  • Bone Morphogenetic Protein 2
  • Drug Carriers
  • Hexuronic Acids
  • Recombinant Proteins
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Glucuronic Acid
  • Collagen
  • Durapatite