Effects of Tunable Keratin Hydrogel Erosion on Recombinant Human Bone Morphogenetic Protein 2 Release, Bioactivity, and Bone Induction

Tissue Eng Part A. 2018 Nov;24(21-22):1616-1630. doi: 10.1089/ten.TEA.2017.0471. Epub 2018 Sep 6.

Abstract

Recombinant human bone morphogenetic protein 2 (rhBMP-2) delivery from collagen sponges for bone formation is an important clinical example of growth factors in tissue engineering. Side effects from rhBMP-2 burst release and rapid collagen resorption have led to investigation of alternative carriers. Here, keratin carriers with tunable erosion rates were formulated by varying disulfide crosslinking via ratios of oxidatively (keratose) to reductively (kerateine) extracted keratin. In vitro rhBMP-2 bioactivity increased with kerateine content, reaching levels greater than with collagen. Heterotopic bone formation in a mouse model depended on the keratin formulation, highlighting the importance of the growth factor carrier.

Keywords: bone morphogenetic protein 2; collagen; drug delivery; kerateine; keratose; synthetic bone graft.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Cell Line
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacology
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Keratins / chemistry
  • Keratins / pharmacology*
  • Mice
  • Osteogenesis / drug effects*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Delayed-Action Preparations
  • Hydrogels
  • Recombinant Proteins
  • Keratins