Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite

Int J Mol Sci. 2021 Dec 28;23(1):283. doi: 10.3390/ijms23010283.

Abstract

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.

Keywords: bone regeneration; critical sized defect; nonunion; pseudarthrosis; silk scaffold.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Anisotropy
  • Apatites / pharmacology*
  • Biomimetic Materials / pharmacology
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone Regeneration / drug effects*
  • Bone and Bones / drug effects
  • Bone and Bones / physiology*
  • Bone and Bones / ultrastructure
  • Caspase 7 / metabolism
  • Caspases / metabolism
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Fibroins / pharmacology*
  • Freezing
  • Humans
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Tissue Scaffolds / chemistry*
  • Transforming Growth Factor beta / pharmacology*
  • X-Ray Microtomography

Substances

  • Apatites
  • Bone Morphogenetic Protein 2
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Adenosine Triphosphate
  • Fibroins
  • Caspase 7
  • Caspases