A composited PEG-silk hydrogel combining with polymeric particles delivering rhBMP-2 for bone regeneration

Mater Sci Eng C Mater Biol Appl. 2016 Aug 1:65:221-31. doi: 10.1016/j.msec.2016.04.043. Epub 2016 Apr 14.

Abstract

Given the fabulous potential of promoting bone regeneration, BMP-2 has been investigated widely in the bone tissue engineering field. A sophisticated biomaterial loaded with BMP-2, which could avoid the required supraphysiological dose leading to high medical costs and risks of complications, has been considered as a promising strategy to treat non-healing bone defects. In this study, we developed a simple approach to engineer a composited hydrogel consisting polymeric particles (PLA/PLGA) used as a BMP-2 delivery vehicle. Compared with other groups, the introduction of PLA into PEG-silk gels endowed the hydrogel new physicochemical characteristics especially hydrophobicity which inhibited the burst release of BMP-2 and enhanced gel's structural stability. Moreover, such composited gels could stabilize entrapped proteins and maintain their bioactivity fully in vitro. In vivo, the bio-degradability experiment demonstrated this system was biocompatible and the reinforced hydrophobicity significantly decreased degradation rate, and in rat critical-sized cranial defects model, the gel containing PLA promoted the most bone formation. These findings demonstrated the introduction of PLA changed physicochemical features of gels more suitable as a BMP-2 carrier indicated by inducing bone regeneration efficiently in large bone defects at low delivered dose and this system may own translational potential.

Keywords: BMP-2 sustained release; Bio-composite; Bone regeneration; Hydrogel.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone Regeneration / drug effects*
  • Bone and Bones / pathology
  • Drug Carriers / chemistry*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Microscopy, Electron, Scanning
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacology
  • Silk / chemistry*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Bone Morphogenetic Protein 2
  • Drug Carriers
  • Recombinant Proteins
  • Silk
  • Hydrogel, Polyethylene Glycol Dimethacrylate