The use of non-viral gene vectors for bioactive poly-(D,L-lactide) implant surfaces in bone tissue engineering

Eur Cell Mater. 2012 Jun 27;23:441-8. doi: 10.22203/ecm.v023a34.

Abstract

The application of scaffolds in bone tissue engineering often comes along with side effects such as poor integrity, low regeneration rates of bone tissue with inadequate functionality, and, in case of non-degradable implants, the necessity of a second removal surgery after therapy. In this study, we coated a bioresorbable FDA-approved poly-(ε-caprolactone)-scaffold for bone regeneration with a poly-(D,L-lactide) layer containing copolymer-protected gene vectors to locally provide bone morphogenetic protein-2 (BMP-2). Results show that the presence of such gene vectors did not affect the distribution and attachment of seeded cells on gene-activated surfaces. BMP-2 was released into cell culture supernatants and furthermore detected in homogenised scaffolds. Increased amounts of osteoblastic markers, such as osteocalcin, osteopontin and the activity of alkaline phosphatase, in gene-activated scaffolds in vitro suggest a transdifferentiation of myoblastic C2C12 cells into the osteoblastic phenotype. With this study we present a new technology to bioactivate implant surfaces with non-viral gene vectors. This tool allows the stimulation of tissue regeneration by a local release of therapeutic proteins in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase
  • Animals
  • Bone Morphogenetic Protein 2* / genetics
  • Bone Morphogenetic Protein 2* / metabolism
  • Bone Morphogenetic Protein 2* / pharmacology
  • Bone Regeneration / genetics
  • Caproates / chemistry
  • Cell Line
  • Cell Transdifferentiation*
  • Genetic Vectors
  • Lactones / chemistry
  • Mice
  • Myoblasts / cytology*
  • Osteocalcin
  • Osteogenesis*
  • Osteopontin
  • Polyesters / chemistry
  • Tissue Engineering / methods*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Caproates
  • Lactones
  • Polyesters
  • Osteocalcin
  • Osteopontin
  • poly(lactide)
  • caprolactone
  • Alkaline Phosphatase