Insulin-like growth factor I-releasing alginate-tricalciumphosphate composites for bone regeneration

Pharm Res. 2005 Jun;22(6):940-50. doi: 10.1007/s11095-005-4589-9. Epub 2005 Jun 8.

Abstract

Purpose: Development and characterization of an in situ-forming, osteoconductive, and growth factor-releasing bone implant.

Methods: Injectable in situ-forming scaffolds were prepared from a 2% (m/v) alginate solution, tricalciumphosphate (TCP) granules, and poly(lactide-co-glycolide) microspheres (MS), loaded with the osteoinductive growth factor insulin-like growth factor I (IGF-I). Scaffolds were prepared by mixing the components followed by hydrogel formation through calcium carbonate-induced physical cross-linking of the alginate at slightly acidic pH. Physical-chemical properties and cell biocompatibility using osteoblast-like cells (MG-63 and Saos-2) of these scaffolds were investigated.

Results: The addition of TCP to the alginate resulted in reduced swelling and gelation time and an increase in stiffness. Osteoblast-like cells (MG-63 and Saos-2) did not show toxic reactions and adhered circumferentially to the TCP granules surface. The addition of the IGF-I MS resulted in an up to sevenfold increased proliferation rate of MG-63 cells as compared to scaffold preparations without IGF-I MS. The alkaline phosphate (ALP) activity-a parameter for osteblastic activity-increased with increasing amounts of TCP in Saos-2 loaded composite scaffolds.

Conclusions: A prototype in situ-hardening composite system for conformal filling of bone defects supporting osteoblastic activity for further clinical testing in relevant fracture models was developed and characterized.

MeSH terms

  • Alginates*
  • Algorithms
  • Alkaline Phosphatase / metabolism
  • Bone Regeneration / drug effects*
  • Calcium Phosphates*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chemical Phenomena
  • Chemistry, Physical
  • DNA / analysis
  • DNA / biosynthesis
  • Delayed-Action Preparations
  • Humans
  • Hydrogels
  • Insulin-Like Growth Factor I / administration & dosage*
  • Insulin-Like Growth Factor I / metabolism
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Rheology
  • Stress, Mechanical

Substances

  • Alginates
  • Calcium Phosphates
  • Delayed-Action Preparations
  • Hydrogels
  • Insulin-Like Growth Factor I
  • DNA
  • Alkaline Phosphatase
  • tricalcium phosphate