Novel Osteoinductive Photo-cross-linkable Chitosan-lactide-fibrinogen Hydrogels Enhance Bone Regeneration in Critical Size Segmental Bone Defects

Abstract

The purpose of this study was to develop and characterize a novel photo-cross-linkable chitosanlactide- fibrinogen (CLF) hydrogel and evaluate the efficacy of bone morphogenetic protein-2 (BMP-2) containing CLF hydrogel for osteogenesis in vitro and in vivo. We synthesized the CLF hydrogels and characterized their chemical structure, degradation rate, compressive modulus, and in vitro BMP-2 release kinetics. We evaluated bioactivities of the BMP-2 containing CLF hydrogels (0, 50, 100, and 500 ng/ml) in vitro using W-20-17 preosteoblast mouse bone marrow stromal cells and C2C12 mouse myoblast cells. The effect of BMP-2 containing CLF gels (0, 0.5, 1, 2, and 5 g) on bone formation was evaluated using rat critical size segmental bone defects for 4 weeks. FTIR spectra and SEM images showed chemical and structural changes by addition of fibrinogen into chitosan-lactide copolymer. Incorporation of fibrinogen molecules significantly increased compressive modulus of the hydrogels. In vitro BMP-2 release study showed initial burst releases from the CLF hydrogels followed by sustained releases, regardless of the concentration of the BMP-2 over 4 weeks. Cells in all groups were viable in the presence of the hydrogels regardless of BMP-2 doses, indicating non-cytotoxicity of hydrogels. Alkaline phosphate activity and mineralization of cells exhibited dose dependence on BMP-2 containing CLF hydrogels. Radiographs, microcomputed tomography, and histology confirmed that the BMP-2 containing CLF hydrogels prompted neo-osteogenesis and accelerated healing of the defects in a dose-dependent manner. Thus the CLF hydrogel is a promising delivery system of growth factors for bone regeneration.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2014
Accession Number
ADA619020

Entities

People

  • Joseph C Wenke
  • Katherine Bedigrew
  • Sangwon Park
  • Sungwoo Kim
  • Teja Guda
  • William J. Maloney
  • Yunzhi P. Yang

Organizations

  • United States Army Institute of Surgical Research

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Bone And Bones
  • Bone Regeneration
  • Cells
  • Chemistry
  • Growth Factors
  • Materials
  • Materials Science
  • Materials Testing
  • Mechanical Properties
  • Microscopes
  • Molecules
  • Osteoblasts
  • Osteogenesis
  • Peptide Growth Factors
  • Polymers
  • Spine
  • X-Ray Computed Tomography

Fields of Study

  • Materials science

Readers

  • Immunology and Pathology
  • Molecular and Cellular Biochemistry
  • Nanoscale Plasmonic Nanotechnology

Technology Areas

  • 5G
  • Microelectronics