期刊
ACTA BIOMATERIALIA
卷 10, 期 12, 页码 5021-5033出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2014.08.028
关键词
Chitosan; Lactide; Fibrinogen; Photo-cross-linkable hydrogel; BMP-2
资金
- DOD [W81XWH-10-1-0966]
- Airlift Research Foundation
- Wallace H. Coulter Foundation
- NIH from NIAMS [R01AR057837]
- NIH from NIDCR [R01DE021468]
The purpose of this study was to develop and characterize a novel photo-cross-linkable chitosan-lactide-fibrinogen (CLF) hydrogel and evaluate the efficacy of bone morphogenetic protein-2 (BMP-2) containing a 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(-1)) 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 mu g) on bone formation was evaluated using rat critical size segmental bone defects for 4 weeks. Fourier transform infrared spectroscopy spectra and scanning electron microscopy images showed chemical and structural changes by the addition of fibrinogen into the chitosan-lactide copolymer. The incorporation of fibrinogen molecules significantly increased the compressive modulus of the hydrogels. The 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. Radiography, 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. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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