期刊
BIOMATERIALS
卷 35, 期 2, 页码 684-698出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.10.005
关键词
BMP; Angiogenesis; Chitosan; Bone regeneration; Nanoparticle
资金
- National Basic Research Program of China (973 Program) [2012CB933600]
- National Natural Science Foundation of China [50973029, 31271011]
- National Science and Technology Support Program [2012BAI17B02]
- Program for New Century Excellent Talents in University [NCET-12-0856]
An ideal bone tissue engineering graft should have both excellent pro-osteogenesis and pro-angiogenesis to rapidly realize the bone regeneration in vivo. To meet this goal, 2-N,6-O-sulfated chitosan (26SCS) based nanoparticle (S-NP) was successfully developed and showed a dose-dependent enhancement on angiogenesis in vitro. For the repair of a critical sized defect in rabbit radius, we developed BMP-2 loaded S-NP (BMP-2/S-NP) with protein loading efficiency of 1.4 +/- 0.2% and fabricated a gelatin sponge (G) based implant loaded with BMP-2/S-NP (BMP-2/S-NP/G). This implant exerted a delivery of BMP-2 with an initial burst release of 15.3 +/- 4.1% in first 24 h and a gradual release for 21 days to 77.8 +/- 3.6%. The in vitro ALP assay revealed that the activity of released BMP-2 from BMP-2/S-NP/G was maintained after 3-d and 7-d delivery and further enhanced after 14-d delivery compared with the original BMP-2. Furthermore, the in vivo effects of BMP-2/S-NP/G on the bone regeneration and vessel formation in the critical sized defect (18 mm) of rabbit radius were investigated by synchrotron radiation-based micro-computed tomography (SR mu CT) imaging, three dimensional micro-computed tomographic (ACT) imaging, histological analysis, immunohistochemistry and biomechanical measurement. Based on the results, both peripheral vessel and new vessel formation were significantly increased by the BMP-2/S-NP/G treatment, along with the bridged defects at as early as 2 weeks, the healed defects at 8 weeks and the reunion of bone marrow cavity at 12 weeks. The results indicated that both controlled release of active BMP-2 and favorable vascularization at the defect site contributed by BMP-2/S-NP/G played a crucial role in accelerating and promoting bone augmentation. This study suggests that BMP-2/S-NP/G demonstrates promise for vascularization and bone regeneration in clinical case of large defect. (C) 2013 Elsevier Ltd. All rights reserved.
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