文献类型：期刊文献

英文题名：Vascularization and bone regeneration in a critical sized defect using 2-N,6-O-sulfated chitosan nanoparticles incorporating BMP-2

作者：Cao, Lingyan[1,2,3];Wang, Jing[1,3];Hou, Juan[1,3];Xing, Wanli[1,3];Liu, Changsheng[1,2,3]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Minist Educ, Key Lab Ultrafine Mat, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Minist Educ, Engn Res Ctr Biomed Mat, Shanghai 200237, Peoples R China

年份：2014

卷号：35

期号：2

起止页码：684

外文期刊名：BIOMATERIALS

收录：;EI(收录号：20134516948889);WOS:【SCI-EXPANDED(收录号:WOS:000328594800008)】；

基金：The authors are indebted to the financial support from the National Basic Research Program of China (973 Program, No. 2012CB933600), National Natural Science Foundation of China (No. 50973029, 31271011), the National Science and Technology Support Program (2012BAI17B02), and the Program for New Century Excellent Talents in University (NCET-12-0856).

语种：英文

外文关键词：BMP; Angiogenesis; Chitosan; Bone regeneration; Nanoparticle

摘要：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.