文献类型：期刊文献

英文题名：Bone regeneration using cell-mediated responsive degradable PEG-based scaffolds incorporating with rhBMP-2

作者：Yang, Fan[1,2,3];Wang, Jing[1,3];Hou, Juan[3];Guo, Han[4];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;[4]Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai Synchrotron Radiat Facil, Shanghai 201800, Peoples R China

年份：2013

卷号：34

期号：5

起止页码：1514

外文期刊名：BIOMATERIALS

收录：;EI(收录号：20125015793852);WOS:【SCI-EXPANDED(收录号:WOS:000313929400008)】；

基金：The authors are indebted to the the financial support from the National Basic Research Program of China (973 Program, 2012CB933600), the National Natural Science Foundation of China (No. 50973029, 50873034, 31271011), and the National Science and Technology Support Program (2012BAI17B02).

语种：英文

外文关键词：Bone regeneration; Degradation; BMP; Scaffold

摘要：The treatment of large osseous defects remains a challenging clinical problem in orthopedic surgery. Particularly, strategies to control the appropriate degradation rate adapting to the tissue reconstruction are of essential for tissue regeneration. Here we report on a strategy to achieve adaptive degradation rate using cell-secreted protease as a switch. Disulfide-containing PEG-based scaffolds have been synthesized, and demonstrated to be responsive to the cell-secreted redox microenvironment Thus, the cell-triggered degradation and liberation of growth factor are achieved. The osteoinductive growth factor, recombinant human bone morphogenetic protein-2 (rhBMP-2), is incorporated into the scaffold for bioactivity promotion. Degradations under the stimuli of reduced glutathione (GSH) at intracellular and extracellular concentrations was studied with the results of duration time ranging from 0.5 h to 22 days regulated by both concentrations of redox medium and polymer precursors. The rhBMP-2 loaded scaffolds evidently induced the ectopic bone formation in the mouse thigh muscles. In addition, we further investigated the in vivo effects of rhBMP-2-loaded scaffolds in a rabbit radius critical defect by radiography, three dimensional micro-computed tomographic (mu CT) and synchrotron radiation-based microcomputed tomography (SR mu CT) imaging, histological analysis, and biomechanical measurement. Scaffolds underwent gradual resorption and replacement by new bone and induced reunion of bone marrow cavity at 12 weeks, much better than the effect of self-repairing group. The results indicated that both osteoinduction and appropriate degradation played a crucial role in accelerating and promoting bone augmentation, as well as effective proangiogenesis. Such a strategy appears promising as 3D temporal scaffolds for potential orthopedic applications. (C) 2012 Elsevier Ltd. All rights reserved.