文献类型：期刊文献

英文题名：Bone regeneration using photocrosslinked hydrogel incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles

作者：Cao, Lingyan[1,2,3];Werkmeister, Jerome A.[2];Wang, Jing[1,3];Glattauer, Veronica[2];McLean, Keith M.[2];Liu, Changsheng[1,3,4]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]CSIRO Mat Sci & Engn, Clayton, Vic 3168, Australia;[3]E China Univ Sci & Technol, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[4]E China Univ Sci & Technol, Engn Res Ctr Biomed Mat, Minist Educ, Shanghai 200237, Peoples R China

年份：2014

卷号：35

期号：9

起止页码：2730

外文期刊名：BIOMATERIALS

收录：;EI(收录号：20140617275089);WOS:【SCI-EXPANDED(收录号:WOS:000332188900017)】；

基金：The authors are indebted to the financial support from the National Basic Research Program of China (973 Program, No. 2012CB933600), Major Program of National Natural Science Foundation of China (No. 50732002), National Natural Science Foundation of China (No. 31271011), and China Scholarship Council (Lingyan Cao).

语种：英文

外文关键词：BMP; Hydrogel; Bone regeneration; Nanoparticle

摘要：Although rhBMP-2 has excellent ability to accelerate the repair of normal bone defects, limitations of its application exist in the high cost and potential side effects. This study aimed to develop a composite photopolymerisable hydrogel incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles (PH/rhBMP-2/NPs) as the bone substitute to realize segmental bone defect repair at a low growth factor dose. Firstly rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles (rhBMP-2/NPs) were prepared and characterized by DLS and TEM. Composite materials, PH/rhBMP-2/NPs were developed and investigated by SEM-EDS as well as a series of physical characterizations. Using hMSCs as an in vitro cell model, composite photopolymerisable hydrogels incorporating NPs (PH/NPs) showed good cell viability, cell adhesion and time dependent cell ingrowth. In vitro release kinetics of rhBMP-2 showed a significantly lower initial burst release from the composite system compared with the growth factor-loaded particles alone or encapsulated directly within the hydrogel, followed by a slow release over time. The bioactivity of released rhBMP-2 was validated by alkaline phosphatase (ALP) activity as well as a mineralization assay. In in vivo studies, the PH/rhBMP-2/NPs induced ectopic bone formation in the mouse thigh. In addition, we further investigated the in vivo effects of rhBMP-2-loaded scaffolds in a rabbit radius critical defect by three dimensional micro-computed tomographic (mu CT) imaging, histological analysis, and biomechanical measurements. Animals implanted with the composite hydrogel containing rhBMP-2-loaded nanoparticles underwent gradual resorption with more pronounced replacement by new bone and induced reunion of the bone marrow cavity at 12 weeks, compared with animals implanted with hydrogel encapsulated growth factors alone. These data provided strong evidence that the composite PH/rhBMP-2/NPs are a promising substitute for bone tissue engineering. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.