期刊
BIOMATERIALS
卷 34, 期 22, 页码 5594-5605出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.04.017
关键词
Glycosaminoglycans; Heparan sulfate; Bone morphogenetic protein; Bone repair
资金
- Biomedical Research Council, Agency for Science, Technology and Research (A*STAR), Singapore
- Institute of Medical Biology (IMB), A*STAR, Singapore
Bone morphogenetic protein (BMP)-2 is a potent bone healing compound produced at sites of bone trauma. Here we present a therapeutic strategy to harness the activity of endogenously produced BMP-2 by delivery of an affinity-matched heparan sulfate (HS) glycos aminoglycan biomaterial that increases the bioavailability, bioactivity and half-life of this growth factor. We have developed a robust, cost effective, peptide-based affinity platform to isolate a unique BMP-2 binding HS variant from commercially available preparations of HS, so removing the manufacturing bottleneck for their translation into the clinic. This affinity-matched HS enhanced BMP-2-induced osteogenesis through improved BMP-2 kinetics and receptor modulation, prolonged pSMAD signaling and reduced interactions with its antagonist noggin. When co-delivered with a collagen implant, the HS was as potent as exogenous BMP-2 for the healing of critical-sized bone defects in rabbits. This affinity platform can be readily tuned to isolate HS variants targeted ata range of clinically-relevant growth and adhesive factors. (C) 2013 Elsevier Ltd. All rights reserved.
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