Affinity-selected heparan sulfate for bone repair

被引：76

作者：

Murali, S. ^{[1
]}

Rai, B. ^{[1
]}

Dombrowski, C. ^{[1
]}

Lee, J. L. J. ^{[1
]}

Lim, Z. X. H. ^{[1
]}

Bramono, D. S. ^{[1
]}

Ling, L. ^{[1
]}

Bell, T. ^{[2
]}

Hinkley, S. ^{[2
]}

Nathan, S. S. ^{[3
]}

Hui, J. H. ^{[3
]}

Wong, H. K. ^{[3
]}

Nurcombe, V. ^{[1
]}

Cool, S. M. ^{[1
,3
]}

机构：

[1] ASTAR, Inst Med Biol, Glycotherapeut Grp, Singapore 138648, Singapore

[2] Ind Res Ltd, Lower Hutt 5040, New Zealand

[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Orthopaed Surg, Singapore 119074, Singapore

来源：

BIOMATERIALS | 2013年 / 34卷 / 22期

关键词：

Glycosaminoglycans; Heparan sulfate; Bone morphogenetic protein; Bone repair; MORPHOGENETIC PROTEIN-2; REGENERATIVE MEDICINE; CONTROLLED-RELEASE; GROWTH-FACTORS; STEM-CELLS; EXPRESSION; PROTEOGLYCANS; DIFFERENTIATION; MODEL; BMP-2;

D O I：

10.1016/j.biomaterials.2013.04.017

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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.

引用

页码：5594 / 5605

页数：12

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