Affinity-selected heparan sulfate for bone repair

Abstract 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 in...

Full description

Saved in:

Bibliographic Details
Published in:	Biomaterials Vol. 34; no. 22; pp. 5594 - 5605
Main Authors:	Murali, S, Rai, B, Dombrowski, C, Lee, J.L.J, Lim, Z.X.H, Bramono, D.S, Ling, L, Bell, T, Hinkley, S, Nathan, S.S, Hui, J.H, Wong, H.K, Nurcombe, V, Cool, S.M
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-07-2013
Subjects:	Advanced Basic Science Alkaline Phosphatase - metabolism Amino Acid Sequence Animals Anticoagulants - pharmacology Bone and Bones - diagnostic imaging Bone and Bones - drug effects Bone and Bones - pathology Bone Matrix - drug effects Bone Matrix - metabolism Bone morphogenetic protein Bone Morphogenetic Protein 2 - chemistry Bone Morphogenetic Protein 2 - metabolism Bone Regeneration - drug effects Bone repair Calcification, Physiologic - drug effects Carrier Proteins - pharmacology Cell Line Core Binding Factor Alpha 1 Subunit - genetics Dentistry Disaccharides - analysis Glycosaminoglycans Heparan sulfate Heparitin Sulfate - pharmacology Humans Male Mice Models, Biological Molecular Sequence Data Osteogenesis - drug effects Protein Stability - drug effects Rabbits Transcription, Genetic - drug effects Wound Healing - drug effects X-Ray Microtomography Heparan sulfate Bone repair Glycosaminoglycans Bone morphogenetic protein
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Abstract 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0142-9612 1878-5905
DOI:	10.1016/j.biomaterials.2013.04.017