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Hyaluronic acid-based hydrogels functionalized with heparin that support controlled release of bioactive BMP-2

Paper ID Volume ID Publish Year Pages File Format Full-Text
6710 513 2012 10 PDF Available
Title
Hyaluronic acid-based hydrogels functionalized with heparin that support controlled release of bioactive BMP-2
Abstract

Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive factor, yet its clinical use is limited by a short biological half-life, rapid local clearance and propensity for side effects. Heparin (HP), a highly sulfated glycosaminoglycan (GAG) that avidly binds BMP-2, has inherent biological properties that may circumvent these limitations. Here, we compared hyaluronan-based hydrogels formulated to include heparin (Heprasil™) with similar gels without heparin (Glycosil™) for their ability to deliver bioactive BMP-2 in vitro and in vivo. The osteogenic activity of BMP-2 released from the hydrogels was evaluated by monitoring alkaline phosphatase (ALP) activity and SMAD 1/5/8 phosphorylation in mesenchymal precursor cells. The osteoinductive ability of these hydrogels was determined in a rat ectopic bone model by 2D radiography, 3D μ-CT and histological analyses at 8 weeks post-implantation. Both hydrogels sustain the release of BMP-2. Importantly, the inclusion of a small amount of heparin (0.3% w/w) attenuated release of BMP-2 and sustained its osteogenic activity for up to 28 days. In contrast, hydrogels lacking heparin released more BMP-2 initially but were unable to maintain BMP-2 activity at later time points. Ectopic bone-forming assays using transplanted hydrogels emphasized the therapeutic importance of the initial burst of BMP-2 rather than its long-term osteogenic activity. Thus, tuning the burst release phase of BMP-2 from hydrogels may be advantageous for optimal bone formation.

Keywords
Bone morphogenetic protein-2; Growth factor; Burst release; Glycosaminoglycan; Mesenchymal cell; Osteogenesis
First Page Preview
Hyaluronic acid-based hydrogels functionalized with heparin that support controlled release of bioactive BMP-2
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 26, September 2012, Pages 6113–6122
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering