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Enhanced Control of In Vivo Bone Formation with Surface Functionalized Alginate Microbeads Incorporating Heparin and Human Bone Morphogenetic Protein-2

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Enhanced Control of In Vivo Bone Formation with Surface Functionalized Alginate Microbeads Incorporating Heparin and Human Bone Morphogenetic Protein-2

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Abbah, Sunny Akogwu Liu, Jing Goh, James Cho Hong Wong, Hee-Kit
Description	Country affiliation: Singapore Author Affiliation: Abbah SA ( Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.)
Abstract	In this study, we tested the hypothesis that a surface functionalization delivery platform incorporating heparin onto strontium alginate microbeads surfaces would convert this 'naive carriers' into 'mini-reservoirs' for localized in vivo delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) that will induce functional bone regeneration. In vitro evaluation confirmed that (1) heparin incorporation could immobilize and prolong rhBMP-2 release for approximately 3 weeks; (2) a significant decrease (p<0.01) in rhBMP-2 burst release is attainable depending on initial protein load; and (3) rhBMP-2 released from surface functionalized microbeads retained bioactivity and stimulated higher alkaline phosphatase activity in cultured C(2)C(12) cells when compared with daily administration of fresh bolus rhBMP-2. Subsequently, surface functionalized microbeads were used for in vivo delivery of rhBMP-2 at local sites of posterolateral spinal fusion surgery in rats. The microbeads were loaded into the pores of medical-grade polyepsilone caprolactone-tricalcium phosphate scaffolds before implantation. Results revealed robust bone formation and a biomechanically solid fusion after 6 weeks. When compared with a control group consisting of an equivalent amount of rhBMP-2 that was directly adsorbed onto bare-surfaced microbeads with no heparin, a 5.3-fold increase in bone volume fraction and a 2.6-fold increase in bending stiffness (flexion/extension) were observed. When compared with collagen sponge carriers of rhBMP-2, a 1.5-fold and a 1.3-fold increase in bone volume fraction and bending stiffness were observed, respectively. More importantly, 3D micro-computed tomography images enabled the visualization of a well-contained newly formed bone at ipsilateral implant sites with surface functionalized rhBMP-2 delivery. This was absent with collagen sponge carriers where newly formed bone tissue was poorly contained and crossed over the posterior midline to contralateral implants. These findings are important because of complications with current rhBMP-2 delivery method, including excessive, uncontrolled bone formation.
File Format	HTM / HTML
ISSN	21524947
e-ISSN	21524955
DOI	10.1089/ten.TEA.2012.0274
Journal	Tissue Engineering Part A
Issue Number	3-4
Volume Number	19
Language	English
Publisher	Mary Ann Liebert, Inc.
Publisher Date	2013-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Biotechnology Alginates Chemistry Bone Morphogenetic Protein 2 Administration & Dosage Bone Regeneration Drug Effects Physiology Heparin Lumbar Vertebrae Growth & Development Spinal Fractures Drug Therapy Animals Capsules Delayed-action Preparations Chemical Synthesis Glucuronic Acid Hexuronic Acids Pathology Rats, Sprague-dawley Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article

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Enhanced Control of In Vivo Bone Formation with Surface Functionalized Alginate Microbeads Incorporating Heparin and Human Bone Morphogenetic Protein-2

The bone morphogenetic protein-2/7 heterodimer is a stronger inducer of bone regeneration than the individual homodimers in a rat spinal fusion model.

Sustained Release of Bone Morphogenetic Protein-2 through Alginate Microbeads Enhances Bone Regeneration in Rabbit Tibial Metaphyseal Defect Model

Controlled delivery of low-dose bone morphogenetic protein-2 using heparin-conjugated fibrin in the posterolateral lumbar fusion of rabbits.

Enhanced bone tissue formation by alginate gel-assisted cell seeding in porous ceramic scaffolds and sustained release of growth factor.

Osteogenic/angiogenic dual growth factor delivery microcapsules for regeneration of vascularized bone tissue.

Floating capsules containing alginate-based beads of salbutamol sulfate: In vitro-in vivo evaluations.

Design and characterization of chitosan-alginate microspheres for ocular delivery of azelastine.

Integration of a novel injectable nano calcium sulfate/alginate scaffold and BMP2 gene-modified mesenchymal stem cells for bone regeneration.

Enhanced Control of In Vivo Bone Formation with Surface Functionalized Alginate Microbeads Incorporating Heparin and Human Bone Morphogenetic Protein-2

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Enhanced Control of In Vivo Bone Formation with Surface Functionalized Alginate Microbeads Incorporating Heparin and Human Bone Morphogenetic Protein-2

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