Aggrecan-Mimetic, Glycosaminoglycan-Containing Nanoparticles for Growth Factor Stabilization and Delivery

The direct delivery of growth factors to sites of tissue healing is complicated by their relative instability. In many tissues, the glycosaminoglycan (GAG) side chains of proteoglycans like aggrecan stabilize growth factors in the pericellular and extracellular space, creating a local reservoir that...

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Bibliographic Details
Published in:Biomacromolecules 2014-02, Vol.15 (2), p.680-689
Main Authors: Place, Laura W, Sekyi, Maria, Kipper, Matt J
Format: Article
Language:English
Subjects:
Aggrecans - chemistry
Animals
Applied sciences
Biological and medical sciences
Cells, Cultured
Drug Delivery Systems
Exact sciences and technology
Female
Fibroblast Growth Factor 2 - chemistry
General pharmacology
Glycosaminoglycans - chemistry
Humans
Medical sciences
Nanoparticles - chemistry
Natural polymers
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Physicochemistry of polymers
Recombinant Proteins - chemistry
Sheep
Starch and polysaccharides
Surface Properties
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Summary:The direct delivery of growth factors to sites of tissue healing is complicated by their relative instability. In many tissues, the glycosaminoglycan (GAG) side chains of proteoglycans like aggrecan stabilize growth factors in the pericellular and extracellular space, creating a local reservoir that can be accessed during a wound healing response. GAGs also regulate growth factor-receptor interactions at the cell surface. Here we report the development of nanoparticles for growth factor delivery that mimic the size, GAG composition, and growth factor binding and stabilization of aggrecan. The aggrecan-mimetic nanoparticles are easy to assemble, and their structure and composition can be readily tuned to alter their physical and biological properties. We use basic fibroblast growth factor (FGF-2) as a model heparin-binding growth factor, demonstrating that aggrecan-mimetic nanoparticles can preserve its activity for more than three weeks. We evaluate FGF-2 activity by measuring both the proliferation and metabolic activity of bone marrow stromal cells to demonstrate that chondroitin sulfate-based aggrecan mimics are as effective as aggrecan, and heparin-based aggrecan mimics are superior to aggrecan as delivery vehicles for FGF-2.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm401736c