Aggrecan-Mimetic, Glycosaminoglycan-Containing Nanoparticlesfor Growth Factor Stabilization and Delivery.

The direct delivery of growth factorsto sites of tissue healingis complicated by their relative instability. In many tissues, theglycosaminoglycan (GAG) side chains of proteoglycans like aggrecanstabilize growth factors in the pericellular and extracellular space,creating a local reservoir that can be accessed during a wound healingresponse. GAGs also regulate growth factor-receptor interactions atthe cell surface. Here we report the development of nanoparticlesfor growth factor delivery that mimic the size, GAG composition, andgrowth factor binding and stabilization of aggrecan. The aggrecan-mimeticnanoparticles are easy to assemble, and their structure and compositioncan be readily tuned to alter their physical and biological properties.We use basic fibroblast growth factor (FGF-2) as a model heparin-bindinggrowth factor, demonstrating that aggrecan-mimetic nanoparticles canpreserve its activity for more than three weeks. We evaluate FGF-2activity by measuring both the proliferation and metabolic activityof bone marrow stromal cells to demonstrate that chondroitin sulfate-basedaggrecan mimics are as effective as aggrecan, and heparin-based aggrecanmimics are superior to aggrecan as delivery vehicles for FGF-2. [ABSTRACT FROM AUTHOR]