1 research outputs found
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 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