Heparin-hyaluronic acid nanofibers for growth factor sequestration in spinal cord repair

Growth factor (GF) delivery is a common strategy for spinal cord injury repair, however, GF degradation can impede long-term therapies. GF sequestration via heparin is known to protect bioactivity after delivery. We tested two heparin modifications, methacrylated heparin and thiolated heparin, and electrospun these with methacrylated hyaluronic acid (MeHA) to form HepMAHA and HepSHHA nanofibers. For loaded conditions, MeHA, HepMAHA, and HepSHHA fibers were incubated with soluble basic fibroblast growth factor (bFGF) or nerve growth factor (NGF) and rinsed with PBS. Control groups were hydrated in PBS. L929 fibroblast proliferation was analyzed after 24 hr of culture in either growth media or bFGF-supplemented media. Dissociated chick dorsal root ganglia neurites were measured after 3 days of cell culture in serum free media (SFM) or NGF-supplemented SFM (SFM + NGF). In growth media, fibroblast proliferation was significantly increased in loaded HepMAHA (α < .05) compared to other groups. In SFM, loaded HepMAHA had the longest average neurite length compared to all other groups. In SFM + NGF, HepMAHA and HepSHHA had increased neurite lengths compared to MeHA, regardless of loading (α < .01), suggesting active sequestration of soluble NGF. HepMAHA is a promising biomaterial for sequestering released GFs in a spinal cord injury environment and will be combined with GF filled microspheres for future studies.