Stimulation of in vivo angiogenesis by cytokine-loaded hyaluronic acid hydrogel implants

• Published in: Biomaterials Vol. 25; no. 14; pp. 2789 - 2798
• Main Authors: Peattie, R.A., Nayate, A.P., Firpo, M.A., Shelby, J., Fisher, R.J., Prestwich, G.D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-06-2004
• Subjects: Angiogenesis; Animals; bFGF; Coated Materials, Biocompatible - chemistry; Cytokine; Cytokines - administration & dosage; Cytokines - chemistry; Drug Delivery Systems - methods; Drug Implants - administration & dosage; Ear Cartilage - blood supply; Ear Cartilage - cytology; Ear Cartilage - drug effects; Fibroblast Growth Factor 2 - administration & dosage; Gels - chemistry; Growth factors; Hyaluronic acid; Hyaluronic Acid - chemistry; Hydrogel; Male; Materials Testing; Mice; Mice, Inbred BALB C; Neovascularization, Physiologic - drug effects; Prostheses and Implants; Vascular Endothelial Growth Factor A - administration & dosage; VEGF; Angiogenesis; VEGF; Cytokine; Hydrogel; Hyaluronic acid; Growth factors; bFGF
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2003.09.054

Crosslinked hyaluronic acid (HA) hydrogels were evaluated for their ability to elicit new microvessel growth in vivo when preloaded with one of two cytokines, vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF). HA film samples were surgically implanted in the ear pinnas of mice, and the ears retrieved 7 or 14 days post implantation. Histologic analysis showed that all groups receiving an implant demonstrated significantly more microvessel density than control ears undergoing surgery but receiving no implant (
p<0.01). Moreover, aqueous administration of either growth factor produced substantially more vessel growth than an HA implant with no cytokine. However, the most striking result obtained was a dramatic synergistic interaction between HA and VEGF. Presentation of VEGF in crosslinked HA generated vessel density of
NI=6.7 at day 14, where
NI is a neovascularization index defined below, more than twice the effect of the sum of HA alone (
NI=1.8) plus VEGF alone (
NI=1.3). This was twice the vessel density generated by co-addition of HA and bFGF (
NI=3.4,
p<0.001). New therapeutic approaches for numerous pathologies could be notably enhanced by the localized, synergistic angiogenic response produced by release of VEGF from crosslinked HA films.