The expression of sonic hedgehog in diabetic wounds following treatment with poly(methacrylic acid-co-methyl methacrylate) beads.

The expression of native sonic hedgehog (Shh) was significantly increased in poly(methacrylic acid-co-methyl methacrylate) bead (MAA) treated wounds at day 4 compared to both poly(methyl methacrylate) bead (PMMA) treated and untreated wounds in diabetic db/db mice. MAA beads also increased the expression of the Shh transcription factor Gli3 at day 4. Previously, topical application of MAA beads (45 mol % methacrylic acid) improved wound closure and blood vessel density in excisional wounds in these mice, while PMMA beads did not. Gene expression within the granulation tissue of healing wounds was studied to provide insight into the mechanism of vessel formation and wound healing in the presence of MAA beads. In addition to the increased expression of Shh, MAA-treated wounds had increased expression of osteopontin (OPN), IL-1β and TNF-α, (at day 7) similar to the previously reported MAA response of macrophage-like and endothelial cells in vitro.