Hyaluronan enhances wound repair and increases collagen III in aged dermal wounds

Age-related changes in the extracellular matrix contribute to delayed wound repair in aging. Hyaluronan, a linear nonsulfated glycosaminoglycan, promotes synthesis and assembly of key extracellular matrix components, such as the interstitial collagens, during wound healing. The biological effects of hyaluronan are mediated, in part, by hyaluronan size. We have previously determined that dermal wounds in aged mice, relative to young mice, have deficits in the generation of lower molecular weight hyaluronan (defined as <300 kDa). Here, we tested the effect of exogenous hyaluronan of 2, 250, or 1,000 kDa sizes on full-thickness excisional wounds in aged mice. Only wounds treated with 250 kDa hyaluronan (HA250) were significantly improved over wounds that received carrier (water) alone. Treatment with HA250 was associated with increased expression of transcripts for the hyaluronan receptors CD44 and RHAMM, as well as collagens III and I. Analyses of dermal protein content by mass spectrometry and Western blotting confirmed significantly increased expression of collagen III in wounds treated with HA250 relative to control wounds. In summary, we find that HA250 improves wound repair and increases the synthesis of collagen III in aged dermal wounds.