Enhancement of Wound Healing in Normal and Diabetic Mice by Topical Application of Amorphous Polyphosphate. Superior Effect of a Host–Guest Composite Material Composed of Collagen (Host) and Polyphosphate (Guest)

Abstract

The effect of polyphosphate (polyP) microparticles on wound healing was tested both in vitro and in a mice model in vivo. Two approaches were used: pure salts of polyphosphate, fabricated as amorphous microparticles (MPs, consisting of calcium and magnesium salts of polyP, "Ca⁻polyp-MPs" and "Mg⁻polyp-MPs"), and host⁻guest composite particles, prepared from amorphous collagen (host) and polyphosphate (guest), termed "col/polyp-MPs". Animal experiments with polyP on healing of excisional wounds were performed using both normal mice and diabetic mice. After a healing period of 7 days "Ca⁻polyp-MP" significantly improved re-epithelialization in normal mice from 31% (control) to 72% (polyP microparticle-treated). Importantly, in diabetic mice, particularly the host⁻guest particles "col/polyp-MP", increased the rate of re-epithelialization to ≈40% (control, 23%). In addition, those particles increased the expression of COL-I and COL-III as well as the expression the α-smooth muscle actin and the plasminogen activator inhibitor-1. We propose that "Ca⁻polyp-MPs", and particularly the host⁻guest "col/polyp-MPs" are useful for topical treatment of wounds.