Abstract: Insufficient metabolic energy, in the form of adenosine triphosphate (ATP), and bacterial infections are among the main causes for the development of chronic wounds. Previously we showed that the physiological inorganic polymer polyphosphate (polyP) massively accelerates wound healing both in animals (diabetic mice) and, when incorporated into mats, in patients with chronic wounds. Here, we focused on a hydrogel-based gel formulation, supplemented with both soluble sodium polyP (Na-polyP) and amorphous calcium polyP nanoparticles (Ca-polyP-NP). Exposure of human epidermal keratinocytes to the gel caused a significant increase in extracellular ATP level, an effect that was even enhanced when Na-polyP was combined with Ca-polyP-NP. Furthermore, it is shown that the added polyP in the gel is converted into a coacervate, leading to encapsulation and killing of bacteria. The data on human chronic wounds showed that the administration of hydrogel leads to the complete closure of these wounds. Histological analysis of biopsies showed an increased granulation of the wounds and an enhanced microvessel formation. The results indicate that the polyP hydrogel, due to its properties to entrap bacteria and generate metabolic energy, is a very promising formulation for a new therapy for chronic wounds.

Key words: Inorganic polyphosphate, NanoparticlesHydrogelCoacervate, Human chronic woundsAntibacterial activity, Metabolic energy