A GMP-compliant formulation of regeneratively active polyphosphate for wound healing and skin regeneration

Abstract

Inorganic polyphosphate (polyP) is a metabolically relevant biopolymer involved in cellular energy storage and ATP-dependent tissue repair, including skin regeneration and wound healing. Here, a Good Manufacturing Practice (GMP)-compliant sodium polyphosphate formulation (Na-polyP-GMP) was developed and evaluated for regenerative applications, with a commercial polyP preparation used for comparison. Na-polyP-GMP exhibited enhanced physicochemical properties, characterized by a narrow, physiologically relevant chain length distribution and a fully amorphous structure, features associated with improved biological performance. In vitro studies using human keratinocytes and SaOS-2 cells indicated that Na-polyP-GMP supports ATP-dependent cell growth, differentiation, and microvilli formation, effects that were attenuated upon enzymatic ATP depletion, highlighting an energy-related mode of action. In exploratory, non-controlled proof-of-concept applications, topical administration of Na-polyP-GMP was associated with accelerated regeneration of a chronic venous ulcer and a therapy-resistant traumatic ulcer in two human patients, as well as with favorable healing of a persistent bacterially infected wound in a dog following failure of standard therapies. In addition, Na-polyP-GMP enhanced hair regeneration in diabetic mice and ex vivo human skin explants, accompanied by increased hair papillae density, stem cell proliferation, and vascularization. Together, these findings support the regenerative potential of Na-polyP-GMP and establish a foundation for its further exploration in wound healing and skin regeneration applications.