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 physi-ological inorganic ...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 physi-ological 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 amor-phous 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 forma-tion.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.展开更多
基金We are very much grateful to Dr.Beate Weidenthaler-Barth(De-partment of Dermatology,University Clinic Mainz)for the very expert histological analyses and the permission to include the images in this study.Moreover,we thank Mrs.Kerstin Bahr,Institute of Functional and Clinical Anatomy,University Medical Center,Mainz(Germany)for her continuous support.In addition,we are thankful to Mrs.Franziska S.Kranz(Medical Center of the Jo-hannes Gutenberg University,Mainz)for her important support.W.E.G.Müller is the holder of an ERC Advanced Investigator Grant(Grant No.268476)In addition,W.E.G.Müller has obtained three ERC-PoC grants(Si-Bone-PoC,Grant No.324564,MorphoVES-PoC,Grant No.662486,and ArthroDUR,Grant No.767234)+3 种基金In addition,this work was supported by grants from the European Commission(Grant Nos.604036 and 311848)the International Human Frontier Science Program,and the BiomaTiCS research initiative of the University Medical Center,Mainz.Further support came from the BMBF(Grant No.13GW0403A/B-SKIN-ENERGY)the BMWi(Grant No.ZF4294002AP9)the China National Key R&D Plan:China-German Cooperation(Grant No.2018YFE0194300).
文摘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 physi-ological 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 amor-phous 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 forma-tion.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.
