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Polyphosphate in Chronic Wound Healing: Restoration of Impaired Metabolic Energy State

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Inorganic Polyphosphates

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 61))

Abstract

Many pathological conditions are characterized by a deficiency of metabolic energy. A prominent example is nonhealing or difficult-to-heal chronic wounds. Because of their unique ability to serve as a source of metabolic energy, inorganic polyphosphates (polyP) offer the opportunity to develop novel strategies to treat such wounds. The basis is the generation of ATP from the polymer through the joint action of two extracellular or plasma membrane-bound enzymes alkaline phosphatase and adenylate kinase, which enable the transfer of energy-rich phosphate from polyP to AMP with the formation of ADP and finally ATP. Building on these findings, it was possible to develop novel regeneratively active materials for wound therapy, which have already been successfully evaluated in first studies on patients.

Xiaohong Wang and Hadrian Schepler contributed equally to this work.

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References

  • Abdel Malik R, Zippel N, Frömel T, Heidler J, Zukunft S, Walzog B, Ansari N, Pampaloni F, Wingert S, Rieger MA, Wittig I, Fisslthaler B, Fleming I (2017) AMP-activated protein kinase α2 in neutrophils regulates vascular repair via hypoxia-inducible factor-1α and a network of proteins affecting metabolism and apoptosis. Circ Res 120:99–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Agren MS (1993) Zinc oxide increases degradation of collagen in necrotic wound tissue. Br J Dermatol 129:221–222

    Article  CAS  PubMed  Google Scholar 

  • Atkinson DE (1968) The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry 7:4030–4034

    Article  CAS  PubMed  Google Scholar 

  • Bae WJ, Auh QS, Kim GT, Moon JH, Kim EC (2016) Effects of sodium tri- and hexameta-phosphate in vitro osteoblastic differentiation in periodontal ligament and osteoblasts, and in vivo bone regeneration. Differentiation 92:257–269

    Article  CAS  PubMed  Google Scholar 

  • Balakrishnan B, Jayakrishnan A (2005) Self-cross-linking biopolymers as injectable in situ forming biodegradable scaffolds. Biomaterials 26:3941–3951

    Article  CAS  PubMed  Google Scholar 

  • Barysch MJ, Läuchli S (2020) Oxygen therapy in wound healing. In: Alavi A, Maibach H (eds) Local wound care for dermatologists. Updates in clinical dermatology. Springer, Cham. https://doi.org/10.1007/978-3-030-28872-3_12

    Chapter  Google Scholar 

  • Beidler SK, Douillet CD, Berndt DF, Keagy BA, Rich PB, Marston WA (2009) Inflammatory cytokine levels in chronic venous insufficiency ulcer tissue before and after compression therapy. J Vasc Surg 49:1013–1020

    Article  PubMed  PubMed Central  Google Scholar 

  • Carling D, Zammit VA, Hardie DG (1987) A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett 223:217–222

    Article  CAS  PubMed  Google Scholar 

  • Chattopadhyay S, Raines RT (2014) Collagen-based biomaterials for wound healing. Biopolymers 101:821–833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chicharro-Alcántara D, Rubio-Zaragoza M, Damiá-Giménez E, Carrillo-Poveda JM, Cuervo-Serrato B, Peláez-Gorrea P, Sopena-Juncosa JJ (2018) Platelet rich plasma: new insights for cutaneous wound healing management. J Funct Biomater 9:10

    Article  PubMed Central  CAS  Google Scholar 

  • Docampo R, Ulrich P, Moreno SN (2010) Evolution of acidocalcisomes and their role in polyphosphate storage and osmoregulation in eukaryotic microbes. Philos Trans R Soc Lond Ser B Biol Sci 365:775–784

    Article  CAS  Google Scholar 

  • Ghahramani Z (2015) Probabilistic machine learning and artificial intelligence. Nature 521:452–459

    Article  CAS  PubMed  Google Scholar 

  • Gosain A, DiPietro LA (2004) Aging and wound healing. World J Surg 28:321–326

    Article  PubMed  Google Scholar 

  • Guo S, DiPietro LA (2010) Factors affecting wound healing. J Dent Res 89:219–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han G, Ceilley R (2017) Chronic wound healing: a review of current management and treatments. Adv Ther 34:599–610

    Article  PubMed  PubMed Central  Google Scholar 

  • Hardie DG (2004) AMP-activated protein kinase: the guardian of cardiac energy status. J Clin Invest 114:465–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785

    Article  CAS  PubMed  Google Scholar 

  • Hardie DG, Hawley SA, Scott JW (2006) AMP-activated protein kinase: development of the energy sensor concept. J Physiol 574:7–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardie DG, Schaffer BE, Brunet A (2016) AMPK: an energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol 26:190–201

    Article  CAS  PubMed  Google Scholar 

  • Hu T, Xu H, Wang C, Qin H, An Z (2018) Magnesium enhances the chondrogenic differentiation of mesenchymal stem cells by inhibiting activated macrophage-induced inflammation. Sci Rep 8:3406

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Huang H, Wang L, Qian F, Chen X, Zhu H, Yang M, Zhang C, Chu M, Wang X, Huang X (2021) Liraglutide via activation of AMP-activated protein kinase-hypoxia inducible factor-1α-heme oxygenase-1 signaling promotes wound healing by preventing endothelial dysfunction in diabetic mice. Front Physiol 12:660263

    Article  PubMed  PubMed Central  Google Scholar 

  • Im MJ, Hoopes JE (1970) Energy metabolism in healing skin wounds. J Surg Res 10:459–464

    Article  CAS  PubMed  Google Scholar 

  • Jang WG, Kim EJ, Lee KN, Son HJ, Koh JT (2011) AMP-activated protein kinase (AMPK) positively regulates osteoblast differentiation via induction of Dlx5-dependent Runx2 expression in MC3T3E1 cells. Biochem Biophys Res Commun 404:1004–1009

    Article  CAS  PubMed  Google Scholar 

  • Jejurikar A, Seow XT, Lawrie G, Martin D, Jayakrishnan A, Grøndahl (2012) Degradable alginate hydrogels crosslinked by the macromolecular crosslinker alginate dialdehyde. J Mater Chem 22:9751–9758

    Google Scholar 

  • Karu TI (2010) Multiple roles of cytochrome c oxidase in mammalian cells under action of red and IR-A radiation. IUBMB Life 62:607–610

    Article  CAS  PubMed  Google Scholar 

  • Kaushika M, Niranjana R, Ramar T, Balaraman M, Pandiyarasan V, Ramachandran C, Oh DH, Devan GV (2019) Investigations on the antimicrobial activity and wound healing potential of ZnO nanoparticles. Appl Surf Sci 479:1169–1177

    Article  CAS  Google Scholar 

  • Kiritsi D, Nyström A (2018) The role of TGFβ in wound healing pathologies. Mech Ageing Dev 172:51–58

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi K, Maeda K, Takefuji M, Kikuchi R, Morishita Y, Hirashima M, Murohara T (2017) Dynamics of angiogenesis in ischemic areas of the infarcted heart. Sci Rep 7:7156

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kogan S, Sood A, Garnick MS (2017) Zinc and wound healing: a review of zinc physiology and clinical applications. Wounds 29:102–106

    PubMed  Google Scholar 

  • Kotwal GJ, Sarojini H, Chien S (2015) Pivotal role of ATP in macrophages fast tracking wound repair and regeneration. Wound Repair Regen 23:724–727

    Article  PubMed  Google Scholar 

  • Lansdown AB (1993) Influence of zinc oxide in the closure of open skin wounds. Int J Cosmet Sci 15:83–85

    Article  CAS  PubMed  Google Scholar 

  • Lansdown AB, Mirastschijski U, Stubbs N, Scanlon E, Agren MS (2007) Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound Repair Regen 15:2–16

    Article  PubMed  Google Scholar 

  • Leyane TS, Jere SW, Houreld NN (2021) Cellular signalling and photobiomodulation in chronic wound repair. Int J Mol Sci 22:11223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin JT, Chen HM, Chiu CH, Liang YJ (2014) AMP-activated protein kinase activators in diabetic ulcers: from animal studies to phase II drugs under investigation. Expert Opin Investig Drugs 23:1253–1265

    Article  CAS  PubMed  Google Scholar 

  • Lin PH, Sermersheim M, Li H, Lee PHU, Steinberg SM, Ma J (2017) Zinc in wound healing modulation. Nutrients 10:pii: E16

    Article  CAS  Google Scholar 

  • Lorenz B, Schröder HC (2001) Mammalian intestinal alkaline phosphatase acts as highly active exopolyphosphatase. Biochim Biophys Acta 1547:254–261

    Article  CAS  PubMed  Google Scholar 

  • Martin YH, Jubin K, Smalley S, Wong JPF, Brown RA, Metcalfe AD (2017) A novel system for expansion and delivery of human keratinocytes for the treatment of severe cutaneous injuries using microcarriers and compressed collagen. J Tissue Eng Regen Med 11:3124–3133

    Article  CAS  PubMed  Google Scholar 

  • Mirastschijski U, Haaksma CJ, Tomasek JJ, Agren MS (2004) Matrix metalloproteinase inhibitor GM 6001 attenuates keratinocyte migration, contraction and myofibroblast formation in skin wounds. Exp Cell Res 299:465–475

    Article  CAS  PubMed  Google Scholar 

  • Mo Y, Sarojini H, Wan R, Zhang Q, Wang J, Eichenberger S, Kotwal GJ, Chien S (2020) Intracellular ATP delivery causes rapid tissue regeneration via upregulation of cytokines, chemokines, and stem cells. Front Pharmacol 10:1502

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moehring F, Cowie AM, Menzel AD, Weyer AD, Grzybowski M, Arzua T, Geurts AM, Palygin O, Stucky CL (2018) Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling. elife 7:pii:e31684

    Article  Google Scholar 

  • Morrissey JH, Choi SH, Smith SA (2012) Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation. Blood 119:5972–5979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Müller WEG, Wang XH, Diehl-Seifert B, Kropf K, Schloßmacher U, Lieberwirth I, Glasser G, Wiens M, Schröder HC (2011) Inorganic polymeric phosphate/polyphosphate is an inducer of alkaline phosphatase and a modulator of intracellular Ca2+ level in osteoblasts (SaOS-2 cells) in vitro. Acta Biomater 7:2661–2671

    Article  PubMed  CAS  Google Scholar 

  • Müller WEG, Tolba E, Dorweiler B, Schröder HC, Diehl-Seifert B, Wang XH (2015a) Electrospun bioactive mats enriched with Ca-polyphosphate/retinol nanospheres as potential wound dressing. Biochem Biophys Rep 3:150–160

    PubMed  PubMed Central  Google Scholar 

  • Müller WEG, Tolba E, Feng Q, Schröder HC, Markl JS, Kokkinopoulou M, Wang XH (2015b) Amorphous Ca2+ polyphosphate nanoparticles regulate the ATP level in bone-like SaOS-2 cells. J Cell Sci 128:2202–2207

    Article  PubMed  CAS  Google Scholar 

  • Müller WEG, Tolba E, Schröder HC, Diehl-Seifert B, Wang XH (2015c) Retinol encapsulated into amorphous Ca2+ polyphosphate nanospheres acts synergistically in MC3T3-E1 cells. Eur J Pharm Biopharm 93:214–223

    Article  PubMed  CAS  Google Scholar 

  • Müller WEG, Tolba E, Schröder HC, Neufurth M, Wang SF, Link T, Al-Nawas B, Wang XH (2015d) A new printable and durable N,O-carboxymethyl chitosan-Ca2+-polyphosphate complex with morphogenetic activity. J Mater Chem B 3:1722–1730

    Google Scholar 

  • Müller WEG, Tolba E, Schröder HC, Wang XH (2015e) Polyphosphate: a morphogenetically active implant material serving as metabolic fuel for bone regeneration. Macromolec Biosci 15:1182–1197

    Article  CAS  Google Scholar 

  • Müller WEG, Tolba E, Schröder HC, Wang SF, Glaßer G, Muñoz-Espí R, Link T, Wang XH (2015f) A new polyphosphate calcium material with morphogenetic activity. Mater Lett 148:163–166

    Article  CAS  Google Scholar 

  • Müller WEG, Ackermann M, Tolba E, Neufurth M, Wang S, Schröder HC, Wang XH (2016) A bio-imitating approach to fabricate an artificial matrix for cartilage tissue engineering using magnesium-polyphosphate and hyaluronic acid. RSC Adv 6:88559–88570

    Article  Google Scholar 

  • Müller WEG, Neufurth M, Tolba E, Ackermann M, Korzhev M, Wang S, Feng Q, Schröder HC, Wang XH (2017a) Bifunctional dentifrice: amorphous polyphosphate a regeneratively active sealant with potent anti-Streptococcus mutans activity. Dent Mater 33:753–764

    Article  PubMed  CAS  Google Scholar 

  • Müller WEG, Relkovic D, Ackermann M, Wang S, Neufurth M, Paravic-Radicevic A, Ushijima H, Schröder HC, Wang XH (2017b) Enhancement of wound healing in normal and diabetic mice by topical application of amorphous polyphosphate – superior effect of the host-guest composite material composed of collagen (host) and polyphosphate (guest). Polymers 9:300

    Article  PubMed Central  CAS  Google Scholar 

  • Müller WEG, Tolba E, Ackermann M, Neufurth M, Wang S, Feng Q, Schröder HC, Wang XH (2017c) Fabrication of amorphous strontium polyphosphate microparticles that induce mineralization of bone cells in vitro and in vivo. Acta Biomater 50:89–101

    Article  PubMed  CAS  Google Scholar 

  • Müller WEG, Wang SF, Ackermann M, Neufurth M, Steffen R, Mecja E, Muñoz-Espí R, Feng QL, Schröder HC, Wang XH (2017d) Rebalancing β-amyloid-induced decrease of ATP level by amorphous nano/micro polyphosphate: suppression of the neurotoxic effect of amyloid β-protein fragment 25-35. Int J Mol Sci 18:2154

    Article  PubMed Central  CAS  Google Scholar 

  • Müller WEG, Wang SF, Neufurth M, Kokkinopoulou M, Feng Q, Schröder HC, Wang XH (2017e) Polyphosphate as a donor of high-energy phosphate for the synthesis of ADP and ATP. J Cell Sci 130:2747–2756

    PubMed  Google Scholar 

  • Müller WEG, Wang SF, Wiens M, Neufurth M, Ackermann M, Relkovic D, Kokkinopoulou M, Feng Q, Schröder HC, Wang XH (2017f) Uptake of polyphosphate microparticles in vitro (SaOS-2 and HUVEC cells) followed by an increase of the intracellular ATP pool size. PLoS One 12(12):e0188977

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Müller WEG, Ackermann M, Tolba E, Neufurth M, Ivetac I, Kokkinopoulou M, Schröder HC, Wang XH (2018a) Role of ATP during the initiation of microvascularization. Acceleration of an autocrine sensing mechanism facilitating chemotaxis by inorganic polyphosphate. Biochemist J 3255–3273

    Google Scholar 

  • Müller WEG, Ackermann M, Wang SF, Neufurth M, Muñoz-Espí R, Feng QL, Schröder HC, Wang XH (2018b) Inorganic polyphosphate induces accelerated tube formation of HUVEC endothelial cells. Cell Mol Life Sci 75:21–32

    Article  PubMed  CAS  Google Scholar 

  • Müller WEG, Wang S, Tolba E, Neufurth M, Ackermann M, Muñoz-Espí R, Lieberwirth I, Glasser G, Schröder HC, Wang XH (2018c) Transformation of amorphous polyphosphate nanoparticles into coacervate complexes: an approach for the encapsulation of mesenchymal stem cells. Small 14:e1801170

    Article  PubMed  CAS  Google Scholar 

  • Müller WEG, Schröder HC, Wang XH (2019a) Inorganic polyphosphates as storage for and generator of metabolic energy in the extracellular matrix. Chem Rev 119:12337–12374

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Müller WEG, Schröder HC, Wang XH (2019b) The phosphoanhydride bond: one cornerstone of life. Biochem (Lond) 41:22–27

    Article  Google Scholar 

  • Müller WEG, Schepler H, Tolba E, Wang SF, Ackermann M, Muñoz-Espí R, Xiao S, Tan RW, She ZD, Neufurth M, Schröder HC, Wang XH (2020) A physiologically active interpenetrating collagen network that supports growth and migration of epidermal keratinocytes: zinc-polyP nanoparticles integrated into compressed collagen. J Mater Chem B 8:5892–5902

    Article  PubMed  Google Scholar 

  • Nesbeth DN, Zaikin A, Saka Y, Romano MC, Giuraniuc CV, Kanakov O, Laptyeva T (2016) Synthetic biology routes to bio-artificial intelligence. Essays Biochem 60:381–391

    Article  PubMed  PubMed Central  Google Scholar 

  • Neufurth M, Wang XH, Wang SF, Steffen R, Ackermann M, Haep ND, Schröder HC, Müller WEG (2017) 3D printing of hybrid (bio)materials for bone tissue engineering: calcium-polyphosphate microparticles encapsulated by polycaprolactone. Acta Biomater 64:377–388

    Article  CAS  PubMed  Google Scholar 

  • Nurden AT (2018) The biology of the platelet with special reference to inflammation, wound healing and immunity. Front Biosci (Landmark Ed) 23:726–751

    Article  CAS  Google Scholar 

  • Oakhill JS, Scott JW, Kemp BE (2009) Structure and function of AMP-activated protein kinase. Acta Physiol (Oxf) 196:3–14

    Article  CAS  Google Scholar 

  • Oakhill JS, Steel R, Chen ZP, Scott JW, Ling N, Tam S, Kemp BE (2011) AMPK is a direct adenylate charge-regulated protein kinase. Science 332:1433–1435

    Article  CAS  PubMed  Google Scholar 

  • Omura J, Satoh K, Kikuchi N, Satoh T, Kurosawa R, Nogi M, Otsuki T, Kozu K, Numano K, Suzuki K, Sunamura S, Tatebe S, Aoki T, Sugimura K, Miyata S, Hoshikawa Y, Okada Y, Shimokawa H (2016) Protective roles of endothelial AMP-activated protein kinase against hypoxia-induced pulmonary hypertension in mice. Circ Res 119:197–209

    Article  CAS  PubMed  Google Scholar 

  • Paneni F, Beckman JA, Creager MA, Cosentino F (2013) Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J 34:2436–2443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pavlica S, Gaunitz F, Gebhardt R (2009) Comparative in vitro toxicity of seven zinc-salts towards neuronal PC12 cells. Toxicol In Vitro 23:653–659

    Article  CAS  PubMed  Google Scholar 

  • Rader BA (2017) Alkaline phosphatase, an unconventional immune protein. Front Immunol 8:897

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Reinke JM, Sorg H (2012) Wound repair and regeneration. Eur Surg Res 49:35–43

    Article  CAS  PubMed  Google Scholar 

  • Rittié L (2016) Cellular mechanisms of skin repair in humans and other mammals. J Cell Commun Signal 10:103–120

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodríguez C, Muñoz M, Contreras C, Prieto D (2021) AMPK, metabolism, and vascular function. FEBS J 288:3746–3771

    Article  PubMed  CAS  Google Scholar 

  • Rolfe DF, Brown GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77:731–758

    Article  CAS  PubMed  Google Scholar 

  • Saghazadeh S, Rinoldi C, Schot M, Kashaf SS, Sharifi F, Jalilian E, Nuutila K, Giatsidis G, Mostafalu P, Derakhshandeh H, Yue K, Swieszkowski W, Memic A, Tamayol A, Khademhosseini A (2018) Drug delivery systems and materials for wound healing applications. Adv Drug Deliv Rev 127:138–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarker B, Papageorgiou DG, Silva R, Zehnder T, Gul-E-Noor F, Bertmer M, Kaschta J, Chrissafis K, Detsch R, Boccaccini AR (2014) Fabrication of alginate-gelatin crosslinked hydrogel microcapsules and evaluation of the microstructure and physico-chemical properties. J Mater Chem B 2:1470–1482

    Article  CAS  PubMed  Google Scholar 

  • Sarker B, Singh R, Zehnder T, Forgber T, Alexiou C, Cicha I, Detsch R, Boccaccini AR (2017) Macromolecular interactions in alginate-gelatin hydrogels regulate the behavior of human fibroblasts. J Bioact Compat Polym 32:309–324

    Article  CAS  Google Scholar 

  • Sarojini H, Billeter AT, Eichenberger S, Druen D, Barnett R, Gardner SA, Galbraith NJ, Polk HC Jr, Chien S (2017) Rapid tissue regeneration induced by intracellular ATP delivery-a preliminary mechanistic study. PLoS One 12:e0174899

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schepler H, Neufurth M, Wang SF, She Z, Schröder HC, Wang XH, Müller WEG (2022) Acceleration of chronic wound healing by bio-inorganic polyphosphate: in vitro studies and first clinical applications. Theranostics 12:18–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schröder HC, Tolba E, Diehl-Seifert B, Wang XH, Müller WEG (2017) Electrospinning of bioactive wound healing nets. In: Müller WEG, Schröder HC, Wang XH (eds) BlueGenics – from gene to bioactive product: exploiting marine genomics for an innovative and sustainable European blue biotechnology industry. Springer, Berlin. Prog Mol Subcell Biol 55:259–290

    Article  PubMed  CAS  Google Scholar 

  • Schröder HC, Wang XH, Müller WEG (2019) Amorphous polyphosphate nanoparticles: application of the morphogenetically active inorganic polymer for personalized tissue regeneration. J Phys D Appl Phys 52:363001

    Article  CAS  Google Scholar 

  • Simbulan-Rosenthal CM, Gaur A, Sanabria VA, Dussan LJ, Saxena R, Schmidt J, Kitani T, Chen YS, Rahim S, Uren A, Crooke E, Rosenthal DS (2015) Inorganic polyphosphates are important for cell survival and motility of human skin keratinocytes. Exp Dermatol 24:636–639

    Article  CAS  PubMed  Google Scholar 

  • Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341:738–746

    Article  CAS  PubMed  Google Scholar 

  • Sorimachi K (1987) Activation of alkaline phosphatase with Mg2+ and Zn2+ in rat hepatoma cells. Accumulation of apoenzyme. J Biol Chem 262:1535–1541

    Article  CAS  PubMed  Google Scholar 

  • Takeo M, Lee W, Ito M (2015) Wound healing and skin regeneration. Cold Spring Harb Perspect Med 5:a023267

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tandara AA, Mustoe TA (2004) Oxygen in wound healing—more than a nutrient. World J Surg 28:294–300

    Google Scholar 

  • Tousoulis D, Papageorgiou N, Androulakis E, Siasos G, Latsios G, Tentolouris K, Stefanadis C (2013) Diabetes mellitus-associated vascular impairment: novel circulating biomarkers and therapeutic approaches. J Am Coll Cardiol 62:667–676

    Article  CAS  PubMed  Google Scholar 

  • Trautmann A (2009) Extracellular ATP in the immune system: more than just a “danger signal”. Sci Signal 2(pe6)

    Google Scholar 

  • Trefts E, Shaw RJ (2021) AMPK: restoring metabolic homeostasis over space and time. Mol Cell 81:3677–3690

    Article  CAS  PubMed  Google Scholar 

  • Ungvari Z, Tarantini S, Donato AJ, Galvan V, Csiszar A (2018) Mechanisms of vascular aging. Circ Res 123:849–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang XH, Ackermann M, Tolba E, Neufurth M, Wurm F, Feng Q, Wang S, Schröder HC, Müller WEG (2016a) Artificial cartilage bio-matrix formed of hyaluronic acid and Mg2+-polyphosphate. Eur Cell Mater 32:271–283

    Article  CAS  PubMed  Google Scholar 

  • Wang XH, Ackermann M, Wang S, Tolba E, Neufurth M, Feng Q, Schröder HC, Müller WEG (2016b) Amorphous polyphosphate/amorphous calcium carbonate implant material with enhanced bone healing efficacy in a critical-size-defect in rats. Biomed Mater 11:035005

    Article  PubMed  CAS  Google Scholar 

  • Wang XH, Schröder HC, Müller WEG (2016c) Polyphosphate as a metabolic fuel in Metazoa: a foundational breakthrough invention for biomedical applications. Biotechnol J 11:11–30

    Article  CAS  PubMed  Google Scholar 

  • Wang XH, Wang S, He F, Tolba E, Schröder HC, Diehl-Seifert B, Müller WEG (2016d) Polyphosphate as a bioactive and biodegradable implant material: induction of bone regeneration in rats. Adv Engin Mat 18:1406–1417

    Article  CAS  Google Scholar 

  • Wang XH, Ackermann M, Neufurth M, Wang SF, Li Q, Feng QL, Schröder HC, Müller WEG (2017) Restoration of impaired metabolic energy balance (ATP pool) and tube formation potential of endothelial cells under “high glucose”, diabetic conditions by the bioinorganic polymer polyphosphate. Polymers 9:575

    Article  PubMed Central  CAS  Google Scholar 

  • Wang XH, Schröder HC, Müller WEG (2018) Amorphous polyphosphate, a smart bioinspired nano−/bio-material for bone and cartilage regeneration: towards a new paradigm in tissue engineering. J Mat Chem B 6:2385–2412

    Article  CAS  Google Scholar 

  • Wang J, Li J, Song D, Ni J, Ding M, Huang J, Yan M (2020a) AMPK: implications in osteoarthritis and therapeutic targets. Am J Transl Res 12:7670–7681

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang SF, Wang XH, Neufurth M, Tolba E, Schepler H, Xiao S, Schröder HC, Müller WEG (2020b) Biomimetic alginate/gelatin cross-linked hydrogels supplemented with polyphosphate for wound healing applications. Molecules 25:5210

    Article  CAS  PubMed Central  Google Scholar 

  • Wang Z, Shen J, Feng E, Jiao Y (2021) AMPK as a potential therapeutic target for intervertebral disc degeneration. Front Mol Biosci 8:789087

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yan Y, Zhou XE, Xu HE, Melcher K (2018) Structure and physiological regulation of AMPK. Int J Mol Sci 19:3534

    Article  PubMed Central  CAS  Google Scholar 

  • Yegutkin GG (2008) Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta 1783:673–694

    Article  CAS  PubMed  Google Scholar 

  • Yi D, Yu H, Lu K, Ruan C, Ding C, Tong L, Zhao X, Chen D (2021) AMPK signaling in energy control, cartilage biology, and osteoarthritis. Front Cell Dev Biol 9:696602

    Article  PubMed  PubMed Central  Google Scholar 

  • Yin J, Xu K, Zhang J, Kumar A, Yu FS (2007) Wound-induced ATP release and EGF receptor activation in epithelial cells. J Cell Sci 120:815–825

    Article  CAS  PubMed  Google Scholar 

  • Yokouchi M, Atsugi T, Logtestijn MV, Tanaka RJ, Kajimura M, Suematsu M, Furuse M, Amagai M, Kubo A (2016) Epidermal cell turnover across tight junctions based on Kelvin’s tetrakaidecahedron cell shape. elife 5:e19593

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu S, Sathi GA, Yamamoto O (2016) In vivo evaluation of wound healing property of zinc smectite using a rat model. J Ceramic Soc Jpn 124:1199–1204

    Google Scholar 

  • Zhang K, Wang S, Zhou C, Cheng L, Gao X, Xie X, Sun J, Wang H, Weir MD, Reynolds MA, Zhang N, Bai Y, Xu HHK (2018) Advanced smart biomaterials and constructs for hard tissue engineering and regeneration. Bone Res 6:31

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgments

W.E.G.M. is a holder of an ERC Advanced Investigator Grant (No. 268476). In addition, W.E.G.M. obtained three ERC-PoC grants (Si-Bone-PoC, No. 324564; MorphoVES-PoC, No. 662486; and ArthroDUR, No. 767234). We also acknowledge funding from the European Commission (grants BIO-SCAFFOLDS No. 604036 and BlueGenics No. 311848). Finally, this work was supported by a grant from the Federal Minister of Education and Research (No. 13GW0403B) and the BiomaTiCS research initiative of the University Medical Center, Mainz.

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    Authors and Affiliations

    1. ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

      Xiaohong Wang, Meik Neufurth, Shunfeng Wang, Heinz C. Schröder & Werner E. G. Müller

    2. Department of Dermatology, University Clinic Mainz, Mainz, Germany

      Hadrian Schepler

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    1. Xiaohong Wang
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    2. Hadrian Schepler
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    6. Werner E. G. Müller
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    Correspondence to Werner E. G. Müller .

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    Editors and Affiliations

    1. ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

      Werner E. G. Müller

    2. ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

      Heinz C. Schröder

    3. Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA

      Patrick Suess

    4. ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

      Xiaohong Wang

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    Wang, X., Schepler, H., Neufurth, M., Wang, S., Schröder, H.C., Müller, W.E.G. (2022). Polyphosphate in Chronic Wound Healing: Restoration of Impaired Metabolic Energy State. In: Müller, W.E.G., Schröder, H.C., Suess, P., Wang, X. (eds) Inorganic Polyphosphates. Progress in Molecular and Subcellular Biology, vol 61. Springer, Cham. https://doi.org/10.1007/978-3-031-01237-2_4

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