Polyphosphate: A Morphogenetically Active Implant Material Serving as Metabolic Fuel for Bone Regeneration

Abstract

The initial mineralization centers during human bone formation onto osteoblasts are composed of CaCO 3 . Those bioseeds are enzymatically formed via carbonic anhydrase(s) in close association with the cell surface of the osteoblasts. Subsequently, the bicarbonate/ carbonate anions are exchanged non-enzymatically by inorganic phosphate [P i ]. One source for the supply of P i is polyphosphate [polyP] which is a physiological polymer, formed in the osteoblasts as well as in the platelets. The energy-rich acid anhydride bonds within the polyP chain are cleaved by phosphatase(s); during this reaction free-energy might be released that could be re-used, as metabolic fuel, for the maintenance of the steady-state concentrations of the substrates/products during mineralization. Finally it is outlined that polyP, as a morphogenetically active scaffold, is even suitable for 3D cell printing.

Artificial cartilage bio-matrix formed of hyaluronic acid and Mg2+-polyphosphate

“…Recently, our group provided experimental evidence that polyphosphate (polyP), abundantly present both intracellularly and extracellularly as well as in blood platelets (Morrissey et al, 2012), could serve as an energy source for the generation of chemically utilisable Gibbs free energy after cleavage by ALP (reviewed in: Müller et al, 2015a;Wang et al, 2016). Blood platelets exist in large numbers in synovial fluids from patients with rheumatoid arthritis but are scarce in fluids from osteoarthritis patients, where the density varies between 0 and 10,000/mm 3 (Farr et al, 1984).…”

A Novel Biomimetic Approach to Repair Enamel Cracks/Carious Damages and to Reseal Dentinal Tubules by Amorphous Polyphosphate

“…Recently we succeeded to fabricate Ca 2+ -polyP salt complexes, nanoparticles and microparticles that are considerably stable and elicit the well-established morphogenetic properties, e.g. the induction of the steady-state-expression of the genes encoding BMP-2 and ALP (reviewed in: [10,13]). Those polyP particles were found to allow the preparation of microspheres that can be potently used as implant material for bone defects [18].…”

“…Recent data indicate that Pi, released from the natural polymer polyphosphate (polyP) through enzymatic, exohydrolytical cleavage via alkaline phosphatase (ALP) acts as a supply of Pi during bone formation [13,14]. This polymer is present in considerable amounts in the circulating blood serum, as well as within cells, especially within blood platelets (reviewed in: [15]).…”

“…ALP and bone morphogenetic protein-2 (BMP-2), as recently reviewed. [12][13][14] Furthermore, in a recent study we recognized that a-polyP microparticles form a tight interaction especially with the dentin of human teeth [17]. This result in concert with the in vivo result showing that polyP, entrapped in PLGA [poly(D,L-lactide-co-glycolide)]-based microspheres, accelerate bone regeneration in calvarial critical-sized defects faster compared to ß-tri-calcium phosphate (ß-TCP) containing spheres [18] suggested an efficient resealing of the dentinal tubules openings as well as a repair of cracks in the enamel.…”

Polyphosphatase PPX1 of <i>Saccharomyces cerevisiae</i> as a Tool for Polyphosphate Assay

“…The signaling cascade including polyP, matrix metalloproteinase (MMP)-3, dentin sialophosphoprotein (DSPP), and dentin matrix protein-1 (DMP-1) is involved in the proliferation of odontoblast-like cells [12]. PolyP is believed to be an active scaffold promising for the treatment of bone diseases, 3D cell printing [13], and the development of bioactive hydrogels capable of enhancing bone tissue growth [14]. Platelet polyP plays an essential role in hemostasis, thrombosis and inflammation [15] [16] and is believed to be a therapeutic target during human blood clotting [17].…”