0000000000148669

AUTHOR

Emad Tolba

0000-0002-3422-2344

Mineralization of bone-related SaOS-2 cells under physiological hypoxic conditions

Inorganic polyphosphate (polyP) is a physiological energy-rich polymer with multiple phosphoric anhydride bonds. In cells such as bone-forming osteoblasts, glycolysis is the main pathway generating metabolic energy in the form of ATP. In the present study, we show that, under hypoxic culture conditions, the growth/viability of osteoblast-like SaOS-2 cells is not impaired. The addition of polyP to those cells, administered as amorphous calcium polyP nanoparticles (aCa-polyP-NP; approximate size 100 nm), significantly increased the proliferation of the cells. In the presence of polyP, the cells produce significant levels of lactate, the end product of anaerobic glycolysis. Under those conditi…

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Bifunctional dentifrice: Amorphous polyphosphate a regeneratively active sealant with potent anti- Streptococcus mutans activity

Abstract Objective In this study we demonstrate that inorganic polyphosphate (polyP) exhibits a dual protective effect on teeth: it elicits a strong antibacterial effect against the cariogenic bacterium Streptococcus mutans and, in form of amorphous calcium polyP microparticles (size of 100–400 nm), it efficiently reseals cracks/fissures in the tooth enamel and dentin. Methods Three different formulations of amorphous polyP microparticles (Ca-polyP, Zn-polyP and Sr-polyP) were prepared. Results Among the different polyP microparticles tested, the Ca-polyP microparticles, as a component of a newly developed formulation of a dentifrice, turned out to be most effective in inhibiting growth of …

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High biocompatibility and improved osteogenic potential of amorphous calcium carbonate/vaterite.

In human bone, amorphous calcium carbonate (ACC) is formed as a precursor of the crystalline carbonated apatite/hydroxyapatite (HA). Here we describe that the metastable ACC phase can be stabilized by inorganic polyphosphate (polyP) that is also used as a phosphate source for the non-enzymatic carbonate/phosphate exchange during HA formation. This polymer was found to suppress the transformation of ACC into crystalline CaCO3 at a percentage of 5% [w/w] ("CCP5") with respect to CaCO3 and almost completely at 10% [w/w] ("CCP10"). Both preparations (CaCO3/polyP) are amorphous, but also contain small amounts of vaterite, as revealed by XRD, FTIR and SEM analyses. They did not affect the growth/…

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Fabrication of amorphous strontium polyphosphate microparticles that induce mineralization of bone cells in vitro and in vivo.

Abstract Here we describe the fabrication process of amorphous strontium-polyphosphate microparticles (“Sr-a-polyP-MP”). The effects of these particles on growth and gene expression were investigated with SaOS-2 cells as well as with human mesenchymal stem cells (MSC) and compared with those particles prepared of amorphous calcium-polyphosphate (“Ca-a-polyP-MP”) and of strontium salt. The results revealed a markedly higher stimulation of growth of MSC by “Sr-a-polyP-MP” compared to “Ca-a-polyP-MP” and a significant increase in mineralization of SaOS-2 cells, as well as an enhanced upregulation of the expression of the genes encoding for alkaline phosphatase and the bone morphogenetic protei…

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Amorphous polyphosphate/amorphous calcium carbonate implant material with enhanced bone healing efficacy in a critical-size defect in rats

In this study the effect of amorphous calcium carbonate (ACC) microparticles and amorphous calcium polyphosphate (polyP) microparticles (termed aCa-polyP-MP) on bone mineral forming cells/tissue was investigated in vitro and in vivo. The ACC particles (termed ACC-P10-MP) were prepared in the presence of Na-polyP. Only the combinations of polyP and ACC microparticles enhanced the proliferation rate of human mesenchymal stem cells (MSCs). Gene expression studies revealed that ACC causes an upregulation of the expression of the cell membrane-associated carbonic anhydrase IX (CA IX; formation of ACC), while the transcript level of the alkaline phosphatase (ALP; liberation of orthophosphate from…

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Morphogenetically active scaffold for osteochondral repair (Polyphosphate/alginate/N,O-carboxymethyl chitosan)

Here we describe a novel bioinspired hydrogel material that can be hardened with calcium ions to yield a scaffold material with viscoelastic properties matching those of cartilage. This material consists of a negatively charged biopolymer triplet, composed of morphogenetically active natural inorganic polyphosphate (polyP), along with the likewise biocompatible natural polymers N,O-carboxymethyl chitosan (N,O-CMC) and alginate. The porosity of the hardened scaffold material obtained after calcium exposure can be adjusted by varying the pre-processing conditions. Various compression tests were applied to determine the local (nanoindentation) and bulk mechanical properties (tensile/compressio…

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A bio-imitating approach to fabricate an artificial matrix for cartilage tissue engineering using magnesium-polyphosphate and hyaluronic acid

Here we describe an artificial cartilage-like material based on a hyaluronic acid-Mg/Ca-polyphosphate paste (HA-aMg/Ca-polyP-p) that is fabricated from a water-soluble Na-salt of energy-rich inorganic polyphosphate (polyP) and soluble hyaluronic acid in the presence of water-insoluble CaCO3. The resulting material, after conversion of Na-polyP into the less soluble Mg/Ca-salt consisting of amorphous Mg/Ca-polyP microparticles, was found to mimic the physiological cartilage tissue and to bind Ca2+ ions present in the synovial fluid. After the Mg2+/Ca2+ exchange and water extrusion, the polyP becomes more stable, but is still susceptible to hydrolytic cleavage by the alkaline phosphatase (ALP…

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Retinol encapsulated into amorphous Ca2+ polyphosphate nanospheres acts synergistically in MC3T3-E1 cells

Both the quality and quantity of collagen, the major structural component of the skin, decrease in aging skin. We succeeded to encapsulate retinol into amorphous inorganic polyphosphate (polyP) nanoparticles together with calcium ions ("aCa-polyP-NP"), under formation of amorphous Ca-polyP/retinol nanospheres ("retinol/aCa-polyP-NS"). The globular nanospheres are not cytotoxic, show an almost uniform size of ≈ 45 nm and have a retinol content of around 25%. Both components of those nanospheres, retinol and the aCa-polyP-NP, if administered together, caused a strong increase in proliferation of mouse calvaria MC3T3 cells. The expressions of collagen types I, II and III genes, but not the exp…

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Biomimetic transformation of polyphosphate microparticles during restoration of damaged teeth.

Abstract Objective In the present study, we investigated the fusion process between amorphous microparticles of the calcium salt of the physiological polymer comprising orthophosphate units, of inorganic polyphosphate (polyP), and enamel. Methods This polymer was incorporated as an ingredient into toothpaste and the fusion process was studied by electron microscopy and by synchrotron-based X-ray tomography microscopy (SRXTM) techniques. Results The data showed that toothpaste, supplemented with the amorphous Ca-polyP microparticles (aCa-polyP-MP), not only reseals tooth defects on enamel, like carious lesions, and dentin, including exposed dentinal tubules, but also has the potential to ind…

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Fabrication of a new physiological macroporous hybrid biomaterial/bioscaffold material based on polyphosphate and collagen by freeze-extraction

We describe the fabrication of a new scaffold, an inorganic–organic hybrid biomaterial, consisting of the physiological polymers: the inorganic polymer polyphosphate (polyP), as well as the organic macromolecules collagen and chondroitin sulfate. The polyP polymer is composed of multiple phosphate orthophosphate units linked together by high-energy phosphoanhydride bonds. Chondroitin sulfate has been included due to its hydrogel-forming properties. In the presence of Ca2+ ions, the randomly coiled polyP reorganizes together with collagen and chondroitin sulfate to linear molecules which undergo hardening. This scaffold is deposited as amorphous Ca–polyP nanoparticles (size ≈20–40 nm large) …

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A new polyphosphate calcium material with morphogenetic activity

Abstract Polyphosphate [polyP] has been proven to elicit morphogenetic activity on bone cells. By applying mild reaction conditions, a Ca-polyP material that displays a hardness of ≈1.3 GPa has been fabricated. The Ca-polyP granules are prone to hydrolytic degradation during in vitro incubation of the cells, suggesting that this property is associated with the observed bioactivity.

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The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations

Graphical abstract The inorganic physiological polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations. This discovery proposes polyphosphate as a new member of the host's antiviral innate immune defense.

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Biosilica-loaded poly(ϵ-caprolactone) nanofibers mats provide a morphogenetically active surface scaffold for the growth and mineralization of the osteoclast-related SaOS-2 cells.

Bioprinting/3D cell printing procedures for the preparation of scaffolds/implants have the potential to revolutionize regenerative medicine. Besides biocompatibility and biodegradability, the hardness of the scaffold material is of critical importance to allow sufficient mechanical protection and, to the same extent, allow migration, cell–cell, and cell–substrate contact formation of the matrix-embedded cells. In the present study, we present a strategy to encase a bioprinted, cell-containing, and soft scaffold with an electrospun mat. The electrospun poly(e-caprolactone) (PCL) nanofibers mats, containing tetraethyl orthosilicate (TEOS), were subsequently incubated with silicatein. Silicate…

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The biomaterial polyphosphate blocks stoichiometric binding of the SARS-CoV-2 S-protein to the cellular ACE2 receptor

The effect of the polyanionic polymer of inorganic polyphosphate (polyP) involved in innate immunity on the binding of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to the cellular ACE2 receptor was studied. The RBD surface comprises a basic amino acid stretch of four arginine residues which interact with the physiological polyP (polyP40) and polyP3. Subsequently, the interaction of RBD with ACE2 is sensitively inhibited. After the chemical modification of arginine, an increased inhibition by polyP, at a 1 : 1 molar ratio (polyP : RBP), is measured already at 0.1 μg mL−1. Heparin was ineffective. The results suggest a potential therapeutic benefit of polyP against SARS-C…

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In Situ Polyphosphate Nanoparticle Formation in Hybrid Poly(vinyl alcohol)/Karaya Gum Hydrogels: A Porous Scaffold Inducing Infiltration of Mesenchymal Stem Cells

Abstract The preparation and characterization of a porous hybrid cryogel based on the two organic polymers, poly(vinyl alcohol) (PVA) and karaya gum (KG), into which polyphosphate (polyP) nanoparticles have been incorporated, are described. The PVA/KG cryogel is prepared by intermolecular cross‐linking of PVA via freeze‐thawing and Ca2+‐mediated ionic gelation of KG to form stable salt bridges. The incorporation of polyP as amorphous nanoparticles with Ca2+ ions (Ca‐polyP‐NP) is achieved using an in situ approach. The polyP constituent does not significantly affect the viscoelastic properties of the PVA/KG cryogel that are comparable to natural soft tissue. The exposure of the Ca‐polyP‐NP w…

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Role of ATP during the initiation of microvascularization: acceleration of an autocrine sensing mechanism facilitating chemotaxis by inorganic polyphosphate

The in vitro tube formation assay with human umbilical vein endothelial cells (HUVEC) was applied to identify the extra- and intracellular sources of metabolic energy/ATP required for cell migration during the initial stage of microvascularization. Extracellularly, the physiological energy-rich polymer, inorganic polyphosphate (polyP), applied as biomimetic amorphous calcium polyP microparticles (Ca-polyP-MP), is functioning as a substrate for ATP generation most likely via the combined action of the alkaline phosphatase (ALP) and the adenylate kinase (AK). The linear Ca-polyP-MP with a size of 40 phosphate units, close to the polyP in the acidocalcisomes in the blood platelets, were found …

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Amorphous Ca2+ polyphosphate nanoparticles regulate the ATP level in bone-like SaOS-2 cells

ABSTRACT Polyphosphate (polyP) is a physiologically occurring polyanion that is synthesized especially in bone-forming osteoblast cells and blood platelets. We used amorphous polyP nanoparticles, complexed with Ca2+, that have a globular size of ∼100 nm. Because polyP comprises inorganic orthophosphate units that are linked together through high-energy phosphoanhydride bonds, we questioned whether the observed morphogenetic effect, elicited by polyP, is correlated with the energy-generating machinery within the cells. We show that exposure of SaOS-2 osteoblast-like cells to polyP results in a strong accumulation of mitochondria and a parallel translocation of the polyP-degrading enzyme alka…

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Amorphous polyphosphate–hydroxyapatite: A morphogenetically active substrate for bone-related SaOS-2 cells in vitro

There is increasing evidence that inorganic calcium-polyphosphates (polyP) are involved in human bone hydroxyapatite (HA) formation. Here we investigated the morphology of the particles, containing calcium phosphate (CaP) with different concentrations of various Na-polyP concentrations, as well as their effects in cell culture. We used both SaOS-2 cells and human mesenchymal stem cells. The polymeric phosphate readily binds calcium ions under formation of insoluble precipitates. We found that addition of low concentrations of polyP (10wt.%, referred to the CaP deposits) results in an increased size of the HA crystals. Surprisingly, at higher polyP concentrations (10wt.%) the formation of cr…

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Amplified morphogenetic and bone forming activity of amorphous versus crystalline calcium phosphate/polyphosphate.

Amorphous Ca-phosphate (ACP) particles stabilized by inorganic polyphosphate (polyP) were prepared by co-precipitation of calcium and phosphate in the presence of polyP (15% [w/w]). These hybrid nanoparticles showed no signs of crystallinity according to X-ray diffraction analysis, in contrast to the particles obtained at a lower (5% [w/w]) polyP concentration or to hydroxyapatite. The ACP/15% polyP particles proved to be a suitable matrix for cell growth and attachment and showed pronounced osteoblastic and vasculogenic activity in vitro. They strongly stimulated mineralization of the human osteosarcoma cell line SaOS-2, as well as cell migration/microvascularization, as demonstrated in th…

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Modular Small Diameter Vascular Grafts with Bioactive Functionalities.

We report the fabrication of a novel type of artificial small diameter blood vessels, termed biomimetic tissue-engineered blood vessels (bTEBV), with a modular composition. They are composed of a hydrogel scaffold consisting of two negatively charged natural polymers, alginate and a modified chitosan, N,O-carboxymethyl chitosan (N,O-CMC). Into this biologically inert scaffold two biofunctionally active biopolymers are embedded, inorganic polyphosphate (polyP) and silica, as well as gelatin which exposes the cell recognition signal, Arg-Gly-Asp (RGD). These materials can be hardened by exposure to Ca(2+) through formation of Ca(2+) bridges between the polyanions, alginate, N,O-CMC, and polyP…

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Two-Armed Activation of Bone Mineral Deposition by the Flavones Baicalin and Baicalein, Encapsulated in Polyphosphate Microparticles

In this study, we investigated the effect of the two flavonoids, baicalin (baicalein 7-O-[Formula: see text]- d-glucuronic acid) and its aglycone, baicalein (5,6,7-trihydroxyflavone), after encapsulation into amorphous calcium polyphosphate (Ca-polyP) microparticles on mineralization of primary human osteoblasts (phOSB). Both flavonoids, which come from root extracts of Scutellaria baicalensis Georgi, are used in Traditional Chinese Medicine, and are nontoxic in cells up to a concentration of 3[Formula: see text][Formula: see text]g/ml. The morphogenetically active, energy-rich Ca-polyP particles with a stoichiometric P:Ca ratio of 1:2 are degraded by cellular alkaline phosphatase (ALP) to…

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Biocalcite and Carbonic Acid Activators

Based on evolution of biomineralizing systems and energetic considerations, there is now compelling evidence that enzymes play a driving role in the formation of the inorganic skeletons from the simplest animals, the sponges, up to humans. Focusing on skeletons based on calcium minerals, the principle enzymes involved are the carbonic anhydrase (formation of the calcium carbonate-based skeletons of many invertebrates like the calcareous sponges, as well as deposition of the calcium carbonate bioseeds during human bone formation) and the alkaline phosphatase (providing the phosphate for bone calcium phosphate-hydroxyapatite formation). These two enzymes, both being involved in human bone for…

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Biomimetic Alginate/Gelatin Cross-Linked Hydrogels Supplemented with Polyphosphate for Wound Healing Applications

In the present study, the fabrication of a biomimetic wound dressing that mimics the extracellular matrix, consisting of a hydrogel matrix composed of non-oxidized and periodate-oxidized marine alginate, was prepared to which gelatin was bound via Schiff base formation. Into this alginate/oxidized-alginate-gelatin hydrogel, polyP was stably but reversibly integrated by ionic cross-linking with Zn2+ ions. Thereby, a soft hybrid material is obtained, consisting of a more rigid alginate scaffold and porous structures formed by the oxidized-alginate-gelatin hydrogel with ionically cross-linked polyP. Two forms of the Zn-polyP-containing matrices were obtained based on the property of polyP to f…

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

Based on natural principles, we developed a novel toothpaste, containing morphogenetically active amorphous calcium polyphosphate (polyP) microparticles which are enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550 ± 120 nm), prepared by co-precipitating soluble Na-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a base toothpaste at a final concentration of 1% or 10%. The “a-polyP/RA-MP” ingredient significantly enhanced the stimulatory effect of the toothpaste on the growth of human mesenchymal stem cells (MSC). This increase was paralleled by an upregulation of the MSC marker genes for osteoblast differ…

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Transformation of Amorphous Polyphosphate Nanoparticles into Coacervate Complexes: An Approach for the Encapsulation of Mesenchymal Stem Cells.

Inorganic polyphosphate [polyP] has proven to be a promising physiological biopolymer for potential use in regenerative medicine because of its morphogenetic activity and function as an extracellular energy-donating system. Amorphous Ca2+ -polyP nanoparticles [Ca-polyP-NPs] are characterized by a high zeta potential with -34 mV (at pH 7.4). This should contribute to the stability of suspensions of the spherical nanoparticles (radius 94 nm), but make them less biocompatible. The zeta potential decreases to near zero after exposure of the Ca-polyP-NPs to protein/peptide-containing serum or medium plus serum. Electron microscopy analysis reveals that the particles rapidly change into a coacerv…

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

The initial mineralization centers during human bone formation onto osteoblasts are composed of CaCO3 . 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 [Pi ]. One source for the supply of Pi 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 …

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Self-Healing Properties of Bioinspired Amorphous CaCO3/Polyphosphate-Supplemented Cement

There is a strong interest in cement additives that are able to prevent or mitigate the adverse effects of cracks in concrete that cause corrosion of the reinforcement. Inorganic polyphosphate (polyP), a natural polymer that is synthesized by bacteria, even those on cement/concrete, can increase the resistance of concrete to progressive damage from micro-cracking. Here we use a novel bioinspired strategy based on polyP-stabilized amorphous calcium carbonate (ACC) to give this material self-healing properties. Portland cement was supplemented with ACC nanoparticles which were stabilized with 10% (w/w) Na&ndash

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Effect of bioglass on growth and biomineralization of SaOS-2 cells in hydrogel after 3D cell bioprinting.

We investigated the effect of bioglass (bioactive glass) on growth and mineralization of bone-related SaOS-2 cells, encapsulated into a printable and biodegradable alginate/gelatine hydrogel. The hydrogel was supplemented either with polyphosphate (polyP), administered as polyP • Ca2+-complex, or silica, or as biosilica that had been enzymatically prepared from ortho-silicate by silicatein. These hydrogels, together with SaOS-2 cells, were bioprinted to computer-designed scaffolds. The results revealed that bioglass (nano)particles, with a size of 55 nm and a molar ratio of SiO2 : CaO : P2O5 of 55 : 40 : 5, did not affect the growth of the encapsulated cells. If silica, biosilica, or polyP …

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Back Cover: Macromol. Biosci. 9/2015

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A new printable and durable N,O-carboxymethyl chitosan–Ca2+–polyphosphate complex with morphogenetic activity

Biomimetic materials have been gaining increasing importance in tissue engineering since they may provide regenerative alternatives to the use of autologous tissues for transplantation. In the present study, we applied for bioprinting of a functionalized three-dimensional template, N,O-carboxymethyl chitosan (N,O-CMC), mimicking the physiological extracellular matrix. This polymer, widely used in tissue engineering, has been provided with functional activity by integration of polyphosphate (polyP), an osteogenically acting natural polymer. The two polymers, N,O-CMC and polyP, are linked together via Ca2+ bridges. This N,O-CMC + polyP material was proven to be printable and durable. The N,O-…

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Polyphosphate as a Bioactive and Biodegradable Implant Material: Induction of Bone Regeneration in Rats

Inorganic polyphosphate (polyP) is a naturally occurring polymer that is bioresorbable and anabolically active on bone forming cells in vitro. In order to demonstrate if polyP also shows morphogenetic activity in vivo, animal studies are performed applying the rat calvarial defect model. Poly(D,L-lactide-co-glycolide) (PLGA) microspheres with a narrow size distribution (≈820 μm) are prepared, containing either encapsulated polyP or β-tricalcium phosphate (β-TCP), used as a reference material. Discs are prepared from the microspheres and inserted into 10 mm large defects created in the calvaria of rats. Both the formation of COL-I and the expression of ALP is upregulated, as well as the exte…

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Biologizing titanium alloy implant material with morphogenetically active polyphosphate

As a further step towards a new generation of bone implant materials, we developed a procedure for biological functionalization of titanium alloy surfaces with inorganic calcium polyphosphate (Ca-polyP). This polymer has been demonstrated to exhibit morphogenetic activity. The coating of titanium oxidized Ti-6Al-4V scaffolds with biologically active amorphous Ca-polyP microparticles is formed by Ca2+ ion bridges to the silane coupling agent APTMS. This surface is durable and stable as an almost homogeneous Ca-polyP layer onto the metal. The homogenously coated Ca-polyP titanium scaffold was found to be biologically active and supported the growth and functional activity of bone cell-related…

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A biomimetic approach to ameliorate dental hypersensitivity by amorphous polyphosphate microparticles.

Abstract Objective Dental hypersensitivity has become one of the most common and most costly diseases in the world, even though those maladies are very rarely life threatening. Using amorphous microparticles, fabricated from the natural polymer (polyphosphate), we intend to reseal the dentinal tubules exposed and reduce by that the hypersensitivity. Methods Amorphous microparticles (termed aCa-polyP-MP) were prepared from Na-polyphosphate (polyP) and CaCl 2 , then incubated with human teeth. The potential of the microparticles to plug the dentinal tubules was determined by microscopic and spectroscopic techniques. Results We demonstrate that, in contrast to polyP, the aCa-polyP-MP efficient…

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Electrospun bioactive mats enriched with Ca-polyphosphate/retinol nanospheres as potential wound dressing

Background While electrospun materials have been frequently used in tissue engineering no wound dressings exist that significantly improved wound healing effectively. Methods We succeeded to fabricate three-dimensional (3D) electrospun poly(D,l-lactide) (PLA) fiber mats into which nanospheres, formed from amorphous calcium polyphosphate (polyP) nanoparticles (NP) and encapsulated retinol (“retinol/aCa-polyP-NS” nanospheres [NS]), had been incorporated. Results Experiments with MC3T3-E1 cells revealed that co-incubation of the cells with Ca-polyP together with retinol (or incubation with retinol/aCa-polyP-NS) resulted in a significant synergistic effect on cell growth compared with particle-…

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

Here we show that inorganic polyphosphate (polyP), a polyanionic metabolic regulator consisting of multiple phosphate residues linked by energy-rich phosphoanhydride bonds, is present in the synovial fluid. In a biomimetic approach, to enhance cartilage synthesis and regeneration, we prepared amorphous polyP microparticles with Mg2+ as counterions. The particles were characterised by X-ray diffraction (XRD), energy-dispersive X-ray (EDX) and Fourier transformed infrared spectroscopic (FTIR) analyses. Similar particles were obtained after addition of Mg2+ ions to a solution containing hyaluronic acid, as a major component of the synovial fluid, and soluble Na-polyP. The viscous paste-like ma…

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A physiologically active interpenetrating collagen network that supports growth and migration of epidermal keratinocytes: zinc-polyP nanoparticles integrated into compressed collagen.

The distinguished property of the physiological polymer, inorganic polyphosphate (polyP), is to act as a bio-intelligent material which releases stimulus-dependent metabolic energy to accelerate wound healing. This characteristic is based on the bio-imitating feature of polyP to be converted, upon exposure to peptide-containing body fluids, from stable amorphous nanoparticles to a physiologically active and energy-delivering coacervate phase. This property of polyP has been utilized to fabricate a wound mat consisting of compressed collagen supplemented with amorphous polyP particles, formed from the inorganic polyanion with an over-stoichiometric ratio of zinc ions. The proliferation and t…

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Electrospinning of Bioactive Wound-Healing Nets

The availability of appropriate dressings for treatment of wounds, in particular chronic wounds, is a task that still awaits better solutions than provided by currently applied materials. The method of electrospinning enables the fabrication of novel materials for wound dressings due to the high surface area and porosity of the electrospun meshes and the possibility to include bioactive ingredients. Recent results show that the incorporation of biologically active inorganic polyphosphate microparticles and microspheres and synergistically acting retinoids into electrospun polymer fibers yields biocompatible and antibacterial mats for potential dressings with improved wound-healing propertie…

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Transformation of Construction Cement to a Self-Healing Hybrid Binder

A new biomimetic strategy to im prove the self-healing properties of Portland cement is presented that is based on the application of the biogenic inorganic polymer polyphosphate (polyP), which is used as a cement admixture. The data show that synthetic linear polyp, with an average chain length of 40, as well as natural long-chain polyP isolated from soil bacteria, has the ability to support self-healing of this construction material. Furthermore, polyP, used as a water-soluble Na-salt, is subject to Na+/Ca2+ exchange by the Ca2+ from the cement, resulting in the formation of a water-rich coacervate when added to the cement surface, especially to the surface of bacteria-containing cement/c…

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Amorphous Polyphosphate and Ca‐Carbonate Nanoparticles Improve the Self‐Healing Properties of both Technical and Medical Cements

Cement is used both as a construction material and for medical applications. Previously, it has been shown that the physiological polymer inorganic polyphosphate (polyP) is morphogenetically active in regeneration of skin, bone, and cartilage. The present study investigates the question if this polymer is also a suitable additive to improve the self-healing capacity not only of construction cement but also of inorganic bone void fillers. For the application in the cement, two different polyP-based amorphous nanoparticles (NP) are prepared, amorphous Ca-polyP NP and amorphous Ca-carbonate (ACC) NP. The particles are integrated into poly(methyl methacrylate) in a concentration ratio of 1:10. …

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Increased Stability of Polysaccharide/Silica Hybrid Sub‐Millicarriers for Retarded Release of Hydrophilic Substances

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