Amorphous Calcium Polyphosphate Research Articles

A two-stage cold isostatic pressing and gelling approach for fabricating a therapeutically loaded amorphous calcium polyphosphate local delivery system.

Local delivery systems have taken on a greater clinical focus for osteomyelitis therapy owing to their ability to overcome many disadvantages of systemic delivery. This study reports for the first time the capacity to fabricate strontium- and vancomycin-doped calcium polyphosphate beads using a two-stage cold isostatic pressing and gelling approach. The fabricated beads were of uniform shape and diameter, and upon gelling exhibited reduced porosity. Of greatest significance in the subsequent invitro study was the improvement of bead long-term structural stability upon vancomycin incorporation; a characteristic that further encourages the extended release of therapeutically relevant levels of antibiotic. Overall, this study provides support for the inclusion of a cold isostatic pressing step in the fabrication of a therapeutically loaded calcium polyphosphate bead-based local delivery system intended for osteomyelitis treatment.

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 differentiation, collagen type I and alkaline phosphatase. In addition, polyP, applied as Zn-polyP microparticles (“Zn-a-polyP-MP”), showed a distinct inhibitory effect on growth of Streptococcus mutans, in contrast to a toothpaste containing the broad-spectrum antibiotic triclosan that only marginally inhibits this cariogenic bacterium. Moreover, we demonstrate that the “a-polyP/RA-MP”-containing toothpaste efficiently repairs cracks/fissures in the enamel and dental regions and reseals dentinal tubules, already after a five-day treatment (brushing) of teeth as examined by SEM (scanning electron microscopy) and semi-quantitative EDX (energy-dispersive X-ray spectroscopy). The occlusion of the dentin cracks by the microparticles turned out to be stable and resistant against short-time high power sonication. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP microparticles enriched with retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity. While the polyP microparticles function as a sealant for dentinal damages and inducer of remineralization processes, the retinyl acetate acts as a regenerative stimulus for collagen gene expression in cells of the surrounding tissue, the periodontium.

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 ortho-phosphate used for bone hydroxyapatite formation. Here we show that the flavone-loaded Ca-polyP microparticles are readily taken up by phOSB, resulting in the accumulation of polyP around the nuclei and the formation of intracellular vesicles containing the ALP. In addition, we demonstrate that baicalin/baicalein causes a rise of the intracellular calcium [Ca[Formula: see text]]i a level which markedly is augmented after encapsulation into Ca-polyP, through activation of the phospholipase C. Moreover, both flavones, either alone or associated with Ca-polyP microparticles, upregulate the expression of the osteoblast calcium efflux channel, the plasma membrane Ca[Formula: see text]-ATPase (PMCA), while the expression of ALP, which promotes bone mineralization, is induced by Ca-polyP and by the flavones only if present in the Ca-polyP-microparticle-associated form. As a result, the extent of bone mineralization is markedly enhanced. Based on the two-armed activating function, new applications of baicalin/baicalein as a component of nutriceuticals for osteoporosis prevention or bone implants can be envisaged.

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

In this manuscript, we fabricated amorphous strontium-polyphosphate microparticles ("Sr-a-polyP-MP") and studied their effects on bone mineral formation in vitro as well as in vivo. In vitro, those particles substantially increased the expression of the genes encoding for alkaline phosphatase, the bone morphogenetic protein 2 and the mineralization. In vivo, the "Sr-a-polyP-MP" packed into PLGA microspheres and implanted into critical-size calvarial defects in rats resulted in a speeded up of the healing/mineralization of the bone defect. Those properties qualify Sr-a-polyP as a suitable biomaterial for bone regenerative implants.

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 polyP) changes only relatively little. In contrast, aCa-polyP-MP primarily induces ALP expression. If both components are applied together a strong stimulation of expression of both marker genes is observed. In order to investigate whether ACC also enhances bone regeneration induced by polyP in vivo, the particles were encapsulated into PLGA (poly(d,l-lactide-co-glycolide)) microspheres (diameter ~800 μm) and implanted into rat critical-size calvarial defects. The studies revealed that animals that received aCa-polyP-MP microspheres showed an increased rate of regeneration compared to β-tri-calcium phosphate (β-TCP) controls. This effect is even accelerated if microspheres with both aCa-polyP-MP and ACC-P10-MP (1 : 1 weight ratio) are applied, resulting in an almost complete restoration of the defect area after 12 weeks. qRT-PCR analyses of tissue sections through the regeneration zone with microspheres containing both aCa-polyP-MP and ACC-P10-MP revealed a significantly higher upregulation of expression of the marker genes compared to each of the components alone. The Young’s moduli for microspheres containing aCa-polyP-MP (1.74 MPa) and aCa-polyP-MP/ACC-P10-MP (2.38 MPa) were markedly higher compared to β-TCP-controls (0.63 mPa). Our results show that the combined application of ACC and Ca-polyP (both in the amorphous state) opens new strategies for the development of regenerative implants for the reconstruction of bone defects.

Structural analysis of xSrO–(50 − x)CaO–50P 2 O 5 glasses with x = 0, 5, or 10 mol% for potential use in a local delivery system for osteomyelitis treatment

The introduction of ions into a local delivery matrix is one method of managing degradation and subsequent release of the incorporated therapeutic agents. Of interest in this study was whether we could modify the structural nature of calcium polyphosphate (CPP) glass and the subsequent therapeutic potential of this local delivery matrix with inclusion of strontium (Sr). We found that adding 10 mol% Sr significantly increased the density and chain length of the glass. There was no significant impact of Sr doping on the subsequent loading of vancomycin into the matrix, or the matrix porosity. The noted differences in structural stability, ion release, and vancomycin release between the un-doped CPP matrices and 10 mol% Sr-doped CPP matrices in vitro are likely a result of a decrease in glass disorder upon Sr addition to the glass and preferential retention of Sr over Ca during matrix degradation. This study has provided further evidence that Sr incorporation may serve to both manipulate antibiotic release from the amorphous CPP matrix and provide a potential source of therapeutic ions for enhanced bone regeneration.

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

BackgroundWhile electrospun materials have been frequently used in tissue engineering no wound dressings exist that significantly improved wound healing effectively. MethodsWe 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. ResultsExperiments 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-free polyP complexed with Ca2+ or amorphous Ca-polyP NPs and retinol alone. Incubation of the cells in the presence of the retinol/aCa-polyP NSs also caused a significant increase of the expression levels of the genes encoding for the fatty acid binding protein 4 (FABP4), as well as of the genes encoding for leptin and the leptin receptor. In contrast, the single components, soluble Na-polyP, complexed to Ca2+, or retinol-free aCa-polyP NPs, and retinol, had no significant effect on the expression of these genes. ConclusionsThese results indicate that the PLA fibers, supplemented with aCa-polyP-NP or retinol/aCa-polyP-NS, elicit morphogenetic activity, suggesting that these fiber mats, along with the antibacterial effect of polyP, have a beneficial potential as wound dressings combining antimicrobial and regenerative (wound healing) properties. General significanceThe PLA-based fiber mats, containing retinol and polyP nanoparticles, provide promising bioactive meshes that are urgently needed as dressings for chronic wounds.

Influence of Particle Size and Soaking Conditions on Rheology and Microstructure of Amorphous Calcium Polyphosphate Hydrogel

Amorphous calcium polyphosphate (ACPP), an inorganic polymer ceramic, has shown promise as a drug delivery matrix following a repeat gelling protocol. This study described a simple method of preparing ACPP hydrogel in the presence of an excess volume of water. The increased water availability accelerates water molecule ingress and microstructural transformation of ACPP hydrogels. The impact of some experimental settings (soaking time, temperature, stirring, and ACPP particle size) on the physiochemical and rheological natures of ACPP hydrogel were investigated and from which possible hydrogel formation mechanisms were inferred. We believe that the formation of ACPP hydrogel is through the mechanisms of intermolecular ionic interaction and entanglement of polyphosphate chains. The potential application of ACPP hydrogel as a ceramic matrix for sustained drug release warrants further investigation.

Control of structural and mechanical properties in bioceramic bone substitutes via additive manufacturing layer stacking orientation

Additive manufacturing (AM) is a promising approach for fabricating structures to serve as bone substitutes, or as biomaterial components in biphasic implants for repair of osteochondral defects. In this study, the three dimensional printing (3DP) AM process was investigated to determine the effect of powder layer orientation on mechanical and structural properties of fabricated parts. Five types of standard cylindrical parts were manufactured via AM with 0°, 30°, 45°, 60° and 90° stacking layer orientations relative to the vertical z-axis of the print bed, using amorphous calcium polyphosphate (CPP) powder of irregular particle shape, average aspect ratio ≈1.70 and particle size between 75 and 150μm. It was concluded that layer orientation had an effect on porosity and compressive strength, based on induced powder particle orientation in the green part during powder layering. The resulting bulk porosity values ranged between 30.0±2.4% and 38.2±2.7%, while the compressive strength ranged between 13.50±1.95MPa and 45.13±6.82MPa. The orientation with the highest compressive strength was 90°, while orientations with the weakest compressive strength were 0° and 45°. Based on these results, it was established that AM-made parts are structurally and mechanically anisotropic. The stacking layer orientation which results in the highest strength performance along a preferred loading orientation can be implemented to further optimize mechanical strength of constructs along the maximum loading direction.

A Processing Approach to Tuning the Drug Delivery Characteristics of Calcium Polyphosphate Matrices

Amorphous calcium polyphosphate (CPP) has potential as an implantable drug delivery matrix by virtue of a low temperature gelling protocol that has been shown to eliminate burst release and extend drug release time from the matrix. However, a greater understanding of this material’s interaction with aqueous environments is needed to more fully exploit this application. Variations in aqueous exposure were assessed using as-made amorphous CPP as well as CPP processed using established low temperature protocols. Solid-state 31P-NMR along with thermal and X-ray diffraction analyses were used to track resulting structural changes. Exposure to aqueous environments caused a reduction in CPP chain length that was dependant on gel time and mode of exposure. Significantly, increased gel times or water availability further resulted in crystallization events upon drying, except in the presence of a buffered solution. In general, drug elution studies showed an increase in the burst release of vancomycin from CPP disks gelled for extended periods, with matrix-water interactions appearing to be most influential during the drug loading stage. Overall, this study shows that CPP drug delivery matrices can be produced with tailored properties by closely controlling CPP-water interactions during processing.

Control of vertebrate skeletal mineralization by polyphosphates.

BackgroundSkeletons are formed in a wide variety of shapes, sizes, and compositions of organic and mineral components. Many invertebrate skeletons are constructed from carbonate or silicate minerals, whereas vertebrate skeletons are instead composed of a calcium phosphate mineral known as apatite. No one yet knows why the dynamic vertebrate skeleton, which is continually rebuilt, repaired, and resorbed during growth and normal remodeling, is composed of apatite. Nor is the control of bone and calcifying cartilage mineralization well understood, though it is thought to be associated with phosphate-cleaving proteins. Researchers have assumed that skeletal mineralization is also associated with non-crystalline, calcium- and phosphate-containing electron-dense granules that have been detected in vertebrate skeletal tissue prepared under non-aqueous conditions. Again, however, the role of these granules remains poorly understood. Here, we review bone and growth plate mineralization before showing that polymers of phosphate ions (polyphosphates: (PO3 −)n) are co-located with mineralizing cartilage and resorbing bone. We propose that the electron-dense granules contain polyphosphates, and explain how these polyphosphates may play an important role in apatite biomineralization.Principal Findings/MethodologyThe enzymatic formation (condensation) and destruction (hydrolytic degradation) of polyphosphates offers a simple mechanism for enzymatic control of phosphate accumulation and the relative saturation of apatite. Under circumstances in which apatite mineral formation is undesirable, such as within cartilage tissue or during bone resorption, the production of polyphosphates reduces the free orthophosphate (PO4 3−) concentration while permitting the accumulation of a high total PO4 3− concentration. Sequestering calcium into amorphous calcium polyphosphate complexes can reduce the concentration of free calcium. The resulting reduction of both free PO4 3− and free calcium lowers the relative apatite saturation, preventing formation of apatite crystals. Identified in situ within resorbing bone and mineralizing cartilage by the fluorescent reporter DAPI (4′,6-diamidino-2-phenylindole), polyphosphate formation prevents apatite crystal precipitation while accumulating high local concentrations of total calcium and phosphate. When mineralization is required, tissue non-specific alkaline phosphatase, an enzyme associated with skeletal and cartilage mineralization, cleaves orthophosphates from polyphosphates. The hydrolytic degradation of polyphosphates in the calcium-polyphosphate complex increases orthophosphate and calcium concentrations and thereby favors apatite mineral formation. The correlation of alkaline phosphatase with this process may be explained by the destruction of polyphosphates in calcifying cartilage and areas of bone formation.Conclusions/SignificanceWe hypothesize that polyphosphate formation and hydrolytic degradation constitute a simple mechanism for phosphate accumulation and enzymatic control of biological apatite saturation. This enzymatic control of calcified tissue mineralization may have permitted the development of a phosphate-based, mineralized endoskeleton that can be continually remodeled.

Amorphous Calcium Polyphosphate Bone Regenerative Materials Based on Calcium Phosphate Glass

We developed new calcium phosphate bone substitute material, amorphous calcium polyphosphate. The new material is synthesized by a cement-like slif-setting reaction with calcium phosphate glass, basic materials and water. In this study, we prepared with CPG, Na2CO3 and NaOH solution. When they are mixed together, amorphous phase was precipitated. The precipitated amorphous phase consisted of polyphosphate chains condensed with Na ions released from Na2CO3 and NaOH. When the amorphous calcium polyphosphate dissolves, inorganic polyphosphates are released into the medium. The inorganic polyphosphates as the dissolution product inducted the calcification of the osteoblast cells. Therefore, in animal test, the new bone formation in rat calvarial defects treated with the new material was significantly higher than sham-surgery control group, especially in the initial stage. The amorphous calcium polyphosphate was biocompatible and bioresorbable and promoted the new bone formation.

Crystalline structure and its effects on the degradation of linear calcium polyphosphate bone substitute

Calcium polyphosphate (CPP) bone substitutes were prepared by gravity sintering crystal transformations. The crystalline structure of CPP was analyzed by Raman spectroscopy and in situ variable temperature XRD. In addition, the variation of CPP in SBF considering as degradation was characterized by monitoring the changes of its compressive strength and weight loss. The results revealed that CPP was inorganic condensed phosphate with linear long chain structure. Amorphous CPP (a-CPP) was initially transformed to crystalline γ-CPP, then crystalline β-CPP with the increase of sintering temperature. The transformation of γ-CPP to β-CPP occurred from 650 to 670 °C. Compressive strength decreased quickly at initial stage for all specimens after immersed in SBF, and thereafter, continued to decrease at a slower rate subsequently. After immersion for 15 and 30 days, the compressive strength of γ-CPP decreased from 13.5 to 7.6 and 4.8 MPa, while β-CPP decreased from 16 to 12 and 8 MPa, respectively. The degradation rate of a-CPP, γ-CPP and β-CPP decreased with time after immersed in SBF. a-CPP had highest degradation rate, which would have been completely degraded in 10 days, and the weight loss ratio of γ-CPP was 28% for 15 days and 35% for 30 days, but the weight loss of β-CPP was only 11% for 30 days. The results therefore revealed that CPPs with different degradation rates could be obtained by controlling crystalline structure.

Fabrication and characterization of porous calcium polyphosphate scaffolds

Porous calcium polyphosphate (CPP) scaffolds with different polymerization degree and crystalline phases were prepared, and then analyzed by scanning electron microscopy (SEM), Thermmogravimetry (TG) and X-ray diffraction (XRD). Number average polymerization degree was calculated by analyzing the calcining process of raw material Ca(H2PO4)2, as a polycondensation reaction. Amorphous CPP were prepared by the quenching from the melt of Ca(H2PO4)2 after calcining, and CPP with different polymerization degree was prepared by controlling the calcining time. Meanwhile, CPP with the same polymerization degree was prepared to amorphous or different crystalline phases CPP which was made from crystallization of amorphous CPP. In vitro degradation studies using 0.1 M of tris-buffered solution were performed to assess the effect of polymerization degree or crystalline phases on mechanical properties and weight loss of the samples. With the increase of polymerization degree, the weight loss during the degradation decreased, contrarily the strength of CPP increased. The degradation velocity of amorphous CPP, α-CPP, β-CPP and γ-CPP with the same polymerization degree decreased in turn at the same period. The full weight loss period of CPP can be controlled between 17 days and more than 1 year. The results of this study suggest that CPP ceramics have potential applications for bone tissue engineering.

Vancomycin release behaviour from amorphous calcium polyphosphate matrices intended for osteomyelitis treatment

Calcium polyphosphate (CPP) antibiotic delivery matrices were prepared using a unique processing technique involving the exposure of antibiotic-loaded CPP pastes to high humidity for 0, 5, or 24 h. After the designated gelling period, samples were dried for a minimum of 24 h. At several time points out to 130 h, the elution medium was monitored for vancomycin, Ca 2+ ion and ortho and poly phosphate release levels. Vancomycin activity was also assessed after 1, 24 and 130 h, while solution 31P-NMR was used to monitor changes in chain length within a 24 hr gelled VCM disc throughout the elution process. The gelling and drying process significantly reduced the rate of vancomycin release during the initial 2–4 h of elution, while extending the effective antibiotic release period by an additional 80 h. The mild conditions associated with matrix fabrication readily allowed for vancomycin incorporation within an environment that did not disrupt antibiotic activity. Throughout the elution process, all sample groups experienced considerable swelling followed by some apparent bulk erosion. Phosphate chain lysis was clearly observed by the end of the elution period. Generally, no strong or consistent correlation existed between matrix degradation and antibiotic release for the treatment groups investigated. An ability to delay antibiotic release using CPPs in conjunction with this protocol supports further investigations into the potential of this matrix as a localized drug delivery system.

In Vitro Degradation Studies of Calcium Polyphosphate Ceramics Prepared by Controlled Degree of Polymerization and Crystallization

Porous calcium polyphosphate(CPP) have been shown to promise for tissue engineered implant application. The process from Ca(H2PO4)2 to CPP, as a polycondensation reaction, has been researched to evaluate the number average degree of polymerization. CPP with different degree of polymerization were prepared by controlling the calcining time. Amorphous and different crystalline CPP were prepared by the quenching from the melt and crystallization of amorphous CPP. Two specimens were soaked into citric acid and tris-buffer solution for 1 to 30 days. The weight loss of CPP with different degree of polymerizations and crystal types are different. With the increasing of degree of polymerization, the weight loss during the degradation is decreasing, contrarily the strength of CPP is increasing. The degradation velocity of amorphous CPP, α-CPP,β-CPP and γ-CPP with the same degree of polymerization decreased in turn at the same period. The full weight loss period of CPP can be changed between 17 days and more than 1 year. The degradation and deposition was faster in the citric acid than the tris-buffer solution.

Phase transformations and structure characterization of calcium polyphosphate during sintering process

Calcium polyphosphate (CPP) may be a promising bone substitute with controllably degraded ability. In this investigation, the effects of sintering temperatures on CPP's phase transformations and microstructure parameters, such as the distribution of crystallite size and micro-strain, were investigated by X-ray diffraction (XRD). The qualitative phase analysis and quantitative phase analysis based on reference intensity ratio (RIR) method were conducted for the CPP sintered at 585, 600, 650, 700, 750, 800 and 900°C. The distribution of crystallite size and micro-strain were calculated with the Warren-Averbach Fourier Transfer method. The results demonstrated that the transformation of amorphous CPP to semi-crystalline CPP occurred below 585°C, and semi-crystalline CPP to γ-CPP at temperature of 585–600°C; γ-CPP to β-CPP at 585–700°C. CPP sintered between 600–700°C were composed of both γ-CPP and β-CPP, and the mass fraction of β-CPP increased with rising of temperature. Above 700°C, the sintered CPP only contained β-CPP. At different ranges of the sintering temperature, the average crystallite size (D) and micro-strain (e) showed significant difference, for example, D and e is about 2.9 nm and 1.68% at 585°C, but D and e was 8.0 to 8.7 nm and 0.159 to 0.134% at 600 and 700°C, respectively. The results of the phase transformations and the variations of microstructure parameters in the present study may be able to provide some fundamental data for explaining CPP degradation phenomena.

Attachment, spreading, and matrix formation by human gingival fibroblasts on porous-structured titanium alloy and calcium polyphosphate substrates.

Porous calcium polyphosphate (CPP) structures represent promising resorbable implant systems that can promote anchorage to connective tissues. Previous studies focused on chondrocyte interactions with CPP, but there are limited data on interactions of soft connective tissue cells with these materials. We studied attachment, spreading, and matrix formation by human gingival fibroblasts when cultured on amorphous and crystalline CPP. Comparison with porous Ti6Al4V substrates of similar volume percent, porosity, and pore size distribution provided evaluations of fibroblast interactions with rapid, moderate, and nonbiodegradable systems, respectively. Cells were incubated on substrates in medium containing ascorbic acid and evaluated at 3, 24, 48, 72, and 96 h after plating. Attached cell counts, cytoplasmic actin filament area, and immunostained extracellular type 1 collagen or fibronectin were quantified by morphometric analyses using epifluorescence microscopy. Cell morphology and substrate interactions were evaluated by scanning electron microscopy. Spreading, attachment, and matrix production were similar for both CPP substrates. In contrast, titanium alloy substrates exhibited threefold more attachment and twofold more spreading than CPP substrates. The area per cell of immunostained extracellular collagen and fibronectin was similar for the three different substrates. The results indicate that the crystallinity and, hence, degradation rate of CPP substrates does not substantially affect the interactions of fibroblasts with CPP materials but that compared with titanium alloy substrates, spreading and attachment are inhibited.

Fabrication of porous calcium polyphosphate implants by solid freeform fabrication: A study of processing parameters andin vitro degradation characteristics

Solid freeform fabrication (SFF) involves the creation of a solid 3-D object of desired shape by successively adding raw materials in particles or layers. Its use in fabricating surgical implants is being explored. The objective of this study was to determine the feasibility of using SFF to build porous parts of calcium polyphosphate (CPP), a linear condensed phosphate that has been suggested as a material for forming bioresorbable skeletal replacement implants. CPP powders (<25 microm in particle size) were added to an UV curable monomer (SOMOS 6110) at a solids loading of 25 vol %, with the addition of a commercial dispersant to prevent particle agglomeration and settling. Viscosity and cure depth measurements were performed to insure that CPP suspension met the requirements deemed necessary for use in SFF. The CPP suspension was bulk cured and sintered in molds in order to assess binder removal and sintering parameters. Using a three-point bend test, the ultimate bending strength and energy-to-fracture of sintered CPP samples simulating parts to be formed by this strategy were characterized. In vitro degradation studies using 0.1M of tris-buffered solution were performed to assess the effect of aging on mechanical properties of the samples as a function of the processing route and resulting structures. The polymer binder successfully was removed from the cured ceramic suspension by developing a procedure that combined slow heating rates with low temperature dwells. Sintering CPP at 585 degrees C for 1 h produced amorphous material samples with average porosity of 27.7 +/- 2.0%. Sintering CPP at 600 degrees C for 1 h produced a crystalline material with samples having an average porosity of 22.9 +/- 1.3%. Crystalline CPP was found to exhibit superior bend strength and toughness compared with amorphous CPP. Both samples experienced a decline in mechanical properties during in vitro degradation; however, the effects were more pronounced with the amorphous CPP samples. Amorphous CPP was found to degrade four times faster than crystalline CPP, as shown by high levels of phosphate present in the degradation solution and a noticeable increase in the porosity of the samples. Crystalline CPP was more resistant to attack as dissolution was limited to surface features of the sintered particles.

Synthesis and Dehydration of Amorphous Calcium Phosphate

Amorphous calcium polyphosphate was prepared by exchange reaction, and the variation in its molecular composition during dehydration was examined. During heating, the material is first hydrolyzed by its own hydration water to form calcium mono- and diphosphates, which again transform into calcium polyphosphate at higher temperatures.