Mark Filiaggi

Gelled Calcium Polyphosphate Matrices Delay Antibiotic Release

Introducing a gelling step during antibiotic incorporation has previously been found to delay vancomycin delivery from a calcium polyphosphate matrix intended for local treatment of bone infections. This study examined the general applicability of this approach using cefuroxime, a lower-molecular-weight antibiotic with different charge characteristics compared with those of vancomycin. A calcium polyphosphate/cefuroxime paste was “gelled” in disk form in a humid environment for 5 or 24 hours prior to drying. Antibiotic release in Tris-buffered saline under gentle agitation was monitored over a seven-day period. While non-gelled samples clearly exhibited a burst release, the gelling process significantly retarded early antibiotic release from five- and 24-hour gelled matrices, yielding a constant release rate over the first four days. Cefuroxime incorporation did not appear to alter matrix structure or degradation. Overall, this non-aggressive process effectively trapped cefuroxime and reduced its release rate, suggesting its potential applicability with molecularly diverse therapeutic agents.

The oral health of ageing baby boomers: a comparison of adults aged 45-64 and those 65 years and older

OBJECTIVES To compare the oral health status of adults aged 45-64 (baby boomers) and those aged 65 and older. METHODS An observational, cross-sectional survey of adults living independently in rural and urban settings in Nova Scotia, Canada was conducted. Using random digit dialing, calibrated interviewers completed a telephone survey, and clinicians calibrated to WHO standards conducted clinical examinations. Weighting was used to correct for sampling bias. RESULTS 747 community dwelling adults completed both the clinical exam and the questionnaire (n=411, age 45-64; n=336, age 65 or older). Rates of edentulism were low (2.6% aged 45-64; 15.7% aged 65+; p<0.001). Untreated root caries was greater in the older dentate group (19.7 vs. 10.1%; p<0.001). Being 65 years of age or older was identified as a predictor of increased decayed, missing, filled teeth, presence of decayed and/or filled roots and presence of attachment loss≥4 mm, but was not a significant predictor of presence of untreated coronal caries. CONCLUSIONS A falling rate of edentulism and a higher risk for root caries with increasing age may predict the need for more complex dental care as our population ages.

Comprehensive study of the chelation and coacervation of alkaline earth metals in the presence of sodium polyphosphate solution.

The effect of chelation of three alkaline earth metals (Ca, Sr, and Ba) by polyphosphates on the pH and viscosity of the solution is examined and correlated to the phosphate glass properties. Also, the impact of the polyphosphate average degree of polymerization (D(p)) as well as the type and amount of chelated divalent cation on the degradation rate of the chains is studied. Subsequently, the number of divalent cations required for polyphosphate chain agglomeration to form a coacervate, and the resulting composition of these coacervates, was investigated. A decrease in polyphosphate solution pH during chelation was routinely obtained, with a sudden shift in the rate of pH drop occurring around a divalent cation/phosphorus molar ratio of 0.18. Longer chains or cations with a smaller ionic radius accelerated the rate of D(p) reduction. The number of divalent cations required for coacervation depends on different variables such as the polyphosphate concentration, the D(p), and the type of divalent cation. The formed coacervate retains the D(p) of polyphosphate originally used for coacervation, and the resulting Ca/P molar ratio depends largely on the amount of calcium being used during coacervation. Overall, this article helps one to understand the coacervation of polyphosphates in order to exploit their potential as a biomaterial.

Rheology of polyphosphate coacervates

Polyphosphate is a highly water-soluble linear polyanion comprised of phosphate groups. A phase separation happens when divalent cations are added to polyphosphate solutions resulting in the formation of polyphosphate coacervates. Such coacervates could potentially be used as a glass precursor or in a variety of bioapplications including microencapsulation. In all of these applications, viscoelastic properties of polyphosphate coacervates directly affect their usage. Here, we show that these polyphosphate coacervates act as extremely viscous Newtonian liquids at low shear rates, with their viscosity highly dependent on the polyphosphate degree of polymerization (Dp) and type of divalent cations (Ca2+, Sr2+, or Ba2+) used for their preparation. For Ca2+-only polyphosphate coacervates, specific viscosity is directly related to Dp1.46 at 20 °C, similar to highly concentrated polymer solutions where chain entanglement is not important. For very long chain polyphosphate coacervates, however, elastic properties are dominant presumably caused by physical chain entanglement. Replacement of a fraction of Ca2+ with Sr2+ or Ba2+ results in coacervates having significantly more elastic characters and profoundly higher viscosity than their Ca2+-only counterparts. Overall, varying polyphosphate chain length and divalent cation type allows one to modify these materials for a desired application.Polyphosphate is a highly water-soluble linear polyanion comprised of phosphate groups. A phase separation happens when divalent cations are added to polyphosphate solutions resulting in the formation of polyphosphate coacervates. Such coacervates could potentially be used as a glass precursor or in a variety of bioapplications including microencapsulation. In all of these applications, viscoelastic properties of polyphosphate coacervates directly affect their usage. Here, we show that these polyphosphate coacervates act as extremely viscous Newtonian liquids at low shear rates, with their viscosity highly dependent on the polyphosphate degree of polymerization (Dp) and type of divalent cations (Ca2+, Sr2+, or Ba2+) used for their preparation. For Ca2+-only polyphosphate coacervates, specific viscosity is directly related to Dp1.46 at 20 °C, similar to highly concentrated polymer solutions where chain entanglement is not important. For very long chain polyphosphate coacervates, however, elastic properties...

Assessing the oral health of an ageing population: methods, challenges and predictors of survey participation

Assessing the oral health of an ageing population: methods, challenges and predictors of survey participation Objectives To examine predictors of participation and to describe the methodological considerations of conducting a two-stage population-based oral health survey. Methods An observational, cross-sectional survey (telephone interview and clinical oral examination) of community-dwelling adults aged 45–64 and ≥65 living in Nova Scotia, Canada was conducted. Results The survey response rate was 21% for the interview and 13.5% for the examination. A total of 1141 participants completed one or both components of the survey. Both age groups had higher levels of education than the target population; the age 45–64 sample also had a higher proportion of females and lower levels of employment than the target population. Completers (participants who completed interview and examination) were compared with partial completers (who completed only the interview), and stepwise logistic regression was performed to examine predictors of completion. Identified predictors were as follows: not working, post-secondary education and frequent dental visits. Conclusion Recruitment, communications and logistics present challenges in conducting a province-wide survey. Identification of employment, education and dental visit frequency as predictors of survey participation provide insight into possible non-response bias and suggest potential for underestimation of oral disease prevalence in this and similar surveys. This potential must be considered in analysis and in future recruitment strategies.

Calcium polyphosphate as an additive to zinc-silicate glass ionomer cements.

Aluminum-free glass ionomer cements (GICs) are under development for orthopedic applications, but are limited by their insufficient handling properties. Here, the addition of calcium polyphosphate (CPP) was investigated as an additive to an experimental zinc-silicate glass ionomer cement. A 50% maximum increase in working time was observed with CPP addition, though this was not clinically significant due to the short working times of the starting zinc-silicate GIC. Surprisingly, CPP also improved the mechanical properties, especially the tensile strength which increased by ∼33% after 30 days in TRIS buffer solution upon CPP addition up to 37.5 wt%. This strengthening may have been due to the formation of ionic crosslinks between the polyphosphate chains and polyacrylic acid. Thus, CPP is a potential additive to future GIC compositions as it has been shown to improve handling and mechanical properties. In addition, CPP may stimulate new bone growth and provide the ability for drug delivery, which are desirable modifications for an orthopedic cement.

Degradation and drug release in calcium polyphosphate bioceramics: an MRI-based characterization.

Degradable, bioceramic bone implants made of calcium polyphosphate (CPP) hold potential for controlled release of therapeutic agents in the treatment of localized bone disease. Magnetic resonance imaging techniques for non-invasively mapping fluid distribution, T(1) and T(2) relaxation times and the apparent diffusion coefficient were performed in conjunction with a drug elution protocol to resolve free and bound water components within the material microstructure in two CPP formulations (G1 and G2). The T(2) maps provided the most accurate estimates of free and bound water, and showed that G1 disks contained a detectable free water component at all times, with drug release dominated by a Fickian diffusion mechanism. Drug release from G2 disks was characterized by a combined diffusional/structural relaxation mechanism, which may be related to the gradual infiltration of a free water component associated with swelling and/or chemical degradation.

Degradation and hemostatic properties of polyphosphate coacervates.

UNLABELLED Sodium polyphosphate is a linear polymer formed from phosphate units linked together by sharing oxygen atoms. Addition of calcium to a solution of sodium polyphosphate results in phase separation and formation of a polyphosphate coacervate best described as a polymeric rich viscoelastic material. Polyphosphate coacervate is an interesting candidate as a biomaterial based on its ability to bind with different cations and to be loaded with drugs. Here, in vitro degradation and hemostatic properties of polyphosphate coacervates are comprehensively evaluated. We show that polyphosphate coacervates degrade and dissolve at a fast rate, losing half of their original mass in a week and transforming to mainly pyrophosphate after 4weeks. This burst dissolution phase happens earlier for the coacervate prepared from very short chain polyphosphate but overall using longer polyphosphate chains does not increase the coacervate longevity significantly. Substitution of Ca with Sr or Ba does not affect the hydrolysis of coacervates but slows down their dissolution into the media. In a whole blood clotting assay, coacervates profoundly decrease the clotting time especially when very long chain polyphosphates are used. While coacervate chain length and divalent cation type were found to significantly affect prothrombin time and thromboplastin time compared to the control, no discernible trends were observed. Platelets adhere in large numbers to coacervates, especially those containing long chain polyphosphate, but the cell morphology observed suggests that they might not to be fully activated. Overall, the long chain polyphosphate coacervate holds a great potential as a resorbable hemostatic agent. STATEMENT OF SIGNIFICANCE Divalent cation additions to a sodium polyphosphate solution result in polyphosphate coacervates, or highly viscous gel-like materials, having great potential in bio-applications such as drug delivery and hemostasis. As these coacervates degrade in aqueous environments, we undertook a comprehensive evaluation to better understand the impact of polyphosphate chain length and divalent cation substitution on this hydrolytic response in order to better predict degradation behavior in the body. Furthermore, there is great interest in the role of polyphosphates in hemostasis following recent publications showing that platelets secrete polyphosphates upon thrombin stimulation. In this paper, we evaluate the hemostatic potential of polyphosphate coacervates as bulk constructs, demonstrating that indeed these materials hold great potential as a degradable hemostatic agent.

Developing an in situ forming polyphosphate coacervate as a new liquid embolic agent: From experimental design to pilot animal study.

UNLABELLED A radiopaque temporary liquid embolic agent was synthesized from polyphosphate (PP) coacervates and optimized using a design of experiments approach. Variables studied were: strontium substitution (0-15 mol%), barium substitution (0-15 mol%), PP concentration and degree of polymerization of the polyphosphate (Dp). The viscosity, radiopacity and cell viability of the resulting coacervates were measured for 60 formulations and response surface modeling was used to determine the optimum coacervate that maximized radiopacity and cell viability. The optimum coacervate made from PP with a large Dp (9.5 g NaPP/100mL, 2.2 mol% Sr, 9 mol% Ba and 3.8 mol% Ca) was taken forward to a pilot animal trial. In this rabbit model, PP embolic agent successfully occluded the central auricular artery with promising biocompatibility. Further study is required to optimize the cohesiveness and clinical effectiveness of PP as an in situ setting temporary embolic agent. STATEMENT OF SIGNIFICANCE This article describes the development of a new radiopaque temporary liquid embolic agent from the optimization using design of experiments to a pilot animal study. Embolization is a minimally invasive interventional radiology procedure used to block blood flow in a targeted blood vessel. This procedure is used to treat many conditions including: tumors, aneurysms and arteriovenous malformations. Currently, no inherent radiopaque embolic agents are available in the clinic, which would allow for direct imaging of the material during the procedure and follow up treatment.

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 in vitro 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.