Impact of trivalent ions on the stability and cohesion of calcium polyphosphate coacervates for embolization applications.

Polyphosphates (PPs) are of interest as temporary in situ setting embolic agents for which cohesive characteristics are vital. Trivalent ions Al3+ and Ga3+ were substituted into calcium PP up to 10 mol % for two PP chain lengths (degree of polymerization, Dp 200 and 9000) and the effect on the dissolution rate of the resulting coacervate was examined. High levels of trivalent ions were found to increase the dissolution rate, especially with aluminum (Al) where the coacervate with the greatest Al content (10 mol %) and larger Dp completely dissolved within the first few hours in tris(hydroxymethyl)aminomethane buffered saline. Conversely, small amounts of trivalent ions slowed the dissolution rate of the coacervates compared to those containing calcium only. The coacervate compositions determined to have the fastest and slowest ion release were evaluated for cohesion upon injection into a simulated blood vessel using a dual lumen needle. PPs with lower trivalent content had a higher coacervate yield overall, with 5% Ga and Dp 200 yielding the smallest proportion of coacervate particulates that could be implicated in unwanted distal embolization. However, further studies are required to evaluate the formation and duration of occlusions in vivo so that the PP composition can best be tailored to meet clinical requirements. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2638-2648, 2019.

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

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.

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.