Mixture designs to assess composition-structure-property relationships in SiO2-CaO-ZnO-La2O3-TiO2-MgO-SrO-Na2O glasses: potential materials for embolization.

Embolization with micron-sized particulates is widely applied to treat uterine fibroids. The objective of this work was to develop mixture designs to predict materials composition-structure-property relationships for the SiO2-CaO-ZnO-La2O3-TiO2-MgO-SrO-Na2O glass system and compare its fundamental materials properties (density and cytocompatibility), against a state-of-the-art embolic agent (contour polyvinyl alcohol) to assess the potential of these materials for embolization therapies. The glass structures were evaluated using ²9Si MAS NMR to identify chemical shift and line width; the particulate densities were determined using helium pycnometry and the cell viabilities were assessed via MTT assay. ²9Si MAS NMR results indicated peak maxima for each glass in the range of -82.3 ppm to -89.9 ppm; associated with Q² to Q³ units in silicate glasses. All experimental embolic compositions showed enhanced in vitro compatibility in comparison to Contour PVA with the exceptions of ORP9 and ORP11 (containing no TiO2). In this study, optimal compositions for cell viability were obtained for the following compositional ranges: 0.095-0.188 mole fraction ZnO; 0.068-0.159 mole fraction La2O3; 0.545-0.562 mole fraction SiO2 and 0.042-0.050 mole fraction TiO2. To ensure ease of producibility in obtaining good melts, a maximum loading of 0.068 mole fraction La2O3 is required. This is confirmed by the desirability approach, for which the only experimental composition (ORP5) of the materials evaluated was presented as an optimum composition; combining high cell viability with ease of production (0.188 mole fraction ZnO; 0.068 mole fraction La2O3; 0.562 mole fraction SiO2 and 0.042 mole fraction TiO2).

Histological analysis of achilles tendons in an overuse rat model.

The purpose of this study was to design an animal model that induces histological changes in Achilles tendons consistent with those cited in the literature for human Achilles tendon disease. Sprague-Dawley rats were subjected to 10 degrees uphill treadmill running on a custom-designed rodent treadmill and at a speed of 17 meters per minute for 1 h, five times per week, over a 12-week treatment period. Subsequent histological analysis revealed alterations in the rat Achilles tendon that were generally consistent with those described in the literature for diseased human tendon tissues. These features include: decreased collagen fiber organization, more intense collagen staining, and increased cell nuclei numbers. Interestingly, though, immunohistochemical cell typing suggests that the observed increased cellularity does not include a significant inflammatory component but is secondary to increased numbers of endothelial cells (i.e., vascularization) and fibroblasts. These histological features likely represent a biological repair/remodeling response resulting from overuse running.

Compaction strategies for modifying the drug delivery capabilities of gelled calcium polyphosphate matrices.

Calcium polyphosphates (CPPs) have shown potential as drug delivery matrices, particularly in treating bone-related chronic diseases such as osteomyelitis, where maintenance of sufficient bactericidal concentrations at the infected bone site is essential. The objective of this study was to incorporate an additional compaction step as part of a gelling protocol to optimize CPP matrix properties while enhancing their drug delivery capabilities. Vancomycin-loaded CPP powders were produced using a previously established gelling and drying protocol, G1, and then subsequently compacted at prescribed levels (30, 113 or 452MPa) before subjecting to an additional gelling and drying protocol (G2). The resulting G2 disks were found to be more homogeneous and dense (p=0.0013) when compared with corresponding G1 disks, though increases in matrix density did not translate into subsequent increases in tensile strength. The compaction regelling protocol did, however, eliminate the burst release phenomena observed with the G1 disks and further extended the release of vancomycin into a clinically acceptable therapeutic range of 3weeks. These changes were associated with the increase in visual homogeneity, the increase in density and a more homogenous dispersion of vancomycin within the G2 disks. The ability to modulate this release profile to a limited extent by altering compaction stress, particle size distribution and regelling time was also demonstrated. Overall, the compaction regelling protocol described here, when used in conjunction with an initial gelling step to achieve matrix drug loading, enhances the flexibility and long-term drug delivery capability of this CPP matrix.