Fifteen different poly[ (amino acid ester)phosphazenes] were synthesized to study their crystalline character and hydrolysis behavior in the solution and solid states. The polyphosphazenes synthesized were poly [ bis(methy1 glycinat-N-y1)phosphazenel , poly[ bis(ethy1 glycinat-N-y1)phosphazenel , poly [bis(tertbutyl glycinat-N-yl)phosphazene], poly[bis(benzyl glycinat-N-yl)phosphazene], poly[bis(methyl alaninat-N-yl)phosphazene], poly[bis(ethyl alaninat-N-yl)phosphazene], poly[bis(tert-butyl alaninat-N-y1)phosphazene] , poly[ bis( benzyl alaninat-N-yl) phosphazene] , poly [bis(methyl valinat-N-yl)phosphazene] , poly-[bis(ethyl valinat-N-y1)phosphazenel , poly [bis(tert-butyl valinat-N-y1)phosphazenel , poly[bis(benzyl valinat-N-y1)phosphazenel , poly[bis(methyl phenylalaninat-N-y1)phosphazenel , poly[bis(ethyl pheny1alaninat-Ny1)phosphazenel , and poly [bis(tert-butyl phenylalaninat-N-y1)phosphazenel . The fully-substituted polymerswere obtained by treatment of poly(dich1orophosphazene) with a large excess of the appropriate amino acid ester. Several of these polymers were crystalline as measured by differential scanning calorimetry and by polarized optical microscopy. Hydrolysis studies were performed to estimate the rates of decomposition of the polymers and the duration over which the polymers maintained their structural integrity. The polymers are potential biomedical materials.
The hydrolytically unstable polyphosphazenes, poly [(imidazolyl) (methylphenoxy) phosphazenes] and poly [ethyl glycinato) (methylphenoxy) phosphazenes], were studied as potential polymeric supports for cells in tissue regeneration. For bone repair, their specific function would be to support osteoblast growth, forming a bone-polymer matrix. MC3T3-E1 cells (an osteogenic cell line) were seeded onto polymer matrices and cell adhesion and growth as well as polymer degradation were examined. Both imidazolyl- and ethyl glycinato-substituted polyphosphazenes supported the growth of MC3T3-E1 cells. An increase in the content of the imidazolyl side group resulted in a reduction in cell attachment and growth on the polymer surface and an increase in the rate of degradation of the polymer. In contrast, substitution with the ethyl glycinato group favored increased cell adhesion and growth and also an increase in the rate of degradation of the polymers. Thus, the polyphosphazenes represent a system whereby cell growth and degradation can be modulated by varying the nature of the hydrolytically unstable side chain. This in vitro evaluation suggests that the polyphosphazenes may be suitable candidate biomaterials for the construction of a cell-polymer matrix for tissue regeneration.
Five different poly[(alkyl ether)phosphazenes] were synthesized for studies of their water solubility as well as the swellabilities of their corresponding hydrogels in aqueous media. They are poly-[bis(methoxyethoxy)phosphazene],poly[bis[(aminoethoxy)ethoxy]phosphazene],poly[bis[(methoxyethoxy)ethoxy] phosphazene], poly[bis[(ethoxyethoxy)ethoxy]phosphazene], and poly [bis [ (butoxyethoxy)ethoxy]phosphazene].Lower critical solution temperatures (LCST) were detected for four of the polymers. This phenomenon was independent of polymer concentration. However, poly[bis[(aminoethoxy)ethoxy]phosphazene] possessed no LCST in aqueous media and remained fully soluble at all polymer concentrations. Hydrogels of these polymers were prepared by subjecting them to y radiation (1, 5, and 10 Mrad). The cross-linked polyphosphazenes behaved in a manner similar to that of their soluble counterparts. As the temperature of the aqueous media was increased, the hydrogels became opaque and released water. During these experiments, the percentage of water lost by the hydrogels was independent of both the pH of the aqueous media and the radiation dose received by the gels. No detectable decomposition of the soluble polymers was found nor was any loss of integrity of the hydrogels detected through several heating and cooling cycles. This solubility phenomenon was characteristic only of the interaction with water and was not detected in organic solvents. The potential biomedical applications of these materials are discussed.
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