Harry R. Allcock

A highly porous 3-dimensional polyphosphazene polymer matrix for skeletal tissue regeneration

Current methods for the replacement of skeletal tissue in general involve the use of autografts or allografts. There are considerable drawbacks in the use of either of these tissues. In an effort to provide an alternative to traditional graft materials, a degradable 3-dimensional (3-D) osteoblast cell-polymer matrix was designed as a construct for skeletal tissue regeneration. A degradable amino acid containing polymer, poly[(methylphenoxy)(ethyl glycinato) phosphazene], was synthesized and a 3-D matrix system was prepared using a salt leaching technique. This 3-D polyphosphazene polymer matrix system, 3-D-PHOS, was then seeded with osteoblast cells for the creation of a cell-polymer matrix material. The 3-D-PHOS matrix possessed an average pore diameter of 165 microns. Environmental scanning electron microscopy revealed a reconnecting porous network throughout the polymer with an even distribution of pores over the surface of the matrix. Osteoblast cells were found attached and grew on the 3-D-PHOS at a steady rate throughout the 21-day period studied in vitro, in contrast to osteoblast growth kinetics on similar, but 2-D polyphosphazene matrices, that showed a decline in cell growth after 7 days. Characterization of 3-D-PHOS osteoblastpolymer matrices by light microscopy revealed cells growing within the pores as well as on surface of the polymer as early as day 1. This novel porous 3-D-PHOS matrix may be suitable for use as a bioerodible scaffold for regeneration of skeletal tissue.

Polyphosphazene/Nano-Hydroxyapatite Composite Microsphere Scaffolds for Bone Tissue Engineering

The nontoxic, neutral degradation products of amino acid ester polyphosphazenes make them ideal candidates for in vivo orthopedic applications. The quest for new osteocompatible materials for load bearing tissue engineering applications has led us to investigate mechanically competent amino acid ester substituted polyphosphazenes. In this study, we have synthesized three biodegradable polyphosphazenes substituted with side groups, namely, leucine, valine, and phenylalanine ethyl esters. Of these polymers, the phenylalanine ethyl ester substituted polyphosphazene showed the highest glass transition temperature (41.6 degrees C) and, hence, was chosen as a candidate material for forming composite microspheres with 100 nm sized hydroxyapatite (nHAp). The fabricated composite microspheres were sintered into a three-dimensional (3-D) porous scaffold by adopting a dynamic solvent sintering approach. The composite microsphere scaffolds showed compressive moduli of 46-81 MPa with mean pore diameters in the range of 86-145 microm. The 3-D polyphosphazene-nHAp composite microsphere scaffolds showed good osteoblast cell adhesion, proliferation, and alkaline phosphatase expression and are potential suitors for bone tissue engineering applications.

Design of synthetic polymeric structures for cell transplantation and tissue engineering.

Two approaches for cell transplantation and new tissue constructions are discussed. In one case, a novel synthetic polyphosphazene has been synthesized that can be gelled by simply adding ions to it at room temperature under aqueous conditions. This polymer has been shown to be compatible for several different cell types. Microcapsular membranes based on the complex of this polymer with poly (L-lysine) allow the inward diffusion of nutrients to nourish the encapsulated cells, but are impermeable to antibodies. In a second approach, biodegradable polyesters have been designed as scaffolds for liver cells and cartilage cells to aid in organ regeneration. Design of the polymer scaffold including the characterization of the surface chemistries for cell attachment, as well as in-vitro and in-vivo data on cell behavior are presented.

Complex formation and ionic conductivity of polyphosphazene solid electrolytes

Abstract The linear poly[(alkoxy)phosphazene], [NP(OC 2 H 4 OC 2 H 4 OCH 3 ) 2 ] n (MEEP), has been synthesized and investigated as a polymeric electrolyte host material. Amorphous solvent free polymersalt complexes formed with a variety of mono-, di-, and trivalent salts and exhibit high ionic conductivity. The conductivity varies with changes in the identify of the cation, the anion and the salt concentration. It also exhibits a non-Arrhenius temperature dependence. For alkali-metal salt complexes the cations and anions both contribute to the ionic conductivity. The complex (LiSO 3 CF 3 ) 0.25 ·MEEP exhibits a conductivity at room temperature which is 2.5 orders of magnitude greater that the corresponding poly(ethylene oxide) complex.

High temperature transport properties of polyphosphazene membranes for direct methanol fuel cells

Experimental methods for studying the conductivity and methanol permeability of proton conductive polymers over a wide range of temperatures have been developed. The proton conductivity and methanol permeability of several polymer electrolyte membranes including sulfonated and phosphonated poly[(aryloxy)phosphazenes] was determined at temperatures up to 120 °C. Nafion 117 membranes were tested using the same methods in order to determine the reliability of the methods. Although the conductivities of the polyphosphazene membranes were either similar to or lower than that of the Nafion 117 membranes, they continue to hold promise for fuel cell applications. We observed similar activation energies of proton conduction for Nafion 117, and for sulfonated and phosphonated polyphosphazene membranes. However, the methanol permeability of a sulfonated membrane was about 8 times lower than that of the Nafion 117 membrane at room temperature although the values were comparable at 120 °C. The permeability of a phosphonated phosphazene derivative was about 40 times lower than that of the Nafion 117 membrane at room temperature and about 9 times lower at 120 °C. This is a significant improvement over the behavior of Nafion 117.

Degradable polyphosphazene/poly(α-hydroxyester) blends: degradation studies

Biomaterials based on the polymers of lactic acid and glycolic acid and their copolymers are used or studied extensively as implantable devices for drug delivery, tissue engineering and other biomedical applications. Although these polymers have shown good biocompatibility, concerns have been raised regarding their acidic degradation products, which have important implications for long-term implantable systems. Therefore, we have designed a novel biodegradable polyphosphazene/poly(a-hydroxyester) blend whose degradation products are less acidic than those of the poly(a-hydroxyester) alone. In this study, the degradation characteristics of a blend of poly(lactide-co-glycolide) (50 :50 PLAGA) and poly[(50% ethyl glycinato)(50% p-methylphenoxy) phosphazene] (PPHOS-EG50) were qualitatively and quantitatively determined with comparisons made to the parent polymers. Circular matrices (14 mm diameter) of the PLAGA, PPHOS-EG50 and PLAGA–PPHOS-EG50 blend were degraded in nonbuffered solutions (pH 7.4). The degraded polymers were characterized for percentage mass loss and molecular weight and the degradation medium was characterized for acid released in non-buffered solutions. The amounts of neutralizing base necessary to bring about neutral pH were measured for each polymer or polymer blend during degradation. The poly(phosphazene)/poly(lactideco-glycolide) blend required significantly less neutralizing base in order to bring about neutral solution pH during the degradation period studied. The results indicated that the blend degraded at a rate intermediate to that of the parent polymers and that the degradation products of the polyphosphazene neutralized the acidic degradation products of PLAGA. Thus, results from these in vitro degradation studies suggest that the PLAGA–PPHOS-EG50 blend may provide a viable improvement to biomaterials based on acid-releasing organic polymers. r 2002 Elsevier Science Ltd. All rights reserved.

Poly[(amino acid ester)phosphazenes] as substrates for the controlled release of small molecules

Three different poly[(amino acid ester)phosphazenes] have been examined in order to investigate their possible use as drug delivery vehicles. The three polymers are poly[di(ethyl glycinato)phosphazene], poly[di(ethyl alanato)phosphazene] and poly[di(benzyl alanato)phosphazene]. These macromolecules either share the same amino acid residue or the same ester group, and this facilitated comparisons of the hydrolytic decomposition and the small molecule release profiles of the polymers. The polymers were synthesized by treatment of poly(dichlorophosphazene) with an excess of the appropriate amino acid ester. Tetrahydrofuran solutions of each polymer were then thoroughly mixed with ethacrynic acid, a diuretic, or Biebrich Scarlet, an azo dye. Films cast from these solutions were immersed in aqueous media (pH 7) at 25 degrees C and at 37 degrees C for approximately 1400 h. During these experiments, the release of the small molecules was monitored by UV/visible spectroscopy. The molecular weight decline and the mass loss of the polyphosphazene films were measured.

Polyphosphazene polymers for tissue engineering: an analysis of material synthesis, characterization and applications

Tissue engineering often utilizes biodegradable polymers in the form of porous scaffolds for regenerating de novo tissues. There is an ever-increasing need for biodegradable polymers as temporary substrates for facilitating tissue regeneration. Compared to the widely used polyesters, polyorthoesters, poly(α-amino acids), and poly(anhydrides), biodegradable polyphosphazenes form a unique class of polymers that has vast potential for tissue engineering applications. Polyphosphazenes are linear high molecular weight polymers with an inorganic backbone consisting of alternating phosphorous and nitrogen atoms with two organic side groups attached to each phosphorous atom. The synthetic flexibility of polyphosphazenes has enabled the development of a wide range of polymers with a variety of physical, chemical and biological properties. These biodegradable polyphosphazenes undergo hydrolytic degradation yielding non-toxic and neutral pH degradation products due to the buffering capacity of phosphates and ammonia that are produced simultaneously during polyphosphazene degradation. This review focuses on synthesis of biodegradable polyphosphazenes, their degradation characteristics, biocompatibility, and their applications as tissue regeneration and controlled delivery matrices with a particular emphasis on systems based on polyphosphazenes alone, polyphosphazene blends and polyphosphazene composites.

Bioerodible polyphosphazenes and their medical potential

An account is presented of the development, evaluation, and current status of an unusual series of polymers optimized specifically for biomedical applications. The polymers are based on the polyphosphazene platform with side groups chosen for their ability to sensitize the polymers to hydrolysis to benign small molecules that can be metabolized or excreted from the body. The largest class of these polymers consists of macromolecules with amino acid ester side groups and these are the main focus of the article. However, a variety of polymers with other side groups also show promise as bioerodible species, and these are mentioned later in the article.

Novel polyphosphazene/poly(lactide-co-glycolide) blends: miscibility and degradation studies

A novel biodegradable polymer blend was developed for potential biomedical applications. A 50:50 poly(lactide-co-glycolide) (PLAGA) was blended in a 50:50 ratio with the followiing polyphosphazenes (PPHOS): poly[(25% ethyl glycinato)(75% p-methylphenoxy)phosphazene[, poly[(50% ethyl glycinato)(50% p-methylphenoxy)phosphazene], and poly[(75% ethyl glycinato)(25% p-methylphenoxy)phosphazene] to obtain Blends A, B, and C, respectively, using a mutual solvent technique. The miscibility of these blends was determined by measuring their glass transition temperature (Tg) using differential scanning calorimetry. After fabrication using a casting technique, the degradation of the matrices was examined. Differential scanning calorimetry showed one glass transition temperature for each blend which was between the Tgs of their respective parent polymers indicating miscibility of the blends. Surface analysis by scanning electron microscopy showed the matrices to have smooth uniform surfaces. Degradation studies showed near-zero order degradation kinetics for the blends with Blends A and B losing 10% of their mass after two weeks and Blend C degrading more rapidly (30% mass loss during the same period). These findings suggest that these novel biodegradable PLAGA/PPHOS blends may be useful for biomedical purposes.