Polyphosphazenes biocompatibility

Deprotection of X, and subsequent oxidation, reduction, and acetylation reactions can, with care, be carried out without decomposition of the inorganic backbone. Reactions of this type are of particular interest for the synthesis of bioactive or biocompatible polyphosphazenes. 

Lora, S., Carenza, M., Palma, G., Pezzin, G., Caliceti, P., Battaglia, P. and Lora, A. (1991) Biocompatible polyphosphazenes by radiation-induced graft copolymerization and heparinization. Birrmaterials, 12(3), 275-280... 

Lora S, Carenza M, Palma G, Caliceti P, Battaglia P and Lora A, Biocompatible polyphosphazene by radiation-induced graft copolymerization and heparinization , Biomaterials, 1991, 12, 275-80. 

Applications. Polymers with small alkyl substituents, particularly (13), are ideal candidates for elastomer formulation because of quite low temperature flexibiUty, hydrolytic and chemical stabiUty, and high temperature stabiUty. The abiUty to readily incorporate other substituents (ia addition to methyl), particularly vinyl groups, should provide for conventional cure sites. In light of the biocompatibiUty of polysdoxanes and P—O- and P—N-substituted polyphosphazenes, poly(alkyl/arylphosphazenes) are also likely to be biocompatible polymers. Therefore, biomedical appHcations can also be envisaged for (3). A third potential appHcation is ia the area of soHd-state batteries. The first steps toward ionic conductivity have been observed with polymers (13) and (15) using lithium and silver salts (78). 

Polyphosphazene films could also be modified very easily by grafting organic polymers onto the surface using chemical, photochemical or y-radiolytic processes. In almost all cases these studies led to the increase in the surface hy-drophilicity and biocompatibility of the phosphazene films without depressing their bulk features. 

The term "bioenertness" is a relative one since few if any synthetic polymers are totally biocompatible with living tissues. The terra is used here on the basis of preUminary in vitro and in vivo tests, together with chemical evaluations based on analogies with other well-tested systems. Two different types of polyphosphazenes are of interest as bioinert materials those with strongly hydrophobic surface characteristics and those with hydrophilic surfaces. These will be considered in turn. 

Both types are hydrophobic materials that, depending on the side group arrangements, can exist as elastomers or as microcrystalline fiber- or film-forming materials. Preliminary studies have suggested that these two classes of polyphosphazenes are inert and biocompatible in subcutaneous tissue implantation experiments. 

Biodegradable polymers, both synthetic and natural, have gained more attention as carriers because of their biocompatibility and biodegradability and therewith the low impact on the environment. Examples of biodegradable polymers are synthetic polymers, such as polyesters, poly(orfho-esters), polyanhydrides and polyphosphazenes, and natural polymers, like polysaccharides such as chitosan, hyaluronic acid and alginates. 

The versatility of water-soluble polyphosphazenes is in the variations in the structures that can be prepared. Structures with a low glass-transition temperature backbone can be modified with a variety of versatile side units. These may find use in solid polymeric ionic conductors, as a means to entrap and immobilize enzymes with retention of enzymic activity, and in biological functions as hydrogels with the capability of exhibiting biocompatibility and... 

Polymer 3.87 has been evaluated as a matrix for the controlled release of progesterone.197 It was first shown that the rate of release of this steroid and of bovine serum albumen can be controlled by variations in the ratio of aryloxy to imidazolyl side groups atached to the polyphosphazene chain. In vitro and in vivo studies were conducted to examine the release rate of labelled steroid from devices implanted subcutaneously in rats. Typical data are shown in Figure 3.22. The biocompatibility of this system, at least in rats, was found to be good. 

Among new applications [192,193] attention has been focused on the biocompatible, bioactive, and biodegradable properties. Dopamine and several enzymes, e.g., trypsine, have been covalently bound to polyphos-phazene chain. AJso anestisics, steroids, and antibacterial agents may be linked to polyphosphazene with promising pharmaceutical applications. 

This chapter on polyphosphazenes provides the reader an overview of the synthesis and side group chemistry in context to the degradation profile and biocompatibility. In addition, it reviews the medical applications developed using biodegradable polyphosphazenes specifically drug delivery matrices and tissue-engineering scaffolds. 

C.T. Laurencin, et al.. The biocompatibility of polyphosphazenes. Evaluation in Bone, in 24th Annual Meeting in Conjunction with 30th International Symposium, San Diego, United States, Society for Biomaterials, 1998. 

Biocompatibility of polyphosphazenes is often mentioned, but few detailed studies about the biocompatibility of polyphosphazenes in vivo have been made. Biocompatibility itself is a v ery complex topic. The biocompatibility of a material is very much dependent upon the situation of testing. Animal species, place of implantation, shape of material, etc., are all very importantfactors that wall determine the biocompatibility of the material. For that reason it is very important that specifications about the test conditions are given. This, however, is often lacking. 

Lora et al, did try to enhance the biocompatibility of poly[bis(trifluoroethoxy)-phosphazenes] (PTFP) and poly[bis(phenoxy)phosphazenes] (PPP) by grafting different side groups on the polymer surface (Figpme 28). Graft copolymerization w ith dimethylaminoethylmethacrylate (DMAEM) onto the polyphosphazene surfaces highly enhances their biocompatibility. Subsequent heparinization has a negative effect, which is more appreciable with the PPP-based samples (Lora et al., 1991). Surface modification of poly[bis(trifluoroethoxy)phosphazene] with... 

In vitro biocompatibility tests were also performed by Neenan et al. (1982). They used heparinized poly[(organo)phosphazenes] to enhance the anti-thrombogenic properties of polyphosphazenes. Films of these materials containing heparine were subjected to bovine blood clotting tests (Figure 29). 

Polyphosphazenes, owing to their inorganic backbone, are characterized by properties that are not common to organic pol5miers, namely low temperature flexibility, nonflammability, good thermal stability, and biocompatibility. 

Biomedical Applications. Biomedical applications were investigated by a number of polyphosphazene research groups (181). The most important studies concerned biocompatibility, biodegradation, enz5une immobilization, and drug delivery (182,183). Polyphosphazene implants and prosthe-ses were also examined. Biocompatibility through appropriate manipulation of surface or bulk chemistry was studied extensively (184). Works on the synthesis and cross-linking of amphiphilic polyphosphazenes (94), heparin immobilization (185-187), and other surface functionalizations (4,101) were reported. 

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