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Biodegradable polyphosphazene biomaterials for tissue engineering and delivery of therapeutics.

Baillargeon AL, Mequanint K - Biomed Res Int (2014)

Bottom Line: Polyphosphazenes are synthesized through a relatively well-known two-step reaction scheme which involves the substitution of the initial linear precursor with a wide range of nucleophiles.The objective of this review is to discuss the suitability of poly(amino acid ester)phosphazene biomaterials in regard to their unique stimuli responsive properties, tunable degradation rates and mechanical properties, as well as in vitro and in vivo biocompatibility.Lastly, the utility of polyphosphazenes is further extended as they are being employed in blend materials for new applications and as another method of tailoring material properties.

View Article: PubMed Central - PubMed

Affiliation: Graduate Program of Biomedical Engineering, Faculty of Engineering, The University of Western Ontario, London, ON, Canada N6A 5B9.

ABSTRACT
Degradable biomaterials continue to play a major role in tissue engineering and regenerative medicine as well as for delivering therapeutic agents. Although the chemistry of polyphosphazenes has been studied extensively, a systematic review of their applications for a wide range of biomedical applications is lacking. Polyphosphazenes are synthesized through a relatively well-known two-step reaction scheme which involves the substitution of the initial linear precursor with a wide range of nucleophiles. The ease of substitution has led to the development of a broad class of materials that have been studied for numerous biomedical applications including as scaffold materials for tissue engineering and regenerative medicine. The objective of this review is to discuss the suitability of poly(amino acid ester)phosphazene biomaterials in regard to their unique stimuli responsive properties, tunable degradation rates and mechanical properties, as well as in vitro and in vivo biocompatibility. The application of these materials in areas such as tissue engineering and drug delivery is discussed systematically. Lastly, the utility of polyphosphazenes is further extended as they are being employed in blend materials for new applications and as another method of tailoring material properties.

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Scheme showing the synthesis and functionalization of poly(dichlorophosphazene) (1b) in the overall synthesis of polyphosphazenes from hexachlorocyclotriphosphazene (1a). Reproduced from [5] by permission of the Royal Society of Chemistry (http://dx.doi.org/10.1039/B926402G).
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sch1: Scheme showing the synthesis and functionalization of poly(dichlorophosphazene) (1b) in the overall synthesis of polyphosphazenes from hexachlorocyclotriphosphazene (1a). Reproduced from [5] by permission of the Royal Society of Chemistry (http://dx.doi.org/10.1039/B926402G).

Mentions: Although the thermal ring polymerization of the trimer (1a) to linear poly(dichlorophosphazene) was attempted in the late 1800s by H. N. Stokes, a useful material that was soluble and capable of being functionalized was not realized until the 1960s. The initial thermal ring opening polymerization performed by Stokes lead to a product that was insoluble, due to crosslinking, and that was readily susceptible to hydrolysis when exposed to moisture [18]. In 1965, Allcock and Kugel [27] were able to synthesis linear poly(dichlorophosphazene) through a well-controlled thermal ring opening polymerization from the cyclic trimer hexachlorocyclotriphosphazene according to Scheme 1. The product obtained was soluble allowing it to be modified further by macromolecular substitution of the reactive P–Cl bonds with organic and organometallic nucleophiles. The thermal ring opening polymerization technique developed by Allcock et al. is the most commonly used route to prepare the linear poly(dichlorophosphazene) precursor [5, 18]. A typical process involves reacting purified hexachlorocyclotriphosphazene trimer at 250°C over 5 days in an evacuated polymerization tube. At this point, soluble poly(dichlorophosphazene) has been formed that can be purified and functionalized via the macromolecular substitution reaction (Scheme 1, 1a→1b) [18]. Despite the success of the bulk phase thermal ring opening polymerization in lab scale syntheses, this method is not economically feasible for large-scale production of polyphosphazene materials. Alternative methods, which will not be discussed in this review, including solution phase thermal ring opening [28], living cationic [29–32], and one-pot De Jaeger [33] polymerization techniques have been reported.


Biodegradable polyphosphazene biomaterials for tissue engineering and delivery of therapeutics.

Baillargeon AL, Mequanint K - Biomed Res Int (2014)

Scheme showing the synthesis and functionalization of poly(dichlorophosphazene) (1b) in the overall synthesis of polyphosphazenes from hexachlorocyclotriphosphazene (1a). Reproduced from [5] by permission of the Royal Society of Chemistry (http://dx.doi.org/10.1039/B926402G).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4022062&req=5

sch1: Scheme showing the synthesis and functionalization of poly(dichlorophosphazene) (1b) in the overall synthesis of polyphosphazenes from hexachlorocyclotriphosphazene (1a). Reproduced from [5] by permission of the Royal Society of Chemistry (http://dx.doi.org/10.1039/B926402G).
Mentions: Although the thermal ring polymerization of the trimer (1a) to linear poly(dichlorophosphazene) was attempted in the late 1800s by H. N. Stokes, a useful material that was soluble and capable of being functionalized was not realized until the 1960s. The initial thermal ring opening polymerization performed by Stokes lead to a product that was insoluble, due to crosslinking, and that was readily susceptible to hydrolysis when exposed to moisture [18]. In 1965, Allcock and Kugel [27] were able to synthesis linear poly(dichlorophosphazene) through a well-controlled thermal ring opening polymerization from the cyclic trimer hexachlorocyclotriphosphazene according to Scheme 1. The product obtained was soluble allowing it to be modified further by macromolecular substitution of the reactive P–Cl bonds with organic and organometallic nucleophiles. The thermal ring opening polymerization technique developed by Allcock et al. is the most commonly used route to prepare the linear poly(dichlorophosphazene) precursor [5, 18]. A typical process involves reacting purified hexachlorocyclotriphosphazene trimer at 250°C over 5 days in an evacuated polymerization tube. At this point, soluble poly(dichlorophosphazene) has been formed that can be purified and functionalized via the macromolecular substitution reaction (Scheme 1, 1a→1b) [18]. Despite the success of the bulk phase thermal ring opening polymerization in lab scale syntheses, this method is not economically feasible for large-scale production of polyphosphazene materials. Alternative methods, which will not be discussed in this review, including solution phase thermal ring opening [28], living cationic [29–32], and one-pot De Jaeger [33] polymerization techniques have been reported.

Bottom Line: Polyphosphazenes are synthesized through a relatively well-known two-step reaction scheme which involves the substitution of the initial linear precursor with a wide range of nucleophiles.The objective of this review is to discuss the suitability of poly(amino acid ester)phosphazene biomaterials in regard to their unique stimuli responsive properties, tunable degradation rates and mechanical properties, as well as in vitro and in vivo biocompatibility.Lastly, the utility of polyphosphazenes is further extended as they are being employed in blend materials for new applications and as another method of tailoring material properties.

View Article: PubMed Central - PubMed

Affiliation: Graduate Program of Biomedical Engineering, Faculty of Engineering, The University of Western Ontario, London, ON, Canada N6A 5B9.

ABSTRACT
Degradable biomaterials continue to play a major role in tissue engineering and regenerative medicine as well as for delivering therapeutic agents. Although the chemistry of polyphosphazenes has been studied extensively, a systematic review of their applications for a wide range of biomedical applications is lacking. Polyphosphazenes are synthesized through a relatively well-known two-step reaction scheme which involves the substitution of the initial linear precursor with a wide range of nucleophiles. The ease of substitution has led to the development of a broad class of materials that have been studied for numerous biomedical applications including as scaffold materials for tissue engineering and regenerative medicine. The objective of this review is to discuss the suitability of poly(amino acid ester)phosphazene biomaterials in regard to their unique stimuli responsive properties, tunable degradation rates and mechanical properties, as well as in vitro and in vivo biocompatibility. The application of these materials in areas such as tissue engineering and drug delivery is discussed systematically. Lastly, the utility of polyphosphazenes is further extended as they are being employed in blend materials for new applications and as another method of tailoring material properties.

Show MeSH