Biodegradable Polyphosphazene Biomaterials for Tissue Engineering and Delivery of Therapeutics

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.

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering

“…Macromolecular substitution reactions allow the introduction of different side groups that detect the polymer properties in a controlled manner[4, 5, 9, 10, 15, 32, 39, 40, 58, 62, 63, 65, 68, 69]. In addition to single side group substitution, multiple substituents can be covalently linked to the polymer backbone (Fig.…”

“…Chemical and physical properties are largely dependent upon the type of side groups attached to the polyphosphazene backbone. Incorporation of different side groups can alter the degradation rate and mechanical properties of the polymer [4, 9, 28, 32, 39-41]. For example, amino acid ester side groups will instigate hydrolysis within the polymer backbone [5, 9, 32, 40, 42] while there is a retardation of hydrolysis in the presence of hydrophobic phenylphenoxy side groups [4, 8, 15, 19, 43].…”

“…Incorporation of different side groups can alter the degradation rate and mechanical properties of the polymer [4, 9, 28, 32, 39-41]. For example, amino acid ester side groups will instigate hydrolysis within the polymer backbone [5, 9, 32, 40, 42] while there is a retardation of hydrolysis in the presence of hydrophobic phenylphenoxy side groups [4, 8, 15, 19, 43]. Unlike the polyester family, amino acid ethyl ester substituted polyphosphazenes undergo hydrolysis generating non-toxic and buffering degradation products composed mainly of phosphate, ammonia, and corresponding side groups [10, 23, 39, 44-47].…”

“…The pH profiles of the media in which these blends degraded were much higher than that of the PLAGA's as the polyphosphazene degradation products were able to neutralize the acidic degradation products from the PLAGA. However, majority of these blend systems do not possess requisite mechanical properties needed for bone tissue engineering [5, 9, 18, 19, 23, 29, 39, 41, 43, 46, 47, 50, 55]. It is still a lingering issue to fabricate completely miscible PPHOS-PLAGA blends with appropriate mechanical properties for bone tissue engineering applications.…”

Vascularization of three-dimensional engineered tissues for regenerative medicine applications

“…Thus, subsequent investigations placed a greater emphasis on utilizing materials that were biodegradable and feasible for implantation [36]. Some of these materials include aliphatic polyester elastomers [37, 38], polyurethanes [39], polylactones [40], polyphosphazenes [41], and tyrosine derived polycarbonates [42, 43] (Table 1). Based on the physical properties of the polymer type, different fabrication approaches have been used to synthesize 3D constructs that promote cell attachment, survival, growth, differentiation and function.…”