The Background and Scope of Polyphosphazenes as Biomedical Materials

  • Harry R. AllcockEmail author
Part of the following topical collections:
  1. Special Edition: Quartet editor Alexander Andrianov


Although many traditional organic polymers have been evaluated for uses in biology and medicine, relatively few have proved to be satisfactory for crucial uses such as surgical sutures or mesh, tissue engineering substrates, controlled drug delivery, or soft matter. A reason for this is that most large-volume commercial polymers are optimized for some mechanical engineering purpose, and biomedical compatibility or bioerodibility is not one of the target properties. Thus, biomedical scientists and engineers have been forced to improvise and compromise by using widely available non-biological polymers, mainly because those materials are already available in commercial quantities. Polyphosphazenes offer an opportunity to solve many of these problems.

Lay Summary

A crucial need exists for new polymers that can be utilized in orthopedics, cardiovascular, dental, neural, or drug delivery applications, yet very few long-existing polymers have properties that are ideal for these medical uses. Our research seeks to design and find methods to synthesize polymeric materials that are specifically designed to solve a range of medical challenges. In our program, we make use of an unusual polymer backbone comprised of alternating phosphorus and nitrogen atoms to which are attached a wide range of organic side groups. This system is unique in the wide range of different property combinations that can be generated, and many of these combinations can be matched precisely to the needs of medical materials.


Polymers Polyphosphazenes Synthesis Biomedical Elastomers Bioerodible Biostable 



The author acknowledges the contributions to our program by 108 graduate students, numerous undergraduates, 36 postdoctoral scientists, and many collaborators. The biomedical funding at different times has been through the U.S. National Institutes of Health, National Science Foundation, the U.S. Army Research Office, The Pennsylvania State University, and private donations.


  1. 1.
    Allcock HR. Chemistry and applications of polyphosphazenes. Hoboken, N.J: Wiley; 2003.Google Scholar
  2. 2.
    Allcock HR, Kugel RL. Synthesis of high polymeric alkoxy- and aryloxy- phosphonitriles. J Am Chem Soc. 1965;87:4216–7.CrossRefGoogle Scholar
  3. 3.
    Allcock HR, Kugel RL, Valan KJ. High molecular weight poly(alkoxy- and aryloxyphosphazenes). Inorg Chem. 1966;5:1709–15.CrossRefGoogle Scholar
  4. 4.
    Allcock HR, Kugel RL. High molecular weight poly(diaminophosphazenes). Inorg Chem. 1966;5:1716–8.CrossRefGoogle Scholar
  5. 5.
    Wisian-Neilson P. Polyphosphazenes from condensation polymerization, Ch. 10. In: Andrianov AK, editor. Biomedical Applications of Polyphosphazenes. Hoboken, N. J: Wiley; 2009. p. 155–16.Google Scholar
  6. 6.
    Matyjaszewski K, Uli F, Montague RA, White ML. Synthesis of polyphosphazenes from phosphoranimines and phosphine azides. Polymer. 1994;35:5005–11.CrossRefGoogle Scholar
  7. 7.
    Honeyman CH, Manners I, Morrissey CT, Allcock HR. Ambient temperature synthesis of poly(dichlorophosphazene) with molecular weight control. J Am Chem Soc. 1995;117:7035–6.CrossRefGoogle Scholar
  8. 8.
    Allcock HR, Nelson JM, Reeves SD, Honeyman CH, Manners I. Ambient temperature direct synthesis of poly(organophosphazenes) via the “living” cationic polymerization of organo-substituted phosphoramines. Macromolecules. 1997;30:50–6.CrossRefGoogle Scholar
  9. 9.
    Nelson JM, Allcock HR. Synthesis of triarmed star polyphosphazenes via the living cationic polymerization of phosphoranimines at ambient temperatures. Macromolecules. 1997;30:1854–6.CrossRefGoogle Scholar
  10. 10.
    Rose SH. Synthesis of phosphonitrilic fluoroelastomers. Polym Lett. 1968;6:837–9.CrossRefGoogle Scholar
  11. 11.
    Tate DP. Polyphosphazene elastomers. J Polymer Sci Polym Lett. 1974;48:33–45.Google Scholar
  12. 12.
    Penton H, Polyphosphazenes R. Performance polymers for specialty applications. Ch 21. In: Zeldin M, et al., editors. Inorganic and Organometallic Polymers. ACS Symposium Series. Washington, DC: American Chemical Society; 1988.Google Scholar
  13. 13.
    Xu L, Li Z, Tian Z, Chen C, Allcock HR, Siedlecki C. A new textured polyphosphazene biomaterial with improved blood coagulation and microbial infection responses. Acta Biomater. 2018;67:87–98.CrossRefGoogle Scholar
  14. 14.
    Modzelewski T, Wilts E, Allcock HR. Elastomeric polyphosphazenes with phenoxy-cyclotriphosphazene side groups. 2015;48:7543–9.Google Scholar
  15. 15.
    Modzelewski T, Wonderling NM, Allcock HR. Phosphazene elastomers containing interdigitated oligo-p-phenoxy side groups. 2015;48:4882–90.Google Scholar
  16. 16.
    Modzelewski T, Allcock HR. An unusual polymer architecture for the generation of elastomeric properties in fluorinated polyphosphazenes. Macromolecules. 2014;47:6776–82.CrossRefGoogle Scholar
  17. 17.
    Prange R, Allcock HR. Telechelic syntheses of the first phosphazene-siloxane block copolymers. Macromolecules. 1999;32:6390–2.CrossRefGoogle Scholar
  18. 18.
    Allcock HR, Kuharcik SE, Nelson CJ. The synthesis and characterization of amino-organosiloxane-bearing polyphosphazenes: new properties by the elimination of hydrogen bonding. Macromolecules. 1996;29:3686–93.CrossRefGoogle Scholar
  19. 19.
    Allcock HR, Kuharcik SE. Hybrid phosphazene-organosilicon polymers. Part II. High polymer and materials synthesis and properties. J Inorg Organ Polym. 1996;6:1–41.CrossRefGoogle Scholar
  20. 20.
    Allcock HR, Smith DE. Surface studies of poly(organophosphazenes) containing dimethylsiloxane grafts. Chem Mater. 1995;7:1469–74.CrossRefGoogle Scholar
  21. 21.
    Powell ES, Chang Y, Allcock HR, Kim C. Self-organization of amphiphilic polyphosphazene-polystyrene block copolymers. Polymer Preprints (ACS Div. Polymer Chem.). 2004;45:49.Google Scholar
  22. 22.
    Allcock HR, Powell ES, Chang Y, Kim C. Synthesis and micellar behavior of amphiphilic polystyrene-poly[bis(methoxyethoxyethoxy)phosphazene] co-polymers. Macromolecules. 2004;37:7163–7.CrossRefGoogle Scholar
  23. 23.
    Allcock HR, Powell ES, Maher AE, Berda EB. Poly(methylmethacrylate)- graft-poly[bis(trifluoroethoxy)phosphazene] copolymers; synthesis characterization and effects of polyphosphazene incorporation. Macro- molecules. 2004;37:5824–9.CrossRefGoogle Scholar
  24. 24.
    Laurencin C, Koh HJ, Neenan TX, Allcock HR, Langer RS. Controlled release using a new bioerodible polyphosphazene matrix system. J Biomed Res. 1987;21:1231–46.CrossRefGoogle Scholar
  25. 25.
    Allcock HR, Morozowich NL. Bioerodible polyphosphazenes and their medical potential. Royal Soc Chem. 2012;3:578–90.Google Scholar
  26. 26.
    Nichol JL, Hotham IT, Allcock HR. Ethoxyphosphazene polymers and their hydrolytic behavior. Macromolecules. 2014;109:92–6.Google Scholar
  27. 27.
    Allcock HR, Scopelianos AG. Synthesis of sugar-substituted cyclic and polymeric phosphazenes and their oxidation, reduction, and acetylation reactions. Macromolecules. 1983;16:715–9.CrossRefGoogle Scholar
  28. 28.
    Peach MS, Kumbar SG, James R, Toti US, Balasubramaniam D, Deng M, et al. Design and optimization of polyphosphazene functionalized fiber matrices for soft tissue engineering. J Biomed Nano- Tech. 2012;8:107–24.CrossRefGoogle Scholar
  29. 29.
    Deng M, Kumbar SG, Nair LS, Weikel AL, Allcock HR, Laurencin CT. Biomimetic structures: biological implications of dipeptide-substituted phosphazene-polymer blend nanofiber matrices for load bearing bone regeneration. Adv Functional Mater. 2011;21:2641–51.CrossRefGoogle Scholar
  30. 30.
    Ogueri KS, Allcock HR, Laurencin CT. Polyphosphazene polymers (2019). In: Encyclopedia of Polymer Science and Technology (Accepted).Google Scholar
  31. 31.
    Deng M, Allcock HR, Laurencin CT, Kumbar SG. Polyphosphazenes as biomaterials. In: Dumitriv V, Popa V, editors. Polymeric Biomaterials. 3rd ed. Boca Raton: CRC Press.Google Scholar
  32. 32.
    Peach MS, Ramos DM, James R, Morozowich NL, Mazzocca AD, Doty SB, et al. Engineered stem cell niche matrices for rotator cuff tendon regenerative engineering. PLOS. 2017:1–19.Google Scholar
  33. 33.
    Cohen S, Bano MC, Visscher KB, Chow M, Allcock HR, Langer RS. An ionically-crosslinkable polyphosphazene: a novel polymer for micro- encapsulation. J Am Chem Soc. 1990;112:7832–3.CrossRefGoogle Scholar
  34. 34.
    Allcock HR, Powell ES, Chang Y, Kim C. Synthesis and micellar behavior of amphiphilic polystyrene-poly[bis(methoxyethoxyethoxy)phosphazene] block copolymers. Macromolecules. 2004;37:7163–7.CrossRefGoogle Scholar
  35. 35.
    Allcock HR, Allen RW, O’Brien JP. Synthesis of platinum derivatives of polymeric and cyclic phosphazenes. J Am Chem Soc. 1977;99:3984–7.CrossRefGoogle Scholar
  36. 36.
    Jun YJ, Kim JI, Jun MJ, Sohn YS. Selective tumor targeting by enhanced permeability and retention effect. Synthesis and antitumor activity of polyphosphazene platinum (II) conjugates. J Inorg Biochem. 2005;99(8):1593–601.CrossRefGoogle Scholar
  37. 37.
    Allcock HR, Kwon S. An ionically-crosslinkable poly[di(phosphazene: Poly- carboxylatophenoxy phosphazene)]. 1989;22:75–9.Google Scholar
  38. 38.
    Selin V, Albright V, Ankner JF, Marin A, Andrianov AK, Sukhishvili SA. Biocompatible nanocoatings of fluorinated polyphosphazenes through aqueous assembly. ACS Appl Mater Interfaces. 2018;10(11):9756–64.CrossRefGoogle Scholar
  39. 39.
    Andrianov AK, Martinez AP, Weidman JL, Marin A, Fuerst TR. Biodegradable PEGylated polyelectrolyte nanocomplexes for protein delivery. Biomacromolecules. 2018;19:3467–78.CrossRefGoogle Scholar
  40. 40.
    Allcock HR, Fuller TJ. Phosphazene high polymers with steroidal side groups. Macromolecules. 1980;13:1338–45.CrossRefGoogle Scholar
  41. 41.
    Crommen J, Vandorpe J, Schacht E. Degradable polyphosphazenes for biomedical applications. J. Controlled Release. 1993;24:I67–180.CrossRefGoogle Scholar
  42. 42.
    Schacht, E.; Crommen, J. Bioerodible Sustained Release Implants. U.S. Patent 4975280A (to Ethyl Corp.) 1989.Google Scholar
  43. 43.
    Hindenlang MD, Soudakov AA, Imler GH, Laurencin CT, Nair LS, Allcock HR. Iodine-containing radio-opaque polyphosphazenes R. S C. Polym Chem. 2010;1:1467–74.CrossRefGoogle Scholar
  44. 44.
    Chhour P, Gallo N, Cheheltani R, Williams D, Al-Zaki A, Paik T, et al. Nanodisco balls: control over surface versus core loading of diagnostically-active nanocrystals into polymer nanoparticles. ACS Nano. 2014;8(9):9143–53.CrossRefGoogle Scholar
  45. 45.
    Bates MC, Yousaf A, Sun L, Barakat M, Kueller A. Translational research and early favorable clinical results of a novel polyphosphazene (polyzene-F) nanocoating. Regen Eng Transl Med. 2019.

Copyright information

© The Regenerative Engineering Society 2019

Authors and Affiliations

  1. 1.Departments of Chemistry, Chemical Engineering, and BioengineeringThe Pennsylvania State UniversityUniversity ParkUSA

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