Skip to main content

Advertisement

SpringerLink
Log in

Recent Trends in the Development of Polyphosphazenes for Bio-applications

  • Review
  • Published:
Regenerative Engineering and Translational Medicine Aims and scope Submit manuscript

Abstract

Recent advances in biomedicine necessitate the critical and systematic review of current trends in the development and modification of biomaterials for biomedical applications. Synthetic polymers continue to play a leading role as biomedical substrates, and polyphosphazenes, as a promising class of biomaterials, have become a research hotspot in the medical and pharmaceutical fields due to their unique properties, such as structural flexibility, property tunability, and diverse functionality. Polyphosphazenes provide an opportunity to combine benefits of organic polymers and inorganic components using an inorganic backbone and organic (or organometallic) side groups. Furthermore, macromolecular substitution different organic groups and active molecules into the polyphosphazene backbone allows for control of the hydrophilic and hydrophobic balance, yielding a wide array of materials. Alongside great tunability, these materials display superior biocompatibility to typical biomaterials and can be blended with other biologically relevant polymers to yield unique erosion profiles and buffering degradation products. Researchers can capitalize on the flexibility of the backbone and multiplicity of the macromolecular substitution reaction to meet various design requirements, including stereochemistry, nanostructure, and topology. Considerable progress has been made using polyphosphazene in the fields of controlled drug/gene/vaccine delivery, regenerative engineering, cell imaging tracking, coating formulations for wound dressing, etc. This includes cyclomatrix-polyphosphazenes, which hold substantial technological prospects with respect to their synthetic design. This review provides a holistic overview of the progress of the recent three years of polyphosphazene-based materials in biomedicine.

Lay Summary

There is a pressing and economic need for new functional polymers that can be employed in numerous biomedical applications, including tissue and regenerative engineering, drug/vaccine/gene delivery, imaging technology, and medical coating formulations. Advances in materials science have enabled the introduction of novel design and synthetic approaches, which involve controlling and manipulating the biomaterial properties and performance on the molecular and atomistic levels. This controlling influence on the structure–property relationship is well prepared to meet biomedical materials’ ever-changing requirements and complexities. While several excellent polymers have emerged in this pursuit, polyphosphazene polymers present a unique avenue to expanding on an existing array of biopolymers and introducing inorganic entities with chemical versatility and neutral bioactivity. Polyphosphazene-based systems could solidify the design framework needed to diversify and personalize biomaterial to suit a wide range of biomedical needs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Reproduced from ref. [11] with permission from the Royal Society of Chemistry

Fig. 3
Fig. 4
Fig. 5

Reproduced from ref. [55] with permission from the Royal Society of Chemistry

Fig. 6

Reproduced from ref. [30]

Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16

Similar content being viewed by others

References

  1. Rothemund S, Teasdale I. Preparation of polyphosphazenes: a tutorial review. Chem Soc Rev. 2016;45:5200–15.

    Article  CAS  Google Scholar 

  2. Andrianov AK, Svirkin YY, LeGolvan MP. Synthesis and biologically relevant properties of polyphosphazene polyacids. Biomacromol. 2004;5:1999–2006.

    Article  CAS  Google Scholar 

  3. Allcock HR. Polyphosphazene elastomers, gels, and other soft materials. Soft Matter. 2012;8:7521–32.

    Article  CAS  Google Scholar 

  4. Teasdale I, Brüggemann O. Polyphosphazenes: multifunctional, biodegradable vehicles for drug and gene delivery. Polymers. 2013;5:161–87.

    Article  Google Scholar 

  5. Ni Z, et al. Recent research progress on polyphosphazene-based drug delivery systems. J Mater Chem B. 2020;8:1555–75.

    Article  CAS  Google Scholar 

  6. Allcock HR, Kugel RL. Synthesis of high polymeric alkoxy- and aryloxyphosphonitriles. J Am Chem Soc. 1960;30:678.

    Google Scholar 

  7. Chen F, Teniola OR, Laurencin CT. Biodegradable polyphosphazenes for regenerative engineering. J Mater Res. 2022;37:1417–28.

    Article  CAS  Google Scholar 

  8. Allcock HR, Morozowich NL. Bioerodible polyphosphazenes and their medical potential. Polym Chem. 2012;3:578–90.

    Article  CAS  Google Scholar 

  9. Wan C, Huang X. Cyclomatrix polyphosphazenes frameworks (Cyclo-POPs) and the related nanomaterials: synthesis, assembly and functionalisation. Mater Today Commun. 2017;11:38–60.

    Article  CAS  Google Scholar 

  10. Andrianov AK, Marin A, Deng J, Fuerst TR. Protein-loaded soluble and nanoparticulate formulations of ionic polyphosphazenes and their interactions on molecular and cellular levels. Mater Sci Eng C. 2020;106: 110179.

    Article  CAS  Google Scholar 

  11. Salinas Y, et al. Dual stimuli-responsive polyphosphazene-based molecular gates for controlled drug delivery in lung cancer cells. RSC Adv. 2020;10:27305–14.

    Article  CAS  Google Scholar 

  12. Quiñones JP, et al. Polyphosphazene-based nanocarriers for the release of agrochemicals and potential anticancer drugs. J Mater Chem B. 2019;7:7783–94.

    Article  Google Scholar 

  13. Grinberg VY, Burova TV, Grinberg NV, Papkov VS, Khokhlov AR. Binding energetics of charged amphiphilic ligands to thermoresponsive biodegradable poly(methoxyethylaminophosphazene) hydrogels. Langmuir. 2019;35:16915–24.

    Article  CAS  Google Scholar 

  14. Abid MA, et al. Synthesis, characterization, hydrolytic degradation, mathematical modeling and antibacterial activity of poly[bis((methoxyethoxy)ethoxy)phosphazene] (MEEP). Polym Bull. 2021;78:6059–72.

    Article  CAS  Google Scholar 

  15. Amin AM, et al. Synthesis, characterization, hydrolytic degradation and mathematical modeling of poly[bis(2(2-methoxyethoxyethoxy diethylamino)phosphazene]. Arab J Sci Eng. 2020;45:241–7.

    Article  CAS  Google Scholar 

  16. Zashikhina N, et al. Synthesis and characterization of macroinitiators based on polyorganophosphazenes for the ring opening polymerization of n-carboxyanhydrides. Polymers. 2021;13:1446.

    Article  CAS  Google Scholar 

  17. Khan RU, et al. Synthesis of polyorganophosphazenes and preparation of their polymersomes for reductive/acidic dual-responsive anticancer drugs release. J Mater Sci. 2020;55:8264–84.

    Article  CAS  Google Scholar 

  18. Khan RU, et al. Synthesis of polyorganophosphazenes and fabrication of their blend microspheres and micro/nanofibers as drug delivery systems. Int J Polym Mater Polym Biomater. 2019;69:545–66.

    Article  Google Scholar 

  19. Wang K, Jiang L, Qiu L. Near infrared light triggered ternary synergistic cancer therapy via L-arginine-loaded nanovesicles with modification of PEGylated indocyanine green. Acta. 2021;140:506–17.

    Google Scholar 

  20. Shahzady TG, et al. Synthesis, characterization and hydrolytic degradation of p-cresol-substituted polyphosphazenes. Arab J Sci Eng. 2019;44:6445–51.

    Article  CAS  Google Scholar 

  21. Ullah RS, et al. Synthesis of polyphosphazene and preparation of microspheres from polyphosphazene blends with PMMA for drug combination therapy. J Mater Sci. 2019;54:745–64.

    Article  CAS  Google Scholar 

  22. Huang Y, et al. Photoluminescent biodegradable polyorganophosphazene: a promising scaffold material for in vivo application to promote bone regeneration. Bioact Mater. 2020;5:102–9.

    Article  Google Scholar 

  23. Ogueri KS, et al. Synthesis, physicochemical analysis, and side group optimization of degradable dipeptide-based polyphosphazenes as potential regenerative biomaterials. ACS Appl Polym Mater. 2019;1:1568–78.

    Article  CAS  Google Scholar 

  24. Huang Y, et al. Biodegradable microspheres made of conductive polyorganophosphazene showing antioxidant capacity for improved bone regeneration. Chem Eng J. 2020;397:125352.

    Article  CAS  Google Scholar 

  25. Ni Z, et al. Polyphosphazene and non-catechol-based antibacterial injectable hydrogel for adhesion of wet tissues as wound dressing. Adv Healthc Mater. 2022;11:2101421.

    Article  CAS  Google Scholar 

  26. Weir MD, Kaner P, Marin A, Andrianov AK. Ionic fluoropolyphosphazenes as potential adhesive agents for dental restoration applications. Regen Eng Transl Med 2021 71. 2021;7:10–20.

    Article  CAS  Google Scholar 

  27. Tong C, et al. Hybrid polyphosphazene-organosilicon polymers as useful elastomers. ACS Appl Polym Mater. 2019;1:1881–6.

    Article  CAS  Google Scholar 

  28. Huang Z, et al. Molecular mechanism study on effect of biodegradable amino acid ester–substituted polyphosphazenes in stimulating osteogenic differentiation. Macromol. Biosci. 2019; 19.

  29. Huang Y, et al. Antibacterial, conductive, and osteocompatible polyorganophosphazene microscaffolds for the repair of infectious calvarial defect. J Biomed Mater Res Part A. 2021. https://doi.org/10.1002/JBM.A.37252.

    Article  Google Scholar 

  30. Ogueri KS, Ogueri KS, Allcock HR, Laurencin CT. A regenerative polymer blend composed of glycylglycine ethyl ester-substituted polyphosphazene and poly(lactic- co -glycolic acid). ACS Appl Polym Mater. 2020;2:1169–79.

    Article  CAS  Google Scholar 

  31. Ogueri KS, et al. In vivo evaluation of the regenerative capability of glycylglycine ethyl ester-substituted polyphosphazene and poly(lactic- co -glycolic acid) blends: a rabbit critical-sized bone defect model. ACS Biomater Sci Eng. 2021;7:1564–72.

    Article  CAS  Google Scholar 

  32. Wu W, et al. On the understanding of dielectric elastomer and its application for all-soft artificial heart. Sci Bull. 2020;66:981–90.

    Article  Google Scholar 

  33. Bouché M, et al. Activatable hybrid polyphosphazene-AuNP nanoprobe for ROS detection by bimodal PA/CT imaging. ACS Appl Mater Interfaces. 2019;11:28648–56.

    Article  Google Scholar 

  34. Zhu W, et al. 131I-Labeled multifunctional polyphosphazene nanospheres for SPECT imaging-guided radiotherapy of tumors. Adv Healthc Mater. 2019;8:1901299.

    Article  CAS  Google Scholar 

  35. Cortes MDLA, et al. Cylindrical micelles by the self-assembly of crystalline-b-coil polyphosphazene-b-P2VP block copolymers. Stabilization of Gold Nanoparticles. Molecules. 2019;24:1772.

    Article  Google Scholar 

  36. Poscher V, Teasdale I, Salinas Y. Surfactant-free synthesis of cyclomatrix and linear organosilica phosphazene-based hybrid nanoparticles. Appl Nano Mater. 2019;2:655–60.

    Article  CAS  Google Scholar 

  37. Aydın M, Aydın B, Sezgintürk MK. Electrochemical immunosensor for CDH22 biomarker based on benzaldehyde substituted poly(phosphazene) modified disposable ITO electrode: a new fabrication strategy for biosensors. Biosens Bioelectron. 2019;126:230–9.

    Article  Google Scholar 

  38. Albright V, et al. Polyphosphazenes enable durable, hemocompatible, highly efficient antibacterial coatings. Biomaterials. 2020;268:120586.

    Article  Google Scholar 

  39. Xu LC, et al. New cross-linkable poly[bis(octafluoropentoxy) phosphazene] biomaterials: synthesis, surface characterization, bacterial adhesion, and plasma coagulation responses. J Biomed Mater Res Part B Appl Biomater. 2020;108:3250–60.

    Article  CAS  Google Scholar 

  40. Albright V, Marin A, Kaner P, Sukhishvili SA, Andrianov AK. New family of water-soluble sulfo-fluoro polyphosphazenes and their assembly within hemocompatible nanocoatings. ACS Appl Bio Mater. 2019;2:3897–906.

    Article  CAS  Google Scholar 

  41. Andrianov AK, et al. In vivo and in vitro potency of polyphosphazene immunoadjuvants with hepatitis C virus antigen and the role of their supramolecular assembly. Cite This Mol Pharm. 2021;18:734.

    Google Scholar 

  42. Marin A, et al. Next generation polyphosphazene immunoadjuvant: synthesis, self-assembly and in vivo potency with human papillomavirus VLPs-based vaccine. Nanomedicine Nanotechnol Biol Med. 2021;33:102359.

    Article  CAS  Google Scholar 

  43. Valencia SM, et al. Improvement of RG1-VLP vaccine performance in BALB/c mice by substitution of alhydrogel with the next generation polyphosphazene adjuvant PCEP. Hum Vaccin Immunother. 2021;17:2748–61.

    Article  CAS  Google Scholar 

  44. Qamar B, et al. Intracellular delivery of active proteins by polyphosphazene polymers. Pharmaceutics. 2021;13:249.

    Article  CAS  Google Scholar 

  45. Andrianov AK, et al. Supramolecular assembly of toll-like receptor 7/8 agonist into multimeric water-soluble constructs enables superior immune stimulation in vitro and in vivo. ACS Appl Bio Mater. 2020;3:3187–95.

    Article  CAS  Google Scholar 

  46. Hsu WH, et al. Structure-optimized interpolymer polyphosphazene complexes for effective gene delivery against glioblastoma. Adv Ther. 2019;2:1800126.

    Article  Google Scholar 

  47. Zhou N, et al. One-pot synthesis of acid-degradable polyphosphazene prodrugs for efficient tumor chemotherapy. J Mater Chem B. 2020;8:10540.

    Article  CAS  Google Scholar 

  48. Ozay H, Ilgin P, Ozay O. Novel hydrogels based on crosslinked chitosan with formyl-phosphazene using Schiff-base reaction. Int J Polym Mater Polym Biomater. 2019;70:246–55.

    Article  Google Scholar 

  49. Mehmood S, et al. Preparation of poly(cyclotriphosphazene-co-piperazine) nanospheres and their drug release behavior. Int J Polym Mater Polym Biomater. 2020;71:139–47.

    Article  Google Scholar 

  50. Jing X, et al. Intelligent nanoflowers: a full tumor microenvironment-responsive multimodal cancer theranostic nanoplatform. Nanoscale. 2019;11:15508–18.

    Article  CAS  Google Scholar 

  51. Örüm SM. Novel cyclomatrix polyphosphazene nanospheres: preparation, characterization and dual anticancer drug release application. Polym Bull. 2021;79:2851–69.

    Article  Google Scholar 

  52. Yurtdaş-Kırımlıoğlu G, Süzen-Demircioğlu Y, Berkman MS, Metinoğlu-Örüm S, Altun E. Synthesis, spectroscopic, thermal properties, in vitro release, and stability studies of ibuprofen-loaded microspheres cross-linked with hexachlorocyclotriphosphazene/octachlorocyclotetraphosphazene. Polym Bull. 2020;78:6221–50.

    Article  Google Scholar 

  53. MetinoğluÖrüm S, SüzenDemircioğlu Y. One-pot synthesis and characterization of crosslinked polyphosphazene dopamine microspheres for controlled drug delivery applications. J Macromol SciPart A. 2019;56:854–9.

    Article  Google Scholar 

  54. Ozay H, Ilgin P, Ozyurt C, Ozay O. The single-step synthesis of thiol-functionalized phosphazene-based polymeric microspheres as drug carrier. Polym Technol Mater. 2020;59:1944–55.

    CAS  Google Scholar 

  55. Jing X, et al. pH/redox dual-stimuli-responsive cross-linked polyphosphazene nanoparticles for multimodal imaging-guided chemo-photodynamic therapy. Nanoscale. 2019;11:9457–67.

    Article  CAS  Google Scholar 

  56. Wang D, et al. Facile preparation of pH/redox dual-responsive biodegradable polyphosphazene prodrugs for effective cancer chemotherapy. Colloids Surfaces B Biointerfaces. 2021;200:111573.

    Article  CAS  Google Scholar 

  57. Onder A, Ozay H. Synthesis and characterization of biodegradable and antioxidant phosphazene-tannic acid nanospheres and their utilization as drug carrier material. Mater Sci Eng C. 2020;120:111723.

    Article  Google Scholar 

  58. Hu X, et al. Facile synthesis of inorganic–organic hybrid fluorescent nanoparticles with AIE feature using hexachlorocyclotriphosphazene as the bridge. J Mol Liq. 2022;345:117693.

    Article  CAS  Google Scholar 

  59. Ding G, et al. Preparation of multiple-spectra encoded polyphosphazene microspheres and application for antibody detection. Polym Bull. 2021. https://doi.org/10.1007/S00289-021-03811-W.

    Article  Google Scholar 

  60. Guo T, et al. Rapid synthesis of amphiphilic europium complexes via ultrasonic treatment-assisted crosslinking reaction. Dye Pigment. 2022;197:109950.

    Article  CAS  Google Scholar 

  61. Bouché M, Cormode DP. Biodegradable AuNP-based plasmonic nanogels as contrast agents for computed tomography and photoacoustics. Biomed Eng Technol. 2022;2393:773–96.

    Article  Google Scholar 

  62. Gascón E, et al. (Amino)cyclophosphazenes as multisite ligands for the synthesis of antitumoral and antibacterial silver(I) complexes. Inorg Chem. 2020;59:2464–83.

    Article  Google Scholar 

  63. Chelike DK, et al. Functionalized iron oxide nanoparticles conjugate of multi-anchored Schiff’s base inorganic heterocyclic pendant groups: cytotoxicity studies. Appl Surf Sci. 2020;501:143963.

    Article  CAS  Google Scholar 

  64. Ogueri KS, Allcock HR, Laurencin CT. Generational biodegradable and regenerative polyphosphazene polymers and their blends with poly (lactic-co-glycolic acid). Prog Polym Sci. 2019;98:101146.

    Article  CAS  Google Scholar 

  65. Gentile P, Chiono V, Carmagnola I, Hatton PV. An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering. Int J Mol Sci. 2014;15:3640–59.

    Article  CAS  Google Scholar 

  66. Fu K, Pack DW, Klibanov AM, Langer R. Visual evidence of acidic environment within degrading poly(lactic-co-glycolic acid) (PLGA) microspheres. Pharm Res. 2000;17:100–6.

    Article  CAS  Google Scholar 

  67. Ge Z, et al. Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model. Biomed Mater. 2009;4:021001.

    Article  Google Scholar 

  68. Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers. 2011;3:1377–97.

    Article  CAS  Google Scholar 

  69. Essa D, Kondiah PPD, Choonara YE, Pillay V. The design of poly(lactide-co-glycolide) nanocarriers for medical applications. Front Bioeng Biotechnol. 2020;8:48.

    Article  Google Scholar 

  70. Echeverria Molina MI, Malollari KG, Komvopoulos K. Design challenges in polymeric scaffolds for tissue engineering. Front Bioeng Biotechnol. 2021;9:617141.

    Article  Google Scholar 

  71. Bu Y, Ma J, Bei J, Wang S. Surface modification of aliphatic polyester to enhance biocompatibility. Front Bioeng Biotechnol. 2019;0:98.

    Article  Google Scholar 

  72. Piotrowska U, Sobczak M, Oledzka E. Characterization of aliphatic polyesters synthesized via enzymatic ring-opening polymerization in ionic liquids. Molecules. 2017;22:923.

    Article  Google Scholar 

  73. Ulery BD, Nair LS, Laurencin CT. Biomedical applications of biodegradable polymers. J Polym Sci Part B Polym Phys. 2011;49:832–64.

    Article  CAS  Google Scholar 

  74. Mouthuy PA, et al. Biocompatibility of implantable materials: an oxidative stress viewpoint. Biomaterials. 2016;109:55–68.

    Article  CAS  Google Scholar 

  75. Wang L, et al. Visual in vivo degradation of injectable hydrogel by real-time and non-invasive tracking using carbon nanodots as fluorescent indicator. Biomaterials. 2017;145:192–206.

    Article  CAS  Google Scholar 

  76. Ahmad D, Patra K, Hossain M. Experimental study and phenomenological modelling of flaw sensitivity of two polymers used as dielectric elastomers. Contin Mech Thermodyn. 2020;32:489–500.

    Article  CAS  Google Scholar 

  77. Brochu P, Pei Q. Dielectric elastomers for actuators and artificial muscles. Electroact Polym Mater. 2012. https://doi.org/10.1007/978-1-4614-0878-9_1.

    Article  Google Scholar 

  78. Andrianov AK, Langer R. Polyphosphazene immunoadjuvants: historical perspective and recent advances. J Control Release. 2021;329:299–315.

    Article  CAS  Google Scholar 

  79. Demarco FF, Corrêa MB, Cenci MS, Moraes RR, Opdam NJM. Longevity of posterior composite restorations: not only a matter of materials. Dent Mater. 2012;28:87–101.

    Article  CAS  Google Scholar 

  80. Albright V, et al. Fluorinated polyphosphazene coatings using aqueous nano-assembly of polyphosphazene polyelectrolytes. ACS Symp Ser. 2018;1298:101–18.

    Article  CAS  Google Scholar 

  81. Selin V, et al. Biocompatible nanocoatings of fluorinated polyphosphazenes through aqueous assembly. ACS Appl Mater Interfaces. 2018;10:9756–64.

    Article  CAS  Google Scholar 

  82. Cheng Y, Feng G, Moraru CI. Micro-and nanotopography sensitive bacterial attachment mechanisms: a review. Front Microbiol. 2019;10:191.

    Article  Google Scholar 

  83. Quan WY, et al. Mussel-inspired catechol-functionalized hydrogels and their medical applications. Molecules. 2019;24:2586.

    Article  CAS  Google Scholar 

  84. Aied A, Greiser U, Pandit A, Wang W. Polymer gene delivery: overcoming the obstacles. Drug Discov Today. 2013;18:1090–8.

    Article  CAS  Google Scholar 

  85. Otsuka T, Kan H-M, Laurencin CT. Regenerative engineering approaches to scar-free skin regeneration. Regen Eng Transl Med. 2022;8(2):225–47. https://doi.org/10.1007/s40883-021-00229-8.

    Article  CAS  Google Scholar 

  86. Ude CC, Shah S, Ogueri KS, Nair LS, Laurencin CT. Stromal vascular fraction for osteoarthritis of the knee regenerative engineering. Regen Eng Transl Med. 2022;8(2):210–24. https://doi.org/10.1007/s40883-021-00226-x.

    Article  Google Scholar 

  87. Mengsteab PY, Freeman J, Barajaa MA, Nair LS, Laurencin CT. Ligament regenerative engineering: braiding scalable and tunable bioengineered ligaments using a bench-top braiding machine. Regen Eng Transl Med. 2021;7(4):524–32. https://doi.org/10.1007/s40883-020-00178-8.

    Article  Google Scholar 

  88. Beachy SH, Nair L, Laurencin C, Tsokas KA, Lundberg MS. Sources of variability in clinical translation of regenerative engineering products: insights from the national academies forum on regenerative medicine. Regen Eng Transl Med. 2020;6(1):1–6. https://doi.org/10.1007/s40883-020-00151-5.

    Article  CAS  Google Scholar 

  89. Tang X, Daneshmandi L, Awale G, Nair LS, Laurencin CT. Skeletal muscle regenerative engineering. Regen Eng Transl Med. 2019;5(3):233–51. https://doi.org/10.1007/s40883-019-00102-9.

    Article  Google Scholar 

  90. Tang X, Saveh-Shemshaki N, Kan H-M, Khan Y, Laurencin CT. Biomimetic electroconductive nanofibrous matrices for skeletal muscle regenerative engineering. Regen Eng Transl Med. 2020;6(2):228–37. https://doi.org/10.1007/s40883-019-00136-z.

    Article  Google Scholar 

  91. Nelson C, Khan Y, Laurencin CT. Nanofiber/microsphere hybrid matrices in vivo for bone regenerative engineering: a preliminary report. Regen Eng Transl Med. 2018;4(3):133–41. https://doi.org/10.1007/s40883-018-0055-1.

    Article  CAS  Google Scholar 

  92. Ogueri KS, Ivirico JLE, Nair LS, Allcock HR, Laurencin CT. Biodegradable polyphosphazene-based blends for regenerative engineering. Regen Eng Transl Med. 2017;3(1):15–31. https://doi.org/10.1007/s40883-016-0022-7.

    Article  CAS  Google Scholar 

  93. Narayanan N, Jiang C, Uzunalli G, Thankappan SK, Laurencin CT, Deng M. Polymeric electrospinning for musculoskeletal regenerative engineering. Regen Eng Transl Med. 2016;2(2):69–84. https://doi.org/10.1007/s40883-016-0013-8.

    Article  Google Scholar 

  94. Kasir R, Vernekar VN, Laurencin CT. Regenerative engineering of cartilage using adipose-derived stem cells. Regen Eng Transl Med. 2015;1(1–4):42–9. https://doi.org/10.1007/s40883-015-0005-0.

    Article  Google Scholar 

  95. Fatemeh S, Hosseini Cato T. Laurencin advanced electrospun nanofibrous stem cell niche for bone regenerative engineering. Regen Eng Transl Med. https://doi.org/10.1007/s40883-022-00274-x.

  96. Esdaille CJ, Ude CC, Laurencin CT. Regenerative engineering animal models for knee osteoarthritis. Regen Eng Transl Med. 2022;8(2):284–97. https://doi.org/10.1007/s40883-021-00225-y.

    Article  Google Scholar 

  97. Benton Swanson W, Mishina Y. New paradigms in regenerative engineering: emerging role of extracellular vesicles paired with instructive biomaterials. Biocell. 2022;46(6):1445–51. https://doi.org/10.32604/biocell.2022.018781.

    Article  Google Scholar 

  98. Zhuge W, Liu H, Wang W, Wang J. Microfluidic bioscaffolds for regenerative engineering. Engineered Regeneration. 2022;3(1):110–20. https://doi.org/10.1016/j.engreg.2021.12.003.

    Article  Google Scholar 

  99. Ryan H, Bister D, Holliday SA, Boehlein J, Lewis A, Silberman J, Allen JB, Moore E. Ancestral background is underreported in regenerative engineering. Regen Eng Transl Med. 2021. https://doi.org/10.1007/s40883-021-00237-8.

  100. Ameer GA. Understanding and harnessing variability in regenerative engineering. Regen Eng Transl Med. 2020;6(4):429–32. https://doi.org/10.1007/s40883-020-00155-1.

    Article  Google Scholar 

  101. Tao F, Cheng Y, Shi X, Zheng H, Du Y, Xiang W, Deng H. Applications of chitin and chitosan nanofibers in bone regenerative engineering. Carbohydr Polym. 2020;230:115658. https://doi.org/10.1016/j.carbpol.2019.115658.

    Article  CAS  Google Scholar 

  102. Wang X, Rivera-Bolanos N, Jiang B, Ameer GA. Advanced functional biomaterials for stem cell delivery in regenerative engineering and medicine. Adv Funct Mater. 2019;29(23):1809009. https://doi.org/10.1002/adfm.201809009.

    Article  CAS  Google Scholar 

  103. Heath DE. A review of decellularized extracellular matrix biomaterials for regenerative engineering applications. Regen Eng Transl Med. 2019;5(2):155–66. https://doi.org/10.1007/s40883-018-0080-0.

    Article  CAS  Google Scholar 

  104. Ma C, Kuzma ML, Bai X, Yang J. Biomaterial-based metabolic regulation in regenerative engineering. Adv Sci. 2019;6(19):1900819. https://doi.org/10.1002/advs.201900819.

    Article  CAS  Google Scholar 

  105. Ong J, Zhao J, Justin AW, Markaki AE. Albumin‐based hydrogels for regenerative engineering and cell transplantation. Biotechnol Bioeng. 2019;116(12):3457–68. https://doi.org/10.1002/bit.27167.

    Article  CAS  Google Scholar 

  106. Moore EM, West JL. Bioactive poly(ethylene glycol) acrylate hydrogels for regenerative engineering. Regen Eng Transl Med. 2019;5(2):167–79. https://doi.org/10.1007/s40883-018-0074-y.

    Article  CAS  Google Scholar 

  107. Bowers DT, Brown JL. Nanofibers as bioinstructive scaffolds capable of modulating differentiation through mechanosensitive pathways for regenerative engineering. Regen Eng Transl Med. 2019;5(1):22–9. https://doi.org/10.1007/s40883-018-0076-9.

    Article  CAS  Google Scholar 

  108. Deng M, Nair LS, Nukavarapu SP, Kumbar SG, Jiang T, Weikel AL, Krogman NR, Allcock HR, Laurencin CT. In situ porous structures: a unique polymer erosion mechanism in biodegradable dipeptide-based polyphosphazene and polyester blends producing matrices for regenerative engineering. Adv Funct Mater. 2010;20(17):2794–806. https://doi.org/10.1002/adfm.201000968.

    Article  CAS  Google Scholar 

  109. Lo KW-H, Ashe KM, Kan HM, Lee DA, Laurencin CT. Activation of cyclic amp/protein kinase: a signaling pathway enhances osteoblast cell adhesion on biomaterials for regenerative engineering. J Orthop Res. 2011;29(4):602–8. https://doi.org/10.1002/jor.21276.

    Article  CAS  Google Scholar 

  110. Deng M, Cushnie EK, Lv Q, Laurencin CT. Poly(lactide-co-glycolide)-hydroxyapatite composites: the development of osteoinductive scaffolds for bone regenerative engineering. MRS Proc. 2012;1417:737. https://doi.org/10.1557/opl.2012.737.

    Article  CAS  Google Scholar 

  111. Deng M, James R, Laurencin CT, Kumbar SG. Nanostructured polymeric scaffolds for orthopaedic regenerative engineering. IEEE Trans Nanobioscience. 2012;11(1):3–14. https://doi.org/10.1109/TNB.2011.2179554.

    Article  Google Scholar 

  112. Lo KW-H, Ulery BD, Kan HM, Ashe KM, Laurencin CT. Evaluating the feasibility of utilizing the small molecule phenamil as a novel biofactor for bone regenerative engineering. J Tissue Eng Regen Med. 2014;8(9):728–36. https://doi.org/10.1002/term.1573.

  113. Laurencin CT, Khan Y. Regenerative engineering. Sci Transl Med. 2012;4(160):160ed9. https://doi.org/10.1126/scitranslmed.3004467.

  114. McLaughlin SW, Nelson SJ, McLaughlin WM, Nair LS, Laurencin CT. Design of nanofibrous scaffolds for skeletal muscle regenerative engineering. J Biomater Tissue Eng. 2013;3(4):385–95. https://doi.org/10.1166/jbt.2013.1107.

    Article  CAS  Google Scholar 

  115. Lo KW-H, Jiang T, Gagnon KA, Nelson C, Laurencin CT. Small-molecule based musculoskeletal regenerative engineering. Trends Biotechnol. 2014;32(2):74–81. https://doi.org/10.1016/j.tibtech.2013.12.002.

    Article  CAS  Google Scholar 

  116. Mikael PE, Amini AR, Basu J, Josefina Arellano-Jimenez M, Laurencin CT, Sanders MM, Barry Carter C, Nukavarapu SP. Functionalized carbon nanotube reinforced scaffolds for bone regenerative engineering: fabrication, in vitro and in vivo evaluation. Biomed Mater. 2014;9(3):035001. https://doi.org/10.1088/1748-6041/9/3/035001.

    Article  CAS  Google Scholar 

  117. Jiang T, Deng M, James R, Nair LS, Laurencin CT. Micro- and nanofabrication of chitosan structures for regenerative engineering. Acta Biomater. 2014;10(4):1632–45. https://doi.org/10.1016/j.actbio.2013.07.003.

    Article  CAS  Google Scholar 

  118. Shelke NB, James R, Laurencin CT, Kumbar SG. Polysaccharide biomaterials for drug delivery and regenerative engineering. Polym Adv Technol. 2014;25(5):448–60. https://doi.org/10.1002/pat.3266.

    Article  CAS  Google Scholar 

  119. Laurencin CT, Ashe KM, Henry N, Kan HM, Lo KW-H. Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications. Drug Discov Today. 2014;19(6):794–800. https://doi.org/10.1016/j.drudis.2014.01.012.

    Article  CAS  Google Scholar 

  120. Cushnie EK, Ulery BD, Nelson SJ, Deng M, Sethuraman S, Doty SB, Lo KWH, Khan YM, Laurencin CT, Chin W-C. Simple signaling molecules for inductive bone regenerative engineering. PLoS ONE. 2014;9(7):e101627. https://doi.org/10.1371/journal.pone.0101627.

    Article  CAS  Google Scholar 

  121. Laurencin CT, James R. Composites and structures for regenerative engineering. MRS Proceedings. 2014;1621:3–15. https://doi.org/10.1557/opl.2014.4.

    Article  CAS  Google Scholar 

  122. Nelson C, Khan Y, Laurencin CT. Nanofiber-microsphere (nano-micro) matrices for bone regenerative engineering: a convergence approach toward matrix design. Regenerative Biomaterials. 2014;1(1):3–9. https://doi.org/10.1093/rb/rbu002.

    Article  Google Scholar 

  123. James R, Harmon MD, Kumbar SG, Laurencin CT. Innovative regenerative engineering technologies for soft tissue regeneration. Technol Innov. 2014;16(3):195–214. https://doi.org/10.3727/194982414X14138187301579.

    Article  CAS  Google Scholar 

  124. Laurencin C, Jiang T, Kumbar S, Nair L. Biologically active chitosan systems for tissue engineering and regenerative medicine. Curr Top Med Chem. 2008;8(4):354–64. https://doi.org/10.2174/156802608783790974.

    Article  Google Scholar 

  125. Yu X, Tang X, Gohil SV, Laurencin CT. Biomaterials for bone regenerative engineering. Adv Healthc Mater. 2015;4(9):1268–85. https://doi.org/10.1002/adhm.201400760.

    Article  CAS  Google Scholar 

  126. James R, Mengsteab P, Laurencin CT. Regenerative engineering: studies of the rotator cuff and other musculoskeletal soft tissues. MRS Advances. 2016;1(18):1255–63. https://doi.org/10.1557/adv.2016.282.

    Article  CAS  Google Scholar 

  127. James R, Laurencin CT. Regenerative engineering and bionic limbs. Rare Metals. 2015;34(3):143–55. https://doi.org/10.1007/s12598-015-0446-0.

    Article  CAS  Google Scholar 

  128. Laurencin CT, Nair LS. Regenerative engineering: approaches to limb regeneration and other grand challenges. Regen Eng Transl Med. 2015;1(1–4):1–3. https://doi.org/10.1007/s40883-015-0006-z.

    Article  Google Scholar 

  129. Vernekar VN, James R, Smith KJ, Laurencin CT. Nanotechnology applications in stem cell science for regenerative engineering. J Nanosci Nanotechnol. 2016;16(9):8953–65. https://doi.org/10.1166/jnn.2016.12738.

    Article  CAS  Google Scholar 

  130. Narayanan G, Vernekar VN, Kuyinu EL, Laurencin CT. Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering. Adv Drug Deliv Rev. 2016;107:247–76. https://doi.org/10.1016/j.addr.2016.04.015.

    Article  CAS  Google Scholar 

  131. Laurencin CT., Nair LS. The Quest toward limb regeneration: a regenerative engineering approach. Regen Biomater. 2016;3(2):123–125. https://doi.org/10.1093/rb/rbw002.

    Article  Google Scholar 

  132. Mengsteab PY, Nair LS, Laurencin CT. The past, present and future of ligament regenerative engineering. Regen Med. 2016;11(8):871–81. https://doi.org/10.2217/rme-2016-0125.

    Article  CAS  Google Scholar 

  133. Xiaoyan T, Yusuf K, Cato L. Electroconductive nanofiber scaffolds for muscle regenerative engineering. Front Bioeng Biotechnol. 2016;4. https://doi.org/10.3389/conf.FBIOE.2016.01.02165.

  134. Escobar Ivirico JL, Bhattacharjee M, Kuyinu E, Nair LS, Laurencin CT. Regenerative engineering for knee osteoarthritis treatment: biomaterials and cell-based technologies. Engineering. 2017;3(1):16–27. https://doi.org/10.1016/J.ENG.2017.01.003.

    Article  Google Scholar 

  135. Narayanan G, Bhattacharjee M, Nair LS, Laurencin CT. Musculoskeletal tissue regeneration: the role of the stem cells. Regen Eng Transl Med. 2017;3(3):133–65. https://doi.org/10.1007/s40883-017-0036-9.

    Article  Google Scholar 

  136. Ifegwu OC, Awale G, Rajpura K, Lo KW-H, Laurencin CT. Harnessing cAMP signaling in musculoskeletal regenerative engineering. Drug Discov Today. 2017;22(7):1027–44. https://doi.org/10.1016/j.drudis.2017.03.008.

    Article  CAS  Google Scholar 

  137. Narayanan G, Nair LS, Laurencin CT. Regenerative engineering of the rotator cuff of the shoulder. ACS Biomater Sci Eng. 2018;4(3):751–86. https://doi.org/10.1021/acsbiomaterials.7b00631.

    Article  CAS  Google Scholar 

  138. Peach MS, Ramos DM, James R, Morozowich NL, Mazzocca AD, Doty SB, Allcock HR, Kumbar SG, Laurencin CT, Engler AJ. Engineered stem cell niche matrices for rotator cuff tendon regenerative engineering. PLOS ONE. 2017;12(4):e0174789. https://doi.org/10.1371/journal.pone.0174789.

    Article  CAS  Google Scholar 

  139. Ogueri KS, Jafari T, Escobar Ivirico JL, Laurencin CT. Polymeric biomaterials for scaffold-based bone regenerative engineering. Regen Eng Transl Med. 2019;5(2):128–54. https://doi.org/10.1007/s40883-018-0072-0.

    Article  CAS  Google Scholar 

  140. Saveh-Shemshaki N, Nair LS, Laurencin CT. Nanofiber-based matrices for rotator cuff regenerative engineering. Acta Biomater. 2019;94:64–81. https://doi.org/10.1016/j.actbio.2019.05.041.

    Article  CAS  Google Scholar 

  141. Barajaa MA, Nair LS, Laurencin CT. Bioinspired scaffold designs for regenerating musculoskeletal tissue interfaces. Regen Eng Transl Med. 2020;6(4):451–83. https://doi.org/10.1007/s40883-019-00132-3.

    Article  Google Scholar 

  142. Matai I, Kaur G, Seyedsalehi A, McClinton A, Laurencin CT. Progress in 3D bioprinting technology for tissue/organ regenerative engineering. Biomaterials. 2020;226:119536. https://doi.org/10.1016/j.biomaterials.2019.119536.

    Article  CAS  Google Scholar 

  143. Laurencin CT, McClinton A. Regenerative cell-based therapies: cutting edge, bleeding edge, and off the edge. Regen Eng Transl Med. 2020;6(1):78–89. https://doi.org/10.1007/s40883-020-00147-1.

    Article  Google Scholar 

  144. Montgomery AB, McClinton A, Nair L, Laurencin CT. Nail matrix regenerative engineering: in vitro evaluation of poly(lactide-co-glycolide)/gelatin fibrous substrates. J Biomed Mater Res A. 2020;108(5):1136–43. https://doi.org/10.1002/jbm.a.36888.

    Article  CAS  Google Scholar 

  145. Ogueri KS, Ogueri KS, Allcock HR, Laurencin CT. Polyphosphazene polymers: the next generation of biomaterials for regenerative engineering and therapeutic drug delivery. J Vac Sci Technol B. 2020;38(3):030801. https://doi.org/10.1116/6.0000055.

    Article  CAS  Google Scholar 

  146. Laurencin CT, Daneshmandi L. Graphene for regenerative engineering. Int J Appl Ceram Eng Sci. 2020;2(3):140–3. https://doi.org/10.1002/ces2.10045.

    Article  CAS  Google Scholar 

  147. Daneshmandi L, Shah S, Jafari T, Bhattacharjee M, Momah D, Saveh-Shemshaki N, Lo KW-H, Laurencin CT. Emergence of the stem cell secretome in regenerative engineering. Trends Biotechnol. 2020;38(12):1373–84. https://doi.org/10.1016/j.tibtech.2020.04.013.

    Article  CAS  Google Scholar 

  148. Daneshmandi L, Barajaa M, Tahmasbi Rad A, Sydlik SA, Laurencin CT. Graphene‐based biomaterials for bone regenerative engineering: a comprehensive review of the field and considerations regarding biocompatibility and biodegradation. Adv Healthc Mater. 2021;10(1):2001414. https://doi.org/10.1002/adhm.202001414.

    Article  CAS  Google Scholar 

  149. Ude CC, Esdaille CJ, Ogueri KS, Kan H-M, Laurencin SJ, Nair LS, Laurencin CT. The mechanism of metallosis after total hip arthroplasty. Regen Eng Transl Med. 2021;7(3):247–61. https://doi.org/10.1007/s40883-021-00222-1.

    Article  Google Scholar 

  150. Hosseini FS, Nair LS, Laurencin CT. Inductive materials for regenerative engineering. J Dent Res. 2021;100(10):1011–9. https://doi.org/10.1177/00220345211010436.

    Article  CAS  Google Scholar 

  151. Prabhath A, Vernekar VN, Vasu V, Badon M, Avochinou J‐E, Asandei AD, Kumbar SG, Weber E, Laurencin CT. Kinetic degradation and biocompatibility evaluation of polycaprolactone-based biologics delivery matrices for regenerative engineering of the rotator cuff. J Biomed Mater Res A. 2021;109(11):2137–53. https://doi.org/10.1002/jbm.a.37200.

    Article  CAS  Google Scholar 

  152. Washington KS, Shemshaki NS, Laurencin CT. The role of nanomaterials and biological agents on rotator cuff regeneration. Regen Eng Transl Med. 2021;7(4):440–9. https://doi.org/10.1007/s40883-020-00171-1.

    Article  Google Scholar 

  153. Ude CC, Shah S, Ogueri KS, Nair LS, Laurencin CT. Stromal vascular fraction for osteoarthritis of the knee regenerative engineering. Regen Eng Transl Med. 2022;8(2):210–24. https://doi.org/10.1007/s40883-021-00226-x.

    Article  Google Scholar 

  154. Hosseini FS, Laurencin CT. Advanced graphene ceramics and their future in bone regenerative engineering. Int J Appl Ceram Technol. 2022;19(2):893–905. https://doi.org/10.1111/ijac.13999.

    Article  CAS  Google Scholar 

  155. Shah S, Esdaille CJ, Bhattacharjee M, Kan H-M, Laurencin CT. The synthetic artificial stem cell (SASC): shifting the paradigm of cell therapy in regenerative engineering. Proc Natl Acad Sci. 2022;119(2):e2116865118. https://doi.org/10.1073/pnas.2116865118.

    Article  CAS  Google Scholar 

Download references

Funding

The study was financially supported by the NIH 1T32AR079114-01 and the Connecticut Convergence Institute.

Author information

Authors and Affiliations

  1. Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT, USA

    Feiyang Chen, Oyindamola R. Teniola, Kenneth S. Ogueri & Cato T. Laurencin

  2. Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA

    Oyindamola R. Teniola

  3. Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, USA

    Kenneth S. Ogueri & Cato T. Laurencin

  4. Biological, Physical and Engineering Sciences, Raymond and Beverly Sackler Center for Biomedical, UConn Health, Farmington, CT, USA

    Cato T. Laurencin

  5. Connecticut Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA

    Cato T. Laurencin

  6. Connecticut Department of Orthopaedic Surgery, UConn Health, Farmington, CT, USA

    Cato T. Laurencin

  7. Institute of Materials Science, University of Connecticut, Storrs, CT, USA

    Cato T. Laurencin

  8. Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, USA

    Cato T. Laurencin

Authors
  1. Feiyang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oyindamola R. Teniola
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenneth S. Ogueri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cato T. Laurencin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cato T. Laurencin.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, F., Teniola, O.R., Ogueri, K.S. et al. Recent Trends in the Development of Polyphosphazenes for Bio-applications. Regen. Eng. Transl. Med. 9, 202–223 (2023). https://doi.org/10.1007/s40883-022-00278-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40883-022-00278-7

Keywords

Search

Navigation