Skip to main content
SpringerLink
Log in

Biodegradable and biocompatible radiopaque iodinated poly-3-hydroxy butyrate: synthesis, characterization and in vitro/in vivo X-ray visibility

  • Original Paper
  • Published:
Polymer Bulletin Aims and scope Submit manuscript

Abstract

Some novel radiopaque biodegradable and biocompatible iodinated polymers based on poly-3-hydroxy butyrate (PHB) were obtained. Following the attachment of diethanol amine to PHB, the hydroxyl ends were capped with 4-iodobenzoic acid and 2,3,5-tri-iodobenzoic acid. In this manner, tri-novel radiopaque polymers were obtained. The resulting polymers were structurally characterized by NMR technique. They were evaluated with respect to their possible use as radiopaque implant biomaterials indicating X-ray visibility in a noninvasive manner using routine X-ray absorption imaging techniques. These polymers exhibited good radiopacity with conventional imaging X-ray techniques in vivo. Additionally, biocompatibility of these iodinated polymers was also evaluated. There were no signs of infection or abscess formation on the surgical area. These novel radiopaque PHBs should be promising biomaterials for a new-generation radiopaque materials.

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
Scheme 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Gross RA, DeMello C, Lenz RW, Brandl H, Fuller RC (1989) The biosynthesis and characterization of poly (β-hydroxyalkanoates) produced by Pseudomonas oleovorans. Macromolecules 22:1106

    CAS  Google Scholar 

  2. Lenz RW, Marchessault RH (2005) Bacterial polyesters: biosynthesis, biodegradable plastics and biotechnology. Biomacromolecules 6:1

    CAS  PubMed  Google Scholar 

  3. Solaiman DKY, Ashby RD, Foglia TA, Marmer WN (2006) Conversion of agricultural feedstock and coproducts into poly(hydroxy alkanoates). Appl Microbiol Biotechnol 71:783

    CAS  PubMed  Google Scholar 

  4. Steinbüchel A (2001) Perspectives for biotechnological production and utilization of biopolymers: metabolic engineering of polyhydroxyalkanoate biosynthesis pathways as a successful example. Macromol Biosci 1:1

    Google Scholar 

  5. Koray O, Koksal MS, Hazer B (2010) Simple production experiment of poly (3-hydroxy butyrate) for science laboratories and its importance for science process skills of prospective teachers. Energy Educ Sci Technol Part B Soc Educ Stud 2, 1–2:39

    Google Scholar 

  6. Steinbüchel A, Valentin HE (1995) Diversity of bacterial polyhydroxyalkanoic acids. FEMS Microbial Lett 128:219

    Google Scholar 

  7. Ishii D, Takisawa K, Matsumoto K, Ooi T, Hikima T, Takata M, Taguchi S, Iwata T (2017) Effect of monomeric composition on the thermal, mechanical and crystalline properties of poly [(R)-lactate-co-(R)-3-hydroxybutyrate]. Polymer 122:169

    CAS  Google Scholar 

  8. Scholz C, Fuller RC, Lenz RW (1994) Growth and polymer incorporation of Pseudomonas oleovorans on alkyl esters of heptanoic acid. Macromolecules 27:2886

    CAS  Google Scholar 

  9. Tappel RC, Kucharski JM, Mastroianni JM, Stipanovic AJ, Nomura CT (2012) Biosynthesis of poly [(R)-3-hydroxyalkanoate] copolymers with controlled repeating unit compositions and physical properties. Biomacromolecules 13:2964

    CAS  PubMed  Google Scholar 

  10. Toraman T, Hazer B (2014) Synthesis and characterization of the novel thermoresponsive conjugates based on poly (3-hydroxy alkanoates). J Polym Environ 22:159

    CAS  Google Scholar 

  11. Hazer DB, Kilicay E, Hazer B (2012) Poly (3-hydroxyalkanoate) s: diversification and biomedical applications: a state of the art review. Mater Sci Eng C 32:637

    CAS  Google Scholar 

  12. Scandola M, Focarete ML, Adamus G, Sikorska W, Baranowska I, Swierczek S, Gnatowski M, Kowalczuk M, Jedlinski Z (1997) Polymer blends of natural poly (3-hydroxybutyrate-co-3-hydroxyvalerate) and a synthetic atactic poly (3-hydroxybutyrate). Characterization and biodegradation studies. Macromolecules 30:2568

    CAS  Google Scholar 

  13. Hazer B, Akyol E, Şanal T, Guillaume S, Çakmakli B, Steinbuchel A (2019) Synthesis of novel biodegradable elastomers based on poly [3-hydroxy butyrate] and poly [3-hydroxy octanoate] via transamidation reactio. Polym Bull. https://doi.org/10.1007/s00289-018-2410-2

    Article  Google Scholar 

  14. Sparks J, Scholz C (2008) Synthesis and characterization of a cationic poly (β-hydroxyalkanoate). Biomacromolecules 9:2091

    CAS  PubMed  Google Scholar 

  15. Lorenzini C, Versace DL, Renard E, Langlois V (2015) Renewable epoxy networks by photoinitiated copolymerization of poly (3-hydroxyalkanoate) s and isosorbide derivatives. React Funct Polym 93:95

    CAS  Google Scholar 

  16. Hazer B (2015) Simple synthesis of amphiphilic poly (3-hydroxy alkanoate) s with pendant hydroxyl and carboxylic groups via thiol-ene photo click reactions. Polym Degrad Stab 119:159

    CAS  Google Scholar 

  17. Abe H, Doi Y, Kumagai Y (1994) 3-hydroxybutyrate-β-6-hydroxyhexanoate] as a compatibilizer for a Biodegradable Blend of Poly [(R)-3-hydroxybutyrate] and Poly (6-hydroxyhexanoate). Macromolecules 27:6012

    CAS  Google Scholar 

  18. Hazer DB, Hazer B (2011) The effect of gold clusters on the autoxidation of poly (3-hydroxy 10-undecenoate-co-3-hydroxy octanoate) and tissue response evaluation. J Polym Res 18:251

    CAS  Google Scholar 

  19. Hazer B (2010) Amphiphilic poly (3-hydroxy alkanoate) s: potential candidates for medical applications. Int J Polym Sci. https://doi.org/10.1155/2010/423460

    Article  Google Scholar 

  20. Chen GQ (2009) A microbial polyhydroxyalkanoates (PHA) based bio-and materials industry. Chem Soc Rev 38:2434

    CAS  PubMed  Google Scholar 

  21. Hazer DB, Bal E, Nurlu G, Benli K, Balcı S, Öztürk F, Hazer B (2013) In vivo application of poly-3-hydroxyoctanoate as peripheral nerve graft. J Zhejiang Univ Sci B (Biomed Biotechnol) 14(11):993

    CAS  Google Scholar 

  22. Hazer B, Steinbüchel A (2007) Increased diversification of polyhydroxyalkanoates by modification reactions for industrial and medical applications. Appl Microbiol Biotechnol 74:1

    CAS  PubMed  Google Scholar 

  23. Arkin AH, Hazer B, Borcakli M (2000) Chlorination of poly (3-hydroxy alkanoates) containing unsaturated side chains. Macromolecules 33:3219

    CAS  Google Scholar 

  24. Arkin AH, Hazer B (2002) Chemical modification of chlorinated microbial polyesters. Biomacromolecules 3(6):1327

    CAS  PubMed  Google Scholar 

  25. Yalcin B, Cakmak M, Arkın AH, Hazer B, Erman B (2006) Control of optical anisotropy at large deformations in PMMA/chlorinated-PHB (PHB-Cl) blends: mechano-optical behavior. Polymer 47:8183

    CAS  Google Scholar 

  26. Arkin AH, Hazer B, Adamus G, Kowalczuk M, Jedlinski Z, Lenz RW (2001) Synthesis of poly (2-methyl-3-hydroxyoctanoate) via anionic polymerization of α-methyl-β-pentyl-β-propiolactone. Biomacromolecules 2(3):623

    CAS  PubMed  Google Scholar 

  27. Wang Q, Qian K, Liu S, Yang Y, Liang B, Zheng C, Yang X, Xu H, Shen AQ (2015) X-ray visible and uniform alginate microspheres loaded with in situ synthesized BaSO4 nanoparticles for in vivo transcatheter arterial embolization. Biomacromolecules 16:1240

    CAS  PubMed  Google Scholar 

  28. Nuutınen J-P, Clerc C, Törmälä P (2003) Mechanical properties and in vitro degradation of self-reinforced radiopaque bioresorbable polylactide fibres. J Biomater Sci Polym Ed 14:665

    PubMed  Google Scholar 

  29. Lee BH, Leon C, McLemore R, Valdez Macias J, Vernon BL (2011) Synthesis and characterization of thermo-sensitive radio-opaque poly (N-isopropylacrylamide-co-PEG-2-iodobenzoate). J Biomater Sci Polym Ed 22:2357

    CAS  PubMed  Google Scholar 

  30. Sang L, Wei Z, Liu K, Song K, Wang J, Qi M (2014) Radiopaque iodinated polyurethane for embolic agents. Acta Polym Sin 1:31

    Google Scholar 

  31. Wei Z, Song P, Sang L, Liu K, Zhou C, Wang Y, Li Y (2014) Radiopaque iodinated poly (ester–urethane) s based on poly (butylene succinate): retarded crystallization and dual recrystallization behaviour. Polymer 55:2751

    CAS  Google Scholar 

  32. Li S, Yu J, Wade MB, Policastro GM, Becker ML (2015) Radiopaque, iodine functionalized, phenylalanine-based poly (ester urea) s. Biomacromolecules 16:615

    CAS  PubMed  Google Scholar 

  33. Meng WJ, Lu XJ, Wang H, Fan TY, Cui DC, Zhang SS, Zheng ZZ, Guan HT, Song L, Zou YH (2015) Preparation and evaluation of biocompatible long-term radiopaque microspheres based on polyvinyl alcohol and lipiodol for embolization. J Biomater Appl 30(2):133–146

    CAS  PubMed  Google Scholar 

  34. Dawlee S, Jayakrishnan A, Jayabalan M (2009) Studies on novel radiopaque methyl methacrylate: glycidyl methacrylate based polymer for biomedical applications. J Mater Sci Mater Med 20:S243–S250

    CAS  PubMed  Google Scholar 

  35. van Hooy-Corstjens CSJ, Aldenhoff YBJ, Knetsch MLW, Govaert LE, Arin E, Erli H, Koole LH (2004) Radiopaque polymeric spinal cages: a prototype study. J Mater Chem 14:3008

    Google Scholar 

  36. Boelen EJH, Lewis G, Xu J, Slots T, Koole LH, van Hooy-Corstjens CSJ (2008) Evaluation of a highly‐radiopaque iodine‐containing acrylic bone cement for use in augmentation of vertebral compression fractures. J Biomed Mater Res 86A:76

    CAS  Google Scholar 

  37. Estep KG, Josef KA, Bacon ER, Illig CR, Toner JL, Mishra D, Blazak WF, Miller DM, Johnson DK, Allen JM, Spencer A, Wilson SA (2000) 1,3,5-Trialkyl-2,4,6-triiodobenzenes: novel X-ray contrast agents for gastrointestinal imaging. J Med Chem 43:1940

    CAS  PubMed  Google Scholar 

  38. Benzina A, Kruft MAB, Bar F, Vanderveen FH, Bastiaansen CW, Heijnen V, Reutelingsperger C, Koole LH (1994) Studies on a new radiopaque polymeric biomaterial. Biomaterials 15:1122

    CAS  PubMed  Google Scholar 

  39. Aldenhoff YBJ, Kruft MAB, Pijpers AP, van der Veen FH, Bulstra SK, Kuijer R, Koole LH (2002) Stability of radiopaque iodine-containing biomaterials. Biomaterials 23:881

    CAS  Google Scholar 

  40. Tuzen M, Sahiner S, Hazer B (2016) Solid phase extraction of lead, cadmium and zinc on biodegradable polyhydroxybutyrate diethanol amine (PHB-DEA) polymer and their determination in water and food samples. Food Chem 210:115

    CAS  PubMed  Google Scholar 

  41. Neises B, Steglich W (1978) Simple method for the esterification of carboxylic acids. Chem Int Ed 17:522

    Google Scholar 

  42. Hazer DB, Hazer B, Dinçer N (2011) Antibacterial effects of laser ablated Ni nanoparticles. J Biomed Biotechnol 2011:956169. https://doi.org/10.1155/2011/956169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hazer DB, Hazer B, Kaymaz F (2009) Synthesis of microbial elastomers based on soybean oily acids. biocompatibility studies. Biomed Mater 4(3):035011. https://doi.org/10.1088/1748-6041/4/3/035011

    Article  CAS  PubMed  Google Scholar 

  44. Shishatskaya EI, Khlusov IA, Volova TGA (2006) A hybrid PHB–hydroxyapatite composite for biomedical application: production, in vitro and in vivo investigation. J Biomater Sci Polym Ed 17(5):481

    CAS  PubMed  Google Scholar 

  45. Nygren CL, Wilson CC, Turner JFC (2005) On the solid state structure of 4-iodobenzoic acid. J Phys Chem A 109:2586

    CAS  PubMed  Google Scholar 

  46. Zhao F, Yao D, Guo R, Deng L, Dong A, Zhang J (2015) Composites of polymer hydrogels and nanoparticulate systems for biomedical and pharmaceutical applications. Nanomaterials (Basel) 5(4):2054

    CAS  Google Scholar 

  47. Rodriguez JN, Yu YJ, Miller MW, Wilson TS, Hartman J, Clubb FJ, Gentry B, Maitland DJ (2012) Opacification of shape memory polymer foam designed for treatment intracranial aneurysms. Ann Biomed Eng 40(4):883

    Google Scholar 

Download references

Acknowledgements

This work was supported by the Kapadokya University (#KÜN.2018-BAGP-001) and Bülent Ecevit University Research Funds (#BEU-2017-72118496-01). The authors thank to Fatih Pekdemir for taking FTIR spectra. This paper has been proofread by Bülent Ecevit University Article Proofreading and Editing Office.

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Bülent Ecevit University, 67100, Zonguldak, Turkey

    Arzu Erol

  2. Department of Surgical Medical Sciences, Department of Brain and Nerve Surgery, Muğla Sıtkı Koçman University, 48000, Muğla, Turkey

    Derya B. Hazer Rosberg

  3. Department of Aircraft Airframe Engine Maintenance, Kapadokya University, 50420, Ürgüp, Nevşehir, Turkey

    Baki Hazer

  4. Department of Chemistry, Department of Nano Technology Engineering, Zonguldak Bülent Ecevit University, 67100, Zonguldak, Turkey

    Baki Hazer

  5. Experimental Application and Research Center, Bezmialem Vakıf University, 34000, Istanbul, Turkey

    Beyza S. Göncü

Authors
  1. Arzu Erol
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derya B. Hazer Rosberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Baki Hazer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beyza S. Göncü
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Baki Hazer.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erol, A., Rosberg, D.B.H., Hazer, B. et al. Biodegradable and biocompatible radiopaque iodinated poly-3-hydroxy butyrate: synthesis, characterization and in vitro/in vivo X-ray visibility. Polym. Bull. 77, 275–289 (2020). https://doi.org/10.1007/s00289-019-02747-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00289-019-02747-6

Keywords

Search

Navigation