Two novel methods for synthesizing poly (propylene fumarate): Technical aspects and role of vacuum and N2 purging effects

Document Type : Original research


1 Department of Medical engineering, Amirkabir University of Technology, Tehran, Iran

2 Department of Analytical Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran

3 Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, P.O. Box: 15875-4413, Tehran, Iran


Poly (propylene fumarate) (PPF), a linear unsaturated polyester consisting of alternating propylene glycol and fumaric acid units, can be cured in vivo to fill the skeletal defects with minimal surgical intervention. Many different methods have been reported for synthesizing PPF, but none of them gives a clear method. The present paper introduces two new methods in PPF synthesis: Modified reflux system (MRS) and mixed reflux-distillation system (MRDS). Similarly, the effects of applying vacuum (vacuum sequence, time, vacuum applying position, and the distance between vacuum applying position and reactor) as well as nitrogen gas (used continuously or only as an N2 blanket) on the PPF synthesis have been studied. The PPF obtained using optimum reaction condition has been characterized by using NMR, FTIR, and GPC analyses. It is demonstrated that the efficiency of MRDS in synthesizing PPF is higher than that of MRS. Nitrogen gas, vacuum applying position, continuously/stepwise-continuously applying vacuum and other parameters show an important role in the polymerization of PPF in both the MRDS and MRS systems.


Main Subjects

  1. Kolybaba M, Tabil L, Panigrahi S, Crerar W, Powell T, Wang B (2003) Biodegradable polymers: Past, present, and future, ASAE Annual Intersectional Meeting Sponsored by the Red River Section of ASAE Quality Inn & Suites, p. 3-4
  2. Peter SJ, Miller ST, Zhu G, Yasko AW, Mikos AG (1998) In vivo degradation of a poly (propylene fumarate)/β-tricalcium phosphate injectable composite scaffold. J Biomed Mater Res 41:1-7
  3. Behravesh E, Yasko AW, Engel PS, Mikos AG (1999) Synthetic biodegradable polymers for orthopaedic applications. Clin Orthop Relat Res 367: S118-S129
  4. Gunatillake PA, Adhikari R (2003) Biodegradable synthetic polymers for tissue engineering. Eur Cell Mater 5: 1-16
  5. Peter SJ, Suggs LJ, Yaszemski MJ, Engel PS, Mikos AG (1999) Synthesis of poly (propylene fumarate) by acylation of propylene glycol in the presence of a proton scavenger. J Biomat Sci- Polym E 10:363-373
  6. Peter SJ, Nolley JA, Widmer MS, Merwin JE, Yaszemski MJ, Yasko AW, Engel PS, Mikos AG (1997) In vitro degradation of a poly (propylene fumarate)/β-tricalcium phosphate composite orthopaedic scaffold. Tissue Eng 3: 207-215
  7. Peter SJ, Yaszemski MJ, Suggs LJ, Payne RG, Langer R, Hayes WC, Unroeg MR, Alemanyh LB, Engeli PS, Mikos AG (1997) Characterization of partially saturated poly (propylene fumarate) for orthopaedic application. J Biomat Sci-Polym E 8: 893-904
  8. Yaszemski MJ, Payne RG, Hayes WC, Langer RS, Aufdemorte TB, Mikos AG (1995) The ingrowth of new bone tissue and initial mechanical properties of a degrading polymeric composite scaffold. Tissue Eng 1: 41-52
  9. Domb AJ, Laurencin CT, Israeli O, Gerhart TN, Langer R (1990) The formation of propylene fumarate oligomers for use in bioerodible bone cement composites. J Polym Sci Pol Chem 28: 973-985
  10. Yaszemski MJ, Payne RG, Hayes WC, Langer R, Mikos AG (1996) In vitro degradation of a poly (propylene fumarate)-based composite material. Biomaterials 17: 2127-2130
  11. Gerhart T, Roux R, Horowitz G, Miller R, Hanff P, Hayes W (1988) Antibiotic release from an experimental biodegradable bone cement. J Orthopaed Res 6: 585-592
  12. Gresser JD, Hsu SH, Nagaoka H, Lyons CM, Nieratko DP, Wise DL, Barabino GA, Trantolo DJ (1995) Analysis of a vinyl pyrrolidone/poly (propylene fumarate) resorbable bone cement. J Biomed Mater Res 29: 1241-1247
  13. Shung AK, Timmer MD, Jo S, Engel PS, Mikos AG (2002) Kinetics of poly (propylene fumarate) synthesis by step polymerization of diethyl fumarate and propylene glycol using zinc chloride as a catalyst. J Biomat Sci-Polym E 13: 95-108
  14. Hakimimehr D, Liu D-M, Troczynski T (2005) In-situ preparation of poly (propylene fumarate)- hydroxyapatite composite. Biomaterials 26: 7297- 7303
  15. Temenoff J, Mikos A (2007) ‘Fumarate-based macromers as scaffolds for tissue engineering applications. In: Topics in tissue engineering, Eds: Ashammakhi N, Reis R, Chiellini E, Citeseer
  16. Beke S, Anjum F, Ceseracciu L, Romano I, Athanassiou A, Diaspro A, Brandi F (2013) Rapid fabrication of rigid biodegradable scaffolds by excimer laser mask projection technique: Acomparison between 248 and 308 nm. Laser Phys 23: 035602
  17. Timmer MD, Ambrose CG, Mikos AG (2003) In vitro degradation of polymeric networks of poly (propylene fumarate) and the crosslinking macromer poly (propylene fumarate)-diacrylate. Biomaterials 24: 571-577
  18. Mitha M, Jayabalan M (2009) Studies on biodegradable and crosslinkable poly (castor oil fumarate)/poly (propylene fumarate) composite adhesive as a potential injectable biomaterial. J Mater Sci-Mater M 20: 203-211
  19. Kamel N, Abou-Aiaad T, Iskander B, Khalil S, Mansour S, Abd-El-Messieh S, Abd-El-Nour KN (2010) Biophysical studies on bone cement composites based on polyester fumarate. J Appl Polym Sci 116: 876-885
  20. Matthews MA (2000) A to Z of thermodynamics by Pierre Perrot (Université des sciences et technologies de Lille). Oxford University Press: Oxford, New York, and Tokyo. 1998. vi+ 329 pp. $65.00. ISBN 0-19-856556-9 (Hardback). J Am Chem Soc 122: 3799-3800
  21. Mark HF, Tobolsky AV (1971) Polymer Science and Materials, Wiley-Interscience
  22. Boenig H, Mark H, Gaylord N, Bikales N. (1969) Encyclopedia of polymer science and technology, Vol 11, Interscience, New York, p.129
  23. Shahbazi S, Jafari Y, Moztarzadeh F, Mir Mohamad Sadeghi G (2014) Evaluation of effective parameters for the synthesis of poly (propylene fumarate) by response surface methodology. J Appl Polym Sci 131: 40932
  24. Stevens MP (1990) Polymer chemistry, Oxford University Press, New York
  25. Mark HF (1970) Encyclopedia of Polymer Science and Technology: Reinforced plastics to starch, Interscience publishers
  26. Kharas GB, Kamenetsky M, Simantirakis J, Beinlich KC, Rizzo AMT, Caywood GA, Watson K (1997) Synthesis and characterization of fumarate-based polyesters for use in bioresorbable bone cement composites. J Appl polym Sci 66: 1123-1137