Preparation of Poly(DL-Lactide/ε-Caprolactone)–β-TCP Composites for Bone Tissue Repair

Year 2019, Volume: 47 Issue: 1, 133 - 141, 01.02.2019

Hasret Tolga Şirin Ebru Akdoğan Erhan Bişkin

Abstract

Poly-D,L-Lactide/ε-caprolactone (PDLLA-ε-CL) and β-tri-calcium phosphate (β-TCP) composites were prepared as an alternative for injectable filling material in bone tissue repair. β-TCP was synthesized by a wet precipitation method and characterised using Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffractometer (XRD), Zeta-SIZER and Brunauer–Emmett–Teller (BET) analyser. PDLLA-ε-CL copolymer was synthesized under nitrogen (N2) atmosphere using ring-opening polymerization in the presence of stannous octoate as a catalyst. The chemical structures of copolymers were determined by FTIR and Proton Nuclear Magnetic Resonance (1H-NMR) analysis. The average molecular weights of copolymers were identified by Gel Permeation Chromatography (GPC). (PDLLA-ε-CL)-β-TCP composites were then prepared by loading differing amounts of β-TCP to the copolymer phase. The resulting composites were easily shaped by hand. The degradation profiles of the composites were determined by monitoring the changes in the molecular weight of the co-polymers over a period of 42 days. Degradation rate of the composites decreased as the percentage of β-TCP in the structure increased.

Keywords

Bio-ceramic, tricalciumphosphate, hard tissue repair, bone filler, Poly(D, L-lactide/ ε -caprolactone

References

• M. Jarcho, R.L. Salsbury, M.B. Thomas, R.H. Doremus, Synthesis and fabrication of β-tricalcium phosphate (whitlockite) ceramics for potential prosthetic applications, J. Mater. Sci., 14 (1979) 142-150.
• 2. J. Enderle, J. Bronzino, Introduction to biomedical engineering, Elsevier, Burlington, USA, 2012
• 3. S. Higashi, T. Yamamuro, T. Nakamura, Y. Ikada, S.-H. Hyon, K. Jamshidi, Polymer-hydroxyapatite composites for biodegradable bone fillers, Biomaterials, 7 (1986) 183-187.
• 4. S.M. Zakaria, S.H.S. Zein, M.R. Othman, F. Yang, J.A. Jansen, Nanophase hydroxyapatite as a biomaterial in advanced hard tissue engineering: a review, Tissue Eng. Part B: Rev., 19 (2013) 431-441.
• 5. J. Park, R. Lakes, Biomaterials: an Introduction, Springer Science Business Media, LLC, New York, USA, 2007
• 6. C. Doyle, E. Tanner, W. Bonfield, In vitro and in vivo evaluation of polyhydroxybutyrate and of polyhydroxybutyrate reinforced with hydroxyapatite, Biomaterials, 12 (1991)
• 841-847. 7. Z. Huang, J. Tian, B. Yu, Y. Xu, Q. Feng, A bone-like nanohydroxyapatite/ collagen loaded injectable scaffold., Biomed. Mater., 4 (2009) 055005.
• 8. W. Thein-Han, R. Misra, Biomimetic chitosan– nanohydroxyapatite composite scaffolds for bone tissue engineering, Acta Biomater., 5 (2009) 1182-1197.
• 9. H. Zhou, J. Lee, Nanoscale hydroxyapatite particles for bone tissue engineering, Acta Biomater., 7 (2011) 2769-2781.
• 10. D. Apelt, F. Theiss, A.O. El-Warrak, K. Zlinszky, R. Bettschart- Wolfisberger, M. Bohner, S. Matter, J.A. Auer, B. von Rechenberg, In vivo behavior of three different injectable hydraulic calcium phosphate cements, Biomaterials, 25 (2004) 1439-1451.
• 11. J.E. Dumas, K. Zienkiewicz, S.A. Tanner, E.M. Prieto, S. Bhattacharyya, S.A. Guelcher, Synthesis and characterization of an injectable allograft bone/polymer composite bone void filler with tunable mechanical properties, Tissue Eng. Part A, 16 (2010) 2505-2518.
• 12. N.L. Ignjatović, C.Z. Liub, J.T. Czernuszka, D.P. Uskokovića, Micro-and nano-injectable composite biomaterials containing calcium phosphate coated with poly (DL-lactideco- glycolide), Acta Biomater., 3 (2007) 927-935.
• 13. J.D. Kretlow, L. Klouda, A.G. Mikos, Injectable matrices and scaffolds for drug delivery in tissue engineering, Adv. Drug Deliver. Rev., 59 (2007) 263-273.
• 14. A. La Gatta, A. De Rosa, P. Laurienzo, M. Malinconico, A novel injectable poly (ε‐caprolactone)/calcium sulfate system for bone regeneration: Synthesis and characterization, Macromol Biosci., 5 (2005) 1108-1117.
• 15. A. López, C. Persson, J. Hilborn, H. Engqvist, Synthesis and characterization of injectable composites of poly [D, Llactide‐ co‐(ε‐caprolactone)] reinforced with β‐TCP and CaCO3 for intervertebral disk augmentation, J. Biomed. Mater. Res. B: Appl. Biomater., 95 (2010) 75-83.
• 16. K.L. Low, S.H. Tan, S.H.S. Zein, J.A. Roether, V. Mouriño, A.R. Boccaccini, Calcium phosphate‐based composites as injectable bone substitute materials, J. Biomed. Mater. Res. Part B: Appl. Biomater., 94 (2010) 273-286. H.T. Sirin et al. / Hacettepe J. Biol. & Chem., 2019, 47 (1), 133–141 141
• 17. K. Rezwan, Q.Z. Chen, J.J. Blaker, A.R. Boccaccini, Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering, Biomaterials, 27 (2006) 3413-3431.
• 18. A. Senköylü, E. Ural, K. Kesencì, A. Sìmşek, S. Ruacan, L. Fambri, C. Migliaresi, E. Pìşkìn, Poly (D, L-lactide/ɛcaprolactone)/ hydroxyapatite composites as bone filler: an in vivo study in rats, Int. J. Artif. Organs, 25 (2002) 1174-1179.
• 19. E. Ural, K. Kesenci, L. Fambri, C. Migliaresi, E. Piskin, Poly (D, L-cactide/ε-caprolactone)/hydroxyapatite composites, Biomaterials, 21 (2000) 2147-2154.
• 20. R.Y. Basha, M. Doble, Design of biocomposite materials for bone tissue regeneration, Mater. Sci., 57 (2015) 452-463.
• 21. B. Torabinejad, J. Mohammadi-Rovshandeh, S.M. Davachi, A. Zamaniana, Synthesis and characterization of nanocomposite scaffolds based on triblock copolymer of L-lactide, ε-caprolactone and nano-hydroxyapatite for bone tissue engineering, Mater. Sci. and Eng. C., 42 (2014) 199- 210.
• 22. H. Nie, C.H. Wang, Fabrication and characterization of PLGA/ HAp composite scaffolds for delivery of BMP-2 plasmid DNA, J. Control. Release, 120 (2007) 111-121.
• 23. Z. Hong, R.L. Reis, J.F. Mano, Preparation and in vitro characterization of novel bioactive glass ceramic nanoparticles, J. Biomed. Mater. Res. A, 88 (2009) 304-313.
• 24. T. Miyai, A. Ito, G. Tamazawa, T. Matsuno, Y. Sogo, C. Nakamura, A. Yamazaki, T. Satoh, Antibiotic-loaded poly-ε- caprolactone and porous β-tricalcium phosphate composite for treating osteomyelitis, Biomaterials, 29 (2008) 350-358.
• 25. F. Yang, J. Wolke, J. Jansen, Biomimetic calcium phosphate coating on electrospun poly (ɛ-caprolactone) scaffolds for bone tissue engineering, Chem. Eng. J., 137 (2008) 154-161.
• 26. V. Guarino, L. Ambrosio, The synergic effect of polylactide fiber and calcium phosphate particle reinforcement in poly ε-caprolactone-based composite scaffolds, Acta Biomater., 4 (2008) 1778-1787.
• 27. C.C.P.M. Verheyen, J.R. De Wijn, C.A. Van Blitterswijk, K. DeGroot, Evaluation of hydroxylapatite/poly (l‐lactide) composites: Mechanical behavior, J. Biomed. Mater. Res., 26 (1992) 1277-1296.
• 28. Y. Kinoshita, M. Matsuo, K. Todoki, S. Ozono, S. Fukuoka, H. Tsuzuki, M. Nakamura, K. Tomihata, T. Shimamoto, Y. Ikada, Alveolar bone regeneration using absorbable poly (L-lactideco- ɛ-caprolactone)/β-tricalcium phosphate membrane and gelatin sponge incorporating basic fibroblast growth factor, Int. J. Oral and Maxillofac. Surg., 37 (2008) 275-281.
• 29. M. K ikuchi, Y. K oyama, T. Y amada, Y. I mamura, T. O kada, N. Shirahama, K. Akita, K. Takakuda, J. Tanaka, Development of guided bone regeneration membrane composed of β-tricalcium phosphate and poly (L-lactide-co-glycolide-co- ε-caprolactone) composites, Biomaterials, 25 (2004) 5979- 5986.
• 30. P. N. Kumta, C. Sfeir, D.H. Lee, D. Olton, D. Cho, Nanostructured calcium phosphates for biomedical applications: novel synthesis and characterization, Acta Biomater., 1 (2005) 65-83.
• 31. S.V. Dorozhkin, Bioceramics of calcium orthophosphates, Biomaterials, 31 (2010) 1465-1485.
• 32. L.L. Hench, Bioceramics: from concept to clinic, J. Am. Ceram. Soc., 74 (1991) 1487-1510.
• 33. S. Raynaud, E. Champion, D. Bernache-Assollant, P. Thomas, Calcium phosphate apatites with variable Ca/P atomic ratio I. Synthesis, characterisation and thermal stability of powders, Biomaterials, 23 (2002) 1065-1072.
• 34. B. Schrader, Infrared and Rarnan spectroscopy: Methods and applications VCH Publishers. Inc., New York, USA, 1995.
• 35. B. Stuart, Infrared spectroscopy, Kirk‐Othmer Encyclopedia of Chemical Technology, (2000) 1-18.
• 36. E. Akdogan, M. Demirbilek, Y. Sen, M.A. Onur, O.K. Azap, E. Sonmez, H.T. Sirin, M. Mutlu, In-vitro and in-vivo bacteria anti-fouling properties of phosphite plasma treated silicone, surface innovations, 7 (2018) 122-132.
• 37. B. Stuart, Infrared spectroscopy: Fundamentals and applications, John Wiley & Sons, Ltd, Weinheim Germany, 2005
• 38. K. Ishikawa, P. Ducheyne, S. Radin, Determination of the Ca/P ratio in calcium-deficient hydroxyapatite using X-ray diffraction analysis, J. Mater. Sci. Mater. Med., 4 (1993) 165- 168.
• 39. M. Akao, H. Aoki, K. Kato, A. Sato, Dense polycrystalline β-tricalcium phosphate for prosthetic applications, J. Mater. Sci. Mater. Med., 17 (1982) 343-346.
• 40. Y. Lemmouchi, E. Schacht, C. Lootens, In vitro release of trypanocidal drugs from biodegradable implants based on poly (ε-caprolactone) and poly(D,L-lactide), J. Control. Release, 55 (1998) 79-85.
• 41. H. Kricheldorf, Syntheses and application of polylactides, Chemosphere, 43 (2001) 49-54.
• 42. L. Wu, J. Ding, In vitro degradation of three-dimensional porous poly (D, L-lactide-co-glycolide) scaffolds for tissue engineering, Biomaterials, 25 (2004) 5821-5830.
• 43. H. Pistner, D.R. Bendi, J. Muhling, J.F. Reuther, Poly (l-lactide): a long-term degradation study in vivo: Part III. Analytical characterization, Biomaterials, 14 (1993) 291-298.
• 44. Y. Ikada, S.H. Hyon, K. Jamshidi, S. Higashi, T. Yamamuro, Y. Katutani, T. Kitsugi, Release of antibiotic from composites of hydroxyapatite and poly(lactic acid), J. Control. Release, 2 (1985) 179-186.