Biodegradable polymer composites with osteogenic potential
https://doi.org/10.20538/1682-0363-2020-4-119-129
Abstract
The aim is to study the basic physico-mechanical properties of hydroxyapatite (HA) composites (up to 25–50 wt%) with polylactide (PLA-HA) and poly(e-caprolactone) (PCL-HA) prepared by melt compounding, as well as the osteogenic potential of PLA-HA in vivo.
Materials and methods. All biodegradable polymer composites were prepared by hot melt compounding and studied by dielectric spectroscopy in frequency domain, optical microscopy, X-ray diffraction analysis and tensile tests. An ability of PLA-5 wt% HA composites prepared by 3D-printing to induce bone tissue growth in vivo was detected with the help of ectopic subcutaneous test in inbred mice.
Results. Values of the real part of complex permittivity of PLA-HA and PCL-HA composites are increased by 15–30% compared to those for initial PLA and PCL, while tand loss factor does not exceed 0.02 for PLA-based composites and 0.2 for PCL-based composites. The crystallinity degree of PLA-HA composites is increased by 3 and 6 times with an increase of HA content from 25 to 50 wt% respectively compared to the indicator for PLA. The crystallinity degree of PCL-HA composites with 25 wt% HA is increased by 2 times compared to the value for PCL. It is due to the fact that HA powder particles play the role of additional nucleation centers. For all this, mechanical strength of composites diminished statistically. Even lowest HA content (5 wt%) in PLA-HA composites prepared by 3D-printing increased the incidence of ectopic osteogenesis by 40%.
Conclusion. Designed biodegradable composites have a potential of practical use for bone tissue engineering.
About the Authors
S. M. LebedevRussian Federation
30, Lenina Av., Tomsk, 634050, Russian Federation
D. M. Chistokhin
Russian Federation
30, Lenina Av., Tomsk, 634050, Russian Federation
S. V. Shchadenko
Russian Federation
30, Lenina Av., Tomsk, 634050, Russian Federation
A. N. Dzuman
Russian Federation
2, Mosсow Tract, Tomsk, 634050, Russian Federation
O. O. Nikolaeva
Russian Federation
45, Gerzena Str., Tomsk, 634061, Russian Federation
D. V. Mitrichenko
Russian Federation
45, Gerzena Str., Tomsk, 634061, Russian Federation
A. V. Prosolov
Russian Federation
45, Gerzena Str., Tomsk, 634061, Russian Federation
I. A. Khlusov
Russian Federation
30, Lenina Av., Tomsk, 634050, Russian Federation
2, Mosсow Tract, Tomsk, 634050, Russian Federation
45, Gerzena Str., Tomsk, 634061, Russian Federation
14, A. Nevskogo Str., Kaliningrad, 236041, Russian Federation
References
1. Hutmacher D.W. Scaffolds in tissue engineering bone and cartilage. Biomaterials. 2000; 21 (24): 2529–2543. DOI: 10.1016/s0142-9612(00)00121-6.
2. Murariu M., Dubois P. PLA composites: from production to properties. Adv. Drug Deliv. Rev. 2016; 107: 17–46. DOI:
3. 1016/j.addr.2016.04.003.
4. Langer R., Vacanti J.P. Tissue engineering. Science. 1993; 260: 920–926. DOI: 10.1126/science.8493529.
5. Gupta A.P., Kumar V. New emerging trends in synthetic biodegradable polymers – polylactide: a critique. Europ. Polym. J. 2007; 43 (10): 4053–4074. DOI: 10.1016/J.EURPOLYMJ.2007.06.045.
6. Jorge P., Domingos M., Gloria A., Ciurana J. BioCell printing: Integrated automated assembly system for tissue engineering constructs. CIRP Annals – Manufacturing Technology. 2011; 60 (1): 271–274. DOI: 10.1016/J.CIRP.2011.03.116.
7. Elzubair A., Elias C.N., Suarez J.C.M., Lopes H.P., Vieira M.V.B. The physical characterization of a thermoplastic polymer for endodontic obturation. J. Dent. 2006; 34 (10): 784–789. DOI: 10.1016/j.jdent.2006.03.002.
8. Hutmacher D.W., Schantz T., Zein I., Ng K.W., Teoh S.H., Tan K.C. Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. J. Biomed. Mater. Res. 2001; 55(2): 203–216. DOI: 10.1002/1097-4636(200105)55: 2<203::aid-jbm1007>3.0.co;2-7.
9. Rohner D., Hutmacher D.W., Cheng T.K., Oberholzer M., Hammer B. In vivo efficacy of bone-marrow-coated polycaprolactone scaffolds for the reconstruction of orbital defects in the pig. J. Biomed. Mater. Res. B: Appl. Biomater. 2003; 66B (2): 574–580. DOI: 10.1002/jbm.b.10037.
10. Tay F.R., Pashley D.H., Williams M.C., Raina R., Loushine R.J., Weller R.N. et al. Susceptibility of a polycaprolactone-based root canal filling material to degradation. I. Alkaline hydrolysis. J. Endodontics. 2005; 31 (8): 593–598. DOI: 10.1097/01.don.0000152301. 72828.61.
11. Chan-Chan L.H., Solis-Correa R., Vargas-Coronado R.F., Cervantes-Uc J.M., Cauich-Rodríguez J.V., Quintana P., Bartolo-Pérez P. Degradation studies on segmented polyurethanes prepared with HMDI, PCL and different chain extenders. Acta Biomaterialia. 2010; 6 (6): 2035–2044. DOI: 10.1016/j.actbio.2009.12.010.
12. Mitchell C.A., Krishnamoorti R. Dispersion of single-walled carbon nanotubes in poly(e-caprolactone). Macromolecules. 2007; 40 (5): 1538–1545. DOI: 10.1021/ma0616054.
13. Raquez J.-M., Habibi Y., Murariu M., Dubois P. Polylactide (PLA)-based nanocomposites. Prog. Polym. Sci. 2013; 38 (10–11): 1504–1542. DOI: 10.1016/j.progpolymsci.2013.05.014.
14. Ray S.S., Bousmina M. Biodegradable polymers and their layered silicate nanocomposites: in green the 21st century materials word. Prog. Mater. Sci. 2005; 50: 962–1079. DOI: 10.1016/j.pmatsci.2005.05.002.
15. Murariu M., Paint Y., Murariu O., Raquez J.-M., Bonnaud L., Dubois P. Current progress in the production of PLA–ZnO nanocomposites: Beneficial effects of chain extender addition on key properties. J. Appl. Polym. Sci. 2015; 132: 42480. DOI: 10.1002/app.42480.
16. Murariu M., Dechief A.L., Bonnaud L., Paint Y., Gallos A., Fontaine G., et al. The production and properties of polylactide composites filled with expanded graphite. Polym. Degrad. Stab. 2010; 95: 889–900. DOI: 10.1016/j.polymdegradstab.2009.12.019.
17. Li S.H., Liu Q., Wijn J.R., Zhou B.L., Groot K. In vitro calcium phosphate formation on a natural composite material, bamboo. Biomaterials. 1997; 18 (5): 389–395. DOI: 10.1016/S0142-9612(96)00122-6.
18. Morvan J., Buyuktanir E., West J.L., Jákli A. Highly piezoelectric biocompatible and soft composite fibers. Appl. Phys. Lett. 2012; 100 (6). DOI: 10.1063/1.3683482.
19. Lebedev S.M., Amitov E.T., Mikutskiy E.A. Biodegradable electrically conductive polycaprolactone-based composites filled with carbon nanotubes. Russian Phys. J. 2020; 62 (10): 1753–1762. DOI: 10.1007/s11182-020-01903-0.
20. Лекишвили М.В., Балберкин А.В., Васильев М.Г., Колондаев А.Ф., Баранецкий А.Л, Буклемишев Ю.В. Первый опыт применения в клинике костной патологии биокомпозиционного материала «Остеоматрикс». Вестник травматологии и ортопедии им. Н.Н. Приорова. 2002; 4: 80–83.
21. Иванов С.Ю., Бизяев Н.Ф., Ломакин М.В., Панин А.М. Клинические результаты использования различных костнопластических материалов при синус-лифтинге. Новое в стоматологии. 1999; 5: 51–54.
22. Аглуллин И.Р., Сафин И.Р. Остеопластика в лечении пациентов с дефектами костной ткани. Поволжский онкологический вестник. 2012; 1: 42–44.
23. Gonçalves E.M., Oliveira F.J., Silva R.F., Neto M.A., Fernandes M.H., Amaral M. et al. Three-dimensional printed PCL-hydroxyapatite scaffolds filled with CNTs for bone cell growth stimulation. J. Biomed. Mater. Res. Part: B. 2016; 104 (6): 1210–1219. DOI: 10.1002/ jbm.b.33432.
24. Akindoyo J.O., Beg M.D.H., Ghazali S., Alam A.K.M.M., Heim H.P., Feldmann M. Synergized poly(lactic acid)- hydroxyapatite composites: Biocompatibility study. J. Appl.Polym. Sci. 2019. DOI: 10.1002/app.47400.
25. Akindoyo J.O., Beg M.D.H., Ghazali S., Heim H.P., Feldmann M. Impact modified PLA-hydroxyapatite composites – thermo-mechanical properties. Comp. Part A: App. Sci. Manufact. 2018; 107: 326–333. DOI: 10.1016/j.compositesa.2018.01.017.
26. Šupová M. Problem of hydroxyapatite dispersion in polymer matrices: a review. J. Mater. Sci. Mater. Med. 2009; 20 (6): 1201–1213. DOI: 10.1007/s10856-009-3696-2.
27. Mao D., Li Q., Bai N., Dong H., Li D. Porous stable poly(lactic acid)/ethyl cellulose/hydroxyapatite composite scaffolds prepared by a combined method for bone regeneration. Carbohydrate Polymers. 2018; 180: 104–111. DOI: 10.1016/j.carbpol.2017. 10.031.
28. Alizadeh-Osgouei M., Li Y., Wen C. A comprehensive review of biodegradable synthetic polymer-ceramic composites and their manufacture for biomedical applications. Bioactive Mater. 2019; 4 (1): 22–36. DOI: 10.1016/j.bioactmat.2018.11.003.
29. Russias J., Saiz E., Nalla R.K., Gryn K., Ritchie R.O., and Tomsia A.P. Fabrication and mechanical properties of
30. PLA/HA composites: а study in vitro degradation. Mater. Sci. Eng. C: Biomim. Supramol. Syst. 2006; 26 (8): 1289–1295. DOI: 10.1016/j.msec.2005.08.004.
31. Ferri J.M., Jorda J., Montanes N., Fenollar O., and Balart R. Manufacturing and characterization of poly(lactic acid) composites with hydroxyapatite. J. Thermoplast. Comp. Mater. 2017; 31 (7): 865–881. DOI: 10.1177/0892705717729014.
32. Zhang H., Mao X., Du Z., Jiang W., Han X., Zhao D. et al. Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model. Sci. Tech. Adv. Mater. 2016; 17 (1). DOI: 10.1080/14686996.2016.1145532.
33. Zhang S.M., Liu J., Zhou W., Cheng L., Guo X.D. Interfacial fabrication and property of hydroxyapatite/polylactide resorbable bone fixation composites. Curr. Appl. Phys. 2005; 5 (5): 516–518. DOI: 10.1016/j.cap.2005.01.023.
34. Shen L., Yang H., Ying J., Qiao F., Peng M. Preparation and mechanical properties of carbon fiber reinforced hydroxyapatite/polylactide biocomposites. J. Mater. Sci. Mater. Med. 2009; 20 (11): 2259–2265. DOI: 10.1007/s10856-009-3785-2.
35. Park S.A., Lee S.H., Kim W.D. Fabrication of porous polycaprolactone/hydroxyapatite (PCL/HA) blend scaffolds using a 3D plotting system for bone tissue engineering. Bioprocess Biosyst. Eng. 2011; 34 (4): 505–513. DOI: 10.1007/s00449-010-0499-2.
36. Kim J.Y., Lee T.-J., Cho D.-W., Kim B.-S. Solid free- form fabrication-based PCL/HA scaffolds fabricated with a multi-head deposition system for bone tissue engineering. J. Biomater. Sci. 2010; 21 (6–7): 951–962. DOI: 10.1163/156856209X458380.
37. Jiang W., Shi J., Li W., Sun K. Morphology, wettability, and mechanical properties of polycaprolactone/hydroxyapatite composite scaffolds with interconnected pore structures fabricated by a mini- deposition system. Polym. Eng. Sci. 2012; 52: 2396–2402. DOI: 10.1002/pen.23193.
38. Chaikina M.V., Uvarov N.F., Ulihin A.S., Khlusov I.A. Mechanochemical synthesis of nanosized functional materials with the apatite-type structure. Problems of Materials Science. 2008; 54 (2): 219–232.
39. Дружинина Т.В., Талалаев С.Я., Закиров Н.П., Щаденко С.В., Хабибулин Ш.А., Хлусов И.А., Литвинова Л.С. Клеточные реакции на трехмерные матриксы из полимолочной кислоты и гидроксиапатита, полученные методом 3D-печати. Бюллетень сибирской медицины. 2016; 15 (5): 16–29.
40. Scott M.A., Levi B., Askarinam A., Nguyen A., Rackohn T., Ting K., Soo C., James A.W. Brief review of models of ectopic bone formation. Stem Cells Dev. 2012; 21 (5): 655– 668. DOI: 10.1089/scd.2011.0517.
41. Bolbasov E.N., Popkov A.V., Popkov D.A., Gorbach E.N., Khlusov I.A., Golovkin A.S., Sinev A., Bouznik V.M., Tverdokhlebov S.I., Anissimov Y.G. Osteoinductive composite coatings for flexible intramedullary nails. Mater. Sci. Eng. C. 2017; 75: 207–220. DOI: 10.1016/j.msec.2017.02.073.
42. Caplan A.I. Mesenchymal stem cells. J. Orthop. Res. 1991; 9 (5): 641–50. DOI: 10.1002/jor.1100090504.
43. Silva C.C., Almeida A.F.L., De Oliveira R.S., Pinheiro A.G., Góes J.C., Sombra A.S.B. Dielectric permittivity and loss of hydroxyapatite screen-printed thick films. J. Mater. Sci. 2003; 38: 3713–3720. DOI: 10.1023/A:1025963728858.
44. Jukkala-Partio K., Laitinen O., Vasenius J., Partio E.K., Toivonen T., Tervahartiala P., Kinnunen J., Rokkanen P. Healing of subcapital femoral osteotomies fixed with self-reinforced poly-L lactide screws. An experimental long-term study in sheep. Arch. Orthop. Trauma Surg. 2002; 122 (6): 360–364 DOI: 10.1007/s00402-001-0379-y.
45. Bostman O.M., Pihlajamaki H.K. Late foreign-body reaction to an intraosseous bioabsorbable polylactic acid screw. A case report. J. Bone Joint. Surg. Am. 1998; 80 (12): 1791–1794. DOI: 10.2106/00004623-199812000-00010.
46. Zhang R., Ma P. X. Porous poly(L-lactic acid)/apatite composites created by biomimetic process. J. Biomed. Mater. Res. 1999; 45 (4): 285–293. DOI: 10.1002/(sici)1097-4636(19990615)45:4<285::aid-jbm2>3.0.co;2-2.
47. Фриденштейн А.Я., Лурия Е.А. Клеточные основы кроветворного микроокружения. М.: Медицина, 1980: 216.
Review
For citations:
Lebedev S.M., Chistokhin D.M., Shchadenko S.V., Dzuman A.N., Nikolaeva O.O., Mitrichenko D.V., Prosolov A.V., Khlusov I.A. Biodegradable polymer composites with osteogenic potential. Bulletin of Siberian Medicine. 2020;19(4):119-129. https://doi.org/10.20538/1682-0363-2020-4-119-129