A study on cytotoxicity, hemocompatibility, and antibacterial properties of tetracycline hydrochloride-loaded PCL-based composite scaffolds for bone tissue engineering

Bohlouli, Mahsa; Tamjid, Elnaz; Mohammadi, Soheila; Nikkhah, Maryam

A study on cytotoxicity, hemocompatibility, and antibacterial properties of tetracycline hydrochloride-loaded PCL-based composite scaffolds for bone tissue engineering

Document Type : Original Research

Authors

Mahsa Bohlouli ¹

Elnaz Tamjid ²

Soheila Mohammadi ³

Maryam Nikkhah ⁴

¹ Department of Interdisciplinary Science and Technology, Tarbiat Modares University

² Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University

³ Department of Nanobiotechnology, Tarbiat Modares UniversityCurrent affiliation: Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences

⁴ Department of Nanobiotechnology, Tarbiat Modares University

Abstract

Since one of the main problems in bone tissue repair is the bacterial infections, recently the development of drug-eluting nanocomposite scaffolds for bone regenerative medicine applications has attracted significant attention. In this study Polycaprolactone (PCL)-based composite scaffolds containing 10vol% of titanium dioxide nanoparticles (~21nm), and bioactive glass particles (~6µm), were prepared without drug and also loaded by Tetracycline hydrochloride (TCH) antibiotic (0.57, 1.15 mg/mL) through solvent casting method for bone tissue engineering applications. Structural characterizations based on Scanning Electron Microscopy (SEM), and FTIR analysis were utilized to study the chemical bonds of glass/ceramic particles, and antibiotic crystals on the surface. In addition, in vitro cytotoxicity, and antibacterial analysis were performed by MTT, and Agar well-diffusion assays, respectively. In this study polymeric and composite scaffolds were fabricated with TCH clusters decorated on the surface. It was shown that the bioactive glass/PCL scaffolds loaded by 0.57 mg/mL of TCH revealed significant antibacterial effect, despite the acceptable cell viability. These scaffolds seem to be of interest as a potential candidate in drug-eluting scaffolds for bone tissue engineering applications.

Keywords

Bone Tissue Engineering

Solvent casting

Tetracycline hydrochloride

Cytotoxicity

Antibacterial effect

composite scaffold

20.1001.1.23222115.1398.11.1.5.0

Subjects

Pharmaceutical Biotechnology

1. Mouriño, V., Boccaccini, A. R. (2009) Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds. Journal of the Royal Society Interface 6, rsif20090379.
2. Tamjid, E., Bagheri, R., Vossoughi, M., Simchi, A. (2011) Effect of TiO2 morphology on in vitro bioactivity of polycaprolactone/TiO2 nanocomposites. Materials Letters 65, 2530-2533.
3. Park, S. A., Lee, S. J., Seok, J. M., Lee, J. H., Kim, W. D., Kwon, I. K. (2018) Fabrication of 3D printed PCL/PEG polyblend scaffold using rapid prototyping system for bone tissue engineering application. Journal of Bionic Engineering 15, 435–442.
4. Ma, J., Lin, L., Zuo, Y., Zou, Q., Ren, X., Li, J., Li, Y. (2019) Modification of 3D printed PCL scaffolds by PVAc and HA to enhance cytocompatibility and osteogenesis. RSC Advances 9, 5338–5346.
5. Chellamani, K., Balaji, R. V., Sudharsan, J. (2013) Antibacterial properties of allopathic drug loaded polycaprolactone nanomembrane. J. Acad. Ind. Res. 2, 341-344.
6. Rezwan, K., Chen, Q., Blaker, J., Boccaccini, A.R. (2006) Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering, Biomaterials 27, 3413-3431.
7. Hench, L. L. (2006) The story of Bioglass®. Journal of Materials Science: Materials in Medicine 17, 967-978.
8. Demers, P., Fraser, D., Goldbloom, R., Haworth, J., LaRochelle, J., MacLean, R., Murray T. K. (1968) Effects of tetracyclines on skeletal growth and dentition. A report by the Nutrition Committee of the Canadian Paediatric Society. Canadian Medical Association Journal 9, 849–854.
9. Chanavaz, M. (1989) Maxillary sinus: anatomy, physiology, surgery, and bone grafting related to implantology-eleven years of surgical experience. The Journal of oral implantology 16, 199-209.
10. Kim, J., Park, S. A., Kim, J., Lee, J. (2018) Fabrication and Characterization of Bioresorbable Drug-coated Porous Sca_olds for Vascular Tissue Engineering. Materials 12, 1438-1447.
11. Goodson, J., Holborow, D., Dunn, R., Hogan, P., Dunham, S. (1983) Monolithic tetracycline-containing fibers for controlled delivery to periodontal pockets. Journal of periodontology 54, 575-579.
12. Chahal, G.S., Chhina, K., Chhabra, V., Bhatnagar, R., Chahal, A. (2014) Effect of citric acid, tetracycline, and doxycycline on instrumented periodontally involved root surfaces: A SEM study. Journal of Indian Society of Periodontology 18, 32–37.
13. Ranjbar-Mohammadi, M., Zamani, M., Prabhakaran, M., Bahrami, S. H., Ramakrishna, S. (2016) Electrospinning of PLGA/gum tragacanth nanofibers containing tetracycline hydrochloride for periodontal regeneration. Materials Science and Engineering: C 58, 521-531.
14. Reichert, J. C., Saifzadeh, S., Wullschleger, M. E., Epari, D. R., Schütz, M. A., Duda, G .N., Schell, H., van Griensven, M., Redl, H., Hutmacher, DW. (2009) The challenge of establishing preclinical models for segmental bone defect research. Biomaterials 30, 2149-2163.
15. Kim, H.W., Knowles, J.C., Kim, H.E. (2004) Hydroxyapatite/poly (ε-caprolactone) composite coatings on hydroxyapatite porous bone scaffold for drug delivery. Biomaterials 25, 1279-1287.
16. Khodir, W.W.A., Guarino, V., Alvarez-Perez, M., Cafiero, C., Ambrosio, L. (2013) Trapping tetracycline-loaded nanoparticles into polycaprolactone fiber networks for periodontal regeneration therapy. Journal of Bioactive and Compatible Polymers 28, 258-273.
17. Shao, W., Liu, H., Wang, S., Wu, J., Huang, M., Min, H. (2016) Controlled release and antibacterial activity of tetracycline hydrochloride-loaded bacterial cellulose composite membranes. Carbohydrate polymers 145, 114-120.
18. Trousdale, W. H., Salib, C. G., Reina, N., Lewallen, E. A., Viste, A., Berry, D. J., Morrey, M. E. , Sanchez-Sotelo, J., van Wijnen, A. J., Abdel, M. P. (2018) A Drug Eluting Scaffold for the Treatment of Arthrofibrosis. TISSUE ENGINEERING: Part C 24, 514-523.
19. Palam, I. E., Arcadio, V., D’Amone, S., Biasiucci, M., Gigli, G., Cortese, B. (2017) Scientific Reports 7, 12672.
20. E. ISO, "10993-5. Biological evaluation of medical devices-Part 5: Tests for in vitro cytotoxicity," Geneva: International Organization for Standardization, 2009.
21. Balouiri, M., Sadiki, M., Ibnsouda, S. K. (2016) Methods for in vitro evaluating antimicrobial activity: A review. Journal of Pharmaceutical Analysis 6, 71-79.
22. El Badry, K.M., Moustaffa, F., Azooz, M., El Batal, F. (2000) Infrared absorption spectroscopy of some bio-glasses before and after immersion in various solutions. Indian Journal of Pure & Applied Physics 3, 741-761.
23. Kim, J.H., Lee, O.J., Sheikh, F.A., Ju, H.W., Moon, B.M., Park, H.J., Park, C.H. (2014) Fabrication and Characterization of PCL/TiO2 Nanoparticle 3D Scaffold. Polymer Korea 38, 150-155.
24. Tamjid, E., Simchi, A., Dunlop, J.W.C., Fratzl, P., Bagheri, R., Vossoughi, M. (2013) Tissue growth into three-dimensional composite scaffolds with controlled micro-features and nanotopographical surfaces. Journal of Biomedical Materials Research A 101, 2796-2807.
25. Mavis, B., Demirtaş, T.T., Gümüşderelioğlu, M., Gündüz, G., Çolak, Ü. (2009) Synthesis, characterization and osteoblastic activity of polycaprolactone nanofibers coated with biomimetic calcium phosphate, Acta biomaterialia 5. 3098-3111.
26. Boccaccini, A. R., Blaker, J. J., Maquet, V., Chung, W., Jérôme, R., Nazhat, S. N. (2006) Poly (D, L-lactide)(PDLLA) foams with TiO2 nanoparticles and PDLLA/TiO2-Bioglass® foam composites for tissue engineering scaffolds. Journal of materials science 41, 3999-4008.
27. Tamjid, E., Bagheri, R., Vossoughi, M., Simchi, A. (2011) Effect of particle size on the in vitro bioactivity, hydrophilicity and mechanical properties of bioactive glass-reinforced polycaprolactone composites. Materials Science and Engineering: C 31, 1526-1533.
28. Bahniuk, M. S., Pirayesh, H., Singh, H. D., Nychka, J. A., Unsworth, L. D. (2012) Bioactive Glass 45S5 Powders: Effect of Synthesis Route and Resultant Surface Chemistry and Crystallinity on Protein Adsorption from Human Plasma. Biointerphases. 7, 1-15.
29. Radda'a, N. S., Goldmann, W. H., Detsch, R., Roether, J. A., Cordero-Arias, L., Virtanen, S., Moskalewicz, T., Boccaccini, A. R. (2017), Surface & Coatings Technology. 327, 146–157.
30. Koohsari, H, Ghaemi, EA, Sheshpoli, M. S., Jahedi, M, Zahiri, M. (2015) The investigation of antibacterial activity of selected native plants from North of Iran. Journal of Medicine and Life 8. 38-42.
31. Goy, R. C., Morais, S.T.B., Assis, O.B.G. (2016) Revista Brasileira de Farmacognosia 26. 122–127.