Kamel BACHIMAM, Ezgi EMÜL, Necdet SAĞLAM, Feza KORKUSUZ

Baicalein Nanofiber Scaffold Containing Hyaluronic Acid and Polyvinyl Alcohol: Preparation and Evaluation

Background/aim: Bone tumor is one of the major causes of tissue bone loss, particularly after performing surgical excision operation to bone lesion that needs to be replaced by biomaterials and ensure a complete filling of tissue-loss spaces. The purpose of our study was to produce a nanofiber-based bone graft scaffold to fill the gaps resulted from bone cancer treatment and also capable of carrying functional molecules that can play a major role in preventing further cancer growth at the targeted bone tissue. Materials and methods: Electrospinning method was used in order to produce nanofibers from different kinds of polymers; Hyaluronic acid HA , Polyethylene oxide PEO and Polyvinyl alcohol PVA blended with different concentrations of herbal antibiotic and anti cancer flavonoid molecules called Baicalein BE . The morphological and chemical structures of scaffold samples were studied using Scanning Electron Microscope SEM , Fourier Transform Infrared-spectroscopy FT-IR and Surface-enhanced Raman spectroscopy SERS Analysis. Results: The results showed production of homogenous nanofibers-based scaffold diameter between 80 nm and 470 nm that contains the polymers used in the spinning process and the entrapped Baicalein molecules within the nanofiber structure. Conclusion: It was concluded that successful formation of bone tissue mimicking scaffold can be achieved by using Electrospinning method that produces nonwoven nanofibers and at the same time can hold functional anticancer agent such as Baicalein, which may allow using these types of scaffold in bone cancer treatment procedures.

Keywords:

Baicalein, hyaluronic acid nanofiber, electrospinning, bone cancer, tissue engineering,

___

1. HeF, Zhang W, Shen Y, Yu P, Bao Q et al. Effects of resection margins on local recurrence of osteosarcoma in extremity and pelvis: Systematic review and meta-analysis. International Journal of Surgery 2016; 36: 283-292. doi: 10.1016/j. ijsu.2016.11.016
2. ChenY, Liu T, Wang K, Hou C, Cai S et al. Baicalein inhibits Staphylococcus aureus biofilm formation and the quorum sensing system in vitro. PloS One 2016; 11 (4): e0153468-e0153468.
3. DindaB, Dinda S, DasSharma S, Banik R, Chakraborty A et al. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. European Journal of Medicinal Chemistry 2017; 131: 68-80. doi: 10.1016/j.ejmech.2017.03.004
4. LiuH, Dong Y, Gao Y, Du Z, Wang Y et al.The fascinating effects of baicalein on cancer: a review. International Journal of Molecular Sciences 2016; 17 (10): 1681.doi: 10.3390/ ijms17101681
5. SaulD, Kling JH, Kosinsky RL, Hoffmann DB, Komrakova M et al. Effect of the lipoxygenase inhibitor baicalein on muscles in ovariectomized rats. Journal of Nutrition and Metabolism 2016; 2016. doi: 10.1155/2016/3703216
6. SaulD, Gleitz S, Nguyen HH, Kosinsky RL, Sehmisch S et al. Effect of the lipoxygenase-inhibitors baicalein and zileuton on the vertebra in ovariectomized rats. Bone 2017; 101: 134-144. doi: 10.1016/j.bone.2017.04.011
7. Li S, Tang J, Chen J, Zhang P, Wang T et al. Regulation of bone formation by baicalein via the mTORC1 pathway. Drug Design, Development and Therapy 2015; 9: 5169-5183.doi: 10.2147/ DDDT.S81578
8. Kim MH, Ryu SH, Bae M, Choi JS, Min Y et al. Baicalein inhibits osteoclast differentiation and induces mature osteoclast apoptosis. Food and Chemical Toxicology 2008; 46 (11): 3375- 3382.doi: 10.1016/j.fct.2008.08.016
9. Wang XH, Guo YW, Tolba E, Kokkinopoulou M, Wiens M et al.Two-armed activation of bone mineral deposition by the flavones baicalin and baicalein, encapsulated in polyphosphate microparticles. The American Journal of Chinese Medicine 2017; 45 (3): 533-555. doi: 10.1142/S0192415X1750032X
10. SomjenD, Katzburg S, Knoll E, Sharon O, Posner GH et al. Vitamin D analogs induce lipoxygenase mRNA expression and activity as well as reactive oxygen species (ROS) production in human bone cells. Journal of Steroid Biochemistry and Molecular Biology 2010; 121 (1-2): 265-267. doi: 10.1016/j. jsbmb.2010.03.047
11. ChenLJ, Hu BB, Shi XL, Ren MM, Yu WB et al. Baicalein enhances the osteogenic differentiation of human periodontal ligament cells by activating the Wnt/β-catenin signaling pathway. Archives of Oral Biology 2017; 78: 100-108.doi: 10.1016/j.archoralbio.2017.01.019
12. LaiCH,Wu YW, Yeh SD, Lin YH, Tsai YH. Effects of 6-hydroxyflavone on osteoblast differentiation in MC3T3-E1 cells. Evidence-Based Complementary and Alternative Medicine 2014; 2014: 924560. doi: 10.1155/2014/924560
13. KimJM, Lee SU, Kim YS, Min YK, Kim SH. Baicalein stimulates osteoblast differentiation via coordinating activation of MAP kinases and transcription factors. Journal of Cellular Biochemistry 2008; 104 (5): 1906-1917.doi: 10.1002/jcb.21760
14. Zhang Y, Song L, Cai L, Wei R, Hu H et al. Effects of baicalein on apoptosis, cell cycle arrest, migration and invasion of osteosarcoma cells. Food and Chemical Toxicology 2013; 53: 325-333. doi: 10.1016/j.fct.2012.12.019
15. RenekerDH, Yarin AL. Electrospinning jets and polymer nanofibers. Polymer 2008; 49 (10): 2387-2425. doi: 10.1016/j. polymer.2008.02.002
16. YoshimotoH, Shin YM, Terai H, Vacanti JP. A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials 2003; 24 (12): 2077-2082. doi: 10.1016/s0142-9612(02)00635-x
17. KimKH, Jeong L, Park HN, Shin SY, Park WHet al.Biological efficacy of silk fibroin nanofiber membranes for guided bone regeneration. Journal of Biotechnology 2005; 120 (3): 327-339. doi: 10.1016/j.jbiotec.2005.06.033
18. EmulE, Saglam S, Ates H, Korkusuz F, Saglam N. Characterization of electrospun nanofibrous scaffolds for nanobiomedical applications. Journal of Electronic Materials 2016; 45 (8): 3835-3841. doi: 10.1007/s11664-016-4549-7
19. Guo S, Miao L, Wang Y, Huang L. Unmodified drug used as a material to construct nanoparticles: delivery of cisplatin for enhanced anti-cancer therapy. Journal of Controlled Release 2014; 174: 137-142. doi: 10.1016/j.jconrel.2013.11.019
20. HeunisT, Botes M, Dicks LM. Encapsulation of Lactobacillus plantarum 423 and its bacteriocin in nanofibers. Probiotics and antimicrobial proteins 2010; 2 (1): 46-51.doi: 10.1007/s12602- 009-9024-9
21. Bachimam K. Production and characterization of hyaluronic acid nanofibers containing TGF-β and baicalein by using electrospinning method. Msc, Hacettepe University, Ankara, Turkey, 2017.
22. Ahire JJ, Robertson DD, van Reenen AJ, Dicks LM. Polyethylene oxide (PEO)-hyaluronic acid (HA) nanofibers with kanamycin inhibits the growth of Listeria monocytogenes. Biomedicine & Pharmacotherapy 2017; 86: 143-148. doi: 10.1016/j. biopha.2016.12.006
23. ToskasG, Cherif C, Hund RD, Laorine E, Mahltig B et al. Chitosan (PEO)/silica hybrid nanofibers as a potential biomaterial for bone regeneration. Carbohydrate Polymers 2013; 94 (2): 713-722. doi: 10.1016/j.carbpol.2013.01.068
24. JiaYT, Gong J, Gu XH, Kim HY, Dong J et al. Fabrication and characterization of poly (vinyl alcohol)/chitosan blend nanofibers produced by electrospinning method. Carbohydrate Polymers 2007; 67 (3): 403-409. doi: 10.1016/j. carbpol.2006.06.010
25. Unsalan O, Erdogdu Y, Gulluoglu MT. FT‐Raman and FT‐IR spectral and quantum chemical studies on some flavonoid derivatives: Baicalein and Naringenin. Journal of Raman Spectroscopy 2009; 40 (5): 562-570. doi: 10.1002/jrs.2166
26. BarzegarF, Bello A, Fabiane M, Khamlich S, Momodu D et al. Preparation and characterization of poly (vinyl alcohol)/ graphene nanofibers synthesized by electrospinning. Journal of Physics and Chemistry of Solids 2015; 77: 139-145. doi: 10.1016/j.jpcs.2014.09.015
27. Venugopal J, Ramakrishna S. Biocompatible nanofiber matrices for the engineering of a dermal substitute for skin regeneration. Tissue Engineering 2005; 11 (5-6): 847-854. doi: 10.1089/ten.2005.11.847
28. Scherer SS, Pietramaggiori G, Matthews J, Perry S, Assmann A et al. Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis. Annals of Surgery 2009; 250 (2): 322-330. doi: 10.1097/SLA.0b013e3181ae9d45
29. Nirmala R, Kalpana D, Jeong JW, Oh HJ, Lee JH et al. Multifunctional baicalein blended poly (vinyl alcohol) composite nanofibers via electrospinning. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2011; 384 (1): 605-611. doi: 10.1016/j.colsurfa.2011.05.009
30. Koh SY, Moon JY, Unno T, Cho SK. Baicalein suppresses stem cell-like characteristics in radio-and chemoresistant MDAMB-231 human breast cancer cells through up-regulation of IFIT2. Nutrients 2019; 11 (3): E624. doi: 10.3390/nu11030624
31. Zhao Z, Liu B, Sun J, Lu L, Liu L et al. Baicalein inhibits orthotopic human non-small cell lung cancer xenografts via Src/ Id1 pathway. Evidence-Based Complementary and Alternative Medicine 2019; 2019: 9806062. doi: 10.1155/2019/9806062
32. Zhang J, Yang W, Zhou YB, Xiang YX, Wang LS et al. Baicalein inhibits osteosarcoma cell proliferation and invasion through the miR-183/Ezrin pathway. Molecular Medicine Reports 2018; 18 (1): 1104-1112.doi: 10.3892/mmr.2018.9036
33. WangY, Cui W, Zhao X, Wen S, Sun Y et al. Bone remodelinginspired dual delivery electrospun nanofibers for promoting bone regeneration. Nanoscale 2019; 11 (1): 60-71.doi: 10.1039/ c8nr07329e
34. Kjalarsdóttir L, Dyrfjörd A, Dagbjartsson A, Laxdal EH, Örlygsson G et al. Bone remodeling effect of a chitosan and calcium phosphate-based composite. Regenerative Biomaterials2019; 6 (4): 241-247. doi: 10.1093/rb/rbz009
35. Rahmanian M, Seyfoori A, Dehghan MM, Eini L, Naghib SM et al. Multifunctional gelatin–tricalcium phosphate porous nanocomposite scaffolds for tissue engineering and local drug delivery: In vitro and in vivo studies. Journal of the Taiwan Institute of Chemical Engineers 2019; 101: 214-220. doi: 10.1016/j.jtice.2019.04.028
36. Chan WP, Huang KC, Bai MY. Silk fibroin protein‐based nonwoven mats incorporating baicalein Chinese herbal extract: preparation, characterizations, and in vivo evaluation. Journal of Biomedical Materials Research Part B: Applied Biomaterials 2017; 105 (2): 420-430. doi: 10.1002/jbm.b.33560