HEMOCOMPATIBILITY STUDIES OF LAYER-BY-LAYER POLYELECTROLYTE COMPLEXES FOR BIO-BASED POLYMERS

  • Mthabisi Talent George Moyo Department of Biomedical Engineering, Faculty of Engineering, Near East University, P.O. Box: 99138, TRNC, Mersin 10 Turkey
  • Terin Adali Department of Medical Biochemistry, Faculty of Medicine, Girne American University, P.O. Box: 99320 Karaman Girne, Turkish Republic of Northern Cyprus (TRNC), Mersin 10 Turkey.
  • Oğuz Han Edebal Clinical Biochemistry Laboratory, Near East University Hospital, P.O. Box: 99138, Turkish Republic of Northern Cyprus (TRNC), Mersin 10 Turkey
  • Ece Bayir Department of Bioengineering, Faculty of Engineering, Ege University, Bornova, 35100 Izmir, Turkey
  • Aylin Şendemir Department of Bioengineering, Faculty of Engineering, Ege University, Bornova, 35100 Izmir, Turkey
Keywords: polyelectrolyte complex, hemocompatibility, thrombogenesis

Abstract

Thrombogenesis is an important issue that causes blood-contacting biomedical device failure. This study focuses on hemocompatibility studies of novel blood-contacting polyelectrolyte complexes (PECs) for biomedical application designs. PEC films were fabricated from biobased polymers of silk fibroin (SF), chitosan (CH), and sodium alginate (AL) through the solvent casting method as well as Layer-by-Layer (LbL) technique. Characterization was carried out by Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Atomic force microscopy (AFM), and Differential scanning calorimetry (DSC) analyses. FTIR spectra displayed all layers’ characteristic peaks of SF, CH, and AL. AFM images indicated that the addition of AL as an outer layer increased surface roughness. DSC analysis suggested that the best thermal stability has been observed with the CH outer layer of PECs. SEM micrograph analysis indicated that the morphologies of PECs were affected by the inclusion of the clopidogrel bisulfate (CLB). Hemocompatibility properties were investigated by complete blood count (CBC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), platelet adhesion, erythrocyte morphology analysis, in vitro cholesterol, and albumin level tests. These hemocompatibility analyses demonstrated that the PEC surfaces provide favourable principles to design and develop non-thrombogenic PECs for blood-contacting biomedical applications

Author Biographies

Terin Adali, Department of Medical Biochemistry, Faculty of Medicine, Girne American University, P.O. Box: 99320 Karaman Girne, Turkish Republic of Northern Cyprus (TRNC), Mersin 10 Turkey.

Department of Biomedical Engineering, Faculty of Engineering, Near East University, P.O. Box: 99138, TRNC, Mersin 10 Turkey

Oğuz Han Edebal, Clinical Biochemistry Laboratory, Near East University Hospital, P.O. Box: 99138, Turkish Republic of Northern Cyprus (TRNC), Mersin 10 Turkey

Medical doctor in Biochemistry. Near East University Hospital, Clinical Biochemistry Laboratory, TRNC, Mersin 10 Turkey

Ece Bayir, Department of Bioengineering, Faculty of Engineering, Ege University, Bornova, 35100 Izmir, Turkey

Researcher at Central Research Test and Analysis Laboratory Application and Research Center (EGE-MATAL), Ege University, Bornova, 35100 Izmir, Turkey

Aylin Şendemir, Department of Bioengineering, Faculty of Engineering, Ege University, Bornova, 35100 Izmir, Turkey

Head of Department of Bioengineering, Faculty of Engineering, Ege University, Bornova, 35100 Izmir, Turkey

References

1 E. Ozkan et al., Bioinspired ultra-low fouling coatings on medical devices to prevent device-associated infections and thrombosis. Journal of colloid and interface science 608 (2022), 1015–1024, doi:10.1016/j.jcis.2021.09.183

2 P. S. Yavvari et al., Emerging biomedical applications of polyaspartic acid-derived biodegradable polyelectrolytes and polyelectrolyte complexes. Journal of materials chemistry B 7.13 (2019), 2102–2122, doi:10.1039/c8tb02962h

3 C. A. Labarrere, E. D. Ali, S. K. Ghassan Thrombogenic and inflammatory reactions to biomaterials in medical devices. Frontiers in Bioengineering and biotechnology 8 (2020), 123, doi:10.1039/ c8tb02962h

4 E. Maretti et al., Chitosan/heparin polyelectrolyte complexes as ion-paring approach to encapsulate heparin in orally administrable SLN: In vitro evaluation. Colloids and Surfaces A: Physicochemical and Engineering Aspects 608 (2021), 125606, doi:10.3389/ fbioe.2020.00123

5 I. H., Jaffer, I. W. Jeffrey, The blood compatibility challenge. Part 1: Blood-contacting medical devices: The scope of the problem. Acta biomaterialia 94 (2019): 2–10. doi:10.1016/j.colsurfa.2020.125606

6 M. Hedayati, M. J. Neufeld, M. M. Reynolds, M. J.Kipper, The quest for blood-compatible materials: Recent advances and future technologies. Mater Sci Eng R Rep. 2019; 138 (July):118–152. doi:10.1016/ j.mser.2019.06.002

7 P. K. Panda, J. M. Yang, Y. H.Chang, Preparation and characterization of ferulic acid-modified water soluble chitosan and poly (-glutamic acid) polyelectrolyte films through layer-by-layer assembly towards protein adsorption. Int J Biol Macromol., 171, (2021), 457–464. doi:10.1016/j.ijbiomac.2020.12.226

8 S. Lefnaoui et al., Design of antihistaminic transdermal films based on alginate–chitosan polyelectrolyte complexes: characterization and permeation studies. Drug development and industrial pharmacy, 44.3 (2018), 432–443. doi:10.1080/03639045.2017.1395461

9 J. Wang et al., Humidity-Triggered Relaxation of Polyelectrolyte Complexes as a Robust Approach to Generate Extracellular Matrix Biomimetic Films. Advanced Healthcare Materials 9.14 (2020), 2000381. doi:10.1002/adhm.202000381

10 M. Shu et al., High strength and antibacterial polyelectrolyte complex CS/HS hydrogel films for wound healing. Soft Matter 15.38 (20–19), 7686–7694. doi:10.1039/c9sm01380f

11 B. D. Ippel, P. Y. W. Dankers, Introduction of Nature’s Complexity in Engineered Blood-compatible Biomaterials. Adv Healthc Mater., 7 (2018) 1, 1–17. doi:10.1002/adhm.201700505

12 J. J. Richardson et al. Innovation in layer-by-layer assembly. Chemical reviews 116.23 (2016), 14828–14867. doi:10.1021/acs.chemrev. 6b00627

13 M. F. Maitz et al. The blood compatibility challenge. Part 4: Surface modification for hemocompatible materials: Passive and active approaches to guide blood-material interactions. Acta Biomaterialia, 94 (2019), 33–43. doi:10.1016/j.actbio.2019.06.019

14 N. Asadi et al. Common biocompatible polymeric materials for tissue engineering and regenerative medicine. Materials Chemistry and Physics 242 (2020), 122528. doi:10.1016/j.matchemphys.2019. 122528

15 R. R. Costa, F. M. Joao Polyelectrolyte multilayered assemblies in biomedical technologies. Chemical Society Reviews 43.10 (2014), 3453–3479. doi:10.1039/C3CS60393H

16 S. Chen, J. Shaoyi, An new avenue to nonfouling materials. Advanced Materials 20.2 (2008): 335–338. doi:10.1002/adma. 200701164

17 S. Pahal et al., Polyelectrolyte multilayers for bio-applications: recent advancements. IET nanobiotechnology 11.8 (2017), 903–908. doi:10.1049/iet-nbt.2017.0007

18 M. Uncu, Silk fibroin as a non-thrombogenic biomaterial. International journal of biological macromolecules (2016). doi:10.1016/ j.ijbiomac.2016.01.088

19 P. Tulay, G. Nanyak, A. Terin, The wonders of silk fibroin biomaterials in the treatment of breast cancer. Critical Reviews™ in Eukaryotic Gene Expression 28.2 (2018). doi:10.1615/CritRev EukaryotGeneExpr.2018021331

20 T. Adali, Synthesis and characterization of noncytotoxic and biodegradable polymethacrylates-grafted chitosan gels. Bio-Medical Materials and Engineering 23.5 (2013), 349–359. doi:10.3233/ BME-130759

21 E. Bahramzadeh, Y. Elvan, T. Adali, Chitosan-graft-poly (N-hydroxy ethyl acrylamide) copolymers: Synthesis, characterization and preliminary blood compatibility in vitro. International journal of biological macromolecules 123 (2019), 1257–1266.

22 Y.-J. Zhang et al., Pharmacokinetic and pharmacodynamic responses to clopidogrel: evidences and perspectives. International Journal of Environmental Research and Public Health 14.3 (2017): 301. doi:10.3390/ijerph14030301

23 Jin, Jianguo, et al. Adenosine diphosphate (ADP)–induced thrombo¬xane A2generation in human platelets requires coordinated signaling through integrin IIb3 and ADP receptors. Blood, The Journal of the American Society of Hematology 99.1 (2002), 193–198. doi:10.1182/blood.V99.1.193

24 S. Ji et al., Segmented scan modes and polarity-based LC-MS for pharmacokinetic interaction study between Fufang Danshen Dripping Pill and Clopidogrel Bisulfate Tablet. Journal of Pharmaceutical and Biomedical Analysis 174 (2019), 367–375. doi:10.1016/ j.jpba.2019.05.055

25 A. A. Shitole et al., Clopidogrel eluting electrospun polyurethane/ polyethylene glycol thromboresistant, hemocompatible nanofibrous scaffolds. Journal of biomaterials applications 33.10 (2019), 1327–1347. doi:10.1177/0885328219832984

26 P. C. F. da Camara et al. Polyelectrolyte multilayers containing a tannin derivative polyphenol improve blood compatibility through interactions with platelets and serum proteins. Materials Science and Engineering: C 112 (2020), 110919. doi:10.1016/j.msec.2020.110919

27 X. Man, J. Jin, B. Zhang, Surface modification of poly (propylene carbonate) by layer-by-layer assembly and its hemocompatibility. RSC Advances 4.73 (2014), 38943–38950. doi:10.1039/c4ra05982d

28 Y. Liu et al., Layer by layer assembled phosphorylcholine groups on paclitaxel/chitosan nanofibers coatings for hemocompatibility improvement. Surface and Coatings Technology 357 (2019), 984–992. doi:10.1016/j.surfcoat.2018.10.074

29 M. Kengo, H. Nara, Construction of stable biological albumin/heparin multilayers for elastic coatings on hydrophobic antithrombogenic artificial blood vessels. Tribology International 156 (2021), 106843. doi:10.1016/j.triboint.2020.106843

30 M. Pandima Devi et al., A novel wound dressing material-fibrin-chitosan-sodium alginate composite sheet. Bulletin of Materials Science 35 (2012), 1157–1163. doi:10.1007/s12034-012-0404-5

31 M. Castel-Molieres et al., Influence of homogenization technique and blend ratio on chitosan/alginate polyelectrolyte complex properties. Journal of Medical and Biological Engineering 38 (2018), 10–21. doi:10.1007/s40846-017-0304-7

32 Y. Wang et al., A biomimetic silk fibroin/sodium alginate composite scaffold for soft tissue engineering. Scientific Reports 6.1 (2016): 39477

33 D. Feng et al. Enhanced mechanical stability and sensitive swelling performance of chitosan/yeast hybrid hydrogel beads. New Journal of Chemistry 40.4 (2016), 3350–3362. doi:10.1039/c5nj02404h

34 L. Jin et al. Effect of sodium alginate type on drug release from chitosan-sodium alginate–based in situ film-forming tablets. AAPS PharmSciTech 21 (2020), 1–9. doi:10.1208/s12249-019-1549-y

35 Pankaj, Shashi Kishor, et al. Physicochemical characterization of plasma-treated sodium caseinate film. Food research international 66 (2014), 438–444. doi:10.1016/j.foodres.2014.10.016

36 Z. Yang et al., Crystallization behavior of poly (-caprolactone)/layered double hydroxide nanocomposites. Journal of applied polymer science 116.5 (2010): 2658–2667. doi:10.1002/app

37 A. M. Mohammed, J. M. Entidhar, Preparation and In-Vitro Evaluation of Clopidogrel Bisulfate Liquisolid Compact. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512) (2018), 135–149. doi:10.31351/vol27iss2pp135-149

38 A. Lowe et al. Effects of Emicizumab on APTT, FVIII assays and FVIII Inhibitor assays using different reagents: Results of a UK NEQAS proficiency testing exercise. Haemophilia 26.6 (2020), 1087–1091. doi:10.1111/hae.14177

39 S. A. L. Ness, M. B. Brooks. Clotting times (aPTT and PT). Interpretation of Equine Laboratory Diagnostics (2017), 139–140. doi:10.1002/9781118922798.ch20

40 D. M. Adcock, R. C. Gosselin, The danger of relying on the APTT and PT in patients on DOAC therapy, a potential patient safety issue. International Journal of Laboratory Hematology 39 (2017), 37–40. doi:10.1111/ijlh.12658

41 N. F. Neamaha, AN Al-Jadaanb Shaker, M. A. Asmaa, Study of some of Novel Selena-Diazole Derivative activities on Hematological Parameters, Differentiate lymphocytes cells in addition to thyroid hormones levels in Female Rats (One of the series of studies on the impact of the new compound). Systematic Reviews in Pharmacy 11.11 (2020). doi:10.31838/srp.2020.11.140

42 H. Ebrahim, F. Asrie, Z. Getaneh, Basic Coagulation Profiles and Platelet Parameters Among Adult Type 1 and Type 2 Diabetes Patients at Dessie Referral Hospital, Northeast Ethiopia: Comparative Cross-Sectional Study. J Blood Med. 12 (2021), 33–42. doi:10.2147/jbm.s287136

43 M. A. Fadel et al. Dielectric properties and in vitro hemocom¬pat¬ibility of Nd: YAG laser-irradiated polyethylene terephthalate. Progress in Biomaterials 9 (2020), 107–114

44 Q. He et al. Positive charge of chitosan retards blood coagulation on chitosan films. Journal of biomaterials applications 27.8 (2013), 1032–1045, doi:10.1177/0885328211432487

45 Z. Hu, S. Lu, Y. Cheng et al. Investigation of the effects of molecular parameters on the hemostatic properties of chitosan. Molecules. 23 (2018) 12, 1–14. doi:10.3390/molecules23123147

46 Fan, Lihong, et al. Synthesis and anticoagulant activity of sodium alginate sulfates. Carbohydrate polymers 83.4 (2011), 1797–1803.

47 P. O. Kwiterovich Jr, Laboratory procedure manual: Total cholesterol, HDL-cholesterol, triglycerides, and LDL-cholesterol. National Health and Nutrition Examination Survey; Centers for Disease Control and Prevention: Atlanta, GA, USA (2004)

48 S. Chinwong, D. Chinwong, A. Mangklabruks. Daily consumption of virgin coconut oil increases high-density lipoprotein cholesterol levels in healthy volunteers: a randomized crossover trial. Evidence-Based Complementary and Alternative Medicine 2017. doi:10.1155/2017/7251562

49 H. Chen et al. Association between serum cholesterol levels and Alzheimer’s disease in China: a case-control study. International Journal of Food Sciences and Nutrition 70.4 (2019), 405–411. doi:10.1080/ 09637486.2018.1508426

50 L. Fernández-Friera et al. Normal LDL-cholesterol levels are associated with subclinical atherosclerosis in the absence of risk factors. Journal of the American College of Cardiology 70.24 (2017), 2979–2991. doi:10.1016/j.jacc.2017.10.024

51 J. Hankins, The role of albumin in fluid and electrolyte balance. Journal of Infusion Nursing 29.5 (2006), 260–265.52

52 A. Akirov, H. Masri-Iraqi, A. Atamna, I. Shimon, Low Albumin Levels Are Associated with Mortality Risk in Hospitalized Patients. Am J Med. 130 (2017) 12, 1465.e11–465.e19. doi:10.1016/ j.amjmed.2017.07.020

53 R. N. Moman, G. Nishant, M. Varacallo. Physiology, albumin. (2017)

54 M. A. Jamiolkowski et al. An in vitro blood flow loop system for evaluating the thrombogenicity of medical devices and biomaterials. ASAIO journal 66.2 (2020), 183–189. doi:10.1097/ MAT.0000000000000958

55 K. Lau et al., Biomimetic silk biomaterials: Perlecan-functionalized silk fibroin for use in blood-contacting devices. Acta Biomaterialia 132 (2021), 162–175. Doi:10.1016/j.actbio.2021.02.014.

56 J. M. Anderson, D. W. Grainger, S. W. Kim, Early events in blood/material interactions. Journal of Controlled Release 330 (2021), 31–35. doi:10.1016/j.jconrel.2020.11.023

57 I. Cockerill et al. Designing better cardiovascular stent materials: A learning curve. Advanced functional materials 31.1 (2021), 2005361.doi:10.1002/adfm.202005361

58 Y. Matsuhashi, K. Sameshima, Y. Yamamoto, M. Umezu, K. Iwasaki, Real-time visualization of thrombus formation at the interface between connectors and tubes in medical devices by using optical coherence tomography. PLoS ONE., 12 (2017) 12, 1–13. doi:10.1371/journal.pone.0188729

59 R. Gbyli et al. Achieving totally local anticoagulation on blood contacting devices. Advanced Materials Interfaces 5.4 (2018), 1700954. .doi:10.1002/admi.201700954

60 I. H. Jaffer et al. Medical device-induced thrombosis: what causes it and how can we prevent it? Journal of Thrombosis and Haemostasis 13 (2015), S72–S81. doi:10.1111/jth.12961

61 M. Reinthaler, S. Braune, A. Lendlein, U. Landmesser, F. Jung, Platelets and coronary artery disease: Interactions with the blood vessel wall and cardiovascular devices. Biointerphases. 2016;11(2). doi:10.1116/1.4953246

62 S. Braune et al. Evaluation of platelet adhesion and activation on polymers: Round-robin study to assess inter-center variability. Colloids and Surfaces B: Biointerfaces 158 (2017), 416–422. doi:10.1016/j.colsurfb.2017.06.053.

63 L. Brancato et al. Surface nanostructuring of parylene-C coatings for blood contacting implants. Materials 11.7 (2018), 1109. doi:10.3390/ma11071109

64 A. De Mel, K. Chaloupka, Y. Malam, A. Darbyshire, B. Cousins, A. M. Seifalian, A silver nanocomposite biomaterial for blood-contacting implants. J Biomed Mater Res - Part A., 100 (2012) A(9), 2348–2357. doi:10.1002/jbm.a.34177

65 X. Tong, Z. Shi, L. Xu et al. Degradation behavior, cytotoxicity, hemolysis, and antibacterial properties of electro-deposited Zn–Cu metal foams as potential biodegradable bone implants. Acta Biomater., 102 (2020), 481–492. doi:10.1016/j.actbio.2019.11.031

66 N. S. Merle, J. Leon, V. Poillerat et al. Circulating FH Protects Kidneys From Tubular Injury During Systemic Hemolysis. Front Immunol. 2020;11. doi:10.3389/fimmu.2020.01772

67 V. Govindarajan, S. Zhu, R. Li et al. Impact of Tissue Factor Localization on Blood Clot Structure and Resistance under Venous Shear. Biophys J., 114 (2018) 4, 978–991. doi:10.1016/j.bpj.2017.12.034

68 J. W. Kuhbier et al. Influence of direct or indirect contact for the cytotoxicity and blood compatibility of spider silk. Journal of Materials Science: Materials in Medicine 28 (2017), 1–9.doi:10.1007/ s10856-017-5936-1

69 G. Totea et al. In vitro hemocompatibility and corrosion behavior of new Zr-binary alloys in whole human blood. Open Chemistry 12.7 (2014), 796–803.doi:10.2478/s11532-014-0535-1

70 M. Weber et al. Blood-contacting biomaterials: in vitro evaluation of the hemocompatibility. Frontiers in bioengineering and biotechnology 6 (2018), 99. doi:10.3389/fbioe.2018.00099

Published
2023-10-03
How to Cite
1.
Moyo MTG, Adali T, Edebal OH, Bayir E, Şendemir A. HEMOCOMPATIBILITY STUDIES OF LAYER-BY-LAYER POLYELECTROLYTE COMPLEXES FOR BIO-BASED POLYMERS. MatTech [Internet]. 2023Oct.3 [cited 2026Aug.14];57(5):525–536. Available from: https://www.mater-tehnol.si/index.php/MatTech/article/view/922