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MWCNT-Loaded PCL/PXS-PCL Bilayer Cardiac Patch for Myocardial Regeneration: An In Vitro and In Vivo Study

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Abstract

Recent progress in develo** cardiac patches for regenerating the myocardium has opened a new hope after myocardial infarction (MI). Herein, we introduce a novel bilayer nanofiber cardiac patch composed of polycaprolactone (PCL), poly(xylitol sebacate) (PXS), and multi-walled carbon nanotubes (MWCNTs). First, we electrospun different monolayer scaffolds, including PCL, PCL/MWCNT, PCL/PXS, and PCL/PXS/MWCNTs, and characterized their physical, mechanical, and biological performance to determine the interaction effects of different material compositions on their scaffold properties. In vitro examinations confirmed the cooperative effect of PXS and MWCNT in blending with PCL to fabricate conductive and well-organized nanofibers with good biocompatibility. Subsequently, a bilayer nanofiber scaffold composed of PCL/PXS/MWCNT nanofibers electrospun over a PCL fibrous layer was fabricated to achieve an efficient structure capable of providing the desirable characteristics of a cardiac patch. The bilayer nature increased the mechanical performance of the PCL/PXS/MWCNT monolayer while preserving its appropriate wettability and acceptable conductivity. Excellent viability and proliferation of H9c2 cells on the bilayer scaffolds were observed in the live/dead assay. Moreover, cell-matrix interaction confirmed that bilayer nanofibers decrease myofibroblast differentiation of seeded NIH3T3 cells, which may be beneficial for cardiac repair post-MI. After transplantation of the bilayer nanofiber onto the infarcted heart of the MI rats for 4 weeks, the ischemic zone decreased, cardiac function significantly improved and very slightly activated macrophages were observed. These findings suggested a potentially durable nanofiber cardiac patch containing PXS for myocardial repair post-MI.

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Data Availability

No datasets were generated or analysed during the current study.

References

  1. Lakshmanan R, Krishnan UM, Sethuraman S (2012) Living cardiac patch: the elixir for cardiac regeneration. Expert Opin Biol Ther 12(12):1623–1640

    Article  CAS  PubMed  Google Scholar 

  2. Sigaroodi F et al (2023) Designing cardiac patches for myocardial regeneration—a review. Int J Polym Mater Polym Biomater, p 1–19

  3. Forte G et al (2012) Substrate stiffness modulates gene expression and phenotype in neonatal cardiomyocytes in vitro. Tissue Eng Part A 18(17–18):1837–1848

    Article  CAS  PubMed  Google Scholar 

  4. He Y et al (2018) Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization. Theranostics 8(18):5159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dwyer KD, Coulombe KLK (2021) Cardiac mechanostructure: using mechanics and anisotropy as inspiration for develo** epicardial therapies in treating myocardial infarction. Bioact Mater 6(7):2198–2220

    CAS  PubMed  PubMed Central  Google Scholar 

  6. D’Urso M, Kurniawan NA (2020) Mechanical and physical regulation of fibroblast–myofibroblast transition: from cellular mechanoresponse to tissue pathology. Front Bioeng Biotechnol 8:609653

    Article  PubMed  PubMed Central  Google Scholar 

  7. Vogt L et al (2019) Poly(ε-caprolactone)/poly(glycerol sebacate) electrospun scaffolds for cardiac tissue engineering using benign solvents. Mater Sci Eng C 103:109712

    Article  Google Scholar 

  8. Frydrych M et al (2015) Biomimetic poly(glycerol sebacate)/poly(l-lactic acid) blend scaffolds for adipose tissue engineering. Acta Biomater 18:40–49

    Article  CAS  PubMed  Google Scholar 

  9. Bruggeman JP et al (2008) Biodegradable poly(polyol sebacate) polymers. Biomaterials 29(36):4726–4735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bruggeman JP, Bettinger CJ, Langer R (2010) Biodegradable xylitol-based elastomers: in vivo behavior and biocompatibility. J Biomed Mater Res Part A 95(1):92–104

    Article  Google Scholar 

  11. Li Y, Thouas GA, Chen Q (2014) Novel elastomeric fibrous networks produced from poly(xylitol sebacate)2:5 by core/shell electrospinning: fabrication and mechanical properties. J Mech Behav Biomed Mater 40:210–221

    Article  PubMed  Google Scholar 

  12. Yang Y et al (2019) Elastic 3D-printed hybrid polymeric scaffold improves cardiac remodeling after myocardial infarction. Adv Healthc Mater 8(10):1900065

    Article  Google Scholar 

  13. Li Y et al (2022) Conductive biomaterials for cardiac repair: a review. Acta Biomater 139:157–178

    Article  CAS  PubMed  Google Scholar 

  14. Zhang YS et al (2015) From cardiac tissue engineering to heart-on-a-chip: beating challenges. Biomed Mater 10(3):034006

    Article  PubMed  PubMed Central  Google Scholar 

  15. Martinelli V et al (2012) Carbon nanotubes promote growth and spontaneous electrical activity in cultured cardiac myocytes. Nano Lett 12(4):1831–1838

    Article  CAS  PubMed  Google Scholar 

  16. Barrejon M et al (2021) Carbon nanotubes for cardiac tissue regeneration: state of the art and perspectives. Carbon 184:641–650

    Article  CAS  Google Scholar 

  17. Lanone S et al (2013) Determinants of carbon nanotube toxicity. Adv Drug Deliv Rev 65(15):2063–2069

    Article  CAS  PubMed  Google Scholar 

  18. Boyles MS et al (2015) Multi-walled carbon nanotube induced frustrated phagocytosis, cytotoxicity and pro-inflammatory conditions in macrophages are length dependent and greater than that of asbestos. Toxicol in Vitro 29(7):1513–1528

    Article  CAS  PubMed  Google Scholar 

  19. Sager TM et al (2014) Effect of multi-walled carbon nanotube surface modification on bioactivity in the C57BL/6 mouse model. Nanotoxicology 8(3):317–327

    Article  CAS  PubMed  Google Scholar 

  20. Huang B (2020) Carbon nanotubes and their polymeric composites: the applications in tissue engineering. Biomanufact Rev 5(1):3

    Article  Google Scholar 

  21. Pok S et al (2014) Biocompatible carbon nanotube–chitosan scaffold matching the electrical conductivity of the heart. ACS Nano 8(10):9822–9832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Meng Z et al (2010) Fabrication and characterization of three-dimensional nanofiber membrance of PCL–MWCNTs by electrospinning. Mater Sci Eng C 30(7):1014–1021

    Article  CAS  Google Scholar 

  23. Yuan X et al (2019) Cellular toxicity and immunological effects of carbon-based nanomaterials. Part Fibre Toxicol 16(1):18

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wang P et al (2015) Multiwall carbon nanotubes directly promote fibroblast-myofibroblast and epithelial-mesenchymal transitions through the activation of the TGF-β/Smad signaling pathway. Small 11(4):446–455

    Article  CAS  PubMed  Google Scholar 

  25. Wang L et al (2017) Electrospun conductive nanofibrous scaffolds for engineering cardiac tissue and 3D bioactuators. Acta Biomater 59:68–81

    Article  CAS  PubMed  Google Scholar 

  26. Roshanbinfar K et al (2020) Nanofibrous composite with tailorable electrical and mechanical properties for cardiac tissue engineering. Adv Funct Mater 30(7):1908612

    Article  CAS  Google Scholar 

  27. Li YF et al (2015) Ultraporous nanofeatured PCL-PEO microfibrous scaffolds enhance cell infiltration, colonization and myofibroblastic differentiation. Nanoscale 7(36):14989–14995

    Article  CAS  PubMed  Google Scholar 

  28. Li F et al (2012) Effect of celecoxib on proliferation, collagen expression, ERK1/2 and SMAD2/3 phosphorylation in NIH/3T3 fibroblasts. Eur J Pharmacol 678(1):1–5

    Article  CAS  PubMed  Google Scholar 

  29. Rahmani M et al (2020) Development of poly(mannitol sebacate)/poly(lactic acid) nanofibrous scaffolds with potential applications in tissue engineering. Mater Sci Eng C 110:110626

    Article  CAS  Google Scholar 

  30. Huang B et al (2019) Fabrication and characterisation of 3D printed MWCNT composite porous scaffolds for bone regeneration. Mater Sci Eng C 98:266–278

    Article  CAS  Google Scholar 

  31. Bashur CA, Dahlgren LA, Goldstein AS (2006) Effect of fiber diameter and orientation on fibroblast morphology and proliferation on electrospun poly(d, l-lactic-co-glycolic acid) meshes. Biomaterials 27(33):5681–5688

    Article  CAS  PubMed  Google Scholar 

  32. Kim HH et al (2016) Effect of fiber diameter on surface morphology, mechanical property, and cell behavior of electrospun poly(ε-caprolactone) mat. Fibers Polym 17:1033–1042

    Article  CAS  Google Scholar 

  33. Chakrapani VY et al (2012) Electrospinning of type I collagen and PCL nanofibers using acetic acid. J Appl Polym Sci 125(4):3221–3227

    Article  CAS  Google Scholar 

  34. Frydrych M, Chen B (2013) Large three-dimensional poly(glycerol sebacate)-based scaffolds—a freeze-drying preparation approach. J Mater Chem B 1(48):6650–6661

    Article  CAS  PubMed  Google Scholar 

  35. Li X et al (2015) Criteria for quick and consistent synthesis of poly(glycerol sebacate) for tailored mechanical properties. Biomacromolecules 16(5):1525–1533

    Article  CAS  PubMed  Google Scholar 

  36. Mousa HM et al (2020) Development of biocompatible tri-layered nanofibers patches with endothelial cells for cardiac tissue engineering. Eur Polym J 129:109630

    Article  CAS  Google Scholar 

  37. Miao J et al (2012) Preparation and characterization of electrospun core sheath nanofibers from multi-walled carbon nanotubes and poly(vinyl pyrrolidone). J Nanosci Nanotechnol 12(3):2387–2393

    Article  CAS  PubMed  Google Scholar 

  38. Lee MC et al (1987) Biaxial mechanical properties of human pericardium and canine comparisons. Am J Physiol Heart Circ Physiol 253(1):H75–H82

    Article  CAS  Google Scholar 

  39. Tang L, Thevenot P, Hu W (2008) Surface chemistry influences implant biocompatibility. Curr Top Med Chem 8(4):270–280

    Article  PubMed  PubMed Central  Google Scholar 

  40. Côté M-F, Doillon CJ (1992) Wettability of cross-linked collagenous biomaterials: in vitro study. Biomaterials 13(9):612–616

    Article  PubMed  Google Scholar 

  41. Kumar S, Bose S, Chatterjee K (2014) Amine-functionalized multiwall carbon nanotubes impart osteoinductive and bactericidal properties in poly(ε-caprolactone) composites. RSC Adv 4(37):19086–19098

    Article  CAS  Google Scholar 

  42. Chen Q, Yang X, Li Y (2012) A comparative study on in vitro enzymatic degradation of poly(glycerol sebacate) and poly(xylitol sebacate). RSC Adv 2(10):4125–4134

    Article  CAS  Google Scholar 

  43. Fardin MA et al (2010) Cell spreading as a hydrodynamic process. Soft Matter 6:4788–4799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Madan S et al (2021) Mitochondria lead the way: mitochondrial dynamics and function in cellular movements in development and disease. Front Cell Dev Biol 9:781933

    Article  PubMed  Google Scholar 

  45. Schroer AK, Merryman WD (2015) Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease. J Cell Sci 128(10):1865–1875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jiang B et al (2020) Stem cell therapy of myocardial infarction: a promising opportunity in bioengineering. Adv Ther (Weinh) 3(3):1900182

    Article  PubMed  Google Scholar 

  47. Kharaziha M et al (2014) Tough and flexible CNT–polymeric hybrid scaffolds for engineering cardiac constructs. Biomaterials 35(26):7346–7354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sun H et al (2006) The in vivo degradation, absorption and excretion of PCL-based implant. Biomaterials 27(9):1735–1740

    Article  CAS  PubMed  Google Scholar 

  49. Malutama Lopes J (2016) The role of macrophage phenotypes M1 and M2 in the foreign body reaction. Faculty of Science and Engineering

  50. Kelly SM et al (2019) Synthesis and characterization of rapidly degrading polyanhydrides as vaccine adjuvants. ACS Biomater Sci Eng 6(1):265–276

    Article  Google Scholar 

  51. Thompson M (2013) Anti-inflammatory properties of xylitol in a model of chronic sinus disease. Dissertation, Griffith University

  52. Chen Q-Z et al (2010) An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart. Biomaterials 31(14):3885–3893

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by Iran National Science Foundation (INSF) with Grant Number of 4000724 and Shahid Beheshti University of Medical Sciences with Grant Number of 28685.

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Authors and Affiliations

  1. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 1968937148, Iran

    Faraz Sigaroodi, Safieh Boroumand, Mahya Rahmani, Simzar Hosseinzadeh, Masoud Soleimani & Mohammad-Mehdi Khani

  2. Research Center for Advanced Technologies in Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Shahram Rabbani

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  1. Faraz Sigaroodi
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Contributions

F.S. conducted the experiment and wrote the original and final drafts. S.B., M.R., Sh.R., S.H., and M.S. participated in the technical support and data screening. M-M.Kh. as a project administration, designed the study, methodology, and reviewed the original manuscript.

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Correspondence to Mohammad-Mehdi Khani.

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Sigaroodi, F., Boroumand, S., Rahmani, M. et al. MWCNT-Loaded PCL/PXS-PCL Bilayer Cardiac Patch for Myocardial Regeneration: An In Vitro and In Vivo Study. J Polym Environ (2024). https://doi.org/10.1007/s10924-024-03355-w

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