Active loading graphite/hydroxyapatite into the stable hydroxyethyl cellulose scaffold nanofibers for artificial cornea application

Abstract

The design of biocompatible porous scaffolds that encourage cell adhesion for corneal tissue engineering applications continues to be challenging. In addition to porous hydrogels, nanofibers that can simulate the extracellular matrix structure for cell adhesion would be beneficial. Graphite and nano-hydroxyapatite (nHA) are two bioactive materials that have been used to improve cell adhesion in scaffolds for corneal tissue engineering. In this study, nanofibers were fabricated from hydroxyethyl cellulose and polyvinyl alcohol (PVA) and cross-linked by glutaraldehyde bound to graphite and nano-hydroxyapatite. This scaffold surrounded a transparent hydrogel core from PVA that was cross-linked by freeze-thawing cycles. The chemical and mechanical evaluations demonstrated that nanofibers met the requirements as a scaffold for corneal tissue engineering. The results showed that when the concentration of nHA was approximately 1.66 wt%, the morphology of human epithelial cells did not change, and clot formation occurred around the scaffold during the 1-week in vivo implantation.

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References

  1. Chahal S, Hussain FSJ, Kumar A, Yusoff MM, Rasad MSBA (2015) Electrospun hydroxyethyl cellulose nanofibers functionalized with calcium phosphate coating for bone tissue engineering. RSC Adv 5:29497–29504

    CAS  Google Scholar 

  2. Chahal S, Hussain FSJ, Kumar A, Rasad MSBA, Yusoff MM (2016) Fabrication, characterization and in vitro biocompatibility of electrospun hydroxyethyl cellulose/poly (vinyl) alcohol nanofibrous composite biomaterial for bone tissue engineering. Chem Eng Sci 144:17–29

    CAS  Google Scholar 

  3. Chahal S, Hussain FSJ, Yusoff MM, Abdull Rasad MSB, Kumar A (2017) Nanohydroxyapatite-coated hydroxyethyl cellulose/poly (vinyl) alcohol electrospun scaffolds and their cellular response. Int J Polym Mater Polym Biomater 66:115–122

    CAS  Google Scholar 

  4. Chaouat M, Le Visage C, Baille WE, Escoubet B, Chaubet F, Mateescu MA, Letourneur DJM (2008) A novel cross‐linked poly (vinyl alcohol)(PVA) for vascular grafts. Adv Func Mater 18:2855–2861

    CAS  Google Scholar 

  5. Destaye AG, Lin CK, Lee CK (2013) Glutaraldehyde vapor cross-linked nanofibrous PVA mat with in situ formed silver nanoparticles. ACS Appl Mater Interfaces 5(11):4745–4752

    CAS  PubMed  Google Scholar 

  6. Dutta D, Zhao T, Cheah KB, Holmlund L, Willcox MD (2017) Activity of a melimine derived peptide Mel4 against Stenotrophomonas, Delftia, Elizabethkingia, Burkholderia and biocompatibility as a contact lens coating. Contact Lens Anterior Eye 40:175–183

    PubMed  Google Scholar 

  7. Evans MD, Chaouk H, Wilkie JS, Dalton BA, Taylor S, Xie RZ, Hughes TC, Johnson G, Mcfarland GA, Griesser HHJB (2011) The influence of surface topography of a porous perfluoropolyether polymer on corneal epithelial tissue growth and adhesion. Biomaterials 32:8870–8879

    CAS  PubMed  Google Scholar 

  8. Fenglan X, Yubao L, Xiaoming Y, Hongbing L, Li Z (2007) Preparation and in vivo investigation of artificial cornea made of nano-hydroxyapatite/poly (vinyl alcohol) hydrogel composite. J Mater Sci - Mater Med 18:635–640

    PubMed  Google Scholar 

  9. Gu M, Wang K, Li W, Qin C, Wang J-J, Dai L (2011) Preparation and characterization of PVA/PU blend nanofiber mats by dual-jet electrospinning. Fibers Polym 12:65–72

    CAS  Google Scholar 

  10. Hassan MI, Sultana N (2017) Characterization, drug loading and antibacterial activity of nanohydroxyapatite/polycaprolactone (nHA/PCL) electrospun membrane. 3 Biotech 7:249

    PubMed  PubMed Central  Google Scholar 

  11. Jiang S, Liu S, Feng W (2011) PVA hydrogel properties for biomedical application. J Mech Behav Biomed Mater 4:1228–1233

    CAS  PubMed  Google Scholar 

  12. Khan MQ, Kharaghani D, Nishat N, Shahzad A, Yamamoto T, Inoue Y, Kim IS (2019) In vitro assessment of dual-network electrospun tubes from poly (1, 4 cyclohexane dimethylene isosorbide terephthalate)/PVA hydrogel for blood vessel application. J Appl Polym Sci 136:47222

    Google Scholar 

  13. Kharaghani D, Meskinfam M, Rezaeikanavi M, Balagholi S, Fazili NJIO, Science V (2015) Synthesis and characterization of hybrid nanocomposite via biomimetic method as an artificial cornea. Invest Ophthalmol Vis Sci 56:5024

    Google Scholar 

  14. Kharaghani D, Khan MQ, Tamada Y, Ogasawara H, Inoue Y, Saito Y, Hashmi M, Kim IS (2018) Fabrication of electrospun antibacterial PVA/Cs nanofibers loaded with CuNPs and AgNPs by an in situ method. Polym Testing 72:315–321

    CAS  Google Scholar 

  15. Kharaghani D, Gitigard P, Ohtani H, Kim KO, Ullah S, Saito Y, Khan MQ, Kim ISJSR (2019a) Design and characterization of dual drug delivery based on in situ assembled PVA/PAN core-shell nanofibers for wound dressing application. Sci Rep 9:1–11

    CAS  Google Scholar 

  16. Kharaghani D, Lee H, Ishikawa T, Nagaishi T, Kim SH, Kim ISJTRJ (2019b) Comparison of fabrication methods for the effective loading of Ag onto PVA nanofibers. Text Res J 89:625–634

    CAS  Google Scholar 

  17. Kobayashi H, Kato M, Taguchi T, Ikoma T, Miyashita H, Shimmura S, Tsubota K, Tanaka J (2004) Collagen immobilized PVA hydrogel–hydroxyapatite composites prepared by kneading methods as a material for peripheral cuff of artificial cornea. Mater Sci Eng, C 24:729–735

    Google Scholar 

  18. Kong B, Mi SJM (2016) Electrospun scaffolds for corneal tissue engineering: a review. Materials 9:614

    PubMed Central  Google Scholar 

  19. Lee H, Xu G, Kharaghani D, Nishino M, Song KH, Lee JS, Kim IS (2017) Electrospun tri-layered zein/PVP-GO/zein nanofiber mats for providing biphasic drug release profiles. Int J Pharm 531:101–107

    CAS  PubMed  Google Scholar 

  20. Li M, Guo Y, Wei Y, Macdiarmid AG, Lelkes PIJB (2006) Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications. Biomaterials 27:2705–2715

    CAS  PubMed  Google Scholar 

  21. Li B, Kan L, Zhang X, Li J, Li R, Gui Q, Qiu D, He F, Ma N, Wang Y (2017) Biomimetic bone-like hydroxyapatite by mineralization on supramolecular porous fiber networks. Langmuir 33:8493–8502

    CAS  PubMed  Google Scholar 

  22. Lin R-R, Mao X, Yu Q-C, Tan B-H (2007) Preparation of bioactive nano-hydroxyapatite coating for artificial cornea. Curr Appl Phys 7:e85–e89

    Google Scholar 

  23. Liu K, Li Y, Xu F, Zuo Y, Zhang L, Wang H, Liao J (2009) Graphite/poly (vinyl alcohol) hydrogel composite as porous ringy skirt for artificial cornea. Mater Sci Eng, C 29:261–266

    Google Scholar 

  24. Miles DH, Thakur A, Cole N, Willcox MD (2007) The induction and suppression of the apoptotic response of HSV-1 in human corneal epithelial cells. Invest Ophthalmol Vis Sci 48:789–796

    PubMed  Google Scholar 

  25. Myung D, Duhamel PE, Cochran JR, Noolandi J, Ta CN, Frank CW (2008) Development of hydrogel-based keratoprostheses: a materials perspective. Biotechnol Prog 24:735–741

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Nuttelman CR et al (2001) Attachment of fibronectin to poly (vinyl alcohol) hydrogels promotes NIH3T3 cell adhesion, proliferation, and migration. J Biomed Mater Res 57:217–223

    CAS  PubMed  Google Scholar 

  27. Ozcelik B, Ho KKK, Glattauer V, Willcox M, Kumar N, Thissen H (2016) Poly (ethylene glycol)-based coatings combining low-biofouling and quorum-sensing inhibiting properties to reduce bacterial colonization. ACS Biomater Sci Eng 3:78–87

    Google Scholar 

  28. Park YR, Ju HW, Lee JM, Kim DK, Lee OJ, Moon BM, Park HJ, Jeong JY, Yeon YK, Park CH (2016) Three-dimensional electrospun silk-fibroin nanofiber for skin tissue engineering. Int J Biol Macromol 93:1567–1574

    CAS  PubMed  Google Scholar 

  29. Parke-Houben R, Fox CH, Zheng LL, Waters DJ, Cochran JR, Ta CN, Frank CW (2015) Interpenetrating polymer network hydrogel scaffolds for artificial cornea periphery. J Mater Sci - Mater Med 26:107

    PubMed  Google Scholar 

  30. Pennington MR, Capriotti JA, Van de Walle GR (2018) In vitro efficacy of povidone iodine and hydroxyethyl cellulose, alone and in combination, against common feline ocular pathogens. Vet J 241:38–41

    CAS  PubMed  Google Scholar 

  31. Pino M, Stingelin N, Tanner K (2008) Nucleation and growth of apatite on NaOH-treated PEEK, HDPE and UHMWPE for artificial cornea materials. Acta Biomater 4:1827–1836

    CAS  PubMed  Google Scholar 

  32. Pollack SV (1984) The wound healing process. Clin Dermatol 2:8–16

    CAS  PubMed  Google Scholar 

  33. Qian D, Chen D, Jin G, Tian HJCJOTER (2017) Biocompatibility of modified nano-hydroxyapatite/polyvinyl alcohol porous composite hydrogel as an artificial corneal material. Chin J Tissue Eng Res 21:3541–3546

    Google Scholar 

  34. Rošic R, Kocbek P, Baumgartner S, Kristl J (2011) Electro-spun hydroxyethyl cellulose nanofibers: the relationship between structure and process. J Drug Deliv Sci Technol 21:229–236

    Google Scholar 

  35. Sinha A, Guha A (2009) Biomimetic patterning of polymer hydrogels with hydroxyapatite nanoparticles. Mater Sci Eng, C 29:1330–1333

    CAS  Google Scholar 

  36. Sinha M, Gupte T (2018) Design and evaluation of artificial cornea with core–skirt design using polyhydroxyethyl methacrylate and graphite. Int Ophthalmol 38:1225–1233

    PubMed  Google Scholar 

  37. Soares PI, Echeverria C, Baptista AC, João CF, Fernandes SN, Almeida AP, Silva JC, Godinho MH, Borges JP (2017) Hybrid polymer composite materials, vol 4. Elsevier, Amsterdam, p 107

    Google Scholar 

  38. Sroka-Bartnicka A, Borkowski L, Ginalska G, Ślósarczyk A, Kazarian SG (2017) Structural transformation of synthetic hydroxyapatite under simulated in vivo conditions studied with ATR-FTIR spectroscopic imaging. Spectrochim Acta Part A Mol Biomol Spectrosc 171:155–161

    CAS  Google Scholar 

  39. Tanpichai S, Oksman K (2016) Cross-linked nanocomposite hydrogels based on cellulose nanocrystals and PVA: mechanical properties and creep recovery. Compos A Appl Sci Manuf 88:226–233

    CAS  Google Scholar 

  40. Wallin RF, Arscott E (1998) A practical guide to ISO 10993-5: cytotoxicity. Med Dev Diagn Ind 20:96–98

    Google Scholar 

  41. Wang J, Gao C, Zhang Y, Wan Y (2010) Preparation and in vitro characterization of BC/PVA hydrogel composite for its potential use as artificial cornea biomaterial. Mater Sci Eng, C 30:214–218

    Google Scholar 

  42. Yamaguchi K, Prabakaran M, Ke M, Gang X, Chung IM, Um IC, Gopiraman M, Kim IS (2016) Highly dispersed nanoscale hydroxyapatite on cellulose nanofibers for bone regeneration. Mater Lett 168:56–61

    CAS  Google Scholar 

  43. Yan L, Zhao B, Liu X, Li X, Zeng C, Shi H, Xu X, Lin T, Dai L, Liu Y (2016) Aligned nanofibers from polypyrrole/graphene as electrodes for regeneration of optic nerve via electrical stimulation. ACS Appl Mater Interfaces 8:6834–6840

    CAS  PubMed  Google Scholar 

  44. Zajaczkowski MB, Cukierman E, Galbraith CG, Yamada KM (2003) Cell-matrix adhesions on poly (vinyl alcohol) hydrogels. Tissue Eng 9:525–533

    CAS  PubMed  Google Scholar 

  45. Zhou H, Wang Z, Cao H, Hu H, Luo Z, Yang X, Cui M, Zhou LJJOBS, Edition Polymer (2019) Genipin-crosslinked polyvinyl alcohol/silk fibroin/nano-hydroxyapatite hydrogel for fabrication of artificial cornea scaffolds—a novel approach to corneal tissue engineering. J Biomater Sci Polym Ed 30:1–16

    Google Scholar 

  46. Zulkifli FH, Hussain FSJ, Harun WSW, Yusoff MM (2019) Highly porous of hydroxyethyl cellulose biocomposite scaffolds for tissue engineering. Int J Biol Macromol 122:562–571

    CAS  PubMed  Google Scholar 

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Correspondence to Mark D. P. Willcox or Ick Soo Kim.

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Kharaghani, D., Dutta, D., Ho, K.K.K. et al. Active loading graphite/hydroxyapatite into the stable hydroxyethyl cellulose scaffold nanofibers for artificial cornea application. Cellulose 27, 3319–3334 (2020). https://doi.org/10.1007/s10570-020-02999-w

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Keywords

  • Artificial cornea
  • Epithelization
  • Corneal tissue engineering
  • Biocompatible scaffolds
  • Cross-linking