Search for biodegradable polymer material for the reconstruction of tympanic membrane defects

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Abstract

BACKGROUND: Biocompatible polymer matrices are extensively investigated as materials for the reconstruction of chronic tympanic perforations.

AIM: This study aimed to evaluate the general and local toxicity and biodegradation and biocompatibility mechanism of samples of two-layer polymer films based on chitosan (CS) and hyaluronic acid (HA).

MATERIALS AND METHODS: Bilayer polymer films were prepared by the casting method using CS solutions with molecular weights of 500 and 900 kDa (CS500 and CS900, respectively) and HA with a molecular weight of 1300 kDa. The samples were also treated at 100°C for 5 min (samples marked with t). The toxicity, biodegradation rate, and biocompatibility of the materials were evaluated in 20 Wistar rats weighing 220–240 g. The rats were observed on days 7, 14, 30, and 50 after subcutaneous implantation.

RESULTS: No acute toxicity, septic or allergic inflammation, or scarring of surrounding tissues was observed during the post-implantation period. The biodegradation rate decreased in the following order: CS500-HA (whitout t) ≥ CS900-HA (whitout t) > CS500-HA (t) > CS900_HA (t). The study demonstrated the effect of CS in different molecular weights and thermal treatment on the degradation rate and polymer implant biodegradation as well as the type of reactive proliferation of the connective tissue.

CONCLUSIONS: These results support further preclinical research on polymer film samples for the development of matrices for tympanoplasties.

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About the authors

Maria Yu. Naumenko

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: naumenkomyu@gmail.com
ORCID iD: 0009-0003-8053-6381
Russian Federation, Saint Petersburg

Petr P. Snetkov

ITMO University; Institute of Macromolecular Compounds; Saint Petersburg State Research Institute of Phthisiopulmonology

Email: ppsnetkov@itmo.ru
ORCID iD: 0000-0001-9949-5709
SPIN-code: 2951-3791
Scopus Author ID: 57205168040

Cand. Sci. (Technology)

Russian Federation, Saint Petersburg; Saint Petersburg; Saint Petersburg

Svetlana A. Morozkina

ITMO University; Institute of Macromolecular Compounds; Saint Petersburg State Research Institute of Phthisiopulmonology

Email: morozkina.svetlana@gmail.com
ORCID iD: 0000-0003-0122-0251
SPIN-code: 3215-0328
Scopus Author ID: 6507035544
ResearcherId: M-1252-2013

Cand. Sci. (Chemistry)

Russian Federation, Saint Petersburg; Saint Petersburg; Saint Petersburg

Anna N. Bervinova

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: anna.bervinova@mail.ru
ORCID iD: 0000-0002-2898-4916

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Galina Yu. Yukina

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: pipson@inbox.ru
ORCID iD: 0000-0001-8888-4135

Cand. Sci. (Biology), Assistant Professor

Russian Federation, Saint Petersburg

Sergei G. Zhuravskii

Academician I.P. Pavlov First St. Petersburg State Medical University

Author for correspondence.
Email: s.jour@mail.ru
Scopus Author ID: 8244733500

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

References

  1. Jumaily M, Franco J, Gallogly JA, et al. Butterfly cartilage tympanoplasty outcomes: A single-institution experience and literature review. Am J Otolaryngol. 2018;39(4):396–400. doi: 10.1016/j.amjoto.2018.03.029
  2. Ghanad I, Polanik MD, Trakimas DR, et al. A systematic review of nonautologous graft materials used in human tympanoplasty. Laryngoscope. 2021;131(2):392–400. doi: 10.1002/lary.28914
  3. Boedts D, De Cock M, Andries L, Marquet J. A scanning electron-microscopic study of different tympanic grafts. Am J Otol. 1990;11(4):274–277.
  4. Johnson F. Polyvinyl in tympanic membrane perforations. Arch Otolaryngol. 1967;86(2):152–155. doi: 10.1001/archotol.1967.00760050154005
  5. Jang CH, Kim W, Moon C, Kim G. Bioprinted collagen-based cell-laden scaffold with growth factors for tympanic membrane regeneration in chronic perforation model. IEEE Trans Nanobioscience. 2022;21(3):370–379. doi: 10.1109/TNB.2021.3085599
  6. Jang CH, Cho YB, Yeo M, et al. Regeneration of chronic tympanic membrane perforation using 3D collagen with topical umbilical cord serum. Int J Biol Macromol. 2013;62:232–240. doi: 10.1016/j.ijbiomac.2013.08.049
  7. Teh BM, Marano RJ, Shen Y, et al. Tissue engineering of the tympanic membrane. Tissue Eng Part B Rev. 2013;19(2):116–132. doi: 10.1089/ten.TEB.2012.0389
  8. Riccardo AA Muzzarelli. Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone. Carbohydrate Polymers. 2009;72(2):167–182. doi: 10.1016/j.carbpol.2008.11.002
  9. Nikolaeva ED. Biopolymers for tissue engineering. Journal of Siberian federal university. Biology. 2014;7(2):222–233. EDN: STXVIP
  10. Kim IY, Seo SJ, Moon HS, et al. Chitosan and its derivatives for tissue engineering applications. Biotechnol Adv. 2008;26(1):1–21. doi: 10.1016/j.biotechadv.2007.07.009
  11. Okamoto Y, Watanabe M, Miyatake K, et al. Effects of chitin/chitosan and their oligomers/monomers on migrations of fibroblasts and vascular endothelium. Biomaterials. 2002;23(9):1975–1979. doi: 10.1016/s0142-9612(01)00324-6
  12. Khor E, Lim LY. Implantable applications of chitin and chitosan. Biomaterials. 2003;24(13):2339–2349. doi: 10.1016/S0142-9612(03)00026-7
  13. Mori T, Okumura M, Matsuura M, et al. Effects of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro. Biomaterials. 1997;18(13):947–951. doi: 10.1016/s0142-9612(97)00017-3
  14. Teh BM, Shen Y, Friedland PL, et al. A review on the use of hyaluronic acid in tympanic membrane wound healing. Expert Opin Biol Ther. 2012;12(1):23–36. doi: 10.1517/14712598.2012.634792
  15. Chen LH, Xue JF, Zheng ZY, et al. Hyaluronic acid, an efficient biomacromolecule for treatment of inflammatory skin and joint diseases: A review of recent developments and critical appraisal of preclinical and clinical investigations. Int J Biol Macromol. 2018;116:572–584. doi: 10.1016/j.ijbiomac.2018.05.068
  16. Vigani B, Rossi S, Sandri G, et al. Hyaluronic acid and chitosan-based nanosystems: a new dressing generation for wound care. Expert Opin Drug Deliv. 2019;16(7):715–740. doi: 10.1080/17425247.2019.1634051
  17. Shi C, Zhu Y, Ran X, et al. Therapeutic potential of chitosan and its derivatives in regenerative medicine. J Surg Res. 2006;133(2):185–192. doi: 10.1016/j.jss.2005.12.013
  18. Kim J, Kim SW, Choi SJ, et al. A healing method of tympanic membrane perforations using three-dimensional porous chitosan scaffolds. Tissue Eng Part A. 2011;17(21–22):2763–2772. doi: 10.1089/ten.TEA.2010.0533
  19. Gribinichenko TN, Uspenskaya MV, Snetkov PP, et al. Bi-layered films based on sodium hyaluronate and chitosan as materials for ENT surgery. IECBES. 2022;338–343. doi: 10.1109/IECBES54088.2022.10079697
  20. Naumenko M, Snetkov P, Gribinichenko T, et al. In vivo biocompatibility and biodegradability of bilayer films based on hyaluronic acid and chitosan for ear, nose and throat surgery. Eng Proc. 2023;56(1):32. doi: 10.3390/ASEC2023-15260
  21. Strukov AI, Kaufman OY. Granulomatous inflammation and granulomatous diseases. Moscow: Meditsina; 1989. 184 p. (In Russ.)
  22. Yukina GY, Zhuravskii SG, Kryzhanovskaya EA, Tomson VV. Reaction of interstitial macrophages and mast cells of rat lungs to parenteral administration of silicon dioxide nanoparticles. Questions of morphology of the XXI century. 2018;282–284. (In Russ.) doi: 10.17513/mjpfi.13003
  23. Popryadukhin PV, Yukina GY, Dobrovolskaya IP, et al. Cell bases of bioresorption of porous 3d-matrixbased on chitosan. Cytology. 2019;61(7):556–563. EDN: DJYPSM doi: 10.1134/S0041377119070071

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2. Fig. 1. Dynamics of the changes in animal weights during the experiment. CS, chitosan; HA, hyaluronic acid

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3. Fig. 2. Implantation zone on postoperative day 3. Implantation of a polymer film from CS900_GA (without t). Reproduced from article [20] with permission from MDPI, 2023

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4. Fig. 3. Dynamics of implantation zone edema. CS, chitosan; HA, hyaluronic acid

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5. Fig. 4. Implantation site (a) and type of matrix in the swelling state (b) at the fixation stage by day 50 of observation. A sample of the CS900_HA (t) film. Macropreparations: (a) magnification ×2 and (b) magnification ×4. Reproduced from article [20] with the permission of MDPI, 2023

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6. Fig. 5. Samples of chitosan material with a molecular weight of 500 kDa and hyaluronic acid on day 50 of implantation. Staining by the Mallory method. Magnification ratio 200: (a), without heat treatment; matrix fragments (indicated by arrows), fibroblasts in the biodegradation zone; (b) with heat treatment; fragments of the matrix material (indicated by arrows)

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7. Fig. 6. Samples of chitosan materials with a molecular weight of 900 kDa and hyaluronic acid on day 50 of implantation. Decay zone of the matrix and the periimplantation capsule stained by the Mallory method. Magnification ratio, 100: (a) without heat treatment and (b) with heat treatment

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