Study of cytotoxicity and analysis of cellular reactions to the implantation of polyurethaneureas with ifosfamide
DOI:
https://doi.org/10.26641/1997-9665.2024.4.52-60Keywords:
polyurethaneureas, ifosfamide, fibroblast tissue culture, implantation test, biocompatibility.Abstract
Background. Society's need for modern implants and tissue engineering products is steadily growing due to the increase in the number of surgical interventions caused by various diseases, injuries and age-related changes. An increasing number of materials based on synthetic polymers, intended for implantation in the tissues of a living organism, are becoming widely used in medical practice. The aim of this work was to study the cytotoxicity and analysis of cellular reactions to the implantation of polyurethaneureas with immobilized ifosfamide, synthesized using 4,4'-diaminodiphenylmethane and 3,6-dioxyoctane-1,8-diamine as macrochain extenders by the method of tissue culture of fibroblasts and by means of the implantation test. Results. Using the method of tissue culture of fibroblast cells, it was shown that the dynamics and nature of the growth of cellular elements during cultivation in experimental vials with composite materials based on polyurethaneureas, including ifosfamide, did not differ significantly from control cultures, which allows us to conclude that the extracts from the studied cells do not have a cytotoxic effect materials on cultured cells. It was established that the implantation of test samples of polyurethaneureas in the body of experimental animals led to the development of cellular reactions typical for aseptic inflammation, without signs of acute inflammatory and other reactive processes. Histological studies have shown that the studied samples are biocompatible with the tissues of experimental animals. Implantation of polymer samples with ifosfamide led to the development of intense cellular reactions in the area where the implants were placed. The content of ifosfamide in the polymer matrix probably affected the proliferation of cellular elements in implantion site, as a result of which regenerative processes were inhibited in the early stages of the study. Conclusion. Based on the results of the research, it was shown that the developed composite materials based on polyurethaneureas with ifosfamide do not have a pronounced cytotoxic effect, are biocompatible and promising materials for use in medical practice during antitumor therapy.
References
- Farag MM. Recent trends on biomaterials for tissue regeneration applications: review. Journal of Materials Science. 2023;58:527-558. https://doi.org/10.1007/s10853-022-08102-x
- Kovylin RS, Aleynik DY, Fedushkin IL. Modern Porous Polymer Implants: Synthesis, Properties, and Application. Polymer Science, Series C. 2021;63:29-46. https://doi.org/10.1134/S1811238221010033
- Al-Shalawi FD, Mohamed Ariff AH, Jung D-W, Mohd Ariffin MKA, Seng Kim CL, Brabazon D, Al-Osaimi MO. Biomaterials as Implants in the Orthopedic Field for Regenerative Medicine: Metal versus Synthetic Polymers. Polymers. 2023;15:2601. https://doi.org/10.3390/polym15122601
- Domingues Goncalves A, Balestri W, Reinwald Y. Biomedical Implants for Regenerative Therapies. Biomaterials. 2020. http://dx.doi.org/10.5772/intechopen.91295
- Ulery BD, Nair LS, Laurencin CT. Biomedical Applications of Biodegradable Polymers. J Polym Sci B Polym Phys. 2011;49(12):832-864. https://doi.org/10.1002/polb.22259
- Ornaghi HL Jr, Monticeli FM, Agnol LD. A Review on Polymers for Biomedical Applications on Hard and Soft Tissues and Prosthetic Limbs. Polymers. 2023;15(19):4034. https://doi.org/10.3390/polym15194034
- Cui M, Chai Z, Lu Y, Zhu J, Chen J. Developments of polyurethane in biomedical applications: A review. Resources Chemicals and Materials. 2023;2(4):262-276. https://doi.org/10.1016/j.recm.2023.07.004
- Stewart SA, Domínguez-Robles J, Donnelly RF, Larrañeta E. Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications. Polymers. 2018;10(12):1379. https://doi.org/10.3390/polym10121379
- Teo AJT, Mishra A, Park I, Kim Y-J, Park W-T, Yoon Y-J. Polymeric Biomaterials for Medical Implants & Devices. ACS Biomaterials Science & Engineering. 2016;2(4):454-472. https://doi.org/10.1021/acsbiomaterials.5b00429
- Avula MN, Rao AN, McGill LD, Grainger DW, Solzbacher F. Foreign body response to subcutaneous biomaterial implants in a mast cell-deficient Kitw-sh murine model. Acta Biomaterialia. 2014;10(5):1856-1863. https://doi.org/10.1016/j.actbio.2013.12.056
- Anderson JM. Biological responses to materials. Annual Review of Materials Research. 2001;31(1):81-110.
- Galatenko NA, Rozhnova RA. [Biologically Active Polymeric Materials for Medicine]. Kyiv: Naukova Dumka; 2013. 210 p. Russian.
- Wang Y, Sun L, Mei Z, Zhang F, He M, Fletcher C, Wang F, Yang J, Bi D, Jiang Y, Liu P. 3D printed biodegradable implants as an individualized drug delivery system for local chemotherapy of osteosarcoma. Materials & Design. 2020;186:108336. https://doi.org/10.1016/j.matdes.2019.108336
- Gladyr I, Kozlova G, Narazhayko L, Galatenko N. [Development and research of polymeric composite materials of medical purpose with ifosfamide on the basis of polyurethanes with isocyanurate fragments]. Polymer Journal. 2020;42(2):125-135. Ukrainian. https://doi.org/10.15407/polymerj.42.02.125
- Prymushko SO, Galatenko NА, Rozhnova RA, Kozlova GA, Gladyr II, Danko NO. Synthesis and research of polyurethane urea with 2-(2-aminoethoxy)ethan-1-amine and 3-{2-[2-(3-aminopropoxy)ethoxy]ethoxy}propane-1-amine as macrochain extenders, and compositions with ifosfamide based on them. Issues of Chemistry and Chemical Technology. 2024;(1):70-80. http:// dx.doi.org/10.32434/0321-4095-2024-152-1-70-80
- Zhang Y, Kawedia J, Myers A, McIntyre C, Anderson P, Kramer M. Physical and chemical stability of high-dose ifosfamide and mesna for prolonged 14-day continuous infusion. Journal of Oncology Pharmacy Practice. 2013;20(1):51-57. https://doi.org/10.1177/1078155213478284
- Prymushko SO, Galatenko NA, Rozhnova RA, Kozlova GA, Gladyr II. Synthesis and investigation of new polyurethaneureas containing 3,6-dioxyoctane-1,8-diamine as a macrochain extender. Polymer Journal. 2022;44(3):231. https://doi.org/10.15407/polymerj.44.03.231
- Prymushko SO, Kozlova GA, Gladyr II, Galatenko NA. Development of medical composite materials with ifosfamide based on polyurethaneureas containing 3,6-dioxyoctane-1,8-diamine in their structure. In: [XXIII International Conference of Students, Postgraduates, and Young Scientists "Modern Problems of Chemistry"; 2022 May 18-20; Kyiv, Ukraine]. 2022. p. 114.
- Burenko HV, Galatenko NA, Kabak KS. [Morfologicheskie i biokhimicheskie aspekti biodestruktsii polimerov]. Kyiv: Naukova Dumka; 1986. 221 p. Russian.
- Lebedev EV, Konstantinov YuB, Galatenko NA, Yatsenko VP, Rozhnova RA, Maksymenko VB, authors: [Toksikologo-gіgієnіchnі ta doklіnіchnі doslіdzhennya polіmernih materіalіv і virobіv na їh osnovі medichnogo priznachennya: metod. vkazіvki]. Kyiv: Naukova dumka; 2009. 99 p. Ukrainian.
- European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes. Strasbourg: Council of Europe; 1986. 53 p.
- Bagrij MM, Dibrova VA, Popadynets OG, Hryshchuk MI, authors: [Metodiki morfologichnikh doslidzhen: monografiya]. Vinniczya: Nova Kniga; 2016. 328 p. Ukrainian.
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