Received: 01.07.2022; Published on-line: 24.08.2022

Rat tissue responses to dacarbazine-containing implants made of cross-linked polyurethane of different densities

N. A. Galatenko 1, R. A. Rozhnova 1, D. V. Kuliesh 1, V. D. Denisenko 1, A. P. Maletskyy 2, N. M. Bigun 3


1 The Institute of Macromolecular Chemistry of the National Academy of Sciences of Ukraine; Kyiv (Ukraine)

2 SI "The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine"; Odesa (Ukraine)

3 Lviv Regional Clinical Hospital; Lviv (Ukraine)

TO CITE THIS ARTICLE: Galatenko NA, Rozhnova RA,  Kuliesh DV, Denisenko VD, Maletskyy AP,  Bigun NM. Rat tissue responses to dacarbazine-containing implants made of cross-linked polyurethane of different densities. J.ophthalmol.(Ukraine).2022;4:40-8.   

Background: Restorative orbital and periorbital surgeries require implantable materials containing antimicrobial and anticancer medications.

Purpose: To assess rat tissue responses to dacarbazine-containing implants made of cross-linked polyurethane of different densities.

Material and Methods: Dacarbazine (DC)-containing polyurethane-urea foam (PUUF) implants were a subject of research. We studied the dynamics of DC release from these implant samples. Soft tissue cellular responses to the developed composites were assessed through the implantation of the latter in Wistar rats.

Results: We found that the number of open pores impacts implant survival. There was no substantial difference in DC release between the PUUF samples with a DC weight percent of 1% and those with a DC weight percent of 0.5% at incubation days 1 to 3. At days 5, 7 and 14, an increase in DC release was higher in the former samples than in the latter samples (64% versus 55%). In animals with a subcutaneously implanted PUUF sample, there was histological evidence of (a) formation of a capsule and tight network of blood vessels surrounding an implanted sample at day 3, and (b) separation of the implanted material from the surrounding tissues by a wide cuff of lymphocytes and a thick connective tissue capsule (CTC) at day 7.

Conclusion: The number of open pores impacts DC release and the speed of connective tissue ingrowth into the porous matrix. It was found that a CTC formed around all implants at early time points and at day 30, which in combination with the presence of DC in composite materials resulted in long-term cellular inflammation at the implant placement site.  

Keywords: cross-linked polyurethane composite implant, dacarbazine deposition and diffusion, cellular response

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Corresponding Author: Maletskii Anatolii, maletskiy@filatov.com.ua 
Author Contribution: 
Galatenko N. A.: concept development, design, data collection, data analysis and interpretation, manuscript preparation/writing/review; 
Rozhnova R. A.: concept development, design, data analysis and interpretation, manuscript preparation/writing/review; 
Kuliesh D. V.: concept development, design, data collection and research, data analysis and interpretation, manuscript preparation/writing/review; 
Denisenko V. D.: conducting research, analysis and interpretation of data, preparation of manuscript; 
Maletskyy A. P.: concept development, design, data analysis and interpretation, manuscript preparation/writing/review; 
Bigun N.M.: data analysis and interpretation, manuscript preparation/writing/review. 
All authors analyzed the results and agreed on the final version of the manuscript.
Conflict of Interests.The authors declare that there is no conflict of interest that could influence their opinion regarding the subject matter or materials described and discussed in this manuscript.
Sources of Support. The article is a part of the research work on the topic "Formation of polymers of different spatial structure and polymer-based compositions for immobilization of biologically active compounds and medicinal substances", registration number #0114U007099.
Disclaimer: The considerations presented in the article are exclusively the author's and do not represent the official position of the institutions.
The research was conducted on animals. The experiment was performed in accordance with the "European Convention for the Protection of Vertebrate Animals Used for Experimental or Other Scientific Purposes" (Strasbourg, 1986). 
Abbreviations: PUUF – polyurethane-urea foam; DC – dacarbazine; CTC – connective tissue capsule