Problems of Radiation Medicine and Radiobiology

M. V. Krasnoselsky¹, O. S. Pushkar¹, L. I. Simonova¹, M. S. Myroshnychenko²

¹State Institution «Institute of Medical Radiology and Oncology named by S.P. Grigoriev National
  Academy of Medical Sciences of Ukraine», 82, Pushkinska St., Kharkiv, 61024, Ukraine
²Kharkiv National Medical University, Nauky Ave., 4, Kharkiv, 61022, Ukraine

THE EFFECT OF PHOTODYNAMIC THERAPY AND PLATELET-ENRICHED PLASMA ON THE HEALING OF SKIN RADIATION ULCERS INFECTED BY STAPHYLOCOCCUS AUREUS

Objective. To determine in experiment the quality of healing of skin radiation ulcers infected with Staphylococcus aureus (S. aureus) under the photodynamic therapy (PDT) administration and the use of platelet-rich plasma (PRP).
Materials and methods. The experiment was performed on 95 male WAG rats of 6 months of age, which were divided into three groups. Group 1 included animals in whom a skin radiation ulcers in the thigh area was simulated, followed by application of a 0.2 ml suspension of reference strain of S. aureus to its surface on the 7th day after irradiation. Group 2 included animals with S. aureus-infected skin radiation ulcers, in whom the PET was administered a day after infection contamination. Group 3 included animals with S. aureus-infected skin radiation ulcers, in whom the PDT was administered a day after infection in the morning, and the PRP was manifold injected in periwound area in the afternoon. The skin with underlying soft tissues from the area of radiation damage were the material for morphological examination. The hematoxylin and eosin, picrofuxin according to van Gizon, Mallory staining were applied to micropreparations. A morphometric study was conducted.
Results. In animals with skin radiation ulcers, in whom the PDT was administered upon infection with S. aureus (group 2), compared with animals with simulated infected skin radiation ulcers without treatment (group 1), The activation (i.e. accelerating) of the healing occurred for the period from the 14^th to the 52^nd day of experiment due to the active processes of wound cleansing from necrotized tissues, less pronounced inflammatory changes in the lesion, and active of appearance and maturation of granulation tissue, less pronounced hemodynamic, ischemic and alternative disorders in the dermis, hypodermis, muscle tissue surrounding the wound cavity, activation of proliferative processes in epithelial layer localized in the marginal parts of the wound. Formation of pathological (hypertrophic or keloid) scar of the skin was the result of healing of skin radiation ulcer infected with S. aureus. In animals with radiation ulcers infected with S. aureus, in the case of PDT and PRP (group 3) the regenerative process was directed not only at accelerating the rate of healing, but also on restoration of original structure of the lost parts of the skin compared with only PDT administration (group 2). Acceleration of the healing of the infected skin radiation ulcer in animals of groups 2 and 3 was due to similar processes.
Conclusions. Photodynamic therapy activates and accelerates the healing process of skin radiation ulcers infected with S. aureus and leads to formation of a pathological scar (hypertrophic or keloid). Healing of the infected S. aureus radiation ulcers occurs more actively upon the photodynamic therapy administration in combination with multiple periwound injections of the platelet-enriched plasma, compared with only photodynamic therapy administration, and finishes with an organotypic regeneration and almost complete skin recovery.
Key words: photodynamic therapy, platelet-rich plasma, radiation skin ulcer, Staphylococcus aureus, morphology.

Problems of Radiation Medicine and Radiobiology.
2020;25:338-352. doi: 10.33145/2304-8336-2020-25-338-352

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1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492.
2. Minailo II, Artemova NA, Demeshko PD. [Radiation therapy in medical practice]. Healthcare. 2017;1:35-43. Russian.
3. Rosenblatt E, Zubizarreta E, editors. Radiotherapy in cancer care: facing the global challenge. Vienna: International atomic energy agency; 2017. 544 p.
4. Semikoz NG, Seleznev KG, Dubrovina IV. [Evaluation of the effectiveness of the gel containing biologically active substances of medicinal leeches for the prevention and treatment of radial epithelial cells in patients with vulvar cancer]. Oncology. 2001;3(2-3):163-165. Russian.
5. Kryachok IA, Ulyanchenko EO, Kadnikova TV, et al. [Remote complications of radiation therapy in patients with malignant neoplasms]. Clinical Oncology. 2017;4(28):59-62. Russian.
6. Topuzov EE, Agishev TT, Bozhok AA, et al. [Clinical and morphological characteristics of damage to the skin and subcutaneous fat after surgery and radiation therapy in patients with breast cancer (literature review)]. Tumor Fem Reprod Syst. 2017;13(1):25-33. Russian.
7. Nesi-Reis V, Lera-Nonose DSSL, Oyama J, Silva-Lalucci MPP, Demarchi IG, Aristides SMA, et al. Contribution of photodynamic therapy in wound healing: a systematic review. Photodiagnosis Photodyn Ther. 2018;21:294-305. doi: 10.1016/j.pdpdt.2017.12.015.
8. Krasnoselsky MV, Simonova LI, Gertman VZ, Pushkar OS, Zavadskaya TS. [Tissue immune cells and their role in the healing processes of infected radiation ulcers under the influence of photodynamic therapy (experimental study)]. Probl Radiac Med Radiobiol. 2019;24:250-260. Ukrainian.
9. Krasnoselsky NV, Simonova LI, Gertman VZ, Pushkar ES. [Influence of photodynamic therapy on the healing of radiation ulcers of the skin infected with Pseudomonas aeruginosa]. Probl Radiac Med Radiobiol. 2017;22:202-207. Russian.
10. Aruin LI. [Quality of healing of gastroduodenal ulcers: functional morphology, the role of methods of pathogenetic therapy]. Contemp Gastroenterol. 2013;5(73):92-103. Russian.
11. Dhurat R, Sukesh M. Principles and methods of preparation of platelet-rich plasma: a review and author's perspective. Journal of Cutaneous and Aesthetic Surgery. 2014;7(4):189-197. doi: 10.4103/0974-2077.150734.
12. Myadelets OD. [Cellular mechanisms of barrier-protective functions of the skin and their disorders in skin pathology]. Vitebsk: Publishing House of Vitebsk State Medical University; 2000. 283 p. Russian.
13. Galimov OV, Tuisin SR, Zakiev TZ, et al. [Biochemical mechanisms of wound healing]. Bashkir Chemical Journal. 2008;15(3):82-83. Russian.
14. Tikhvinskaya OA, Volkova NA, Rogulskaya EYu, et at. [Healing of excisional skin wounds in mice in the presence of matrices from blood plasma]. Bull Probl Biol Med. 2018;4(2/147):307-312. Russian.
15. Vlasov OO, Kovalov GO, Myroshnychenko MS. Morphological features of a cold skin wound under the influence of an extract of cryopreserved skin fragments of piglets (experimental study). Wiadomosci Lekarskie. 2020. No. 73(2). P. 306-311.
16. Baitinger VF, Paityan KG. [Morphofunctional features of pathological skin scars: the state of the issue]. Iss Reconstruct Plastic Surg. 2013;1(44):28-34. Russian.
17. Bobr OA, Myadelets OD, Dubovsky VV. [Population dynamics of mast cells during the wound process in rats subjected to hypobiotic conditions (starvation, hypothermia)]. Bull VSMU. 2006;5(4):21-27. Russian.
18. Simonova-Pushkar LI, Sklyar NI, Gertman VZ, et al. [The use of antibacterial photodynamic therapy in the treatment of infected radiation skin lesions in experiment]. Exp Clin Med. 2015;3(68):34-39. Ukrainian.
19. Serov VV, Shekhter AB. [Connective tissue (functional morphology and general pathology)]. Moscow: Meditsina, 1981. 312 p. Russian.
20. Vlasov OO, Kovalov GO, Myroshnychenko MS. Morphological assessment of wound healing after creodestruction of skin using an aqueous colloidal solution of C60 fullerenes. Wiadomosci Lekarskie. 2020;73(4):642-647.
21. Malik SV, Rybalka JV, Osipov OS, Verba AV. [Optimization of treatment of patients with chronic wounds]. Clin Surg. 2017;10:49-50. Ukrainian.