urmjУральский медицинский журналUral Medical Journal2949-4389Ural State Medical University10.52420/2071-5943-2024-23-1-24-36HTTLINurmj-1423Research ArticleОригинальные статьи | Original articlesOriginal articlesСравнение эффективности способов получения и введения стромально-васкулярной фракции жировой ткани на экспериментальной модели донорской раны у обожженныхComparison of the Effectiveness of Methods for Obtaining and Application the Stromal-Vascular Fraction of Adipose Tissue in an Experimental Model of a Donor Wound in Burnshttps://orcid.org/0000-0002-4563-5478КолошеинН. А.KolosheinN. A.

Никита Анатольевич Колошеин — младший научный сотрудник Университетской клиники

Нижний Новгород

Nikita A. Koloshein — Junior Researcher of the University Clinic

Nizhny Novgorod

n.koloshein@mail.ruhttps://orcid.org/0000-0002-9555-190XРябковМ. Г.RyabkovM. G.

Максим Георгиевич Рябков — доктор медицинских наук, доцент, ведущий научный сотрудник группы термической травмы (взрослых) Университетской клиники

Нижний Новгород

Maksim G. Ryabkov — Doctor of Sciences (Medicine), Associate Professor, Leading Researcher of the Group of Burn Trauma (Adult), University Clinic

Nizhny Novgorod

maxim-ryabkov@yandex.ruhttps://orcid.org/0000-0002-8815-9651ЕгорихинаМ. Н.EgorikhinaM. N.

Марфа Николаевна Егорихина — кандидат биологических наук, заведующий научной лаборатории клеточных технологий

Нижний Новгород

Marfa N. Egorikhina — Candidate of Sciences (Biology), Head of the Laboratory of Cell Technologies

Nizhny Novgorod

egorihina.marfa@yandex.ruhttps://orcid.org/0000-0002-8191-7739ТимофееваЛ. Б.TimofeevaL. B.

Лидия Борисовна Тимофеева — кандидат биологических наук, доцент кафедры гистологии с цитологией и эмбриологией

Нижний Новгород

Lidiya B. Timofeeva — Candidate of Sciences (Biology), Associate Professor of the Department of Histology with Cytology and Embryology

Nizhny Novgorod

bioli@mail.ruhttps://orcid.org/0000-0003-0707-892XПеретягинП. В.PeretyaginP. V.

Пётр Владимирович Перетягин — младший научный сотрудник экспериментально-биологической клиники центральной научно-исследовательской лаборатории

Нижний Новгород

Petr V. Peretyagin — Junior Researcher of the Experimental Biological Clinic of the Central Research Laboratory

Nizhny Novgorod

peretyaginpv@gmail.comhttps://orcid.org/0000-0003-1959-2766АрефьевИ. Ю.ArefevI. Yu.

Игорь Юрьевич Арефьев — кандидат медицинских наук; директор Университетской клиники

Нижний Новгород

Igor Yu. Arefev — Candidate of Sciences (Medicine); Director of the University Clinic

Nizhny Novgorod

arefev_i@pimunn.netПриволжский исследовательский медицинский университетРоссияPrivolzhsky Research Medical UniversityRussian Federation2024060320242312436Copyright © Колошеин Н.А., Рябков М.Г., Егорихина М.Н., Тимофеева Л.Б., Перетягин П.В., Арефьев И.Ю., 20242024Колошеин Н.А., Рябков М.Г., Егорихина М.Н., Тимофеева Л.Б., Перетягин П.В., Арефьев И.Ю.Koloshein N.A., Ryabkov M.G., Egorikhina M.N., Timofeeva L.B., Peretyagin P.V., Arefev I.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.umjusmu.ru/jour/article/view/1423Введение

Введение. Оптимальный способ получения и введения стромально-васкулярной фракции (СВФ) жировой ткани для лечения донорских ран у обожженных не определен.

Цель работы — сравнить эффективность стромально-васкулярной фракции жировой ткани в лечении донорских ран в зависимости от способа обработки (механического и ферментативного) и пути введения (подкожного, внутрикожного) в ткани.

Материал и методы

Материал и методы. Крысы «Вистар» (n = 30) разделены на 2 исследуемые группы: в первой (фСВФ) применена ферментная обработка жировой ткани (n = 10), во второй (мСВФ) — механическая (n = 10). Еще 10 крыс использовались как группа доноров жировой ткани. Всем животным моделировали глубокий ожог, а через 4 дня формировали еще 2 донорские раны, забирая расщепленный дермотрансплантат: в одну из ран препарат вводили внутрикожно, в другую — подкожно. Через 14 суток оценивали площадь эпителизации, показатель микроциркуляции и микроструктуру кожи.

Результаты

Результаты. Доля полностью эпителизированных донорских ран в группе фСВФ составила 85 %, в группе мСВФ — 55 % (р < 0,05). Показатель микроциркуляции достоверно сокращался при внутрикожном введении в группе фСВФ (р < 0,01), а при подкожном — в группе мСВФ (р < 0,05). По данным гистоморфометрии при внутрикожном введении фСВФ толщина эпидермиса и слоя грануляционной ткани меньше, чем в группе мСВФ (р < 0,01). При этом относительная плотность коллагеновых волокон в грануляционной ткани была значимо выше после введения фСВФ, чем после мСВФ (р < 0,01). Сравнение путей введения препарата показало: существенных различий при использовании фСВФ не выявлено; при использовании мСВФ предпочтителен подкожный путь введения, т. к. он сопровождался значимо меньшей толщиной грануляционной ткани (р < 0,01).

Заключение

Заключение. Ферментативно обработанная стромально-васкулярная фракция жировой ткани имеет преимущества перед механически обработанной: эффективность фСВФ одинаково высока при внутрикожном и подкожном введении, что подтверждается структурой и кровообращением в новообразованной коже. При использовании мСВФ внутрикожное введение наименее эффективно, а подкожное сопровождается умеренно выраженной положительной динамикой в микроструктуре кожи донорских ран.

Introduction

Introduction. The optimal method of obtaining and application a stromal-vascular fraction (SVF) of adipose tissue in the treatment of donor wounds in burned patients has not been determined.

Objective — to compare the effectiveness of the stromal-vascular fraction of adipose tissue in the treatment of donor wounds, depending on the method of obtaining (mechanical and enzymatic) and the injection (subdermal, intradermal) into the tissue.

Material and methods

Material and methods. Wistar rats (n = 30) were divided into 2 investigated groups: in the first group (eSVF) enzymatic processing of adipose tissue (n = 10) was used, in the second group (mSVF) mechanical processing was used (n = 10). Another 10 rats were used as adipose tissue donors’ group. A deep burn was created in all animals, and after 4 days two more donor wounds were created by taking a split thickness skin autograft: the stromal-vascular fraction was injected intradermally into one of the wounds, subdermally into the other. After 14 days, the area of epithelialization, the microcirculation index and the histological microstructure of the skin were evaluated.

Results

Results. The proportion of completely epithelized donor wounds in the eSVF-group was 85 %, in the mSVF-group — 55 % (p < 0.05). The index of microcirculation significantly decreased after intradermal injections in the eSVF-group (p < 0.01), and after subdermal injections — in the mSVF-group (p < 0.05). According to histomorphometry, with intradermal injections of eSVF, the thickness of the epidermis and the layer of granulation tissue is less than in the mSVF group (p < 0.01). At the same time, the relative density of collagen fibers in the granulation tissue was significantly higher after the injections of eSVF than after mSVF (p < 0.01). Comparison of injections of the stromal-vascular fraction showed: no significant differences were found when using eSVF; when using mSVF, the subdermal injections are preferable, since it was accompanied by a significantly lower thickness of granulation tissue (p < 0.01).

Conclusions

Conclusions. The enzymatically obtained stromal-vascular fraction of adipose tissue has advantages over the mechanically obtained one: the efficiency of eSVF is equally high when used with intradermally and subdermally injections, which are confirmed by the structure and blood circulation in the newly formed skin. When using mSVF, intradermal injections are the least effective, and subdermal injections are accompanied by a moderately pronounced positive dynamic in the microstructure of the skin of donor wounds.

мало манипуляционные технологиистромально-васкулярная фракциядонорские раныожогиstromal-vascular fractiondonor sites woundburnsИсследование выполнено в рамках государственного задания Министерства здравоохранения РФ «Разработка технологий восстановления раневых дефектов кожного покрова с применением оригинального биомедицинского клеточного продукта и мало манипуляционных клеточных технологий» № 62.7– 2021 (государственная регистрация РК 208.090.01; ЕГИСУ № 121022500010-6; дата регистрации 26.02.2021).The study was funded by the Ministry of Health of the Russian Federation “Development of Technologies for the Healing of Skin Wounds with Using an Original Biomedical Cell Product and Minimal Manipulative Cell Technologies” No. 62.7–2021 (state registration number RК 208.090.01; EGISU registration number: 121022500010–6; date of registration February 26, 2021).ReferencesGao X, Zhang M, Lin Y, Li D, Zhang L. Combined Complex skin repair in patient with extensive burns: A case report. Journal of Burn Care & Research. 2021;42(5):1053–1056. DOI: https://doi.org/10.1093/jbcr/irab037.Gao X, Zhang M, Lin Y, Li D, Zhang L. Combined Complex skin repair in patient with extensive burns: A case report. Journal of Burn Care & Research. 2021;42(5):1053–1056. DOI: https://doi.org/10.1093/jbcr/irab037.Alekseev AA, Bobrovnikov AE, Bogdanov V. V. Meaning of innovative technologies for improvement of results in treating burned patients. Medical Alphabet. 2020;(13):44–47. (In Russ.). DOI: https://doi.org/10.33667/2078-5631-2020-13-44-47.Alekseev AA, Bobrovnikov AE, Bogdanov V. V. Meaning of innovative technologies for improvement of results in treating burned patients. Medical Alphabet. 2020;(13):44–47. (In Russ.). DOI: https://doi.org/10.33667/2078-5631-2020-13-44-47.Luck J, Smith OJ, Malik D, Mosahebi A. Protocol for a systematic review of autologous fat grafting for wound healing. Systematic Reviews. 2018;7(1):99. DOI: https://doi.org/10.1186/s13643-018-0769-7.Luck J, Smith OJ, Malik D, Mosahebi A. Protocol for a systematic review of autologous fat grafting for wound healing. Systematic Reviews. 2018;7(1):99. DOI: https://doi.org/10.1186/s13643-018-0769-7.Malik D, Luck J, Smith OJ, Mosahebi A. A systematic review of autologous fat grafting in the treatment of acute and chronic cutaneous wounds. Plastic and Reconstructive Surgery — Global Open. 2020;8(5):e2835. DOI: https://doi.org/10.1097/GOX.0000000000002835.Malik D, Luck J, Smith OJ, Mosahebi A. A systematic review of autologous fat grafting in the treatment of acute and chronic cutaneous wounds. Plastic and Reconstructive Surgery — Global Open. 2020;8(5):e2835. DOI: https://doi.org/10.1097/GOX.0000000000002835.Vasil’ev VS, Vasil’ev SA, Karpov IA, Dimov GP, Teryushkova ZhI, Gromov IA, et al. The possibilities for the application of the stromal-vascular fraction of the adipose tissue in plastic surgery. Annaly plasticheskoy, rekonstruktivnoy i esteticheskoy hirurgii. 2017;(2):82–92. (In Russ.). EDN: https://elibrary.ru/xmfkzn.Vasil’ev VS, Vasil’ev SA, Karpov IA, Dimov GP, Teryushkova ZhI, Gromov IA, et al. The possibilities for the application of the stromal-vascular fraction of the adipose tissue in plastic surgery. Annaly plasticheskoy, rekonstruktivnoy i esteticheskoy hirurgii. 2017;(2):82–92. (In Russ.). EDN: https://elibrary.ru/xmfkzn.De Francesco F, Mannucci S, Conti G, Dai Prè E, Sbarbati A, Riccio M. A Non-enzymatic method to obtain a fat tissue derivative highly enriched in Adipose Stem Cells (ASCs) from human lipoaspirates: Preliminary results. International Journal of Molecular Sciences. 2018;19(7):2061. DOI: https://doi.org/10.3390/ijms19072061.De Francesco F, Mannucci S, Conti G, Dai Prè E, Sbarbati A, Riccio M. A Non-enzymatic method to obtain a fat tissue derivative highly enriched in Adipose Stem Cells (ASCs) from human lipoaspirates: Preliminary results. International Journal of Molecular Sciences. 2018;19(7):2061. DOI: https://doi.org/10.3390/ijms19072061.Andia I, Maffulli N, Burgos-Alonso N. Stromal vascular fraction technologies and clinical applications. Expert Opinion on Biological Therapy. 2019;19(12):1289–1305. DOI: https://doi.org/10.1080/14712598.2019.1671970.Andia I, Maffulli N, Burgos-Alonso N. Stromal vascular fraction technologies and clinical applications. Expert Opinion on Biological Therapy. 2019;19(12):1289–1305. DOI: https://doi.org/10.1080/14712598.2019.1671970.SundarRaj S, Deshmukh A, Priya N. Development of a system and method for automated isolation of stromal vascular fraction from adipose tissue lipoaspirate. Stem Cells International. 2015;2015:109353. DOI: https://doi.org/10.1155/2015/109353.SundarRaj S, Deshmukh A, Priya N. Development of a system and method for automated isolation of stromal vascular fraction from adipose tissue lipoaspirate. Stem Cells International. 2015;2015:109353. DOI: https://doi.org/10.1155/2015/109353.Copcu HE, Oztan S. New mechanical fat separation technique: Adjustable Regenerative Adipose-tissue Transfer (ARAT) and Mechanical Stromal Cell Transfer (MEST). Aesthetic Surgery Journal Open Forum. 2020;2(4):ojaa035. DOI: https://doi.org/10.1093/asjof/ojaa035.Copcu HE, Oztan S. New mechanical fat separation technique: Adjustable Regenerative Adipose-tissue Transfer (ARAT) and Mechanical Stromal Cell Transfer (MEST). Aesthetic Surgery Journal Open Forum. 2020;2(4):ojaa035. DOI: https://doi.org/10.1093/asjof/ojaa035.Copcu HE. Indication-based protocols with different solutions for mechanical stromal-cell transfer. Scars, Burns & Healing. 2022;8:20595131211047830. DOI: https://doi.org/10.1177/20595131211047830.Copcu HE. Indication-based protocols with different solutions for mechanical stromal-cell transfer. Scars, Burns & Healing. 2022;8:20595131211047830. DOI: https://doi.org/10.1177/20595131211047830.Jeyaraman M, Muthu S, Sharma S, Ganta C, Ranjan R, Jha SK. Nanofat: A therapeutic paradigm in regenerative medicine. World Journal of Stem Cells. 2021;13(11):1733–1746. DOI: https://doi.org/10.4252/wjsc.v13.i11.1733.Jeyaraman M, Muthu S, Sharma S, Ganta C, Ranjan R, Jha SK. Nanofat: A therapeutic paradigm in regenerative medicine. World Journal of Stem Cells. 2021;13(11):1733–1746. DOI: https://doi.org/10.4252/wjsc.v13.i11.1733.Gatiatulina ER, Manturova NE, Dimov GP, Vasiliyev VS, Teryushkova ZhI. Adipose-derived stromal vascular fraction: mechanism of action, prospects and risks of local application. Plastic Surgery and Aesthetic Medicine. 2019;(2):43–48. (In Russ.). DOI: https://doi.org/10.17116/plast.hirurgia201902143.Gatiatulina ER, Manturova NE, Dimov GP, Vasiliyev VS, Teryushkova ZhI. Adipose-derived stromal vascular fraction: mechanism of action, prospects and risks of local application. Plastic Surgery and Aesthetic Medicine. 2019;(2):43–48. (In Russ.). DOI: https://doi.org/10.17116/plast.hirurgia201902143.Nilforoushzadeh MA, Sisakht MM, Amirkhani MA, Seifalian AM, Banafshe HR, Verdi J, et al. Engineered skin graft with stromal vascular fraction cells encapsulated in fibrin-collagen hydrogel: A clinical study for diabetic wound healing. Journal of Tissue Engineering and Regenerative Medicine. 2020;14(3):424–440. DOI: https://doi.org/10.1002/term.3003.Nilforoushzadeh MA, Sisakht MM, Amirkhani MA, Seifalian AM, Banafshe HR, Verdi J, et al. Engineered skin graft with stromal vascular fraction cells encapsulated in fibrin-collagen hydrogel: A clinical study for diabetic wound healing. Journal of Tissue Engineering and Regenerative Medicine. 2020;14(3):424–440. DOI: https://doi.org/10.1002/term.3003.Samoilov AS, Astrelina TA, Aksenenko AV. Application of cell technologies in thermal burn damage to skin (Practical experience in State Research Center — Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia). Saratov Journal of Medical Scientific Research. 2019;15(4):999–1004. (In Russ.). EDN: https://elibrary.ru/uairnp.Samoilov AS, Astrelina TA, Aksenenko AV. Application of cell technologies in thermal burn damage to skin (Practical experience in State Research Center — Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia). Saratov Journal of Medical Scientific Research. 2019;15(4):999–1004. (In Russ.). EDN: https://elibrary.ru/uairnp.Koloshein NA. Application of autological adipose tissue and its products in the treatment of infected wounds of different genesis. Journal of Experimental and Clinical Surgery. 2022;15(3):268–277. (In Russ.). DOI: https://doi.org/10.18499/2070-478X-2022-15-3-268-277.Koloshein NA. Application of autological adipose tissue and its products in the treatment of infected wounds of different genesis. Journal of Experimental and Clinical Surgery. 2022;15(3):268–277. (In Russ.). DOI: https://doi.org/10.18499/2070-478X-2022-15-3-268-277.Kim BS, Chen SH, Vasella M, Guidi M, Gousopoulos E, Lindenblatt N, et al. In vivo evaluation of mechanically processed stromal vascular fraction in a chamber vascularized by an arteriovenous Shunt. Pharmaceutics. 2022;14(2):417. DOI: https://doi.org/10.3390/pharmaceutics14020417.Kim BS, Chen SH, Vasella M, Guidi M, Gousopoulos E, Lindenblatt N, et al. In vivo evaluation of mechanically processed stromal vascular fraction in a chamber vascularized by an arteriovenous Shunt. Pharmaceutics. 2022;14(2):417. DOI: https://doi.org/10.3390/pharmaceutics14020417.Uraloğlu M, Livaoğlu M, Agdoğan Ö, Mungan S, Alhan E, Karaçal N. An evaluation of five different dressing materials on split-thickness skin graft donor site and full-thickness cutaneous wounds: An experimental study. International Wound Journal. 2014;11(1):85–92. DOI: https://doi.org/10.1111/j.1742-481X.2012.01071.x.Uraloğlu M, Livaoğlu M, Agdoğan Ö, Mungan S, Alhan E, Karaçal N. An evaluation of five different dressing materials on split-thickness skin graft donor site and full-thickness cutaneous wounds: An experimental study. International Wound Journal. 2014;11(1):85–92. DOI: https://doi.org/10.1111/j.1742-481X.2012.01071.x.Yurova YuV, Zinoviev EV, Krylov KM, Soloshenko VV. Perspectives of use laser doppler flowmetry for accurate determination оf degree of a burn at prehospital stage. Emergency Medical Care. 2019;20(4):33–36. (In Russ.). DOI: https://doi.org/10.24884/2072-6716-2019-20-4-33-36.Yurova YuV, Zinoviev EV, Krylov KM, Soloshenko VV. Perspectives of use laser doppler flowmetry for accurate determination оf degree of a burn at prehospital stage. Emergency Medical Care. 2019;20(4):33–36. (In Russ.). DOI: https://doi.org/10.24884/2072-6716-2019-20-4-33-36.Gushchin YaA, Kovaleva MA. Comparative morphology of human and laboratory animals (short paper). Laboratory Animals for Science. 2019;(2). DOI: https://doi.org/10.29296/2618723X-2019-02-06.Gushchin YaA, Kovaleva MA. Comparative morphology of human and laboratory animals (short paper). Laboratory Animals for Science. 2019;(2). DOI: https://doi.org/10.29296/2618723X-2019-02-06.Burusapat C, Supawan M, Pruksapong C, Pitiseree A, Suwantemee C. Topical aloe vera gel for accelerated wound healing of split-thickness skin graft donor sites: A double-blind, randomized, controlled trial and systematic review. Plastic and Reconstructive Surgery. 2018;142(1):217–226. DOI: https://doi.org/10.1097/PRS.0000000000004515.Burusapat C, Supawan M, Pruksapong C, Pitiseree A, Suwantemee C. Topical aloe vera gel for accelerated wound healing of split-thickness skin graft donor sites: A double-blind, randomized, controlled trial and systematic review. Plastic and Reconstructive Surgery. 2018;142(1):217–226. DOI: https://doi.org/10.1097/PRS.0000000000004515.Vaheb M, Kohestani BM, Karrabi M, Khosrojerdi M, Khajeh M, Shahrestanaki E, et al. Evaluation of dried amniotic membrane on wound healing at split-thickness skin graft donor sites: A randomized, placebo-controlled, double-blind trial. Advances in Skin & Wound Care. 2020;33(12):636–641. DOI: https://doi.org/10.1097/01.ASW.0000695752.52235.e3.Vaheb M, Kohestani BM, Karrabi M, Khosrojerdi M, Khajeh M, Shahrestanaki E, et al. Evaluation of dried amniotic membrane on wound healing at split-thickness skin graft donor sites: A randomized, placebo-controlled, double-blind trial. Advances in Skin & Wound Care. 2020;33(12):636–641. DOI: https://doi.org/10.1097/01.ASW.0000695752.52235.e3.Momeni M, Fallah N, Bajouri A, Bagheri T, Orouji Z, Pahlevanpour P, et al. A randomized, double-blind, phase I clinical trial of fetal cell-based skin substitutes on healing of donor sites in burn patients. Burns. 2019;45(4):914–922. DOI: https://doi.org/10.1016/j.burns.2018.10.016.Momeni M, Fallah N, Bajouri A, Bagheri T, Orouji Z, Pahlevanpour P, et al. A randomized, double-blind, phase I clinical trial of fetal cell-based skin substitutes on healing of donor sites in burn patients. Burns. 2019;45(4):914–922. DOI: https://doi.org/10.1016/j.burns.2018.10.016.Bliley JM, Argenta A, Satish L, McLaughlin MM, Dees A, Tompkins-Rhoades C, et al. Administration of adipose-derived stem cells enhances vascularity, induces collagen deposition, and dermal adipogenesis in burn wounds. Burns. 2016;42(6):1212–1222. DOI: https://doi.org/10.1016/j.burns.2015.12.007.Bliley JM, Argenta A, Satish L, McLaughlin MM, Dees A, Tompkins-Rhoades C, et al. Administration of adipose-derived stem cells enhances vascularity, induces collagen deposition, and dermal adipogenesis in burn wounds. Burns. 2016;42(6):1212–1222. DOI: https://doi.org/10.1016/j.burns.2015.12.007.Kaita Y, Tarui T, Yoshino H, Matsuda T, Yamaguchi Y, Nakagawa T, et al. Sufficient therapeutic effect of cryopreserved frozen adipose-derived regenerative cells on burn wounds. Regenerative Therapy. 2019;10:92–103. DOI: https://doi.org/10.1016/j.reth.2019.01.001.Kaita Y, Tarui T, Yoshino H, Matsuda T, Yamaguchi Y, Nakagawa T, et al. Sufficient therapeutic effect of cryopreserved frozen adipose-derived regenerative cells on burn wounds. Regenerative Therapy. 2019;10:92–103. DOI: https://doi.org/10.1016/j.reth.2019.01.001.Kim I, Bang SI, Lee SK, Park SY, Kim M, Ha H. Clinical implication of allogenic implantation of adipogenic differentiated adipose-derived stem cells. Stem Cells Translational Medicine. 2014;3(11):1312–1321. DOI: https://doi.org/10.5966/sctm.2014-0109.Kim I, Bang SI, Lee SK, Park SY, Kim M, Ha H. Clinical implication of allogenic implantation of adipogenic differentiated adipose-derived stem cells. Stem Cells Translational Medicine. 2014;3(11):1312–1321. DOI: https://doi.org/10.5966/sctm.2014-0109.Chicharro D, Carrillo JM, Rubio M, Cugat R, Cuervo B, Guil S, et al. Combined plasma rich in growth factors and adipose-derived mesenchymal stem cells promotes the cutaneous wound healing in rabbits. BMC Veterinary Research. 2018;14(1):288. DOI: https://doi.org/10.1186/s12917-018-1577-y.Chicharro D, Carrillo JM, Rubio M, Cugat R, Cuervo B, Guil S, et al. Combined plasma rich in growth factors and adipose-derived mesenchymal stem cells promotes the cutaneous wound healing in rabbits. BMC Veterinary Research. 2018;14(1):288. DOI: https://doi.org/10.1186/s12917-018-1577-y.Enciso N, Avedillo L, Fermín ML, Fragío C, Tejero C. Regenerative potential of allogeneic adipose tissue-derived mesenchymal cells in canine cutaneous wounds. Acta Veterinaria Scandinavica. 2020;62(1):13. DOI: https://doi.org/10.1186/s13028-020-0511-z.Enciso N, Avedillo L, Fermín ML, Fragío C, Tejero C. Regenerative potential of allogeneic adipose tissue-derived mesenchymal cells in canine cutaneous wounds. Acta Veterinaria Scandinavica. 2020;62(1):13. DOI: https://doi.org/10.1186/s13028-020-0511-z.Kao HK, Hsu HH, Chuang WY, Chang KP, Chen B, Guo L. Experimental study of fat grafting under negative pressure for wounds with exposed bone. British Journal of Surgery. 2015;102(8):998–1005. DOI: https://doi.org/10.1002/bjs.9826.Kao HK, Hsu HH, Chuang WY, Chang KP, Chen B, Guo L. Experimental study of fat grafting under negative pressure for wounds with exposed bone. British Journal of Surgery. 2015;102(8):998–1005. DOI: https://doi.org/10.1002/bjs.9826.Maharlooei MK, Bagheri M, Solhjou Z, Jahromi BM, Akrami M, Rohani L, et al. Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats. Diabetes Research and Clinical Practice. 2011;93(2):228–234. DOI: https://doi.org/10.1016/j.diabres.2011.04.018.Maharlooei MK, Bagheri M, Solhjou Z, Jahromi BM, Akrami M, Rohani L, et al. Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats. Diabetes Research and Clinical Practice. 2011;93(2):228–234. DOI: https://doi.org/10.1016/j.diabres.2011.04.018.Zhou Y, Zhao B, Zhang XL, Lu YJ, Lu ST, Cheng J, et al. Combined topical and systemic administration with human adipose-derived mesenchymal stem cells (hADSC) and hADSC-derived exosomes markedly promoted cutaneous wound healing and regeneration. Stem Cell Research & Therapy. 2021;12(1):257. DOI: https://doi.org/10.1186/s13287-021-02287-9.Zhou Y, Zhao B, Zhang XL, Lu YJ, Lu ST, Cheng J, et al. Combined topical and systemic administration with human adipose-derived mesenchymal stem cells (hADSC) and hADSC-derived exosomes markedly promoted cutaneous wound healing and regeneration. Stem Cell Research & Therapy. 2021;12(1):257. DOI: https://doi.org/10.1186/s13287-021-02287-9.Huang SP, Hsu CC, Chang SC, Wang CH, Deng SC, Dai NT, et al. Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound healing in a murine model of a full-thickness defect. Annals of Plastic Surgery. 2012;69(6):656–662. DOI: https://doi.org/10.1097/SAP.0b013e318273f909.Huang SP, Hsu CC, Chang SC, Wang CH, Deng SC, Dai NT, et al. Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound healing in a murine model of a full-thickness defect. Annals of Plastic Surgery. 2012;69(6):656–662. DOI: https://doi.org/10.1097/SAP.0b013e318273f909.Jahanian M, Hoseini S, Atashi A, Saberi M, Hoseini SA, Mozaffari K, et al. Evaluation of Acellular Dermal Matrix (ADM) as a scaffold for adipose-derived stem cell transfer in the rat model. World Journal of Plastic Surgery. 2021;10(2):67–75. DOI: https://doi.org/10.52547/wjps.10.2.67.Jahanian M, Hoseini S, Atashi A, Saberi M, Hoseini SA, Mozaffari K, et al. Evaluation of Acellular Dermal Matrix (ADM) as a scaffold for adipose-derived stem cell transfer in the rat model. World Journal of Plastic Surgery. 2021;10(2):67–75. DOI: https://doi.org/10.52547/wjps.10.2.67.Mammucari M, Paolucci T, Russo D. A call to action by the Italian mesotherapy society on scientific research. Drug Design, Development and Therapy. 2021;15:3041–3047. DOI: https://doi.org/10.2147/DDDT.S321215.Mammucari M, Paolucci T, Russo D. A call to action by the Italian mesotherapy society on scientific research. Drug Design, Development and Therapy. 2021;15:3041–3047. DOI: https://doi.org/10.2147/DDDT.S321215.Ryabkov MG, Spiridonov AA, Beschastnov VV, Tixonova OA, Leontev AE. Treatment of chronic wounds by combination of autodermatoplasty and lipotransfer. Clinical and Experimental Surgery. 2018;4(22):17–23. (In Russ.). DOI: https://doi.org/10.24411/2308-1198-2018-14002.Ryabkov MG, Spiridonov AA, Beschastnov VV, Tixonova OA, Leontev AE. Treatment of chronic wounds by combination of autodermatoplasty and lipotransfer. Clinical and Experimental Surgery. 2018;4(22):17–23. (In Russ.). DOI: https://doi.org/10.24411/2308-1198-2018-14002.Mordyakov AE, Charyshkin AL. Evaluation of local treatment of donor sites wounds in patients with deep burns. Pirogov Russian Journal of Surgery = Khirurgiya. Zurnal im. N. I. Pirogova. 2018;(11):49–52. (In Russ.). DOI: https://doi.org/10.17116/hirurgia201811149.Mordyakov AE, Charyshkin AL. Evaluation of local treatment of donor sites wounds in patients with deep burns. Pirogov Russian Journal of Surgery = Khirurgiya. Zurnal im. N. I. Pirogova. 2018;(11):49–52. (In Russ.). DOI: https://doi.org/10.17116/hirurgia201811149.Yurova YuV, Shlyk IV. Influence of microbial wound dissemination and microcirculation on the results of skin engraftment. Grekov’s Bulletin of Surgery. 2013;172(1):060–064. (In Russ.). EDN: https://elibrary.ru/prycvf.Yurova YuV, Shlyk IV. Influence of microbial wound dissemination and microcirculation on the results of skin engraftment. Grekov’s Bulletin of Surgery. 2013;172(1):060–064. (In Russ.). EDN: https://elibrary.ru/prycvf.Bi H, Li H, Zhang C, Mao Y, Nie F, Xing Y, et al. Stromal vascular fraction promotes migration of fibroblasts and angiogenesis through regulation of extracellular matrix in the skin wound healing process. Stem Cell Research & Therapy. 2019;10(1):302. DOI: https://doi.org/10.1186/s13287-019-1415-6.Bi H, Li H, Zhang C, Mao Y, Nie F, Xing Y, et al. Stromal vascular fraction promotes migration of fibroblasts and angiogenesis through regulation of extracellular matrix in the skin wound healing process. Stem Cell Research & Therapy. 2019;10(1):302. DOI: https://doi.org/10.1186/s13287-019-1415-6.

The authors declare that there are no conflicts of interest present.