Влияние гидрогеля на основе экстракта миомы матки на остеогенную активность остеобластов

Актуальность. Внеклеточный матрикс играет ключевую роль в поддержании гомеостаза и регенерации костной ткани, определяя условия дифференцировки и межклеточных взаимодействий. Нативный внеклеточный матрикс представляет собой сложную трехмерную сеть структурных белков, гликопротеинов и протеогликанов, обеспечивающих механическую поддержку клеток и передачу регуляторных сигналов. Традиционные 2D-системы культивирования не позволяют в полной мере воспроизводить сложную организацию клеточного микроокружения, поэтому актуальной задачей является разработка трехмерных систем для изучения процессов дифференцировки и ремоделирования костной ткани in vitro.
Цель. Оценка биосовместимости гидрогеля на основе экстракта миомы матки и его влияния на остеогенную дифференцировку остеобластов в моно- и сокультуре с эндотелиальными клетками.
Материалы и методы. Экстракт миомы матки выделяли по модифицированной методике, разработанной для получения Matrigel® из саркомы Энгельбрета-Хольма-Сварма мышей. Клеточную суспензию остеобластов смешивали с экстрактом миомы матки на холоде, затем смесь инкубировали при 37 °C для образования гидрогеля. Остеобласты культивировали в гидрогеле в виде моно- и сокультуры с эндотелиальными клетками в остеогенной среде. Жизнеспособность и морфологию клеток оценивали методом прижизненной микроскопии. Минерализацию внеклеточного матрикса определяли методом окраски ализариновым красным.
Результаты. Установлено, что гидрогель на основе экстракта миомы матки обладает высокой биосовместимостью в отношении остеобластов – поддерживает их жизнеспособность, способствует дифференцировке в остеоцитоподобные клетки и усиливает минерализацию внеклеточного матрикса. В сокультуре остеобластов с эндотелиальными клетками эффект усиливался, что указывает на важную роль межклеточных взаимодействий.
Заключение. Гидрогель на основе экстракта миомы матки представляет собой перспективную 3D-модель культивирования для изучения процессов остеогенной дифференцировки остеобластов.

1. Андреева Е. Р., Матвеева Д. К., Жидкова О. В., Буравкова Л. Б. Внеклеточный матрикс как фактор регуляции физиологического микроокружения клетки. Успехи физиологических наук. 2024;55(1):16‒30. https://doi.org/10.31857/s0301179824010033, https://elibrary.ru/xjcavk

2. Cheong S, Peng Y, Lu F, He Y. Structural extracellular matrix-mediated molecular signaling in wound repair and tissue regeneration. Biochimie. 2025;229:58–68. https://doi.org/10.1016/j.biochi.2024.10.003

3. Kamal KM, Ghazali AR, Selvarajah GT, et al. The extracellular matrix: structure, composition, biological functions, diseases, and therapeutic targets. Molecular Biomedicine. 2026;7(1):38. https://doi.org/10.1186/s43556-026-00436-1

4. Liu N, Shi Y, Li J, et al. Morphology-guided cellular behavior modulation with 3D-printed engineered ECM. Cell Biomaterials. 2025;1:100090. https://doi.org/10.1016/j.celbio.2025.100090

5. Zhao T, Huang Y, Zhu J, et al. Extracellular matrix signaling cues: biological functions, diseases, and therapeutic targets. MedComm (Beijing). 2025;6. https://doi.org/10.1002/mco2.70281

6. Kolb AD, Bussard KM. The Bone extracellular matrix as an ideal milieu for cancer cell metastases. Cancers. 2019;11(7):1020. https://doi.org/10.3390/cancers11071020

7. Lin X, Patil S, Gao Y-G, Qian A. The bone extracellular matrix in bone formation and regeneration. Front Pharmacol. 2020;11. https://doi.org/10.3389/fphar.2020.00757

8. Cai W, Huo Y, Liu Y, et al. Biomechanics in bone regeneration and mechanobiology in osteoblasts: Fundamental concepts and recent progress. Eng Medicine. 2025;2:100057. https://doi.org/10.1016/j.engmed.2025.100057

9. Li M, Zhang A, Li J, et al. Osteoblast/fibroblast coculture derived bioactive ECM with unique matrisome profile facilitates bone regeneration. Bioact Mater. 2020;5(4):938–48. https://doi.org/10.1016/j.bioactmat.2020.06.017

10. Perepletchikova D, Malashicheva A. Communication between endothelial cells and osteoblasts in regulation of bone homeostasis: Notch players. Stem Cell Res Ther. 2025;16(1):56. https://doi.org/10.1186/s13287-025-04176-x

11. Dalle Carbonare L, Cominacini M, Trabetti E, et al. The bone microenvironment: new insights into the role of stem cells and cell communication in bone regeneration. Stem Cell Res Ther. 2025;16(1):169. https://doi.org/10.1186/s13287-025-04288-4

12. Huang G, Hou T, Song D, Meng T. The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis. J Bone Oncol. 2025;55:100729. https://doi.org/10.1016/j.jbo.2025.100729

13. Amirazad H, Dadashpour M, Zarghami N. Application of decellularized bone matrix as a bioscaffold in bone tissue engineering. J Biol Eng. 2022;16:1. https://doi.org/10.1186/s13036-021-00282-5

14. Li C, An N, Song Q, et al. Enhancing organoid culture: harnessing the potential of decellularized extracellular matrix hydrogels for mimicking microenvironments. J Biomed Sci. 2024;31(1):96. https://doi.org/10.1186/s12929-024-01086-7

15. Guo X, Liu B, Zhang Y, et al. Decellularized extracellular matrix for organoid and engineered organ culture. J Tissue Eng. 2024;15. https://doi.org/10.1177/20417314241300386

16. Kibbey MC. Maintenance of the EHS sarcoma and Matrigel preparation. Journal of Tissue Culture Methods. 1994;16(3–4):227–230. https://doi.org/10.1007/BF01540656

17. Wolff L, Hendrix S. Rethinking Matrigel: The complex journey to matrix alternatives in organoid culture. Advanced Science. 2025;12:47. https://doi.org/10.1002/advs.202508734

18. Islam MS, Ciavattini A, Petraglia F, et al. Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for future therapeutics. Hum Reprod Update. 2018;24(1):59–85. https://doi.org/10.1093/humupd/dmx032

19. Saad EE, Michel R, Borahay MA. Immunosuppressive tumor microenvironment and uterine fibroids: Role in collagen synthesis. Cytokine Growth Factor Rev. 2024;75:93–100. https://doi.org/10.1016/j.cytogfr.2023.10.002

20. Yang Q, Ciebiera M, Bariani MV, et al. Comprehensive review of uterine fibroids: developmental origin, pathogenesis, and treatment. Endocr Rev. 2022;43(4):678–719. https://doi.org/10.1210/endrev/bnab039

21. Kostina D, Lobov A, Klausen P, et al. Isolation of human osteoblast cells capable for mineralization and synthetizing bone-related proteins in vitro from adult bone. Cells. 2022;11(21):3356. https://doi.org/10.3390/cells11213356

22. Kottmann V, Nienhaus M, et al. From bone homeostasis to skeletal metastasis and osteosarcoma: Insights into osteoclast and osteoblast roles in bone remodelling and cancer. Biochimica et Biophysica Acta ‒ Reviews on Cancer. 2026;1881(2):189551. https://doi.org/10.1016/j.bbcan.2026.189551

23. Li S, Cai X, Guo J, et al. Cell communication and relevant signaling pathways in osteogenesis–angiogenesis coupling. Bone Res. 2025;13(1):45. https://doi.org/10.1038/s41413-025-00417-0

24. Ma C, Du T, Niu X, Fan Y. Biomechanics and mechanobiology of the bone matrix. Bone Res. 2022;10(1):59. https:// doi.org/10.1038/s41413-022-00223-y

25. Emami A, Izadi E, Oskouie IM. Preservation of extracellular matrix in decellularized bone scaffolds: Strategies, challenges, and future directions. Tissue Cell. 2025;97:103047. https://doi.org/10.1016/j.tice.2025.103047

26. Li M, Liu X, Tian E, Liao W. The role of collagen in mechanotransduction and its influence on bone metabolic activity. Int J Biol Macromol. 2025;318:144968. https://doi.org/10.1016/j.ijbiomac.2025.144968

27. Brown M, Li J, Moraes C, et al. Decellularized extracellular matrix: New promising and challenging biomaterials for regenerative medicine. Biomaterials. 2022;289:121786. https:// doi.org/10.1016/j.biomaterials.2022.121786

28. Guo W-Y, Wang W-H, et al. Decellularised extracellular matrix-based injectable hydrogels for tissue engineering applications. Biomaterials translational. 2024;5(2):114–128. https://doi.org/10.12336/biomatertransl.2024.02.003

29. Gkantzou E, Rodríguez-Rojas A, et al. Decellularized extracellular matrix for organoids development and 3D Bioprinting. Organoids. 2026;5(1):2. https://doi.org/10.3390/organoids5010002

30. Zhang X, Chen X, et al. Decellularized extracellular matrix scaffolds: Recent trends and emerging strategies in tissue engineering. Bioact Mater. 2022;10:15–31. https://doi.org/10.1016/j.bioactmat.2021.09.014

31. Yang H, Xia J, et al. From production to the clinic: decellularized extracellular matrix as a biomaterial for tissue engineering and regenerative medicine. Bioengineering. 2025;13(1):24. https://doi.org/10.3390/bioengineering13010024

32. Liang R, Pan R, et al. Decellularized extracellular matrices for skin wound treatment. Materials. 2025;18(12):2752. https://doi.org/10.3390/ma18122752

33. Zhu Y, Yang W, et al. Constructing biomimetic microenvironments for liver regeneration. J Nanobiotechnology. 2025;23(1):655. https://doi.org/10.1186/s12951-025-03729-9

34. Kim JW, Nam SA, et al. Kidney decellularized extracellular matrix enhanced the vascularization and maturation of human kidney organoids. Advanced Science. 2022;9(15). https://doi.org/10.1002/advs.202103526

35. Liu W, Zhang X, et al. Decellularized extracellular matrix materials for treatment of ischemic cardiomyopathy. Bioact Mater. 2024;33:460–482. https://doi.org/10.1016/j.bioactmat.2023.10.015

36. Rusinova TV, Vinogradov RA, Asyakina AS, et al. Decellularized nerve scaffold in a rat model of extensive peripheral nerve damage. Modern Technologies in Medicine. 2025;17(6):16. https://doi.org/10.17691/stm2025.17.6.02

37. Kim Y-H, Cidonio G, Kanczler JM, et al. Human bone tissue-derived ECM hydrogels: Controlling physicochemical, biochemical, and biological properties through processing parameters. Bioact Mater. 2025;43:114–128. https://doi.org/10.1016/j.bioactmat.2024.09.007

38. Go YY, Kim SE, Cho GJ, et al. Differential effects of amnion and chorion membrane extracts on osteoblast-like cells due to the different growth factor composition of the extracts. PLoS One. 2017;12(8):e0182716. https://doi.org/10.1371/journal.pone.0182716

39. Kang B-J, Ryu H-H, Park S-S, et al. Effect of Matrigel on the osteogenic potential of canine adipose tissue-derived mesenchymal stem cells. J Vet Med Sci. 2012;74(7):827–836. https://doi.org/10.1292/jvms.11-0484

40. Tangporncharoen R, Silathapanasakul A, Tragoonlugkana P, et al. The extracts of osteoblast developed from adipose-derived stem cell and its role in osteogenesis. J Orthop Surg Res 2024;19(1):255. https://doi.org/10.1186/s13018-024-04747-3

41. Wei B, Chen Y, Zhang S, et al. Proteins extracted from placenta regulate osteogenic differentiation of human mesenchymal stem cells. Tissue Cell. 2025;96:103015. https:// doi.org/10.1016/j.tice.2025.103015

42. Coyle A, Chakraborty A, et al. In vitro engineered ECM-incorporated hydrogels for osteochondral tissue repair: a cell-free approach. Adv Healthc Mater. 2025;14(4). https://doi.org/10.1002/adhm.202402701

43. Dekker M, Hipwood L, et al. Bone-derived dECM hydrogels support tunable microenvironments for in vitro osteogenic differentiation. Adv Healthc Mater. 2026;15(1). https://doi.org/10.1002/adhm.202501350

44. Fu T, Liang P, et al. Matrigel scaffolding enhances BMP9-induced bone formation in dental follicle stem/precursor cells. Int J Med Sci. 2019;16(4):567–575. https://doi.org/10.7150/ijms.30801

45. Jeon J, Lee MS, Yang HS. Differentiated osteoblasts derived decellularized extracellular matrix to promote osteogenic differentiation. Biomater Res. 2018;22(1). https://doi.org/10.1186/s40824-018-0115-0

46. Nasello G, Alamán-Díez P, et al. Primary human osteoblasts cultured in a 3D microenvironment create a unique representative model of their differentiation into osteocytes. Front Bioeng Biotechnol. 2020;8. https://doi.org/10.3389/fbioe.2020.00336

47. Maggio N, Banfi A. The osteo-angiogenic signaling crosstalk for bone regeneration: harmony out of complexity. Curr. Opin. Biotechnol. 2022;76:102750. https://doi.org/10.1016/j.copbio.2022.102750

48. Perepletchikova D, Kuchur P, Basovich L, et al. Endothelial- mesenchymal crosstalk drives osteogenic differentiation of human osteoblasts through Notch signaling. Cell Communication and Signaling. 2025;23(1):100. https://doi.org/10.1186/s12964-025-02096-0

49. Wang T, Yao H, Jin F, et al. Bidirectional regulation between bone and vasculature: Mechanisms of osteogenesis and angiogenesis. J Adv Res. 2026. https://doi.org/10.1016/j.jare.2026.02.042

50. Yang Q, Liu S, et al. A new paradigm in bone tissue biomaterials: Enhanced osteogenesis–angiogenic coupling by targeting H-type blood vessels. Biomaterials. 2026;324:123423. https://doi.org/10.1016/j.biomaterials.2025.123423

51. Laude M, Kolliopoulos V, et al. Extracellular-matrix-based materials from decellularized tissue: opportunities, challenges, and future directions in regenerative medicine. Adv Healthc Mater. 2026;15(1). https://doi.org/10.1002/adhm.202502107

52. Parasuraman G, Rani J MS, et al. Matrigel-encapsulated articular cartilage derived fibronectin adhesion assay derived chondroprogenitors for enhanced chondrogenic differentiation: An in vitro evaluation. Tissue Cell. 2025;92:102638. https://doi.org/10.1016/j.tice.2024.102638