Эквиваленты кожи, полученные на основе 3D-биопечати и фибробластов, для заживления ран и регенерации

Интенсивное развитие персонифицированной медицины раскрывает новые возможности разработки технологий регенеративной медицины и трансляции этих разработок в клинику. Одним из интенсивно развиваемых направлений в создании новых лечебных подходов является использование биопечати для изготовления конструкций тканей и органов. Особое внимание привлекает разработка кожных эквивалентов, способных воспроизводить сложную архитектурную организацию и функциональные свойства тканей кожи. В обзоре проведен анализ публикаций, представленных в базах данных Scopus, PubMed и RSCI, охватывающих области биопечати, тканевой инженерии и регенеративной медицины. Использовались опубликованные данные, посвященные разработке биоматериалов, протоколам 3D-биопечати, характеристикам биопечатных кожных конструкций и результатам как доклинических, так и клинических исследований, актуальные по состоянию на сентябрь 2025 года. Анализ показал, что одним из наиболее перспективных направлений является оптимизация 3D-биопечати кожных конструкций, основанных на использовании фибробластов, кератиноцитов и инновационных биоматериалов, таких как гидрогели, коллагеновые матрицы и GelMA. Эти технологии позволяют создавать полнослойные, васкуляризированные структуры, обеспечивая достаточно высокую точность пространственного распределения клеток и поддержку микросреды, необходимой для регенерации тканей. Дальнейшие исследования по оптимизации параметров печати, правильному выбору компонентов биочернил, интеграции фибробластов и других клеточных компонентов позволят более точно моделировать дермальные слои и стимулировать процессы регенерации. Применение дополнительных биологических факторов будет способствовать формированию устойчивой сосудистой сети, лучшей приживляемости конструкций, что значительно улучшит функциональную интеграцию напечатанных конструкций в ткани организма-реципиента. Таким образом, интеграция передовых методов 3D-биопечати, оптимизированных биочернил и мультиклеточных конструкций открывает перспективы создания кожных эквивалентов нового поколения, которые смогут не только ускорить процесс регенерации, но и обеспечить эстетически оптимальный результат для пациентов, страдающих от серьезных ожогов, травм и других повреждений кожи.

1. Murphy SV, Atala A. 3D Bioprinting of Tissues and Organs. Nature Biotechnology. 2014;32(8):773–785. DOI: 10.1038/nbt.2958

2. Ma X, Liu J, Zhu W, Tang M, Lawrence N, Yu C, et al. 3D Bioprinting of Functional Tissue Models for Personalized Drug Screening and In Vitro Disease Modeling. Advanced Drug Delivery Reviews. 2018;132:235–251. DOI: 10.1016/j.addr.2018.06.011

3. Bishop ES, Mostafa S, Pakvasa M, Luu HH, Lee JM, Wolf JM, et al. 3-D Bioprinting Technologies in Tissue Engineering and Regenerative Medicine: Current and Future Trends. Genes and Diseases. 2017;4(4):185–195. DOI: 10.1016/j.gendis.2017.10.002

4. Ravanbakhsh H, Karamzadeh V, Bao G, Mongeau L, Juncker D, Zhang YS. Emerging Technologies in Multi-Material Bioprinting. Advanced Materials. 2021;33(49):e2104730. DOI: 10.1002/adma.202104730

5. Saifullah Q, Sharma A. Current trends on innovative technologies in topical wound care for advanced healing and management. Current drug research reviews. 2024;16(3):319–332. DOI: 10.2174/0125899775262048230925054922

6. Kammona O, Tsanaktsidou E, Kiparissides C. Recent Developments in 3D-(Bio)printed Hydrogels as Wound Dressings. Gels. 2024;10(2):147. DOI: 10.3390/gels10020147

7. Amini-Nik S, Yousuf Y, Jeschke MG. Scar management in burn injuries using drug delivery and molecular signaling: Current treatments and future directions. Advanced Drug Delivery Reviews. 2018;123:135–154. DOI: 10.1016/j.addr.2017.07.017

8. Perez-Valle A, Del Amo C, Andia I. Overview of Current Advances in Extrusion Bioprinting for Skin Applications. International Journal of Molecular Sciences. 2020;21(18):6679. DOI: 10.3390/ijms21186679

9. Hierner R, Degreef H, Vranckx JJ, Garmyn M, Massage P, van Brussel M. Skin grafting and wound healing — the «dermato-plastic team approach». American Journal of Clinical Dermatology. 2005;23:343–352.

10. Greenwood JE, Clausen J, Kavanagh S. Experience with Biobrane: uses and caveats for success. Eplasty. 2009;9:e25.

11. Потекаев НН, Фриго НВ, Петерсен ЕВ. Искусственная кожа: виды, области применения. Клиническая дерматология и венерология. 2017;16(6):7–15.

12. Billingham RE, Reynolds J. Transplantation studies on sheets of pure epidermal epithelium and on epidermal cell suspensions. British journal of plastic surgery. 1952;5(1):25–36.

13. Karasek MA, Charlton ME. Growth of postembryonic skin epithelial cells on collagen gels. Journal of Investigative Dermatology. 1971;56(3):205–210.

14. Fredriksson C, Kratz G, Huss F. Transplantation of cultured human keratinocytes in single cell suspension: A comparative in vitro study of different application techniques. Burns. 2008;34(2):212–219.

15. Green H. Regeneration of the skin after grafting of epidermal cultures. Lab Invest. 1989;60(5):583–584.

16. Phillips TJ, Kehinde O, Green H, Gilchrest BA. Treatment of skin ulcers with cultured epidermal allografts. Journal of the American Academy of Dermatology. 1989;21(2):191–199.

17. Королева ТА. Клеточные технологии в лечении детей с глубокими ожогами кожи (обзор литературы). Росcийский вестник. 2013;3(3):35–42.

18. Bell E, Sher S, Hull B, Merrill C, Rosen S, Chamson A, et al. The reconstitution of living skin. Journal of Investigative Dermatology. 1983;81(1):2s–10s.

19. Steffens D, Mathor MB, Santi BT, Luco DP, Pranke P. Development of a biomaterial associated with mesenchymal stem cells and keratinocytes for use as a skin substitute. Regenerative Medicine. 2015;10(8):975–987.

20. Саркисов ДС, Алексеев АА, Глушенков ЕВ. Теоретические и практические аспекты использования культивированных фибробластов при восстановлении целостности кожного покрова. Вестник РАМН. 1994;7:6–11.

21. Зорин ВЛ, Зорина АИ, Петракова ОС, Черкасов ВР. Дермальные фибробласты для лечения дефектов кожи. Гены и клетки. 2009;4:26-40.

22. Wood FM, Stoner ML, Fowler BV, Fear MW. The use of a non-cultured autologous cell suspension and Integra dermal regeneration template to repair full-thickness skin wounds in a porcine model: a one-step process. Burns. 2007;33(6):693–700.

23. Винник ЮС, Салмина АБ, Дробушевская АИ, Теплякова ОВ, Пожиленкова ЕА, Зыкова ЛД. Клеточные технологии и тканевая инженерия в лечении длительно не заживающих ран. Вестник экспериментальной и клинической хирургии. 2011;4:392–397.

24. Moiemen NS, Vlachou E, Staiano JJ, Thawy Y, Frame JD. Reconstructive surgery with Integra dermal regeneration template: histologic study, clinical evaluation, and current practice. Plastic and Reconstructive Surgery. 2006;117:160s–174s.

25. Wainwright DJ. Use of an acellular allograft dermal matrix (AlloDerm) in the management of full-thickness burns. Burns. 1995;21:243–248.

26. Eaglstein WH, Falanga V. Tissue engineering and the development of Apligraf a human skin equivalent. Adv Wound Care (New Rochelle). 1998;11:1–8.

27. Steiglitz BM, Maher RJ, Gratz KR, Schlosser S, Foster J, Pradhan-Bhatt S, et al. The viable bioengineered allogeneic cellularized construct StrataGraft® synthesizes, deposits, and organizes human extracellular matrix proteins into tissue type-specific structures and secretes soluble factors associated with wound healing. Burns. 2024;50(2):424–432. DOI: 10.1016/j.burns.2023.06.001

28. Atala A, Kasper FK, Mikos AG. Engineering complex tissues. Science Translational Medicine. 2012;4:3307-3339.

29. Park KM, Yang JA, Jung H, Yeom J. In situ supramolecular assembly and modular modification of hyaluronic acid hydrogels for 3D cellular engineering. ACS Nano. 2012;6:2960–2968.

30. Zhong S. P., Zhang Y. Z., Lim C. T. Tissue scaffolds for skin wound healing and dermal reconstruction. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology. 2010;2:510–525.

31. Hansbrough J. F., Cooper M. L., Cohen R., Spielvogel R., Greenleaf G., Bartel R. L., Naughton G. Evaluation of a biodegradable matrix containing cultured human fibroblasts as a dermal replacement beneath meshed skin grafts on athymic mice. Surgery. 1992;111:438–46.

32. Ikada Y. Challenges in tissue engineering. Journal of the Royal Society Interface. 2006;3:589–601.

33. Netzlaff F, Kaca M, Bock U, Haltner-Ukomadu E, Meiers P, Lehr C-M, Schaefer UF. Permeability of the reconstructed human epidermis model Episkin in comparison to various human skin preparations. European journal of pharmaceutics and biopharmaceutics. 2007;66:127–34.

34. Duval K, Grover H, Han L-H, Mou Y, Pegoraro AF, Fredberg J, Chen Z. Modeling physiological events in 2D vs. 3D cell culture. Physiology. 2017;32:266–277. DOI: 10.1152/physiol.00036.2016

35. Nikolova MP, Chavali MS. Recent advances in biomaterials for 3D scaffolds: a review. Bioactive Materials. 2019;4:271–292. DOI: 10.1016/j.bioactmat.2019.10.005

36. Foresti R, Rossi S, Pinelli S, Alinovi R, Sciancalepore C, Delmonte N, et al. In-Vivo Vascular Application via Ultra-Fast Bioprinting for Future 5D Personalised Nanomedicine. Scientific Reports. 2020;10(1):3205. DOI: 10.1038/s41598-020-60196-y

37. Amaya-Rivas JL, Perero BS, Helguero CG, Hurel JL, Peralta JM, Flores FA, Alvarado JD. Future Trends of Additive Manufacturing in Medical Applications: An Overview. Heliyon. 2024;10:e26641. DOI: 10.1016/j.heliyon.2024.e26641

38. Melchels FPW, Domingos MAN, Klein TJ, Malda J, Bartolo PJ, Hutmacher DW. Additive manufacturing of tissues and organs. Progress in Polymer Science. 2012;37(8):1079–1104. DOI: 10.1016/j.progpolymsci.2011.11.007

39. Semba JA, Mieloch AA, Rybka JD. Introduction to the State-of-the-Art 3D Bioprinting Methods, Design, and Applications in Orthopedics. Bioprinting. 2020;18:e00070. DOI: 10.1016/j.bprint.2019.e00070

40. Kačarević ŽP, Rider PM, Alkildani S, Retnasingh S, Smeets R, Jung O, et al. An Introduction to 3D Bioprinting: Possibilities, Challenges and Future Aspects. Materials (Basel). 2018;11(11):2199. DOI: 10.3390/ma11112199

41. Olejnik A, Semba JA, Kulpa A, Dańczak-Pazdrowska A, Rybka JD, Gornowicz-Porowska J. 3D Bioprinting in Skin Related Research: Recent Achievements and Application Perspectives. ACS Synthetic Biology. 2022;11(1):26–38. DOI: 10.1021/acssynbio.1c00547

42. Askari M, Naniz MA, Kouhi M, Saberi A, Zolfagharian A, Bodaghi M. Recent Progress in Extrusion 3D Bioprinting of Hydrogel Biomaterials for Tissue Regeneration: A Comprehensive Review with Focus on Advanced Fabrication Techniques. Biomaterials Science. 2021;9(3):535–573. DOI: 10.1039/D0BM00973C

43. Albanna M, Binder KW, Murphy SV, Kim J, Qasem SA, Zhao W, et al. In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds. Scientific Reports. 2019;9(1):1–15. DOI: 10.1038/s41598-018-38366-w

44. Miguel SP, Cabral CSD, Moreira AF, Correia IJ. Production and Characterization of a Novel Asymmetric 3D Printed Construct Aimed for Skin Tissue Regeneration. Colloids Surfaces B Biointerfaces. 2019;181:994–1003. DOI: 10.1016/j.colsurfb.2019.06.063

45. Ventura RD. An Overview of Laser-Assisted Bioprinting (LAB) in Tissue Engineering Applications. Medical Lasers. 2021;10(2):76–81. DOI: 10.25289/ML.2021.10.2.76

46. Derakhshanfar S, Mbeleck R, Xu K, Zhang X, Zhong W, Xing M. 3D Bioprinting for Biomedical Devices and Tissue Engineering: A Review of Recent Trends and Advances. Bioactive Materials. 2018;3(2):144–156. DOI: 10.1016/j.bioactmat.2017.11.008

47. Chameettachal S, Pati F. “Inkjet-Based 3D Bioprinting”. In: Khademhosseini A., editor. 3D Bioprinting in Regenerative Engineering: Principles and Applications (2018). P. 99–118.

48. Gopinathan J, Noh I. Recent trends in bioinks for 3D printing. Biomaterials Research. 2018;22:1–15. DOI: 10.1186/s40824-018-0122-1

49. Baltazar T, Jiang B, Moncayo A, Merola J, Albanna MZ, Saltzman WM, Pober JS. 3D Bioprinting of an Implantable Xeno-Free Vascularized Human Skin Graft. Bioengineering and Translational Medicine. 2022;8(1):e10324. DOI: 10.1002/btm2.10324

50. Cavallo A, Al Kayal T, Mero A, Mezzetta A. Fibrinogen-Based Bioink for Application in Skin Equivalent 3D Bioprinting. Journal of Functional Biomaterials. 2023;14(9):459. DOI: 10.3390/jfb14090459

51. Jiao T, Lian Q, Lian W, Wang Y, Li D, Reis RL, Oliveira JM. Properties of Collagen/Sodium Alginate Hydrogels for Bioprinting of Skin Models. Journal of Bionic Engineering. 2023;20:105–118. DOI: 10.1007/s42235-022-00251-8

52. Liu J, Zhou Z, Zhang M, Song F, Feng C, Liu H. Simple and Robust 3D Bioprinting of Full-Thickness Human Skin Tissue. Bioengineered. 2022;13(4):10087–10097. DOI: 10.1080/21655979.2022.2063651

53. Somasekharan LT, Raju R, Kumar S, Geevarghese R, Nair RP, Kasoju N, Bhatt A. Biofabrication of Skin Tissue Constructs Using Alginate, Gelatin and Diethylaminoethyl Cellulose Bioink. International Journal of Biological Macromolecules. 2021;189:398–409. DOI: 10.1016/j.ijbiomac.2021.08.114

54. Li M, Sun L, Liu Z, Shen Z, Cao Y, Han L, et al. 3D Bioprinting of Heterogeneous Tissue-Engineered Skin Containing Human Dermal Fibroblasts and Keratinocytes. Biomaterials Science. 2023;11:2461–2477.

55. Dai LG, Dai NT, Chen TY, Kang LY, Hsu S. A Bioprinted Vascularized Skin Substitute With Fibroblasts, Keratinocytes, and Endothelial Progenitor Cells for Skin Wound Healing. Bioprinting. 2022;28:e00237.

56. Hafezi F, Shorter S, Tabriz AG, Hurt A, Elmes V, Boateng J, Douroumis D. Bioprinting and Preliminary Testing of Highly Reproducible Novel Bioink for Potential Skin Regeneration. Pharmaceutics. 2020;12(6):550. DOI: 10.3390/pharmaceutics12060550

57. Desanlis A, Albouy M, Rousselle P, Thepot A, Santos MD, Auxenfans C, Marquette C. Validation of an Implantable Bioink Using Mechanical Extraction of Human Skin Cells: First Steps to a 3D Bioprinting Treatment of Deep Second Degree Burn. Journal of Tissue Engineering and Regenerative Medicine. 2021;15(1):37–48. DOI: 10.1002/term.3148

58. Jorgensen AM, Gorkun A, Mahajan N, Willson K, Clouse C, Jeong CG, et al. Multicellular bioprinted skin facilitates human-like skin architecture in vivo. Science Translational Medicine. 2023;4(15):eadf7547. DOI: 10.1126/scitranslmed.adf7547

59. Choi KY, Ajiteru O, Hong H, Suh YJ, Sultan MT, et al. A digital light processing 3D-printed artificial skin model and full-thickness wound models using silk fibroin bioink. Acta Biomater. 2023;1(164):159–174. DOI: 10.1016/j.actbio.2023.04.034

60. Zhang D, Lai L, Fu H, Fu Q, Chen M. 3D-Bioprinted Biomimetic Multilayer Implants Comprising Microfragmented Adipose Extracellular Matrix and Cells Improve Wound Healing in a Murine Model of Full-Thickness Skin Defects. ACS Appl Mater Interfaces. 2023;15(25):29713–29728. DOI: 10.1021/acsami.2c21629

61. Huyan Y, Lian Q, Zhao T, Li D, He J. Pilot Study of the Biological Properties and Vascularization of 3D Printed Bilayer Skin Grafts. International Journal of Bioprinting. 2020;6(1):246. DOI: 10.18063/ijb.v6i1.246

62. Jin R, Cui Y, Chen H, Zhang Z, Weng T, Xia S, et al. Three-dimensional bioprinting of a full-thickness functional skin model using acellular dermal matrix and gelatin methacrylamide bioink. Acta Biomater. 2021;131:248–261. DOI: 10.1016/j.actbio.2021.07.012

63. Lee HR, Park JA, Kim S, Jo Y, Kang D, Jung S. 3D Microextrusion-Inkjet Hybrid Printing of Structured Human Skin Equivalents. Bioprinting. 2021;22:e00143.

64. Qian Z, Sharma D, Jia W, Radke D, Kamp T, Zhao F. Engineering Stem Cell Cardiac Patch with Microvascular Features Representative of Native Myocardium. Theranostics. 2019;9:2143–2157. DOI: 10.7150/thno.29552

65. Plikus MV, Wang X, Sinha S, Forte E, Thompson SM, Herzog EL, et al. Fibroblasts: Origins, Definitions, and Functions in Health and Disease. Cell. 2021;184(15):3852–3872. DOI: 10.1016/j.cell.2021.06.024

66. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453:314–321. DOI: 10.1038/nature07039

67. Knoedler S, Broichhausen S, Guo R, Dai R, Knoedler L, Kauke-Navarro M, et al. Fibroblasts — the cellular choreographers of wound healing. Frontiers in Immunology. 2023;14:1233800. DOI: 10.3389/fimmu.2023.1233800

68. Madelaire CB, Klink AC, Israelsen WJ, Hindle AG. Fibroblasts as an experimental model system for the study of comparative physiology. Comparative Biochemistry and Physiology B. 2022;260:110735. DOI: 10.1016/j.cbpb.2022.110735

69. Wahlsten A, Rütsche D, Nanni M, Giampietro C, Biedermann T, Reichmann E, Mazza E. Mechanical stimulation induces rapid fibroblast proliferation and accelerates the early maturation of human skin substitutes. Biomaterials. 2021;273:120779. DOI: 10.1016/j.biomaterials.2021

70. Kim Y, Park N, Rim YA, Nam Y, Jung H, Lee K, Ju JH. Establishment of a complex skin structure via layered co-culture of keratinocytes and fibroblasts derived from induced pluripotent stem cells. Stem Cell Research and Therapy. 2018;9:1–10. DOI: 10.1186/s13287-018-0958-2

71. Ramin S, Shariati P, Shokrgozar MA, Vossoughi M, Eslamifar A. In vitro Coculture of human skin keratinocytes and fibroblasts on a biocompatible and biodegradable scaffold. Iranian Biomedical Journal. 2009;13:169–177.

72. Lee J, Rabbani C, Gao H, Steinhart M, Woodruff BM, Pflum ZE, et al. Hair-bearing human skin generated entirely from pluripotent stem cells. Nature. 2020;582(7812):399–404. DOI: 10.1038/s41586-020-2352-3

73. Cheng RY, Eylert G, Gariepy JM, He S, Ahmad H, Gao Y, et al. Handheld instrument for wound-conformal delivery of skin precursor sheets improves healing in full-thickness burns. Biofabrication. 2020;12(2):025002. DOI: 10.1088/1758-5090/ab6413

74. Boyce ST, Simpson PS, Rieman MT, Warner PM, Yakuboff KP, Bailey JK, et al. Randomized, paired-site comparison of autologous engineered skin substitutes and split-thickness skin graft for closure of extensive, full-thickness burns. Journal of Burn Care and Research. 2017;38(2):61–70. DOI: 10.1097/BCR.0000000000000401

75. Germain L, Larouche D, Nedelec B, Perreault I, Duranceau L, Bortoluzzi P, et al. Autologous bilayered self-assembled skin substitutes (SASSs) as permanent grafts: a case series of 14 severely burned patients indicating clinical effectiveness. European Cells and Materials. 2018;36:128–141. DOI: 10.22203/eCM.v036a10

76. Riehl BD, Park J-H, Kwon IK, Lim JY. Mechanical stretching for tissue engineering: two-dimensional and three-dimensional constructs. Tissue Engineering — Part B: Reviews. 2012;18(4):288–300. DOI: 10.1089/ten.teb.2011.0465

77. Хесуани ЮД, Сергеева НС, Миронов ВА, Мустафин АГ, Каприн АД. Введение в 3D-биопринтинг: история формирования направления, принципы и этапы биопечати. 2018;14(3):40–47.

78. Mironov V, Kasyanov V, Markwald RR. Organ printing: from bioprinter to organ biofabrication line. Current Opinion in Biotechnology. 2011;22(5):667–673. DOI: 10.1016/j.cop-bio.2011.02.006

79. Amirsadeghi A, Jafari A, Eggermont LJ, Hashemi SS, Bencherif SA, Khorram M. Vascularization strategies for skin tissue engineering. Biomaterials Science. 2020;8(15):4073–4094.

80. Yang GH, Kang D, An S, Ryu JY, Lee K, Kim JS, et al. Advances in the development of tubular structures using extrusion-based 3D cellprinting technology for vascular tissue regenerative applications. Biomaterials Research. 2022;26(1):73.

81. Jiang H, Li X, Chen T, Liu Y, Wang Q, Wang Z, Jia J. Bioprinted vascular tissue: Assessing functions from cellular, tissue to organ levels. Materials Today Bio. 2023;23:100846. DOI: 10.1016/j.mtbio.2023.100846

82. Summerfield A, Meurens F, Ricklin ME. The Immunology of the Porcine Skin and Its Value as a Model for Human Skin. Molecular Immunology. 2015;66(1):14–21. DOI: 10.1016/j.molimm.2014.10.023

83. Sullivan TP, Eaglstein WH, Davis SC, Mertz P. The Pig as a Model for Human Wound Healing. Wound Repair and Regeneration. 2001;9(2):66–76. DOI: 10.1046/j.1524-475X.2001.00066.x

84. Kantaros A, Ganetsos T, Petrescu FIT, Alysandratou E. Bioprinting and Intellectual Property: Challenges, Opportunities, and the Road Ahead. Bioengineering (Basel). 2025;12(1):76. DOI: 10.3390/bioengineering12010076

85. Yadav R, Kumar R, Kathpalia M, Ahmed B, Dua K, Gulati M, et al. Innovative approaches to wound healing: insights into interactive dressings and future directions. Journal of Materials Chemistry B. 2024;12(33):7977–8006. DOI: 10.1039/d3tb02912c

86. Zhu M, Wang Y, Ferracci G, Zheng J, Cho NJ, Lee BH. Gelatin Methacryloyl and Its Hydrogels With an Exceptional Degree of Controllability and Batch-To-Batch Consistency. Scientific Reports. 2019;9(1):6863. DOI: 10.1038/s41598-019-42186-x

87. Nocera AD, Comín R, Salvatierra NA, Cid MP. Development of 3D printed fibrillar collagen scaffold for tissue engineering. Biomedical Microdevices. 2018;20(2):1–13. DOI: 10.1007/s10544-018-0270-z

88. Osidak EO, Karalkin PA, Osidak MS, Parfenov VA, Sivogrivov DE, Pereira FDAS, et al. Viscoll collagen solution as a novel bioink for direct 3D bioprinting. Journal of Materials Science: Materials in Medicine. 2019;30(3):31. DOI: 10.1007/s10856-019-6233-y

89. Heidenreich AC, Pérez-Recalde M, González Wusener A, Hermida ÉB. Collagen and chitosan blends for 3D bioprinting: A rheological and printability approach. Polymer Testing. 2020;82:106297. DOI: 10.1016/j.polymertesting.2019.106297

90. Lee V, Singh G, Trasatti JP, Bjornsson C, Xu X, Tran TN, et al. Design and fabrication of human skin by three-dimensional bioprinting. Tissue Engineering — Part C: Methods. 2014;20(6):473–484. DOI: 10.1089/ten.TEC.2013.0335

91. Kim BS, Kwon YW, Kong JS, Park GT, Gao G, Han W, et al. 3D cell printing of in vitro stabilized skin model and in vivo pre-vascularized skin patch using tissue-specific extracellular matrix bioink: A step towards advanced skin tissue engineering. Biomaterials. 2018;168:38–53. DOI: 10.1016/j.biomaterials.2018.03.040

92. Ковылин РС, Алейник ДА, Федюшкин ИЛ. Современные пористые полимерные имплантаты: получение, свойства, применение. Высокомолекулярные соединения С. 2021;63(1):33–53.

93. Simunovic F, Finkenzeller G. Vascularization strategies in bone tissue engineering. Cells. 2021;10(7):1749. DOI: 10.3390/cells10071749

94. Hutton DL, Moore EM, Gimble JM, Grayson WL. Platelet-derived growth factor and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells. Tissue Engineering — Part A. 2013;19:2076–2086. DOI: 10.1089/ten.TEA.2012.0752

95. Piard C, Luthcke R, Kamalitdinov T, Fisher J. Sustained delivery of vascular endothelial growth factor from mesoporous calcium-deficient hydroxyapatite microparticles promotes in vitro angiogenesis and osteogenesis. Journal of Biomedical Materials Research. 2021;109:1080–1087. DOI: 10.1002/jbm.a.37100

96. Farokhi M, Mottaghitalab F, Ai J, Shokrgozar MA. Sustained release of platelet-derived growth factor and vascular endothelial growth factor from silk/calcium phosphate/PLGA based nanocomposite scaffold. International Journal of Pharmaceutics. 2013;454:216–225. DOI: 10.1016/j.ijpharm.2013.06.080

97. Chen EP, Toksoy Z, Davis BA, Geibel JP. 3D Bioprinting of Vascularized Tissues for in vitro and in vivo Applications. Frontiers in Bioengineering and Biotechnology. 2021;9:664188. DOI: 10.3389/fbioe.2021.664188

98. Mathur V, Agarwal P, Kasturi M, Srinivasan V, Seetharam RN, Vasanthan KS. Innovative bioinks for 3D bioprinting: Exploring technological potential and regulatory challenges. Journal of Tissue Engineering. 2025;16:1-31. DOI: 10.1177/20417314241308022

99. Yaneva A, Shopova D, Bakova D, Mihaylova A, Kasnakova P, Hristozova M, Semerdjieva M. The Progress in Bioprinting and Its Potential Impact on Health-Related Quality of Life. Bioengineering (Basel). 2023;10(8):910. DOI: 10.3390/bioengineering10080910

100. Lam EHY, Yu F, Zhu S, Wang Z. 3D Bioprinting for Next-Generation Personalized Medicine. International Journal of Molecular Sciences. 2023;24(7):6357. DOI: 10.3390/ijms24076357

101. Егоров ИА, Семенчук ОВ. Применение технологии 3D-печати в медицине. Кронос. 2022;7(4):29–32. DOI: 10.52013/2658-7556-66-4-8

102. Шутова АА, Бегишев ИР. Этические принципы создания и применения биопринтных технологий. Russian Journal of Economics and Law. 2025;19(2):448–463. DOI: 10.21202/2782-2923.2025.2.448-463

103. Kreimendahl F, Köpf M, Thiebes AL, Duarte Campos DF, Blaeser A, Schmitz-Rode T, et al. Three-Dimensional Printing and Angiogenesis: Tailored Agarose-Type I Collagen Blends Comprise Three-Dimensional Printability and Angiogenesis Potential for Tissue-Engineered Substitutes. Tissue Engineering Part C: Methods. 2017;23(10):604–615. DOI: 10.1089/ten.TEC.2017.0234

104. Аймалетдинов АМ, Маланьева АГ, Тамбовский МА, Закирова ЕЮ. 3D-биопечать, как метод тканевой инженерии: применение и перспективы. Биотехнология. 2024;40(2):3–22.

105. Zhuang Y, Cui W. Biomaterial-based delivery of nucleic acids for tissue regeneration. Advanced Drug Delivery Reviews. 2021;176:113885. DOI: 10.1016/j.addr.2021.113885

106. Fu H, Zhang D, Zeng J, Fu Q, Chen Z, Sun X, et al. Application of 3D-printed tissue-engineered skin substitute using innovative biomaterial loaded with human adipose-derived stem cells in wound healing. International Journal of Bioprinting. 2023;9(2):674. DOI: 10.18063/ijb.v9i2.674

107. Budharaju H, Sundaramurthi D, Sethuraman S. Embedded 3D bioprinting — An emerging strategy to fabricate biomimetic & large vascularized tissue constructs. Bioactive Materials. 2023;32:356–384. DOI: 10.1016/j.bioactmat.2023.10.012

108. Mobaraki M, Ghaffari M, Yazdanpanah A, Luo Y, Mills DK. Bioinks and bioprinting: A focused review. Bioprinting. 2020;18:e00080.

109. Shende P, Trivedi R. 3D Printed Bioconstructs: Regenerative Modulation for Genetic Expression. Stem Cell Reviews and Reports. 2021;17(4):1239–1250. DOI: 10.1007/s12015-021-10120-2

110. Bremer J, van den Akker PC. In Vivo Models for the Evaluation of Antisense Oligonucleotides in Skin. Methods in Molecular Biology. 2022;2434:315–320. DOI: 10.1007/978-1-0716-2010-6_21

111. Makalish TP, Golovkin IO, Oberemok VV, Laikova KV, Temirova ZZ, Serdyukova OA, et al. Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression. International Journal of Molecular Sciences. 2021;22(3):1022. DOI: 10.3390/ijms22031022

112. Shahin H. Keratinocytes and adipose-derived mesenchymal stem cells: The heir and the spare to regenerative cellular therapies for difficult-to-heal skin wounds. Sweden: Linkoping University (2023).

113. Sekar MP, Budharaju H, Zennifer A, Sethuraman S, Vermeulen N, Sundaramurthi D, Kalaskar DM. Current standards and ethical landscape of engineered tissues-3D bioprinting perspective. Journal of Tissue Engineering. 2021;12:20417314211027677. DOI: 10.1177/20417314211027677