Обоснование. Создание материалов, замещающих костные дефекты, несмотря на множество работ, остается актуальной проблемой в ортопедии и травматологии. Одна из наиболее важных задач — создание условий для адекватной трофики костного имплантата.

Цель — проанализировать современные подходы к васкуляризации костных скаффолдов и оценить их адекватность в моделях in vivo.

Материалы и методы. Представлен обзор литературных данных, посвященный методам васкуляризации костных скаффолдов. Поиск литературы осуществляли в базах данных PubMed, ScienceDirect, eLibrary, Google Scholar в период с 2013 по 2023 г. по ключевым словам. Выявлен 271 источник. После исключения проанализированы 95 статей, результаты 38 оригинальных исследований и одного обзора литературы.

Результаты. Вне зависимости от метода предварительной васкуляризации скаффолдов костные имплантаты проявляют выраженные остеоиндуктивные свойства и способствуют ускоренному восстановлению костной ткани. Конструкции на основе твердых полимеров и кальций-фосфатных соединений также выполняют остеокондуктивную функцию. В качестве основного типа клеток используют мезенхимные стволовые клетки, а также клетки сосудистого типа, которые в синергии оказывают положительный эффект на ремоделирование костного дефекта. Для направленной дифференцировки в остеогенном направлении применяют костный морфогенетический белок, а для дифференцировки в сосудистом направлении — фактор роста эндотелия сосудов.

Заключение. В настоящее время не существует общепринятого метода васкуляризации скаффолдов, отсутствуют и данные о сравнительной эффективности методов васкуляризации, при этом в исследованиях на животных моделях продемонстрировано положительное влияние преваскуляризованных образцов на скорость восстановления как незначительных, так и критических дефектов.

prevascularized bone scaffoldsarteriovenous loops3D bioprintingcell sheetsпреваскуляризованные костные скаффолдыартериовенозные петли3D-биопечатьклеточные листы1.Kneser U, Kaufmann PM, Fiegel HC, et al. Long-term differentiated function of heterotopically transplanted hepatocytes on three-dimensional polymer matrices. J Biomed Mater Res. 1999;47(4):494–503. doi: 10.1002/(sici)1097-4636(19991215)47:4<494::aid-jbm5>3.0.co;2-lKneser U., Kaufmann P.M., Fiegel H.C., et al. Long-term differentiated function of heterotopically transplanted hepatocytes on three-dimensional polymer matrices // J Biomed Mater Res. 1999. Vol. 47, N. 4. P. 494–503. doi: 10.1002/(sici)1097-4636(19991215)47:4<494::aid-jbm5>3.0.co;2-lKneser U, Kaufmann PM, Fiegel HC, et al. Long-term differentiated function of heterotopically transplanted hepatocytes on three-dimensional polymer matrices. J Biomed Mater Res. 1999;47(4):494–503. doi: 10.1002/(sici)1097-4636(19991215)47:4<494::aid-jbm5>3.0.co;2-l2.Kushchayeva Y, Pestun I, Kushchayev S, et al. Advancement in the treatment of osteoporosis and the effects on bone healing. J Clin Med. 2022;11(24):7477. doi: 10.3390/jcm11247477Kushchayeva Y., Pestun I., Kushchayev S., et al. Advancement in the treatment of osteoporosis and the effects on bone healing // J Clin Med. 2022. Vol. 11, N. 24. P. 7477. doi: 10.3390/jcm11247477Kushchayeva Y, Pestun I, Kushchayev S, et al. Advancement in the treatment of osteoporosis and the effects on bone healing. J Clin Med. 2022;11(24):7477. doi: 10.3390/jcm112474773.You Q, Lu M, Li Z, et al. Cell sheet technology as an engineering-based approach to bone regeneration. Int J Nanomedicine. 2022;17:6491–6511. doi: 10.2147/IJN.S382115You Q., Lu M., Li Z., et al. Cell sheet technology as an engineering-based approach to bone regeneration // Int J Nanomedicine. 2022. Vol. 17. P. 6491–6511. doi: 10.2147/IJN.S382115You Q, Lu M, Li Z, et al. Cell sheet technology as an engineering-based approach to bone regeneration. Int J Nanomedicine. 2022;17:6491–6511. doi: 10.2147/IJN.S3821154.Zhang J, Huang Y, Wang Y, et al. Construction of biomimetic cell-sheet-engineered periosteum with a double cell sheet to repair calvarial defects of rats. J Orthop Translat. 2022;38:1–11. doi: 10.1016/j.jot.2022.09.005Zhang J., Huang Y., Wang Y., et al. Construction of biomimetic cell-sheet-engineered periosteum with a double cell sheet to repair calvarial defects of rats // J Orthop Translat. 2023. Vol. 38. P. 1–11. doi: 10.1016/j.jot.2022.09.005Zhang J, Huang Y, Wang Y, et al. Construction of biomimetic cell-sheet-engineered periosteum with a double cell sheet to repair calvarial defects of rats. J Orthop Translat. 2022;38:1–11. doi: 10.1016/j.jot.2022.09.0055.Pirraco RP, Iwata T, Yoshida T, et al. Endothelial cells enhance the in vivo bone-forming ability of osteogenic cell sheets. Lab Invest. 2014;94(6):663–673. doi: 10.1038/labinvest.2014.55Pirraco R.P., Iwata T., Yoshida T., et al. Endothelial cells enhance the in vivo bone-forming ability of osteogenic cell sheets // Lab Invest. 2014. Vol. 94, N. 6. P. 663–673. doi: 10.1038/labinvest.2014.55Pirraco RP, Iwata T, Yoshida T, et al. Endothelial cells enhance the in vivo bone-forming ability of osteogenic cell sheets. Lab Invest. 2014;94(6):663–673. doi: 10.1038/labinvest.2014.556.Kawecki F, Galbraith T, Clafshenkel WP, et al. In vitro prevascularization of self-assembled human bone-like tissues and preclinical assessment using a rat calvarial bone defect model. Materials (Basel). 2021;14(8):2023. doi: 10.3390/ma14082023Kawecki F., Galbraith T., Clafshenkel W.P., et al. In vitro prevascularization of self-assembled human bone-like tissues and preclinical assessment using a rat calvarial bone defect model // Materials (Basel). 2021. Vol. 14, N. 8. P. 2023. doi: 10.3390/ma14082023Kawecki F, Galbraith T, Clafshenkel WP, et al. In vitro prevascularization of self-assembled human bone-like tissues and preclinical assessment using a rat calvarial bone defect model. Materials (Basel). 2021;14(8):2023. doi: 10.3390/ma140820237.Ren L, Ma D, Liu B, et al. Preparation of three-dimensional vascularized MSC cell sheet constructs for tissue regeneration. Biomed Res Int. 2014;2014. doi: 10.1155/2014/301279Ren L., Ma D., Liu B., et al. Preparation of three-dimensional vascularized MSC cell sheet constructs for tissue regeneration // Biomed Res Int. 2014. Vol. 2014. doi: 10.1155/2014/301279Ren L, Ma D, Liu B, et al. Preparation of three-dimensional vascularized MSC cell sheet constructs for tissue regeneration. Biomed Res Int. 2014;2014. doi: 10.1155/2014/3012798.Guo T, Yuan X, Li X, et al. Bone regeneration of mouse critical-sized calvarial defects with human mesenchymal stem cell sheets co-expressing BMP2 and VEGF. J Dent Sci. 2023;18(1):135–144. doi: 10.1016/j.jds.2022.06.020Guo T., Yuan X., Li X., et al. Bone regeneration of mouse critical-sized calvarial defects with human mesenchymal stem cell sheets co-expressing BMP2 and VEGF // J Dent Sci. 2023. Vol. 18, N. 1. P. 135–144. doi: 10.1016/j.jds.2022.06.020 2023Guo T, Yuan X, Li X, et al. Bone regeneration of mouse critical-sized calvarial defects with human mesenchymal stem cell sheets co-expressing BMP2 and VEGF. J Dent Sci. 2023;18(1):135–144. doi: 10.1016/j.jds.2022.06.0209.Lin Z, Zhang X, Fritch MR, et al. Engineering pre-vascularized bone-like tissue from human mesenchymal stem cells through simulating endochondral ossification. Biomaterials. 2022;283. doi: 10.1016/j.biomaterials.2022.121451Lin Z., Zhang X., Fritch M.R., et al. Engineering pre-vascularized bone-like tissue from human mesenchymal stem cells through simulating endochondral ossification // Biomaterials. 2022. Vol. 283. doi: 10.1016/j.biomaterials.2022.121451Lin Z, Zhang X, Fritch MR, et al. Engineering pre-vascularized bone-like tissue from human mesenchymal stem cells through simulating endochondral ossification. Biomaterials. 2022;283. doi: 10.1016/j.biomaterials.2022.12145110.Zhang H, Zhou Y, Yu N, et al. Construction of vascularized tissue-engineered bone with polylysine-modified coral hydroxyapatite and a double cell-sheet complex to repair a large radius bone defect in rabbits. Acta Biomater. 2019;91:82–98. doi: 10.1016/j.actbio.2019.04.024Zhang H., Zhou Y., Yu N., et al. Construction of vascularized tissue-engineered bone with polylysine-modified coral hydroxyapatite and a double cell-sheet complex to repair a large radius bone defect in rabbits // Acta Biomater. 2019. Vol. 91. P. 82–98. doi: 10.1016/j.actbio.2019.04.024Zhang H, Zhou Y, Yu N, et al. Construction of vascularized tissue-engineered bone with polylysine-modified coral hydroxyapatite and a double cell-sheet complex to repair a large radius bone defect in rabbits. Acta Biomater. 2019;91:82–98. doi: 10.1016/j.actbio.2019.04.02411.Zhang D, Gao P, Li Q, et al. Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats. Stem Cell Res Ther. 2017;8(1):134. doi: 10.1186/s13287-017-0592-4Zhang D., Gao P., Li Q., et al. Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats // Stem Cell Res Ther. 2017. Vol. 8, N. 1. P. 134. doi: 10.1186/s13287-017-0592-4Zhang D, Gao P, Li Q, et al. Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats. Stem Cell Res Ther. 2017;8(1):134. doi: 10.1186/s13287-017-0592-412.Zhu W, Qu X, Zhu J, et al. Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture. Biomaterials. 2017;124:106–115. doi: 10.1016/j.biomaterials.2017.01.042Zhu W., Qu X., Zhu J., et al. Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture // Biomaterials. 2017. Vol. 124. P. 106–115. doi: 10.1016/j.biomaterials.2017.01.042Zhu W, Qu X, Zhu J, et al. Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture. Biomaterials. 2017;124:106–115. doi: 10.1016/j.biomaterials.2017.01.04213.Zhang W, Feng C, Yang G, et al. 3D-printed scaffolds with synergistic effect of hollow-pipe structure and bioactive ions for vascularized bone regeneration. Biomaterials. 2017;135:85–95. doi: 10.1016/j.biomaterials.2017.05.005Zhang W., Feng C., Yang G., et al. 3D-printed scaffolds with synergistic effect of hollow-pipe structure and bioactive ions for vascularized bone regeneration // Biomaterials. 2017. Vol. 135. P. 85–95. doi: 10.1016/j.biomaterials.2017.05.005 2017Zhang W, Feng C, Yang G, et al. 3D-printed scaffolds with synergistic effect of hollow-pipe structure and bioactive ions for vascularized bone regeneration. Biomaterials. 2017;135:85–95. doi: 10.1016/j.biomaterials.2017.05.00514.Wang X, Yunru Y, Chaoyu Y, et al. Microfluidic 3D printing responsive scaffolds with biomimetic enrichment channels for bone regeneration. Adv Funct Mater. 2021;31(40). doi: 10.1002/adfm.202105190Wang X., Yunru Y., Chaoyu Y., et al. Microfluidic 3D printing responsive scaffolds with biomimetic enrichment channels for bone regeneration // Adv Funct Mater. 2021. Vol. 31, N. 40. doi: 10.1002/adfm.202105190Wang X, Yunru Y, Chaoyu Y, et al. Microfluidic 3D printing responsive scaffolds with biomimetic enrichment channels for bone regeneration. Adv Funct Mater. 2021;31(40). doi: 10.1002/adfm.20210519015.Xu J, Shen J, Sun Y, et al. In vivo prevascularization strategy enhances neovascularization of β-tricalcium phosphate scaffolds in bone regeneration. J Orthop Translat. 2022;37:143–151. doi: 10.1016/j.jot.2022.09.001Xu J., Shen J., Sun Y., et al. In vivo prevascularization strategy enhances neovascularization of β-tricalcium phosphate scaffolds in bone regeneration // J Orthop Translat. 2022. Vol. 37. P. 143–151. doi: 10.1016/j.jot.2022.09.001Xu J, Shen J, Sun Y, et al. In vivo prevascularization strategy enhances neovascularization of β-tricalcium phosphate scaffolds in bone regeneration. J Orthop Translat. 2022;37:143–151. doi: 10.1016/j.jot.2022.09.00116.Lin Y, Shen J, Sun Y, et al. In vivo prevascularization strategy enhances neovascularization of β-tricalcium phosphate scaffolds in bone regeneration. J Orthop Translat. 2022;35(7):1031–1041. doi: 10.1016/j.jot.2022.09.001 2019Lin Y., Shen J., Sun Y., et al. In vivo prevascularization strategy enhances neovascularization of β-tricalcium phosphate scaffolds in bone regeneration // J Orthop Translat. 2022. Vol. 35, N. 7. P. 1031–1041. doi: 10.1016/j.jot.2022.09.001 2019Lin Y, Shen J, Sun Y, et al. In vivo prevascularization strategy enhances neovascularization of β-tricalcium phosphate scaffolds in bone regeneration. J Orthop Translat. 2022;35(7):1031–1041. doi: 10.1016/j.jot.2022.09.001 201917.Mishra R, Roux BM, Posukonis M, et al. Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds. Biomaterials. 2016;77:255–266. doi: 10.1016/j.biomaterials.2015.10.026Mishra R., Roux B.M., Posukonis M., et al. Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds // Biomaterials. 2016. Vol. 77. P. 255–266. doi: 10.1016/j.biomaterials.2015.10.026Mishra R, Roux BM, Posukonis M, et al. Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds. Biomaterials. 2016;77:255–266. doi: 10.1016/j.biomaterials.2015.10.02618.Buckley C, Madhavarapu S, Kamara Z, et al. In vivo evaluation of the regenerative capacity of a nanofibrous, prevascularized, load-bearing scaffold for bone tissue engineering. Regen Eng Transl Med. 2023. doi: 10.1007/s40883-023-00303-3Buckley C., Madhavarapu S., Kamara Z., et al. In vivo evaluation of the regenerative capacity of a nanofibrous, prevascularized, load-bearing scaffold for bone tissue engineering // Regen Eng Transl Med. 2023. doi: 10.1007/s40883-023-00303-3Buckley C, Madhavarapu S, Kamara Z, et al. In vivo evaluation of the regenerative capacity of a nanofibrous, prevascularized, load-bearing scaffold for bone tissue engineering. Regen Eng Transl Med. 2023. doi: 10.1007/s40883-023-00303-319.Nulty J, Freeman FE, Browe DC, et al. 3D bioprinting of prevascularised implants for the repair of critically-sized bone defects. Acta Biomater. 2021;126:154–169. doi: 10.1016/j.actbio.2021.03.003Nulty J., Freeman F.E., Browe D.C., et al. 3D bioprinting of prevascularised implants for the repair of critically-sized bone defects. Acta Biomater. 2021. Vol. 126. P. 154–169. doi: 10.1016/j.actbio.2021.03.003Nulty J, Freeman FE, Browe DC, et al. 3D bioprinting of prevascularised implants for the repair of critically-sized bone defects. Acta Biomater. 2021;126:154–169. doi: 10.1016/j.actbio.2021.03.00320.Hann SY, Cui H, Esworthy T, et al. Recent advances in 3D printing: vascular network for tissue and organ regeneration. Transl Res. 2019;211:46–63. doi: 10.1016/j.trsl.2019.04.002Hann S.Y., Cui H., Esworthy T., et al. Recent advances in 3D printing: vascular network for tissue and organ regeneration // Transl Res. 2019. Vol. 211. P. 46–63. doi: 10.1016/j.trsl.2019.04.002Hann SY, Cui H, Esworthy T, et al. Recent advances in 3D printing: vascular network for tissue and organ regeneration. Transl Res. 2019;211:46–63. doi: 10.1016/j.trsl.2019.04.00221.Li C, Han X, Ma Z, et al. Engineered customizable microvessels for progressive vascularization in large regenerative implants. Adv Healthc Mater. 2022;11(4). doi: 10.1002/adhm.202101836Li C., Han X., Ma Z., et al. Engineered customizable microvessels for progressive vascularization in large regenerative implants // Adv Healthc Mater. 2022. Vol. 11, N. 4. doi: 10.1002/adhm.202101836Li C, Han X, Ma Z, et al. Engineered customizable microvessels for progressive vascularization in large regenerative implants. Adv Healthc Mater. 2022;11(4). doi: 10.1002/adhm.20210183622.Anada T, Pan CC, Stahl AM, et al. Vascularized bone-mimetic hydrogel constructs by 3d bioprinting to promote osteogenesis and angiogenesis. Int J Mol Sci. 2019;20(5):1096. doi: 10.3390/ijms20051096Anada T., Pan C.C., Stahl A.M., et al. Vascularized bone-mimetic hydrogel constructs by 3D bioprinting to promote osteogenesis and angiogenesis // Int J Mol Sci. 2019. Vol. 20, N. 5. P. 1096. doi: 10.3390/ijms20051096Anada T, Pan CC, Stahl AM, et al. Vascularized bone-mimetic hydrogel constructs by 3d bioprinting to promote osteogenesis and angiogenesis. Int J Mol Sci. 2019;20(5):1096. doi: 10.3390/ijms2005109623.Kuss MA, Wu S, Wang Y, et al. Prevascularization of 3D printed bone scaffolds by bioactive hydrogels and cell co-culture. J Biomed Mater Res B Appl Biomater. 2018;106(5):1788–1798. doi: 10.1002/jbm.b.33994Kuss M.A., Wu S., Wang Y., et al. Prevascularization of 3D printed bone scaffolds by bioactive hydrogels and cell co-culture // J Biomed Mater Res B Appl Biomater. 2018. Vol. 106, N. 5. P. 1788–1798. doi: 10.1002/jbm.b.33994Kuss MA, Wu S, Wang Y, et al. Prevascularization of 3D printed bone scaffolds by bioactive hydrogels and cell co-culture. J Biomed Mater Res B Appl Biomater. 2018;106(5):1788–1798. doi: 10.1002/jbm.b.3399424.Shabunin AS, Asadulaev MS, Vissarionov SV, et al. Surgical treatment of children with extensive bone defects (literature review). Pediatric Traumatology, Orthopaedics and Reconstructive Surgery. 2021;9(3):353–366. EDN: XHHVUM doi: 10.17816/PTORS65071Шабунин А.С., Асадулаев М.С., Виссарионов С.В., и др. Хирургическое лечение детей с обширными дефектами костной ткани (обзор литературы) // Ортопедия, травматология и восстановительная хирургия детского возраста. 2021. Т. 9, № 3. C. 353–366. EDN: XHHVUM doi: 10.17816/PTORS65071Shabunin AS, Asadulaev MS, Vissarionov SV, et al. Surgical treatment of children with extensive bone defects (literature review). Pediatric Traumatology, Orthopaedics and Reconstructive Surgery. 2021;9(3):353–366. EDN: XHHVUM doi: 10.17816/PTORS6507125.Weigand A, Beier JP, Hess A, et al. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization. Tissue Eng Part A. 2015;21(9–10):1680–1694. doi: 10.1089/ten.TEA.2014.0568Weigand A., Beier J.P., Hess A., et al. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization // Tissue Eng Part A. 2015. Vol. 21, N. 9–10. P. 1680–1694. doi: 10.1089/ten.TEA.2014.0568Weigand A, Beier JP, Hess A, et al. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization. Tissue Eng Part A. 2015;21(9–10):1680–1694. doi: 10.1089/ten.TEA.2014.056826.Steiner D, Reinhardt L, Fischer L, et al. Impact of endothelial progenitor cells in the vascularization of osteogenic scaffolds. Cells. 2022;11(6):926. doi: 10.3390/cells11060926Steiner D., Reinhardt L., Fischer L., et al. Impact of endothelial progenitor cells in the vascularization of osteogenic scaffolds // Cells. 2022. Vol. 11, N. 6. doi: 10.3390/cells11060926Steiner D, Reinhardt L, Fischer L, et al. Impact of endothelial progenitor cells in the vascularization of osteogenic scaffolds. Cells. 2022;11(6):926. doi: 10.3390/cells1106092627.Koepple C, Pollmann L, Pollmann NS, et al. Microporous polylactic acid scaffolds enable fluorescence-based perfusion imaging of intrinsic in vivo vascularization. Int J Mol Sci. 2023;24(19). doi: 10.3390/ijms241914813Koepple C., Pollmann L., Pollmann N.S., et al. Microporous polylactic acid scaffolds enable fluorescence-based perfusion imaging of intrinsic in vivo vascularization // Int J Mol Sci. 2023. Vol. 24, N. 19. doi: 10.3390/ijms241914813Koepple C, Pollmann L, Pollmann NS, et al. Microporous polylactic acid scaffolds enable fluorescence-based perfusion imaging of intrinsic in vivo vascularization. Int J Mol Sci. 2023;24(19). doi: 10.3390/ijms24191481328.Kratzer S, Arkudas A, Himmler M, et al. Vascularization of poly-ε-caprolactone-collagen i-nanofibers with or without sacrificial fibers in the neurotized arteriovenous loop model. Cells. 2022;11(23). doi: 10.3390/cells11233774Kratzer S., Arkudas A., Himmler M., et al. Vascularization of poly-ε-caprolactone-collagen i-nanofibers with or without sacrificial fibers in the neurotized arteriovenous loop model // Cells. 2022. Vol. 11, N. 23. doi: 10.3390/cells11233774Kratzer S, Arkudas A, Himmler M, et al. Vascularization of poly-ε-caprolactone-collagen i-nanofibers with or without sacrificial fibers in the neurotized arteriovenous loop model. Cells. 2022;11(23). doi: 10.3390/cells1123377429.Eweida A, Flechtenmacher S, Sandberg E, et al. Systemically injected bone marrow mononuclear cells specifically home to axially vascularized tissue engineering constructs. PLoS One. 2022;17(8). doi: 10.1371/journal.pone.0272697Eweida A., Flechtenmacher S., Sandberg E., et al. Systemically injected bone marrow mononuclear cells specifically home to axially vascularized tissue engineering constructs // PLoS One. 2022. Vol. 17, N. 8. doi: 10.1371/journal.pone.0272697 2022Eweida A, Flechtenmacher S, Sandberg E, et al. Systemically injected bone marrow mononuclear cells specifically home to axially vascularized tissue engineering constructs. PLoS One. 2022;17(8). doi: 10.1371/journal.pone.027269730.Vaghela R, Arkudas A, Gage D, et al. Microvascular development in the rat arteriovenous loop model in vivo – A step by step intravital microscopy analysis. J Biomed Mater Res A. 2022;110(9):1551–1563. doi: 10.1002/jbm.a.37395Vaghela R., Arkudas A., Gage D., et al. Microvascular development in the rat arteriovenous loop model in vivo – a step by step intravital microscopy analysis // J Biomed Mater Res A. 2022. Vol. 110, N. 9. P. 1551–1563. doi: 10.1002/jbm.a.37395Vaghela R, Arkudas A, Gage D, et al. Microvascular development in the rat arteriovenous loop model in vivo – A step by step intravital microscopy analysis. J Biomed Mater Res A. 2022;110(9):1551–1563. doi: 10.1002/jbm.a.3739531.Kim BS, Chen SH, Vasella M, 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: 10.3390/pharmaceutics14020417Kim B.S., Chen S.H., Vasella M., et al. In vivo evaluation of mechanically processed stromal vascular fraction in a chamber vascularized by an arteriovenous shunt // Pharmaceutics. 2022. Vol. 14, N. 2. P. 417. doi: 10.3390/pharmaceutics14020417Kim BS, Chen SH, Vasella M, 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: 10.3390/pharmaceutics1402041732.Yuan Q, Bleiziffer O, Boos AM, et al. PHDs inhibitor DMOG promotes the vascularization process in the AV loop by HIF-1a up-regulation and the preliminary discussion on its kinetics in rat. BMC Biotechnol. 2014;14:112. doi: 10.1186/s12896-014-0112-xYuan Q., Bleiziffer O., Boos A.M., et al. PHDs inhibitor DMOG promotes the vascularization process in the AV loop by HIF-1a up-regulation and the preliminary discussion on its kinetics in rat // BMC Biotechnol. 2014. Vol. 14, N. 1. P. 112. doi: 10.1186/s12896-014-0112-xYuan Q, Bleiziffer O, Boos AM, et al. PHDs inhibitor DMOG promotes the vascularization process in the AV loop by HIF-1a up-regulation and the preliminary discussion on its kinetics in rat. BMC Biotechnol. 2014;14:112. doi: 10.1186/s12896-014-0112-x33.Biggemann J, Pezoldt M, Stumpf M, et al. Modular ceramic scaffolds for individual implants. Acta Biomater. 2018;80:390–400. doi: 10.1016/j.actbio.2018.09.008Biggemann J., Pezoldt M., Stumpf M., et al. Modular ceramic scaffolds for individual implants // Acta Biomater. 2018. Vol. 80. P. 390–400. doi: 10.1016/j.actbio.2018.09.008 2018Biggemann J, Pezoldt M, Stumpf M, et al. Modular ceramic scaffolds for individual implants. Acta Biomater. 2018;80:390–400. doi: 10.1016/j.actbio.2018.09.00834.Kengelbach-Weigand A, Thielen C, Bäuerle T, et al. Personalized medicine for reconstruction of critical-size bone defects – a translational approach with customizable vascularized bone tissue. NPJ Regen Med. 2021;6(1):49. doi: 10.1038/s41536-021-00158-8Kengelbach-Weigand A., Thielen C., Bäuerle T., et al. Personalized medicine for reconstruction of critical-size bone defects – a translational approach with customizable vascularized bone tissue // NPJ Regen Med. 2021. Vol. 6, N. 1. P. 49. doi: 10.1038/s41536-021-00158-8Kengelbach-Weigand A, Thielen C, Bäuerle T, et al. Personalized medicine for reconstruction of critical-size bone defects – a translational approach with customizable vascularized bone tissue. NPJ Regen Med. 2021;6(1):49. doi: 10.1038/s41536-021-00158-835.Wu X, Wang Q, Kang N, et al. The effects of different vascular carrier patterns on the angiogenesis and osteogenesis of BMSC-TCP-based tissue-engineered bone in beagle dogs. J Tissue Eng Regen Med. 2017;11(2):542–552. doi: 10.1002/term.2076Wu X., Wang Q., Kang N., et al. The effects of different vascular carrier patterns on the angiogenesis and osteogenesis of BMSC-TCP-based tissue-engineered bone in beagle dogs // J Tissue Eng Regen Med. 2017. Vol. 11, N. 2. P. 542–552. doi: 10.1002/term.2076Wu X, Wang Q, Kang N, et al. The effects of different vascular carrier patterns on the angiogenesis and osteogenesis of BMSC-TCP-based tissue-engineered bone in beagle dogs. J Tissue Eng Regen Med. 2017;11(2):542–552. doi: 10.1002/term.207636.Yang YP, Gadomski BC, Bruyas A, et al. Investigation of a prevascularized bone graft for large defects in the ovine tibia. Tissue Eng Part A. 2021;27(23–24):1458–1469. doi: 10.1089/ten.TEA.2020.0347Yang Y.P., Gadomski B.C., Bruyas A., et al. Investigation of a prevascularized bone graft for large defects in the ovine tibia // Tissue Eng Part A. 2021. Vol. 27, N. 23–24. P. 1458–1469. doi: 10.1089/ten.TEA.2020.0347Yang YP, Gadomski BC, Bruyas A, et al. Investigation of a prevascularized bone graft for large defects in the ovine tibia. Tissue Eng Part A. 2021;27(23–24):1458–1469. doi: 10.1089/ten.TEA.2020.034737.Yang YP, Labus KM, Gadomski BC, et al. Osteoinductive 3D printed scaffold healed 5 cm segmental bone defects in the ovine metatarsus. Sci Rep. 2021;11(1). doi: 10.1038/s41598-021-86210-5Yang Y.P., Labus K.M., Gadomski B.C., et al. Osteoinductive 3D printed scaffold healed 5 cm segmental bone defects in the ovine metatarsus // Sci Rep. 2021. Vol. 11, N. 1. P. 6704. doi: 10.1038/s41598-021-86210-5Yang YP, Labus KM, Gadomski BC, et al. Osteoinductive 3D printed scaffold healed 5 cm segmental bone defects in the ovine metatarsus. Sci Rep. 2021;11(1). doi: 10.1038/s41598-021-86210-538.Vidal L, Brennan MÁ, Krissian S, et al. In situ production of pre-vascularized synthetic bone grafts for regenerating critical-sized defects in rabbits. Acta Biomater. 2020;114:384–394. doi: 10.1016/j.actbio.2020.07.030Vidal L., Brennan M.Á., Krissian S., et al. In situ production of pre-vascularized synthetic bone grafts for regenerating critical-sized defects in rabbits // Acta Biomater. 2020. Vol. 114. P. 384–394. doi: 10.1016/j.actbio.2020.07.030Vidal L, Brennan MÁ, Krissian S, et al. In situ production of pre-vascularized synthetic bone grafts for regenerating critical-sized defects in rabbits. Acta Biomater. 2020;114:384–394. doi: 10.1016/j.actbio.2020.07.03039.Kawai T, Pan CC, Okuzu Y, et al. Combining a vascular bundle and 3D printed scaffold with BMP-2 improves bone repair and angiogenesis. Tissue Eng Part A. 2021;27(23–24):1517–1525. doi: 10.1089/ten.TEA.2021.0049Kawai T., Pan C.C., Okuzu Y., et al. Combining a vascular bundle and 3D printed scaffold with bmp-2 improves bone repair and angiogenesis // Tissue Eng Part A. 2021. Vol. 27, N. 23–24. P. 1517–1525. doi: 10.1089/ten.TEA.2021.0049Kawai T, Pan CC, Okuzu Y, et al. Combining a vascular bundle and 3D printed scaffold with BMP-2 improves bone repair and angiogenesis. Tissue Eng Part A. 2021;27(23–24):1517–1525. doi: 10.1089/ten.TEA.2021.0049