无支架3D工程化脂肪的构建
Construction of Scaffold-Free 3D Engineered Adipose
DOI: 10.12677/ACM.2024.141008, PDF,   
作者: 高博涛:西安医学院,陕西 西安;空军军医大学第一附属医院整形外科,陕西 西安;秦子矜:空军军医大学第一附属医院整形外科,陕西 西安
关键词: 脂肪组织工程无支架自组装生物反应器磁悬浮Adipose Tissue Engineering Scaffold-Free Self-Assembly Bioreactors Magnetic Levitation
摘要: 脂肪组织工程是创伤、肿瘤切除后软组织缺损潜在的治疗方法,大多数方法都依赖于使用外源性3D支架来再生脂肪组织。近年来,随着生物制造技术的不断发展,无支架3D工程化脂肪的制备已成为一种备受关注的生物制造方法。由于无支架组织结构不需要细胞粘附在外源材料上并且只涉及细胞和细胞衍生基质,因此无支架组织工程比基于支架的方法提供了许多优势:1) 没有引入任何外源性杂质;2) 小分子扩散、细胞之间的信号传递、细胞迁移不受移植后的影响;3) 仅依赖细胞产生基质。本文综述了脂肪组织工程的三种主要无支架方法:自组装技术,生物反应器和磁悬浮技术,详细阐述了近年来的研究进展及优缺点。
Abstract: Adipose tissue engineering is a potential treatment for soft tissue defects after trauma and tumor resection, most of which rely on the use of exogenous 3D scaffolds to regenerate adipose tissue. In recent years, with the continuous development of biomanufacturing technology, the preparation of stent-free 3D engineered fats has become a kind of biomanufacturing method. Since stentless tissue structures do not require cell adherence to foreign materials and involve only cells and cell-derived matrices, stentless tissue engineering offers many advantages over stent-based approaches: 1) No exogenous impurities are introduced; 2) The diffusion of small molecules, signal transmission be-tween cells and cell migration were not affected by transplantation; 3) Matrix production depends only on cells. In this paper, three main stent-free methods for adipose tissue engineering, self-assembly, bioreactor and magnetic levitation, are reviewed. The research progress, advantages and disadvantages in recent years are described in detail.
文章引用:高博涛, 秦子矜. 无支架3D工程化脂肪的构建[J]. 临床医学进展, 2024, 14(1): 55-62. https://doi.org/10.12677/ACM.2024.141008

参考文献

[1] Fischbach, C., Seufert, J., Staiger, H., et al. (2004) Three-Dimensional in Vitro Model of Adipogenesis: Comparison of Culture Conditions. Tissue Engineering, 10, 215-229. [Google Scholar] [CrossRef] [PubMed]
[2] Fischbach, C., Spruss, T., Weiser, B., et al. (2004) Generation of Mature Fat Pads in Vitro and in Vivo Utilizing 3-D Long-Term Culture of 3T3-L1 Preadipocytes. Experimental Cell Research, 300, 54-64. [Google Scholar] [CrossRef] [PubMed]
[3] Patrick Jr., C.W., Zheng, B., Johnston, C., et al. (2002) Long-Term Implantation of Preadipocyte-Seeded PLGA Scaffolds. Tissue Engineering, 8, 283-293. [Google Scholar] [CrossRef] [PubMed]
[4] Patrick Jr., C.W., Chauvin, P.B., Hobley, J., et al. (1999) Preadipocyte Seeded PLGA Scaffolds for Adipose Tissue Engineering. Tissue Engineering, 5, 139-151. [Google Scholar] [CrossRef] [PubMed]
[5] Alhadlaq, A., Tang, M. and Mao, J.J. (2005) Engineered Adipose Tis-sue from Human Mesenchymal Stem Cells Maintains Predefined Shape and Dimension: Implications in Soft Tissue Augmentation and Reconstruction. Tissue Engineering, 11, 556-566. [Google Scholar] [CrossRef] [PubMed]
[6] Hong, L., Peptan, I., Clark, P., et al. (2005) Ex Vivo Adipose Tissue Engineering by Human Marrow Stromal Cell Seeded Gelatin Sponge. Annals of Biomedical Engineering, 33, 511-517. [Google Scholar] [CrossRef] [PubMed]
[7] Neubauer, M., Hacker, M., Bauer-Kreisel, P., et al. (2005) Adi-pose Tissue Engineering Based on Mesenchymal Stem Cells and Basic Fibroblast Growth Factor in Vitro. Tissue Engi-neering, 11, 1840-1851. [Google Scholar] [CrossRef] [PubMed]
[8] Guilak, F., Cohen, D.M., Estes, B.T., et al. (2009) Control of Stem Cell Fate by Physical Interactions with the Extracellular Matrix. Cell Stem Cell, 5, 17-26. [Google Scholar] [CrossRef] [PubMed]
[9] Girandon, L., Kregar-Velikonja, N., Božikov, K., et al. (2011) In Vitro Models for Adipose Tissue Engineering with Adipose-Derived Stem Cells Using Different Scaffolds of Natural Origin. Folia Biologica, 57, 47-56.
[10] Stacey, D.H., Hanson, S.E., Lahvis, G., et al. (2009) In Vitro Adipogenic Dif-ferentiation of Preadipocytes Varies with Differentiation Stimulus, Culture Dimensionality, and Scaffold Composition. Tissue Engineering Part A, 15, 3389-3399. [Google Scholar] [CrossRef] [PubMed]
[11] Yang, Y.I., Kim, H.I., Choi, M.Y., et al. (2010) Ex Vivo Organ Culture of Adipose Tissue for in Situ Mobilization of Adipose-Derived Stem Cells and Defining the Stem Cell Niche. Journal of Cellular Physiology, 224, 807-816. [Google Scholar] [CrossRef] [PubMed]
[12] Von Heimburg, D., Zachariah, S., Heschel, I., et al. (2001) Human Preadi-pocytes Seeded on Freeze-Dried Collagen Scaffolds Investigated in Vitro and in Vivo. Biomaterials, 22, 429-438. [Google Scholar] [CrossRef
[13] Kimura, Y., Ozeki, M., Inamoto, T., et al. (2003) Adipose Tissue Engineering Based on Human Preadipocytes Combined with Gelatin Microspheres Containing Basic Fibroblast Growth Factor. Biomaterials, 24, 2513-2521. [Google Scholar] [CrossRef
[14] Halbleib, M., Skurk, T., De Luca, C., et al. (2003) Tissue Engineering of White Adipose Tissue Using Hyaluronic Acid-Based Scaffolds. I: In Vitro Differentiation of Human Ad-ipocyte Precursor Cells on Scaffolds. Biomaterials, 24, 3125-3132. [Google Scholar] [CrossRef
[15] Marler, J.J., Guha, A., Rowley, J., et al. (2000) Soft-Tissue Augmentation with Injectable Alginate and Syngeneic Fibroblasts. Plastic and Reconstructive Surgery, 105, 2049-2058. [Google Scholar] [CrossRef] [PubMed]
[16] Choi, Y.S., Park, S.N. and Suh, H. (2005) Adipose Tissue Engineering Using Mesenchymal Stem Cells Attached to Injectable PLGA Spheres. Biomaterials, 26, 5855-5863. [Google Scholar] [CrossRef] [PubMed]
[17] Kral, J.G. and Crandall, D.L. (1999) Development of a Human Adipocyte Synthetic Polymer Scaffold. Plastic and Reconstructive Surgery, 104, 1732-1738. [Google Scholar] [CrossRef] [PubMed]
[18] Timmins, N.E. and Nielsen, L.K. (2007) Generation of Multicellular Tumor Spheroids by the Hanging-Drop Method. Methods in Molecular Medicine, 140, 141-151. [Google Scholar] [CrossRef] [PubMed]
[19] Sart, S., Agathos, S.N., Li, Y., et al. (2016) Regulation of Mesenchymal Stem Cell 3D Microenvironment: From Macro to Microfluidic Bioreactors. Biotechnology Journal, 11, 43-57. [Google Scholar] [CrossRef] [PubMed]
[20] Anil-Inevi, M., Yaman, S., Yildiz, A.A., et al. (2018) Biofab-rication of in Situ Self Assembled 3D Cell Cultures in a Weightlessness Environment Generated using Magnetic Levita-tion. Scientific Reports, 8, Article No. 7239. [Google Scholar] [CrossRef] [PubMed]
[21] Bohrnsen, F., Lindner, U., Meier, M., et al. (2009) Murine Mesenchymal Progenitor Cells from Different Tissues Differentiated via Mesenchymal Microspheres into the Mesoder-mal Direction. BMC Molecular and Cell Biology, 10, Article No. 92. [Google Scholar] [CrossRef] [PubMed]
[22] Mandl, M., Viertler, H.P., Hatzmann, F.M., et al. (2022) An Organ-oid Model Derived from Human Adipose Stem/ Progenitor Cells to Study Adipose Tissue Physiology. Adipocyte, 11, 164-174. [Google Scholar] [CrossRef] [PubMed]
[23] Baraniak, P.R. and Mcdevitt, T.C. (2012) Scaffold-Free Culture of Mesenchymal Stem Cell Spheroids in Suspension Preserves Multilineage Potential. Cell and Tissue Research, 347, 701-711. [Google Scholar] [CrossRef] [PubMed]
[24] Wang, Y.H., Wu, J.Y., Chou, P.J., et al. (2014) Characterization and Evaluation of the Differentiation Ability of Human Adipose-Derived Stem Cells Growing in Scaf-fold-Free Suspension Culture. Cytotherapy, 16, 485-495. [Google Scholar] [CrossRef] [PubMed]
[25] Shen, J.X., Couchet, M., Dufau, J., et al. (2021) 3D Adipose Tissue Culture Links the Organotypic Microenvironment to Improved Adipogenesis. Advanced Science (Weinh), 8, e2100106. [Google Scholar] [CrossRef] [PubMed]
[26] Fitzgerald, S.J., Cobb, J.S., Janorkar, A.V. (2020) Comparison of the Formation, Adipogenic Maturation, and Retention of Human Adipose-Derived Stem Cell Spheroids in Scaffold-Free Culture Techniques. Journal of Biomedical Materials Research Part B, 108, 3022-3032. [Google Scholar] [CrossRef] [PubMed]
[27] Vallee, M., Cote, J.F. and Fradette, J. (2009) Adipose-Tissue Engineering: Taking Advantage of the Properties of Human Adipose-Derived Stem/Stromal Cells. Pathologie Biologie (Paris), 57, 309-317. [Google Scholar] [CrossRef] [PubMed]
[28] Vermette, M., Trottier, V., Menard, V., et al. (2007) Production of a New Tissue-Engineered Adipose Substitute from Human Adipose-Derived Stromal Cells. Biomaterials, 28, 2850-2860. [Google Scholar] [CrossRef] [PubMed]
[29] Verseijden, F., Posthumus-Van, Sluijs, S.J., Farrell, E., et al. (2010) Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon Im-plantation. Cell Transplantation, 19, 1007-1020. [Google Scholar] [CrossRef
[30] Miyamoto, Y., Ikeuchi, M., Noguchi, H., et al. (2017) Enhanced Adipogenic Differentiation of Human Adipose-Derived Stem Cells in an in Vitro Microenvironment: The Preparation of Adipose-Like Microtissues Using a Three-Dimensional Culture. Cell Medicine, 9, 35-44. [Google Scholar] [CrossRef
[31] Miyagawa, Y., Okita, H., Hiroyama, M., et al. (2011) A Micro-fabricated Scaffold Induces the Spheroid Formation of Human Bone Marrow-Derived Mesenchymal Progenitor Cells and Promotes Efficient Adipogenic Differentiation. Tissue Engineering Part A, 17, 513-521. [Google Scholar] [CrossRef] [PubMed]
[32] Matsuda, Y., Ishiwata, T., Kawamoto, Y., et al. (2010) Morpholog-ical and Cytoskeletal Changes of Pancreatic Cancer Cells in Three-Dimensional Spheroidal Culture. Medical Molecular Morphology, 43, 211-217. [Google Scholar] [CrossRef] [PubMed]
[33] Ho Ye, S., Watanabe, J., Takai, M., et al. (2006) High Functional Hollow Fiber Membrane Modified with Phospholipid Polymers for a Liver Assist Bioreactor. Biomaterials, 27, 1955-1962. [Google Scholar] [CrossRef] [PubMed]
[34] Monga, S.P., Hout, M.S., Baun, M.J., et al. (2005) Mouse Fetal Liver Cells in Artificial Capillary Beds in Three- Dimensional Four-Compartment Bioreactors. The American Jour-nal of Pathology, 167, 1279-1292. [Google Scholar] [CrossRef
[35] Chen, C., Chen, K. and Yang, S.T. (2003) Effects of Three-Dimensional Culturing on Osteosarcoma Cells Grown in a Fibrous Matrix: Analyses of Cell Morphology, Cell Cycle, and Apoptosis. Biotechnology Progress, 19, 1574-1582. [Google Scholar] [CrossRef] [PubMed]
[36] Lin, H.J., O’shaughnessy, T.J., Kelly, J., et al. (2004) Neural Stem Cell Differentiation in a Cell-Collagen-Bioreactor Culture System. Developmental Brain Research, 153, 163-173. [Google Scholar] [CrossRef] [PubMed]
[37] Haut, B., Amor, H.B., Coulon, L., et al. (2003) Hydrody-namics and Mass Transfer in a Couette-Taylor Bioreactor for the Culture of Animal Cells. Chemical Engineering Science, 58, 777-784. [Google Scholar] [CrossRef
[38] Gomes, M.E., Bossano, C.M., Johnston, C.M., et al. (2006) In Vitro Localization of Bone Growth Factors in Constructs of Biodegradable Scaffolds Seeded with Marrow Stromal Cells and Cultured in a Flow Perfusion Bioreactor. Tissue Engineering, 12, 177-188. [Google Scholar] [CrossRef] [PubMed]
[39] Lv, D., Hu, Z., Lu, L., et al. (2017) Three-Dimensional Cell Culture: A Powerful Tool in Tumor Research and Drug Discovery. Oncology Letters, 14, 6999-7010. [Google Scholar] [CrossRef] [PubMed]
[40] Hidalgo-Bastida, L.A., Thirunavukkarasu, S., Griffiths, S., et al. (2012) Modeling and Design of Optimal Flow Perfusion Bioreactors for Tissue Engineering Applications. Biotechnology & Bi-oengineering, 109, 1095-109. [Google Scholar] [CrossRef] [PubMed]
[41] Riddle, R.C., Taylor, A.F., Genetos, D.C., et al. (2006) MAP Kinase and Calcium Signaling Mediate Fluid Flow-Induced Human Mesenchymal Stem Cell Proliferation. American Journal of Physiology-Cell Physiology, 290, C776-C784. [Google Scholar] [CrossRef] [PubMed]
[42] Yamamoto, K., Sokabe, T., Watabe, T., et al. (2005) Fluid Shear Stress Induces Differentiation of Flk-1-Positive Embryonic Stem Cells into Vascular Endothelial Cells in Vitro. The American Journal of Physiology-Heart and Circulatory Physiology, 288, H1915-H1924. [Google Scholar] [CrossRef] [PubMed]
[43] Born, G., Plantier, E., Nannini, G., et al. (2022) Mini- and Mac-ro-Scale Direct Perfusion Bioreactors with Optimized Flow for Engineering 3D Tissues. Biotechnology Journal, 18, e2200405. [Google Scholar] [CrossRef] [PubMed]
[44] Martin, Y. and Vermette, P. (2005) Bioreactors for Tissue Mass Culture: Design, Characterization, and Recent Advances. Biomaterials, 26, 7481-7503. [Google Scholar] [CrossRef] [PubMed]
[45] Gerlach, J.C., Lin, Y.C., Brayfield, C.A., et al. (2012) Ad-ipogenesis of Human Adipose-Derived Stem Cells within Three-Dimensional Hollow Fiber-Based Bioreactors. Tissue Engineering Part C: Methods, 18, 54-61. [Google Scholar] [CrossRef] [PubMed]
[46] Mirica, K.A., Ilievski, F., Ellerbee, A.K., et al. (2011) Using Mag-netic Levitation for Three Dimensional Self-Assembly. Advanced Materials, 23, 4134-4140. [Google Scholar] [CrossRef] [PubMed]
[47] Yaman, S., Anil-Inevi, M., Ozcivici, E., et al. (2018) Magnetic Force-Based Microfluidic Techniques for Cellular and Tissue Bioengineering. Frontiers in Bioengineering and Biotech-nology, 6, Article 192. [Google Scholar] [CrossRef] [PubMed]
[48] Daquinag, A.C., Souza, G.R. and Kolonin, M.G. (2013) Adipose Tissue Engineering in Three-Dimensional Levitation Tissue Culture System Based on Magnetic Nanoparticles. Tissue Engineering Part C: Methods, 19, 336-344. [Google Scholar] [CrossRef] [PubMed]
[49] Tseng, H., Daquinag, A.C., Souza, G.R., et al. (2018) Three-Dimensional Magnetic Levitation Culture System Simulating White Adipose Tissue. Methods in Molecular Biolo-gy, 1773, 147-154. [Google Scholar] [CrossRef] [PubMed]
[50] Abakumov, M.A., Semkina, A.S., Skorikov, A.S., et al. (2018) Toxicity of Iron Oxide Nanoparticles: Size and Coating Effects. Journal of Biochemical and Molecular Toxicology, 32, e22225. [Google Scholar] [CrossRef] [PubMed]
[51] Alarifi, S., Ali, D., Alkahtani, S., et al. (2014) Iron Oxide Nanopar-ticles Induce Oxidative Stress, DNA Damage, and Caspase Activation in the Human Breast Cancer Cell Line. Biological Trace Element Research, 159, 416-424. [Google Scholar] [CrossRef] [PubMed]
[52] Feng, Q., Liu, Y., Huang, J., et al. (2018) Uptake, Distribution, Clearance, and Toxicity of Iron Oxide Nanoparticles with Different Sizes and Coatings. Scientific Reports, 8, Article No. 2082. [Google Scholar] [CrossRef] [PubMed]
[53] Ge, S., Nemiroski, A., Mirica, K.A., et al. (2020) Magnet-ic Levitation in Chemistry, Materials Science, and Biochemistry. Angewandte Chemie International Edition, 59, 17810-17855. [Google Scholar] [CrossRef] [PubMed]
[54] Durmus, N.G., Tekin, H.C., Guven, S., et al. (2015) Magnetic Levitation of Single Cells. Proceedings of the National Academy of Sciences of the United States of America, 112, E3661-E3668. [Google Scholar] [CrossRef] [PubMed]
[55] Simon, M. and Geim, A.K. (2000) Diamagnetic Levitation: Flying Frogs and Floating Magnets (Invited). Journal of Applied Physics, 87, 6200-6204. [Google Scholar] [CrossRef
[56] Sarigil, O., Anil-Inevi, M., Yilmaz, E., et al. (2019) Label-Free Densi-ty-Based Detection of Adipocytes of Bone Marrow Origin Using Magnetic Levitation. Analyst, 144, 2942-2953. [Google Scholar] [CrossRef
[57] Gao, Q.-H., Zhang, W.-M., Zou, H.-X., et al. (2019) Label-Free Ma-nipulation via the Magneto-Archimedes Effect: Fundamentals, Methodology and Applications. Materials Horizons, 6, 1359-1379. [Google Scholar] [CrossRef
[58] Tasoglu, S., Kavaz, D., Gurkan, U.A., et al. (2013) Paramagnetic Levi-tational Assembly of Hydrogels. Advanced Materials, 25, 1137-1143. [Google Scholar] [CrossRef] [PubMed]
[59] Yaman, H. (2018) Exploring Dementia Management Attitudes in Primary Care: A Key Informant Survey to Primary Care Physicians in 25 European Countries. International Psychogeri-atrics, 30, 1413-1414. [Google Scholar] [CrossRef
[60] Hassounah, N.B., Malladi, V.S., Huang, Y., et al. (2019) Identi-fication and Characterization of an Alternative Cancer-Derived PD-L1 Splice Variant. Cancer Immunology, Immuno-therapy, 68, 407-420. [Google Scholar] [CrossRef] [PubMed]
[61] Tocchio, A., Durmus, N.G., Sridhar, K., et al. (2018) Magnetical-ly Guided Self-Assembly and Coding of 3D Living Architectures. Advanced Materials, 30, Article 1705034. [Google Scholar] [CrossRef] [PubMed]
[62] Gupta, T., Aithal, S., Mishriki, S., et al. (2020) Label-Free Magnet-ic-Field-Assisted Assembly of Layer-on-Layer Cellular Structures. ACS Biomaterials Science and Engineering, 6, 4294-4303. [Google Scholar] [CrossRef] [PubMed]
[63] Tasoglu, S., Khoory, J.A., Tekin, H.C., et al. (2015) Levita-tional Image Cytometry with Temporal Resolution. Advanced Materials, 27, 3901-3908. [Google Scholar] [CrossRef] [PubMed]
[64] Turker, E., Demircak, N. and Arslan-Yildiz, A. (2018) Scaffold-Free Three-Dimensional Cell Culturing Using Magnetic Levitation. Biomaterials Science, 6, 1745-1753. [Google Scholar] [CrossRef
[65] Souza, G.R., Molina, J.R., Raphael, R.M., et al. (2010) Three-Dimensional Tissue Culture Based on Magnetic Cell Levitation. Nature Nanotechnology, 5, 291-296. [Google Scholar] [CrossRef] [PubMed]
[66] Sarigil, O., Anil-Inevi, M., Firatligil-Yildirir, B., et al. (2021) Scaf-fold-Free Biofabrication of Adipocyte Structures with Magnetic Levitation. BiotechnolBioeng, 118, 1127-1140. [Google Scholar] [CrossRef] [PubMed]