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3D打印聚合物生物材料在骨组织工程中的应用
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Abstract:
聚合物是由重复单体组成的大分子,这些单体可以来源于自然资源或人工合成。由于其卓越的物理化学性质和功能特性,聚合物在生物医学领域,特别是在组织工程中,受到了广泛关注。3D打印技术是一种通过数字模型逐层添加材料来制造三维物体的工艺,其与聚合物在骨组织工程中的结合已经得到了广泛认可。本综述概述了3D打印聚合物生物材料在骨组织工程中的应用。文章首先讨论了骨再生的基本过程,然后介绍了聚合物成分和3D打印技术的选择。此外,本综述全面阐述了3D打印聚合物生物材料的功能特性设计。最后,讨论了3D打印聚合物生物材料在骨组织工程中应用的现状、挑战及未来发展方向。
Polymers are large molecules composed of repeating subunits called monomers, which can be derived from both natural sources and synthetic processes. Due to their exceptional physicochemical properties and functional characteristics, polymers have garnered significant attention in the biomedical field, particularly in tissue engineering. 3D printing technology, a process that manufactures three-dimensional objects by sequentially adding material based on digital models, has been widely recognized for its integration with polymers in bone tissue engineering. This review provides an overview of 3D-printed polymeric biomaterials in bone tissue engineering. It begins with a discussion of the fundamental process of bone regeneration, followed by a component selection for polymers and 3D printing technologies. Additionally, this review comprehensively addresses the functional properties design of 3D-printed polymeric biomaterials. Finally, the current status, challenges, and future directions for the application of 3D-printed polymeric biomaterials in bone tissue engineering are discussed.
[1] | Clézardin, P., Coleman, R., Puppo, M., Ottewell, P., Bonnelye, E., Paycha, F., et al. (2021) Bone Metastasis: Mechanisms, Therapies, and Biomarkers. Physiological Reviews, 101, 797-855. https://doi.org/10.1152/physrev.00012.2019 |
[2] | Ayers, C., Kansagara, D., Lazur, B., Fu, R., Kwon, A. and Harrod, C. (2023) Effectiveness and Safety of Treatments to Prevent Fractures in People with Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-Analysis for the American College of Physicians. Annals of Internal Medicine, 176, 182-195. https://doi.org/10.7326/m22-0684 |
[3] | Yu, B. and Wang, C. (2022) Osteoporosis and Periodontal Diseases—An Update on Their Association and Mechanistic Links. Periodontology 2000, 89, 99-113. https://doi.org/10.1111/prd.12422 |
[4] | Miron, R.J. (2023) Optimized Bone Grafting. Periodontology 2000, 94, 143-160. https://doi.org/10.1111/prd.12517 |
[5] | Urban, I.A., Montero, E., Amerio, E., Palombo, D. and Monje, A. (2023) Techniques on Vertical Ridge Augmentation: Indications and Effectiveness. Periodontology 2000, 93, 153-182. https://doi.org/10.1111/prd.12471 |
[6] | Urban, I., Montero, E., Sanz‐Sánchez, I., Palombo, D., Monje, A., Tommasato, G., et al. (2023) Minimal Invasiveness in Vertical Ridge Augmentation. Periodontology 2000, 91, 126-144. https://doi.org/10.1111/prd.12479 |
[7] | Yu, S., Saleh, M.H.A. and Wang, H. (2023) Simultaneous or Staged Lateral Ridge Augmentation: A Clinical Guideline on the Decision‐Making Process. Periodontology 2000, 93, 107-128. https://doi.org/10.1111/prd.12512 |
[8] | Sun, W., Ye, B., Chen, S., Zeng, L., Lu, H., Wan, Y., et al. (2023) Neuro-Bone Tissue Engineering: Emerging Mechanisms, Potential Strategies, and Current Challenges. Bone Research, 11, Article No. 65. https://doi.org/10.1038/s41413-023-00302-8 |
[9] | Sivakumar, P.M., Yetisgin, A.A., Sahin, S.B., Demir, E. and Cetinel, S. (2022) Bone Tissue Engineering: Anionic Polysaccharides as Promising Scaffolds. Carbohydrate Polymers, 283, Article ID: 119142. https://doi.org/10.1016/j.carbpol.2022.119142 |
[10] | Zhang, Z., Hao, Z., Xian, C., Fang, Y., Cheng, B., Wu, J., et al. (2022) Neuro-Bone Tissue Engineering: Multiple Potential Translational Strategies between Nerve and Bone. Acta Biomaterialia, 153, 1-12. https://doi.org/10.1016/j.actbio.2022.09.023 |
[11] | Guo, L., Liang, Z., Yang, L., Du, W., Yu, T., Tang, H., et al. (2021) The Role of Natural Polymers in Bone Tissue Engineering. Journal of Controlled Release, 338, 571-582. https://doi.org/10.1016/j.jconrel.2021.08.055 |
[12] | Lewns, F.K., Tsigkou, O., Cox, L.R., Wildman, R.D., Grover, L.M. and Poologasundarampillai, G. (2023) Hydrogels and Bioprinting in Bone Tissue Engineering: Creating Artificial Stem‐Cell Niches for in Vitro Models. Advanced Materials, 35, e2301670. https://doi.org/10.1002/adma.202301670 |
[13] | Wang, J., Wu, Y., Li, G., Zhou, F., Wu, X., Wang, M., et al. (2024) Engineering Large‐Scale Self‐Mineralizing Bone Organoids with Bone Matrix‐Inspired Hydroxyapatite Hybrid Bioinks. Advanced Materials, 36, e2309875. https://doi.org/10.1002/adma.202309875 |
[14] | Kim, W., Jang, C.H. and Kim, G. (2022) Bone Tissue Engineering Supported by Bioprinted Cell Constructs with Endothelial Cell Spheroids. Theranostics, 12, 5404-5417. https://doi.org/10.7150/thno.74852 |
[15] | Laird, N.Z., Acri, T.M., Tingle, K. and Salem, A.K. (2021) Gene-and RNAi-Activated Scaffolds for Bone Tissue Engineering: Current Progress and Future Directions. Advanced Drug Delivery Reviews, 174, 613-627. https://doi.org/10.1016/j.addr.2021.05.009 |
[16] | Adithya, S.P., Sidharthan, D.S., Abhinandan, R., Balagangadharan, K. and Selvamurugan, N. (2020) Nanosheets-incorporated Bio-Composites Containing Natural and Synthetic Polymers/ceramics for Bone Tissue Engineering. International Journal of Biological Macromolecules, 164, 1960-1972. https://doi.org/10.1016/j.ijbiomac.2020.08.053 |
[17] | Khorsandi, D., Fahimipour, A., Abasian, P., Saber, S.S., Seyedi, M., Ghanavati, S., et al. (2021) 3D and 4D Printing in Dentistry and Maxillofacial Surgery: Printing Techniques, Materials, and Applications. Acta Biomaterialia, 122, 26-49. https://doi.org/10.1016/j.actbio.2020.12.044 |
[18] | Donos, N., Akcali, A., Padhye, N., Sculean, A. and Calciolari, E. (2023) Bone Regeneration in Implant Dentistry: Which Are the Factors Affecting the Clinical Outcome? Periodontology 2000, 93, 26-55. https://doi.org/10.1111/prd.12518 |
[19] | Calciolari, E., Corbella, S., Gkranias, N., Viganó, M., Sculean, A. and Donos, N. (2023) Efficacy of Biomaterials for Lateral Bone Augmentation Performed with Guided Bone Regeneration. A Network Meta‐Analysis. Periodontology 2000, 93, 77-106. https://doi.org/10.1111/prd.12531 |
[20] | Khare, D., Basu, B. and Dubey, A.K. (2020) Electrical Stimulation and Piezoelectric Biomaterials for Bone Tissue Engineering Applications. Biomaterials, 258, Article ID: 120280. |
[21] | Abbas, M., Alqahtani, M.S. and Alhifzi, R. (2023) Recent Developments in Polymer Nanocomposites for Bone Regeneration. International Journal of Molecular Sciences, 24, Article 3312. https://doi.org/10.3390/ijms24043312 |
[22] | Qing, Y., Li, R., Li, S., Li, Y., Wang, X. and Qin, Y. (2020) Advanced Black Phosphorus Nanomaterials for Bone Regeneration. International Journal of Nanomedicine, 15, 2045-2058. https://doi.org/10.2147/ijn.s246336 |
[23] | Perrin, S. and Colnot, C. (2022) Periosteal Skeletal Stem and Progenitor Cells in Bone Regeneration. Current Osteoporosis Reports, 20, 334-343. https://doi.org/10.1007/s11914-022-00737-8 |
[24] | Tao, J., Miao, R., Liu, G., Qiu, X., Yang, B., Tan, X., et al. (2022) Spatiotemporal Correlation between HIF‐1α and Bone Regeneration. The FASEB Journal, 36, e22520. https://doi.org/10.1096/fj.202200329rr |
[25] | Toledano-Osorio, M., Manzano-Moreno, F.J., Ruiz, C., Toledano, M. and Osorio, R. (2021) Testing Active Membranes for Bone Regeneration: A Review. Journal of Dentistry, 105, Article ID: 103580. https://doi.org/10.1016/j.jdent.2021.103580 |
[26] | Gou, M., Wang, H., Xie, H. and Song, H. (2024) Macrophages in Guided Bone Regeneration: Potential Roles and Future Directions. Frontiers in Immunology, 15, Article 1396759. https://doi.org/10.3389/fimmu.2024.1396759 |
[27] | Xie, C., Ye, J., Liang, R., Yao, X., Wu, X., Koh, Y., et al. (2021) Advanced Strategies of Biomimetic Tissue‐Engineered Grafts for Bone Regeneration. Advanced Healthcare Materials, 10, e2100408. https://doi.org/10.1002/adhm.202100408 |
[28] | Fu, J., Wang, Y., Jiang, Y., Du, J., Xu, J. and Liu, Y. (2021) Systemic Therapy of MSCs in Bone Regeneration: A Systematic Review and Meta-Analysis. Stem Cell Research & Therapy, 12, Article No. 377. https://doi.org/10.1186/s13287-021-02456-w |
[29] | Olchowy, A., Olchowy, C., Zawiślak, I., Matys, J. and Dobrzyński, M. (2024) Revolutionizing Bone Regeneration with Grinder-Based Dentin Biomaterial: A Systematic Review. International Journal of Molecular Sciences, 25, Article 9583. https://doi.org/10.3390/ijms25179583 |
[30] | Lo, K.W. (2022) Effects on Bone Regeneration of Single-Dose Treatment with Osteogenic Small Molecules. Drug Discovery Today, 27, 1538-1544. https://doi.org/10.1016/j.drudis.2022.02.020 |
[31] | Zhao, X., Yao, M., Wang, Y., Feng, C., Yang, Y., Tian, L., et al. (2025) Neuroregulation during Bone Formation and Regeneration: Mechanisms and Strategies. ACS Applied Materials & Interfaces, 17, 7223-7250. https://doi.org/10.1021/acsami.4c16786 |
[32] | Li, X., Zhao, Y., Miao, L., An, Y., Wu, F., Han, J., et al. (2025) Strategies for Promoting Neurovascularization in Bone Regeneration. Military Medical Research, 12, Article No. 9. https://doi.org/10.1186/s40779-025-00596-1 |
[33] | Schindeler, A., McDonald, M.M., Bokko, P. and Little, D.G. (2008) Bone Remodeling during Fracture Repair: The Cellular Picture. Seminars in Cell & Developmental Biology, 19, 459-466. https://doi.org/10.1016/j.semcdb.2008.07.004 |
[34] | Lu, Y., Mai, Z., Cui, L. and Zhao, X. (2023) Engineering Exosomes and Biomaterial-Assisted Exosomes as Therapeutic Carriers for Bone Regeneration. Stem Cell Research & Therapy, 14, Article No. 55. https://doi.org/10.1186/s13287-023-03275-x |
[35] | Murphy, S.V., De Coppi, P. and Atala, A. (2019) Opportunities and Challenges of Translational 3D Bioprinting. Nature Biomedical Engineering, 4, 370-380. https://doi.org/10.1038/s41551-019-0471-7 |
[36] | Saleh Alghamdi, S., John, S., Roy Choudhury, N. and Dutta, N.K. (2021) Additive Manufacturing of Polymer Materials: Progress, Promise and Challenges. Polymers, 13, Article 753. https://doi.org/10.3390/polym13050753 |
[37] | Chia, H.N. and Wu, B.M. (2015) Recent Advances in 3D Printing of Biomaterials. Journal of Biological Engineering, 9, Article No. 4. https://doi.org/10.1186/s13036-015-0001-4 |
[38] | Li, X., Liu, B., Pei, B., Chen, J., Zhou, D., Peng, J., et al. (2020) Inkjet Bioprinting of Biomaterials. Chemical Reviews, 120, 10793-10833. https://doi.org/10.1021/acs.chemrev.0c00008 |
[39] | Heinrich, M.A., Liu, W., Jimenez, A., Yang, J., Akpek, A., Liu, X., et al. (2019) 3D Bioprinting: From Benches to Translational Applications. Small, 15, e1805510. https://doi.org/10.1002/smll.201805510 |
[40] | Hutmacher, D.W., Schantz, T., Zein, I., Ng, K.W., Teoh, S.H. and Tan, K.C. (2001) Mechanical Properties and Cell Cultural Response of Polycaprolactone Scaffolds Designed and Fabricated via Fused Deposition Modeling. Journal of Biomedical Materials Research, 55, 203-216. https://doi.org/10.1002/1097-4636(200105)55:2<203::aid-jbm1007>3.3.co;2-z |
[41] | Li, J., Rossignol, F. and Macdonald, J. (2015) Inkjet Printing for Biosensor Fabrication: Combining Chemistry and Technology for Advanced Manufacturing. Lab on a Chip, 15, 2538-2558. https://doi.org/10.1039/c5lc00235d |
[42] | Williams, J.M., Adewunmi, A., Schek, R.M., Flanagan, C.L., Krebsbach, P.H., Feinberg, S.E., et al. (2005) Bone Tissue Engineering Using Polycaprolactone Scaffolds Fabricated via Selective Laser Sintering. Biomaterials, 26, 4817-4827. https://doi.org/10.1016/j.biomaterials.2004.11.057 |
[43] | Qin, T., Li, X., Long, H., Bin, S. and Xu, Y. (2020) Bioactive Tetracalcium Phosphate Scaffolds Fabricated by Selective Laser Sintering for Bone Regeneration Applications. Materials, 13, Article 2268. https://doi.org/10.3390/ma13102268 |
[44] | Yue, K., Trujillo-de Santiago, G., Alvarez, M.M., Tamayol, A., Annabi, N. and Khademhosseini, A. (2015) Synthesis, Properties, and Biomedical Applications of Gelatin Methacryloyl (Gelma) Hydrogels. Biomaterials, 73, 254-271. https://doi.org/10.1016/j.biomaterials.2015.08.045 |
[45] | Gudapati, H., Yan, J., Huang, Y. and Chrisey, D.B. (2014) Alginate Gelation-Induced Cell Death during Laser-Assisted Cell Printing. Biofabrication, 6, Article ID: 035022. https://doi.org/10.1088/1758-5082/6/3/035022 |
[46] | Ozbolat, I.T. and Hospodiuk, M. (2016) Current Advances and Future Perspectives in Extrusion-Based Bioprinting. Biomaterials, 76, 321-343. https://doi.org/10.1016/j.biomaterials.2015.10.076 |
[47] | Koushik, T.M., Miller, C.M. and Antunes, E. (2023) Bone Tissue Engineering Scaffolds: Function of Multi‐Material Hierarchically Structured Scaffolds. Advanced Healthcare Materials, 12, e2202766. https://doi.org/10.1002/adhm.202202766 |
[48] | Kang, H., Hollister, S.J., La Marca, F., Park, P. and Lin, C. (2013) Porous Biodegradable Lumbar Interbody Fusion Cage Design and Fabrication Using Integrated Global-Local Topology Optimization with Laser Sintering. Journal of Biomechanical Engineering, 135, Article ID: 101013. https://doi.org/10.1115/1.4025102 |
[49] | Han, Y., Jia, B., Lian, M., Sun, B., Wu, Q., Sun, B., et al. (2021) High-Precision, Gelatin-Based, Hybrid, Bilayer Scaffolds Using Melt Electro-Writing to Repair Cartilage Injury. Bioactive Materials, 6, 2173-2186. https://doi.org/10.1016/j.bioactmat.2020.12.018 |
[50] | Gómez-Barrena, E., Rosset, P., Gebhard, F., Hernigou, P., Baldini, N., Rouard, H., et al. (2019) Feasibility and Safety of Treating Non-Unions in Tibia, Femur and Humerus with Autologous, Expanded, Bone Marrow-Derived Mesenchymal Stromal Cells Associated with Biphasic Calcium Phosphate Biomaterials in a Multicentric, Non-Comparative Trial. Biomaterials, 196, 100-108. https://doi.org/10.1016/j.biomaterials.2018.03.033 |
[51] | Schuckert, K., Jopp, S. and Teoh, S. (2009) Mandibular Defect Reconstruction Using Three-Dimensional Polycaprolactone Scaffold in Combination with Platelet-Rich Plasma and Recombinant Human Bone Morphogenetic Protein-2: De Novo Synthesis of Bone in a Single Case. Tissue Engineering Part A, 15, 493-499. https://doi.org/10.1089/ten.tea.2008.0033 |
[52] | Nakamura, A., Murata, D., Fujimoto, R., Tamaki, S., Nagata, S., Ikeya, M., et al. (2021) Bio-3D Printing IPSC-Derived Human Chondrocytes for Articular Cartilage Regeneration. Biofabrication, 13, Article ID: 044103. https://doi.org/10.1088/1758-5090/ac1c99 |
[53] | Tang, M., Xie, Q., Gimple, R.C., Zhong, Z., Tam, T., Tian, J., et al. (2020) Three-Dimensional Bioprinted Glioblastoma Microenvironments Model Cellular Dependencies and Immune Interactions. Cell Research, 30, 833-853. https://doi.org/10.1038/s41422-020-0338-1 |
[54] | Wang, M.M., Flores, R.L., Witek, L., Torroni, A., Ibrahim, A., Wang, Z., et al. (2019) Dipyridamole-Loaded 3D-Printed Bioceramic Scaffolds Stimulate Pediatric Bone Regeneration in Vivo without Disruption of Craniofacial Growth through Facial Maturity. Scientific Reports, 9, Article No. 18439. https://doi.org/10.1038/s41598-019-54726-6 |
[55] | Suarez-Martinez, A.D., Sole-Gras, M., Dykes, S.S., Wakefield, Z.R., Bauer, K., Majbour, D., et al. (2021) Bioprinting on Live Tissue for Investigating Cancer Cell Dynamics. Tissue Engineering Part A, 27, 438-453. https://doi.org/10.1089/ten.tea.2020.0190 |
[56] | Li, X., Lv, H., Zhao, R., Ying, M., Samuriwo, A.T. and Zhao, Y. (2021) Recent Developments in Bio-Scaffold Materials as Delivery Strategies for Therapeutics for Endometrium Regeneration. Materials Today Bio, 11, Article ID: 100101. https://doi.org/10.1016/j.mtbio.2021.100101 |
[57] | Zhang, M., Hu, W., Cai, C., Wu, Y., Li, J. and Dong, S. (2022) Advanced Application of Stimuli-Responsive Drug Delivery System for Inflammatory Arthritis Treatment. Materials Today Bio, 14, Article ID: 100223. https://doi.org/10.1016/j.mtbio.2022.100223 |
[58] | Huang, K., Lin, Y., Shie, M. and Lin, C. (2018) Effects of Bone Morphogenic Protein-2 Loaded on the 3D-Printed MesoCS Scaffolds. Journal of the Formosan Medical Association, 117, 879-887. https://doi.org/10.1016/j.jfma.2018.07.010 |
[59] | Ajdary, R., Huan, S., Zanjanizadeh Ezazi, N., Xiang, W., Grande, R., Santos, H.A., et al. (2019) Acetylated Nanocellulose for Single-Component Bioinks and Cell Proliferation on 3D-Printed Scaffolds. Biomacromolecules, 20, 2770-2778. https://doi.org/10.1021/acs.biomac.9b00527 |
[60] | Han, S.H., Cha, M., Jin, Y., Lee, K. and Lee, J.H. (2020) BMP-2 and HMSC Dual Delivery onto 3D Printed Pla-Biogel Scaffold for Critical-Size Bone Defect Regeneration in Rabbit Tibia. Biomedical Materials, 16, Article ID: 015019. https://doi.org/10.1088/1748-605x/aba879 |
[61] | Feng, C., Zhang, W., Deng, C., Li, G., Chang, J., Zhang, Z., et al. (2017) 3D Printing of Lotus Root‐Like Biomimetic Materials for Cell Delivery and Tissue Regeneration. Advanced Science, 4, Article ID: 1700401. https://doi.org/10.1002/advs.201700401 |
[62] | Li, W., Wang, M., Ma, H., Chapa-Villarreal, F.A., Lobo, A.O. and Zhang, Y.S. (2023) Stereolithography Apparatus and Digital Light Processing-Based 3D Bioprinting for Tissue Fabrication. iScience, 26, Article ID: 106039. https://doi.org/10.1016/j.isci.2023.106039 |
[63] | Saitta, L., Cutuli, E., Celano, G., Tosto, C., Sanalitro, D., Guarino, F., et al. (2023) Projection Micro-Stereolithography to Manufacture a Biocompatible Micro-Optofluidic Device for Cell Concentration Monitoring. Polymers, 15, Article 4461. https://doi.org/10.3390/polym15224461 |
[64] | O’Halloran, S., Pandit, A., Heise, A. and Kellett, A. (2022) Two‐Photon Polymerization: Fundamentals, Materials, and Chemical Modification Strategies. Advanced Science, 10, e2204072. https://doi.org/10.1002/advs.202204072 |
[65] | Getzler, Y.D.Y.L. and Mathers, R.T. (2022) Sustainable Polymers: Our Evolving Understanding. Accounts of Chemical Research, 55, 1869-1878. https://doi.org/10.1021/acs.accounts.2c00194 |
[66] | Wang, F., Tankus, E.B., Santarella, F., Rohr, N., Sharma, N., Märtin, S., et al. (2022) Fabrication and Characterization of PCL/HA Filament as a 3D Printing Material Using Thermal Extrusion Technology for Bone Tissue Engineering. Polymers, 14, Article 669. https://doi.org/10.3390/polym14040669 |
[67] | Zhang, L., Onat, B., Dusson, G., McSloy, A., Anand, G., Maurer, R.J., et al. (2022) Equivariant Analytical Mapping of First Principles Hamiltonians to Accurate and Transferable Materials Models. npj Computational Materials, 8, Article No. 158. https://doi.org/10.1038/s41524-022-00843-2 |
[68] | Francés-Herrero, E., Lopez, R., Hellström, M., de Miguel-Gómez, L., Herraiz, S., Brännström, M., et al. (2022) Bioengineering Trends in Female Reproduction: A Systematic Review. Human Reproduction Update, 28, 798-837. https://doi.org/10.1093/humupd/dmac025 |
[69] | Lu, Z., Wang, T. and Zhang, R. (2023) Editorial: Affective Brain-Computer Interface in Emotion Artificial Intelligence and Medical Engineering. Frontiers in Computational Neuroscience, 17, Article 1237252. https://doi.org/10.3389/fncom.2023.1237252 |
[70] | Zhang, P., Ji, L., Zhou, G. and Yao, X. (2022) A Commentary on the Practice of Integrated Medical Curriculum in the Interdisciplinary Field of Medical Engineering. Annals of Medicine, 54, 812-819. https://doi.org/10.1080/07853890.2022.2050421 |