增材制造技术助力骨科临床治疗——上海第九人民医院骨科创新的医疗增材制造技术丨AMF论文推荐

引用论文

Wei Yang, Shasha Liu, Liang Deng, Dinghao Luo, Zhaoyang Ran, Tinglong Chen, Lei Wang, Kai Xie, Junxiang Wu, Wenbo Jiang, Ping Liu, Jingke Fu, Yongqiang Hao, Kerong Dai. Additive Manufacturing Technology Lends Wings to Orthopedic Clinical Treatment - The Innovative Development of Medical Additive Manufacturing in Shanghai Ninth People's Hospital. Additive Manufacturing Frontiers, 2024, 200176.

https://doi.org/10.1016/j.amf.2024.200176.

文章链接：

1研究现状

在戴尅戎院士和郝永强教授的领导下，上海市第九人民医院骨科成功将3D打印技术应用于定制关节置换、修复骨缺损、复杂骨折固定和脊柱疾病治疗，显著提升了治疗效果。目前，团队正积极研发新型生物材料，优化3D打印工艺，以提高植入物的生物相容性和活性，致力于制造更符合人体工程学的骨科植入物，满足临床需求。

Fig. 1. Timeline of personalized prostheses development and some key milestones achieved by the Orthopedics Department Shanghai Ninth People's Hospital

2研究难点或瓶颈

首先，开发与天然骨相似的人工骨材料，需具备支撑、保护、生物安全性等特性，但医用级原材料选择有限；其次，骨科支架与不同组织间的不匹配问题，需提高机械稳定性和骨整合效果；最后，生物3D打印材料范围有限，制造精度需提升，且面临严格的安全评估和法规挑战。这些难点共同制约了3D打印技术在骨科临床的广泛应用。

3展望

3D打印技术在骨科医学领域的未来发展将继续深化个性化医疗，通过精确匹配患者解剖结构，提升植入物适配性和手术成功率。随着生物材料科学的发展，4D打印技术有望制造出更复杂的生物组织和器官，优化再生效果。技术的优化将提高制造精度和速度，降低成本，提高性价比，更有利于推动3D打印技术的普及。同时，法规和标准化的完善将为临床应用提供安全指导。九院成功案例也证实了，医工结合将促进新技术研发，提高服务质量。加强教育培训将提升医疗人员对3D打印技术的掌握，提供更精准的医疗服务。智能化和自动化的发展将进一步提高3D打印的设计和制造效率。这些趋势预示着3D打印技术将在骨科医学领域发挥更加关键的作用。

4代表性图片

Fig. 2. 3D-printing hip prostheses used for revision total hip arthroplasty with complex acetabular bone defects. (A) Preoperative and postoperative X-ray examinations; (B) Standard design process for the integrated revision prosthesis; (C) Computer simulation of the prosthesis installation; (D) Intraoperative prosthesis installation and comparison of implant overlap; Parts A-D adapted form Ref. [7] Elsevier

Fig. 3. Definition and 3D design diagrams of bone defect ranges: (A) 3D design of preoperative prosthesis for bone defect range into types I-V; (B) Definitions for bone defect type classification; (C) 3D design diagrams of preoperative prosthesis for bone defects in subtypes A and B; (D) Definitions for bone defect subtype classification; Parts A-D adapted form Ref. [9] Elsevier

Fig. 4. Research results from Prof. Hao's group on titanium alloy stent: (A) Evaluation of scaffold aperture: (a) Scaffolds used in the in vitro experiment; (b) Cell adhesion on the tested scaffolds; (c) Scaffolds used in vivo experiments and gross specimens at different time points (3, 6 and 12 months); Part A adapted form Ref. [10] Nature Publishing Group; (B) Design and characterization of porous scaffolds with different rod geometries: (a) Design drawings; (b) General images of porous scaffolds; (c) Distribution of MC3T3-E1 cells on three scaffolds with different rod structures; Part B adapted form Ref. [14] Springer; (C) Effect of partially melted particles: (a) Surface morphology characterization of five Ti6Al4V implants; (b) Representative images of methicillin-resistant MRSA and E.coli grown on the five Ti6Al4V implants; (c) Adhesion and morphology of hBMSCs after 1 day and alizarin-red staining of calcium nodules after 21 days; Part C adapted form Ref. [15] the Association of Bone and Joint Surgeons; (D) Effect of polymetallic alloys: (a) Computer-aided design and SEM micrographs of blank scaffolds; (b) Three-dimensional reconstruction from tomographic images; (c) Fluorescent double label detection; (d) SEM micrographs showing bone microstructure (gray areas indicate new bone); Part D adapted form Ref. [17] ACS

Fig. 5. Research results from Prof. Hao's group on bio-functional metal implants: (A) Evaluation of bio-functional metal implants: (a) Porous Ta and porous Ti6Al4V scaffolds used in vitro, with hBMSCs adhering to the scaffolds; (b) SEM micrographs showing bone apposition and microstructure on porous scaffolds at different positions at 4, 6, and 12 weeks (gray areas indicate new bone); Part A adapted form Ref. [24] ACS; (B) Design and antibacterial activity of 3D-printed JDBM implants, both in vitro and in vivo; Part B adapted form Ref. [32] Elsevier; (C) Biodegradable magnesium screw: preoperative and postoperative radiographs of a young female patient with a trimalleolar fracture and a mid-age female patient with a medial malleolar fracture; Part C adapted form Ref. [33] Elsevier; (D) Images and SEM surface micrographs of Mg alloy scaffolds, as well as Micro-CT, HE, and Masson’s trichrome staining of femoral samples of osteoporotic rats; Part D adapted form Ref. [34] Whioce Publishing Pte. Ltd.

Fig. 6. Repair and reconstruction with biological 3D-printed bioactive scaffolds following tibial tumor resection: (A) Imaging examination of lower left extremity (a-d); (B) Computer-aided design and printing of the bioactive scaffold; (C) Tumor resection of the left tibia and implantation of the bioprinted scaffold; (D) Postoperative X-ray and CT examination of the lower left extremity; Parts A-D adapted form Ref. [50] Whioce Publishing Pte. Ltd.

关于团队

作者团队介绍

郝永强（通讯作者），医学博士，上海交通大学医学院附属第九人民医院骨科主任医师，上海交通大学医学院教授，博士生导师，国家重点研发计划首席科学家。上海市卫建委重点专科生物医用材料学科带头人、上海市医学3D打印技术临床转化工程研究中心主任、上海骨科创新器械与个性化医学工程技术研究中心主任、骨科行政副主任。秉承 “理念为先，创新引领；以临床需求为导向，以临床转化为牵引，依托国际前沿技术，医工合作，产学研结合”。近年来，主持国家科技部重点研发计划（3D打印个性化硬组织重建植入器械）、科技部“863”（高强韧医用镁合金材料）与“973”（新型医用材料的功能化设计及生物适配）子课题、国家自然科学基金等国家级课题7项；主持上海市高峰学科建设项目、上海市临床重点专科项目、上海市申康医院发展中心新兴前沿技术项目及疑难疾病精准诊治攻关项目、上海市科委医学领域科技支撑项目等省部级课题12项。在国内外知名学术杂志上发表研究论文145余篇，其中，以第一/通讯作者在Adv Funct Mater（3篇，IF:16.8）、Mol Cancer（1篇，IF 15.3）、Biomaterials（3篇，IF:10.3）等期刊上发表SCI论文62篇，已获国家专利授权47项，获计算机软件著作权3项。创建3D打印个性化病变模型、个性化手术辅助导板及个性化3D打印金属重建假体的“三位一体”个性化医疗模式及骨肿瘤精准切除与个体化重建的关键技术体系，研究成果居于世界先进水平。自主研发的3D打印个性化骨盆重建假体获国内首张备案许可证。以第一完成人获得上海市科学技术进步奖一等奖1项、中国产学研合作创新成果奖一等奖1项、上海市康复医学科技奖一等奖1项；获中国高校科学技术奖二等奖（2001年）、中华医学科技奖三等奖（2002年）（第5完成人）、上海市科技进步三等奖（2004年）（第2完成人）各1项。2018年获《科学中国人》年度人物。

团队研究方向

1․ 个性化骨肿瘤及复杂骨疾病诊疗关键技术及应用研究

1）骨肿瘤安全切除边界的智能化精准确定；

2）建立复杂骨缺损个性化重建假体的设计及制备技术体系与制定标准；

3）个性化骨缺损修复重建的外科技术创新；

2․ 3D打印医学应用的基础与临床研究

1）3D生物打印基础及临床应用研究；

2）3D打印建模及骨肿瘤相关计算机辅助手术规划系统设计；

3）骨盆肿瘤及内植物有限元分析；

3․ 新型骨修复材料的基础与转化研究

1）生物可降解镁合金的基础与临床研究；

2）生物功能内植物材料的基础及临床应用研究；

3）功能涂层工艺及临床应用研究；

4）3D打印新材料的开发及应用基础研究；

4․骨与转移性骨肿瘤的基础、临床技术创新及转化研究

1）转移性骨肿瘤的发生机制研究；

2）骨与转移性骨肿瘤微创治疗新技术；

3）骨肉瘤化疗药物敏感性及调控机制；

5․ 生物打印活性组织器官关键技术及转化研究

1）生物打印活性骨内植物关键技术研究

2）生物打印活性内植物基础及临床前研究

近年团队发表文章

[1] Cao BJ, Lin JM, Tan J, Li JX, Ran ZY, Deng L, Hao YQ, 3D-printed vascularized biofunctional scaffold for bone regeneration, International Journal of Bioprinting, 2023, 9(3), 702.

[2] Cao BJ, Li JX, Wang XW, Ran ZY, Tan J, Deng L, Hao YQ, Mechanosensitive miR-99b mediates the regulatory effect of matrix stiffness on bone marrow mesenchymal stem cell fate both in vitro and in vivo, APL Bioengineering, 7, 016106 (2023).

[3] Tan J, Li J, Ran Z, Wu J, Luo D, Cao B, Deng L, Li X, Jiang W, Xie K, Wang L, Hao Y, Accelerated fracture healing by osteogenic Ti45Nb implants through the PI3K-Akt signaling pathway, Bio-Design and Manufacturing, 2023, 6, 718-734.

[4] Tan J, Ren L, Xie K, Wang L, Jiang W, Guo Y, Hao Y. Functionalized TiCu/TiCuN coating promotes osteoporotic fracture healing by upregulating the Wnt/beta-catenin pathway, Regenerative Biomaterials, 2023, 10, 2056-3418.

[5] Ran Z, Wang Y, Li J, Xu W, Tan J, Cao B, Luo D, Ding Y, Wu J, Wang L, Xie K, Deng L, Fu P, Sun X, Shi L, Hao Y, 3D-printed biodegradable magnesium alloy scaffolds with zoledronic acid-loaded ceramic composite coating promote osteoporotic bone defect repair, International Journal of Bioprinting, 2023, 9(5), 401-417.

[6] Luo DH, Hao YQ, Status and prospect of 3D print-assisted personalized pelvic lesion reconstruction, Chinese Journal of Bone and Joint Surgery, 2023, 16, 72-76.

[7] Li J, Zhong H, Cao B, Ran Z, Tan J, Deng L, Hao Y, Yan J. Comparative Study of 3D-Printed Porous Titanium Alloy with Rod Designs of Three Different Geometric Structures for Orthopaedic Implantation, Acta Metall. Sin. (Engl. Lett.) (2023). https://doi.org/10.1007/s40195-023-01573-0.

[8] Hao Y, Cao B, Deng L, Li, J, Ran Z, Wu J, Pang B, Tan J, Luo D, Wu W, The first 3D-bioprinted personalized active bone to repair bone defects: A case report, International Journal of Bioprinting, 2023, 9, 70-75.

[9] 罗丁豪,郝永强.3D打印辅助个性化骨盆病损重建的现状与展望[J].中华骨与关节外科杂志,2023,16(01):72-76.

[10] Lu, Z.; Miao, X.; Zhang, C.; Sun, B.; Skardal, A.; Atala, A.; Ai, S.; Gong, J.; Hao, Y.*; Zhao, J.*; Dai, K.*. An osteosarcoma-on-a-chip model for studying osteosarcoma matrix-cell interactions and drug responses. BIOACTIVE MATERIALS. 2024. 10.1016/j.bioactmat.2023.12.005

[11] Wang, H.; Guo, J.; Yang, Y.; Wang, N.; Yang, X.; Deng, L.; Cao, X.; Ran, Z.; Fang, D.; Xu, K.; Zhu, Y.; Zhao, J.*; Fu, J.*; Hao, Y.*. CuFeS2 nanozyme regulating ROS/GSH redox induces ferroptosis-like death in bacteria for robust anti-infection therapy. MATERIALS & DESIGN. 2024. 10.1016/j.matdes.2024.112809.

[12] Lian, M., Qiao, Z., Qiao, S., Zhang, X., Lin, J., Xu, R., Zhu, N., Tang, T., Huang, Z., Jiang, W., Shi, J., Hao, Y. *, Lai, H. *, & Dai, K. Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical Porous Scaffolds with Neuro-Promotive Properties for Enhancing Innervated Bone Regeneration. ACS NANO. 2024. 10.1021/acsnano.3c11890

[13] Meng, X.; Liu, Z.; Yang, Y.; Li, J.; Ran, Z.; Zhu, Y.; Fu, J.*; He, Y.*; Hao, Y.. Engineered Microcystis aerugiosa Hydrogel as an Anti-Tumor Therapeutic by Augmenting Tumor Immunogenicity and Immune Responses. ADVANCED FUNCTIONAL MATERIALS. 2024. 10.1002/adfm.202305915

[14] Meng, X.; Liu, Z.; Deng, L.; Yang, Y.; Zhu, Y.; Sun, X.; Hao, Y. *; He, Y. *; Fu, J. *. Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity. ADVANCED SCIENCE. 2024. 10.1002/advs.202401269.

作者：杨威

责任编辑：李娜

责任校对：金程

审核：张强

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