引用論文

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.

文章鏈接：

1研究現狀

在戴尅戎院士和郝永強教授的領導下，上海市第九人民醫院骨科成功將3D打印技術應用于定制關節置換、修復骨缺損、復雜骨折固定和脊柱疾病治療，顯著提升了治療效果。目前，團隊正積極研發新型生物材料，優化3D打印工藝，以提高植入物的生物相容性和活性，致力于制造更符合人體工程學的骨科植入物，滿足臨床需求。

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

2研究難點或瓶頸

首先，開發與天然骨相似的人工骨材料，需具備支撐、保護、生物安全性等特性，但醫用級原材料選擇有限；其次，骨科支架與不同組織間的不匹配問題，需提高機械穩定性和骨整合效果；最后，生物3D打印材料范圍有限，制造精度需提升，且面臨嚴格的安全評估和法規挑戰。這些難點共同制約了3D打印技術在骨科臨床的廣泛應用。

3展望

3D打印技術在骨科醫學領域的未來發展將繼續深化個性化醫療，通過精確匹配患者解剖結構，提升植入物適配性和手術成功率。隨著生物材料科學的發展，4D打印技術有望制造出更復雜的生物組織和器官，優化再生效果。技術的優化將提高制造精度和速度，降低成本，提高性價比，更有利于推動3D打印技術的普及。同時，法規和標準化的完善將為臨床應用提供安全指導。九院成功案例也證實了，醫工結合將促進新技術研發，提高服務質量。加強教育培訓將提升醫療人員對3D打印技術的掌握，提供更精準的醫療服務。智能化和自動化的發展將進一步提高3D打印的設計和制造效率。這些趨勢預示著3D打印技術將在骨科醫學領域發揮更加關鍵的作用。

4代表性圖片

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.

關于團隊

作者團隊介紹

郝永強（通訊作者），醫學博士，上海交通大學醫學院附屬第九人民醫院骨科主任醫師，上海交通大學醫學院教授，博士生導師，國家重點研發計劃首席科學家。上海市衛建委重點專科生物醫用材料學科帶頭人、上海市醫學3D打印技術臨床轉化工程研究中心主任、上海骨科創新器械與個性化醫學工程技術研究中心主任、骨科行政副主任。秉承 “理念為先，創新引領；以臨床需求為導向，以臨床轉化為牽引，依托國際前沿技術，醫工合作，產學研結合”。近年來，主持國家科技部重點研發計劃（3D打印個性化硬組織重建植入器械）、科技部“863”（高強韌醫用鎂合金材料）與“973”（新型醫用材料的功能化設計及生物適配）子課題、國家自然科學基金等國家級課題7項；主持上海市高峰學科建設項目、上海市臨床重點專科項目、上海市申康醫院發展中心新興前沿技術項目及疑難疾病精準診治攻關項目、上海市科委醫學領域科技支撐項目等省部級課題12項。在國內外知名學術雜志上發表研究論文145余篇，其中，以第一/通訊作者在Adv Funct Mater（3篇，IF:16.8）、Mol Cancer（1篇，IF 15.3）、Biomaterials（3篇，IF:10.3）等期刊上發表SCI論文62篇，已獲國家專利授權47項，獲計算機軟件著作權3項。創建3D打印個性化病變模型、個性化手術輔助導板及個性化3D打印金屬重建假體的“三位一體”個性化醫療模式及骨腫瘤精準切除與個體化重建的關鍵技術體系，研究成果居于世界先進水平。自主研發的3D打印個性化骨盆重建假體獲國內首張備案許可證。以第一完成人獲得上海市科學技術進步獎一等獎1項、中國產學研合作創新成果獎一等獎1項、上海市康復醫學科技獎一等獎1項；獲中國高校科學技術獎二等獎（2001年）、中華醫學科技獎三等獎（2002年）（第5完成人）、上海市科技進步三等獎（2004年）（第2完成人）各1項。2018年獲《科學中國人》年度人物。

團隊研究方向

1? 個性化骨腫瘤及復雜骨疾病診療關鍵技術及應用研究

1）骨腫瘤安全切除邊界的智能化精準確定；

2）建立復雜骨缺損個性化重建假體的設計及制備技術體系與制定標準；

3）個性化骨缺損修復重建的外科技術創新；

2? 3D打印醫學應用的基礎與臨床研究

1）3D生物打印基礎及臨床應用研究；

2）3D打印建模及骨腫瘤相關計算機輔助手術規劃系統設計；

3）骨盆腫瘤及內植物有限元分析；

3? 新型骨修復材料的基礎與轉化研究

1）生物可降解鎂合金的基礎與臨床研究；

2）生物功能內植物材料的基礎及臨床應用研究；

3）功能涂層工藝及臨床應用研究；

4）3D打印新材料的開發及應用基礎研究；

4?骨與轉移性骨腫瘤的基礎、臨床技術創新及轉化研究

1）轉移性骨腫瘤的發生機制研究；

2）骨與轉移性骨腫瘤微創治療新技術；

3）骨肉瘤化療藥物敏感性及調控機制；

5? 生物打印活性組織器官關鍵技術及轉化研究

1）生物打印活性骨內植物關鍵技術研究

2）生物打印活性內植物基礎及臨床前研究

近年團隊發表文章

[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] 羅丁豪,郝永強.3D打印輔助個性化骨盆病損重建的現狀與展望[J].中華骨與關節外科雜志,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：楊 威

責任編輯：李 娜

責任校對： 金 程

審 核： 張 強

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