Research progress in three-dimensional-printed bone scaffolds combined with vascularized tissue flaps for segmental bone defect reconstruction_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

段其达 , 邵鸿运 , 骆宁 , 王富洋 , 程亮亮 ,  应嘉蔚 ,  赵德伟

DUAN Qida, SHAO Hongyun, LUO Ning, WANG Fuyang, CHENG Liangliang, YING Jiawei, ZHAO Dewei Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian Liaoning, 116001, P. R. China;

Corresponding author：

应嘉蔚, Email: yingjiawei19@163.com; 赵德伟, Email: zhaodewei2016@163.com

Keywords：

Segmental bone defect; three-dimensional-printed; artificial bone scaffold; vascularized tissue flap; biomaterial

DOI：

10.7507/1002-1892.202503081

Video：

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Objective The research progress on repairing segmental bone defects using three-dimensional (3D)-printed bone scaffolds combined with vascularized tissue flaps in recent years was reviewed and summarized. Methods Relevant literature was reviewed to summarize the application of 3D-printed technology in artificial bone scaffolds made from different biomaterials, as well as methods for repairing segmental bone defects by combining these scaffolds with various vascularized tissue flaps. Results The combination of 3D-printed artificial bone scaffolds with different vascularized tissue flaps has provided new strategies for repairing segmental bone defects. 3D-printed artificial bone scaffolds include 3D-printed polymer scaffolds, bio-ceramic scaffolds, and metal scaffolds. When these scaffolds of different materials are combined with vascularized tissue flaps (e.g., omental flaps, fascial flaps, periosteal flaps, muscular flaps, and bone flaps), they provide blood supply to the inorganic artificial bone scaffolds. After implantation into the defect site, the scaffolds not only achieve structural filling and mechanical support for the bone defect area, but also promote osteogenesis and vascular regeneration. Additionally, the mechanical properties, porous structure, and biocompatibility of the 3D-printed scaffold materials are key factors influencing their osteogenic efficiency. Furthermore, loading the scaffolds with active components such as osteogenic cells and growth factors can synergistically enhance bone defect healing and vascularization processes. Conclusion The repair of segmental bone defects using 3D-printed artificial bone scaffolds combined with vascularized tissue flap transplantation integrates material science technologies with medical therapeutic approaches, which will significantly improve the clinical treatment outcomes of segmental bone defect repair.

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1. Myeroff C, Archdeacon M. Autogenous bone graft: donor sites and techniques. J Bone Joint Surg (Am), 2011, 93(23): 2227-2236.
2. Zhu Y, Gu Y, Qiao S, et al. Bacterial and mammalian cells adhesion to tantalum-decorated micro-/nano-structured titanium. J Biomed Mater Res A, 2017, 105(3): 871-878.
3. Menger MM, Laschke MW, Nussler AK, et al. The vascularization paradox of non-union formation. Angiogenesis, 2022, 25(3): 279-290.
4. Stegen S, Carmeliet G. Metabolic regulation of skeletal cell fate and function. Nat Rev Endocrinol, 2024, 20(7): 399-413.
5. Rouwkema J, Khademhosseini A. Vascularization and angiogenesis in tissue engineering: Beyond creating static networks. Trends Biotechnol, 2016, 34(9): 733-745.
6. Huang J, Han Q, Cai M, et al. Effect of angiogenesis in bone tissue engineering. Ann Biomed Eng, 2022, 50(8): 898-913.
7. Beier JP, Horch RE, Hess A, et al. Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model. J Tissue Eng Regen Med, 2010, 4(3): 216-223.
8. Wang L, Fan H, Zhang ZY, et al. Osteogenesis and angiogenesis of tissue-engineered bone constructed by prevascularized β-tricalcium phosphate scaffold and mesenchymal stem cells. Biomaterials, 2010, 31(36): 9452-9461.
9. Simunovic F, Finkenzeller G. Vascularization strategies in bone tissue engineering. Cells, 2021, 10(7): 1749. doi: 10.3390/cells10071749.
10. Yu H, Xu M, Duan Q, et al. 3D-printed porous tantalum artificial bone scaffolds: fabrication, properties, and applications. Biomed Mater, 2024, 19(4). doi: 10.1088/1748-605X/ad46d2.
11. Twohig C, Helsinga M, Mansoorifar A, et al. A dual-ink 3D printing strategy to engineer pre-vascularized bone scaffolds in-vitro. Mater Sci Eng C Mater Biol Appl, 2021, 123: 111976. doi: 10.1016/j.msec.2021.111976.
12. Gómez Amador AM, Venturini Avendano RA, González AQ, et al. Mechanical characterization and testing of multi-polymer combinations in 3D printing. Heliyon, 2025, 11(3): e42420. doi: 10.1016/j.heliyon.2025.e42420.
13. Osman MA, Virgilio N, Rouabhia M, et al. Development and characterization of functional polylactic acid/chitosan porous scaffolds for bone tissue engineering. Polymers (Basel), 2022, 14(23): 5079. doi: 10.3390/polym14235079.
14. Kazemi N, Hassanzadeh-Tabrizi SA, Koupaei N, et al. Incorporation of forsterite nanoparticles in a 3D printed polylactic acid/polyvinylpyrrolidone scaffold for bone tissue regeneration applications. Int J Biol Macromol, 2025, 305(Pt 1): 141046. doi: 10.1016/j.ijbiomac.2025.141046.
15. Hogan KJ, Öztatlı H, Perez MR, et al. Development of photoreactive demineralized bone matrix 3D printing colloidal inks for bone tissue engineering. Regen Biomater, 2023, 10: rbad090. doi: 10.1093/rb/rbad090.
16. Ansari MAA, Golebiowska AA, Dash M, et al. Engineering biomaterials to 3D-print scaffolds for bone regeneration: practical and theoretical consideration. Biomater Sci, 2022, 10(11): 2789-2816.
17. Vallet-Regí M, Colilla M, González B. Medical applications of organic-inorganic hybrid materials within the field of silica-based bioceramics. Chem Soc Rev, 2011, 40(2): 596-607.
18. Wang B, Ye X, Chen G, Zhang Y, Zeng Z, Liu C, et al. Fabrication and properties of PLA/beta-TCP scaffolds using liquid crystal display (LCD) photocuring 3D printing for bone tissue engineering. Front Bioeng Biotechnol. 2024;12: 1273541.
19. Chen L, Zhang S, Duan Y, et al. Silicon-containing nanomedicine and biomaterials: materials chemistry, multi-dimensional design, and biomedical application. Chem Soc Rev, 2024, 53(3): 1167-1315.
20. Perić Kačarević Ž, Rider P, Alkildani S, et al. An introduction to bone tissue engineering. Int J Artif Organs, 2020, 43(2): 69-86.
21. Huang G, Pan ST, Qiu JX. The osteogenic effects of porous tantalum and titanium alloy scaffolds with different unit cell structure. Colloids Surf B Biointerfaces, 2022, 210: 112229. doi: 10.1016/j.colsurfb.2021.112229.
22. Lee JW, Wen HB, Gubbi P, et al. New bone formation and trabecular bone microarchitecture of highly porous tantalum compared to titanium implant threads: A pilot canine study. Clin Oral Implants Res, 2018, 29(2): 164-174.
23. Park EK, Lim JY, Yun IS, et al. Cranioplasty enhanced by three-dimensional printing: Custom-made three-dimensional-printed titanium implants for skull defects. J Craniofac Surg, 2016, 27(4): 943-949.
24. Hamid KS, Parekh SG, Adams SB. Salvage of severe foot and ankle trauma with a 3D printed scaffold. Foot Ankle Int, 2016, 37(4): 433-439.
25. Liu B, Ma Z, Li J, et al. Experimental study of a 3D printed permanent implantable porous Ta-coated bone plate for fracture fixation. Bioact Mater, 2021, 10: 269-280.
26. Zhao D, Cheng L, Lu F, et al. Design, fabrication and clinical characterization of additively manufactured tantalum hip joint prosthesis. Regen Biomater, 2024, 11: rbae057. doi: 10.1093/rb/rbae057.
27. Putra NE, Mirzaali MJ, Apachitei I, et al. Multi-material additive manufacturing technologies for Ti-, Mg-, and Fe-based biomaterials for bone substitution. Acta Biomater, 2020, 109: 1-20.
28. Karunakaran R, Ortgies S, Tamayol A, et al. Additive manufacturing of magnesium alloys. Bioact Mater, 2020, 5(1): 44-54.
29. Li Y, Jahr H, Pavanram P, et al. Additively manufactured functionally graded biodegradable porous iron. Acta Biomater, 2019, 96: 646-661.
30. Mishra DK, Pandey PM. Mechanical behaviour of 3D printed ordered pore topological iron scaffold. Materials Science and Engineering: A, 2020, 783: 139293. doi: 10.1016/j.msea.2020.139293.
31. Li Y, Li W, Bobbert FSL, et al. Corrosion fatigue behavior of additively manufactured biodegradable porous zinc. Acta Biomater, 2020, 106: 439-449.
32. Zhang X, Mao J, Zhou Y, et al. Mechanical properties and osteoblast proliferation of complex porous dental implants filled with magnesium alloy based on 3D printing. J Biomater Appl, 2021, 35(10): 1275-1283.
33. Wang JL, Xu JK, Hopkins C, et al. Biodegradable magnesium-based implants in orthopedics-a general review and perspectives. Adv Sci (Weinh), 2020, 7(8): 1902443. doi: 10.1002/advs.201902443.
34. Xia D, Qin Y, Guo H, et al. Additively manufactured pure zinc porous scaffolds for critical-sized bone defects of rabbit femur. Bioact Mater, 2022, 19: 12-23.
35. Olszta MJ, Cheng X, Jee SS, et al. Bone structure and formation: A new perspective. Materials Science and Engineering: R: Reports, 2007, 58(3-5): 77-116.
36. Liu X, Huang W, Fu H, et al. Bioactive borosilicate glass scaffolds: improvement on the strength of glass-based scaffolds for tissue engineering. J Mater Sci Mater Med, 2009, 20(1): 365-372.
37. El-Rashidy AA, El Moshy S, Radwan IA, et al. Effect of polymeric matrix stiffness on osteogenic differentiation of mesenchymal stem/progenitor cells: Concise review. Polymers (Basel), 2021, 13(17): 2950. doi: 10.3390/polym13172950.
38. Murphy CM, Matsiko A, Haugh MG, et al. Mesenchymal stem cell fate is regulated by the composition and mechanical properties of collagen-glycosaminoglycan scaffolds. J Mech Behav Biomed Mater, 2012, 11: 53-62.
39. Abdelaziz AG, Nageh H, Abdo SM, et al. A review of 3D polymeric scaffolds for bone tissue engineering: Principles, fabrication techniques, immunomodulatory roles, and challenges. Bioengineering (Basel), 2023, 10(2): 204. doi: 10.3390/bioengineering10020204.
40. Yazdanpanah Z, Johnston JD, Cooper DML, et al. 3D bioprinted scaffolds for bone tissue engineering: State-of-the-art and emerging technologies. Front Bioeng Biotechnol, 2022, 10: 824156. doi: 10.3389/fbioe.2022.824156.
41. Van Bael S, Chai YC, Truscello S, et al. The effect of pore geometry on the in vitro biological behavior of human periosteum-derived cells seeded on selective laser-melted Ti6Al4V bone scaffolds. Acta Biomater, 2012, 8(7): 2824-2834.
42. Jin J, Wang D, Qian H, et al. Precision pore structure optimization of additive manufacturing porous tantalum scaffolds for bone regeneration: A proof-of-concept study. Biomaterials, 2025, 313: 122756. doi: 10.1016/j.biomaterials.2024.122756.
43. Wang ZH, Zhang M, Liu ZW, et al. Biomimetic design strategy of complex porous structure based on 3D printing Ti-6Al-4V scaffolds for enhanced osseointegration. Materials & Design, 2022, 218: 110721. doi: 10.1016/j.matdes.2022.110721.
44. Xia P, Luo Y. Vascularization in tissue engineering: The architecture cues of pores in scaffolds. J Biomed Mater Res B Appl Biomater, 2022, 110(5): 1206-1214.
45. Wang Z, Wang C, Li C, et al. Analysis of factors influencing bone ingrowth into three-dimensional printed porous metal scaffolds: A review. Journal of Alloys and Compounds, 2017, 717: 271-285.
46. Hudák R, Schnitzer M, Králová ZO, et al. Additive manufacturing of porous Ti6Al4V alloy: Geometry analysis and mechanical properties testing. Applied Sciences-Basel, 2021, 11(6). doi: 10.3390/app11062611.
47. Guerrero J, Ghayor C, Bhattacharya I, et al. Osteoconductivity of bone substitutes with filament-based microarchitectures: Influence of directionality, filament dimension, and distance. Int J Bioprint, 2022, 9(1): 626. doi: 10.18063/ijb.v9i1.626.
48. Mitra D, Whitehead J, Yasui OW, et al. Bioreactor culture duration of engineered constructs influences bone formation by mesenchymal stem cells. Biomaterials, 2017, 146: 29-39.
49. Williams DF. On the mechanisms of biocompatibility. Biomaterials, 2008, 29(20): 2941-2953.
50. Bian N, Chu C, Rung S, et al. Immunomodulatory biomaterials and emerging analytical techniques for probing the immune micro-environment. Tissue Eng Regen Med, 2023, 20(1): 11-24.
51. Chu S, Li L, Zhang J, et al. Hierarchical interconnected porous scaffolds with regulated interfacial nanotopography exhibit antimicrobial, alleviate inflammation, neovascularization, and tissue integration for bone regeneration. Biomaterials, 2025, 318: 123186. doi: 10.1016/j.biomaterials.2025.123186.
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Chinese Journal of Reparative and Reconstructive Surgery

Latest ArticlesResearch progress in three-dimensional-printed bone scaffolds combined with vascularized tissue flaps for segmental bone defect reconstruction

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