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REVIEW ARTICLE

Bioactive integration and stimuli-responsive therapeutic regulation in additively manufactured metallic orthopedic implants

Yi Mao1† ,  Yihong Li1† ,  Yi Li2 ,  Chee Kai Chua3 ,  Qi Li4* ,  Liqiang Wang1*
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1 State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
2 Department of Neurosurgery, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
3 Department of Mechanical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei, China
4 Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
†These authors contributed equally to this work.
IJB, 026220218 https://doi.org/10.36922/IJB026220218
Received: 26 May 2026 | Revised: 10 June 2026 | Accepted: 6 July 2026 | Published online: 9 July 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Additive manufacturing (AM) has accelerated the evolution of metallic orthopedic implants from passive structural substitutes toward multifunctional therapeutic platforms. Leveraging the geometric freedom and compositional flexibility of AM, bioactive substances can be integrated into metallic implants through multiple strategies to regulate the peri-implant microenvironment and enhance tissue regeneration. This review summarizes recent advances in bioactive integration and responsive therapeutic release in additively manufactured metallic orthopedic implants. First, major biofunctionalization strategies are discussed, including surface modification, bulk alloying, and structurally integrated reservoirs. These approaches enable the incorporation of antibacterial, osteogenic, angiogenic, and immunomodulatory functions through localized delivery of antibiotics, bioactive ions, peptides, growth factors, and small-molecule therapeutics. Subsequently, recent progress in stimuli-responsive release systems is reviewed, including endogenous stimuli such as pH, enzymes, and reactive oxygen species, as well as exogenous stimuli such as light, magnetic fields, and electrical stimulation, which enable on-demand and microenvironment-adaptive therapy. The relationships among implant architecture, bioactive integration, and dynamic therapeutic regulation are further discussed to highlight the unique advantages of AM in constructing multifunctional implants. Finally, current challenges associated with multifunctional AM metallic implants are discussed, particularly the need to achieve synergistic biofunctionality, maintain structural and mechanical integrity under process constraints, ensure predictable therapeutic release, and establish reliable process–structure–property relationships. This review provides insights into the development of intelligent metallic implants that simultaneously provide mechanical support and actively regulate therapy.

Graphical abstract
Keywords
Additive manufacturing
Metallic implants
Biofunctionalization
Surface modification
Stimuli-responsive release
Funding
The authors acknowledge the financial supports from the National Key Research and Development Program of China (grant no. 2024YFE0109000), the Fundamental Research Funds for the Central Universities (project number YG2024LC04), the Fundamental Research Funds for the Central Universities (grant no. YG2023QNA21), the Establishment and Application of Traditional Chinese and Western Medicine Collaborative Diagnosis and Treatment Center for Major Difficult Diseases (ZY[2025-2027]-2-1-4), the Three-year Action Plan of Shanghai Municipality for Further Accelerating the Inheritance, the Innovation and Development of Traditional Chinese Medicine: Shanghai High Level Talent Guiding Project in Traditional Chinese Medicine (grant no. ZY [2021-2023]-0403), the Shanghai Municipal Health Commission Scientific Research project plan (grant no. 202340059), the Collaborative Traditional Chinese Medicine and Western Medicine Guiding Project of General Hospital (grant no. ZXXT-202308), the Standardization Project of Traditional Chinese Medicine (2025BZ026), and the 2nd national Western medicine doctor studying TCM excellent talents research plan (2023.6-2026.5).
Conflict of interest
Both Chee Kai Chua and Liqiang Wang serve the Editorial Board of this journal as Editor-in-Chief and Editorial Board Member, respectively, but they were not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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