AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB026220218
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REVIEW ARTICLE
Early Access

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 Material Science and Engineering, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
2 Department of Neurosurgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Street, Shanghai 200011, China
3 Wuhan University of Science and Technology, No. 947 Heping Avenue, Wuhan 430081, Hubei, China
4 Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 Yishan Road, Shanghai, 200233, China
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/ )
Abstract

Additive manufacturing (AM) has accelerated the evolution of metallic orthopedic implants from passive structural substitutes toward multifunctional therapeutic platforms. Benefiting from 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 improve 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 triggered by pH, enzymes, and reactive oxygen species, as well as exogenous regulation through 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 in terms of achieving synergistic biofunctionality, maintaining structural and mechanical integrity under process constraints, ensuring predictable therapeutic release, and establishing reliable process structure property relationships.This review provides insights into the development of intelligent metallic implants capable of simultaneously achieving mechanical support and active therapeutic regulation.

Keywords
Additive manufacturing
Metallic implants
Biofunctionalization
Surface modification
Stimuli-responsive release
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing