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REVIEW ARTICLE

Intelligent bioprinting of biomimetic hemostatic constructs: From bioink design and programmable fabrication to preclinical validation for non-compressible hemorrhage

Yanhong Pei1† ,  Zhenyue Zhang2,3† ,  Yifan Wang3† ,  Zicheng Zhang3 ,  Xiaoya Li4 ,  Yanli Yuan5 ,  Aiyuan Wang1* ,  Jiantao Li3* ,  Zheng Wang3,5* ,  Xin Yin3*
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1 Institute of Orthopedics, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Lab of Musculoskeletal Trauma & War Injuries, National Clinical Research Center for Orthopedics and Sports Medicine, Senior Department of Orthopedics, The Fourth Medical Center, Chinese PLA General Hospital, Beijing , China
2 Department of Orthopaedics, Nankai University School of Medicine, Tianjin , China
3 National Clinical Research Center for Orthopedics and Sports Medicine, Senior Department of Orthopedics, The Fourth Medical Center, Chinese PLA General Hospital, Beijing , China
4 Senior Department of Orthopedics, The Fourth Medical Center, Chinese PLA General Hospital, Beijing , China
5 Department of Spine Surgery, Senior Department of Orthopedics, The Fourth Medical Center, Chinese PLA General Hospital, Beijing , China
†These authors contributed equally to this work.
IJB, 026410441 https://doi.org/10.36922/IJB026410441
Received: 8 September 2026 | Revised: 18 October 2026 | Accepted: 21 October 2026 | Published online: 3 November 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

Non-compressible hemorrhage (NCH) remains a leading cause of preventable trauma mortality because conventional gauze and oxidized cellulose act as passive barriers, whereas fibrin sealants depend on patient-derived fibrinogen; neither is reliable in coagulopathic patients. Recent convergence of bioink engineering, 3D/4D bioprinting, and artificial intelligence (AI)-assisted material design enables the fabrication of biomimetic hemostatic constructs with programmable composition, multiscale architecture, and dynamic responsiveness. This review critically examines how intelligent bioprinting—integrating stimuli-responsive bioinks, multi-axis extrusion/digital light processing printing, and AI-guided bioink optimization—fundamentally differs from conventional biomaterial fabrication in recapitulating the structural mechanics of natural thrombi. We first analyze the structure–function relationships of native fibrin/platelet/red blood cell networks that should be mimicked by bioprinted constructs. We then systematically compare bioink formulations (natural biopolymers, synthetic peptides, cell-membrane-coated nano-vectors, and inorganic–organic composites) across four bioprinting-relevant dimensions: printability, post-printing bioactivity, wet-tissue adhesion strength, and burst pressure. We further evaluate cross-tier preclinical validation, including microfluidic thrombosis-on-chip, small-animal models, and lethal large-animal NCH models (porcine liver/spleen/junctional injury), with explicit differentiation from rodent wound-healing studies. Finally, we identify translational bottlenecks (rheological paradox, Good Manufacturing Practice scale-up, regulatory pathways) and articulate future directions: AI-guided bioink discovery, organ-on-chip patient-specific screening, and deployable 4D-printed hemostats. By bridging biomimetic design, programmable fabrication, and quantitative translational evaluation, intelligent bioprinting offers a manufacturable and clinically translatable route to next-generation NCH therapeutics.

Graphical abstract
Keywords
Non-compressible hemorrhage
Hemostatic biomaterials
Intelligent bioprinting
Bioink engineering
Organ-on-chip models
AI-assisted material design
Biomimetic microstructures
Wet adhesion
Funding
This work was supported by the National Natural Science Foundation of China (82606665); Key Project of Independent Innovation Science Foundation, The Fourth Medical Center of Chinese PLA General Hospital (2026-4ZX-ZD-03); Frontier Research Direction, Beijing Natural Science Foundation – Fengtai Innovation Joint Fund (L241042); National Natural Science Foundation of China (82372499; 82572707‬), and the Natural Science Foundation of Beijing (L244017).
Conflict of interest
The authors declare no conflicts of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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