Abstract
The outbreak of infectious diseases and rapid pathogens’ evolution have highlighted the urgency for developing new therapeutics to protect public health and the economy from massive loss. Drug discovery for infectious diseases involves a multi-stage and multi-disciplinary pipeline, often leading to increased risk and mortality due to the prolonged course. However, advancements in technology have been reshaping the field by offering alternative in vitro models—facilitating drug discovery, studying the mechanism of infectious diseases, and developing patient-specific solutions. Recently, 3D bioprinting has been emerging as a revolutionary technology that enables researchers to precisely create custom 3D constructs that mimic human physiology and can be used as either platforms for delivering therapeutics and/or cells locally or in vitro tissue models for drug screening. Herein, we shed light on recent advancements in the use of 3D bioprinting technologies to introduce platforms employed for fabricating 3D structures to control and study infectious diseases.
1 Introduction
Infectious diseases and epidemics caused by the emergence of new or resistant pathogens have been life-threatening for both humans and livestock. Infection occurs by entering the body and multiplying of microorganisms, including viruses, bacteria, fungi and parasites which can spread from person to person, animal to human, or via a contaminated environment (Baker et al., 2022; Piret and Boivin, 2021). Currently, preventing the spread of the disease is at the forefront of infection management, with rapid development of vaccines and therapeutics playing an indispensable role (Ellwanger et al., 2021; Nii-Trebi, 2017). Drug development for infectious diseases is a complex and multistage procedure which includes screening drug candidates, preclinical studies, clinical trials and regulatory approval, making the process slow and costly (DiMasi et al., 2020). In fact, about 90% of drugs face failure in the clinical trial stages. Using 2D cultures during preclinical tests is one of the contributing factors to this low success rate, as these models lack sufficient relevance to human microenvironments and fail to produce accurate data in terms of drug diffusion, efficacy and safety (Zimmerling and Chen, 2020). Therefore, there is a pressing need to explore novel approaches as alternative for conventional methods that can speed up the drug discovery process, yet mimic in vivo human microenvironments.
3D bioprinting has been emerging as a novel technology, capable of orchestrating the three-dimensional structures in a precise and consistent layer-by-layer fashion (Tripathi et al., 2020). These 3D arrangements are composed of living cells, biologically active substances and biomaterial inks which have been widely used for tissue engineering and regenerative medicine (TERM), as well as disease modelling purposes (Yu et al., 2021; Maia et al., 2023; Juraski et al., 2023; Jabbari et al., 2025). 3D bioprinting has offered the capability to create complex and functional 3D models of tissues and organs which enable researchers and clinicians to study the mechanisms of diseases, test new drugs and develop personalized treatments (Maia et al., 2023; Yang et al., 2024a; Kashkooli et al., 2025). To date, a variety of 3D bioprinting techniques such as inkjet-based, laser-assisted and extrusion-based have been developed to engineer constructs that accurately resemble human physiology (Wu et al., 2023; Vanaei et al., 2021). More recently, hybrid technologies that combine different techniques such as volumetric bioprinting, melt extrusion, fused deposition modelling with electrospinning and microfluidic-assisted bioprinting, enhanced by computer-aided design (CAD) fabrication of obtained models from medical images have been coming to the fore and offer precise control over spatiotemporal deposition (Mohammadi and Cidonio, 2023; Koch et al., 2021; Lee et al., 2022; Liu et al., 2022; Mohammadi et al., 2024).
While the application of 3D bioprinting technology in TERM, cancer therapy and biomaterial research has been reported in details elsewhere (D’Alessandro et al., 2024; Bini et al., 2023a; Bini et al., 2023b; Tabriz and Douroumis, 2022), the advancements and impacts of 3D bioprinting in infection studies remain less explored. Herein, we delve into the reasons behind using this novel technology, summarize and report its innovations, aiding infection research and highlight the biomaterial inks explored so far.
2 The need for alternative methods in preclinical research
Drug discovery is a lengthy and costly process that conventionally takes 10–15 years from early studies on molecular target or the disease pathways to the final approval of the drug candidate to be used in clinic. This process is even more challenging in infectious diseases, mainly due to the frequent emergence of drug resistant pathogens and therapeutic failure (Si et al., 2022). Essential phases in this process are: 1- Discovery and development, 2- preclinical research, 3- clinical research, 4- FDA review and 5- post-market safety monitoring. All these are essential phases, aimed at identification, optimization and ensuring the safety and effectiveness of a promising compound (Singh et al., 2023; Maranesi et al., 2025). Key steps among these phases are preclinical demonstration of formulation, validation, pharmacokinetics, and pharmacodynamics, to assess whether a compound is likely to cause serious impairment. To this point, animal models have been playing a crucial role in the assessment of toxicology, efficacy and potential side effects of newly developed drugs (MacLeod et al., 2024; Jena et al., 2025; Schaller et al., 2025). However, apart from the high cost of animal research, there have been several reports, suggesting that the animal models might be poor predictors of drug safety and human reactions (Bracken, 2009; Van Norman, 2019). Technology advancements, ethical concerns and the urge for more efficient and predictive preclinical models have led to a substantial transformation in preclinical research, mainly in search for alternative methods for animal experiments (Kiani et al., 2022; Marenzana and Vande Velde, 2015).
2.1 Principle of the 3Rs: Replace, reduce and refine
For over 50 years, the principle of the 3Rs has been shaping the frameworks for performing more humane animal studies. This principle aims to maximize the use of non-animal methods, such as in vitro techniques and computer models; experiment design aimed at minimizing the number of animals while still obtaining valid and reproducible results, and making use of the appropriate technologies to diminish the pain and suffering of animals. Recently, the FDA has announced its plan to phase out animal testing of monoclonal antibodies, and eventually other drugs, which marks a monumental turn in the drug development process. In this regard, researchers are encouraged to utilize 3D tissue cultures, organ-on-a-chip, and AI models to accelerate the development, standardization, and validation of new substances in preclinical settings, as well as study disease mechanisms. While relevant to infection research, the exploration of organ-on-a-chip and AI models is beyond the scope of this review and are reported in detail elsewhere (Vashishat et al., 2024; Gangwal and Lavecchia, 2025; Rudroff, 2024). Therefore, in the next section we review the application of 3D bioprinting in constructing 3D tissue cultures and its innovations in infection management.
3 Application of 3D bioprinting in infection management
3D cell cultures, due to better interaction of cells either with each other and the surrounding extracellular matrix (ECM) offer a more physiologically relevant niche that to a degree mimic in vivo conditions (Ca et al., 2022). The bioprinted tissues have shown high levels of similarity to native tissues; therefore hold a great potential for studying different aspects of infection such as barrier functions of tissues, pathogens behavior, and the treatment (Yi et al., 2021). In the following, we focus on the tissues/organs with both high infectious diseases relevance and availability of bioprinted models for studying infection—as certain districts still lack sufficient published work to support a robust discussion.
3.1 3D bioprinted constructs for prevention/treatment of wound infection
Skin is susceptible to several injuries, including burns, wounds, infections, trauma, and chronic diseases, which disintegrate the structure and damage the function of skin. The healing process of skin, schematically shown in Figure 1A, involves hemostasis, inflammatory reaction, cell proliferation and tissue remodeling—with phagocytic leukocytes, fibroblasts, endothelial and keratinocytes participating in the process (Zhao et al., 2023; Mohammadi et al., 2023). Wound closure is a vital step towards a successful wound healing process which may increase the risk of infection if delayed. Primary closure can be achieved by suturing small wounds, but grafting skin substitutes is required for larger wounds (Wallace et al., 2023). 3D bioprinting has shown fascinating capability to create hierarchical, interconnected and macro/microporous skin scaffolds and wound dressing, made of bioinks, to be aligned with the injured tissue. These constructs not only recapitulate the complexity of human tissue, but also can carry antimicrobial compounds to minimize the risk of starting infection and biofilm formation while accelerating the healing process (Guptha et al., 2024; van Charante et al., 2023). For instance, curcumin and lignin were combined with poly (caprolactone) to prepare an antimicrobial and anti-inflammatory wound dressing. The dressing was 3D printed with semi-solid extrusion method and supplied a sustained release of bioactive agents, resulting in ≈99% prevention of Staphylococcus aureus adhesion (Domínguez-Robles et al., 2023).
FIGURE 1
To be used as skin substitutes, the selected bioinks in 3D bioprinted constructs must meet a number of criteria, including biocompatibility, degradability, printability, and mechanical and biochemical characteristics close to those of native skin. While providing temporary ECM scaffolds for regulating cell behavior, the bioinks eventually determine the success of the printing process. Therefore, it is important that the printed construct maintains its structural integrity upon placement in defect zone, and ensures integration and interaction without triggering a negative immune response (Zhang et al., 2023). The bioinks are usually composed of a hydrogel form of biomaterials to encapsulate different cell types and provide adhesive sites to carry bioactive agents, cell adhesion, proliferation and differentiation (Matai et al., 2020). Printability of bioinks highly depends on rheological properties of the used biomaterials in their hydrogel phase. While hydrogels with higher viscosity have shown higher stiffness, therefore better structural stability of the printed construct, they might cause damage to the encapsulated cells. On the other hand, low viscosity hydrogels are more pleasant to cells, yet make it difficult to create a stable and functional structure (He et al., 2016; Lee et al., 2020). Considering importance of proper viscosity in balancing mechanical properties, Bian et al. suggested an artificial skin substitute using gelatin–hyaluronan hydrogels laden with human dermal fibroblasts, combined with patterned collagen-mimicking nanofibrous films to enhance tensile strength and direct cell behavior. Human keratinocytes were seeded to form the epidermis, resulting in a graded construct with gradient porosity and improved mechanical integrity (Bian et al., 2024).
3.2 3D bioprinted antimicrobial scaffolds
Bone is susceptible to severe defects, stemming from various causes such as trauma, tumors, poor prognosis, and congenital conditions. Adhesion of Staphylococcal species, specifically S. aureus is often considered as the main cause of bone infection (Du et al., 2023). Treating infections in the presence of bone defects imposes significant challenges to the orthopedics field. 3D printing of biocompatible antimicrobial scaffolds with appropriate mechanical strength is an enticing approach to overcome concerns of microbial infection, as shown in Figure 1B. To this end, combination of biodegradable materials including polymers, ceramics, graphene, bioglass or metals with antibiotics, antimicrobial peptides or nanoparticles has gained significant attention (Yang et al., 2024b; Xu et al., 2024; Cheng et al., 2021).
Blending antimicrobial compounds with scaffold materials in a desired ratio and subsequent fabrication is the most common method to create antimicrobial scaffolds. Bai et al. used melt electrohydrodynamic 3D printing to fabricate a composite antimicrobial scaffold made of PCL/polyethylene glycol/roxithromycin. In vitro drug release study demonstrated an initial burst release followed by sustained drug release behavior that was effective against E. coli and S. aureus (Bai et al., 2020). Moreover, Tan et al. designed 3D-printed calcium phosphate scaffolds integrating MXene and berberine, as shown in Figures 1C–E, employing photothermal stimulation to trigger sustained antibacterial release and effective healing of infected mandibular bone defects in vivo (Tan et al., 2024). Expanding on this concept, Zhang et al. introduced a three-phase bionic scaffold created by extrusion 3D bioprinting where antimicrobial, immunomodulatory, and regenerative cues are sequentially delivered, resulting in high bacterial clearance and robust tissue restoration in animal models (Zhang et al., 2024). Moreover, as shown in Figure 2A, Hu et al. developed multifunctional scaffolds loaded with TP-Mg nanoparticles, demonstrating potent local infection control and enhanced bone formation in large infectious bone defects (Hu et al., 2024). These studies collectively illustrate the capability of 3D bioprinting to deliver complex therapeutic strategies for bone infection management, underscoring its potential to synchronize infection eradication with accelerated bone healing in translational research. These developments signal growing opportunities for highly personalized solutions.
FIGURE 2
The application of 3D printed antimicrobial scaffolds is not limited to treating infection at bone defects site. Over the past decade, antimicrobial hydrogel scaffolds have been developed for regenerative endodontic procedures. Effective disinfection of root canal is a vital step toward dental pulp stem cell tissue regeneration. However, eliminating resistant microorganisms and residual bacteria during decontamination remained challenging. Ortega et al. loaded gelatin biomaterial ink with 150 μg mL-1 and 250 μg mL-1 benzyldimethyldodecylammonium chloride and printed the 3D construct by an extrusion-based 3D printer, using a 27G nozzle. The 3D printed scaffolds exhibited antimicrobial and antibiofilm activity against endodontic pathogens, including Enterococcus faecalis, Porphyromonas gingivalis, and Streptococcus mutans (Ortega et al., 2025).
3.3 3D bioprinted in vitro models for respiratory infection studies
The outbreak of COVID-19 pandemic in 2020 has brought viral infections into the spotlight of prevention strategies and treatment. Upon entering the human body, a virus binds to specific receptors on the host cell surface, penetrates and releases its genome (Ciotti et al., 2020; Wu et al., 2020; Hwang et al., 2023). Although the immune system is typically capable of eliminating viruses via various mechanisms such as cytotoxic cells, interferons and antibodies, the viral infection can spread to other organs through blood vessels if the natural defense system is not strong enough (Hwang et al., 2023). The transmission of viruses into organs can further lead to cell death, severe inflammation and impaired organ function (Fenner et al., 1987).
Due to the rapid spread of newly emerging viral infections and high death toll, as seen in the latest pandemic, potential therapeutics must be developed without delay. However, because of complex mechanism of viral infection and difficulties in obtaining sufficient number of human airway epithelial cells, current 2D and animal models have been falling short in fully recapitulate the transmission rate and route, disease mechanism and pathogenesis of such infection. Lee et al. utilized micro-extrusion and inkjet printing to replicate the architecture and function of the lower respiratory tract by 3D bioprinting a multilayered airway structure laden with endothelial cells, ECM and human lung cell-derived epithelium. The model facilitated molecular profiling of tissue-specific markers and SARS-CoV-2 entry mediator and served as a platform to study host transcriptomic responses and the efficacy of antiviral drugs such as remdesivir and molnupiravir (Lee et al., 2024). Similarly, micro-extrusion bioprinting of alginate, gelatin, hyaluronic acid, collagen, and laminin-521 was used to create a 3D lung model composed of endothelial cells, primary fibroblasts, macrophage cells, and respiratory epithelial cells. This multi-cellular model was used to study infection dynamics with influenza A virus and the Sars-Cov2 omicron variant, over the course of 21 days (Berg et al., 2025).
Bioprinted in vitro models have demonstrated an enormous potential as a platform for evaluation of viral infection and antiviral drugs. Despite recent advancements, many models have used immortalized cell lines which may not fully represent human tissue behavior. Therefore, the incorporation of human primary cells or induced pluripotent stem cell (iPSC)-derived cells would facilitate the translation of research findings to clinical settings.
3.4 Urinary tract
New applications of 3D bioprinting are revolutionizing the management of urinary tract infections and tissue repair. For instance, as shown in Figure 2D Eugster et al have successfully led an experimental study where a extrusion 3D-printed stents with cannabidiol release was produced for localized treatment of urinary tract infections, demonstrating greater efficacy in vitro than traditional systemic therapy (Eugster et al., 2025). Furthermore, as shown in Figure 2B, Kyser et al utilized extrusion 3D printing to create urinary catheters tube with probiotic Lactobacillus rhamnosus to prevent catheter-associated urinary tract infections (CAUTI) (Kyser et al., 2025). The catheter was tested in vitro under artificial urine flow to assess the stability and the biofilm formation. The constructs maintained their shape and mass for 7 days, with stable L. rhamnosus biofilm not removed by the artificial urine media flow. The results indicate that printed scaffolds with probiotics may be effective candidates for preventing CAUTI. These applications have shown how 3D bioprinting can support the development of treatment in urinary tract infection.
3.5 Female reproductive system
3D bioprinting has emerged as a promising technology for the treatment and study of infections within the female reproductive system. Experimental studies demonstrate the development of innovative extrusion 3D bioprinted scaffolds incorporating Lactobacillus crispatus aimed at preventing bacterial vaginal infections leading to bacterial vaginosis (Kyser et al., 2023). In vitro studies demonstrated that probiotic-laden scaffolds effectively inhibited pathogenic colonization, showcasing the potential for localized and sustained probiotic delivery. Building upon infection treatment, subsequent work by Utomo et al focused on 3D-printed vaginal devices, loaded with metronidazole for bacterial vaginosis, showing prolonged drug release and therapeutic promise (Utomo et al., 2023). Additionally, efforts to repair tissue damage following infections have been made. In fact, Zheng et al developed a novel bioink combining vaginal extracellular matrix (vECM), GelMA, and silk fibroin. This composite supported stem cell viability and enhanced tissue regeneration in a rabbit vaginal defect model, significantly improving angiogenesis, epithelialization, and muscle function (Zheng et al., 2024). Furthermore, 3D bioprinting allows biological models to be reproduced that would normally be impossible to explore. Thus, Sun et al advanced the modeling of placental infections through a 3D bioprinted placenta-on-a-chip platform, enabling in vitro studies of maternal-fetal barrier infections and drug testing (Sun et al., 2025). Collectively, these experimental approaches emphasize the versatility of 3D bioprinting not only in combating infections but also in facilitating tissue regeneration and studying complex infection dynamics. As the field evolves, such technologies hold great promise for personalized and effective therapies in female reproductive health.
3.6 Gastrointestinal tract
3D bioprinting has enabled the creation of engineered constructs and models that advance treatment and mechanistic understanding in gastrointestinal infections. Jiang et al presented a multifunctional bilayer scaffold printed via extrusion 3D bioprinting, incorporating apoptotic extracellular vesicles (ApoEVs) and antibacterial coacervates to prevent infection and promote healing in intestinal wound models, showing enhanced epithelial closure and antibacterial efficacy (Jiang et al., 2025). Vera et al developed a gut-on-chip system with 3D bioprinted villi structures and electrodes for real-time monitoring of the intestinal barrier, enabling high-fidelity simulation of microbial infection and drug screening (Vera et al., 2024). Abdollahi et al engineered a biomimetic 3D substrate mimicking villus-crypt architecture, achieving rapid tissue differentiation and improved natural antimicrobial peptide production, leading to reduced pathogenic infection in cultured gut tissues, as shown in Figure 2C (Abdollahi et al., 2025). Torras et al designed crypt-villus 3D constructs using customized digital light processing-based stereolithography (DLP-SLA) bioprinting, enabling direct bacterial infection modeling and immune response studies within in vitro intestinal tissues (Torras et al., 2023).
Together, these studies demonstrate how bioprinting enables spatially precise, functional models and scaffolds that both treat and replicate complex gut infection processes, paving the way for personalized tissue therapies and mechanistic research in gastrointestinal disease.
4 Conclusion
3D bioprinting presents unique advantages for infection studies, including the ability to create physiologically relevant models, engineer personalized therapeutic constructs, and facilitate the controlled delivery of drugs and bioactive agents. These technologies allow for precise structural design and can mimic the cellular and extracellular environments found in human tissues, improving the relevance of experimental infection models.
Nonetheless, despite significant advances, several limitations are highlighted in the review. The selection and optimization of bioinks is critical: while higher viscosity hydrogels improve mechanical stability, they may compromise cell viability. Low viscosity hydrogels enhance cell preservation but can make maintaining construct integrity difficult. Many in vitro bioprinted models still rely on immortalized cell lines, which do not fully replicate native human tissue responses, limiting translational potential. Looking ahead, it is vital to put efforts into ensuring long-term cell viability, proper vascularization and upscaling the manufacturing process. Furthermore, consideration should be given to ensure that the complex interaction between different cell types and organs and cell migration is achieved. To address the inherent limitations of single tissue or organ infection, integrating multi-organ-on-a-chip (multi-OoC) platforms with 3D bioprinting can offer a promising path. In fact, many pathogens impact the human body systemically; meaning they breach the epithelial barriers and interact with the host immune system and distal organs. Combined use of multi-OoC and 3D bioprinting, although is still in its infancy, further enables cross-organ communication that leads to a more precise disease modeling—thereby facilitating drug screening and development of personalized treatments.
Overall, while 3D bioprinting offers transformative possibilities for infection management and research, further refinement in material properties and cellular composition is required to enhance clinical translation and model reliability.
Statements
Author contributions
SM: Writing – review and editing, Data curation, Visualization, Writing – original draft, Investigation, Conceptualization. WU: Writing – review and editing, Funding acquisition. AF: Writing – review and editing, Funding acquisition. CS: Writing – review and editing. GR: Writing – review and editing, Funding acquisition. SD: Investigation, Writing – review and editing, Funding acquisition, Writing – original draft, Conceptualization, Visualization, Data curation, Project administration.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This research was partially funded by grants from: ERC-2019-Synergy Grant (ASTRA, n. 855923); EIC-2022-PathfinderOpen (ivBM-4PAP, n. 101098989); Project “National Center for Gene Therapy and Drugs based on RNA Technology” (CN00000041) financed by Next-Generation EU PNRR MUR—M4C2—Action 1.4—Call “Potenziamento strutture di ricerca e creazione di “campioni nazionali di R&S” (CUP J33C22001130001). Horizon Europe MSCA DN-ID grant (grant number 101073263), Stop Spread Bad Bugs (SSBB) consortium. This work was carried out within the project “CERES–CErebral three-dimensional bioprinted biological REplica for drug Screening and development”, funded under the cascade call within the Program “D3 4 HEALTH–Digital Driven Diagnostics, prognostics and therapeutics for sustainable Healthcare” (Project Code PNC0000001), financed by the National Recovery and Resilience Complementary Investment Plan (PNC–Italian Ministry of Economy and Finance Decree, 15 July 2021), CUP B53C22005980001. This initiative is funded by the European Union–NextGenerationEU, under the Italian National Recovery and Resilience Plan (PNRR).
Conflict of interest
Authors SM and AF were employed by Hylomorph AG, Technopark.
The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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Summary
Keywords
3D bioprinting, biomaterials, disease modeling, drug discovery, in vitro, multicellular systems
Citation
Mohammadi S, Unger WWJ, Ferrari A, Sanchini C, Ruocco G and D’Alessandro S (2026) Bridging biology and technology: the rise of 3D bioprinting advancements in infection research. Front. Bioeng. Biotechnol. 14:1764653. doi: 10.3389/fbioe.2026.1764653
Received
10 December 2025
Revised
25 December 2025
Accepted
09 January 2026
Published
23 January 2026
Volume
14 - 2026
Edited by
Andrea Banfi, University of Basel, Switzerland
Reviewed by
Roberta Rovelli, University of Siena, Italy
Updates
Copyright
© 2026 Mohammadi, Unger, Ferrari, Sanchini, Ruocco and D’Alessandro.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Salvatore D’Alessandro, salvatore.dalessandro@iit.it
ORCID: Sajad Mohammadi, orcid.org/0000-0001-6878-0099; Wendy Unger, orcid.org/0000-0001-9484-261X; Caterina Sanchini, orcid.org/0000-0002-5659-769X; Giancarlo Ruocco, orcid.org/0000-0002-2762-9533; Salvatore D’Alessandro, orcid.org/0000-0001-7983-2085
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.