Biopolymer Scaffolds in 3D Tissue Models: Advancing Antimicrobial Drug Discovery and Bacterial Pathogenesis Studies—A Scoping Review
Abstract
1. Introduction
2. Materials and Methods
2.1. Eligibility Criteria
2.2. Information Sources and Search Strategy
2.3. Selection of Sources of Evidence
2.4. Data Charting Process
2.5. Data Items
2.6. Critical Appraisal of Individual Sources of Evidence
2.7. Synthesis of Results
3. Results
3.1. Limitations of Conventional (2D) Models for Infection Studies and Drug Discovery
3.2. Fundamentals of Tissue Bioengineering for 3D Infection Models
3.2.1. Biocompatible Materials and Their Properties
3.2.2. Techniques for 3D Model Construction
3.3. Applications of 3D Models in Bacterial Pathogenesis Studies
3.4. Three-Dimensional Models for Antimicrobial Drug Discovery and Screening
3.5. Challenges and Future Perspectives
4. Discussion
4.1. Evaluating the Efficacy and Potential of 3D Models
4.2. A Critical Research Gap in Antimicrobial Drug Discovery
4.3. The Way Forward: Bridging the Gap
4.4. Limitations of This Scoping Review
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
2D | Two-dimensional |
3D | Three-dimensional |
AMR | Antimicrobial Resistance |
CC BY | Creative Commons Attribution |
ECM | Extracellular Matrix |
E. coli | Escherichia coli |
LIMAV | Interdisciplinary Laboratory of Advanced Materials |
MeSH | Medical Subject Headings |
MCP-1 | Monocyte Chemoattractant Protein-1 |
MRSA | Methicillin-resistant Staphylococcus aureus |
MSSA | Methicillin-sensitive Staphylococcus aureus |
PCL | Polycaprolactone |
PET | Polyethylene terephthalate |
PLA | Poly(lactic acid) |
PMMA | Poly(methyl methacrylate) |
PPGTAIR | Graduate Program in Technologies Applied to Animals of Regional Interest |
PRISMA | Preferred Reporting Items for Systematic Reviews and Meta-Analyses |
S. aureus | Staphylococcus aureus |
TNF-α | Tumor Necrosis Factor-alpha |
UFPI | Federal University of Piauí |
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Section | Item | Checklist Item | Page |
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Title | 1 | Identify the report as a scoping review. | 1 |
Abstract | 2 | Provide a structured summary that includes (as applicable): background, objectives, eligibility criteria, sources of evidence, charting methods, results, and conclusions that relate to the review questions and objectives. | 1 |
Introduction | 3 | Describe the rationale for the review in the context of what is already known. Explain why the review questions/objectives lend themselves to a scoping review approach. | 1–3 |
4 | Provide an explicit statement of the questions and objectives being addressed with reference to their key elements (e.g., population or participants, concepts, and context) or other relevant key elements used to conceptualize the review questions and/or objectives. | 2–3 | |
Methods | 5 | Indicate whether a review protocol exists; state if and where it can be accessed (e.g., a Web address); and if available, provide registration information, including the registration number. | 3 |
6 | Specify characteristics of the sources of evidence used as eligibility criteria (e.g., years considered, language, and publication status), and provide a rationale. | 4–6 | |
7 | Describe all information sources in the search (e.g., databases with dates of coverage and contact with authors to identify additional sources), as well as the date the most recent search was executed. | 4–6 | |
8 | Present the full electronic search strategy for at least 1 database, including any limits used, such that it could be repeated. | 4–6 | |
9 | State the process for selecting sources of evidence (i.e., screening and eligibility) included in the scoping review. | 4–6 | |
10 | Describe the methods of charting data from the included sources of evidence (e.g., calibrated forms or forms tested before use, whether charting was done independently or in duplicate) and any processes for obtaining and confirming data from investigators. | 4–6 | |
11 | List and define all variables for which data were sought and any assumptions and simplifications made. | 4–6 | |
12 | If done, provide a rationale for conducting a critical appraisal of included sources of evidence; describe the methods used and how this information was used in any data synthesis (if appropriate). | 4–6 | |
13 | Describe the methods of handling and summarizing the data that were charted. | 4–6 | |
Results | 14 | Give numbers of sources of evidence screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally using a flow diagram. | |
15 | For each source of evidence, present characteristics for which data were charted and provide the citations. | 5 | |
16 | If done, present data on critical appraisal of included sources of evidence (see item 12). | None | |
17 | For each included source of evidence, present the relevant data that were charted that relate to the review questions and objectives. | 7 and 8 | |
18 | Summarize and/or present the charting results as they relate to the review questions and objectives. | 7 and 8 | |
Discussion | 19 | Summarize the main results (including an overview of concepts, themes, and types of evidence available), link to the review questions and objectives, and consider the relevance to key groups. | 8–13 |
20 | Discuss the limitations of the scoping review process. | 12 | |
21 | Provide a general interpretation of the results with respect to the review questions and objectives, as well as potential implications and/or next steps. | 13 | |
Funding | 22 | Describe sources of funding for the included sources of evidence, as well as sources of funding for the scoping review. Describe the role of the funders of the scoping review. | 13 |
Keyword | Database | ||
---|---|---|---|
PubMed | Scopus | Web of Science | |
drug screening | 51.780 | 119.636 | 70.001 |
bacterial pathogenesis | 85.223 | 15.690 | 13.704 |
host–pathogen interaction | 23.707 | 25.614 | 6.322 |
3D tissue model | 6.198 | 14.979 | 13.856 |
bioengineered models | 39.103 | 802 | 3.174 |
antimicrobial drug discovery | 7.868 | 3.184 | 4.923 |
3D tissue model AND drug screening | 740 | 1.356 | 1.067 |
3D tissue model AND bioengineered models | 2.090 | 194 | 440 |
3D tissue model AND host–pathogen interaction | 78 | 99 | 59 |
3D tissue model AND bacterial pathogenesis | 49 | 20 | 21 |
3D tissue model AND antimicrobial drug discovery | 13 | 1 | 2 |
3D tissue model AND bioengineered models AND drug screening | 295 | 39 | 68 |
3D tissue model AND bioengineered models AND host–pathogen interaction | 17 | 5 | 2 |
3D tissue model AND bioengineered models AND bacterial pathogenesis | 10 | 0 | 1 |
3D tissue model AND bioengineered models AND antimicrobial drug discovery | 2 | 0 | 0 |
TOTAL | 217.173 | 181.619 | 113.640 |
Model Type | Biomaterials | Main Application | Pathogen/Microbiota | Reference | |
---|---|---|---|---|---|
Bioprinting-Based Models | 3D Bioprinted Bacterial Biofilms | Alginate Bioink | Antimicrobial Drug Testing, Biofilm Study | E. coli, S. aureus (MSSA/MRSA), P. aeruginosa | [76] |
PCL/Alginate 3D-Printed Scaffold | PCL, Sodium Alginate | Dual Drug Delivery, Antimicrobial Activity | S. aureus | [77] | |
3D Printed PMMA/PLA Beads/Filaments | PMMA, PLA, Silicone oil | Antimicrobial Drug Delivery | E. coli, S. aureus | [78] | |
3D Printed Bacteria-Laden Materials | Hyaluronate, Kappa-Carrageenan, Fumed Silica (Flink) | Functional Living Materials, Bioremediation | A. xylinum, B. subtilis | [79] | |
Organoid/ Spheroid Derived Models | Human Small Intestinal Epithelium (Enteroid-derived) | 3D Silk Scaffolds | Host–Pathogen Interaction | E. coli | [80] |
Anatomical Gingival Tissue Model | Silk Biopolymer Scaffolds | Host-Microbiome Interaction | Oral Microbiome | [81] | |
Electrospinning and Porous Scaffolds | Human Gut Microbiota Model | Electrospun Gelatin Structure | Bacterial Biofilm, Microbiota Culture | Human Fecal Microbiota, selected gut microbes | [82] |
Collagen/Hydrogel-Based Tissue Models | Skin Epidermis Model (co-culture) | Hydrogel-supported Cellulose Matrix | Antimicrobial Testing, Host Response | Polymicrobial Wound Biofilms | [83] |
Gut Mucosal Microenvironment (Flipwell System) | PET membrane with Collagen (PureCol) & Poly-D-Lysine | Host-Microbiota Interaction, Immunomodulation | B. subtilis, Gut Microbiota | [84] | |
Cervicovaginal Epithelia Model | Collagen coating on Transwell inserts | Host–Pathogen Interaction, Microbiota | C. trachomatis, N. gonorrhoeae, Vaginal Microbiota | [85] | |
Standardized Wounded Human Skin Model | Rat-tail Collagen Matrix | Antimicrobial Testing, Host Response | S. aureus, P. aeruginosa | [86] | |
Other Innovative Methods | Microstructured Bacterial Microenvironments | Photoresponsive Protein Hydrogels | Bacterial Microenvironment Control | Motile Bacteria (general) | [87] |
Human Pleura Organotypic Co-Culture | Not explicitly stated (implied matrix) | Host–Pathogen Interaction, Biofilm Study | S. aureus | [88] |
Feature/Parameter | 2D Culture Models | 3D Bioengineered Models |
---|---|---|
Drug diffusion | Rapid, uniform diffusion; overestimates efficacy | Controlled, heterogeneous diffusion; mimics tissue and biofilm barriers |
Antibacterial effects | Often show higher sensitivity to antimicrobials (false positives) | Demonstrates realistic resistance levels, consistent with in vivo infections |
Biofilm architecture | Poorly represented; limited extracellular matrix | Recapitulates biofilm complexity, extracellular polymeric substances, and gradients |
Drug delivery systems | PET membrane coated with PureCol (Collagen) & Poly-d-Lysine | Host-Microbiota Interaction, Immunomodulation |
Cervicovaginal Epithelia Model | Limited to soluble compounds in media | Enables evaluation of sustained release (scaffolds, hydrogels, beads) and multi-drug delivery |
Host–pathogen interactions | Minimal immune or inflammatory response | Incorporates immune-like responses (cytokines, chemokines, cell recruitment) |
Clinical predictability | Low; poor correlation with in vivo outcomes | High; closer approximation of pharmacokinetics and pharmacodynamics in human tissues |
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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Santos, J.d.A.; Coelho, A.d.A. Biopolymer Scaffolds in 3D Tissue Models: Advancing Antimicrobial Drug Discovery and Bacterial Pathogenesis Studies—A Scoping Review. J. Pharm. BioTech Ind. 2025, 2, 15. https://doi.org/10.3390/jpbi2030015
Santos JdA, Coelho AdA. Biopolymer Scaffolds in 3D Tissue Models: Advancing Antimicrobial Drug Discovery and Bacterial Pathogenesis Studies—A Scoping Review. Journal of Pharmaceutical and BioTech Industry. 2025; 2(3):15. https://doi.org/10.3390/jpbi2030015
Chicago/Turabian StyleSantos, Jailson de Araújo, and Ariel de Almeida Coelho. 2025. "Biopolymer Scaffolds in 3D Tissue Models: Advancing Antimicrobial Drug Discovery and Bacterial Pathogenesis Studies—A Scoping Review" Journal of Pharmaceutical and BioTech Industry 2, no. 3: 15. https://doi.org/10.3390/jpbi2030015
APA StyleSantos, J. d. A., & Coelho, A. d. A. (2025). Biopolymer Scaffolds in 3D Tissue Models: Advancing Antimicrobial Drug Discovery and Bacterial Pathogenesis Studies—A Scoping Review. Journal of Pharmaceutical and BioTech Industry, 2(3), 15. https://doi.org/10.3390/jpbi2030015