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Open research questions in 3D Printing in Biomedical Research

735 gap statements mined from 3D Printing in Biomedical Research papers in our 7.9M-paper local library, which holds 3,561 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Although further studies involving quantitative filament mechanical characterization, long-term stability evaluation, and in vivo performance are warranted, the present work establishes a strong foundation for the future clinical translation of personalized PZA therapy.

    Development and Evaluation of Pyrazinamide-Loaded Immediate Release 3D-printed Tablets for Personalized Tuberculosis Therapy via Fused Deposition Modeling · 2026 · DOI

  • A major limitation is that many studies remain at the proof-of-concept stage, with outcomes dependent on nanoparticle labeling, magnetic field strength and gradient, cell density, assembly conditions, and culture parameters that are not consistently standardized or quantitatively compared across studies.

    Magnetic Cell Assembly for Engineering Living Building Blocks: Principles, Strategies, and Biomedical Applications · 2026 · DOI

  • We have detailed how microgels, engineered from biocompatible biopolymer networks, resolve these limitations by functioning as programmable reservoirs that shield sensitive bioactives from oxidative, thermal, and photochemical degradation.

    Food-Grade Microgels for Age-Related Macular Degeneration: Design, Fabrication, and Targeted Delivery · 2026 · DOI

  • Often, however, the possible use is currently still restricted and limited by obstacles and technical challenges, so that a meaningful and profitable use in the future still requires further work on the simple implementation, changes in legal framework and reproducible biological standard procedures including the generation and usage of robust biosensor strains.

    Microfluidic-Based Whole-Cell Biosensor Systems—Challenges and Future Applications · 2026 · DOI

  • To better mimic the native ultrathin basement membrane, membrane thickness remains one of the existing challenges. While thinner membranes allow for higher hydraulic and diffusive permeability, they often do not have in vivo-like membrane surface and stiffness properties.

    Membrane-Integrated Organ-on-a-Chip Systems · 2026 · DOI

  • This is particularly relevant to cervical cancer, where disease management is strongly affected by complex pelvic anatomy, heterogeneous tumor geometry, cervicovaginal tissue characteristics, and the need for precise local intervention. In brachytherapy, 3D-printed polymeric devices have shown clear procedural relevance.

    Polymer-Based Additive Manufacturing in Cervical Cancer Management: A Review · 2026 · DOI

  • Collagen-I densification presents a specific challenge for in-chip scaffold fabrication, as it can compromise scaffold anchorage, lumen alignment, and perfusion compatibility. The need to balance the degree of crosslinking and the mechanical properties of the collagen-I constructs. The challenge of maintaining the integrity of the scaffold during perfusion and mechanical stimulation.

    In-chip volumetric printing of perfusable and stretchable collagen-I scaffolds for mammary tissue models · 2026 · DOI

  • The lack of positional control in static culture. The absence of shear stress in static culture. The need for integrated biosensing in organoid culture.

    Microfluidic engineering for organoid formation, cultivation, and sensing · 2026 · DOI

  • A significant limitation of this study is the small number of organoid cell lines used in the experiments. The lack of standardization for canine intestinal organoid cultures in both 3D and 2D systems has been previously mentioned, and our group has made efforts to streamline standardized culture techniques, now published in two manuscripts.

    A Preclinical Model to Assess Intestinal Barrier Integrity Using Canine Enteroids and Colonoids · 2025 · DOI

  • Several technical and translational challenges must be addressed to enable broader application and clinical implementation. First, the development of mechanically robust, biocompatible, and degradable materials remains a priority—especially those capable of responding to environmental stimuli, such as temperature, pH, or mechanical stress.

    Advances in Digital Light Processing (DLP) Bioprinting: A Review of Biomaterials and Its Applications, Innovations, Challenges, and Future Perspectives · 2025 · DOI

  • Future research should focus on improving material properties, hybrid fabrication strategies, and automated post-processing to enhance the feasibility of AM in tissue engineering and regenerative medicine.

    Biomaterial-Based Additive Manufactured Composite/Scaffolds for Tissue Engineering and Regenerative Medicine: A Comprehensive Review · 2025 · DOI

  • Second, robust vascularization and stable perfusion channels are complicated to model and are often lacking, which can compromise nutrient and oxygen gradients. The integration of real-time biosensors (such as TEER, lactate, and oxygen) remains rare but is potentially essential for drug screening. Bubble formation, inconsistent flow, and channel occlusion continue to limit reproducibility in long-term experiments.

    Developments and Applications of Liver-on-a-Chip Technology—Current Status and Future Prospects · 2025 · DOI

  • These materials have the potential to reduce the complexity of the pharmaceutical industry in the future by overcoming the existing limitations and fostering innovation. Using artificial intelligence (AI), addressing rare diseases, and exploring underserved medical areas, advanced materials can further develop drug delivery systems to improve patient outcomes globally (Figure 5).

    Revolutionizing Drug Delivery: The Impact of Advanced Materials Science and Technology on Precision Medicine · 2025 · DOI

  • Despite significant progress, several challenges remain, including scalability, cost-effectiveness, immune compatibility, and regulatory hurdles. Addressing these limitations is critical to ensuring the successful clinical translation of these therapies.

    Advances in Drug Delivery Integrated with Regenerative Medicine: Innovations, Challenges, and Future Frontiers · 2025 · DOI

  • All of the previous studies are promising for alopecia treatment; some studies lack long-term stability and efficacy data. The study by Zhang et al. showed promising results for quercetinloaded zinc mesoporous silica nanoparticles, but the short duration (14 days) limits our ability to assess long-term efficacy and safety.

    The Future of Alopecia Treatment: Plant Extracts, Nanocarriers, and 3D Bioprinting in Focus · 2025 · DOI

  • This invented technology is not only devoid of solvent usage but also eliminates the need for using multivalent cations, e.g., Ca+2, by relying on a lab-on-a-chip technique with hydrodynamic flow focused mixing of the fluids in order to produce less dispersed and more homogeneous nanoparticles.

    A Green, Solvent- and Cation-Free Approach for Preparing 5-Fluorouracil-Loaded Alginate Nanoparticles Using Microfluidic Technology · 2025 · DOI

  • Its capacity to challenge the “one-size-fits-all” approach is especially important in paediatrics, where age-, weight-, and condition-specific dosing needs, as well as challenges related to swallowability and palatability, often restrict the effectiveness of traditional dosage forms.

    Three-Dimensionally Printed Paediatric Medicines: Formulation, Process, and Regulatory Considerations · 2025 · DOI

  • In particular, using Micro-CT to validate internal architecture provides novel insight into structure–performance relationships, which has been underexplored in earlier studies.

    Advancing Personalized Medicine Through FDM 3D Printing: Ketoprofen Tablets with Customizable Drug Release Profiles and In Silico Simulation · 2025 · DOI

  • Nevertheless, numerous authors concur that in many studies, the mechanical and biological properties of the fabricated materials are not fully investigated.

    From Waste to Innovation: A Circular Economy Approach for Tissue Engineering by Transforming Human Bone Waste into Novel Collagen Membranes · 2025 · DOI

  • Three-dimensional (3D) bioprinting has rapidly evolved from a novel biofabrication tool into an indispensable cornerstone of tissue engineering and regenerative medicine.

    Advances in 3D Bioprinting for Scaffold-Based and Scaffold-Free Tissue Engineering and Regenerative Medicine · 2026 · DOI

  • The marked spatial and temporal heterogeneity of the TME continues to limit the effectiveness of both modern anticancer therapies and TCM-based interventions. In this context, microfluidic technology has emerged as a valuable experimental platform for reconstructing complex biological microenvironments in a controllable and dynamic manner.

    Tumor Microenvironment-on-a-Chip: Construction and Application in Traditional Chinese Medicine Anti-Tumor Therapy · 2026 · DOI

  • Overcoming limited biological fidelity and poor reproducibility of current hydrogel bioinks.

    Polymer Network Engineering of Hydrogel Bioinks for Skin Regeneration: From Molecular Design to Adaptive Biofabrication · 2026 · DOI

  • The field of cardiovascular tissue engineering has advanced significantly, owing to progress in 3D bioprinting and bioink technologies. However, fully replicating the complex hierarchical structure and function of the cardiovascular system remains challenging.

    Three-Dimensional Printing and Bioprinting Strategies for Cardiovascular Constructs: From Printing Inks to Vascularization · 2025 · DOI

  • The integration of CI, especially ML, has shown great potential in advancing 3D printing for drug delivery applications. CI-driven approaches have proven useful in predicting material printability, optimizing drug release rates, designing complex structures, ensuring quality control, and improving manufacturing processes.

    Use of Computational Intelligence in Customizing Drug Release from 3D-Printed Products: A Comprehensive Review · 2025 · DOI

  • Investigating the use of AI and automated biofabrication to improve reproducibility and facilitate adaptation to patient-specific wound geometries. Developing standardized manufacturing and regulatory criteria for hydrogel bioinks. Improving biological fidelity and immune compatibility of hydrogel bioinks.

    Polymer Network Engineering of Hydrogel Bioinks for Skin Regeneration: From Molecular Design to Adaptive Biofabrication · 2026 · DOI

Most-cited papers in 3D Printing in Biomedical Research

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735 gap statements have been mined from 3D Printing in Biomedical Research papers in our 7.9M-paper local library, which holds 3,561 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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