Commercial photopolymer resins used in additive manufacturing are typically designed to be chemically inert, ensuring print fidelity and long-term stability. However, the ability to chemically functionalize printed surfaces would significantly expand the integration of commercial 3D printing with bioanalytical and lab-on-a-chip systems. Here, we introduce a materials-design strategy in which chemical functionality is incorporated directly into the resin formulation. Addition of a copolymerizable acrylamide monomer produces an activation-ready photopolymer resin with surface-accessible functionality suitable for post-print modification, thereby reducing dependence on geometry-sensitive surface-treatment methods. The modified resin retains low autofluorescence and micron-scale printing resolution, maintaining compatibility with fluorescence-based microfluidic assays. The functionalized surface enables glutaraldehyde-mediated immobilization of model proteins, including bovine haemoglobin and bovine serum albumin. Successful protein immobilization was verified by protein staining and wettability measurements, while selective recognition by fluorescent molecularly imprinted nanoparticles revealed highly specific binding under static and flow conditions, with dissociation constants (Kd) of 2.57 and 53.0 nM for target binding. By incorporating modification-ready functionality into a commercial photopolymer resin while preserving its printing and optical properties, this work provides a practical strategy for the rapid fabrication of protein-functionalized 3D-printed microfluidic devices.
Bone tissue exhibits pronounced spatial heterogeneity in structure, composition, and mechanical properties, which is essential for effective load bearing and regeneration. Conventional homogeneous scaffolds often fail to reproduce these features, thereby limiting their functional and clinical performance. Recent advances in bioprinting have enabled the fabrication of non-uniform bone scaffolds with spatially controlled architectural, material, and biological gradients tailored to site-specific functional demands. This review critically examines current strategies for the design and fabrication of non-uniform bone scaffolds. Bioprinting technologies that enable gradient control, including multi-material extrusion, microfluidic-based printheads, and hybrid manufacturing approaches, are discussed. Material strategies such as composite gradients, hierarchical porosity, and nano- to micro-scale compositional variations are analyzed in terms of their mechanical performance and biological relevance. In addition, spatially regulated bioactive modulation using cells, growth factors, and extracellular vesicles is reviewed from a practical and translational perspective. Imaging-guided and patient-specific case studies are highlighted to illustrate the clinical potential of non-uniform scaffold designs, while key technical, biological, and regulatory challenges are critically assessed. Finally, emerging directions, including 4D bioprinting, computational digital twins, and standardized manufacturing pathways, are discussed. Overall, this review underscores that function-driven, non-uniform scaffold design represents a promising route toward more effective and clinically translatable strategies for bone regeneration.
The development of models for neurodegenerative and neurovascular diseases has become crucial for understanding complex biological processes, including the progression of Alzheimer’s disease, stroke, and glioblastoma. Traditional in vitro systems have significant limitations in replicating the intricate interactions between the blood-brain barrier (BBB), endothelial cells, and surrounding tissues. This review explores a novel strategy to enhance disease modeling technology through the integration of 3D bioprinting with microfluidic chips. This advanced approach enables the precise creation of dynamic tissue constructs that emulate the physiological microenvironment of the neurovascular unit, facilitating studies on drug cytotoxicity, cell differentiation, and intercellular signaling. Furthermore, the platform offers promising applications for identifying therapeutic targets and designing miniaturized biosensor-embedded MEMS (micro-electro-mechanical systems) and NEMS (nano-electro-mechanical systems) for the sensitive detection of disease biomarkers. The integrated platform further incorporates design modifications, including optimized microchannel geometry, bioprinted three-dimensional cellular architectures, and improved spatial organization of biological components within the microfluidic chip. These engineering advancements enhance cell viability, physiological cell-cell and cell-matrix interactions, nutrient and oxygen diffusion, and overall biomimetic functionality, while clearly demonstrating the contribution of 3D bioprinting to improved device performance, experimental reproducibility, and biological relevance for neurovascular disease modeling and therapeutic evaluation. The system is particularly suited for modeling the pathophysiological conditions of neurovascular and neurodegenerative diseases, such as Alzheimer’s disease, stroke, and brain cancer (glioblastoma), in a controlled and reproducible manner. This capability was demonstrated through preclinical and co-clinical drug trials, generating functional data to support effective therapeutic interventions. Additionally, the study highlights the creation of pathophysiological models incorporating neural, endothelial, and adjacent cell types to investigate neural–microvascular interactions. The integrated platform serves as a powerful tool for evaluating drug efficacy, deciphering disease mechanisms, and advancing personalized medicine approaches. These findings underscore the transformative potential of combining 3D bioprinting and microfluidic technologies to develop highly functional models for neurodegenerative and neurovascular diseases, offering significant value for translational biomedical research.
Three-dimensional (3D) printing has advanced additive manufacturing by enabling the fabrication of complex, application-specific structures across biomedical, pharmaceutical, and industrial fields. However, conventional layer-by-layer deposition presents inherent limitations, including slow production rates, material constraints, and structural inconsistencies. This review critically evaluates recent innovative developments in advanced 3D bioprinting/biofabrication technologies, namely Volumetric Additive Manufacturing (VAM), Freeform Reversible Embedding of Suspended Hydrogels (FRESH), and Embedded Multi-Material Extrusion Bioprinting (EMMB), which introduce novel fabrication strategies to overcome these limitations. Techniques are examined in terms of their working principles, material compatibility, resolution, structural fidelity, and suitability for tissue engineering, drug delivery, and regenerative medicine. The review also addresses ongoing challenges, including bioink optimization, interfacial control in multi-material systems, and achieving scalability without compromising functionality. Future perspectives include the integration of hybrid manufacturing, artificial intelligence (AI) for real-time process optimization, and microscale fabrication strategies targeting medical microdevices and micro-electro-mechanical systems (MEMS). By providing a comparative overview of conventional and emerging 3D printing techniques, this work outlines a path toward the next generation of high-precision, multifunctional biofabrication platforms capable of supporting personalized therapeutic solutions and complex prototyping across diverse domains.
