Skin functions as a primary protective barrier against mechanical injury, microbial invasion, and dehydration. Extensive trauma and chronic diseases pose significant clinical challenges to wound healing. Conventional wound dressings and skin substitutes often lack the structural and biochemical sophistication to dynamically interact with the wound. Hyaluronic acid (HA), a key glycosaminoglycan in the extracellular matrix, has emerged as a versatile biomaterial for wound repair due to its biocompatibility, hydration capacity, and intrinsic bioactivity. However, native HA suffers from limitations such as rapid degradation and poor mechanical strength, necessitating advanced engineering strategies, including chemical modification, biofunctionalization, and compositing, to enhance its versatility. Three-dimensional bioprinting has recently emerged as a transformative technology, enabling the precise deposition of HA-based biomaterials to form biomimetic constructs with spatial heterogeneity. In this review, we first elucidate the mechanism by which HA orchestrates the wound healing cascade, followed by a list of engineered approaches to enhance HA’s functionality. This review then focuses on the capabilities of mainstream bioprinting technologies for fabricating HA-based wound dressings and stratified skin substitutes. Finally, we discuss prevailing challenges and outline future perspectives, emphasizing innovations in dynamic biomaterials, hybrid bioprinting strategies, and the integration of artificial intelligence to advance the clinical translation of HA products for wound healing.

Hydrogels, three-dimensional (3D) printing, and 3D bioprinting hold considerable promise for biomedical applications. Compared to conventional hydrogel fabrication strategies triggered by light, heat, or crosslinking agents, acoustic-assisted hydrogel fabrication, 3D printing, and 3D bioprinting offer unique advantages, including superior tissue penetration, high spatiotemporal controllability, and enhanced biosafety. This review systematically elucidates the significant potential and innovative mechanisms of ultrasound as a unique physical stimulus in these fields. This review highlights the fundamental principles of acoustic effects—cavitation, mechanical effects, and thermal effects—and their roles in hydrogel preparation. We then comprehensively discuss the multiple pathways for acoustic-assisted hydrogel fabrication, including cavitation-triggered free-radical polymerization, mechanically/thermally induced polymerization, liposome-mediated and enzyme-catalyzed polymerization, self-assembly systems for polymerization, and homogenization effects in polymerization, highlighting their respective applications in biomedicine and other related fields. Subsequently, advances in the emerging field of acoustic-assisted 3D printing and 3D bioprinting are reviewed in detail, ranging from the acoustic triggering of 3D printing with thermally curable/free-radical polymerization inks to micrometer-scale 3D bioprinting using cell-laden bioinks. Finally, this review highlights current bottlenecks and future research directions in acoustic-assisted hydrogel fabrication, 3D printing, and 3D bioprinting.

Three-dimensional (3D) printing has evolved into a valuable adjunct in neurosurgery, enabling patient-specific surgical planning, simulation, education, and implant fabrication. Although its technical feasibility and clinical utility are well documented, institutional integration and further development across European neurosurgical departments remain insufficiently defined. Two cross-sectional online surveys were conducted among European neurosurgeons in 2020 and 2025. The initial survey was distributed via the European Association of Neurosurgical Societies (EANS), while the follow-up survey was disseminated through national neurosurgical societies and direct re-contact of prior participants. A total of 172 completed questionnaires from 44 countries were included. Descriptive and comparative statistical analyses were performed using chi-square or Fisher’s exact tests with false discovery rate correction. Between 2020 and 2025, a significant maturation of 3D printing practices was observed. Routine or regular departmental use increased, whereas single-case-only applications declined significantly (20.0% vs. 0%; p = 0.01). Responsibility for printing shifted markedly toward in-house production: neurosurgeon-led printing increased from 0% to 20.68% (p < 0.001), while reliance on external providers decreased from 21.81% to 0% (p < 0.01). Implant fabrication emerged as a novel clinical application (0% vs. 27.58%; p < 0.001). Diversification of printing technologies and improved cost efficiency were reported; however, formal quality management procedures remained limited. Major barriers included restricted time resources, insufficient institutional support, and high costs. Over five years, 3D printing in European neurosurgery has transitioned from sporadic, externally dependent use toward structured, institutionally integrated workflows with expanding clinical applications. Standardized quality assurance, regulatory clarity, and high-quality prospective outcome studies are essential to further establish 3D printing as a routine clinical technology.

Infected wounds pose a significant clinical challenge, as persistent bacterial colonization exacerbates inflammation, disrupts the local immune microenvironment, and delays tissue repair. Here, we report the development of a 3D printing dual-crosslinked hydrogel scaffold loaded with ginger-derived exosome-like vesicles (GPP@G-ELNs) to promote healing of infected full-thickness wounds. The hydrogel was fabricated by combining GelMA-PBA and PVA to form a dual-network structure, followed by photo-crosslinking and 3D printing, and then loaded with G-ELNs. The bioactivity of the scaffold was evaluated in an infected rat wound model, focusing on wound closure, angiogenesis, antibacterial efficacy, and immunomodulatory effects. Treatment with GPP@G-ELNs hydrogel significantly accelerated wound healing, reduced inflammatory cell infiltration, promoted collagen deposition, and enhanced angiogenesis. Moreover, the hydrogel exhibited potent antibacterial activity, with ginger-derived exosomes playing a critical role in modulating macrophage polarization and controlling local immune responses. These findings demonstrate that the 3D printing GPP@G-ELNs hydrogel provides an integrated platform for infection control, immunoregulation, and tissue regeneration, offering promising potential for clinical application in the management of infected wounds.

Biodegradable polymers are increasingly recognized as key enablers of sustainable additive manufacturing (AM), offering a unique combination of environmental degradability, tunable mechanical performance, and compatibility across diverse printing platforms. This review examines recent advances in the molecular design, composite formulation, and three-dimensional printing of biodegradable thermoplastics, including polylactic acid, polycaprolactone, poly(butylene adipate-co-terephthalate), and polybutylene succinate, across major AM platforms such as fused deposition modeling, direct ink writing, and digital light processing. Particular emphasis is placed on structure–property–function–degradation relationships that influence rheological behavior, interlayer adhesion, mechanical anisotropy, and life-cycle performance. Material engineering strategies, including polymer blending, reactive compatibilization, nanofiller reinforcement, and platform-specific parameter optimization, are critically examined for their capacity to enhance print fidelity and enable precise control over degradation kinetics. Representative applications in biomedical scaffolds, controlled drug delivery systems, agricultural devices, and compostable packaging demonstrate how deliberate material–process integration can achieve both functional performance and temporally programmed degradation. Furthermore, sustainable design paradigms, such as design for degradation, life-cycle synchronization, topology-driven material minimization, and circular manufacturing frameworks, are discussed as essential for transitioning AM from rapid prototyping to responsible large-scale production. Despite substantial progress, challenges remain in mechanical robustness, material standardization, and end-of-life infrastructure. Addressing these limitations will require coordinated advances in polymer chemistry, processing science, and life-cycle engineering to establish truly circular, high-performance biodegradable AM systems.

Organoids are three-dimensional multicellular models generated through the intrinsic self-organization of stem cells and have emerged as powerful platforms for disease modeling, drug screening, and precision medicine. However, most organoids cultured in vitro lack a functional vascular interface, which restricts oxygen and nutrient transport, leading to central hypoxia and necrosis and ultimately limiting long-term maintenance, maturation, and translational applicability. To address this bottleneck, a range of three-dimensional bioprinting and biofabrication strategies have been developed to support vascularized organoid and organoid-inspired models. Importantly, current technologies do not yet routinely permit the direct fabrication of physiologically complete 1–10 μm capillary beds within organoids. Instead, their major contributions lie in the generation of perfusable mesoscale conduits, endothelialized hollow channels, multicellular architectures, microfluidic perfusion platforms, and self-organizing microenvironments that, together, facilitate vascular integration and maturation. In this review, we summarize the major biofabrication approaches relevant to vascularized organoid models, emphasizing their roles in vascular manufacturing, technical strengths, and limitations. We further discuss material systems specifically relevant to organoid vascular fabrication, including sacrificial materials, endothelialization-supportive matrices, mechanically stable, perfusion-compatible supports, and organ-specific ECM-derived bioinks. In addition, we analyze key vascularization-enabling strategies, such as endothelialized template formation, multicellular bioprinting, dynamic perfusion, microfluidic integration, and self-organization-assisted maturation. By comparing organ-specific requirements across brain, tumor, cardiac, hepatic, renal, pulmonary, pancreatic, and intestinal models, we further highlight how vascular scale, endothelial phenotype, structural hierarchy, and functional endpoints differ by application. Finally, we discuss the major unresolved challenges, particularly the gap between printable mesoscale channels and physiological capillary networks, the mismatch between generic endothelial sources and organ-specific vascular phenotypes, and the lack of standardized functional criteria for evaluating vascularization. Overall, future progress should depend less on direct capillary-scale printing alone and more on integrating biofabrication, perfusion engineering, and developmental self-organization to achieve reproducible, functionally meaningful vascularized organoid models.

Reproducing the continuous compositional and cellular transitions found in native tissues remains a major challenge in extrusion-based bioprinting, which typically generates constructs composed of discrete regions and imposes stringent rheological requirements on bioinks. Microfluidic bioprinting offers new opportunities to reproduce tissue heterogeneity by enabling controlled mixing of biomaterials and cell populations during extrusion. In this study, we present a coaxial microfluidic bioprinting strategy for fabricating hydrogel scaffolds with continuous cellular gradients using low-viscosity self-assembling peptide bioinks. The system combines three independently controlled syringe pumps with a 3D-printed coaxial nozzle containing a screw-like passive mixer. Two low-viscosity RADA16-I peptide solutions containing different cell populations are mixed in situ, while a methylcellulose–alginate shell stabilizes the filament during printing and supports post-printing self-assembly of the core hydrogel. Computational simulations confirm efficient mixing within the nozzle, and fluorescence imaging demonstrates smooth compositional transitions along printed filaments. The system enables the fabrication of scaffolds containing co-culture gradients of endothelial cells and mesenchymal stem cells, which remain viable and display cell-type-specific organization. Overall, this approach enables the printing of soft peptide hydrogels and the fabrication of biomimetic constructs with continuous cellular transitions, highlighting its potential for tissue engineering and regenerative medicine.

Bone tumors are malignant diseases that pose a serious threat to human health, with an increasing incidence rate. Traditional two-dimensional cell cultures and mouse xenograft models have limitations in replicating the complexity of the tumor microenvironment and in accurately mimicking in vivo physiological conditions. Three-dimensional bioprinting technology, as an advanced biofabrication technique, can efficiently, economically, and consistently construct tumor models with complex geometric structures by precisely controlling the spatial distribution of cells, growth factors, and biomaterials. Three-dimensional printed bone tumor models based on bioinks possess higher biological fidelity and physiological relevance, realistically recreating the complex structure and function of the tumor microenvironment and accurately simulating tumor heterogeneity, cell migration, proliferation, invasion, and intercellular interactions. This technology can not only effectively simulate key biological processes of tumor development and progression but also accurately evaluate the response of tumor cells to novel anticancer drugs, supporting the realization of personalized precision medicine. Therefore, three-dimensional bioprinting technology provides a powerful scientific tool and new research ideas for the mechanistic study of bone tumors, the screening and optimization of anticancer drugs, and the development of personalized treatment plans.

Impaired bone regeneration in osteoporosis primarily stems from a local pathological microenvironment characterized by high levels of reactive oxygen species (ROS), which severely inhibits osteogenic differentiation and angiogenesis. To address this challenge, this study engineered a 3D-printed multifunctional composite scaffold consisting of an α-tricalcium phosphate/zinc oxide (α-TCP/ZnO) matrix loaded with chlorogenic acid–europium (CGA–Eu) metal-phenolic network nanoparticles. The incorporation of ZnO effectively buffered the acidity generated by α-TCP degradation, thereby maintaining a physiological pH environment favorable for regeneration. Furthermore, CGA–Eu endowed the scaffold with potent antioxidant capacity, enabling it to efficiently scavenge excessive ROS and significantly alleviate oxidative damage in vitro. Biological evaluations confirmed that the sustained release of Eu3+, Zn2+, and CGA cooperatively promoted osteogenic differentiation of bone marrow mesenchymal stem cells and angiogenic activity in human umbilical vein endothelial cells. In an ovariectomized rat cranial defect model, the composite scaffold effectively accelerated bone mass accumulation and enhanced angiogenesis. In conclusion, this dual microenvironment-regulating strategy, which integrates pH buffering, ROS scavenging, and sustained osteo-angiogenic ion delivery, offers a promising scaffold design for osteoporotic bone defect repair.

Piston extrusion-based 3D bioprinting is a widely used technology in tissue engineering; however, the phenomenon of extrusion hysteresis severely constrains its printing accuracy. This study investigates the hysteresis mechanism using a low-viscosity gelatin hydrogel as a model material and develops effective control strategies through mathematical modeling. Rheological characterization determined the material’s gelation point (29.8 °C)and the optimal printing temperature window. Subsequently, precise syringe temperature control was achieved using a heat transfer model, which exhibited a low prediction error of only 0.0065 °C. We constructed an extrusion hysteresis model that simultaneously accounts for the elastic deformation of the syringe and the compressibility of the material. A static model derived from mechanical analysis provided a formula for calculating the extrusion hysteresis volume, while a dynamic model revealed that the resulting flow rate follows an exponential decay law. Experimental validation assessed the influences of critical parameters, including piston velocity (0.020–0.030 mm/s), nozzle diameter (0.46–0.75 mm), temperature (30–35 °C), and various material types. The results demonstrated that the compressible model predictions aligned well with experimental data. However, the finest nozzle (0.46 mm) exhibited larger errors, attributed to rapid heat dissipation and increased susceptibility to premature gelation. Based on the dynamic model, we propose a control strategy employing a premature extrusion stop with adjusted movement speed. Printing experiments confirmed that for low-viscosity hydrogels, this strategy reduced accidental deposition in non-printing areas compared to standard retraction (withdrawal) strategies. This research provides a theoretical framework for optimizing the accuracy of piston extrusion systems and advances the mitigation of defects caused by extrusion hysteresis in the 3D printing of low-viscosity hydrogels.

Tubular hydrogel scaffolds facilitate nutrient and oxygen transport, making them particularly suitable for culturing cells with high metabolic demands. In this study, a double-network hydrogel scaffold with a tubular structure was fabricated using coaxial extrusion-based 3D printing. The hydrogel was composed of sodium alginate and polyacrylamide, and its biocompatibility was assessed through cell culture experiments. The results show that the crosslinking sequence, material composition, and printing parameters were the main factors affecting the macrostructure, microstructure, and mechanical properties of the hydrogel. The CA-PAm hydrogel, in which alginate was ionically crosslinked before subsequent acrylamide (AAm) polymerization under UV exposure, exhibited a more compact microstructure and superior mechanical performance. By optimizing the material composition, the CA-PAm hydrogel achieved a tensile strength of 809.80 kPa and an elongation at break of 217.07%. In addition, the inner-to-outer flow-rate ratio and the platform moving speed are critical factors determining the tubular structural parameters and 3D structural stability. The hydrogel leachate assay showed 89.8% cell viability, and perfusion culture within the tubular scaffold showed an MEF survival rate of 85.4% after three days, indicating good biocompatibility of the scaffold. These results show that crosslinking-sequence reconfiguration is a practical strategy for matching hydrogel network formation with the requirements of coaxial tubular printing and provides a feasible route for fabricating mechanically robust and cytocompatible hollow hydrogel scaffolds for tissue engineering.

Plant-based food inks are formulations of edible biomaterials derived from plants for printing customized three-dimensional (3D) foods or meals. Extrusion-based 3D food printing has emerged as a promising technique for producing digitally designed meals with tailored geometry, texture, and nutritional composition. These printed structures hold significant potential for personalized nutrition by enabling the development of foods aligned with individual dietary needs, metabolic responses, and sensory preferences. Successful printing and downstream dietary applications depend critically on the functional properties of food inks, including rheological behavior, printability, mechanical stability, and compatibility with nutrient or bioactive incorporation, as well as the selection of printing parameters. This review synthesizes the latest developments in plant-based ingredients and food-grade materials suitable for 3D printing, with emphasis on protein isolates, hydrocolloids, fibers, lipids, and fruit- and vegetable-derived matrices. It further examines advances in 3D food printing technologies and their capacity for customization across shape, texture, and spatial nutrient distribution. The integration of artificial intelligence (AI)-based health monitoring is discussed as an emerging framework for real-time dietary adjustment, leveraging biosensors and predictive algorithms to support precision nutrition. Key consumer, safety, cybersecurity, and regulatory considerations are evaluated to contextualize the broader adoption of AI-guided, 3D-printed personalized meals. Finally, major challenges and future research directions are identified, including the development of next-generation printable materials, the creation of closed-loop AI–printer–sensor platforms, clinical validation for chronic disease management, and strategies to improve sustainability and scalability.

Osteochondral defects remain a major clinical challenge due to the complex hierarchical structure, marked mechanical gradients, and distinct biological requirements of cartilage, calcified cartilage, and subchondral bone. Extrusion-based three-dimensional bioprinting has emerged as a promising strategy for osteochondral repair, enabling the spatially controlled deposition of cells, biomaterials, and bioactive factors to fabricate constructs with region-specific compositions and architectures. Among the available material systems, combinations of hydrogels and thermoplastics have attracted increasing attention, as they integrate the favourable biological microenvironment of hydrogels with the mechanical strength, structural stability, and printability of thermoplastics. This synergy makes them particularly suitable for the fabrication of biomimetic osteochondral scaffolds with multiphasic and gradient features. This review systematically summarises the application of hydrogel/thermoplastic combinations in extrusion-based bioprinting for osteochondral repair, with particular emphasis on their role in addressing the structural, mechanical, and biological requirements of osteochondral regeneration. It discusses the design requirements for osteochondral scaffolds, the properties and crosslinking strategies of hydrogel bioinks, the function of thermoplastic frameworks in mechanical reinforcement, and current approaches for constructing multilayered and gradient scaffolds. The review also analyses current limitations, including challenges related to printability, material compatibility, interlayer bonding, degradation mismatch, and long-term functional performance. Overall, this work provides a comprehensive overview of hydrogel/thermoplastic composite systems and highlights their potential to advance the development of clinically relevant bioprinted scaffolds for osteochondral repair.

Accurate assessment of residual liver regeneration following hepatocellular carcinoma resection remains a major challenge due to the dynamic nature of the regenerative process and limitations in conventional image-based evaluation. This study develops a three-dimensional (3D) bioprinted personalized repair scaffold based on multimodal fusion of computed tomography (CT) and magnetic resonance imaging (MRI). Multi-temporal CT/MRI images of patients with hepatocellular carcinoma were acquired, registered, and preprocessed using standardization. A dual-channel deep learning network was employed to achieve high-precision liver segmentation and multimodal fusion 3D reconstruction. Using the deformation field from non-rigid registration, the dynamic changes in residual liver volume after surgery were accurately tracked, and the geometry of the resected cavity was extracted to serve as the basis for scaffold design. Subsequently, the internal pore gradient was optimized by combining regeneration rate data. Using a gelatin methacryloyl (GelMA)/hyaluronic acid (HA) composite bio-ink, a repair scaffold with a personalized shape and functional internal structure was manufactured via digital light processing photopolymerization 3D printing. Experiments showed that, in terms of structural fidelity, the GelMA/HA composite scaffold exhibited excellent performance in overall shape fidelity (94.82%) and key structural wall thickness deviation (12.3 μm). Regarding in vitro cell compatibility, the relative cell proliferation rate achieved 0.85 ± 0.04 under low-serum conditions. In vitro experiments have shown that the scaffold has good cell compatibility and structural stability, providing a theoretical and technical approach for precise repair after liver cancer surgery.

Surface overcuring in volumetric additive manufacturing (VAM) occurs when material, process, and hardware parameters are not properly coordinated, leading to unintended polymerization near the vat boundary and impaired printability. Here, we develop a generalized theoretical model to predict the spatial light-dose distribution within rotating ink and to investigate the effects of key physical parameters, including projection beam size, vat dimensions, occlusion size, and material absorbance, on the onset of surface overcuring. The results show that this defect can be effectively suppressed through the synergistic regulation of these parameters. Specifically, lower material absorbance, smaller vat diameters, and narrower projection beams concentrate higher light energy in the central region of the vat while reducing energy deposition near the sidewalls, thereby promoting earlier solidification in the target region and preventing surface overcuring. Based on this model, a printing process window for suppressing surface overcuring is established as a quantitative guide for the design and fabrication of complex structures by VAM. The practical utility of this process window is further demonstrated through the successful fabrication of functional pH-responsive single- and multi-material drug delivery systems with controllable drug-release profiles. Overall, this study expands the printable design space of VAM for complex three-dimensional structures and provides a practical framework for more advanced applications.

Digital light processing (DLP) bioprinting enables the fabrication of stem cell-derived liver organoids into biomimetic architectures. However, preserving quiescent hepatic stellate cells (HSCs) within human liver organoids during DLP printing remains challenging, as the mechanical requirements for print fidelity often conflict with the compliant microenvironment necessary for maintaining HSC quiescence. To address this limitation, we delineated the printable window of induced pluripotent stem cell (iPSC)-derived HSCs that balances printability with resistance to activation. Notably, day 10 HSCs retained a quiescent phenotype, contributing to the assembly of multicellular organoids without fibrotic activation. We subsequently evaluated the stress-relaxation properties of poly(ethylene glycol) diacrylate (PEGDA)–gelatin methacryloyl (GelMA) and F127DA–GelMA hydrogels, demonstrating that fast-relaxing inner hydrogels preserved the compact cellular morphology of liver organoids, suppressed activation-associated gene expression, and protected HSCs from fibrotic conversion. This highlights that stress relaxation, rather than stiffness alone, is critical for cellular adaptation. Then, we developed a DLP-bioprinted macroencapsulation platform integrating stage-selected iPSC-derived HSCs, stress relaxation-tuned hydrogels, and a protective outer shell. The DLP-printed outer shell conferred structural integrity to the macroencapsulated construct, enabling successful implantation in immunocompetent mice with high graft viability and minimal alpha-smooth muscle actin (α-SMA) expression in iPSC-derived liver organoids containing HSCs. In summary, this study establishes a coordinated strategy harmonizing HSC selection, matrix mechanics, and bioprinting design to balance biological and mechanical demands, yielding structurally stable, physiologically relevant liver organoids while preventing fibrotic activation during biofabrication.

Decellularized uterine extracellular matrix (dUECM) is promising for uterine tissue engineering because of its inherent bioactivity and structural complexity. However, transforming dUECM into porous, functional 3D constructs remains a significant challenging. This study aimed to: (1) synthesize dUECM using a modified decellularization protocol and formulate it into a hydrogel ink, and (2) to fabricate 3D-printed constructs from this ink to assess their capacity to support human uterine myometrial cell growth in vitro. Porcine uterine tissues were decellularized using 1% Triton™ X-100 with varying concentrations of sodium dodecyl sulfate (SDS) (0.1–1.5%) for 48–72 h. The resulting dUECM was characterized using DNA and glycosaminoglycan (GAG) quantification, Picrosirius Red-polarized light microscopy, routine histology, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and thermogravimetric analysis (TGA). To prepare the ink, dUECM powder was enzymatically digested with pepsin and subsequently blended with 2% and 3% alginate to obtain a printable hydrogel formulation. Constructs were fabricated using extrusion-based 3D printing and assessed for filament fidelity, swelling, degradation behavior, and mechanical properties. Biocompatibility was evaluated using hTERT-HM myometrial cells through MTT metabolic assays, Live/Dead staining, and immunohistochemical α-SMA staining. The optimal protocol (1% Triton™ X-100 + 1% SDS for 48 h) reduced DNA to 51.3 ± 9 ng/mg while retaining a high level of GAGs (54.9 ± 7.6 μg/mg). Preservation of the ECM structure was confirmed by spectroscopy analyses. The 3% Alg + 1.5% dUECM hydrogel exhibited suitable printability (1.5 ± 0.2), swelling capacity (47 ± 12%), degradation resistance (94 ± 18% mass retention), and mechanical strength (decreasing from 323 kPa to 175 kPa over 14 days), along with high viability and proliferation (258 ± 13%). The developed dUECM-based hydrogel supports 3D bioprinting with strong mechanical and biological performance, offering a promising platform for uterine tissue engineering.

Diabetic wound healing remains a significant clinical challenge due to persistent infection and impaired tissue regeneration. This study presents a biomimetic, 3D-bioprinted bilayer hydrogel dressing with spatially compartmentalized functions to address these divergent requirements. The upper layer comprises chitosan hydrogel embedded with silver nanoparticles to provide rapid, broad-spectrum antibacterial activity against surface pathogens, and the lower layer consists of methacrylated silk fibroin hydrogel co-encapsulating epidermal stem cell-derived exosomes and metformin to create a pro-regenerative microenvironment in the deeper wound bed. Comprehensive in vitro characterization confirmed distinct physicochemical properties between the antibacterial upper layer and the porous, pro-healing lower layer. The upper layer exhibited synergistic bactericidal effects against Staphylococcus aureus and Escherichia coli, while the lower layer promoted M2 macrophage polarization, endothelial cell migration, and angiogenesis-related gene expression. In a diabetic mouse model of infected full-thickness wounds, compared to monolayer controls, the bilayer dressing significantly accelerated wound closure by increasing granulation tissue formation and neovascularization, while reducing bacterial burden. This compartmentalized design effectively integrates the complementary demands of infection control and tissue regeneration, offering a promising strategy for managing chronic diabetic ulcers.

Three-dimensional bioprinting combined with induced pluripotent stem cells (iPSCs) offers a practical route to building human tissue models with improved structural and functional relevance. By controlling cell placement and local microenvironments, these systems better reproduce tissue organization and multicellular interactions than conventional culture methods. This review provides a comprehensive analysis of recent advances in iPSC-based bioprinting, with a focus on how biofabrication strategies shape tissue organization and function. Recent work has shifted the field away from simply achieving structural fidelity toward maintaining stable and reproducible function. Progress in bioink design, vascularization strategies, and multi-material printing has enabled the generation of cardiac tissues with perfusable networks, neural constructs with coordinated activity, and metabolic tissues with sustained functional output. These advances have strengthened the use of bioprinted tissues in disease modeling and drug evaluation. Evidence from early clinical studies suggests that translation is currently driven by modular and well-defined products rather than fully printed organs. Cardiac patches, dopaminergic progenitor cell therapies, stem cell–derived islets, and retinal implants illustrate how simpler, function-oriented constructs can meet clinical and manufacturing requirements. The review further discusses key challenges for clinical translation, including tissue maturation, manufacturing scalability, and regulatory standardization. By connecting technological advances with emerging clinical evidence, this review establishes a conceptual framework for translating iPSC-based bioprinting into practical therapeutic applications.

Additive manufacturing (AM; commonly known as three-dimensional [3D] printing) has gained widespread adoption across diverse fields owing to its high precision, capability to directly fabricate complex geometries, and support for personalized customization. Elastomeric polymers, which combine excellent elastic recovery with multifunctional properties, have converged with 3D printing to establish the emerging field of 3D-printed elastomers, thereby overcoming limitations of traditional manufacturing in design freedom and functional integration. This review systematically surveys advances in 3D-printed elastomers over the past five years. It focuses on the characteristics and suitability of mainstream processes, including material extrusion, material jetting, and photopolymerization, and provides detailed classifications of polyurethane-based, silicone-based, polyolefin-based, and bio-based matrix materials. The design and processing principles, core breakthroughs, and current technical bottlenecks of functional elastomers are comprehensively outlined, while summarizing demonstrated applications in biomedicine, flexible electronics, soft robotics, industrial manufacturing, and consumer products. Nevertheless, key challenges remain for 3D-printed elastomers, including balancing competing material properties, reconciling process throughput with dimensional precision, ensuring reliability in extreme environments, and enabling large-scale manufacturing. The review concludes by outlining future directions, such as the design of dynamic and adaptive polymer networks, the development of green and sustainable materials, and convergence-driven interdisciplinary innovation, thereby providing guidance for future research and industrial translation.

Titanium and its alloys have become the primary materials for orthopedic implants due to their excellent biocompatibility, mechanical properties, and corrosion resistance. However, traditional manufacturing techniques struggle to achieve complex porous structures, and their insufficient surface bioactivity limits their clinical performance. Additive manufacturing (AM) technology enables the precise fabrication of titanium implants with personalized shape, biomimetic porous structures, and gradient mechanical properties. The controllable porosity, pore size, and pore shape not only achieve mechanical compatibility with human bone tissue, but also provide an optimal microenvironment for cell adhesion, proliferation, and vascularization. During the process of designing porous structures, the auxiliary roles of finite element analysis (FEA) and machine learning (ML) play a crucial role in performance prediction and process optimization. To further enhance the bioactivity of AM titanium alloys, surface modification techniques such as mechanical, physical, chemical, and electrochemical methods have been widely employed. These modified coatings significantly improve the osseointegration efficiency, antibacterial properties, and corrosion resistance of implants without compromising the mechanical integrity of the substrate. Currently, AM titanium alloy implants have been successfully applied in joint replacements, dental prosthetics, and other fields. Through the synergistic effect of personalized design and surface functionalization, they demonstrate superior clinical application potential compared to traditional implants. This article systematically reviews the porous structure design, surface modification techniques, and application progress of AM titanium alloy implants, aiming to provide valuable insights for clinical applications.

Stimuli-responsive biomaterials have progressively developed over the last decade in three-dimensional (3D) bioprinting, enabling dynamic regulation of bioink rheological and processing properties, printing fidelity, and the functional maturation of printed constructs. However, the rapid expansion of responsive materials and bioprinting technologies has led to fragmented and non-standardized definitions of biomaterials and bioinks, resulting in inconsistent classification approaches and complicating the analysis, comparison, and design of emerging systems. This highlights the lack of a unified framework for biomaterial selection for bioprinting. This perspective introduces the bioprinting biomaterials classification (BBC) as a conceptual framework that provides a structured and design-oriented basis for biomaterial selection for bioprinting by linking stimuli-responsive behavior with stage-specific functional requirements across the bioprinting process. The BBC framework classifies biomaterials according to two complementary dimensions: stimulus category (physical, chemical, and biological stimuli) and functional roles across the bioprinting lifecycle (bioink preparation, printing process, post-printing maturation, and in vivo function). This two-level biofunctional classification connects material responsiveness with biofabrication processes and enables a systematic approach to selecting and applying responsive biomaterials based on their stage-specific functional roles. It provides a systematic framework for positioning responsive biomaterials within the biofabrication context and supports a more structured and application-driven approach to biomaterial selection and design in bioprinting systems. By addressing the current lack of structured strategies for biomaterial selection for bioprinting, the BBC framework offers a foundational step toward a more rational and consistent design of responsive biomaterials in advanced biofabrication systems.

The pronounced spatial heterogeneity and dynamic evolution of the tumor microenvironment represent key factors limiting the sustained therapeutic efficacy of anti-tumor drugs in solid tumors. Traditional drug delivery strategies often rely on spatiotemporally uniform delivery profiles, making it difficult to match the complex structural organization and continuously evolving biological states within tumor tissues. This results in uneven drug distribution, limited therapeutic windows, and the development of drug resistance. In recent years, 3D-printing and bioprinting technologies, as layer-by-layer manufacturing methods based on digital design, have provided new solutions for constructing drug delivery systems with modifiable structures, partitioned spatial organization, and programmable time-release capabilities. By precisely controlling the arrangement of materials, bioactive molecules, and cells in three-dimensional space, these systems can not only achieve fine spatiotemporal regulation of the drug delivery process but also integrate cells, extracellular matrix, and mechanical cues during delivery, thereby partially reshaping the tumor microenvironment. This paper systematically reviews the design strategies and latest advancements of 3D-printing and bioprinting delivery systems in achieving spatiotemporally controllable drug delivery within the tumor microenvironment, focusing on their advantages in spatial regulation, temporal response, and tumor microenvironment reprogramming, while analyzing the current key challenges and clinical translation prospects, aiming to provide references for the rational design of next-generation tumor delivery systems.

The hydrophobicity of 3D-printed polycaprolactone (PCL) scaffolds leads to insufficient cell adhesion, limiting their application in bone repair. This study constructed zeolitic imidazolate framework-8 (ZIF-8) modified PCL scaffolds with different coating densities and systematically evaluated their physicochemical properties and osteogenic effects. The results showed that low-density ZIF-8-coated PCL scaffolds exhibited better biocompatibility and osteogenic differentiation promotion capacity, while maintaining structural stability and mechanical properties. Mechanistically, the low-density coating can induce macrophages toward M2 polarization, thereby forming a more favorable osteogenic immune microenvironment. Simultaneously, in a rat skull defect model, this scaffold significantly promoted new bone regeneration and defect repair. This study indicates that ZIF-8 coating density is a key parameter affecting the immunomodulatory osteogenic efficacy of PCL scaffolds, providing a basis for the design and optimization of metal–organic framework-based coated scaffolds.

Magnetic liquid metal soft robots hold promise for minimally invasive interventions in complex in vivo environments, yet their fabrication challenges must simultaneously achieve structural customization, spatial magnetic programming, and rapid conductive network construction. Here, we present a magnetic-field-assisted 3D printing strategy to fabricate soft robots with programmable magnetic domains and magnetothermal therapeutic capabilities. Using acid-assisted de-oxidation and silver (Ag)-coated neodymium–iron–boron (NdFeB) particles to enhance wetting, we prepared magnetic liquid metals that exhibit magnetic-field-induced coalescence and achieved an order-of-magnitude increase in electrical conductivity. Furthermore, a geometry-dependent model based on eddy-current losses revealed that printed paths significantly improve heating efficiency under alternating magnetic fields. Leveraging a locally oriented magnetic field during printing, we encoded spatially resolved hard-magnetic domains, yielding predictable 3D deformation and multiple gaits, including grasping, crawling, and rolling. Finally, we demonstrated localized magnetothermal heating in ex vivo porcine colon tissues, validated by thermal measurements and finite-element simulations. This study offers a manufacturable, programmable, and scalable liquid metal additive manufacturing platform for personalized magnetically driven magnetothermal therapy in complex biological environments.

Repairing critical-sized, load-bearing bone defects remains a formidable clinical challenge, primarily due to the mechanical fragility of traditional bioceramics. This study systematically compared the bone regenerative efficacy of surface-microstructured three-dimensional (3D)-printed porous titanium (3D-SMPT) and reinforced biphasic calcium phosphate (RBCP) ceramics. In vitro evaluations demonstrated that a biomimetic coating effectively overcame titanium’s bioinertness, thereby endowing 3D-SMPT with excellent biocompatibility and osteoinductivity comparable to those of RBCP. In vivo cross-species assessments revealed significant biomechanical differences: in a low-load rabbit ulnar model, both scaffolds exhibited equivalent osteogenesis. However, in a true weight-bearing beagle femoral model, RBCP suffered severe structural collapse due to inherent brittleness. In stark contrast, leveraging its cortical bone-matched compressive strength (83.14 MPa, approximately 10-fold higher than that of RBCP at 7.68 MPa) and interconnected porosity, 3D-SMPT maintained long-term mechanical stability, effectively mitigating stress shielding to facilitate massive mature bone ingrowth and robust osseointegration. In conclusion, 3D-SMPT achieves a perfect integration of bioactivity and load-bearing stability, overcoming the inherent fragility of traditional ceramics and offering a highly promising clinical alternative for the repair of massive load-bearing bone defects.

The high heterogeneity and complex cellular interactions within the tumor microenvironment (TME) pose a fundamental challenge to both cancer research and drug development. Conventional in vitro models fail to faithfully recapitulate the pathological features of tumors, thereby limiting the translation of basic research findings into clinical practice. Although patient-derived tumor organoids preserve the genetic and structural hallmarks of primary tumors, they are inherently constrained by limited control over spatial cellular organization, insufficient recapitulation of the biomimetic microenvironment, and a lack of model standardization. Three-dimensional (3D) bioprinting, characterized by precise spatial manipulation and multi-material deposition, offers a transformative strategy to address these limitations by converting key TME variables into programmable design parameters. Through the rational design of bioinks and optimization of printing parameters, bioprinting enables the programmable patterning of cells, extracellular matrix components, and bioactive factors, substantially enhancing the structural reproducibility, physiological relevance, and functional integrity of tumor organoids. This review systematically summarizes recent advances in bioprinted tumor organoids, with a focus on mainstream bioprinting technologies, the regulation of key process parameters, bioink design strategies for TME reconstruction, and the complete pipeline of organoid fabrication. We further delineate the translational impact of these models across personalized medicine, high-throughput drug discovery, immunotherapy evaluation, and the mechanistic dissection of drug resistance. We also discuss the current challenges in technical reproducibility, scalable manufacturing, ethical governance, and regulatory compliance. Finally, we outline future directions, including multimodal technological integration, four-dimensional (4D) bioprinting, tumor-on-a-chip platforms, and interdisciplinary innovation. Collectively, the convergence of bioprinting and tumor organoid technologies offers a robust platform for constructing highly biomimetic tumor models, dissecting tumor biology, and advancing precision oncology. This programmable reconstruction paradigm may help bridge the gap between basic cancer research, preclinical drug testing, and clinically actionable decision-making.

Microtia is a congenital malformation of the external part of the human ear. Recently, bioprinted auricles have been implanted in the first human patient. The remaining challenge in bioprinting of human ear is a post-implantation maintenance of bioprinted auricular construct size and shape. We hypothesize that the use of polylactide stiffeners will enable bioprinting of hybrid auricular constructs with stable post-implantation size and shape. Using the hybrid bioprinting method, auricular implants consisting of a custom-shaped polyurethane frame with polylactide stiffeners and filled with collagen hydrogel containing chondrocytes were printed. Mechanical testing of the implants was performed and it was shown that adding stiffeners to the frame increased the resistance of the structure to deformation. The implants were sutured under the temporal fascia in two mini-pigs for three months, after which a histologic and immunohistochemical study was performed. The formation of regenerated connective tissue with its own vascular network was observed, filling the entire volume of the implant. There was no evidence of inflammation or rejection. The implants maintained their size and shape after implantation. Thus, the in vivo evaluation of the auricular implant bioprinted by the described hybrid method gave satisfactory results in preclinical testing and the next logical step is a clinical translation.

Cholangiocarcinoma (CCA) shows marked interpatient heterogeneity in chemotherapy response, highlighting the need for physiologically relevant, standardized, and reproducible in vitro models for individualized drug screening. However, Matrigel-based organoid models lack hepatobiliary extracellular matrix cues, and many bioprinting strategies rely on dissociated or fragmented organoids, disrupting native architecture and spatial organization. To address these limitations, we developed a composite bioink for direct bioprinting of patient-derived CCA organoid (CCAO) fragments that retained multicellular organization, enabling standardized culture, imaging, and drug-response evaluation. Although decellularized liver matrix (DLM) was used to reconstruct the tissue-specific microenvironment, its weak gelation, poor mechanical properties, and limited printability restricted its application. Tris(2,2’-bipyridyl)ruthenium(II)/sodium persulfate (Ru/SPS) and gelatin methacryloyl (GelMA) were introduced to improve photocrosslinking, mechanical support, and printability. DLM retained key components of the hepatic extracellular matrix, including collagen, fibronectin, laminin, and glycosaminoglycans. With GelMA and Ru/SPS, the bioink achieved rapid visible-light crosslinking (405 nm, 50 seconds), tunable mechanical properties, and good extrusion-printing compatibility. Among the tested formulations, the DLM-Ru/SPS:GelMA (4:1) group showed the best balance of printability, transparency, and organoid-compatible microstructure. Using this optimized bioink, organoid fragments were patterned and reassembled into viable spheroids that retained key CCA features and maintained high viability (>80%). The platform also enabled reproducible assessment of drug response, demonstrating dose-dependent cisplatin sensitivity and enhanced cytotoxicity with cisplatin–gemcitabine treatment. In summary, this study established a DLM-based direct bioprinting platform for CCAOs and a standardized system for individualized therapeutic evaluation.

In situ bioprinting is an emerging technology that directly deposits bioinks on demand within clinical environments to generate targeted tissue structures. It integrates the printing and implantation processes, allowing the printed constructs to interact directly with the host biological microenvironment. This technology reduces the risk of contamination during transplantation and improves operational precision, thus demonstrating broad application prospects in fields such as tissue repair and biomedical sensor fabrication. This article discusses the following aspects: (i) from the perspective of control strategies, it summarizes the developmental trend of in situ bioprinting from open-loop control toward closed-loop control, and outlines key procedures including geometric reconstruction, conformal slicing, infill trajectory planning, and parameter mapping in in situ bioprinting; (ii) with reference to body-surface and open-exposure scenarios, minimally invasive intervention scenarios, remote energy-driven scenarios, and biosensing scenarios, this review discusses the demands faced by in situ bioprinting in different application settings, the design logic of bioinks, and representative research progress; (iii) the printable characteristics and application boundaries of natural polymers, synthetic polymers, and 4D smart materials in in situ bioprinting are summarized. Finally, the challenges faced by this technology and its potential directions for improvement in the future are also discussed.