Volumetric additive manufacturing (AM) is a novel AM method that offers advantages such as fast printing speed and isotropic mechanical properties. As an important branch of volumetric AM, computed axial lithography (CAL) based on azimuthal projections and rotational printing has attracted great attention and has been widely used in recent years. Here, we focus on the projection algorithms of CAL, which is critical to the printing quality, including its fidelity and accuracy. Different optimization methods, including iterative optimization of projection space and objective model, optimization for the optical influences of materials, and optimizations with hardware upgrades, are summarized. The features and advantages of different projection optimization algorithms are also analyzed and discussed, which could promote the application and development of volumetric AM.

Significant efforts have been made to advance bioprinted scaffold research in cell biology, tissue engineering, and drug screening studies. Ideal scaffolds should demonstrate suitable mechanical properties, excellent biocompatibility, and bioactivities. However, the design and preparation of such scaffolds are challenging. Imaging modalities, including magnetic resonance imaging, micro-computed tomography, ultrasound imaging, optical coherence tomography, and confocal laser scanning microscopy, are commonly used to visualize the interior architecture of bioprinted scaffolds, as well as the surrounding cells and tissues. The obtained bioimages provide direct insight into the biological functionalities of the scaffold, though their interpretation may lead to differing viewpoints and even debates. This review explores deep learning (DL) methods employed for image analysis, including restoration, segmentation, and classification. First, current DL methods for biological image processing are summarized, such as convolutional neural network, U-Net, and generative adversarial network. The corresponding outcomes of these methods reveal cell–scaffold and tissue–scaffold interactions, providing guidance for scaffold design in specific applications. Thereafter, the challenges and limitations of DL applications are highlighted, such as building DL models using smaller bioimage datasets, interpreting DL models, vision-language model-guided bioimage analysis, and developing intelligent analysis platforms. Hence, this review would mark a paradigm shift in polymer scaffold designs and the associated performance.

Three-dimensional (3D) cell cultures are increasingly being used in a variety of contexts (e.g., drug discovery, disease modeling, and tissue engineering), as they offer the potential to increase physiological relevance compared to traditional monolayer cultures, while simultaneously reducing cost and time compared to in vivo models. Taking a cue from nature, researchers often create 3D cell cultures using hydrogels that can closely mimic the extracellular matrix that most mammalian cells are surrounded by in vivo. However, aside from the collective physical 3D arrangement itself, the physiology of the culture depends highly on the microenvironment, which is defined by the 3D cell culture shape and the complex combination of biochemical, biophysical, and biomechanical stimuli. Microfluidic devices offer researchers the tantalizing opportunity to precisely define and influence this microenvironment. Furthermore, they additionally enable the integration of external functional components for active stimulation and monitoring of cultured cells. Pushing for ever-more-realistic culture conditions has, however, increased the complexity that is required of these microfluidic culture systems, making their fabrication more difficult. In this regard, 3D printing is becoming an increasingly popular solution, as it offers researchers not only the ability to fabricate highly complex structures but also to benefit from rapid prototyping and customization of existing designs. This review discusses common challenges that researchers currently face when integrating hydrogel-embedded cells into 3D-printed microfluidic cell culture devices and seeks to offer a comprehensive overview of recent advancements aimed at addressing these challenges.

Organoids are three-dimensional (3D) and multicellular structures that more closely mimic the architecture and functions of human organs. These in vitro systems are derived from pluripotent stem cells, tissue-resident stem cells, or organ-specific progenitors. Despite their potential, conventional organoid development methods are limited by inconsistencies in formation and the absence of complete microenvironmental cues, which reduce reproducibility in larger organ models. In contrast, 3D bioprinting techniques offer a precise layer-by-layer construction approach that enables superior spatial control, scalability, and uniformity in organoid formation. In this review, we examine the principles, strengths, applications, and limitations of these imaging methods, offering insights into their potential to drive further innovations in the rapidly evolving field of organoid imaging. To track the dynamic processes of cell growth, differentiation, and organization during organoid development and maturation, advanced imaging technologies are crucial. Traditional optical imaging methods, however, require exogenous labeling agents to enhance contrast, which can damage samples through photobleaching and phototoxicity. Label-free and real-time imaging modalities, by contrast, offer non-invasive and non-destructive monitoring of organoids, preserving sample integrity and enabling longitudinal studies. This review highlights the benefits of bioprinting technologies in overcoming current limitations in organoid development and provides a comprehensive overview of label-free and real-time imaging technologies for organoids. In this review, we examine the principles, strengths, applications, and limitations of these imaging methods, offering insights into their potential to drive further innovations in the rapidly evolving field of organoid imaging.

In orthopedics, infectious bone defects face a formidable challenge, considering the critical issues of infection control and bone regeneration during treatment. Although numerous biomaterials have been developed to address these therapeutic challenges, most fail to meet the high regeneration requirements of infectious bone defects with complex pathological environments. There is an urgent need for the rational design of multifunctional bioactive scaffolds that integrate antimicrobial treatments with bone regeneration capabilities. Three-dimensional (3D) printing, a powerful manufacturing technique, holds great promise in fabricating complex bone tissue engineering scaffolds with highly personalized customization. The 3D-printed bioactive scaffolds possess excellent biocompatibility, outstanding antimicrobial properties, appropriate mechanical strength, and bone regeneration ability, making them a highly attractive, emerging strategy for overcoming the challenges of infectious bone defect repair. This review first discusses the therapeutic challenges of infectious bone defects and the desirable features of ideal bone implants, followed by a systematic overview of recent advancements in 3D printing technologies and biomaterials used to fabricate 3D-printed bioactive scaffolds for infectious bone defects. Finally, we highlight the advantages, potential breakthroughs, and challenges of 3D-printed bioactive scaffolds in repairing infectious bone defects.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy with increasing incidence worldwide, causing a severe impact on the quality of life and survival rate of affected patients. Traditional tumor models have significant limitations in studying biological properties, tumor microenvironment, and treatment response, and the difficulty in obtaining HNSCC specimens has hampered our understanding and the development of treatment for the disease. Recent rapid development in bioprinting has provided new possibilities for tumor model construction, enabling precise control of cell arrangement and tissue structure to be more realistically simulated tumor biological properties. This review summarizes the latest progress of bioprinting in HNSCC tumor model construction, explores the application of different bioprinting technologies, the properties of constructed tumor models, and the potential applications of these models in drug screening and individualized treatment, aiming to provide reference and inspiration for future research and treatment of HNSCC.

With the rapid advancement of three-dimensional (3D) bioprinting technology, its applications in tissue engineering and regenerative medicine have garnered increasing attention. Tendon–bone healing is a complex biological process, making injuries to the tendon–bone interface challenging to repair. Fortunately, 3D bioprinting provides numerous innovative solutions. Herein, we summarize the current state of 3D bioprinting technology in tendon–bone healing, exploring the latest developments in biomaterials, printing technologies, cell carriers, and preclinical research. In conclusion, the article discusses the current challenges faced in this field and outlines future research directions with careful consideration, providing valuable insights for ongoing investigations.

Microneedle (MN) patches have emerged as a promising drug delivery technology for wound healing treatments, offering several advantages over traditional administration methods, including minimal invasiveness, precise drug delivery, and minimal pain. This review explores the basic principles of MN patch technology, three-dimensional (3D) printing-assisted fabrication techniques, and the key considerations in designing effective MN patches for regenerative medicine. Moreover, the in vivo applications of the MN patches in wound healing, tissue regeneration, and drug delivery are discussed in detail. Finally, the challenges and future research directions of the MN patch technology are discussed, highlighting its potential to revolutionize personalized medication.

Despite the self-healing ability of bone tissue, the treatment of critical-size defects and the limited regenerative process in osteoporosis or avascular necrosis demand special medical attention. One of the goals of bone tissue engineering is to develop new patient-specific solutions for bone repair. In this study, we focus on the fabrication of degradable subchondral bone scaffolds made of highly loaded polycaprolactone (PCL) using direct ink writing. Barium titanate (BTO) and the bioactive glass 45S5 (BG) were used as filler materials to modify the material’s piezoelectric, mechanical, and bioresponsive properties. The mechanical properties of our composites are in the range of spongy bone, and a compressive modulus of around 181 MPa was achieved for PCL/BTO and 98.3 MPa for PCL/BTO/BG scaffolds. The use of 40 vol.% BTO in combination with PCL showed piezoelectric properties in the range of bone tissue with a d33 of 0.75 pC/N. While adding BG decreases the piezoelectric properties, it increases the bioactivity and the osteogenic response of primary human osteoblasts. In summary, these novel material compositions provide a promising approach for developing multiphasic scaffolds for bone tissue engineering.

In recent years, engineered conductive myocardial patches have gained increasing attention for their potential in repairing myocardial infarction (MI). However, the traditional fabrication process of these patches often includes the use of toxic conductive monomers and crosslinking agents, along with harsh physical treatments such as low-temperature drying. These elements not only hinder the effective in situ loading of myocardial cells but also limit the efficiency and retention of cell seeding post-fabrication. To address these challenges, we developed an innovative approach using a granular composite hydrogel, comprising myocardial cell-laden microgels integrated with an interstitial conductive matrix, capable of being printed into 3D complex electroactive cardiac patches. We used microfluidic technology to encapsulate cardiomyocytes in microgels. Furthermore, we integrated the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styre ne sulfonate) into a GelMA prepolymer to fabricate a conductive matrix. This matrix was subsequently combined with microgels to form a conductive bioink, which was then utilized for printing a conductive myocardial patch. The results demonstrated that the myocardial cell-laden microgels within the patches maintained robust viability and functionality. Moreover, the patches exhibited electrical conductivity aligned with physiological levels and possessed the requisite mechanical properties for structural support to the infarcted heart. We found that these conductive cell-laden patches significantly improved left ventricular remodeling and heart function post-infarction in a rat model of MI. We believe that the design and engineering of conductive cellular myocardium patches represent a significant advancement in the treatment of MI.

Biofabrication has proven to be a versatile and valuable tool for tissue engineering and cancer research, enabling the mimicry of various tumor microenvironments. In the present study, four different cell lines, including two melanoma cell lines, Mel Im and Mel Wei, and two breast cancer cell lines, MDA-MB-231 and MCF-7, were tested in combination with four distinct hydrogels. The hydrogels used were a composite ink of alginate, hyaluronic acid, and gelatin (Alg/HA/Gel), pre-crosslinked oxidized alginate with gelatin (ADA-GEL), alginate with methylcellulose (Meth-Alg), and acrylated hyaluronic acid (HAA). Rheological analysis, shear stress calculations, printability assays, and dynamic mechanical analysis were performed on all hydrogels. The cell lines were then mixed into the hydrogels, printed, and examined over 14 days, with a focus on cell survival, metabolic activity, and cell cycle analysis using fluorescent ubiquitination-based cell cycle indicator reporters. The results showed that all hydrogels were printable, with Meth-Alg being the softest gel. The cell lines survived the printing process in all bioinks, but there were significant differences in the metabolic activity and the predominant cell cycle stage. In Alg/HA/Gel, the cells grew in spheroid colonies. ADA-GEL proved to be a good bioink, supporting proliferation, migration, and high metabolic activity across all cell lines, while Meth- Alg offered pore structures conducive to cell spreading and proliferation. However, HAA resulted in the lowest cell number and metabolic activity across all cell lines, likely due to its high polymer content, which induced senescence. Our data demonstrated that each of these bioinks presents unique advantages for breast cancer and melanoma research models.

Harnessing the advantage of both naturally derived polymers and nanostructured materials, the current study presents a novel multicomponent hydrogel system double-reinforced with two complementary nanofillers, specifically designed for bioprinting-based tissue engineering applications. In a bioinspired approach, cellulose nanofibrils (CNFs) and polyhedral silsesquioxanes (PSS) nanoparticles were embedded in a proteinaceous–polysaccharidic matrix. To synthesize a robust platform for 3D bioprinting, methacrylate-modified biopolymers were ultraviolet-crosslinked, ensuring optimal conditions for cell encapsulation. The nanocomposite bioinks were supplemented with bone morphogenetic protein 2 (BMP-2), a potent osteogenic factor, to enhance the osteogenic differentiation of preosteoblasts. The 3D scaffold morphology was investigated, with a focus on PSS dispersion, porosity, and geometrical properties of the constructs. Swelling studies confirmed that all hydrogel samples retained their hydrophilic nature, though a slight reduction in swelling capacity was observed upon PSS incorporation. In vitro cytocompatibility tests demonstrated the beneficial effects of CNFs and PSS on cell growth. In vivo studies further revealed that hydrogels supplemented with nanostructured fillers and BMP-2 significantly enhanced osteogenesis, both in osteogenic and non-osteogenic regions. These findings prove that growth factor-reinforced scaffolds hold great potential in addressing the challenges of biomaterial research and represent a promising strategy for hard tissue regeneration.

Based on interdisciplinary approaches, bioprinting methods aim to create and design highly organized 2D and 3D cultures. In this context, it has been more than a decade since laser-induced forward transfer (LIFT) was studied on a lab scale for its ability to transfer biomaterials, specifically bioink loaded with living cells, onto a substrate. Extreme physical and mechanical phenomena contribute to the jetting dynamic of the targeted bioink, raising a spontaneous biological question: does this process negatively affect the survival rate of transferred cells? This study demonstrates that laser pulse durations in the range of picoseconds to nanoseconds do not directly affect cell viability, indicating that LIFT is a valuable bioprinting method for transferring living cells. Moreover, we highlight the necessity of using hydrogel coatings on the surface of the receiver substrate to guarantee optimal post-printing viability of the cells. We demonstrate that the nature of the hydrogel also contributes to the resolution of the printed pattern. Among the tested materials, Matrigel demonstrated all the qualities required to ensure successful printing and should therefore be considered for future work. Overall, the results show the suitability of our LIFT setup for printing living cells in the picosecond regime with a high survival rate, paving the way for a wide range of biological applications.

Zirconia (ZrO2) implants have shown promising outcomes in the restoration of tooth loss. However, the discrepancy between the elastic modulus of ZrO2 implants and alveolar bone can cause a stress-shielding effect at the bone–implant interface, leading to progressive damage and possibly resulting in the clinical failure of the implant treatment. Functionally graded porous implants present a promising solution to this issue. Triply periodic minimal surfaces (TPMS) have attracted growing interest due to their ability to create 3D interconnected and continuous pore structures. Dental implants, especially around the neck region, experience both compressive and tensile stresses within the surrounding bone. ZrO2, being a brittle material, is more susceptible to tensile stress than compressive stress, making flexural strength a critical property for evaluating its performance. The objective of this research is to assess the flexural properties, biological performance, and permeability of gradient sheet-network TPMS ZrO2 specimens printed by vat photopolymerization (VPP). In vitro evaluations of the biological properties revealed that the Schwarz-P structure had the most significant effects in promoting the proliferation of rat bone marrow stem cells and enhancing the expression of osteogenic-related genes. However, it also exhibited the lowest flexural strength and permeability. In contrast, the Diamond structure displayed good flexural strength, structural stability, and effectively promoted osteogenic-related gene expression, presenting a well-balanced combination of mechanical and biological properties. This suggests its potential for further development into 3D-printed functional gradient ZrO₂ implants.

Current therapies for articular cartilage defects or degeneration, such as osteoarthritis, remain largely unsatisfactory. There are significant clinical demands for the development of more efficient approaches to enhance the repair or regeneration of articular cartilage lesions. In this study, a newly defined alginate-gelatin (A-G) composite bioink was synthesized using the carbodiimide chemistry crosslinking method. Then, the dual-crosslinking (DC) bioscaffolds containing both chemical and ionic networks were fabricated by 3D-bioprinting technique and Ca2+ treatment. Mimicking the mechanical properties of the pericellular matrix of native articular cartilage, the optimized networks formed in the DC bioscaffolds provided a desirable Young’s modulus and geometric constraints, which were superior to that of the single-crosslinking control group. Chondrocytes encapsulated in the 3D printed A-G-DC bioscaffolds exhibited above 95% viability and higher proliferation rate compared to those in the alginate-only group after 7 days of in vitro culture. Chondrogenic differentiation in vitro was improved in the A-G-DC bioscaffolds compared to that of the alginate-only group, indexed by upregulation of chondrogenic marker gene expression, including SOX9, COL2A1, COMP, and ACAN. In subcutaneous transplantation and osteochondral defect models in severe combined immunodeficiency mice, the A-G-DC bioscaffolds exhibited superior chondrogenesis and repair capacity compared to the alginate-only or no-implant control groups. This was evidenced by increased expression of SOX9 and collagen type II (Col II) and higher ICRS II scores. These findings demonstrate that the biomechanically inspired A-G composite bioink and the 3D-printed A-G-DC bioscaffolds possess excellent cell biocompatibility, satisfactory biomechanical properties, and the ability to promote chondrogenesis, making them a promising candidate for enhancing cartilage regeneration in patients with articular cartilage lesions.

3D bioprinting creates biological structures by layering bioinks with living cells or biomaterials. Microextrusion, a type of 3D bioprinting, uses pneumatic, piston, or screw methods to extrude bioink precisely. The reliability of 3D bioprinting depends on bioink characteristics, printing conditions, and printer accuracy. Thus, a 3D bioprinter that effectively controls these factors is essential to facilitate 3D bioprinting. In this study, we developed a high-precision 3D bioprinter system (HP-BPS) with a high-accuracy 3D plotting system and a screw-based dispenser. Evaluation of reducers installed on the X- and Y-axis driving systems decreased motion error by up to 97%. Geometric errors of the HP-BPS were measured using a laser interferometry system. Through the application of iterative position error compensation techniques, a position accuracy within ±2.0 μm was achieved. In specific carboxymethyl cellulose concentrations (15% and 20%), the HP-BPS was able to produce uncollapsed bioink struts. The HP-BPS successfully fabricated 1 × 1 mm2 bioscaffolds with 0.2 mm struts by design of experiments and response surface methodology. These results suggest the potential of the HP-BPS for various tissue engineering applications in soft tissue construction, such as skin and blood vessels.

Osteoarthritis is a highly prevalent rheumatic musculoskeletal disorder that often results in both physiological dysfunction and psychological distress. Although many tissue engineering approaches have been proposed for tissue regeneration, the mechanical properties of many scaffolds remain insufficient to fully meet the mechanical demands within the joint. This paper presents a computational investigation and structural design for creating an osteochondral interface scaffold using extrusion-based 3D printing. A finite element method-based mechanics simulation model was employed to evaluate the effects of load-bearing forces on various scaffold designs, enabling the analysis of stress distribution within the biomimetic osteochondral interface. Several structures of osteochondral interface scaffolds were fabricated, demonstrating controllable mechanical properties. The proposed biomimetic osteochondral interface manifested comprehensive mechanical performance, with bonding strength, compressive strength, and shear strength reaching 128, 277, and 276 kPa, respectively. Our research can benefit the future development in tissue engineering and regenerative medicine.

This study aimed to improve the treatment of open bone defects by developing a hybrid scaffold that enhances bone regeneration and prevents infections. Polycaprolactone (PCL) scaffolds were incorporated for mechanical support, while bacterial cellulose (BC) membranes facilitated psoralen (Pso) delivery. PCL scaffolds were fabricated via three-dimensional (3D) printing, and BC was extracted from fungi to prepare three types of scaffolds as follows: PCL, BC–PCL, and BC–Pso–PCL. The scaffolds were characterized through scanning electron microscopy, contact angle measurement, and infrared spectroscopy. Biocompatibility was assessed by cytotoxicity (CCK-8) assay, cell migration assay, live/dead cell staining, and cell proliferation experiments. Antibacterial effects were tested under a simulated bacterial environment. Osteogenic performance was evaluated by alkaline phosphatase (ALP) activity, Alizarin red staining (ARS), and immunofluorescence after osteogenic induction. Quantitative reverse transcriptase PCR (qRT-PCR) and Western blotting were performed to analyze bone regeneration and angiogenesis markers. Bone regeneration efficacy was assessed in vivo using a 5 mm critical-sized cranial bone defect model in rats. Biocompatibility studies demonstrated that all three scaffolds showed good biocompatibility. BC–Pso–PCL scaffold effectively inhibited Staphylococcus aureus growth. The ALP staining and ARS following osteogenic induction indicated that the BC–Pso–PCL group exhibited superior ALP activity and mineralized nodule formation compared to other groups. Subsequent immunofluorescence, qRT-PCR, and Western blot further confirmed the superior osteogenic performance of the BC–Pso–PCL scaffold. In vivo experiments demonstrated that the BC–Pso–PCL scaffold achieved the highest level of new bone formation in rat cranial defects. In conclusion, the BC–Pso–PCL scaffold demonstrated superior biocompatibility in cytotoxicity, cell migration, live/dead staining, and proliferation assays, while also promoting bone regeneration and angiogenesis. The in vivo study further confirmed its superior potential in bone formation. These findings highlight the BC–Pso– PCL hybrid scaffold as a promising implantable scaffold for treating open bone defects, with potential for future clinical applications.

Wound healing is a multifaceted biological process that necessitates the development of advanced materials that can effectively support tissue regeneration and repair. The fabrication of bioengineered wound dressings has evolved significantly, with three-dimensional (3D) bioprinting emerging as a promising method to produce personalized, structurally stable hydrogels. In this study, we leveraged extrusion-based 3D bioprinting technology to develop gelatin-hyaluronic acid (GEL-HA) hydrogels, incorporating thymoquinone (TQ), a bioactive compound known for its regenerative properties. The use of 3D printing allowed for precise control over the scaffold’s architecture, optimizing its compressive strength and resilience while creating a bioactive, biocompatible platform for wound healing applications. This enables precise control over their architecture and mechanical properties to enhance wound healing where it offers promising potential as biocompatible scaffolds for wound healing applications due to their favorable physicochemical properties and ability to promote cell proliferation and migration. GEL-HA hydrogels were fabricated with varying HA concentrations (0.1–1.0 wt%), and the effects on the gelation process and physical characteristics were evaluated. Results showed that the ideal gelation temperature for the GEL-HA hydrogel was 22 °C, with the inclusion of HA reducing polymerization time. The printed hydrogels exhibited high water retention (>1000%) and satisfactory mechanical properties, with a degree of crosslinking of up to 40.21%. Furthermore, the hydrogels demonstrated a low biodegradation rate (less than 0.300 mg/h) and favorable water vapor transmission rate (WVTR) in a range of 2000– 3000 gm–2day–1, which are crucial for maintaining a moist environment for wound healing. The incorporation of TQ further enhanced the biocompatibility and cellular proliferation of human dermal fibroblasts (HDFs). Cell viability assays indicated that TQ promoted HDFs growth at concentrations of 0.005–0.1 μg/mL without toxicity. Moreover, the wound scratch assay demonstrated that TQ facilitated cell migration, with the optimum concentration of 0.1 μg/mL showing the most significant effect. The GEL-HA-TQ hydrogel also supported HDFs attachment and proliferation, as confirmed by live and dead cell staining, also with Ki67 level assessment, and collagen type-I immunocytochemistry. These findings suggest that GEL-HA hydrogels, combined with TQ, provide a promising and biocompatible platform for wound healing. It effectively promotes cell viability, migration, and extracellular matrix synthesis, which could be beneficial in regenerative medicine and tissue engineering applications.

Currently, a substantial number of patients suffer from the distress of skin defects. Tissue-engineered skin represents a promising alternative therapeutic option for these patients. However, the currently available tissue-engineered skin products still exhibit significant limitations, including poor long-term viability and a lack of appendages. The advent of three-dimensional (3D) printing technology and organoid formation techniques provides a promising avenue for addressing these challenges. In this study, we constructed a scaffold using 3D printing with sodium alginate (NaAlg)/gelatin (GEL)/alginate lyase hydrogel, which has controllable pore size and degradation rate. This scaffold provides a favorable microenvironment for the colonization and functional maturation of hair follicular hanging drops within artificially organized skin. In vitro observations revealed the regeneration of hair follicles and the high expression of hair follicle-specific markers, LIM homeobox 2 (LHX2), and cytokeratin 17 (CK17). In addition, we studied the follicular polarization of the engineered skin compared to normal skin and attempted to identify possible underlying mechanisms. In conclusion, our findings present a novel strategy for establishing artificial skin with appendages.

Interbody fusion cages are key implants in spinal interbody fusion surgeries. For the novel biodegradable interbody fusion cages that can be gradually absorbed and replaced in the body, the formulation system of the materials plays a crucial role in their long-term biocompatibility and mechanical stability. In this study, PCL/ HA composites with high hydroxyapatite (HA) mass fractions (25, 30, 35, 40%) and different polycaprolactone (PCL) molecular weights (50 and 80 kDa) were fabricated. Biodegradable PCL/HA interbody fusion cages of different material systems were printed by polymer melt differential three-dimensional (3D) printing technology. In vitro degradation tests were conducted in a simulated in vivo environment to quantitatively analyze the stability and degradation behavior of PCL/HA interbody fusion cages with different material compositions and molecular weights in an artificially simulated body fluid environment, and their mechanical properties under loads. The cytotoxicity assays of the material were also conducted. The findings revealed that the degradation rate of the interbody fusion cage accelerated as the HA content increased. The strength and stiffness of each material system exceeded the minimum requirement for human cancellous bone. When the HA content was the same, the degradation rate of the high molecular weight (80 kDa) interbody fusion cage was faster compared to that of the 50 kDa molecular weight cage. When the HA mass fraction was below 30wt%, the compressive strength and compressive modulus of the fusion cage increased with increasing HA content. However, when the HA mass fraction exceeded 30wt%, the mechanical properties of the fusion cage worsened with higher HA content. A comparative analysis of material properties indicated that when the HA content was 30wt%, the fusion cage exhibited a moderate degradation rate, high compressive strength and modulus, and excellent 3D printing performance, making it the formulation system with the best overall performance. In addition, the PCL material, which was also used in most literature, exhibited varying levels of cytotoxicity depending on the cytotoxicity testing method. Further animal implantation experiments of spinal fusion cages require the selection of medical-grade implant materials.

The fabrication of bioartificial tissue substitutes is a complex process that relies on the application of innovative biomaterials and manufacturing techniques enabling the generation of cell-laden scaffolds mimicking natural tissue interfaces. Among the many biomaterials, gelatin methacryloyl (GelMA) hydrogels have shown great potential for three-dimensional (3D) bioprinting-based tissue engineering due to their high biocompatibility, biodegradability, and tunable mechanical properties. In this study, the potential use of hybrid hydrogels based on GelMA and a highly purified graphene-derivative (BioGraph) as biomaterials bioinks for extrusion-based 3D bioprinting was investigated. Formulations containing BioGraph concentrations of up to 0.1% w/v were well-suited for this technique, showing good extrudability with reduced clogging at the printing temperatures, effective photocrosslinking at the irradiances tested, high shape fidelity, and high resolution of the printed scaffold. In situ photocrosslinking tests revealed that BioGraph concentration decreased the speed of the photocrosslinking and the stiffness of the cured matrix. In vitro studies indicated that BioGraph content ≤0.1% w/v did not have an adverse impact on the viability and proliferation of rat adipose-derived mesenchymal stem cells (r-AMSCs). Similarly, acellular scaffolds implanted subcutaneously in rats showed a local macrophage-mediated inflammatory reaction and a collagen encapsulation process without any affection of surrounded host tissues. The addition of lower concentrations of BioGraph (0.025% w/v) to the matrix resulted in enhanced macrophagic interactions and scaffold degradation in vivo, and r-AMSCs growth and proliferation in vitro. In conclusion, the GelMA–BioGraph hybrid hydrogels developed here demonstrate enhanced rheological and biological properties, tailored for extrusion-based 3D bioprinting with applications in the engineering of soft (neural, liver, etc.) or hard (bone) tissues.

Implant failure due to osteoporosis remains a significant clinical challenge that requires further investigation and resolution. The immunomodulatory properties of bone implant materials are of great significance for the regulation of bone immune microenvironment to promote osteogenesis. This study aims to utilize 3D printing technology to develop a personalized porous tantalum-based MZIF-8-PDA@PTa scaffold and to achieve uniform control of melatonin (MT) and ZIF-8 nano-drug controlled delivery system through polydopamine coating, as well as investigate the effects of osteoporosis on bone regeneration and osseointegration. The MZIF-8-PDA@ PTa scaffold displayed favorable biocompatibility, biodegradability, and mechanical properties, thereby providing an optimal microenvironment for new bone formation. Additionally, the findings indicated that the MZIF-8-PDA@PTa scaffold was capable of recruiting and stimulating M2 macrophage polarization, inhibiting inflammation, and promoting the proliferation and differentiation of bone marrow mesenchymal stem cells. Scaffolds were implanted into the distal femurs of ovariectomized (OVX) rats to ultimately promote bone regeneration and osseointegration in an osteoporotic environment. Moreover, transcriptome sequencing revealed that the MZIF-8-PDA@PTa scaffold was able to promote osteogenic differentiation and mineralization via the P38-MAPK signaling pathway in BMSC cells. Taken together, the MZIF-8-PDA@PTa scaffold enhances bone regeneration and osseointegration in osteoporotic environments through the modulation of macrophage M2 polarization. Consequently, this study offers an alternative approach to creating biomaterials suitable for individuals with osteoporosis.

Additive manufacturing, particularly in bioprinting, relies on precise slicing algorithms to define printing paths. While traditional planar slicing methods impose geometric limitations, non-planar and multi-axis approaches have emerged to enhance surface quality and manufacturing efficiency. Among these, cylindrical slicing algorithms offer a novel strategy for optimizing material deposition on rotating mandrels. This study aims to implement a novel non-planar slicing algorithm capable of planning extrusion-based printing processes on a rotating mandrel. The algorithm partitions the initial volume into concentric cylindrical layers, each defined by an increasing radius around the mandrel’s core. In the first step, the geometry is sectioned with a plane passing through the mandrel’s axis and then unrolled to produce a volume lying on a planar face. This transformation, applicable to geometries regardless of axial symmetry, facilitates the application of conventional or custom planar/non-planar slicing algorithms. Subsequently, the calculated trajectories are rewrapped, transforming the planar layers into a series of coaxial cylindrical layers aligned around the mandrel. To validate the slicer’s functionality, a rotating spindle was developed and integrated as a fourth motion axis into a previously designed multi-material, multi-scale 3D bioprinter. This system incorporates both an extrusion-based bioprinting unit and a fused filament fabrication unit. The algorithm enables full control over key printing parameters, such as layer thickness, layer width, and infill patterns. Testing on multiple 3D models relevant to biomedical applications demonstrated the algorithm’s robust performance.

3D-printed porous bionic scaffolds are used to imitate irregular bone shapes and provide a suitable growth environment for integrated bone tissue. Although many bionic structures have emerged, it remains to be determined which structure has the best osseointegration ability. In this study, we found that the trabecular bone structure is ellipsoid-like by scanning human bone specimens. It is speculated that the bionic scaffold produced using the ellipsoid intersection model has better osseointegration properties. Subsequently, computer-aided design was used to contrive porous scaffolds with pores of three different geometric shapes, including tetrahedron (TBC), Schwarz-P (P), and ellipsoid bionic (EB) structures. The scaffolds were prepared by selective laser melting with similar porosities (65%) and pore sizes (480 μm). Mechanical tests have proven the scaffolds to have high accuracy and good mechanical properties. Subsequently, three scaffolds were implanted into the lateral condyle femur of rabbits. Micro-computed tomography quantitative analysis and hard tissue section staining were performed on samples harvested 6 and 12 weeks after surgery. The results demonstrated the advantage of EB structure in bone ingrowth, consistent with the results of the in vitro cell experiments. According to computer fluid dynamics simulations, the EB structure has the most appropriate internal streamline structure and the best wall shear stress distribution for cell proliferation, demonstrating its benefits in osseointegration. The pore geometry has a significant effect on the osseointegration of the scaffold. The EB structure, proposed for the first time in this study, demonstrates significantly superior osseointegration compared to the regular TBC structure and P-curved surface structure, thereby providing a reference for future research on optimal 3D-printed bionic porous scaffolds.

Nerve guide conduits (NGCs) are promising alternatives to autografts for the treatment of peripheral nerve injuries. These conduits are designed to replace the nerve tissue that has been damaged or removed from the injured nerve region. An ideal nerve conduit should effectively bridge the nerve gap and induce nerve cell growth and regeneration. Current FDA-approved NGCs predominantly address gaps smaller than 2 cm and are fabricated from rigid synthetic polymers. Nevertheless, cells prefer softer substrates that more closely mimic the extracellular matrix (ECM). While hydrogels emerge as an ideal ECM-mimicking material, their application is limited by challenges in suturing, maintaining structural integrity, and susceptibility to rapid biodegradation. In this study, we propose a tri-layered NGC biofabricated by combining melt-electrowriting (MEW) and extrusion-based bioprinting, thereby facilitating three functionalities—the outer layer of MEW-polycaprolactone (PCL) fiber monophasic structure for mechanical integrity, the middle layer of MEW-PCL aligned fibers providing topographical cues for axonal directionality, and the inner bioprinted gelatin methacryloyl layer for encapsulating cells in an ECM-mimicking matrix (~7 kPa stiffness matching nerve tissues). In addition to having tunable mechanical properties (by changing the outer layer design), these biocompatible materials are cost-effective, easily biofabricated, highly tunable for drug-loading, and can support the growth, proliferation, and differentiation of human neural stem cells to peripheral neurons, making the proposed tri-layered NGCs promising candidates for treating long nerve gap injuries.

Digital light processing (DLP) 3D printing technology exhibits remarkable potential in dental manufacturing due to its exceptional precision, customization capabilities, and rapid prototyping abilities. Compared to crown and bridge restorations produced through milling and sintering, resin restorations fabricated using DLP printing technology offer higher accuracy and more efficient and economical processing methods. However, the clinical application of DLP-printed tooth crowns and bridge prostheses is limited by their poor mechanical properties and biocompatibility. In this study, a light-curing resin matrix was formulated using urethane dimethacrylate, poly(propylene glycol) dimethacrylate, and a novel photoinitiator 2,4,6-trimethylbenzoyl bis(p-tolyl) phosphine oxide. Silane-modified nano-silica (SiO2) was used as a reinforcing filler to achieve different solid contents in the resin matrix. Four groups of DLP-printed dental nanocomposite resins (DNRs) were prepared with varying solid contents: 16, 19, 22, and 25 wt%. Subsequently, comprehensive evaluations were conducted on the rheological properties, flexural strength, compressive strength, hardness, water absorption capacity, solubility, double bond conversion efficiency, and light transmittance of DNRs with different solid contents. The esthetic properties and biocompatibility of DNRs were further assessed using gingival fibroblasts. The results demonstrated that incorporating 19 wt% SiO2 nanoparticles into the resin matrix significantly enhanced both physical– mechanical properties and biocompatibility of DNRs. In conclusion, the DLP-printed dental nanocomposite with a solid content of 19 wt% exhibited excellent physical– mechanical properties and biocompatibility, suggesting its potential for application in crown and bridge restorations for DLP-printed teeth.

Bone tissue engineering (BTE) aims to repair bone defects using biocompatible materials with tailored geometries and pore structures, providing appropriate mechanical support and control over biodegradation kinetics to promote bone growth. In this study, we utilized digital light processing (DLP) 3D printing to fabricate scaffolds with varying pore sizes using polymer–ceramic slurries composed of polylactic acid (PLA) as the main polymer matrix, incorporated with hydroxyapatite (HA) and bioactive borate glass (BBG) at various ratios. We studied the effect of composition on rheological behavior, printability, mechanical properties, bioactivity, degradation rate, and biocompatibility. While HA increased viscosity and reduced printing accuracy, it also improved mechanical properties and bioactivity. BBG increased the hydrophilicity and shape fidelity of the scaffold. Both HA and BBG enhanced the compressive mechanical properties by reinforcing the polymer matrix with ceramic particles. To study the scaffold’s bioactivity, samples were immersed in simulated body fluid for 4 weeks. Both ceramic additives enhanced the bioactivity of PLA scaffolds, evidenced by the formation of a secondary HA layer on the scaffold surface. Among the scaffolds studied, PLA-BBG exhibited the highest osteocyte viability, followed by PLA-HA and then plain PLA samples. Our findings highlight the potential of DLP 3D printing for the fabrication of tailored polymer–ceramic scaffolds for BTE and other biomedical applications.

Extrusion-based bioprinting (EBB) is an efficient, simple, and cost-effective bioprinting technique. However, due to the high complexity of biomaterial inks, a trial-and-error approach is typically required for determining the optimal printing parameter configurations. Thus, the quality and reproducibility of printed scaffolds remain a concern. In this study, we integrated flow sensing into the EBB and replaced conventional fixed-value printing parameters by capturing the time-series data of all printing parameters to enhance the monitoring of the printing process. To improve the EBB adaptability, we conducted experiments with three biomaterial inks with distinct properties under various parameter configurations to achieve ink-insensitive linewidth prediction through the construction and assessment of deep learning models. Additionally, two explainable artificial intelligence methods were used to analyze the decision-making process of the deep learning model. This analysis not only enhanced model reliability but also identified key features in printing parameters and time-series data. These results can be used to improve the efficiency and quality of the EBB processes by using various biomaterial inks.

Patient-specific three-dimensional (3D)-printed titanium alloy implants often face challenges such as stress shielding and inadequate osseointegration. This study investigated the effects of lattice designs and growth factor-enriched sticky bone on bone ingrowth and mechanical bond strength at the implant–bone interface of large-scale bone defects at the distal femur condyle in a New Zealand rabbit model. Hollow cylindrical implants (length: 12 mm; diameter: 6 mm [outer], 2 mm [inner]) with diamond (DU) and randomly deformed spherical (YMR) lattices were designed and implanted into rabbit femoral condyles. Platelet-rich fibrin (PRF) was prepared using a novel negative pressure centrifuge and mixed with synthetic bone graft material to form sticky bone, which was used to fill the implant cavities. Micro-computed tomography (CT) imaging assessed bone ingrowth volume across zones, while mechanical testing evaluated shear bond strength. The results demonstrated that growth factors are the primary driver of bone ingrowth and mechanical strength. Bone growth volume increased significantly in zone A (implant cavity), with sticky bone yielding a 6.9-fold increase for DU (6.66 mm³ vs. 45.89 mm³) and a 3.5-fold increase for YMR (14.68 mm³ vs. 51.95 mm³). Across zones B and C (lattice layers), YMR lattices consistently outperformed DU in promoting bone growth and stability. Push-out tests demonstrated shear bond strengths of 2.78 MPa for DU and 2.83 MPa for YMR with growth factors, compared to 1.71 MPa for controls. This study highlights the critical role of growth factors in enhancing bone integration and demonstrates the complementary benefits of optimized lattice designs, particularly YMR, in improving osseointegration and mechanical stability. The findings provide a promising strategy for using 3D-printed titanium alloy implants with sticky bone systems to address large bone defects in clinical applications.