3D Printing Research Articles

Three-dimensional printing in modern orthopedic trauma surgery: a comprehensive analysis of technical evolution and clinical translation

Three-dimensional (3D) printing has emerged as a transformative technology in orthopedic trauma surgery, offering unprecedented possibilities for personalized surgical solutions. Despite its increasing adoption, there remains a lack of comprehensive reviews systematically evaluating its technical considerations and evidence-based outcomes across different anatomical regions. Through systematic review of literature from major databases and analysis of clinical evidence, this comprehensive review examines the current state of advanced 3D printing technologies in orthopedic trauma. We analyze four major additive manufacturing methodologies: vat photopolymerization for surgical guides, material extrusion for anatomical models, powder bed fusion for implants, and emerging bioprinting approaches. The integration of these technologies has substantially improved surgical outcomes through three primary approaches: preoperative planning with anatomical modeling, intraoperative guidance using custom surgical guides, and patient-specific implant solutions. Systematic analysis demonstrates significant improvements in surgical precision, operative efficiency, and anatomical restoration across various fracture patterns. While challenges in manufacturing protocols, quality control standards, and regulatory frameworks persist, ongoing innovations in materials science, digital workflow optimization, and clinical validation continue to expand the applications. This review provides a systematic framework integrating technical principles and clinical applications of 3D printing in orthopedic trauma surgery, offering practical guidelines while highlighting future research directions.

Advances in application of digital technologies in surgery for ankylosing spondylitis

To explore the application progress and clinical value of digital technologies in the surgical treatment of ankylosing spondylitis (AS). By systematically reviewing domestic and international literature, the study summarized the specific application scenarios, operational procedures, and technical advantages of digital technologies [including preoperative three-dimensional (3D) planning, intraoperative real-time navigation, robot-assisted surgery, and 3D printing] in AS surgery, and analyzed their impact on surgical accuracy, complication rates, and clinical outcomes. Digital technologies significantly improve the precision and safety of AS surgery. Preoperative 3D planning enables personalized surgical protocols; intraoperative navigation systems dynamically adjusts surgical trajectories, reducing the risk of iatrogenic injury; robot-assisted surgery can minimize human errors and enhance implant positioning accuracy; 3D-printed anatomical models and guides optimize the correction of complex spinal deformities. Furthermore, the combined applications of these technologies shorten operative time, reduce intraoperative blood loss, decrease postoperative complications (e.g., infection, nerve injury), and accelerate functional recovery. Through multidimensional integration and innovation, digital technologies provide a precise and minimally invasive solution for AS surgical treatment. Future research should focus on their synergy with biomaterials and intelligent algorithms to further refine surgical strategies and improve long-term prognosis.

3D Printing of an Electrolyzer and its Validation for School Educational Purposes

3D Printing of an Electrolyzer and its Validation for School Educational Purposes

Thermoresponsive polymers for cell support: poloxamers as a case study of promise and challenge.

Thermoresponsive biomaterials have the potential to improve the complexity of in vitro models, to generate dynamically controlled extracellular microenvironments and act as in situ forming drug delivery systems. Due to its known biocompatibility and ease of use, poloxamer 407 (P407), also known as pluronic F127, has attracted significant attention as a component for next-generation cell culture and biomedical applications. P407 display rapid gelation into hydrogels with facile ease-of-handling, and which possess good shear-thinning properties that enable 3D printability with high fidelity. Although P407 has been extensively used as a support matrix for cell proliferation, differentiation and the on-demand release of biomolecules and drugs, significant issues relating to mechanical stability under physiological conditions limit its application. Multiple protocols report the use of P407 'hydrogel' for a variety of applications but often do not emphasise its inherent limitations at the concentrations described. Here we emphasise the disparity between written protocols and what specifically constitutes a hydrogel, showing selected examples from the literature and suggesting clarifications in the language used in describing P407 supports. We describe progress in the field, which is accelerating in part due to development of multi-network hydrogels that include P407 as a stabiliser, for shear-thinning and as a sacrificial component aiding 3D printing. We also contrast P407 to a panel of other promising thermoresponsive systems that have emerged as alternative biomaterials. Finally, we briefly discuss challenges and new opportunities in the field. This includes evaluation of the relative merits of current thermoresponsive polymer systems as they are formulated for use, also by advanced manufacturing, in next-generation 4D-responsive functional hydrogel networks for cell culture automation and as components in responsive-release devices.

Statistical Modeling and Multi‐Objective Optimization of Embedded 3D Printing Process Parameters for Tubular Scaffolds

ABSTRACTThe development of tissue‐engineered tubular scaffolds requires precise control over fabrication parameters to ensure optimal mechanical performance. This study focuses on statistical modeling and multi‐objective optimization of embedded 3D printing process parameters for polylactic acid (PLA) and polypropylene carbonate (PPC) tubular scaffolds. A central composite design is used to evaluate the effects of layer thickness, print speed, and polymer concentration on radial load and shrinkage. The results indicate that shrinkage is minimized at lower layer thickness, reduced print speed, and higher polymer concentration. The radial load increases up to an optimal point with increasing print speed before decreasing. Further, the load is observed to increase with decreasing layer thickness and higher polymer concentration. A multi‐objective optimization based on a genetic algorithm is implemented to determine the optimum parameters for minimizing shrinkage and maximizing load. To validate the optimized parameters, a case study is conducted by fabricating a tracheal scaffold and comparing its mechanical properties with a native goat trachea. The results confirm that the scaffold achieves comparable mechanical properties to those of native goat trachea, demonstrating the effectiveness of the proposed methodology. The study highlights the importance of statistical modeling and optimization in improving scaffold fabrication for tissue engineering applications.

Application of 3-Dimensional Printing in Brain Surgery From 2015 to 2024: A Bibliometric Analysis.

This study uses bibliometric analysis and knowledge mapping methods to systematically explore the emerging research frontiers and development trajectories of 3-dimensional (3D) printing technology in the application of brain surgery, and provides new clues and research directions for future research by exploring hotspots and new topics. A comprehensive literature search was conducted through the Scientific Citation Index Core Collection (WoSCC) database on March 21, 2025 to identify relevant articles and reviews published between January 2015 and December 2024 on the application of 3D printing technology in brain surgery. For data analysis and visualization, we used CiteSpace and VOSviewer software to conduct rigorous bibliometric analysis and build knowledge domain maps. The authors' analysis covered 2982 papers contributed by 5550 authors from 1174 institutions in 90 regions, published in 236 journals. The authors have observed a steady increase in the number of publications annually, with Europe, Asia, North America, and Oceania leading the way in research output. The United States is in a leading position in research in this field. The University of London became the leading research institution in this field. The Journal of Craniofacial Surgery has made significant contributions to this field, with Tillinger Florian M being the most published and cited author. The most influential research hotspots focus on virtual surgical planning, tissue engineering, 3D printing and finite element analysis. The latest hotspots and research frontiers include 3D printing, augmented reality and reconstructive surgery. 3D printing technology has made significant progress in the field of brain surgery and has become a research frontier for continuous development in the field of medical innovation.

Integrating 3D Printing with Injection Molding for Improved Manufacturing Efficiency

This study investigates a hybrid manufacturing approach that combines 3D printing and injection molding to extend the limitations of each individual technique. Injection molding is often limited by high initial tooling costs, long lead times, and restricted geometric flexibility, whereas 3D-printed molds tend to suffer from material degradation, extended cooling times, and lower surface quality. By integrating 3D-printed molds into the injection-molding process, this hybrid method enables the production of complex geometries with improved cost-efficiency. The approach is demonstrated using a range of polymeric materials, including ABS, nylon, and polyurethane foam—each selected to enhance the mechanical and thermal performance of the final products. Finite element method (FEM) analysis was conducted to assess thermal distribution, deformation, and stress during manufacturing. Results indicated that both temperature and stress remained within safe operational limits for 3D-printed materials. An economic analysis revealed substantial cost savings compared to fully 3D-printed components, establishing hybrid manufacturing as a viable and scalable alternative. This method offers broad industrial applicability, delivering enhanced mechanical properties, design flexibility, and reduced production costs.

Engineering Cures: The Role of 3D Printing in Modern Medicine

Abstract: The use of 3D printing technology in pharmacy and healthcare is transforming drug development and patient care. This cutting-edge method allows for the creation of personalized medications, tailored drug delivery systems, and medical devices designed specifically for individual patients. 3D printing makes it possible to produce complex dosage forms, such as controlled-release formulations, multi-drug combinations, and adjustable-dose tablets, which improve therapeutic outcomes while reducing side effects. Additionally, it enables on-demand manufacturing of medicines, lessening the dependence on traditional pharmaceutical supply chains and providing a solution to drug shortages. Beyond its pharmaceutical applications, 3D printing is enhancing patient care by facilitating the production of custom implants, prosthetics, and medical devices. This technology also encourages better patient adherence by personalizing medications, addressing challenges like pill burden and taste preferences. Patents have been granted for methods utilizing 3D printing to produce customized tablets featuring controlled release profiles, multi-drug combinations, and customizable dosages specific to individual patient requirements. This review emphasizes the revolutionary impact of 3D printing in pharmacy and healthcare, focusing on personalized drug formulations, customized drug delivery systems, and tailored medical devices. It highlights advancements in controlled-release medications, multi-drug regimens, on-demand production, and enhanced patient compliance, promoting a more effective, patient-centric healthcare system.

Therapeutic Implants: Mechanobiologic Enhancement of Osteogenic, Angiogenic, and Myogenic Responses in Human Mesenchymal Stem Cells on 3D-Printed Titanium Truss.

This study investigates the effect of mechanotransduction on human mesenchymal stem cells (hMSCs) attached to structural elements of an implant, specifically a titanium truss element. It is found that surface features generated by 3D printing technology promote osteogenic activity, comparable to conventional treatments such as acid etching. Cell morphology and differentiation are evaluated using test coupons with either smooth or rough surface features. hMSCs on smooth titanium surfaces exhibit a flat, spread morphology consistent with fibrous tissue formation. In contrast, cells on 3D printed hierarchical surfaces cluster within surface asperities, resembling a trabecular bone-like orientation, and exhibited enhanced osteogenic gene expression. Building on this static surface-induced osteogenesis, we further investigated the effect of load-induced strain on hMSCs attached to the rough surface. Upon applying dynamic mechanical loading, RNA-sequencing analysis reveals that strain not only amplified osteogenic gene expression but also significantly upregulated angiogenic and myogenic pathways compared with static conditions. These findings demonstrate a synergistic effect between surface topography and mechanical strain in promoting osteogenesis. This study highlights the potential of utilizing mechanical strain through an implant's structural design to enhance osteogenic responses, offering valuable insights for the development of next-generation therapeutic implants.

Macro-Micro analysis of scaffold properties and study of biological properties of 3D printed hydroxyapatite/β-Tricalcium phosphate scaffolds influenced by polyvinyl alcohol concentration

The concentration of the binder is a key factor affecting the quality of 3D-printed bone scaffolds. This study analyzed the influence of polyvinyl alcohol (PVA) aqueous solution concentration on the properties of hydroxyapatite (HA)/β-tricalcium phosphate (β-TCP) bone scaffolds from both microscopic and macroscopic perspectives using molecular dynamics (MD) simulations and experimental research. In the MD simulations, the changes in chain length corresponding to different concentrations were used to analyze the microscopic interactions between PVA and the powder material system. In the experiments, the solid content, zeta potential, and extrusion rheological properties of the slurry were analyzed under PVA concentrations ranging from 5% to 15% by mass. Bone scaffolds were then fabricated using 3D printing and freeze-drying processes, and the changes in porosity, mechanical properties, dimensional shrinkage, and swelling effect of the scaffolds were examined. Finally, the biological properties of the scaffolds were verified through in vitro experiments. The results showed that the hydrogen bonds and ionic bonds formed between PVA and the powder materials are the main forces for adhesion, and the increase in chain length, which leads to an increase in Cauchy pressure, enhances the basic mechanical properties of the material. Slurries with higher PVA concentrations have higher solid content and shear-thinning capabilities, ensuring better printability, and the resulting bone scaffolds exhibit higher mechanical properties and drying shrinkage characteristics. However, this also leads to lower porosity and swelling rates. In vitro experiments revealed that an increase in PVA aqueous solution concentration results in decreased porosity and ion concentration of the bone scaffolds, thereby reducing their bioactivity. The conclusions drawn from this study can be used to predict the performance of slurries and bone scaffolds at different binder concentrations, providing a theoretical basis for the selection of binder concentration in 3D-printed bone scaffolds.

Effects of Process Parameters on Tensile Properties of 3D-Printed PLA Parts Fabricated with the FDM Method

This study investigates the influence of key fused deposition modeling (FDM) process parameters, namely, print speed, infill percentage, layer thickness, and layer width, on the tensile properties of PLA specimens produced using 3D printing technology. A Taguchi L9 orthogonal array was employed to design the experiments efficiently, enabling the systematic evaluation of parameter effects with fewer tests. Tensile strength and elongation at break were measured for each parameter combination, and statistical analyses, including the signal-to-noise (S/N) ratio and analysis of variance (ANOVA), were conducted to identify the most significant factors. The results showed that infill percentage significantly affected tensile strength, while layer thickness was the dominant factor influencing elongation. The highest tensile strength (47.84 MPa) was achieved with the parameter combination of 600 mm/s print speed, 100% infill percentage, 0.4 mm layer thickness, and 0.4 mm layer width. A linear regression model was developed to predict tensile strength with an R2 value of 83.14%, and probability plots confirmed the normal distribution of the experimental data. This study provides practical insights into optimizing FDM process parameters to enhance the mechanical performance of PLA components, supporting their use in structural and functional applications.

Primary Evaluation of Three-Dimensional Printing-Guided Endodontics in the Dog Maxillary

This study aims to evaluate the feasibility and accuracy of 3D printing-guided endodontics in the maxillary teeth of dogs. CT data from a Beagle dog were processed to create a 3D model of the maxilla, and virtual root canal pathways were established using SOLIDWORKS software (version 29.0.0.5028). Guided endodontic templates were 3D printed and tested in vitro on 20 maxillary teeth (excluding the third molars), with 36 root canals treated using both guided and conventional methods. Results indicated that 3D printing-guided endodontics provided accurate root canal pathways, with minimal deviations in length (average 3.08 ± 1.75%) and angular alignment (average 2.06° ± 0.5°) compared to conventional methods. This research represents a significant step forward in the application of 3D printing technology in veterinary endodontics, offering a promising alternative to traditional methods for treating complex dental conditions in dogs.

Three-Dimensional-Printed Ordered Bredigite Scaffolds with Dual Bioactivities Promote Osteochondral Regeneration.

Osteochondral tissues have limited self-healing abilities, making it challenging to achieve complete healing following injury. Osteochondral defects present significant clinical challenges. Bredigite (BRT, Ca7MgSi4O16) bioceramic scaffolds exhibit excellent physicochemical properties, biocompatibility, osteoinductivity, and osteoconductivity, making them promising candidates for osteochondral repair and regeneration. Herein, a BRT bioceramic was fabricated into structurally ordered scaffolds (BRT-O) and random morphology scaffolds (BRT-R) by using 3D printing techniques, while the tricalcium phosphate (TCP) scaffolds that are used in the clinic were fabricated as controls. The physicochemical properties, effects on bone marrow-derived stem cells (BMSCs) and chondrocytes in vitro, and performance in cartilage and subchondral bone regeneration were evaluated and compared among the three scaffolds. The results showed that the BRT-O scaffolds possessed the highest compressive strength, controllable biodegradability, and ability to regulate the local microenvironment by releasing bioactive ion products and altering the pH. In vitro, BRT-O scaffolds significantly enhanced the migration and osteogenic/chondrogenic differentiation of BMSCs, as well as the adhesion and maturation of chondrocytes. In vivo experiments revealed that the BRT-O scaffolds promoted the simultaneous and effective regeneration of hyaline cartilage and subchondral bone in rabbit osteochondral defect models. In summary, the monophasic BRT-O scaffold demonstrated dual bioactivity, promoting both osteogenesis and chondrogenesis, and thus, it holds significant clinical potential for osteochondral defect repair.

The effect of 3D printing technology combined with Morse taper and platform switching design on microleakage performance of dental implants.

This study aims to investigate the effects of a Morse taper connection combined with platform switching design and hydroxyapatite (HA) coating on the mechanical properties, bacterial leakage, bioactivity, and osteogenic properties of dental implants. Four groups of models (platform switching of 0 and 0.6mm; Morse taper of 0° and 10°) were determined through three-dimensional finite element analysis and labeled as TI, P, T, and PT groups. The dental implants were fabricated using selective laser melting and then surface-modified with sandblasting, acid etching, and HA coating. The physicochemical properties of the implants were measured using scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive spectrometry (EDS), and profilometry. Bacterial leakage was detected by colony counting. Finally, the biocompatibility, bioactivity, and osteogenic capacity of the implants were assessed through cell culture, immunohistochemistry, and Western blot. Significant differences were observed between the PT and Ti groups in terms of morphology, mechanical properties, and bacterial leakage. HA coating significantly enhanced the bioactivity of the implants. Implants modified by sandblasting, acid etching, and HA coating exhibited better biocompatibility, bioactivity, and osteogenic capacity compared to unmodified implants. Additionally, the PT group showed a significant improvement in reducing bacterial leakage. The Morse taper connection combined with platform switching design places less stress on the implant system than conventional platform-docked implants. The narrowing of the abutment neck is more favorable for the attachment of osteoblast-associated cells.

Accuracy Assessment of 3D-Printed Surgical Guides for Palatal Miniscrew Placement: A Retrospective Study

Background: The aim of this retrospective study was to conduct an in vivo evaluation of the accuracy of surgical guides obtained via 3D printing technology that were used to transfer the 3D software-planned position and axis during palatal miniscrew placement. Methods: Twenty-four Caucasian subjects with permanent dentition underwent a CBCT examination to plan palatal skeletal anchorage using two miniscrews in the anterior palatal arch. A specific software function capable of identifying and displaying all CBCT scans passing through the planned miniscrew axis was used to identify the scan showing the maximum discrepancy between the planned and final miniscrew placement. The maximum insertion angle discrepancy and the maximum linear difference between the head and tip of the miniscrew were measured on the overlaid 3D STL models of the planned miniscrew position at CBCT with the final clinical position of the miniscrew. Results: Descriptive and inferential statistics were performed. On average, there was a discrepancy between the planned insertion axis and the final insertion axis of 2.95° (SD ± 1.13°), with a 10 mm miniscrew length. Conclusion: Three-dimensional I.-printed surgical guides for palatal miniscrew placement show a mean deviation of 2.95° from the planned position, indicating good but improvable accuracy in placement.

Automatic optimization of heart valve prosthesis – a genetic algorithm-based approach

Introduction. The development of new and improvement of existing models of bioprosthetic heart valves is an important task of current engineering of medical devices. Developing the geometry of the key component of the prosthesis the valve apparatus can significantly improve its durability and, therefore, the clinical effectiveness of interventions on heart valves.Aim: To develop a method for the automatic optimization of the leaflet apparatus of a heart valve prosthesis using the NSGA-II genetic algorithm. The primary goal is to reduce mechanical stress, enhance hydrodynamic efficiency, and improve biomechanical durability, ultimately increasing the lifespan of prosthetic valves and reducing the risk of complications.Material and Methods. The study integrates parametric modeling, numerical analysis, and directed optimization. Leaflet geometry generation was performed using Python and computer-aided design (CAD) tools. Biomechanical analysis was conducted using the finite element method (FEM) in Abaqus/CAE. Optimization was implemented via the NSGA-II algorithm, which automatically selects balanced solutions based on multiple criteria: leaflet opening and closing area, mechanical stress levels, and deformation degree. A total of 250 generations of geometries were formed. The optimized design was prototyped using 3D printing with polymeric materials.Results. The optimization process significantly reduced stress in the leaflet apparatus and improved its functional characteristics. The algorithm's performance showed that optimal parameter improvements occurred by the 42nd and 58th generations, after which the evolution of results stabilized. The final model demonstrated a moderate opening area (66% of the maximum, 2.7 cm²), minimal closing area (1%), maximum stress of 0.89 MPa, and no significant deformations. However, the 3D prototyping process revealed technical challenges, including defects caused by support structures during printing.Conclusion. The developed automatic optimization algorithm for the leaflet apparatus of heart valve prostheses has proven effective in enhancing mechanical stability and hydrodynamic efficiency. This approach significantly reduces design time and minimizes subjective engineering decisions. However, the identified prototyping challenges necessitate further refinement, including alternative manufacturing methods. Future research will focus on improving material biocompatibility and experimental validation of the optimized models.

Food Toxicology and Safety: Evaluating Dietary Risks and Functional Ingredients

ABSTRACTFood remains a fundamental determinant of human health, with significant implications for disease prevention, longevity, and overall quality of life. This review critically examines the multifaceted relationship between dietary patterns, food‐derived carcinogens, metabolic health outcomes, and technological innovations in the modern food system. Empirical evidence indicates that specific dietary behaviors—such as excessive intake of red and processed meats, low consumption of vegetables and fruits, and habitual intake of sugar‐sweetened beverages—are associated with increased risks of obesity, Type 2 diabetes, cardiovascular disease, and several types of cancer. Mechanistically, foodborne carcinogens may exert harmful effects through multiple biological pathways, including the dysregulation of gene expression, interference with DNA repair, alteration of cell cycle progression, and inhibition of apoptosis. Dietary exposure to compounds such as heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), acrylamide, nitrosamines, and mycotoxins has been shown to significantly elevate the risk of malignancies and contribute to the development of metabolic disorders. In response to these challenges, recent advancements in food science and technology are paving the way for novel preventive strategies. Innovations such as blockchain‐enabled traceability, CRISPR‐Cas gene editing for nutrient optimization, and 3D food printing for personalized nutrition are being actively explored for their potential to enhance food safety and reduce exposure to harmful substances. Furthermore, emerging tools like bioprocessing for food preservation, nanotechnology for precision nutrient delivery, smart packaging technologies, and precision fermentation are redefining sustainable food production while mitigating toxicological risks. Future directions should emphasize the development of functional foods enriched with bioactive phytochemicals, the implementation of technological interventions to improve traceability and contamination control, and the strengthening of global regulatory frameworks—including pesticide regulation and food labeling policies. Collaborative efforts among researchers, food technologists, public health professionals, and policymakers, alongside consumer education, are essential to fostering a resilient and health‐oriented global food system.

3D printing of a low-cost videolaryngoscope for tracheal intubation

Videolaryngoscopes have been designed to improve the success rate of tracheal intubation on the first attempt; however, their high cost, especially in low- and middle-income countries, is a major disadvantage. Considering the clinical importance of this device, the Engineering School in partnership with the Anesthesiology Department developed a videolaryngoscope using three-dimensional (3D) printing technology at a more affordable cost. The methodology consisted of three stages: prospecting, modeling and prototyping, and realistic simulation on airway mannequins. The primary objective was to describe the creation and development process of the prototypes. The secondary objective was to determine the final production cost. This was an applied project utilizing an exploratory and descriptive approach. The study was developed during the COVID-19 pandemic, between May 2020 and June 2021, at the School of Engineering and in the realistic simulation room at the university hospital. Ten prototypes were produced before the final product, and they were subjected to strength and bending tests and evaluated on airway training mannequins to simulate the procedure conducted by anesthesiologists. As a result, we obtained a resistant, and low-cost device, named VLG3DUFF.

Improving quality control in 3D printing: a method for G-code-based geometry reconstruction in material extrusion

ABSTRACT Additive Manufacturing (AM) enables the creation of complex structures through a layer-by-layer material deposition process, offering significant advantages over traditional subtractive manufacturing. Among the various AM technologies, Material Extrusion (MEX), also known as Fused Deposition Modelling (FDM), is widely used due to its low cost and simplicity. This paper presents the development of an algorithm to reconstruct the sliced geometry from G-code in MEX processes, addressing the need for accurate representation and analysis of printed parts. The implemented algorithm (by MATLAB) interprets G-code commands to recreate the 3D structure of the part, allowing to view and verify the nozzle path, optimise printing parameters, and check the quality. Furthermore, the algorithm facilitates comparative analysis with the original 3D model, identifies potential issues, and implements the mechanical properties prediction by converting the G-code into a fine STL file. The algorithm’s output provides valuable insights into the internal structure, showing material distribution and void presence, supporting further research and industrial applications. This advancement significantly contributes to the digital process chain in AM, aligning with the goals of Industry 5.0 by promoting an integration from design to process control.

Cascade upconversion: a strategy enabling four-photon lithography in weak light intensity

Multiphoton lithography offers the minimum feature size available in submicron scale true 3D printing, but excessive femtosecond laser intensity prevents it from leading to higher photon counts. To circumvent away this effect, we present a cascade upconversion strategy, which is a combination of two efficient two-photon upconversion processes to achieve four-photon photopolymerization. In order to demonstrate the advantages and feasibility of this approach, we combine excited state absorption upconversion using high concentration Ho3+/Yb3+ doped upconversion nanoparticles with triplet-triplet annihilation upconversion to fabricate 3D polymer structures by low-cost continuous wave 980 nm laser at 105 W/cm2. This method overcomes the diffusivity caused by isotropy of nanoparticles luminescence, and achieves two orders of magnitude reduction in feature size while maintaining the advantages of true 3D printing (fast, freedom, high quality) and using near infrared light. This new strategy provides a general way for designing four-photon and even six-photon multiphoton lithography in weak light intensity.