Comparative study of nasal cavity drug delivery efficiency with different nozzles in a 3D printed model.

Background: Nasal sprays are widely used in treating nasal and sinus diseases; however, there are very few studies on the drug delivery efficiency of nasal sprays. In this study, the drug delivery efficiency of three different nasal spray devices was evaluated in vitro using a 3D printed cast model of nasal cavity. Methods: Three nasal spray devices with different nozzles and angles of administration were used in the 3D model of the nasal cavity and paranasal sinuses. The spraying area (SA), maximal spraying distance (MSD), and spraying distribution scores on the nasal septum and lateral nasal wall were recorded. Results: Different nasal spray devices have their own characteristics, including volume of each spray, SA, and plume angle. The SA of the three nozzles on the nasal septum increased with an increasing angle of administration. When the angle of administration was 50°, each nozzle reached the maximal SA. There was no statistically significant difference in MSD among the three nozzles at the three angles. The total scores for each nozzle using the three different spraying angles were as follows: nozzle A, 40° > 30° > 50°; nozzle B, 30° > 40° > 50°; and nozzle C, 30° > 40° > 50°. The total scores for different nozzles using the same angle were statistically significantly different and the scores for nozzle C were the highest. Nozzle C had the minimum plume angle. None of the three nozzles could effectively delivered drugs into the middle meatus at any angle in this model. Conclusions: The design of the nozzle affects drug delivery efficiency of nasal spray devices. The ideal angle of administration is 50°. The nozzle with smaller plume angle has higher drug delivery efficiency. Current nasal spray devices can easily deliver drugs to most areas of the nasal cavity, such as the turbinate, nasal septum, olfactory fissure, and nasopharynx, but not the middle meatus. These findings are meaningful for nozzle selection and device improvements.

Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis.

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.

Application of multiplanar reconstruction and 3D printing in anterior cruciate ligament revision. / 多平面重建及3D打印在前交叉韧带翻修术中的应用.

OBJECTIVES: Anterior cruciate ligament injury is the most common type of knee joint ligament injury. Anterior cruciate ligament reconstruction has a high failure rate, with bone tunnel abnormalities as the most significant factor in these failures. Digital orthopedic technology can effectively develop implementation plans for the revision, thus increasing the success rate. This study aims to develop a surgical plan for anterior cruciate ligament revision by employing multiplanar reconstruction (MPR) for measuring bone tunnel position and diameter, and simulating bone tunnel creation via 3D printing preoperatively. METHODS: A total of 12 patients who underwent anterior cruciate ligament revision at the Third Xiangya Hospital of Central South University between 2014 and 2021 were retrospectively studied. The data included patient demographics, preoperative formulated knee joint 3D printing models, and preoperative knee CT scans. The study measured the bone tunnel's diameter and position to guide the establishment of revision bone tunnels during surgery, reassessed the postoperative bone tunnels, and evaluated knee joint functional scores [including International Knee Documentation Committee Knee Evaluation Form (IKDC) score, Lysholm score, and Tegner exercise level score]. RESULTS: Preoperative measurements revealed suboptimal femoral tunnels positions in 4 patients and tibial tunnels positions in 2 patients. MPR and 3D printing technology were used to guide the establishment of a new bone canal during surgery, and postoperative measurements were satisfactory for all patients. Preoperative measurements demonstrated the interclass correlation coefficient for femoral tunnels and tibial tunnels diameters were 0.843 (P<0.05) and 0.889 (P<0.001), respectively. Meanwhile, the intraclass correlation coefficient were 0.811 (P<0.05) and 0.784 (P<0.05), respectively. The intraoperative diameter of femoral and tibial tunnels showed excellent correlation with postoperative CT measurements, with intraclass correlation coefficient values of 0.995 (P<0.001) and 0.987 (P<0.001), respectively. All bone tunnel positions were within the normal range. At the final follow-up, knee joint function scores in all 12 patients improved significantly compared to pre-surgery (P<0.001), and the reoperation rate was zero. CONCLUSIONS: MPR and 3D printing technology can accurately measure the parameters of reconstructed anterior cruciate ligament bone tunnels. Personalized revision plans for patients with reconstruction failure enhances the success rate of revision surgery and improves patient prognosis.

A 3D-Printed and Freely Available Device to Measure the Zebrafish Optokinetic Response Before and After Injury.

Zebrafish eyes are anatomically similar to humans and have a higher percentage of cone photoreceptors more akin to humans than most rodent models, making them a beneficial model organism for studying vision. However, zebrafish are different in that they can regenerate their optic nerve after injury, which most other animals cannot. Vision in zebrafish and many other vertebrate animals, including humans, can be accessed using the optokinetic response (OKR), which is an innate eye movement that occurs when tracking an object. Because fish cannot use an eye chart, we utilize the OKR that is present in virtually all vertebrates to determine if a zebrafish has vision. To this end, we have developed an inexpensive OKR setup that uses 3D-printed and off-the-shelf parts. This setup has been designed and used by undergraduate researchers and is also scalable to a classroom laboratory setup. We demonstrate that this setup is fully functional for assessing the OKR, and we use it to illustrate the return of the OKR following optic nerve injury in adult zebrafish.

Experimental investigation of ultrasonic assisted coating on three-point bending behavior of 3D printed polymeric bone plates for biomedical applications.

3D printed Poly Lactic Acid (PLA) bone plates exhibit limited three-point bending strength, restricting their viability in biomedical applications. The application of polydopamine (PDM) enhances the three-point bending strength by undergoing covalent interactions with PLA molecular structure. However, the heavy nature of PDM particles leads to settling at the container base at higher coating solution concentrations. This study investigates the impact of ultrasonic-assisted coating parameters on the three-point bending strength. Utilizing Response Surface Methodology (RSM) for statistical modeling, the study examines the influence of ultrasonic vibration power (UP), coating solution concentration (CC), and submersion time (TIME). RSM optimization recommended 100 % UP, 6 mg/ml CC, and 150 min TIME, resulting in maximum three-point bending strength of 83.295 MPa. Microscopic images from the comparative analysis revealed non-uniform coating deposition with mean thickness of 6.153 µm under normal coating. In contrast, ultrasonic-assisted coating promoted uniform deposition with mean thickness of 18.05 µm. The results demonstrate that ultrasonic-assisted coating induces PDM particle collision, preventing settling at the container base, and enhances three-point bending strength by 7.27 % to 23.24 % compared to the normal coating condition. This study emphasizes on the potential of ultrasonic-assisted coating to overcome the limitations of direct immersion coating technique.

Influence of Breath-Mimicking Ventilated Incubation on Three-Dimensional Bioprinted Respiratory Tissue Scaffolds.

Development of respiratory tissue constructs is challenging due to the complex structure of native respiratory tissue and the unique biomechanical conditions induced by breathing. While studies have shown that the inclusion of biomechanical stimulus mimicking physiological conditions greatly benefits the development of engineered tissues, to our knowledge no studies investigating the influence of biomechanical stimulus on the development of respiratory tissue models produced through three-dimensional (3D) bioprinting have been reported. This paper presents a study on the utilization of a novel breath-mimicking ventilated incubator to impart biomechanical stimulus during the culture of 3D respiratory bioprinted constructs. Constructs were bioprinted using an alginate/collagen hydrogel containing human primary pulmonary fibroblasts with further seeding of human primary bronchial epithelial cells. Biomechanical stimulus was then applied via a novel ventilated incubator capable of mimicking the pressure and airflow conditions of multiple breathing conditions: standard incubation, shallow breathing, normal breathing, and heavy breathing, over a two-week time period. At time points between 1 and 14 days, constructs were characterized in terms of mechanical properties, cell proliferation, and morphology. The results illustrated that incubation conditions mimicking normal and heavy breathing led to greater and more continuous cell proliferation and further indicated a more physiologically relevant respiratory tissue model.

3D printing processes in precise drug delivery for personalized medicine.

With the advent of personalized medicine, the drug delivery system will be changed significantly. The development of personalized medicine needs the support of many technologies, among which three-dimensional printing (3DP) technology is a novel formulation-preparing process that creates 3D objects by depositing printing materials layer-by-layer based on the computer-aided design method. Compared with traditional pharmaceutical processes, 3DP produces complex drug combinations, personalized dosage, and flexible shape and structure of dosage forms (DFs) on demand. In the future, personalized 3DP drugs may supplement and even replace their traditional counterpart. We systematically introduce the applications of 3DP technologies in the pharmaceutical industry and summarize the virtues and shortcomings of each technique. The release behaviors and control mechanisms of the pharmaceutical DFs with desired structures are also analyzed. Finally, the benefits, challenges, and prospects of 3DP technology to the pharmaceutical industry are discussed.

3D printed orthopedic prostheses for domestic and wild birds-case reports.

Regardless of the species, birds are exposed to injuries that lead to amputation of part of the body structure and often euthanasia. Based on the need for new technologies that improve the quality of life of birds with locomotor problems, the present case reports aimed to describe the development of custom-made three-dimensional (3D) prostheses for domestic and wild birds that suffered amputation or malformation of the hind limb. Using the measurements of the bird, a digital model was created for 3D printing using fused deposition modeling technology (FDM) by the Brazilian company 3D Medicine. In this study we report the use of 3D prosthesis for the rehabilitation of three birds with locomotor disorders in Brazil, the animals adapted to the custom-made prosthesis with an improvement in quality of life, better distribution of body weight, locomotion, and landing. This study describes the development of 3D prostheses for birds in Brazil, the first report of this technology for these species, and the pioneering development of socket prostheses for small birds. 3D prostheses offer a high-efficiency solution to improve the quality of life of animals with amputations and malformations of the hind limbs. In addition, 3D technology provides valuable tools for veterinary medicine, developing custom-made models for the most different anatomical demands of animal patients.

Physical and Computational Modeling for Transcatheter Structural Heart Interventions.

Structural heart disease interventions rely heavily on preprocedural planning and simulation to improve procedural outcomes and predict and prevent potential procedural complications. Modeling technologies, namely 3-dimensional (3D) printing and computational modeling, are nowadays increasingly used to predict the interaction between cardiac anatomy and implantable devices. Such models play a role in patient education, operator training, procedural simulation, and appropriate device selection. However, current modeling is often limited by the replication of a single static configuration within a dynamic cardiac cycle. Recognizing that health systems may face technical and economic limitations to the creation of "in-house" 3D-printed models, structural heart teams are pivoting to the use of computational software for modeling purposes.

Formulating biopharmaceuticals using three-dimensional printing.

Additive manufacturing, commonly referred to as three-dimensional (3D) printing, has the potential to initiate a paradigm shift in the field of medicine and drug delivery. Ever since the advent of the first-ever United States Food and Drug Administration (US FDA)-approved 3D printed tablet, there has been an increased interest in the application of this technology in drug delivery and biomedical applications. 3D printing brings us one step closer to personalized medicine, hence rendering the "one size fits all" concept in drug dosing obsolete. In this review article, we focus on the recent developments in the field of modified drug delivery systems in which various types of additive manufacturing technologies are applied.

Educational simulator for mastoidectomy considering mechanical properties using 3D printing and its usability evaluation.

Complex temporal bone anatomy complicates operations; thus, surgeons must engage in practice to mitigate risks, improving patient safety and outcomes. However, existing training methods often involve prohibitive costs and ethical problems. Therefore, we developed an educational mastoidectomy simulator, considering mechanical properties using 3D printing. The mastoidectomy simulator was modeled on computed tomography images of a patient undergoing a mastoidectomy. Infill was modeled for each anatomical part to provide a realistic drilling sensation. Bone and other anatomies appear in assorted colors to enhance the simulator's educational utility. The mechanical properties of the simulator were evaluated by measuring the screw insertion torque for infill specimens and cadaveric temporal bones and investigating its usability with a five-point Likert-scale questionnaire completed by five otolaryngologists. The maximum insertion torque values of the sigmoid sinus, tegmen, and semicircular canal were 1.08 ± 0.62, 0.44 ± 0.42, and 1.54 ± 0.43 N mm, displaying similar-strength infill specimens of 40%, 30%, and 50%. Otolaryngologists evaluated the quality and usability at 4.25 ± 0.81 and 4.53 ± 0.62. The mastoidectomy simulator could provide realistic bone drilling feedback for educational mastoidectomy training while reinforcing skills and comprehension of anatomical structures.

Biomimetic design and clinical application of Ti-6Al-4V lattice hemipelvis prosthesis for pelvic reconstruction.

OBJECTIVE: This study aims to biomimetic design a new 3D-printed lattice hemipelvis prosthesis and evaluate its clinical efficiency for pelvic reconstruction following tumor resection, focusing on feasibility, osseointegration, and patient outcomes. METHODS: From May 2020 to October 2021, twelve patients with pelvic tumors underwent tumor resection and subsequently received 3D-printed lattice hemipelvis prostheses for pelvic reconstruction. The prosthesis was strategically incorporated with lattice structures and solid to optimize mechanical performance and osseointegration. The pore size and porosity were analyzed. Patient outcomes were assessed through a combination of clinical and radiological evaluations. RESULTS: Multiple pore sizes were observed in irregular porous structures, with a wide distribution range (approximately 300-900 µm). The average follow-up of 34.7 months, ranging 26 from to 43 months. One patient with Ewing sarcoma died of pulmonary metastasis 33 months after surgery while others were alive at the last follow-up. Postoperative radiographs showed that the prosthesis's position was consistent with the preoperative planning. T-SMART images showed that the host bone was in close and tight contact with the prosthesis with no gaps at the interface. The average MSTS score was 21 at the last follow-up, ranging from 18 to 24. There was no complication requiring revision surgery or removal of the 3D-printed hemipelvis prosthesis, such as infection, screw breakage, and prosthesis loosening. CONCLUSION: The newly designed 3D-printed lattice hemipelvis prosthesis created multiple pore sizes with a wide distribution range and resulted in good osteointegration and favorable limb function.

A realistic aneurysm clipping simulation combining 3D-printed and placenta-based models-how I do it.

INTRODUCTION: Neurovascular surgery, particularly aneurysm clipping, is a critical skill for aspiring neurosurgeons. However, hands-on training opportunities are limited, especially with the growing popularity of endovascular techniques. To address this challenge, we present a novel neurovascular surgical training station that combines synthetic 3D-printed models with placental vascular structures to create a semi-realistic surgical field. METHODS: Our model consists of three components: a 3D-printed skull replica with anatomical landmarks, a malleable silicone parenchyma with a Sylvian fissure, and vascular layers (placenta). The placental vascular layer is catheterized and perfused to replicate pulsatile flow, offering a realistic aneurysm simulation. This innovative training station provides a cost-effective solution (approximately 200 USD once) without ethical constraints. Surgeons can practice essential skills such as Sylvian fissure dissection, managing anatomical constraints like bone, and achieving proximal vascular control. The model's realism allows for training in various scenarios, including clipping with different hand orientations and handling ruptures realistically. CONCLUSION: Our neurovascular surgical station bridges the gap between existing training models, offering affordability, ecological considerations, and minimal ethical concerns. It empowers neurosurgery residents to refine their skills in handling both emergencies and elective cases under close-to-real surgical conditions, with the potential for independent practice and senior supervision.

Chairside digital design and manufacturing method for children's band and loop space maintainers.

OBJECTIVES: This study proposes a chairside digital design and manufacturing method for band and loop space maintainers and preliminarily validates its clinical feasibility. METHODS: Clinical cases of 10 children requiring space maintenance caused by premature loss of primary teeth were collected. Intraoral scan data of the affected children were also collected to establish digital models of the missing teeth. Using a pediatric band and loop space maintainer design software developed by our research team, a rapid personalized design of band and loop structures was achieved, and a digital model of an integrated band and loop space maintainer was ultimately generated. A chairside space maintainer was manufactured through metal computer numerical control machining for the experimental group, whereas metal 3D printing in the dental laboratory was used for the control group. A model fitting assessment was conducted for the space maintainers of both groups, and senior pediatric dental experts were invited to evaluate the clinical feasibility of the space maintainers with regard to fit and stability using the visual analogue scale scoring system. Statistical analysis was also performed. RESULTS: The time spent in designing and manufacturing the 10 space maintainers of the experimental group was all less than 1 h. Statistical analysis of expert ratings showed that the experimental group outperformed the control group with regard to fit and stability. Both types of space maintainers met clinical requirements. CONCLUSIONS: The chairside digital design and manufacturing method for pediatric band and loop space maintainers proposed in this study can achieve same-day fitting of space maintainers at the first appointment, demonstrating good clinical feasibility and significant potential for clinical application.

Versatile xanthan gum-based support bath material compatible with multiple crosslinking mechanisms: rheological properties, printability, and cytocompatibility study.

Extrusion-based bioprinting is a promising technology for the fabrication of complex three-dimensional (3D) tissue-engineered constructs. To further improve the printing accuracy and provide mechanical support during the printing process, hydrogel-based support bath materials have been developed. However, the gel structure of some support bath materials can be compromised when exposed to certain bioink crosslinking cues, hence their compatibility with bioinks can be limited. In this study, a xanthan gum-based composite support material compatible with multiple crosslinking mechanisms is developed. Different support bath materials can have different underlying polymeric structures, for example, particulate suspensions and polymer solution with varying supramolecular structure) and these properties are governed by a variety of different intermolecular interactions. However, common rheological behavior can be expected because they have similar demonstrated performance and functionality. To provide a detailed exploration/identification of the common rheological properties expressed by different support bath materials from a unified perspective, benchmark support bath materials from previous studies were prepared. A comparative rheological study revealed both the structural and shear behavior characteristics shared by support bath materials, including yield stress, gel complex moduli, shear-thinning behavior, and self-healing properties. Gel structural stability and functionality of support materials were tested in the presence of various crosslinking stimuli, confirming the versatility of the xanthan-based support material. We further investigated the effect of support materials and the diameter of extrusion needles on the printability of bioinks to demonstrate the improvement in bioink printability and structural integrity. Cytotoxicity and cell encapsulation viability tests were carried out to confirm the cell compatibility of the xanthan gum-based support bath material. We propose and demonstrate the versatility and compatibility of the novel support bath material and provide detailed new insight into the essential properties and behavior of these materials that serve as a guide for further development of support bath-based 3D bioprinting.

Wet 3D printing of biodegradable porous scaffolds to enable room-temperature deposition modeling of polymeric solutions for regeneration of articular cartilage.

Tissue engineering has emerged as an advanced strategy to regenerate various tissues using different raw materials, and thus it is desired to develop more approaches to fabricate tissue engineering scaffolds to fit specific yet very useful raw materials such as biodegradable aliphatic polyester like poly (lactide-co-glycolide) (PLGA). Herein, a technique of 'wet 3D printing' was developed based on a pneumatic extrusion three-dimensional (3D) printer after we introduced a solidification bath into a 3D printing system to fabricate porous scaffolds. The room-temperature deposition modeling of polymeric solutions enabled by our wet 3D printing method is particularly meaningful for aliphatic polyester, which otherwise degrades at high temperature in classic fuse deposition modeling. As demonstration, we fabricated a bilayered porous scaffold consisted of PLGA and its mixture with hydroxyapatite for regeneration of articular cartilage and subchondral bone. Long-termin vitroandin vivodegradation tests of the scaffolds were carried out up to 36 weeks, which support the three-stage degradation process of the polyester porous scaffold and suggest faster degradationin vivothanin vitro. Animal experiments in a rabbit model of articular cartilage injury were conducted. The efficacy of the scaffolds in cartilage regeneration was verified through histological analysis, micro-computed tomography (CT) and biomechanical tests, and the influence of scaffold structures (bilayerversussingle layer) onin vivotissue regeneration was examined. This study has illustrated that the wet 3D printing is an alternative approach to biofabricate tissue engineering porous scaffolds based on biodegradable polymers.

Modulus-tunable multifunctional hydrogel ink with nanofillers for 3D-Printed soft electronics.

Seamless integration and conformal contact of soft electronics with tissue surfaces have emerged as major challenges in realizing accurate monitoring of biological signals. However, the mechanical mismatch between the electronics and biological tissues impedes the conformal interfacing between them. Attempts have been made to utilize soft hydrogels as the bioelectronic materials to realize tissue-comfortable bioelectronics. However, hydrogels have several limitations in terms of their electrical and mechanical properties. In this study, we present the development of a 3D-printable modulus-tunable hydrogel with multiple functionalities. The hydrogel has a cross-linked double network, which greatly improves its mechanical properties. Functional fillers such as XLG or functionalized carbon nanotubes (fCNT) can be incorporated into the hydrogel to provide tunable mechanics (Young's modulus of 10-300 kPa) and electrical conductivity (electrical conductivity of ∼20 S/m). The developed hydrogel exhibits stretchability (∼1000% strain), self-healing ability (within 5 min), toughness (400-731 kJ/m3) viscoelasticity, tissue conformability, and biocompatibility. Upon examining the rheological properties in the modulated region, hydrogels can be 3D printed to customize the shape and design of the bioelectronics. These hydrogels can be fabricated into ring-shaped strain sensors for wearable sensor applications.

Evaluation of stress-controlled high-cycle fatigue characteristics in PLA-wood fused deposition modeling 3D-printed parts under bending loads.

PLA (Poly-lactic acid)-wood provides more biodegradability through natural fibers, a significant advantage of pure PLA. Nevertheless, these bio-composites may have inferior mechanical properties compared to non-degradable polymer composites, considering the lower strength of natural particles compared to synthetic fibers. This research examines the fatigue behavior of additive-manufactured biopolymer PLA-wood and assesses its comparability with pure PLA. Therefore, solid fatigue test samples were printed using the FDM (fused deposition modeling) method. Afterward, fully reversed rotary bending fatigue experiments were performed at 4 different stress levels (7.5 to 15 MPa) to extract the S-N curve of PLA-wood. Moreover, the fatigue fracture surfaces of the PLA-wood were investigated and compared at the highest and lowest stress levels using an FE-SEM (Field Emission Scanning Electron Microscopy), indicating more ductile fracture marks at higher stress levels. The fatigue lifetime of the PLA-wood decreased by 87.48% at the highest stress level (15 MPa), rather than the result at the lowest stress level (7.5 MPa). Additionally, the results demonstrated that the fatigue characteristics of the printed pure PLA and PLA-wood were comparable, suggesting that the 3D-printed PLA-wood with the used printing parameters can be an alternative choice.

Recent advances on enhancing 3D printing quality of protein-based inks: A review.

3D printing is an additive manufacturing technology that locates constructed models with computer-controlled printing equipment. To achieve high-quality printing, the requirements on rheological properties of raw materials are extremely restrictive. Given the special structure and high modifiability under external physicochemical factors, the rheological properties of proteins can be easily adjusted to suitable properties for 3D printing. Although protein has great potential as a printing material, there are many challenges in the actual printing process. This review summarizes the technical considerations for protein-based ink 3D printing. The physicochemical factors used to enhance the printing adaptability of protein inks are discussed. The post-processing methods for improving the quality of 3D structures are described, and the application and problems of fourth dimension (4D) printing are illustrated. The prospects of 3D printing in protein manufacturing are presented to support its application in food and cultured meat. The native structure and physicochemical factors of proteins are closely related to their rheological properties, which directly link with their adaptability for 3D printing. Printing parameters include extrusion pressure, printing speed, printing temperature, nozzle diameter, filling mode, and density, which significantly affect the precision and stability of the 3D structure. Post-processing can improve the stability and quality of 3D structures. 4D design can enrich the sensory quality of the structure. 3D-printed protein products can meet consumer needs for nutritional or cultured meat alternatives.