Research and progress of three-dimensional printing in the field of hepatopancreatobiliary surgery / 中华肝胆外科杂志

Three-dimensional (3D) printing is an additive manufacturing technology, which is widely used in automobile, aerospace, food, medicine and other fields. 3D printing technology brings novel solutions for precision medicine. In the field of hepatopancreatobiliary surgery, 3D printing is used in medical education, surgical simulation, patient-specific liver models printing in hepatectomy and liver transplantation. In the future, with the discovery and application of high-tech materials, 3D printing technology will be further developed in hepatopancreatobiliary surgery, and hepatobiliary surgery will usher in a new spring. This paper will review the application and future prospects of 3D printing technology in hepatopancreatobiliary surgery.

Emerging trends in organ-on-a-chip systems for drug screening

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

Frontier hotspots and research progress on 3D bioprinting in organ reconstruction / 器官移植

3D bioprinting is an advanced manufacturing technology that utilizes biomaterials and bioactive components to manufacture artificial tissues and organs. It has been widely applied in multiple medical fields and possesses outstanding advantages in organ reconstruction. In recent years, 3D bioprinted organs have made an array of groundbreaking achievements. Nevertheless, it is still in the exploratory stage of research and development and still has bottleneck problems, which can not be applied in organ transplantation in vivo. In this article, the application of 3D printing technology in medicine, characteristics of 3D bioprinting technology, research hotspots and difficulties in bionic structure, functional reconstruction and immune response of 3D bioprinted organs, and the latest research progress on 3D bioprinting technology were illustrated, and the application prospect of 3D bioprinting technology in the field of organ reconstruction was elucidated, aiming to provide novel ideas for the research and clinical application of organ reconstruction and artificial organ reconstruction, and promote the development of organ transplantation and individualized medicine.

Research advances of three-dimensional bioprinting technology in urinary system tissue engineering / 生物医学工程学杂志

For the damage and loss of tissues and organs caused by urinary system diseases, the current clinical treatment methods have limitations. Tissue engineering provides a therapeutic method that can replace or regenerate damaged tissues and organs through the research of cells, biological scaffolds and biologically related molecules. As an emerging manufacturing technology, three-dimensional (3D) bioprinting technology can accurately control the biological materials carrying cells, which further promotes the development of tissue engineering. This article reviews the research progress and application of 3D bioprinting technology in tissue engineering of kidney, ureter, bladder, and urethra. Finally, the main current challenges and future prospects are discussed.

Aplicações da manufatura aditiva em oftalmologia / Applications of additive manufacturing in ophthalmology

RESUMO A manufatura aditiva, mais popularmente conhecida como impressão tridimensional, baseia-se no desenvolvimento de um objeto com a ajuda de um software de desenho assistido por computador seguido de sua impressão por meio da deposição de uma matéria-prima, camada por camada, para a construção do produto desejado. Existem vários tipos de técnicas de impressão tridimensional, e o tipo de processo de impressão escolhido depende da aplicação específica do objeto a ser desenvolvido, dos materiais a serem utilizados e da resolução necessária à impressão do produto final. A impressão tridimensional abriu perspectivas na pesquisa e revolucionou o campo das ciências da saúde, com a possibilidade de criação e de desenvolvimento de produtos personalizados de maneira rápida, econômica e de forma mais centralizada do que no processo de manufatura tradicional. As tecnologias de manufatura aditiva remodelaram os diagnósticos médicos; as medidas preventivas e pré-operatórias; o tratamento e a reabilitação, assim como os processos de engenharia de tecidos nos últimos anos. Na oftalmologia, as aplicações da impressão tridimensional são extensas. Modelos anatômicos para aplicação na área da educação e planejamentos cirúrgicos, desenvolvimento de implantes, lentes, equipamentos para diagnósticos, novas aplicações terapêuticas e desenvolvimento de tecidos oculares já estão em desenvolvimento. Por possuir um campo amplo e ser alvo de pesquisa constante, a área oftalmológica permite que a manufatura aditiva ainda seja amplamente utilizada a favor dos médicos e dos pacientes.

ABSTRACT Additive manufacturing, more popularly known as three-dimensional (3D) printing, is based on the development of an object with the help of computer-aided design software followed by its printing through the deposition of a material, layer by layer, to create the desired product. There are several types of 3D printing techniques and the type of printing process chosen depends on the specific application of the object to be developed, the materials to be used, and the resolution required to print the final product. 3D printing has brought new perspectives to research and revolutionized the field of health sciences, with the possibility of creating and developing customized products in a faster, more economical, and more centralized way than in the traditional manufacturing process. Additive manufacturing technologies have reformulated medical diagnostics, preventive, preoperative, treatment, and rehabilitation, as well as tissue engineering processes in recent years. In ophthalmology, the applications of 3D printing are extensive. Anatomical models for application in education and surgical planning, development of implants, lenses, diagnostic equipment, new therapeutic applications, and development of ocular tissues (3D bioprinting) are already under development. As it has a wide field and is the subject of constant research, the ophthalmic area allows additive manufacturing to still be widely used in favor of doctors and patients.

Preparation and application of decellularized extracellular matrix bioink: a review / 生物工程学报

Decellularized extracellular matrix (dECM), which contains many proteins and growth factors, can provide three-dimensional scaffolds for cells and regulate cell regeneration. 3D bioprinting can print the combination of dECM and autologous cells layer by layer to construct the tissue structure of carrier cells. In this paper, the preparation methods of tissue and organ dECM bioink from different sources, including decellularization, crosslinking, and the application of dECM bioink in bioprinting are reviewed, with future applications prospected.

Insights into the applications of 3D bioprinting for bioremediation technologies / 生物工程学报

A plethora of organic pollutants such as pesticides, polycyclic and halogenated aromatic hydrocarbons, and emerging pollutants, such as flame retardants, is continuously being released into the environment. This poses a huge threat to the society in terms of environmental pollution, agricultural product quality, and general safety. Therefore, effective removal of organic pollutants from the environment has become an important challenge to be addressed. As a consequence of the recent and rapid developments in additive manufacturing, 3D bioprinting technology is playing an important role in the pharmaceutical industry. At the same time, an increasing number of microorganisms suitable for the production of biomaterials with complex structures and functions using 3D bioprinting technology, have been identified. This article briefly discusses the principles, advantages, and disadvantages of different 3D bioprinting technologies for pollutant removal. Furthermore, the feasibility and challenges of developing bioremediation technologies based on 3D bioprinting have also been discussed.

Application of 3D bio-printing technology in tracheal reconstruction / 国际外科学杂志

At present, trachea reconstruction by tissue engineering technology of 3D bio-printing has become an ideal method for repairing long-segment trachea after injury, and how to select printing materials to manufacture appropriate tissue engineering trachea is the key to ensure the perfect survival of trachea grafts in the human body. Bioink is a cellular formula containing bioactive ingredients that could make or break the 3D printed tissue-engineered trachea. It is particularly important to find a bio-ink that has good biocompatibility and can print biological structures with high mechanical strength. This paper aims to review the advantages and disadvantages of bio-ink made of different materials, current application status and clinical application of 3D printed tissue-engineered trachea, so as to promote the clinical transformation of tissue-engineered trachea as soon as possible and put into practical clinical application systematically.

Three-dimensional bioprinting of osteochondral composite tissue with innovative bio-ink and PCL to repair articular cartilage defects / 中华骨科杂志

Objective:A new type of bio-ink and polycaprolactone (PCL) were used to construct an integrated osteochon-dral composite tissue block by multi-nozzle 3D bioprinter. And the repair results to osteochondral defects were evaluated.Methods:In freeze-drying group: Freeze-dried composite scaffold made by silk fibroin (SF) and β-tricalcium phosphate was used to repair osteochondral defects, as control. In the 3D printing group: PCL was used to printed a hollow multi-layer cylinder frame by 3D biological printer. Extracellular matrix, SF and bone marrow mesenchymal stem cells were used as chondral bio-ink. Then, chon-dral bio-ink was used to print tissue-engineered cartilage on top of PCL frame. Before implantation of cartilage defect, autogenous cancellous bone was filled in PCL frame, then the tissue-engineered osteochondral composite was used to repair osteochondral defects. In mosaic group: Autologous osteochondral transplantation was performed. The repair results of the above three groups were compared by histological score, biochemical analysis and biomechanical test to evaluate the effect of repairing rabbit cartilage defects.Results:The compression modulus of neo-cartilage in the 3D print group 2.56±0.30 MPa was close to that of the mosaic group 2.51±0.13 MPa ( P>0.05), and significantly higher than that of freeze-dried group 1.37±0.14 MPa ( F=11.058, P<0.05). The sGAG contents in the 3D print group 14.49±0.7 μg/mg was close to that of the mosaic group 14.98±0.81 μg/mg ( P>0.05), and significantly higher than that of freeze-dried group 8.72±0.73 μg/mg ( F=20.973, P<0.05). However, there was no significant difference in collagen content between the three groups ( P>0.05). The results of ICRS cartilage repair histology score showed that the scores of the 3D print group were close to those of the mosaic group in the matrix, cell distribution, cell viability and subchondral bone ( P>0.05), and were significantly higher than those of freeze-dried group in the surface and cartilage mineralization scores ( F=19.544, P<0.05). Conclusion:Using the new bio-ink to make bone cartilage composite scaffold by 3D bio printing can simplify the construction of tissue-engineered bone cartilage composite tissue in vitro, and can repair cartilage defects in vivo.

Printability-A key issue in extrusion-based bioprinting / 药物分析学报

Three-dimensional(3D)extrusion-based bioprinting is widely used in tissue engineering and regener-ative medicine to create cell-incorporated constructs or scaffolds based on the extrusion technique.One critical issue in 3D extrusion-based bioprinting is printability or the capability to form and maintain reproducible 3D scaffolds from bioink(a mixture of biomaterials and cells).Research shows that printability can be affected by many factors or parameters,including those associated with the bioink,printing process,and scaffold design,but these are far from certain.This review highlights recent de-velopments in the printability assessment of extrusion-based bioprinting with a focus on the definition of printability,printability measurements and characterization,and printability-affecting factors.Key issues and challenges related to printability are also identified and discussed,along with approaches or strategies for improving printability in extrusion-based bioprinting.

Focus on periodontal engineering by 3D printing technology ­ a systematic review / Enfoque en la ingeniería periodontal mediante la tecnología de impresión 3D: una revisión sistemática

Three-dimensional (3D) bioprinting of cells is an emerging area of research but has not been explored yet in the context of periodontal tissue engineering. Objetive: This study reports on the optimization of the 3D bioprinting scaffolds and tissues used that could be applied clinically to seniors for the regenerative purpose to meet individual patient treatment needs. Material and Methods: We methodically explored the printability of various tissues (dentin pulp stem/progenitor cells, periodontal ligament stem/progenitor cells, alveolar bone stem/progenitor cells, advanced platelet-rich fibrin and injected platelet-rich fibrin) and scaffolds using 3D printers pertaining only to periodontal defects. The influence of different printing parameters with the help of scaffold to promote periodontal regeneration and to replace the lost structure has been evaluated. Results: This systematic evaluation enabled the selection of the most suited printing conditions for achieving high printing resolution, dimensional stability, and cell viability for 3D bioprinting of periodontal ligament cells. Conclusion: The optimized bioprinting system is the first step towards the reproducible manufacturing of cell laden, space maintaining scaffolds for the treatment of periodontal lesions.

La bioimpresión tridimensional (3D) de células es un área emergente de investigación, pero aún no se ha explorado en el contexto de la ingeniería de tejidos periodontales. Objetivo: Este estudio informa sobre la optimización de los tejidos y andamios de bioimpresión 3D utilizados que podrían aplicarse a personas mayores en el entorno clínico con fines regenerativos para satisfacer las necesidades de tratamiento de cada paciente. Material y Métodos: Exploramos metódicamente la capacidad de impresión de varios tejidos (células madre / progenitoras de la pulpa de dentina, células madre / progenitoras del ligamento periodontal, células madre / progenitoras de hueso alveolar, fibrina rica en plaquetas avanzada y fibrina rica en plaquetas inyectada) y andamios utilizando impresoras 3D que pertenecen solo a defectos periodontales. Se ha evaluado la influencia de diferentes parámetros de impresión con la ayuda de andamios para promover la regeneración periodontal y reemplazar la estructura perdida. Resultados: Esta evaluación sistemática permitió la selección de las condiciones de impresión más adecuadas para lograr una alta resolución de impresión, estabilidad dimensional y viabilidad celular para la bioimpresión 3D de células del ligamento periodontal. Conclusión: El sistema de bioimpresión optimizado es el primer paso hacia la fabricación reproducible de andamios de mantenimiento de espacio cargados de células para el tratamiento de lesiones periodontales

Aplicaciones actuales de la impresión cardiaca en 3D / Current applications of cardiac 3D printing

Resumen En esta revisión se abordan las diversas aplicaciones actuales de la impresión tridimensional en enfermedades cardiovasculares, sus limitaciones y dirección a futuro. Se enfatiza en el área de educación, en la cual ha tenido impacto significativo en la experiencia del paciente y del médico, además de beneficios éticos con respecto a la comparación con el uso de cadáveres o modelos animales; también, en el área de planificación quirúrgica donde se optimiza el proceso operatorio y se dan mejoras en los resultados; seguidamente, se explica el área de impresión cardiaca personalizada, que se ha implementado especialmente en casos de anomalías cardiacas congénitas debido a que son muy heterogéneas entre los pacientes y esto permite un estudio individualizado de las mismas con el fin de buscar tratamientos óptimos a mediano y largo plazo. Finalmente se profundiza sobre bioimpresión, la cual constituye el campo con mayor potencial y se ha desarrollado alrededor del reemplazo de estructuras cardiacas como válvulas, investigación de efectos terapéuticos de fármacos y colocación de células con funciones regenerativas. Se concluye lo promisoria que es la impresión cardiaca tridimensional y los múltiples beneficios que puede brindarle a la comunidad médica y a los pacientes.

Abstract For this review the current applications and uses of three-dimensional printing will be studied in cardiovascular diseases, as well as its limitations and future directions. Regarding the education field, it has had a significant impact on the experience of physicians as well as patients, furthermore considering the ethical benefits with regards to the comparison of the use of cadaveric or animal models. Advantages may also be contemplated when discussing surgical planning, where this technology optimizes the surgical process and provides better results. Moreover, patient specific three- dimensional cardiac printing has been applied in cases of congenital heart abnormalities due to its variability among patients, where these models allow for an individual study in search of optimal treatments in the medium and long term. Finally, bioprinting is studied, which constitutes the most promising field, and has developed around the replacement of cardiac structures, such as valves, investigation on therapeutic effects of drugs and cell placement with regenerative functions. In conclusion, the optimistic and favorable future of this technology can be presumed, alongside its multiple benefits that could contribute to the medical community and to the patients.

Evolution and progress of replacement therapy, materials and reconstruction of long ureteral injuries / 中国组织工程研究

BACKGROUND: It is very difficult for urologists to choose what kind of substitute and how to reconstruct the long ureteral injuries to restore the integrity and function of the ureter. OBJECTIVE: To review recent progress and the evolution trends in the reconstruction methods of long ureteral injuries. METHODS: Relevant articles published from 1950 to 2019 were searched in PubMed, Web of Science, MEDLINE, and WanFang databases. The keywords were “ureteral injuries, ureteral replacement, biomaterial, tissue engineering, 3D bioprinting” in English and Chinese, respectively. The articles addressing ureteral replacement materials and reconstruction of ureteral injuries were selected. RESULTS AND CONCLUSION: In the reconstruction of long ureteral injury, the earliest repair method is to use autologous tissues, such as ileal, bladder muscle flap (Boari flap), and buccal mucosa graft. But such operations are difficult to avoid the damage to the surrounding tissues and organs. After that, various non-biomaterials were produced for ureteral replacement, but failed due to immune rejection and lack of peristalsis. With the development of cytology, biology and materials, the damaged tissues and organs have been regenerated by using autologous cells. Due to the development of regenerative medicine and three-dimensional printing technology, complex multi-component and multi-layered hollow tube structures that similar to their internal counterparts can be generated with three-dimensional bioprinting. But three-dimensional bioprinting cannot reconstruct the ureter and bladder with normal peristalsis and contraction function.

Optimization of the coaxial cell printing performance of bioink and printing of tissue-engineered scaffolds with vascular-like structure / 中国组织工程研究

BACKGROUND: Cells cannot survive in the area 200 µm away from nutrients in vitro. Vascular network construction is crucial for thick tissue and organ regeneration in tissue engineering. Coaxial cell printing provides a new way to construct vascular-like channels in vitro. OBJECTIVE: To optimize the coaxial cell printing performance of bioink and to build the tissue-engineered scaffolds with vascular-like structure. METHODS: The aseptic sodium alginate solution was prepared by intermittent pasteurization and then frozen. Freeze-dried powder of aseptic silk fibroin was prepared from degummed silk and sealed. The thawed sodium alginate solution was added to the silk fibroin protein freeze-dried powder and human umbilical vein endothelial cells were added to prepare the bioink. The outer axis of the biological three-dimensional printer was connected with the bioink, and the inner axis was connected with the crosslinking agent. The scaffolds were prepared by coaxial printing, and performed by optical coherence tomography, scanning electron microscopy observation and tensile test. Coaxial scaffolds were made by freeze-preserved sodium alginate solution for 7 days with human umbilical vein endothelial cells. Coaxial scaffolds were also made by freeze-dried sodium alginate solution for 7 days with human umbilical vein endothelial cells and silk fibroin protein sealed for 6 months. The cell survival rate was detected by dead and alive staining after 24 hours of culture in vitro. Vascular-like scaffolds with series and parallel structures were designed and printed. The cell proliferation was detected after 1, 3, 7, 10, and 14 days of culture. RESULTS AND CONCLUSIONS: (1) The optical coherence tomography showed that the maximum printing height of the bioink was 9 layers and the overall thickness was about 4.4 mm. Scanning electron microscopy showed that the outer wall of hollow fiber-filament of vascular-like scaffolds presented irregular strip-shaped crimp with micron-scale internal connected pore structure, while the inner wall of hollow fiber-filament had denser pore structure. (2) The elastic modulus of silk protein freeze-dried scaffold was higher than that of sodium alginate solution (P < 0.05). (3) The cell survival rate of scaffolds treated with sodium alginate solution for 7 days was (86.7±3.4)%, and that of scaffolds treated with silk protein freeze-dried powder for 7 days was (98.1±1.2)%, indicating that the sodium alginate solution freeze- preserved for 7 days was free of bacteria and the shelf-life of silk protein could be up to 6 months. (4) The proliferation activity of cells cultured with parallel structure for 7, 10, and 14 days was higher than that with series structure (P < 0.05). (5) These results imply that the scaffolds have good biocompatibility and mechanical properties.

Application and progress of umbilical cord Mesenchymal stem cells in bone tissue engineering / 中国组织工程研究

BACKGROUND: As seed cells, human umbilical cord mesenchymal stem cells have many advantages, such as a broad array of sources, easy access, low immunogenicity, osteogenic differentiation potential, high proliferation and self-renewal ability. In recent years, there are more and more reports about their application for bone tissue engineering. OBJECTIVE: To summarize isolation, culture, osteogenic induction and scaffolds. METHODS: The first author searched CNKI and PubMed databases with key words of “human umbilical cord mesenchymal stem cells, isolation, culture, osteogenic differentiation, scaffold, bone tissue engineering” in both Chinese and English, so as to review the relevant literature from 2004 to 2020. Finally, 104 articles were included. RESULTS AND CONCLUSION: There are different methods of isolation and culture of umbilical cord mesenchymal stem cells. Serum-free or animal serum substitute culture system and co-culture technique have made great progress, and three-dimensional culture system will be the development direction in the future. The exact mechanisms of osteogenic differentiation of umbilical cord mesenchymal stem cells are unclear, which need further elucidation. To date, it is still the focus of researchers to develop composite scaffolds with better properties. Bio-printing technology has primarily solve the difficult problem of controlling precisely the complex inner structure of the scaffolds at the micron scale and fabricating individual scaffolds, bringing great hope for bone tissue engineering. The design and fabrication of scaffolds with multiple ideal compositions (including biocompatibility, high porosity at the micro and macro level, mechanical properties, related absorption and so on) and the less clinical side effects remain one of the key challenges in bone tissue engineering.

Diffusion tensor imaging predicting locomotor function recovery with 3D printing scaffold after spinal cord injury / 中国组织工程研究

BACKGROUND: Diffusion tensor imaging, as a relatively new method based on MRI, has become an important means of examination and diagnosis in the field of neuroimaging. OBJECTIVE: To investigate the role of using diffusion tensor tensor imaging data to predict 3D-bioprinted collagen/silk fibroin scaffolds in the locomotor function recovery after spinal cord injury. METHODS: Ordinary and 3D-bioprinted collagen/silk fibroin scaffold were prepared. Forty adult female SD rats provided by the Laboratory Animal Center of the Academy of Military Medical Sciences of the People’s Liberation Army were randomly divided into four groups with 10 rats in each group. In the sham operation group, only T10 vertebral plate was removed. In the model group, spinal cord injury was induced by total transection of spinal cord at T10 segment. In the ordinary collagen scaffold and 3D-printed scaffold groups, after induction of T10 spinal cord injury, ordinary collagen scaffold and 3D-printed scaffold were implanted, respectively. At 1, 2, 3, 4, 6 and 8 weeks after surgery, Basso, Beattie and Bresnahan (BBB) locomotor function scoring and oblique plate test of the hind limbs were carried out. At 8 weeks after surgery, electrophysiological test of the hind limbs was performed to evaluate locomotor function. At 8 weeks after surgery, diffusion tensor imaging of the lumbar spine was performed and the correlation between diffusion tensor imaging parameter and rat locomotor function was analyzed. Animal experiments were approved by the Animal Ethics Committee of Characteristic Medical Center of the Chinese people’s Armed Police Force (approval No. 27653/58). RESULTS AND CONCLUSION: (1) From 3 weeks after surgery, BBB score in the 3D-printed group was significantly higher than that in the model and ordinary collagen scaffold groups (P < 0.05 or P < 0.01). From 2 weeks after surgery, the slope angle in the 3D-printed scaffold group was significantly higher than that in the model and ordinary scaffold groups (P < 0.05 or P < 0.01). (2) The amplitude of motor evoked potential in the 3D-printed scaffold group was significantly greater than that in the model and ordinary collagen scaffold groups (P < 0.05 or P < 0.01). The latency of motor evoked potential in the 3D-printed scaffold group was significantly shorter than that in the model and ordinary collagen scaffold groups (P < 0.05 or P < 0.01). (3) Diffusion tensor imaging showed that the nerve fiber trajectories in the three groups were irregular and lacked the continuity of nerve fibers, but the number of regenerated nerve fiber bundles in the 3D-printed collagen scaffold group was greater than that in the model and ordinary collagen scaffold groups (P < 0.01). The fractional anisotropy at 9, 7.5, 4.5, -3, -6, -7.5, -9 mm from the center of spinal cord injury in 3D-printed collagen scaffold group was significantly higher than that in model and ordinary collagen scaffold groups (P < 0.05 or P < 0.01). (4) The BBB score, slope angle, amplitude of motor evoked potential, latency of motor evoked potential were positively correlated with the fractional anisotropy value of diffusion tensor imaging from head to tail of rats. (5) These results suggest that diffusion tensor imaging can be used as an effective predictor to evaluate the recovery of neurological function after spinal cord injury in experimental animals and clinical cases.

The application and prospects of three dimensional bioprinting in urinary system reconstruction / 生物医学工程学杂志

Three dimensional (3D) bioprinting is a new biological tissue engineering technology in recent years. The development of 3D bioprinting is conducive to solving the current problems of clinical tissue and organ repairing. This article provides a review about the clinical and research status of 3D bioprinting and urinary system reconstruction. Furthermore, the feasibility and clinical value of 3D bioprinting in urinary system reconstruction will be also discussed.

Bioprinted HepG2 cells for studying sonodynamic anticancer activity of chlorine e6 / 药学学报

This paper showed bioprinted HepG2 tumor tissues used for studying the sonodynamic anticancer activity of chlorine e6 (Ce6). HepG2 cells were printed by using alginate/gelatin/hydroxyethyl cellulose composite biomaterial as bio ink and cell viability was detected with Live-Dead assay and MTT proliferation. The ultrasonic intensities of self-built micro ultrasonic device under different powers were estimated by using the temperature change caused by the conversion of acoustic energy to heat energy. Ce6 of 14.3 and 28.6 μg·mL-1 were acted on two-dimensional cultured and three-dimensional printed HepG2 cells, and the antitumor activity of Ce6 was detected by MTT method with ultrasound intensity of 0.15 W·cm2 for 60 s. The results showed that the activities of bioprinted HepG2 cells were as high as 95%, and tumor microspheres were formed after 7 days of culture. The ultrasound intensity was lower than 3 W·cm2, which belonged to low ultrasound intensity and had no damage to normal hepatocyte LO2 cells. By comparing the antitumor activity of Ce6 on 2D cultured and printed HepG2 cells, it was found that the anticancer activity of Ce6 on bioprinted HepG2 cells was 63.4% lower than that on 2D culture cells, indicating the acoustic drug resistance of three-dimensional tumor model. Bioprinted tumor tissues show the potential in the application of in vitro activity evaluation models for sonodynamic therapy.

Regenerative Medicine of the Bile Duct: Beyond the Myth

Cholangiopathies are rare diseases of the bile duct with high mortality rates. The current treatment for cholangiopathies is liver transplantation, but there are significant obstacles including a shortage of donors and a high risk of complications. Currently, there is only one available medicine on the market targeting cholangiopathies, and the results have been inadequate in clinical therapy. To overcome these obstacles, many researchers have used human induced pluripotent stem cells (hPSC) as a source for cholangiocyte-like cell generation and have incorporated advances in bioprinting to create artificial bile ducts for implantation and transplantation. This has allowed the field to move dramatically forward in studies of biliary regenerative medicine. In this review, the authors provide an overview of cholangiocytes, the organogenesis of the bile duct, cholangiopathies, and the current treatment and advances that have been made that are opening new doors to the study of cholangiopathies.