Three‐dimensionally printed constructs are static and do not recapitulate the dynamic nature of tissues. Four‐dimensional (4D) bioprinting has emerged to include conformational changes in printed ...structures in a predetermined fashion using stimuli‐responsive biomaterials and/or cells. The ability to make such dynamic constructs would enable an individual to fabricate tissue structures that can undergo morphological changes. Furthermore, other fields (bioactuation, biorobotics, and biosensing) will benefit from developments in 4D bioprinting. Here, the authors discuss stimuli‐responsive biomaterials as potential bioinks for 4D bioprinting. Natural cell forces can also be incorporated into 4D bioprinted structures. The authors introduce mathematical modeling to predict the transition and final state of 4D printed constructs. Different potential applications of 4D bioprinting are also described. Finally, the authors highlight future perspectives for this emerging technology in biomedicine.
Four‐dimensional (4D) bioprinting has emerged to include conformational changes in printed structures in a predetermined fashion using stimuli‐responsive biomaterials and/or cells. Here, different potential applications of 4D bioprinting are described.
This article is part of an AFOB (Asian Federation of Biotechnology) Special issue. To learn more about the AFOB visit www.afob.org.
Cell separation is a key step in many biomedical research areas including biotechnology, cancer research, regenerative medicine, and drug discovery. While conventional cell sorting approaches have ...led to high‐efficiency sorting by exploiting the cell's specific properties, microfluidics has shown great promise in cell separation by exploiting different physical principles and using different properties of the cells. In particular, label‐free cell separation techniques are highly recommended to minimize cell damage and avoid costly and labor‐intensive steps of labeling molecular signatures of cells. In general, microfluidic‐based cell sorting approaches can separate cells using “intrinsic” (e.g., fluid dynamic forces) versus “extrinsic” external forces (e.g., magnetic, electric field, etc.) and by using different properties of cells including size, density, deformability, shape, as well as electrical, magnetic, and compressibility/acoustic properties to select target cells from a heterogeneous cell population. In this work, principles and applications of the most commonly used label‐free microfluidic‐based cell separation methods are described. In particular, applications of microfluidic methods for the separation of circulating tumor cells, blood cells, immune cells, stem cells, and other biological cells are summarized. Computational approaches complementing such microfluidic methods are also explained. Finally, challenges and perspectives to further develop microfluidic‐based cell separation methods are discussed.
Separation of targeted cells from a heterogeneous population of cells is a crucial step in many biomedical applications, including cancer research, regenerative medicine, and diagnosis. This work discusses fundamentals and applications of different microfluidic‐based cell separation methods by using different physical properties of cells in a label‐free manner.
Advances in biomaterial synthesis and fabrication, stem cell biology, bioimaging, microsurgery procedures, and microscale technologies have made minimally invasive therapeutics a viable tool in ...regenerative medicine. Therapeutics, herein defined as cells, biomaterials, biomolecules, and their combinations, can be delivered in a minimally invasive way to regenerate different tissues in the body, such as bone, cartilage, pancreas, cardiac, skeletal muscle, liver, skin, and neural tissues. Sophisticated methods of tracking, sensing, and stimulation of therapeutics in vivo using nano‐biomaterials and soft bioelectronic devices provide great opportunities to further develop minimally invasive and regenerative therapeutics (MIRET). In general, minimally invasive delivery methods offer high yield with low risk of complications and reduced costs compared to conventional delivery methods. Here, minimally invasive approaches for delivering regenerative therapeutics into the body are reviewed. The use of MIRET to treat different tissues and organs is described. Although some clinical trials have been performed using MIRET, it is hoped that such therapeutics find wider applications to treat patients. Finally, some future perspective and challenges for this emerging field are highlighted.
Current and future minimally invasive and regenerative therapeutics are reviewed together with delivery routes and tools. Regenerative therapeutics based on cells, biomaterials, biomolecules, and their combinations for different organs are described. The integration of minimally invasive approaches with robotics, regenerative therapeutics, and imaging techniques is also introduced. In addition, related challenges and future directions are discussed.
There is an increasing need to develop conducting hydrogels for bioelectronic applications. In particular, poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hydrogels have become a ...research hotspot due to their excellent biocompatibility and stability. However, injectable PEDOT:PSS hydrogels have been rarely reported. Such syringe‐injectable hydrogels are highly desirable for minimally invasive biomedical therapeutics. Here, an approach is demonstrated to develop injectable PEDOT:PSS hydrogels by taking advantage of the room‐temperature gelation property of PEDOT:PSS. These PEDOT:PSS hydrogels form spontaneously after syringe injection of the PEDOT:PSS suspension into the desired location, without the need of any additional treatments. A facile strategy is also presented for large‐scale production of injectable PEDOT:PSS hydrogel fibers at room temperature. Finally, it is demonstrated that these room‐temperature‐formed PEDOT:PSS hydrogels (RT‐PEDOT:PSS hydrogel) and hydrogel fibers can be used for the development of soft and self‐healable hydrogel bioelectronic devices.
A poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) suspension forms hydrogel at room temperature after being mixed with surfactants. Taking advantage of these room‐temperature formed hydrogels, various applications are presented including injectable conducting fillers, injectable conducting microfibers, and water‐healable conductors. These new demonstrations encourage further development of PEDOT:PSS hydrogels for potential biomedical applications.
Implants are being continuously developed to achieve personalized therapy. With the advent of 3-dimensional (3D) printing, it is becoming possible to produce customized precisely fitting implants ...that can be derived from 3D images fed into 3D printers. In addition, it is possible to combine various materials, such as ceramics, to render these constructs osteoconductive or growth factors to make them osteoinductive. Constructs can be seeded with cells to engineer bone tissue. Alternatively, it is possible to load cells into the biomaterial to form so called bioink and print them together to from 3D bioprinted constructs that are characterized by having more homogenous cell distribution in their matrix. To date, 3D printing was applied in the clinic mostly for surgical training and for planning of surgery, with limited use in producing 3D implants for clinical application. Few examples exist so far, which include mostly the 3D printed implants applied in maxillofacial surgery and in orthopedic surgery, which are discussed in this report. Wider clinical application of 3D printing will help the adoption of 3D printers as essential tools in the clinics in future and thus, contribute to realization of personalized medicine.
Next generation engineered tissue constructs with complex and ordered architectures aim to better mimic the native tissue structures, largely due to advances in 3D bioprinting techniques. Extrusion ...bioprinting has drawn tremendous attention due to its widespread availability, cost‐effectiveness, simplicity, and its facile and rapid processing. However, poor printing resolution and low speed have limited its fidelity and clinical implementation. To circumvent the downsides associated with extrusion printing, microfluidic technologies are increasingly being implemented in 3D bioprinting for engineering living constructs. These technologies enable biofabrication of heterogeneous biomimetic structures made of different types of cells, biomaterials, and biomolecules. Microfluiding bioprinting technology enables highly controlled fabrication of 3D constructs in high resolutions and it has been shown to be useful for building tubular structures and vascularized constructs, which may promote the survival and integration of implanted engineered tissues. Although this field is currently in its early development and the number of bioprinted implants is limited, it is envisioned that it will have a major impact on the production of customized clinical‐grade tissue constructs. Further studies are, however, needed to fully demonstrate the effectiveness of the technology in the lab and its translation to the clinic.
Extrusion bioprinting is introduced and the applications, limitations, and recent advances are discussed. Furthermore, the integration of microfluidic technologies with extrusion bioprinting for controlled biofabrication of 3D constructs to better mimic human tissue is outlined. Although the field is still developing, it is envisioned that it can have a huge impact on biofabrication of customized heterogeneous 3D tissues in near future.
Cochlear implants are neural implant devices that aim to restore hearing in patients with severe sensorineural hearing impairment. Here, the main goal is to successfully place the electrode array in ...the cochlea to stimulate the auditory nerves through bypassing damaged hair cells. Several electrode and electrode array parameters affect the success of this technique, but, undoubtedly, the most important one is related to electrodes, which are used for nerve stimulation. In this paper, we provide a comprehensive resource on the electrodes currently being used in cochlear implant devices. Electrode materials, shape, and the effect of spacing between electrodes on the stimulation, stiffness, and flexibility of electrode-carrying arrays are discussed. The use of sensors and the electrical, mechanical, and electrochemical properties of electrode arrays are examined. A large library of preferred electrodes is reviewed, and recent progress in electrode design parameters is analyzed. Finally, the limitations and challenges of the current technology are discussed along with a proposal of future directions in the field.
Strong, stretchable, and durable biomaterials with shape memory properties can be useful in different biomedical devices, tissue engineering, and soft robotics. However, it is challenging to combine ...these features. Semi‐crystalline polyvinyl alcohol (PVA) has been used to make hydrogels by conventional methods such as freeze–thaw and chemical crosslinking, but it is formidable to produce strong materials with adjustable properties. Herein, a method to induce crystallinity and produce physically crosslinked PVA hydrogels via applying high‐concentration sodium hydroxide into dense PVA polymer is introduced. Such a strategy enables the production of physically crosslinked PVA biomaterial with high mechanical properties, low water content, resistance to injury, and shape memory properties. It is also found that the developed PVA hydrogel can recover 90% of plastic deformation due to extension upon supplying water, providing a strong contraction force sufficiently to lift objects 1100 times more than their weight. Cytocompatibility, antifouling property, hemocompatibility, and biocompatibility are also demonstrated in vitro and in vivo. The fabrication methods of PVA‐based catheters, injectable electronics, and microfluidic devices are demonstrated. This gelation approach enables both layer‐by‐layer and 3D printing fabrications.
This work introduces a facile strategy to induce crystallinity and produce physically crosslinked polyvinyl alcohol biomaterials with high mechanical properties, stable chemistry, resistance to injury, and shape memory properties. Fabrication methods for producing hydrogel‐based catheters, injectable electronics and microfluidic devices are discussed, using 3D printing and layer‐by‐layer methods.
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