The development of 3D in vitro models capable of recapitulating native tumor microenvironments could improve the translatability of potential anticancer drugs and treatments. Here, 3D bioprinting ...techniques are used to build tumor constructs via precise placement of living cells, functional biomaterials, and programmable release capsules. This enables the spatiotemporal control of signaling molecular gradients, thereby dynamically modulating cellular behaviors at a local level. Vascularized tumor models are created to mimic key steps of cancer dissemination (invasion, intravasation, and angiogenesis), based on guided migration of tumor cells and endothelial cells in the context of stromal cells and growth factors. The utility of the metastatic models for drug screening is demonstrated by evaluating the anticancer efficacy of immunotoxins. These 3D vascularized tumor tissues provide a proof‐of‐concept platform to i) fundamentally explore the molecular mechanisms of tumor progression and metastasis, and ii) preclinically identify therapeutic agents and screen anticancer drugs.
A migration‐inducing, vascularized tumor model platform is created via 3D bioprinting of cells, natural hydrogels, and programmable release capsules. These cell‐laden architectures are designed to recapitulate the primary characteristics of metastasis. The 3D models both physically and chemically reconstruct the tumor microenvironments with high spatiotemporal resolution, offering a tool to bridge the gap between monolayer cell culture and animal models.
The ability to construct multiplexed micro-systems for fluid regulation could substantially impact multiple fields, including chemistry, biology, biomedicine, tissue engineering, and soft robotics, ...among others. 3D printing is gaining traction as a compelling approach to fabricating microfluidic devices by providing unique capabilities, such as 1) rapid design iteration and prototyping, 2) the potential for automated manufacturing and alignment, 3) the incorporation of numerous classes of materials within a single platform, and 4) the integration of 3D microstructures with prefabricated devices, sensing arrays, and nonplanar substrates. However, to widely deploy 3D printed microfluidics at research and commercial scales, critical issues related to printing factors, device integration strategies, and incorporation of multiple functionalities require further development and optimization. In this review, we summarize important figures of merit of 3D printed microfluidics and inspect recent progress in the field, including ink properties, structural resolutions, and hierarchical levels of integration with functional platforms. Particularly, we highlight advances in microfluidic devices printed with thermosetting elastomers, printing methodologies with enhanced degrees of automation and resolution, and the direct printing of microfluidics on various 3D surfaces. The substantial progress in the performance and multifunctionality of 3D printed microfluidics suggests a rapidly approaching era in which these versatile devices could be untethered from microfabrication facilities and created on demand by users in arbitrary settings with minimal prior training.
The development of methods for the 3D printing of multifunctional devices could impact areas ranging from wearable electronics and energy harvesting devices to smart prosthetics and human–machine ...interfaces. Recently, the development of stretchable electronic devices has accelerated, concomitant with advances in functional materials and fabrication processes. In particular, novel strategies have been developed to enable the intimate biointegration of wearable electronic devices with human skin in ways that bypass the mechanical and thermal restrictions of traditional microfabrication technologies. Here, a multimaterial, multiscale, and multifunctional 3D printing approach is employed to fabricate 3D tactile sensors under ambient conditions conformally onto freeform surfaces. The customized sensor is demonstrated with the capabilities of detecting and differentiating human movements, including pulse monitoring and finger motions. The custom 3D printing of functional materials and devices opens new routes for the biointegration of various sensors in wearable electronics systems, and toward advanced bionic skin applications.
A multifunctional three‐dimensional (3D) printing approach is employed to fabricate 3D tactile sensors under ambient conditions conformally onto freeform surfaces. The sensors can detect and differente human motions, including pulse monitoring and finger movements. This custom 3D printing of functional materials and devices opens new routes toward the biointegration of various sensors in wearable electronic systems.
Conventional 3D printing technologies typically rely on open‐loop, calibrate‐then‐print operation procedures. An alternative approach is adaptive 3D printing, which is a closed‐loop method that ...combines real‐time feedback control and direct ink writing of functional materials in order to fabricate devices on moving freeform surfaces. Here, it is demonstrated that the changes of states in the 3D printing workspace in terms of the geometries and motions of target surfaces can be perceived by an integrated robotic system aided by computer vision. A hybrid fabrication procedure combining 3D printing of electrical connects with automatic pick‐and‐placing of surface‐mounted electronic components yields functional electronic devices on a free‐moving human hand. Using this same approach, cell‐laden hydrogels are also printed on live mice, creating a model for future studies of wound‐healing diseases. This adaptive 3D printing method may lead to new forms of smart manufacturing technologies for directly printed wearable devices on the body and for advanced medical treatments.
An adaptive 3D printing system capable of printing functional conductive inks and bioinks on moving freeform surfaces yields wireless electronics on a moving human hand and cell‐laden biostructures on mice. The concept of printing functional and biological materials via an autonomous, adaptive 3D printing system suggests a new paradigm for printing on‐the‐fly wearable electronics on moving targets and for surgical applications.
The development of a method for efficiently harvesting energy from the human body could enable extraordinary advances in biomedical devices and portable electronics. Being electromechanically ...coupled, nanopiezoelectrics represent a promising new materials paradigm for scavenging otherwise wasted energy, with the ultimate goal of replacing or augmenting batteries. Of particular interest is developing biomechanical energy nanogenerators that are highly efficient, but with flexible form factors for wearable or implantable applications. This perspective presents an overview of the opportunities, progresses, and challenges in the rapidly accelerating field of nanopiezoelectrics. The combination of new nanomaterial properties, novel assembly strategies, and breakthrough device performance metrics suggests a rich platform for a host of exciting avenues in fundamental research and novel applications.
This perspective reviews recent advances in using piezoelectric nanomaterials to develop highly efficient, flexible energy harvesters for biomechanical power conversion.
3D printed deformable sensors Zhu, Zhijie; Park, Hyun Soo; McAlpine, Michael C
Science advances,
06/2020, Letnik:
6, Številka:
25
Journal Article
Recenzirano
Odprti dostop
The ability to directly print compliant biomedical devices on live human organs could benefit patient monitoring and wound treatment, which requires the 3D printer to adapt to the various ...deformations of the biological surface. We developed an in situ 3D printing system that estimates the motion and deformation of the target surface to adapt the toolpath in real time. With this printing system, a hydrogel-based sensor was printed on a porcine lung under respiration-induced deformation. The sensor was compliant to the tissue surface and provided continuous spatial mapping of deformation via electrical impedance tomography. This adaptive 3D printing approach may enhance robot-assisted medical treatments with additive manufacturing capabilities, enabling autonomous and direct printing of wearable electronics and biological materials on and inside the human body.
Rapid, simple, and cost-effective diagnostics are needed to improve healthcare at the point of care (POC). However, the most widely used POC diagnostic, the lateral flow immunoassay (LFA), is ...∼1000-times less sensitive and has a smaller analytical range than laboratory tests, requiring a confirmatory test to establish truly negative results. Here, a rational and systematic strategy is used to design the LFA contrast label (i.e., gold nanoparticles) to improve the analytical sensitivity, analytical detection range, and antigen quantification of LFAs. Specifically, we discovered that the size (30, 60, or 100 nm) of the gold nanoparticles is a main contributor to the LFA analytical performance through both the degree of receptor interaction and the ultimate visual or thermal contrast signals. Using the optimal LFA design, we demonstrated the ability to improve the analytical sensitivity by 256-fold and expand the analytical detection range from 3 log10 to 6 log10 for diagnosing patients with inflammatory conditions by measuring C-reactive protein. This work demonstrates that, with appropriate design of the contrast label, a simple and commonly used diagnostic technology can compete with more expensive state-of-the-art laboratory tests.
RATIONALE:One goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that ...replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be achieved using 3-dimensional bioprinting. Yet, inclusion of contiguous, living muscle to support pump function has not been achieved. This is largely due to the challenge of attaining high densities of cardiomyocytes—a notoriously nonproliferative cell type. An alternative strategy is to print with human induced pluripotent stem cells, which can proliferate to high densities and fill tissue spaces, and subsequently differentiate them into cardiomyocytes in situ.
OBJECTIVE:To develop a bioink capable of promoting human induced pluripotent stem cell proliferation and cardiomyocyte differentiation to 3-dimensionally print electromechanically functional, chambered organoids composed of contiguous cardiac muscle.
METHODS AND RESULTS:We optimized a photo-crosslinkable formulation of native ECM (extracellular matrix) proteins and used this bioink to 3-dimensionally print human induced pluripotent stem cell–laden structures with 2 chambers and a vessel inlet and outlet. After human induced pluripotent stem cells proliferated to a sufficient density, we differentiated the cells within the structure and demonstrated function of the resultant human chambered muscle pump. Human chambered muscle pumps demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing. The connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease.
CONCLUSIONS:This advance represents a critical step toward generating macroscale tissues, akin to aggregate-based organoids, but with the critical advantage of harboring geometric structures essential to the pump function of cardiac muscle. Looking forward, human chambered organoids of this type might also serve as a test bed for cardiac medical devices and eventually lead to therapeutic tissue grafting.
The development of a method for integrating highly efficient energy conversion materials onto soft, biocompatible substrates could yield breakthroughs in implantable or wearable energy harvesting ...systems. Of particular interest are devices which can conform to irregular, curved surfaces, and operate in vital environments that may involve both flexing and stretching modes. Previous studies have shown significant advances in the integration of highly efficient piezoelectric nanocrystals on flexible and bendable substrates. Yet, such inorganic nanomaterials are mechanically incompatible with the extreme elasticity of elastomeric substrates. Here, we present a novel strategy for overcoming these limitations, by generating wavy piezoelectric ribbons on silicone rubber. Our results show that the amplitudes in the waves accommodate order-of-magnitude increases in maximum tensile strain without fracture. Further, local probing of the buckled ribbons reveals an enhancement in the piezoelectric effect of up to 70%, thus representing the highest reported piezoelectric response on a stretchable medium. These results allow for the integration of energy conversion devices which operate in stretching mode via reversible deformations in the wavy/buckled ribbons.
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