Mobile micro-and nanorobots have been proposed for future biomedical applications, such as diagnostics and targeted delivery. For their translation to clinical practice, biocompatibility and biodegradability of micro-and nanorobots are required aspects. The fabrication of smallscale robots with non-cytotoxic biodegradable soft components will allow for enhanced device assimilation, optimal tissue interaction and minimized immune reactions. We report the 3D microfabrication of biodegradable soft helical microswimmers via two-photon polymerization of the nontoxic photocrosslinkable hydrogel gelatin methacryloyl (GelMA). GelMA microswimmers are fabricated with user-defined geometry and rendered magnetically responsive by decorating their surface with magnetic nanoparticles. In contrast to previous rigid helical microrobots, our soft helical microswimmers can corkscrew above the step-out frequency with relatively high values of forward velocity, suggesting an unprecedented selfadaptive behavior. Cytotoxicity assays show the toxicity of GelMA is at least three orders of
Neurodegenerative diseases generally result in irreversible neuronal damage and neuronal death. Cell therapy shows promise as a potential treatment for these diseases. However, the therapeutic targeted delivery of these cells and the in situ provision of a suitable microenvironment for their differentiation into functional neuronal networks remain challenging. A highly integrated multifunctional soft helical microswimmer featuring targeted neuronal cell delivery, on-demand localized wireless neuronal electrostimulation, and post-delivery enzymatic degradation is introduced. The helical soft body of the microswimmer is fabricated by two-photon lithography of the photocurable gelatin-methacryloyl (GelMA)-based hydrogel. The helical body is then impregnated with composite multiferroic nanoparticles displaying magnetoelectric features (MENPs). While the soft GelMA hydrogel chassis supports the cell growth, and is degraded by enzymes secreted by cells, the MENPs allow for the magnetic transportation of the bioactive chassis, and act as magnetically mediated electrostimulators of neuron-like cells. The unique combination of the materials makes these microswimmers highly integrated devices that fulfill several requirements for their future translation to clinical applications, such as cargo delivery, cell stimulation, and biodegradability. The authors envision that these devices will inspire new avenues for targeted cell therapies for traumatic injuries and diseases in the central nervous system.
Motile metal−organic frameworks (MOFs) are potential candidates to serve as small‐scale robotic platforms for applications in environmental remediation, targeted drug delivery, or nanosurgery. Here, magnetic helical microstructures coated with a kind of zinc‐based MOF, zeolitic imidazole framework‐8 (ZIF‐8), with biocompatibility characteristics and pH‐responsive features, are successfully fabricated. Moreover, it is shown that this highly integrated multifunctional device can swim along predesigned tracks under the control of weak rotational magnetic fields. The proposed systems can achieve single‐cell targeting in a cell culture media and a controlled delivery of cargo payloads inside a complex microfluidic channel network. This new approach toward the fabrication of integrated multifunctional systems will open new avenues in soft microrobotics beyond current applications.
Metal-organic frameworks (MOFs) are a class of crystalline materials constructed from organic linkers and inorganic nodes. MOFs typically possess ultra-high surface areas and pore volumes; thus, they are ideal candidates for biomedical applications. Zinc Imidazolate Framework 8 (ZIF-8) has been widely established in the literature as a potential candidate for on-demand drug delivery applications due to its remarkable loading capacity, stability in physiological environments, and pH triggered controlled drug release. Using ZIF-8 for in vivo applications requires a clear understanding of the interaction of ZIF-8 with biological tissue. In this work, we investigated the biocompatibility of ZIF-8 towards six different cell lines representing various body parts (kidney, skin, breast, blood, bones, and connective tissue). Our results suggested that ZIF-8 has no significant cytotoxicity up to a threshold value of 30 µg/mL. Above 30 µg/mL the cytotoxicity is shown to result from the effect of released Zinc ions (Zn 2+) on the mitochondrial ROS production, causing cell cycle arrest in the G2/M phase due to irreversible DNA damage, and ultimately initiating cellular apoptosis pathways. Due to this insight, we then encapsulated the hormone insulin into ZIF-8 and compared its drug delivery capabilities to the aforementioned cytotoxicity values. Our results suggest that ZIF-8 is suitable for therapeutic applications and furthermore, establish a clear understanding of the interaction of ZIF-8 and its constituents with various cell lines including, and highlight the important biocompatibility factors that must be considered for future in vivo testing.
Wireless piezoelectric microrobots are biomedical devices with a potential use in high-precision minimally invasive therapies.
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