Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery.

Bacterial biohybrids, composed of self-propelling bacteria carrying micro/nanoscale materials, can deliver their payload to specific regions under magnetic control, enabling additional frontiers in minimally invasive medicine. However, current bacterial biohybrid designs lack high-throughput and facile construction with favorable cargoes, thus underperforming in terms of propulsion, payload efficiency, tissue penetration, and spatiotemporal operation. Here, we report magnetically controlled bacterial biohybrids for targeted localization and multistimuli-responsive drug release in three-dimensional (3D) biological matrices. Magnetic nanoparticles and nanoliposomes loaded with photothermal agents and chemotherapeutic molecules were integrated onto Escherichia coli with ~90% efficiency. Bacterial biohybrids, outperforming previously reported E. coli-based microrobots, retained their original motility and were able to navigate through biological matrices and colonize tumor spheroids under magnetic fields for on-demand release of the drug molecules by near-infrared stimulus. Our work thus provides a multifunctional microrobotic platform for guided locomotion in 3D biological networks and stimuli-responsive delivery of therapeutics for diverse medical applications.

3D Printing of Elastomeric Bioinspired Complex Adhesive Microstructures.

Bioinspired elastomeric structural adhesives can provide reversible and controllable adhesion on dry/wet and synthetic/biological surfaces for a broad range of commercial applications. Shape complexity and performance of the existing structural adhesives are limited by the used specific fabrication technique, such as molding. To overcome these limitations by proposing complex 3D microstructured adhesive designs, a 3D elastomeric microstructure fabrication approach is implemented using two-photon-polymerization-based 3D printing. A custom aliphatic urethane-acrylate-based elastomer is used as the 3D printing material. Two designs are demonstrated with two combined biological inspirations to show the advanced capabilities enabled by the proposed fabrication approach and custom elastomer. The first design focuses on springtail- and gecko-inspired hybrid microfiber adhesive, which has the multifunctionalities of side-surface liquid super-repellency, top-surface liquid super-repellency, and strong reversible adhesion features in a single fiber array. The second design primarily centers on octopus- and gecko-inspired hybrid adhesive, which exhibits the benefits of both octopus- and gecko-inspired microstructured adhesives for strong reversible adhesion on both wet and dry surfaces, such as skin. This fabrication approach could be used to produce many other 3D complex elastomeric structural adhesives for future real-world applications.

High-Yield Production of Biohybrid Microalgae for On-Demand Cargo Delivery.

Biohybrid microswimmers exploit the swimming and navigation of a motile microorganism to target and deliver cargo molecules in a wide range of biomedical applications. Medical biohybrid microswimmers suffer from low manufacturing yields, which would significantly limit their potential applications. In the present study, a biohybrid design strategy is reported, where a thin and soft uniform coating layer is noncovalently assembled around a motile microorganism. Chlamydomonas reinhardtii (a single-cell green alga) is used in the design as a biological model microorganism along with polymer-nanoparticle matrix as the synthetic component, reaching a manufacturing efficiency of ≈90%. Natural biopolymer chitosan is used as a binder to efficiently coat the cell wall of the microalgae with nanoparticles. The soft surface coating does not impair the viability and phototactic ability of the microalgae, and allows further engineering to accommodate biomedical cargo molecules. Furthermore, by conjugating the nanoparticles embedded in the thin coating with chemotherapeutic doxorubicin by a photocleavable linker, on-demand delivery of drugs to tumor cells is reported as a proof-of-concept biomedical demonstration. The high-throughput strategy can pave the way for the next-generation generation microrobotic swarms for future medical active cargo delivery tasks.

Nanoerythrosome-functionalized biohybrid microswimmers.

Biohybrid microswimmers, which are realized through the integration of motile microscopic organisms with artificial cargo carriers, have a significant potential to revolutionize autonomous targeted cargo delivery applications in medicine. Nonetheless, there are many open challenges, such as motility performance and immunogenicity of the biological segment of the microswimmers, which should be overcome before their successful transition to the clinic. Here, we present the design and characterization of a biohybrid microswimmer, which is composed of a genetically engineered peritrichously flagellated Escherichia coli species integrated with red blood cell-derived nanoliposomes, also known as nanoerythrosomes. Initially, we demonstrated nanoerythrosome fabrication using the cell extrusion technique and characterization of their size and functional cell membrane proteins with dynamic light scattering and flow cytometry analyses, respectively. Then, we showed the construction of biohybrid microswimmers through the conjugation of streptavidin-modified bacteria with biotin-modified nanoerythrosomes by using non-covalent streptavidin interaction. Finally, we investigated the motility performance of the nanoerythrosome-functionalized biohybrid microswimmers and compared it with the free-swimming bacteria. The microswimmer design approach presented here could lead to the fabrication of personalized biohybrid microswimmers from patients' own cells with high fabrication efficiencies and motility performances.