tract delivery, [10] in vivo drug or antigen delivery, [11,12] and collective and dynamic gastric delivery via micromotor pills. [13] While Mg micromotors have been widely tested for dynamic in vivo delivery applications, their ability to manipulate, carry, and transport living cells has not been explored.Along the line of micromotor design, significant progress has been made recently toward creating biohybrid micromotors that combine cellular components and synthetic micro/nanoscale materials. Such cell-based micromotors offer considerable promise for diverse in vivo biomedical applications owing to their biocompatibility and biological functionality of the cellular component. [14] Live cells can thus be integrated with artificial substrates to produce functional biohybrid devices that possess new and improved capabilities. Such cell-based micromotors can be classified in two types. The first one relies on the intrinsic motility of live cells, such as spermatozoa, [15] bacteria, [16] and cardiomyocytes, [17] for transporting artificial material payloads. The microorganisms thus act as engines to form active biohybrid swimming systems powered by cellular actuation. The second type consists of cell-based materials, such as cell membranes, and synthetic micromotors that provide the motion. Such combination of micromotors with cell components confers the micromotor with cell-like properties [18,19] and improved biofunctionality. [20] Besides cell membrane-coated micromotors, various types of cells have also been used in biomedical applications due to their large drug loading capacity, [21] natural homing tendency toward inflammation sites, [22] and easy genetic engineering for gene delivery. [23] The combination of intact cells and engineered motors has resulted in several cellbased biohybrid micromotor designs for diverse applications, including stem cell-based motors for drug delivery, [24] red blood cell-motors for on-demand cargo delivery, [25] and NIH 3T3 cellbased motors for precise control and patterning. [26] Although such cell-based motors have demonstrated clear advantages as drug delivery carriers, it will be particularly interesting to explore the possibility of integrating intact live cells with biocompatible and biodegradable artificial micromotors, such as the Mg-based micromotors, to form a biohybrid motor system, which can potentially be applied for in vivo operations. Magnesium (Mg)-based micromotors are combined with live macrophage (MΦ) cells to create a unique MΦ-Mg biohybrid motor system. The resulting biomotors possess rapid propulsion ability stemming from the Mg micromotors and the biological functions provided by the live MΦ cell. To prepare the biohybrid motors, Mg microparticles coated with titanium dioxide and poly(l-lysine) (PLL) layers are incubated with live MΦs at low temperature. The formation of such biohybrid motors depends on the relative size of the MΦs and Mg particles, with the MΦ swallowing up Mg particles smaller than 5 µm. The experimental results and numerical simulations ...

As the most common nutritional disorder, iron deficiency represents a major public health problem with broad impacts on physical and mental development. However, treatment is often compromised by low iron bioavailability and undesired side effects. Here, we report on the development of active mineral delivery vehicles using Mg-based micromotors, which can autonomously propel in gastrointestinal fluids, aiding in the dynamic delivery of minerals. Iron and selenium are combined as a model mineral payload in the micromotor platform. We demonstrate the ability of our mineral-loaded micromotors to replenish iron and selenium stores in an anemic mouse model after 30 days of treatment, normalizing hematological parameters such as red blood count, hemoglobin, and hematocrit. Additionally, the micromotor platform exhibits no toxicity after the treatment regimen. This proof-of-concept study indicates that micromotor-based active delivery of mineral supplements represents an attractive approach toward alleviating nutritional deficiencies.

A tubular micromotor with spatially resolved compartments is presented towards efficient sitespecific cargo delivery, with a back-end zinc (Zn) propellant engine segment and an upfront cargo-This article is protected by copyright. All rights reserved. 2 loaded gelatin segment further protected by a pH-responsive cap. The multi-compartment micromotors display strong gastric-powered propulsion with tunable lifetime depending on the Zn segment length. Such propulsion significantly enhances the motor distribution and retention in the gastric tissues, by pushing and impinging the front-end cargo segment onto the stomach wall. Once the micromotor penetrates the gastric mucosa (pH ≥ 6.0), its pH-responsive cap dissolves, promoting the autonomous localized cargo release. The fabrication process, physicochemical properties, and propulsion behavior are systematically tested and discussed. Using a mouse model, the multicompartment motors, loaded with a model cargo, demonstrate a homogeneous cargo distribution along with ~4-fold enhanced retention in the gastric lining compared to mono-compartment motors, while showing no apparent toxicity. Therapeutic payloads can also be loaded into the pH-responsive cap, in addition to the gelatin-based compartment, leading to concurrent delivery and sequential release of dual cargos towards combinatorial therapy. Overall, this multi-compartment micromotor system provides unique features and advantages that will further advance the development of synthetic micromotors for active transport and localized delivery of biomedical cargos.

Here the fabrication of a zinc (Zn) microrocket pill is reported, and its unique features toward active and enhanced oral delivery application are demonstrated. By loading Zn‐based tubular microrockets into an orally administrable pill formulation, the resulting Zn microrocket pill can rapidly dissolve in the stomach, releasing numerous encapsulated Zn microrockets that are instantaneously activated and then propel in the gastric fluid. The released Zn microrockets display efficient propulsion without being affected by the presence of the inactive excipient materials of the pill. An in vivo retention study performed in mice clearly shows that the active pill dissolution and powerful acid‐driven Zn microrocket propulsion greatly enhance the microrocket retention within the gastric tissue without causing toxic effects. By combining the active delivery feature of Zn microrockets with the oral administration of a pill, the Zn microrocket pill holds considerable potential for active oral delivery of various therapeutics for diverse medical applications.

Majority of drugs are administered orally, yet their efficient absorption is often difficult to achieve, with a low dose fraction reaching the blood compartment. Here, a microstirring pill technology is reported with built‐in mixing capability for oral drug delivery that greatly enhances bioavailability of its therapeutic payload. Embedding microscopic stirrers into a pill matrix enables faster disintegration and dissolution, leading to improved release profiles of three widely used model drugs, aspirin, levodopa, and acetaminophen, without compromising their loading. Unlike recently developed drug‐carrying nanomotors, drug molecules are not associated with the microstirrers, and hence there is no limitation on the loading capacity. These embedded microstirrers are fabricated through the asymmetric coating of titanium dioxide thin film onto magnesium microparticles. In vitro tests illustrate that the embedded microstirrers lead to substantial enhancement of local fluid transport. In vivo studies using murine and porcine models demonstrate that the localized stirring capability of microstirrers leads to enhanced bioavailability of drug payloads. Such improvements are of considerable importance in clinical scenarios where fast absorption and high bioavailability of therapeutics are critical. The encouraging results obtained in porcine model suggest that the microstirring pill technology has translational potential and can be developed toward practical biomedical applications.