With natural evolution, honeybee stinger with microbarbs can easily penetrate and trap in the skin of hostile animals to inject venom for self-defense. We proposed a novel three-dimensional additive manufacturing method, namely magnetorheological drawing lithography, to efficiently fabricate a bioinspired microneedle imitating a honeybee stinger. Under the assistance of an external magnetic field, a parent microneedle was directly drawn on the pillar tip, and tilted microbarbs were subsequently formed on the four sides of the parent microneedle. Compared with the barbless microneedle, the microstructured barbs enable the bioinspired microneedle for easy skin insertion and difficult removal. The extraction-penetration force ratio of the bioinspired microneedle was triple that of the barbless microneedle. The stress concentration at the barbs helps to reduce the insertion force of the bioinspired microneedle by minimizing the frictional force, whereas it increases the adhesion force by interlocking the barbs in the tissue during retraction. Such finds may provide an inspiration for further design of barbed microtip-based microneedles for tissue adhesion, transdermal drug delivery, biosignal recording, and so on.

Microneedle arrays (MAs) are among the most promising transdermal drug delivery systems in the last decades due to its minimally invasive nature, convenient operation, and first-pass-metabolism avoidance. However, most MA fabrication methods are difficult to operate, need multiple steps, or require expensive equipment. A novel magnetorheological drawing lithography approach was proposed to rapidly fabricate a flexible microneedle array (FMA) for transdermal drug delivery. A 3D structural liquid MA was drawn in one step from the droplets of curable magnetorheological fluid and maintained its shape under an external magnetic field. The liquid MA was subsequently solidified and sputter-coated with the Ti/Au film to fabricate FMA. FMA morphology, mechanical properties, and transdermal drug delivery performance in vitro were experimentally investigated. FMA consisted of a 5 × 5 cone-shaped microneedle array on a PET flexible substrate. FMA exhibited good strength and excellent penetration performance. It could easily penetrate into skin without breakage, creating microchannels for the promotion of skin permeability. Drugs could be well permeated and diffused in the skin along the microchannels created by FMA. Finally, a dissolvable microneedle array (DMA) was also fabricated by a micromolding technique using FMA as a master template. The DMA exhibited good dissolvable and permeable performance in the agarose block.

Magnetoactive soft material (MASM) is distinguished for multifunctional shape manipulations under magnetic actuation, thereby holding a great promise in soft robotics, actuators, electronics, and metamaterials. However, the current research of MASM with continuum hard-magnetic profiles focuses little on the transformation mechanism, high dimensional shape transformation, and multistable locomotion. Herein, we developed a systematic methodology for programmable transformation and controllable locomotion of MASM with 3D-patterned continuum magnetization. An iterative computational model based on the equilibrium between magnetic torque and deformation-induced elastic torque was developed for precise prediction of MASM transformation. Multidimensional and complex shape manipulation ability of MASM was demonstrated by magnetically actuated transformations, including 1D to 2D, 2D to 3D, and 3D to 4D transformations of solid MASM, 2D to 3D pattern transformation of MASM-based elastin-like mesh, and 3D to 4D transformation of MASM-based cuboidal lattice. Multistable and controllable locomotion of MASM was verified by multimodal locomotion behaviors of a scallop-inspired robot for wall climbing in a dry frame and drug delivery in wet stomach, including roll, open, and close under self-locked and unlocked states.

No abstract

To date, only approximately 20 drugs synthesized with small molecules have been approved by the FDA for use in traditional transdermal patches (TTP) owing to the extremely low permeation rate of the skin barrier for macromolecular drugs. A novel touch-actuated microneedle array patch (TMAP) was developed for transdermal delivery of liquid macromolecular drugs. TMAP is a combination of a typical TTP and a solid microneedle array (MA). High doses of liquid drug formulations, especially heat-sensitive compounds can be easily filled and stored in the drug reservoir of TMAPs. TMAP can easily penetrate the skin and automatically retract from it to create microchannels through the stratum corneum (SC) layer using touch-actuated ‘press and release’ actions for passive permeation of liquid drugs. Comparison of subcutaneous injection, TTP, solid MA, and dissolvable MA, indicated that insulin-loaded TMAP exhibited the best hypoglycemic effect on type 1 diabetic rats. A ‘closed-loop’ permeation control was also provided for on-demand insulin delivery based on feedback of blood glucose levels (BGLs). Twenty IU-insulin-loaded TMAP maintained the type 1 diabetic rats in a normoglycemic state for approximately 11.63 h, the longest therapeutic duration among all previously reported results on microneedle-based transdermal patches. TMAP possesses excellent transdermal drug delivery capabilities.