Direct 3D printing of triple-responsive nanocomposite hydrogel microneedles for controllable drug delivery.

Hydrogel microneedle patches have emerged as promising platforms for painless, minimally invasive, safe, and portable transdermal drug administration. However, the conventional mold-based fabrication processes and inherent single-functionality of such microneedles present significant hurdles to broader implementation. Herein, we have developed a novel approach utilizing a precursor solution of robust nanocomposite hydrogels to formulate photo-printable inks suitable for the direct 3D printing of high-precision, triple-responsive hydrogel microneedle patches through digital light processing (DLP) technology. The ink formulation comprises four functionally diverse monomers including 2-(dimethylamino)ethyl methacrylate, N-isopropylacrylamide, acrylic acid, and acrylamide, which were crosslinked by aluminum hydroxide nanoparticles (AH NPs) acting as both reinforcing agents and crosslinking centers. This results in the formation of a nanocomposite hydrogel characterized by exceptional mechanical strength, an essential attribute for the 3D printing of hydrogel microneeedle patches. Furthermore, this innovative 3D printing strategy facilitates facile customization of microneedle geometry and patch dimensions. As a proof-of-concept, we employed the fabricated hydrogel microneedles for transdermal delivery of bovine serum albumin (BSA). Importantly, these hydrogel microneedles displayed no cytotoxic effects and exhibited triple sensitivity to pH, temperature and glucose levels, thereby enabling more precise on-demand drug delivery. This study provides a universal method for the rapid fabrication of hydrogel microneedles with smart responsiveness for transdermal drug delivery applications.

Multi-material 3D printed eutectogel microneedle patches integrated with fast customization and tunable drug delivery.

Microneedle patches are emerging multifunctional platforms for transdermal diagnostics and drug delivery. However, it still remains challenging to develop smart microneedles integrated with customization, sensing, detection and drug delivery by 3D printing strategy. Here, we present an innovative but facile strategy to rationally design and fabricate multifunctional eutectogel microneedle (EMN) patches via multi-material 3D printing. Polymerizable deep eutectic solvents (PDES) were selected as printing inks for rapid one-step fabrication of 3D printing functional EMN patches due to fast photopolymerization rate and ultrahigh drug solubility. Moreover, stretchable EMN patches incorporating rigid needles and flexible backing layers were easily realized by changing PDES compositions of multi-material 3D printing. Meanwhile, we developed multifunctional smart multi-material EMN patches capable of performing wireless monitoring of body movements, painless colorimetric glucose detection, and controlled transdermal drug delivery. Thus, such multi-material EMN system could provide an effective platform for the painless diagnosis, detection, and therapy of a variety of diseases.

Transparent, Mechanically Robust, Adhesive, Temperature-Tolerant, and 3D Printable Nanocomposite Ionogels for Flexible Sensors.

Ionogels are emerging as soft materials for flexible strain sensors. However, the integration of multiple functionalities into a single ionogel for diverse applications in complex scenarios remains a challenge. In this study, we present a multifunctional nanocomposite ionogel that combines high strength, transparency, stretchability, temperature tolerance, adhesiveness, and 3D printing capabilities. The ionogels are fabricated through a one-step photopolymerization process involving acrylic acid and 2-acrylamide-2-methylpropanesulfonic acid in an ionic liquid, with Al(OH)3 nanoparticles serving as cross-linkers. The resulting ionogels exhibit robust noncovalent interactions, including ionic coordination, hydrogen bonding, and ionic dipole interactions, providing exceptional mechanical strength, conductivity, and wide temperature tolerance while ensuring strong adhesion to various substrates. Wearable strain sensors based on these ionogels can accurately detect and differentiate a range of movements, from large body motions such as bending limbs to subtle distinctions such as writing different letters. Additionally, the pregel solution can serve as printing ink for the rapid and efficient mass production of 3D printed high-precision microcircuits. Impressively, the nanocomposite ionogels exhibit a high latent heat value of 240 J g-1 at a melting temperature of -65 °C, suggesting significant potential for cold energy storage in ultralow-temperature cold-chain transportation systems. Thus, these outstanding features of the ionogels offer a promising strategy for advancing wearable electronics and cold energy storage systems.