Programmable Photoswitchable Microcapsules Enable Precise and Tailored Drug Delivery from Microfluidics.

The development of precision personalized medicine poses a significant need for the next generation of advanced diagnostic and therapeutic technologies, and one of the key challenges is the development of highly time-, space-, and dose-controllable drug delivery systems that respond to the complex physiopathology of patient populations. In response to this challenge, an increasing number of stimuli-responsive smart materials are integrated into biomaterial systems for precise targeted drug delivery. Among them, responsive microcapsules prepared by droplet microfluidics have received much attention. In this study, we present a UV-visible light cycling mediated photoswitchable microcapsule (PMC) with dynamic permeability-switching capability for precise and tailored drug release. The PMCs were fabricated using a programmable pulsed aerodynamic printing (PPAP) technique, encapsulating an aqueous core containing magnetic nanoparticles and the drug doxorubicin (DOX) within a poly(lactic-co-glycolic acid) (PLGA) composite shell modified by PEG-b-PSPA. Selective irradiation of PMCs with ultraviolet (UV) or visible light (Vis) allows for high-precision time-, space-, and dose-controlled release of the therapeutic agent. An experimentally validated theoretical model was developed to describe the drug release pattern, holding promise for future customized programmable drug release applications. The therapeutic efficacy and value of patternable cancer cell treatment activated by UV radiation is demonstrated by our experimental results. After in vitro transcatheter arterial chemoembolization (TACE), PMCs can be removed by external magnetic fields to mitigate potential side effects. Our findings demonstrate that PMCs have the potential to integrate embolization, on-demand drug delivery, magnetic actuation, and imaging properties, highlighting their immense potential for tailored drug delivery and embolic therapy.

On-chip modeling of tumor evolution: Advances, challenges and opportunities.

Tumor evolution is the accumulation of various tumor cell behaviors from tumorigenesis to tumor metastasis and is regulated by the tumor microenvironment (TME). However, the mechanism of solid tumor progression has not been completely elucidated, and thus, the development of tumor therapy is still limited. Recently, Tumor chips constructed by culturing tumor cells and stromal cells on microfluidic chips have demonstrated great potential in modeling solid tumors and visualizing tumor cell behaviors to exploit tumor progression. Herein, we review the methods of developing engineered solid tumors on microfluidic chips in terms of tumor types, cell resources and patterns, the extracellular matrix and the components of the TME, and summarize the recent advances of microfluidic chips in demonstrating tumor cell behaviors, including proliferation, epithelial-to-mesenchymal transition, migration, intravasation, extravasation and immune escape of tumor cells. We also outline the combination of tumor organoids and microfluidic chips to elaborate tumor organoid-on-a-chip platforms, as well as the practical limitations that must be overcome.

Microneedle array facilitates hepatic sinusoid construction in a large-scale liver-acinus-chip microsystem.

Hepatic sinusoids play a key role in maintaining high activities of liver cells in the hepatic acinus. However, the construction of hepatic sinusoids has always been a challenge for liver chips, especially for large-scale liver microsystems. Herein, we report an approach for the construction of hepatic sinusoids. In this approach, hepatic sinusoids are formed by demolding a self-developed microneedle array from a photocurable cell-loaded matrix in a large-scale liver-acinus-chip microsystem with a designed dual blood supply. Primary sinusoids formed by demolded microneedles and spontaneously self-organized secondary sinusoids can be clearly observed. Benefiting from significantly enhanced interstitial flows by formed hepatic sinusoids, cell viability is witnessed to be considerably high, liver microstructure formation occurs, and hepatocyte metabolism is enhanced. In addition, this study preliminarily demonstrates the effects of the resulting oxygen and glucose gradients on hepatocyte functions and the application of the chip in drug testing. This work paves the way for the biofabrication of fully functionalized large-scale liver bioreactors.

A glomerulus chip with spherically twisted cell-laden hollow fibers as glomerular capillary tufts.

Glomerulus-on-a-chip, as a promising alternative for drug nephrotoxicity evaluation, is attracting increasing attention. For glomerulus-on-a-chip, the more biomimetic the chip is, the more convincing the application of the chip is. In this study, we proposed a hollow fiber-based biomimetic glomerulus chip that can regulate filtration in response to blood pressure and hormone levels. On the chip developed here, bundles of hollow fibers were spherically twisted and embedded in designed Bowman's capsules to form spherical glomerular capillary tufts, with podocytes and endotheliocytes cultured on the outer and inner surfaces of the hollow fibers, respectively. We evaluated the morphology of cells, the viability of cells, and the metabolic function of cells in terms of glucose consumption and urea synthesis by comparing the results obtained under fluidic and static conditions, confirmed the barrier function of the endotheliocyte-fiber membrane-podocyte structure by monitoring the diffusion of fluorescein isothiocyanate (FITC)-labeled inulin, albumin and IgG, and, for the first time, achieved on-chip filtration regulation in response to the hormone atrial natriuretic peptide. In addition, the application of the chip in the evaluation of drug nephrotoxicity was also preliminarily demonstrated. This work offers insights into the design of a more physiologically similar glomerulus on a microfluidic chip.

On-chip construction of a fully structured scaffold-free vascularized renal tubule.

Renal tubule chips have emerged as a promising platform for drug nephrotoxicity testing. However, the reported renal tubule chips hardly replicate the unique structure of renal tubules with thick proximal and distal tubules and a thin loop of Henle. In this study, we developed a fully structured scaffold-free vascularized renal tubule on a microfluidic chip. On the chip, the renal epithelial cell-laden hollow calcium-polymerized alginate tube with thick segments at both ends and a thin middle segment was U-shaped embedded in collagen hydrogel, parallel to the endothelial cell-laden hollow calcium-polymerized alginate tube with uniform tube diameter. After the alginate tubes were on-chip degraded, the renal epithelial cells and endothelial cells automatically attached to the collagen hydrogel and proliferated to form the renal tubule with proximal tubule, loop of Henle and distal tubule as well as peritubular blood vessel. We evaluated the viability of cells on the hollow alginate tubes, characterized the distribution and morphology of cells before and after the degradation of the alginate tube, and confirmed the proliferation of cells and the metabolic function of cells in terms of ATP synthesis, fibronectin secretion and VEGFR2 expression on the chip. The enhanced metabolic functions of renal epithelial cells and endothelial cells were preliminarily demonstrated. This study provides new insights into designing a more biomimetic renal tubule on a microfluidic chip.

Advances on microfluidic paper-based electroanalytical devices.

Since the inception of the first electrochemical devices on paper substrates, many different reports of microfluidic paper-based electroanalytical devices (µPEDs), innovative hydrophobic barriers and electrode fabrication processes have allowed the incorporation of diverse materials, resulting in different applications and a boost in performance. These advancements have led to the creation of paper-based devices with comparable performance to many standard conventional devices, with the added benefits of pumpless fluidic transport, component separation and reagent storage that can be exploited to automate and handle sample preprocessing. Herein, we review µPEDs, summarize the characteristics and functionalities of µPEDs, such as separation, fluid flow control and storage, and outline the conventional and emerging fabrication and modification approaches for µPEDs. We also examine the recent application of µPEDs in biomedicine, the environment, and food and water safety, as well as some limitations and challenges that must be addressed.