Slippery Liquid-Attached Surface for Robust Biofouling Resistance

Materials for biodevices and bioimplants commonly suffer from unwanted but unavoidable biofouling problems due to the nonspecific adhesion of proteins, cells, or bacteria. Chemical coating or physical strategies for reducing biofouling have been pursued, yet highly robust antibiofouling surfaces that can persistently resist contamination in biological environments are still lacking. In this study, we developed a facile method to fabricate a highly robust slippery and antibiofouling surface by conjugating a liquid-like polymer layer to a substrate. This slippery liquid-attached (SLA) surface was created via a one-step equilibration reaction by tethering methoxy-terminated polydimethylsiloxane (PDMS-OCH3) polymer brushes onto a substrate to form a transparent “liquid-like” layer. The SLA surface exhibited excellent sliding behaviors toward a wide range of liquids and small particles and antibiofouling properties against the long-term adhesion of small biomolecules, proteins, cells, and bacteria. Moreover, in contrast to superomniphobic surfaces and liquid-infused porous surfaces (SLIPS) requiring micro/nanostructures, the SLA layer could be obtained on smooth surfaces and maintain its biofouling resistance under abrasion with persistent stability. Our study offers a simple method to functionalize surfaces with robust slippery and antibiofouling properties, which is promising for potential applications including medical implants and biodevices

Transdermal Delivery of Living and Biofunctional Probiotics through Dissolvable Microneedle Patches

Bioactive functional probiotics play an important role in many health applications such as maintaining skin health and the immunity of the human host. Artificial supplementation of probiotics would enhance immune functions as well as regulate skin health. However, simple and effective methods to deliver probiotics into the dermis to regulate local dermal tissue are still lacking. Furthermore, microneedles have been used for transdermal drug delivery in a pain-free manner, yet there were few reported methods to deliver living microbes via microneedles. In this work, we developed a technique to deliver bioactive functional probiotics, using lactobacillus as the model probiotic, into local dermis by dissolvable microneedles. The transdermal delivery of probiotics might enhance local skin regulation and immunity, and dissolvable microneedles served as a safe and pain-free tool for dermal microbial delivery. Lactobacillus was encapsulated in dissolvable microneedles with high viability by a centrifugation casting method. The microneedles rapidly dissolved after skin penetration, releasing the lactobacillus into the subcutaneous space, without causing local tissue irritation. The lactobacillus was functionally bioactive following transdermal delivery, actively synthesizing lactic acid both ex vivo and in vivo. Our technique provided a safe, effective, and convenient approach for the transdermal delivery of probiotics into local skin, with the potential to improve skin health and immunity

Multifunctional Branched Nanostraw-Electroporation Platform for Intracellular Regulation and Monitoring of Circulating Tumor Cells

Downstream analysis of circulating tumor cells (CTCs) has provided new insights into cancer research. In particular, the detection of CTCs, followed by the regulation and monitoring of their intracellular activities, can provide valuable information for comprehensively understanding cancer pathogenesis and progression. However, current CTC detection techniques are rarely capable of in situ regulation and monitoring of the intracellular microenvironments of cancer cells over time. Here, we developed a multifunctional branched nanostraw (BNS)-electroporation platform that could effectively capture CTCs and allow for downstream regulation and monitoring of their intracellular activities in a real-time and in situ manner. The BNSs possessed numerous nanobranches on the outer sidewall of hollow nanotubes, which could be conjugated with specific antibodies to facilitate the effective capture of CTCs. Nanoelectroporation could be applied through the BNSs to nondestructively porate the membranes of the captured cells at a low voltage, allowing the delivery of exogenous biomolecules into the cytosol and the extraction of cytosolic contents through the BNSs without affecting cell viability. The efficient delivery of biomolecules (e.g., small molecule dyes and DNA plasmids) into cancer cells with spatial and temporal control and, conversely, the repeated extraction of intracellular enzymes (e.g., caspase-3) for real-time monitoring were both demonstrated. This technology can provide new opportunities for the comprehensive understanding of cancer cell functions that will facilitate cancer diagnosis and treatment

Injectable Slippery Lubricant-Coated Spiky Microparticles with Persistent and Exceptional Biofouling-Resistance

Injectable micron-sized particles have historically achieved promising applications, but they continued to suffer from long-term biofouling caused by the adhesions of biomolecules, cells, and bacteria. Recently, a slippery lubricant infusion porous substrate (SLIPS) exhibited robust antiadhesiveness against many liquids; however, they were constructed using a 2D substrate, and they were not suitable for in vivo applications, such as injectable biomaterials. Inspired by SLIPS, here, we report the first case of injectable solid microparticles coated with a lubricating liquid surface to continuously resist biofouling. In our design, microparticles were attached with nanospikes and fluorinated to entrap the lubricant. The nanospikes enabled the lubricant-coated spiky microparticles (LCSMPs) to anomalously disperse in water despite the attraction between the surfaces of the microparticles. This result indicated that the LCSMPs exhibited persistent anomalous dispersity in water while maintaining a robust lubricating surface layer. LCSMPs prevented the adhesion of proteins, mammalian cells, and bacteria, including Escherichia coli and Staphylococcus aureus. LCSMPs also reduced in vivo fibrosis while conventional microparticles were heavily biofouled. This technology introduced a new class of injectable anti-biofouling microparticles with reduced risks of inflammation and infections

Biodegradable Therapeutic Microneedle Patch for Rapid Antihypertensive Treatment

A hypertensive emergency causes severe cardiovascular diseases accompanied by acute target organ damage, requiring rapid and smooth blood pressure (BP) reduction. Current medicines for treating hypertensive emergencies, such as sodium nitroprusside (SNP), require careful dose control to avoid side effects (e.g., cyanide poisoning). The clinical administration of SNP using intravenous injection or drip further restrict its usage for first aid or self-aid in emergencies. Here, we developed an antihypertensive microneedle (aH-MN) technique to transdermally deliver SNP in combination with sodium thiosulfate (ST) as a cyanide antidote in a painless way. Dissolvable microneedles loaded with SNP and ST were fabricated via the centrifugation casting method, where the SNPs were stably packaged in microneedles and would be immediately released into the systemic circulation via subcutaneous capillaries when aH-MNs penetrated the skin. The antihypertensive effects were demonstrated on spontaneously hypertensive rat models. Rapid and potent BP reduction was achieved via aH-MN treatment, fulfilling clinical BP-control requirements for hypertensive emergencies. The side effects including skin irritation and target organ damage of aH-MN therapies were evaluated; the combinative delivery of ST effectively suppressed these side effects induced by the consecutive intake of SNP. This study introduces an efficient and patient-friendly antihypertensive therapy with a favorable side-effect profile, particularly a controllable and self-administrable approach to treat hypertensive emergencies

Protection of Nanostructures-Integrated Microneedle Biosensor Using Dissolvable Polymer Coating

Real-time transdermal biosensing provides a direct route to quantify biomarkers or physiological signals of local tissues. Although microneedles (MNs) present a mini-invasive transdermal technique, integration of MNs with advanced nanostructures to enhance sensing functionalities has rarely been achieved. This is largely due to the fact that nanostructures present on MNs surface could be easily destructed due to friction during skin insertion. In this work, we reported a dissolvable polymer-coating technique to protect nanostructures-integrated MNs from mechanical destruction during MNs insertion. After penetration into the skin, the polymer could readily dissolve by interstitial fluids so that the superficial nanostructures on MNs could be re-exposed for sensing purpose. To demonstrate this technique, metallic and resin MNs decorated with vertical ZnO nanowires (vNWs) were employed as an example. Dissolvable poly­(vinyl pyrrolidone) was spray-coated on the vNW-MNs surface as a protective layer, which effectively protected the superficial ZnO NWs when MNs penetrated the skin. Transdermal biosensing of H2O2 biomarker in skin tissue using the polymer-protecting MNs sensor was demonstrated both ex vivo and in vivo. The results indicated that polymer coating successfully preserved the sensing functionalities of the MNs sensor after inserting into the skin, whereas the sensitivity of the MN sensor without a coating protection was significantly compromised by 3-folds. This work provided unique opportunities of protecting functional nanomodulus on MNs surface for minimally invasive transdermal biosensing