Skin and soft tissue infections (SSTIs) caused by methicillin‐resistant Staphylococcus aureus (MRSA) are a major healthcare burden, often treated with intravenous injection of the glycopeptide antibiotic vancomycin (VAN). However, low local drug concentration in the skin limits its treatment efficiency, while systemic exposure promotes the development of resistant bacterial strains. Topical administration of VAN on skin is ineffective as its high molecular weight prohibits transdermal penetration. In order to implement a local VAN delivery, microneedle (MN) arrays with a water‐insoluble support layer for the controlled administration of VAN into the skin are developed. The utilization of such a support layer results in water‐insoluble needle shafts surrounded by drug‐loaded water‐soluble tips with high drug encapsulation. The developed MN arrays can penetrate the dermal barriers of both porcine and fresh human skin. Permeation studies on porcine skin reveal that the majority of the delivered VAN is retained within the skin. It is shown that the VAN‐MN array reduces MRSA growth both in vitro and ex vivo on skin. The developed VAN‐MN arrays may be extended to several drugs and may facilitate localized treatment of MRSA‐caused skin infections while minimizing adverse systemic effects.

Polyurethane-based hydrogels are relatively inexpensive and mechanically robust biomaterials with ideal properties for various applications, including drug delivery, prosthetics, implant coatings, soft robotics, and tissue engineering. In this report, a simple method is presented for synthesizing and casting biocompatible polyurethane-poly(ethylene glycol) (PU-PEG) hydrogels with tunable mechanical properties, nonfouling characteristics, and sustained tolerability as an implantable material or coating. The hydrogels are synthesized via a simple one-pot method using commercially available precursors and low toxicity solvents and reagents, yielding a consistent and biocompatible gel platform primed for long-term biomaterial applications. The mechanical and physical properties of the gels are easily controlled by varying the curing concentration, producing networks with complex shear moduli of 0.82-190 kPa, similar to a range of human soft tissues. When evaluated against a mechanically matched poly(dimethylsiloxane) (PDMS) formulation, the PU-PEG hydrogels demonstrated favorable nonfouling characteristics, including comparable adsorption of plasma proteins (albumin and fibrinogen) and significantly reduced cellular adhesion. Moreover, preliminary murine implant studies reveal a mild foreign body response after 41 days. Due to the tunable mechanical properties, excellent biocompatibility, and sustained in vivo tolerability of these hydrogels, it is proposed that this method offers a simplified platform for fabricating soft PU-based biomaterials for a variety of applications.

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Cancer treatment with chemotherapeutic drugs remains to be challenging to the physician due to limitations associated with lack of efficacy or high toxicities. Typically, chemotherapeutic drugs are administered intravenously, leading to high drug concentrations that drive efficacy but also lead to known side effects. Delivery of drugs through transdermal microneedles (MNs) has become an important alternative treatment approach. Such delivery options are well suited for chemotherapeutic drugs in which sustained levels would be desirable. In the context of developing a novel approach, laser induced forward transfer (LIFT) was applied for bioprinting of gemcitabine (Gem) to coat polymethylmethacrylate MNs. Gem, a chemotherapeutic agent used to treat various types of cancer, is a good candidate for MN-assisted transdermal delivery to improve the pharmacokinetics of Gem while reducing efficiency limitations. LIFT bioprinting of Gem for coating of MNs with different drug amounts and successful transdermal delivery in mice is presented in this study. Our approach produced reproducible, accurate, and uniform coatings of the drug on MN arrays, and on in vivo transdermal application of the coated MNs in mice, dose-proportional concentrations of Gem in the plasma of mice was achieved. The developed approach may be extended to several chemotherapeutics and provide advantages for metronomic drug dosing.

PTT, nanoparticles (NPs) can be used to convert electromagnetic radiation to heat. Increasing the local temperature in the skin may improve the therapeutic outcome of various diseases, such as skin tumors and cancer, or bacterial, parasitic, and viral skin infections. [1] Target temperatures for PTT often range from 38 to 55 °C with a heating above ≈50 °C causing protein denaturation and tissue coagulation which may interfere with successful therapy. [4] The therapeutic effect of hyperthermia is to i) induce cellular apoptosis and necrosis in cells, ii) increase the blood flow, and iii) elicit immune responses. [1,4] Furthermore, combining hyperthermia with pharmaceutical treatments may reduce the required drug dose, which is specifically relevant for the prevention of further development of drug resistance. [5] For successful application of PTT in dermatological conditions, it is required that the heat is evenly distributed into potentially deep layers of the skin. [6] Microneedle (MN) arrays have been extensively studied in recent years for PTT-based skin therapy [7,8] and the photothermal agents that have been delivered via MNs include silica-coated lanthanum hexaboride, [9][10][11] gold nanorods [6,12,13] and nanocages, [14] Prussian blue NPs, [15] graphene oxide NPs, [16,17] black phosphorus quantum dots, [18] indocyanine green, [19][20][21] CuO 2 NPs, [22] and Nb 2 C nanosheets. [23] In all those examples, the photothermal agent is active in the near-infrared (NIR) wavelength region which avoids nonspecific thermal damage to tissue. [24] Importantly, MN-assisted delivery of PTT can enhance treatment outcomes in cancers and reduce bacterial infections while distributing the hyperthermia evenly and deep into the skin. [8] However, the broad employment of photothermal MN arrays is prohibited due to high production costs of some photothermal agents (e.g., gold nanorods), their poor long-term stability, and/or degradation by photobleaching (e.g., indocyanine green). [5,25] The lack of high photothermal efficiency of some proposed PTT-based MNs systems also requires high laser intensities up to 5 W cm −2 . [9,13,26] Such high laser intensities may limit clinical translation of MN arrays for PTT since laser intensities above 0.3-1.0 W cm −2 at 780-1050 nm are the maximum permissible exposure limit to skin according to the American National Standard for Safe Use of Lasers. [27] Furthermore, Near-infrared (NIR) photothermal therapy by microneedles (MNs) exhibits high potential against skin diseases. However, high costs, photobleaching of organic agents, low long-term stability, and potential nanotoxicity limit the clinical translation of photothermal MNs. Here, photothermal MNs are developed by utilizing Au nanoaggregates made by flame aerosol technology and incorporated in water-insoluble polymer matrix to reduce intradermal nanoparticle (NP) deposition. The individual Au interparticle distance and plasmonic coupling within the nanoaggregates are controlled by the addition of a spacer during their synthesis renderi...