The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs) for regenerative medicine applications. The resulting ECOs closely resemble primary cholangiocytes in terms of their transcriptomic profile and functional properties. We explore the regenerative potential of these organoids in vivo and demonstrate that ECOs self-organize into bile duct-like tubes expressing biliary markers following transplantation under the kidney capsule of immunocompromised mice. In addition, when seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary characteristics. The resulting bioengineered tissue can reconstruct the gallbladder wall and repair the biliary epithelium following transplantation into a mouse model of injury. Furthermore, bioengineered artificial ducts can replace the native CBD, with no evidence of cholestasis or occlusion of the lumen. In conclusion, ECOs can successfully reconstruct the biliary tree, providing proof of principle for organ regeneration using human primary cholangiocytes expanded in vitro.

Microcantilever bending can be reversibly driven by conformational changes of phosphate containing polyelectrolyte brushes when exposed to different pH or salt solutions. The deflection of the cantilevers allows a detailed analysis of the properties of polymer brushes, while these systems are also a first step toward polymer-based nanoactuators.

This paper describes the electroactuation of microcantilevers coated on one side with cationic polyelectrolyte brushes. We observed very strong cantilever deflection by alternating the potential on the cantilever between +0.5 and -0.5 V at frequencies up to 0.25 Hz. The actuation resulted from significant increases in the expansive stresses in the polymer brush layer at both negative and positive potentials. However, the deflection at negative bias was significantly larger. We have developed a theoretical framework that correlates conformational changes of the polymer chains in the brush layer with the reorganization of ions due to the potential bias. The model predicts a strong increase in the polymer volume fraction, close to the interface, which results in large expansive stresses that bend the cantilever at negative potentials. The model also predicts that the actuation responds much stronger to negative potentials than positive potentials, as observed in the experiments.

Ar apidly formed supramolecular polypeptideDNAh ydrogel was prepared and used for in situ multilayer three-dimensional bioprinting for the first time.Byalternative deposition of two complementary bio-inks,designed structures can be printed. Based on their healing properties and high mechanical strengths,t he printed structures are geometrically uniform without boundaries and can keep their shapes up to the millimeter scale without collapse.3 Dc ell printing was demonstrated to fabricate live-cell-containing structures with normal cellular functions.T ogether with the unique properties of biocompatibility,p ermeability,a nd biodegradability,t he hydrogel becomes an ideal biomaterial for 3D bioprinting to produce designable 3D constructs for applications in tissue engineering.

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The therapeutic replacement of diseased tubular tissue is hindered by the availability and suitability of current donor, autologous and synthetically derived protheses. Artificially created, tissue engineered, constructs have the potential to alleviate these concerns with reduced autoimmune response, high anatomical accuracy, long-term patency and growth potential. The advent of 3D bioprinting technology has further supplemented the technological toolbox, opening up new biofabrication research opportunities and expanding the therapeutic potential of the field. In this review, we highlight the challenges facing those seeking to create artificial tubular tissue with its associated complex macro- and microscopic architecture. Current biofabrication approaches, including 3D printing techniques, are reviewed and future directions suggested.

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Antimicrobial resistance (AMR) is an issue of upmost global importance, with an annually increasing mortality rate and growing economic burden. Poor antimicrobial stewardship has resulted in an abundance and diverse range of antimicrobial resistance mechanisms. To tackle AMR effectively, better diagnostic tests must be developed in order to improve antibiotic stewardship and reduce the emergence of antibiotic resistant organisms. This study employs a low-cost, commercially available screen printed electrode modified with an agarose-based hydrogel deposit to monitor bacterial growth using the techniques of electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) giving rise to a new approach to measuring susceptibility. Susceptible and drug resistant Staphylococcus aureus strains were deposited onto agarose gel modified electrodes which contained clinically important antibiotics to establish growth profiles for each bacterial strain and monitor the influence of the antibiotic on bacterial growth. The results show that S. aureus is able to grow on electrodes modified with gel containing no antibiotic, but is inhibited when the gel modified electrode is seeded with antibiotic. Conversely, methicillin-resistant S. aureus (MRSA; the drug resistant strain) is able to grow on gel modified electrodes containing clinically relevant concentrations of antibiotic. Results show rapid growth profiles, with possible time to results for antibiotic susceptibility < 45 minutes, a significant improvement on the current gold standards of at least 1-2 days.