We report the synthesis of thermo-responsive polymer brushes with Upper Critical Solution Temperature (UCST)-type behaviour on glass to provide a new means to control cell attachment. Thermoresponsive poly(N-acryloyl glycinamide)-statpoly(N-phenylacrylamide) (PNAGAm-PNPhAm) brushes with three different monomer ratios were synthesized to give tunable phase transition temperatures (Tp) in solution. Surface energies of surface-grafted brushes of these polymers at 25, 32, 37 and 50 C were calculated from contact angle measurements and atomic force microscopy (AFM) studies confirmed that these polymers were highly extended at temperatures close to Tp in physiologically-relevant media. Importantly, NIH-3T3 cells were attached on the collapsed PNAGAm-PNPhAm brush surface at 30 C after 20 h incubation, while release of cells from the extended brushes was observed within 2 h after the culture temperature was switched to 37 C. Furthermore, the changes in cell attachment followed changes in the Lewis base component of surface energy. The results indicate that, in contrast to the established paradigm of enhanced cell attachment to surfaces where polymers are above a Lower Critical Solution Temperature (LCST), these novel substrates enable detachment of cells from surfaces at temperatures above a UCST. In turn these responsive materials open new avenues for the use of polymer-modified surfaces to control cell attachment for applications in cell manufacture and regenerative medicine.
Some forms of bovine lactoferrin (bLf) are effective in delaying Clostridioides difficile growth and preventing toxin production. However, therapeutic use of bLf may be limited by protein stability issues. The objective of this study was to prepare and evaluate colon-targeted, pHtriggered alginate microparticles loaded with bioactive bLf and to evaluate their anti-C. difficile defence properties in vitro. Different forms of metal-bound bLf were encapsulated in alginate microparticles using an emulsification/internal gelation method. The microparticles were coated with chitosan to control protein release. In vitro drug release studies were conducted in pH-simulated gastrointestinal conditions to investigate the release kinetics of encapsulated protein. No significant release of metal-bound bLf was observed at acidic pH; however, on reaching simulated colonic pH, most of the encapsulated lactoferrin was released. The application of bLf (5mg/mL) delivered from alginate microparticles to human intestinal epithelial cells (hIECs) significantly reduced the cytotoxic effects of toxins A and B as well as bacterial supernatant on Caco-2 and Vero cells, respectively. These results are the first to suggest that alginate-bLf microparticles show protective effects against C. difficile toxin-mediated epithelial damage and impairment of barrier function in hIECs. The future potential of lactoferrin-loaded alginate microparticles against C. difficile deserves further study.
Novel magnetothermally responsive core–shell microparticles have been synthesized.
Introduction Self expanding metallic stents (SEMS) can resolve obstruction due to colorectal cancer (CRC), enabling subsequent elective rather than emergency surgery. This study compared the outcomes after stenting and subsequent elective surgery versus emergency surgery (ES) for obstructing CRC. Methods Prospectively collected data from a consecutive series of 153 patients with large bowel obstruction secondary to CRC, presenting to a single NHS Trust from April 2010 to March 2017, were retrospectively analysed. Of these, 41 (26.8%) had stenting as a bridge to surgery (SBTS) followed by elective surgery and 112 (73.2%) had ES. Primary outcomes were mortality rates after surgery at 30 days, 90 days and 1 year. Secondary outcomes were the rates of stoma formation and anastomotic leak (both clinical and radiological). Results Thirty-day mortality was 7.3% with SBTS and 12.5% with ES. Ninety-day mortality was 7.3% with SBTS and 17.9% with ES. One-year mortality was 19.5% with SBTS and 32.1% with ES. The anastomotic leak rate was 7.1% with SBTS and 14.0% with ES. The rate of stoma formation was 39.0% with SBTS and 33.0% with ES. With cancers proximal to the splenic flexure excluded, stoma rates were 38.5% with SBTS and 54.2% with ES. Conclusions Without adjustment for confounding variables superiority of SBTS over ES cannot be inferred. But these results suggest SBTS can be a safe alternative to ES and may offer advantages in respect of stoma and leak rates.
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