Nature provides many examples of soft gel-like materials where performance is determined by tuning time-dependent mechanical properties with dynamic bonding interactions between biomacromolecules.[1] Accordingly, synthetic gels that contain dynamic bonding interactions have undergone intense investigation in fundamental and applied material science. The balance of solid-like and fluid-like behavior in these gel networks results from the binding equilibrium of reversible crosslinks between polymer chains. [2][3][4][5] Contemporary research on gels has focused on self-assembled systems [6][7][8][9][10][11][12][13][14][15] usually exploiting hydrogen bonding interactions. However, gels crosslinked with reversible covalent bonding chemistries [16][17][18] would provide an energetically favorable, [19] specific and controlled mechanism for engineering functional dynamic networks. [20][21][22][23][24] We have synthesized hydrogel networks that form in the physiological pH range by the reversible covalent interaction of polymer-bound phenylboronic acid and salicylhydroxamic acid (Fig. 1). These gels demonstrate a spectrum of pH-dependent viscoelastic behavior that can be controlled by the chemical composition of the polymer backbone. Moreover, the reversible crosslinks allow these networks to restructure dynamically and self-heal after mechanical disruption. Phenylboronate-salicylhydroxamate gels provide a new class of self-assembled materials enabling precise control over network viscoelasticity and pH responsiveness. Water-soluble polymers containing 10 mol % phenylboronic acid (PBA) or 10 mol % salicylhydroxamic acid (SHA) were synthesized by free-radical polymerization of functionalized monomers with 2-hydroxypropylmethacrylamide (HPMA) or acrylic acid (AA; Fig. 1b). When aqueous solutions of PBA and SHA containing polymers are mixed at physiological pH, the PBA and SHA moieties associate to form coordinate covalent bonds [25][26][27] (PBA-SHA; Fig. 1a). c Figure 1. Self-healing, viscoelastic hydrogel networks are formed using reversible covalent crosslinking chemistry. a) Covalent bonds that form between polymer-bound phenylboronic acid (PBA) and salicylhydroxamic acid (SHA) have pH-dependent binding equilibria that are shifted to the uncrosslinked state under acidic conditions. b) Linear water-soluble polymers containing either PBA or SHA moieties can be easily synthesized with different polymer backbones (e.g., 2-hydroxypropylmethacrylamide (HPMA) or acrylic acid (AA)) of controlled molar feed ratios. Two degrees of substitution for each polymer were made with x = 90 mol % or 95 mol % (see Supporting Information Table S1 for details). c) When PBA-and SHA-containing polymer solutions are mixed under physiological conditions, a reversible semisolid gel forms due to the dynamic restructuring of the crosslinked gel network. The specific pH range at which gels behave reversibly can be controlled with choice of polymer backbone (in b); HPMA-based PBA-SHA crosslinked gels are reversible at mildly acidic pH (pH 4-5) whi...

BACKGROUND An intraoperative concurrence of mean arterial pressure <75 mmHg, minimum alveolar concentration <0.8 and bispectral index <45 has been termed a “triple low” state. An association between triple low and postoperative mortality has been reported, but was not replicated in a subsequent study. We pooled existing data from clinical trials to further evaluate the purported association in an observational study. METHODS This retrospective observational study included 13,198 patients from three clinical trials: B-Unaware, BAG-RECALL, and Michigan Awareness Control Study. Patients with greater than 15 not necessarily consecutive minutes of triple low were propensity matched to controls with similar characteristics and comorbidities. A multivariable Cox proportional hazards model was used to evaluate the association between triple low duration and postoperative mortality. RESULTS Thirty-day mortality was 0.8% overall, 1.9% in the triple low cohort, and 0.4% in the non-triple low cohort (Odds Ratio (OR) [95% Confidence Interval (CI)] = 5.16 [4.21 to 6.34]). After matching and adjusting for comorbidities, cumulative duration of triple low was significantly associated with an increased risk of mortality at 30 days (Hazard Ratio (HR) 1.09 [1.07 to 1.11] per 15 minutes) and 90 days (HR 1.09 [1.08 to 1.11] per 15 minutes). CONCLUSIONS There is a weak independent association between the triple low state and postoperative mortality, and our propensity-matched analysis does not suggest that this is an epiphenomenon.