ABC block copolymer micelles driving the thermogelation:Scattering, imaging and spectroscopy

Thermoresponsive polymers have attracted much scientific attention due to their capacity for temperature-driven hydrogel formation. For biomedical applications, such as drug delivery, this transition should be tuned below body temperature to facilitate controlled and targeted drug release. We have recently developed a thermoresponsive polymer that forms gel at low concentrations (2 w/w%) in aqueous media and offers a cost-effective alternative to thermoresponsive systems currently being applied in clinics. This polymer is an ABC triblock terpolymer, where A, B, and C correspond to oligo(ethylene glycol) methyl ether methacrylate with average Mn 300 g mol−1 (OEGMA300), n-butyl methacrylate (BuMA), and di(ethylene glycol) methyl ether methacrylate (DEGMA). To investigate the self-assembly and the gelation mechanism in diluted solutions, we used small-angle neutron scattering (SANS) on 1 w/w% (below the gelation concentration) and 5 w/w% solutions (above the gelation concentration). As a comparison, we also investigated the solutions of the most studied thermoresponsive polymer, namely, Pluronic F127, an ABA triblock bipolymer made of ethylene glycol (A) and propylene glycol (B) blocks. SANS revealed that the in-house synthesised polymer forms elliptical cylinders, whose length increases significantly with temperature. In contrast, Pluronic F127 solutions form core-shell spherical micelles, which slightly elongate with temperature. Transmission electron microscopy images support the SANS findings, with tubular/worm structures being present. Variable-temperature circular dichroism (CD) and proton nuclear magnetic resonance (1H NMR) spectroscopy experiments reveal insights on the tacticity, structural changes, and molecular origin of the self-assembly

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Regular and Inverse Polyampholyte Hydrogels: A Detailed Comparison

Two series of polyampholyte (PA) hydrogels were prepared via reversible addition–fragmentation chain transfer polymerization, followed by removal of the protecting group of the acidic monomer repeating units (methacrylic acid, MAA), which were common in both series. One series bore (pyridin-2-yl)­methyl methacrylate (2PyMMA) basic monomer repeating units, whereas the second series carried basic monomer repeating units of 2-(dimethylamino)­ethyl methacrylate (DMAEMA). The 2PyMMA-MAA combination in the first series had the peculiarity that the basic 2PyMMA units were more acidic than the MAA units, thus resulting in so-called “inverse PA” hydrogels. The DMAEMA-MAA pair in the other series led to “regular PA” hydrogels in which the basicity and acidity of the two types of units were in the conventional sense. The swelling and hydrogen ion equilibrium properties of the two series were explored and thoroughly compared to each other. The aqueous degrees of swelling of inverse PA hydrogels were found to be generally lower than those of the regular ones due to the more hydrophobic character of the 2PyMMA basic units employed in inverse compared to those (DMAEMA) in regular PA gels. The aqueous swelling pH-profiles in both series of PA hydrogels presented a minimum. However, this swelling minimum was deeper and wider in the case of inverse PA hydrogels, because of the greater hydrophobicity of the basic (2PyMMA) units and the greater difference in the effective p<i>K</i> values of the two types of units (2PyMMA-MAA) in inverse PA hydrogels, respectively. This larger separation of the p<i>K</i>’s in inverse PA gels was directly confirmed from the hydrogen ion titration curves of all the gels. Finally, the isoelectric points of inverse PA hydrogels possessed no detectable dependence on PA composition, which must be contrasted to the strong composition-dependence of the isoelectric points of regular PAs

Thermoresponsive tetrablock terpolymers: effect of architecture and composition on Gelling behavior

Thermoresponsive gels are an exciting class of materials with many bioapplications, like tissue engineering and drug delivery, but they are also used in formulation industry and 3-D printing. For these applications to be feasible, the gelation temperature must be tailored. Here, it is reported how the gelation temperature is affected and can be tailored by varying the architecture of tetrablock terpolymers. Specifically, 15 copolymers based on penta(ethylene glycol) methyl ether methacrylate (PEGMA, A block), n-butyl methacrylate (BuMA, B block), and the thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA, C block) were synthesized using group transfer polymerization. Nine tetrablock copolymers of varying architectures, and one triblock copolymer for comparison, with constant molar mass and composition were fabricated. Specifically, the polymers that were investigated are (i) three polymers that contain two A blocks (ABCA, ABAC, and ACAB), (ii) three polymers that contain two B blocks (BACB, BABC, and ABCB), (iii) three polymers that contain two C blocks (CABC, CACB, and ACBC), and (iv) one ABC triblock terpolymer that was synthesized as the control polymer. Then, the five more promising architectures were chosen, and five more polymers with a slightly different composition were synthesized and characterized. Interestingly, it was demonstrated that the block position (architecture) has a significant effect on self-assembly (micelle formation), cloud point, and the rheological and gelling properties of the polymers with two of the tetrablocks showing promise as injectable gels. Specifically, the ACBC terpolymer with 20–30–50 w/w % PEGMA–BuMA–DMAEMA formed gels at at lower concentration but at higher temperatures than the ABC triblock copolymer that was synthesized as a control. On the other hand, the BABC terpolymer with 30–35–45 w/w % PEGMA–BuMA–DMAEMA formed gels at the same concentrations as the ABC triblock control polymer but at lower and more desirable temperatures, slightly below body temperature

Unveiling the Rational Development of Stimuli-Responsive Silk Fibroin-Based Ionogel Formulations

We present an approach for the rational development of stimuli-responsive ionogels which can be formulated for precise control of multiple unique ionogel features and fill niche pharmaceutical applications. Ionogels are captivating materials, exhibiting self-healing characteristics, tunable mechanical and structural properties, high thermal stability, and electroconductivity. However, the majority of ionogels developed require complex chemistry, exhibit high viscosity, poor biocompatibility, and low biodegradability. In our work, we overcome these limitations. We employ a facile production process and strategically integrate silk fibroin, the biocompatible ionic liquids (ILs) choline acetate ([Cho][OAc]), choline dihydrogen phosphate ([Cho][DHP]), and choline chloride ([Cho][Cl]), traditional pharmaceutical excipients, and the model antiepileptic drug phenobarbital. In the absence of ILs, we failed to observe gel formation; yet in the presence of ILs, thermoresponsive ionogels formed. Systems were assessed via visual tests, transmission electron microscopy, confocal reflection microscopy, dynamic light scattering, zeta potential and rheology measurements. We formed diverse ionogels of strengths ranging between 18 and 642 Pa. Under 25 °C storage, formulations containing polyvinylpyrrolidone (PVP) showed an ionogel formation period ranging over 14 days, increasing in the order of [Cho][DHP], [Cho][OAc], and [Cho][Cl]. Formulations lacking PVP showed an ionogel formation period ranging over 32 days, increasing in the order of [Cho][OAc], [Cho][DHP] and [Cho][Cl]. By heating from 25 to 60 °C, immediately following preparation, thermoresponsive ionogels formed below 41 °C in the absence of PVP. Based on our experimental results and density functional theory calculations, we attribute ionogel formation to macromolecular crowding and confinement effects, further enhanced upon PVP inclusion. Holistically, applying our rational development strategy enables the production of ionogels of tunable physicochemical and rheological properties, enhanced drug solubility, and structural and energetic stability. We believe our rational development approach will advance the design of biomaterials and smart platforms for diverse drug delivery applications