On the electrical conductivity of alginate hydrogels

Hydrogels have been extensively used in the field of biomedical applications, offering customisable natural, synthetic or hybrid materials, particularly relevant in the field of tissue engineering. In the bioelectronics discipline hydrogels are promising mainly as sensing platforms with or without encapsulated cells, showing great potential in healthcare and medicine. However, to date there is little data in the literature which characterises the electrical properties of tissue engineering materials which are relevant to bioelectronics. In this work we present electrical characterization of alginate hydrogels, a natural polysaccharide, using a four-probe method similar to electrical impedance spectroscopy. The acquired conductance data show distinct frequency dependent features that change as a function of alginate and crosslinker concentration reflecting ion kinetics inside the measured sample. Furthermore, the presence of NIH 3T3 fibroblasts encapsulated in the hydrogels matrix was found to alter the artificial tissue’s electrical properties. The method used provides valuable insight to the frequency dependent electrical response of the resulting systems. It is hoped that the outcomes of this research will be of use in the development of cell/electronic interfaces, possibly towards diagnostic biosensors and therapeutic bioelectronics

Transient bioimpedance monitoring of mechanotransduction in artificial tissue during indentation

Mechanotransduction is of fundamental importance in cell physiology, facilitating sensing in touch and hearing as well as tissue development and wound healing. This study used an impedance sensor to monitor the effective resistance and permittivity of artificial tissues, alginate hydrogel with encapsulated fibroblasts, which were kept viable through the use of a bespoke microfluidic system. The observed transient impedance responses upon the application of identical compressive normal loads differed between acellular hydrogels and hydrogels in which fibroblasts were encapsulated. These differences resulted from changes in the conductivity and permeability of the hydrogel due to the presence of the encapsulated fibroblasts, and transient changes in ion concentrations due to mechanotransduction effects

Anisotropic dehydration of hydrogel surfaces

Efforts to develop tissue-engineered skin for regenerative medicine have explored natural, synthetic, and hybrid hydrogels. The creation of a bilayer material, with the stratification exhibited by native skin is a complex problem. The mechanically robust, waterproof epidermis presents the stratum corneum at the tissue/air interface, which confers many of these protective properties. In this work we explore the effect of high temperatures on alginate hydrogels, which are widely employed for tissue engineering due to their excellent mechanical properties and cellular compatibility. In particular, we investigate the rapid dehydration of the hydrogel surface which occurs following local exposure to heated surfaces with temperatures in the range 100-200 oC. We report the creation of a mechanically strengthened hydrogel surface, with improved puncture resistance and increased coefficient of friction, compared to the unheated surface. The use of a mechanical restraint during heating promoted differences in the rate of mass loss; the rate of temperature increase within the hydrogel, in the presence and absence of restraint, is simulated and discussed. It is hoped that the results will be of use in the development of processes suitable for preparing skin-like analogues; application areas could include wound healing and skin restoration

ADIPOR1 (adiponectin receptor 1)

Review on ADIPOR1 (adiponectin receptor 1), with data on DNA, on the protein encoded, and where the gene is implicated

Mechanical properties of alginate hydrogels manufactured using external gelation

Alginate hydrogels are commonly used in biomedical applications such as scaffolds for tissue engineering, drug delivery, and as a medium for cell immobilization. Multivalent cations are often employed to create physical crosslinks between carboxyl and hydroxyl moieties on neighbouring polysaccharide chains, creating hydrogels with a range of mechanical properties. This work describes the manufacture and characterisation of sodium alginate hydrogels using the divalent cations Mg2+, Ca2+ and Sr2+ to promote gelation via non-covalent crosslinks. The gelation time and Young’s modulus are characterised as a function of cation and alginate concentrations. The implications of this work towards the use of environmental elasticity to control stem cell differentiation are discussed

Active screen plasma nitriding enhances cell attachment to polymer surfaces

Active screen plasma nitriding (ASPN) is a well-established technique used for the surface modification of materials, the result of which is often a product with enhanced functional performance. Here we report the modification of the chemical and mechanical properties of ultra-high molecular weight poly(ethylene) (UHMWPE) using 80:20 (v/v) N2/H2 ASPN, followed by growth of 3T3 fibroblasts on the treated and untreated polymer surfaces. ASPN-treated UHMWPE showed extensive fibroblast attachment within 3 h of seeding, whereas fibroblasts did not successfully attach to untreated UHMWPE. Fibroblast coated surfaces were maintained for up to 28 days, monitoring their metabolic activity and morphology throughout. The chemical properties of the ASPN-treated UHMWPE surface were studied using X-ray photoelectron spectroscopy, revealing the presence of C N, C N, and C N chemical bonds. The elastic modulus, surface topography, and adhesion properties of the ASPN-treated UHMWPE surface were studied over 28 days during sample storage under ambient conditions and during immersion in two commonly used cell culture media

Application of the method of auxiliary sources in optical diffraction microscopy

The Method of Auxiliary Sources is used for characterisation of grating defects. Grating profiles are characterised by best fit matching of a library of diffraction efficiencies with numerical simulated diffraction efficiencies with defects. It is shown that the presented method can solve the inverse problem with an accuracy usually thought to require rigorous electromagnetic theories

Clinical and genetic predictors of weight gain in patients diagnosed with breast cancer

Background: Post-diagnosis weight gain in breast cancer patients has been associated with increased cancer recurrence and mortality. Our study was designed to identify risk factors for this weight gain and create a predictive model to identify a high-risk population for targeted interventions. Methods: Chart review was conducted on 459 breast cancer patients from Northwestern Robert H. Lurie Cancer Centre to obtain weights and body mass indices (BMIs) over an 18-month period from diagnosis. We also recorded tumour characteristics, demographics, clinical factors, and treatment regimens. Blood samples were genotyped for 14 single-nucleotide polymorphisms (SNPs) in fat mass and obesity-associated protein (FTO) and adiponectin pathway genes (ADIPOQ and ADIPOR1). Results: In all, 56% of patients had >0.5 kg m–2 increase in BMI from diagnosis to 18 months, with average BMI and weight gain of 1.9 kg m–2 and 5.1 kg, respectively. Our best predictive model was a primarily SNP-based model incorporating all 14 FTO and adiponectin pathway SNPs studied, their epistatic interactions, and age and BMI at diagnosis, with area under receiver operating characteristic curve of 0.85 for 18-month weight gain. Conclusion: We created a powerful risk prediction model that can identify breast cancer patients at high risk for weight gain

Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial

Elacestrant; Càncer de mamaElacestrant; Cáncer de mamaElacestrant; Breast cancerPURPOSE Patients with pretreated estrogen receptor (ER)–positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer have poor prognosis. Elacestrant is a novel, oral selective ER degrader that demonstrated activity in early studies. METHODS This randomized, open-label, phase III trial enrolled patients with ER-positive/HER2-negative advanced breast cancer who had one-two lines of endocrine therapy, required pretreatment with a cyclin-dependent kinase 4/6 inhibitor, and ≤ 1 chemotherapy. Patients were randomly assigned to elacestrant 400 mg orally once daily or standard-of-care (SOC) endocrine monotherapy. Primary end points were progression-free survival (PFS) by blinded independent central review in all patients and patients with detectable ESR1 mutations. RESULTS Patients were randomly assigned to elacestrant (n = 239) or SOC (n = 238). ESR1 mutation was detected in 47.8% of patients, and 43.4% received two prior endocrine therapies. PFS was prolonged in all patients (hazard ratio = 0.70; 95% CI, 0.55 to 0.88; P = .002) and patients with ESR1 mutation (hazard ratio = 0.55; 95% CI, 0.39 to 0.77; P = .0005). Treatment-related grade 3/4 adverse events occurred in 7.2% receiving elacestrant and 3.1% receiving SOC. Treatment-related adverse events leading to treatment discontinuations were 3.4% in the elacestrant arm versus 0.9% in SOC. Nausea of any grade occurred in 35.0% receiving elacestrant and 18.8% receiving SOC (grade 3/4, 2.5% and 0.9%, respectively). CONCLUSION Elacestrant is the first oral selective ER degrader demonstrating a significant PFS improvement versus SOC both in the overall population and in patients with ESR1 mutations with manageable safety in a phase III trial for patients with ER-positive/HER2-negative advanced breast cancer

TGFBR1*6A and Int7G24A variants of transforming growth factor-β receptor 1 in Swedish familial and sporadic breast cancer

Two common variants in transforming growth factor-β receptor 1 (TGFBR1), TGFBR1*6A and Int7G24A, A allele, have been shown to act as low-penetrance tumour susceptibility alleles in several common cancers, including breast cancer. We evaluated the TGFBR1 9A/6A and Int7G24A variant frequencies in two breast cancer cohorts; a population-based cohort of breast cancer with defined family history (n=459) and in breast cancer patients from a familial cancer clinic (n=340) and in 856 controls from the Stockholm region. The familial patients from both cohorts were further divided into high- and low-risk familial breast cancer based on pedigree analysis. There was no overall association with either variant and breast cancer risk. The TGFBR1*6A allelic frequency was, however, higher in low-risk familial breast cancer (0.138), compared to controls (0.106; P=0.04). No significant difference was found in the high-risk familial (0.102) or sporadic cases (0.109; P=0.83 and 0.83, respectively). TGFBR1*6A carrier status was further associated with a high-grade sporadic breast cancer (odds ratio: 2.27; 95% confidence interval: 1.01–5.11; P=0.049). These results indicate that the TGFBR1*6A variant may be associated with an increased risk of low-risk familial breast cancer and might be a marker for poorly differentiated breast cancer. The Int7G24A variant was not associated with breast cancer risk or clinical presentation of the disease including prognosis in our material