pH-temperature Responsive Hydrogel-Mediated Delivery of Exendin-4 Encapsulated Chitosan Nanospheres for Sustained Therapeutic Efficacy in Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (T2D) is a chronic, obesity-related, and inflammatory disorder characterize by insulin resistance, inadequate insulin secretion, hyperglycemia, and excessive glucagon secretion. Exendin-4 (EX), a clinically established antidiabetic medication that acts as a glucagon-like peptide-1 receptor agonist, is effective in lowering glucose levels and stimulating insulin secretion while significantly reducing hunger. However, the requirement for multiple daily injections due to EX's short half-life is a significant limitation in its clinical application, leading to high treatment costs and patient inconvenience. To address this issue, an injectable hydrogel system is developed that can provide sustained EX release at the injection site, reducing the need for daily injections. In this study, the electrospray technique is examine to form EX@CS nanospheres by electrostatic interaction between cationic chitosan (CS) and negatively charged EX. These nanospheres are uniformly dispersed in a pH-temperature responsive pentablock copolymer, which forms micelles and undergoes sol-to-gel transition at physiological conditions. Following injection, the hydrogel gradually degraded, exhibiting excellent biocompatibility. The EX@CS nanospheres are subsequently released, maintaining therapeutic levels for over 72 h compared to free EX solution. The findings demonstrate that the pH-temperature responsive hydrogel system containing EX@CS nanospheres can be a promising platform for the treatment of T2D.     

Gelation Kinetics and Mechanical Properties of Thiol-Tetrazole Methylsulfone Hydrogels Designed for Cell Encapsulation

Hydrogel precursors that crosslink within minutes are essential for the development of cell encapsulation matrices and their implementation in automated systems. Such timescales allow sufficient mixing of cells and hydrogel precursors under low shear forces and the achievement of homogeneous networks and cell distributions in the 3D cell culture. The previous work showed that the thiol-tetrazole methylsulfone (TzMS) reaction crosslinks star-poly(ethylene glycol) (PEG) hydrogels within minutes at around physiological pH and can be accelerated or slowed down with small pH changes. The resulting hydrogels are cytocompatible and stable in cell culture conditions. Here, the gelation kinetics and mechanical properties of PEG-based hydrogels formed by thiol-TzMS crosslinking as a function of buffer, crosslinker structure and degree of TzMS functionality are reported. Crosslinkers of different architecture, length and chemical nature (PEG versus peptide) are tested, and degree of TzMS functionality is modified by inclusion of RGD cell-adhesive ligand, all at concentration ranges typically used in cell culture. These studies corroborate that thiol/PEG-4TzMS hydrogels show gelation times and stiffnesses that are suitable for 3D cell encapsulation and tunable through changes in hydrogel composition. The results of this study guide formulation of encapsulating hydrogels for manual and automated 3D cell culture.     

The Mechanical and Biological Performance of Photopolymerized Gelatin-Based Hydrogels as a Function of the Reaction Media

From the first experiments with biomaterials to mimic tissue properties, the mechanical and biochemical characterization has evolved extensively. Several properties can be described, however, what should be essential is to conduct a proper and physiologically relevant characterization. Herein, the influence of the reaction media (RM) and swelling media (SM)–phosphate buffered saline (PBS) and Dulbecco's modified Eagle's medium (DMEM) with two different glucose concentrations–is described in gelatin methacrylamide (GelMA) hydrogel mechanics and in the biological behavior of two tumoral cell lines (Caco-2 and HCT-116). All scaffolds are UV-photocrosslinked under identical conditions and evaluated for mass swelling ratio and stiffness. The results indicate that stiffness is highly susceptible to the RM, but not to the SM. Additionally, PBS-prepared hydrogels exhibited a higher photopolymerization degree according to high resolution magic-angle spinning (HR-MAS) NMR. These findings correlate with the biological response of Caco-2 and HCT-116 cells seeded on the substrates, which demonstrated flatter morphologies on stiffer hydrogels. Overall, cell viability and proliferation are excellent for both cell lines, and Caco-2 cells displayed a characteristic apical-basal polarization based on F-actin/Nuclei fluorescence images. These characterization experiments highlight the importance of conducting mechanical testing of biomaterials in the same medium as cell culture.     

Biodegradable Sodium Alginate/Carrageenan/Cellulose Composite Hydrogel Wound Dressings Containing Herbal Extracts for Promoting Blood Coagulation and Wound Healing

Accelerating the coagulation process and preventing wound infection are major challenges in the wound care process. Therefore, new multifunctional wound dressings with procoagulant, antibacterial, and antioxidant properties have enormous potential for clinical application. In this work, biodegradable hydrogels containing herbal extracts are prepared for wound dressings. First, the active ingredients are extracted from Amaranthus spinosus (A. spinosus) and Rubia cordifolia (R. cordifolia) and added to the hydrogels prepared from microcrystalline cellulose (MCC), carrageenan, and sodium alginate. Then the composite hydrogels are air-dried to obtain the wound dressings. The wound dressings prepared in this work have good biocompatibility and moisture retention. The mechanical properties of the wound dressings are further improved with the addition of MCC. Besides, the wound dressings have excellent procoagulant, antibacterial, and antioxidant properties due to the presence of R. cordifolia extract. Overall, the most effective group of wound dressings with different ingredient formulations reduces clotting time by 75% and largely inhibits bacterial growth. The wound dressings perform well in the animal wound models to promote wound healing. These results indicate that the hydrogel wound dressings prepared in this work have great potential for medical applications.     

Fenugreek hydrogel–agarose composite entrapped gold nanoparticles for acetylcholinesterase based biosensor for carbamates detection

A biosensor was fabricated to detect pesticides in food samples. Acetylcholinesterase was immobilized in a novel fenugreek hydrogel–agarose matrix with gold nanoparticles. Transparent thin films with superior mechanical strength and stability were obtained with 2% fenugreek hydrogel and 2% agarose. Immobilization of acetylcholinesterase on the membrane resulted in high enzyme retention efficiency (92%) and a significantly prolonged shelf life of the enzyme (half-life, 55 days). Transmission electron microscopy revealed that, gold nanoparticles (10–20 nm in diameter) were uniformly dispersed in the fenugreek hydrogel–agarose–acetylcholinesterase membrane. This immobilized enzyme-gold nanoparticle dip-strip system detected various carbamates, including carbofuran, oxamyl, methomyl, and carbaryl, with limits of detection of 2, 21, 113, and 236 nM (S/N = 3), respectively. Furthermore, the fabricated biosensor exhibited good testing capabilities when used to detect carbamates added to various fruit and vegetable samples.     

温敏性纤维素/聚Ν-异丙基丙烯酰胺复合水凝胶的固体核磁共振表征及动力学研究

利用半互穿网络方法将具有温度响应的高分子聚N-异丙基丙烯酰胺( PNIPAM)与天然纤维素复合得到温敏性水凝胶。通过固体核磁共振的1 H,13 C CP/MAS(交叉极化/魔角旋转)和QCP(定量交叉极化)等实验手段对复合凝胶的结构进行了定性及定量研究,并利用固体静态变温核磁共振实验和偶极滤波-自旋扩散实验研究了复合凝胶中PNIPAM分子链段的动力学行为。     

Multicomponent Molecular Orbital–Climbing Image–Nudged Elastic Band Method to Analyze Chemical Reactions Including Nuclear Quantum Effect

To analyze the H/D isotope effects on hydrogen transfer reactions in XHCHCHCHY?XCHCHCHYH (X, Y=O, NH, or CH₂) including the nuclear quantum effect of proton and deuteron, we propose a multicomponent molecular orbital‐climbing image‐nudged elastic band (MC_MO–CI–NEB) method. We obtain not only transition state structures but also minimum‐energy paths (MEPs) on the MC_MO effective potential energy surface by using MC_MO–CI–NEB method. We find that nuclear quantum effect affects not only stationary‐point geometries but also MEPs and electronic structures in the reactions. We clearly demonstrate the importance of including nuclear quantum effects for H/D isotope effect on rate constants (k_H/k_D).     

Role of a high ground-state centrifugal barrier in the breakup of the 31Ne nucleus

An analysis of the breakup of the \begin{document}$ ^{31}{\rm Ne} $\end{document} weakly-bound neutron-halo system on a lead target is presented, considering the \begin{document}$ 2p_{3/2} $\end{document} and \begin{document}$ 1f_{7/2} $\end{document} ground-state configurations. It is shown that a high centrifugal barrier almost wipes out the breakup channel, thus assimilating the breakup of a weakly-bound system to that of a tightly-bound system, and also reduces the range of the monopole nuclear potential. Consequently, a high centrifugal barrier prevents the suppression of the Coulomb-nuclear interference (CNI) peak by weakening couplings to the breakup channel and reducing the range of the monopole nuclear potential, two main factors that would otherwise suppress such a peak. The present study also identifies couplings to the breakup channel and a long-ranged monopole nuclear potential as the main factors that lead to the suppression of the CNI peak. A low centrifugal barrier together with a Coulomb barrier would also effectively prevent the suppression of the CNI peak in proton-halos as reported in the case of the \begin{document}$ ^8{\rm B} $\end{document} proton-halo.     

Synthesis of dual pH- and temperature-sensitive poly(N-isopropylacrylamide-co-acrylic acid)/sewage sludge ash hydrogel with the simultaneously high performance of swelling and deswelling

An advanced dual pH- and temperature-sensitive hydrogel (NASH2.5) was optimally synthesized through modification of N-isopropylacrylamide (NIPAM) hydrogel with introducing 5 mol% acrylic acid (AA) and 2.5 wt% sewage sludge ash (SSA). The swelling kinetic results showed that NASH2.5 exhibited both high equilibrium swelling ratio and swelling rate, which was attributed to the higher porous structure as shown in scanning electron microscope, and the more hydrogen bonding formed inside of the hydrogel as investigated in Fourier transform infrared spectrometer. In addition, its curve was better fitted to the pseudo-second-order model, indicating that the water absorption process was dominated by chemisorption through forming the hydrogen bonding among the water molecules and carboxyl/silanol groups of the hydrogel. Compared with the pure NIPAM hydrogel, the water transport mechanism switched from Case I diffusion to Case II diffusion by introduction of AA and further SSA. Furthermore, through the results of the deswelling kinetics in pH value change (from 9 to 4 and 2, respectively), temperature value change (from 25 to 40, 50, and 60°C, respectively), and dual pH and temperature values changes, NASH2.5 not only presented a high pH sensitivity, but also showed high sensitive to temperature by achieving high water recovery ratio in rapid dehydrated rate. Therefore, the dual stimuli-sensitive hydrogel with the simultaneously high performance of swelling and deswelling would provide a suitable alternative for specific applications such as pollutant adsorption.