Biomacromolecules最新文献

The number of methylene groups between strongly interacting functional groups within polymer repeating units induces even-odd effects on thermal and mechanical properties. However, detailed studies correlating the even-odd effect with structural changes are still lacking. In this work, we establish correlations between the structure and thermal properties of poly(ester amide)s containing long alkyl chain lengths. The even-odd effect impacts the thermal properties, including the melting temperature and crystallinity degree. It influences the spherulitic morphology of poly(ester amide)s, controlling the appearance of banding. We demonstrate that even-odd effects in poly(ester amides)s persist even with 27 CH₂ groups within the repeating unit, an effect due to strong hydrogen bonds caused by the amide groups. Our X-ray studies reveal that the even-odd effect originates from changes in the crystalline structure of the materials. This work helps elucidate the role of strong intermolecular interactions (i.e., hydrogen bonding) on the even-odd effect in long-chain poly(ester amides).

Here, we present a modular synthesis as well as physicochemical and biological evaluation of a new series of amphiphilic dendrons carrying triphenylphosphonium groups at their periphery. Within the series, the size and mutual balance of lipophilic and hydrophilic domains are systematically varied, changing the dendron shape from cylindrical to conical. In physiological solution, the dendrons exhibit very low critical micelle concentrations (2.6-4.9 μM) and form stable and uniform micelles 6-12 nm in diameter, depending on dendron shape; the results correlate well with molecular dynamics simulations. The compounds show relatively high cytotoxicity (IC₅₀ 1.2-21.0 μM) associated with micelle formation and inversely related to the size of assembled particles. Depending on their shape, the dendrons show promising results in terms of dendriplex formation and antibacterial activity. In addition to simple amphiphilic dendrons, a fluorescently labeled analogue was also prepared and utilized as an additive visualizing the dendron's cellular uptake.

Molecular dynamics (MD) simulations were conducted to investigate the hydrogen-bond (H-bond) structure and its impact on the tensile strength of hydrated amorphous cellulose. The study identifies a stable intramolecular H-bond between the hydroxyl group at position 3 and the ether oxygen at position 5 (OH3···O5). Intermolecularly, the hydroxyl groups at positions 2 (OH2) and 6 (OH6) form stable H-bonds. Young's modulus, maximum tensile strength, and corresponding strain were calculated as functions of moisture content, while the H-bond network, water cluster formation, and cellulose chain orientation during tensile simulations were analyzed to elucidate mechanical properties. The substitution effect of cellulose on Young's modulus is also examined, revealing that the substitution of OH3 for a hydrophobic group minimally affects Young's modulus, but substitutions at OH2 and OH6 significantly reduce tensile strength due to their roles as key intermolecular H-bond donor sites.

This work presents supramolecular coassembled nucleobase copolymers with transitional morphologies upon pH changes (from 7.4 to 10). Uracil- and adenine-containing copolymers were prepared by RAFT, which allowed us to finely tailor the polymerization degree and the composition. The coassembled formulations prepared in an aqueous buffer at two distinct pH (7.4 and 10) formed spherical morphologies at physiological pH. The increase of the pH induced the apparition of various large, irreversible anisotropic supramolecular architectures. Isothermal titration calorimetry revealed that the coassembly at pH 7.4 was mainly guided by H-bonds between complementary nucleobases, while the experiments conducted at pH 10 showed that the assemblies were mainly driven by hydrophobic interactions. These results highlight that the nature of supramolecular interactions (H-bonds or hydrophobic interactions) has a great influence on the morphology of nucleobase-containing coassemblies when changing the pH. These findings may provide further perspectives in the field of advanced nanomaterials.

An intelligent insulin delivery system targeting intestinal absorption and glucose responsiveness can enhance the bioavailability through oral insulin therapy, offering promising diabetes treatment. In this paper, a glucose and pH dual-response polymer hydrogel using carboxymethyl agarose modified with 3-amino-phenylboronic acid and l-valine (CPL) was developed as an insulin delivery carrier, exhibiting excellent biocompatibility and effective insulin encapsulation. The insulin encapsulated in the hydrogel (Ins-CPL) was released in a controlled manner in response to the in vivo stimulation of blood glucose and pH levels with higher levels of intracellular uptake and utilization of insulin in the intestinal environment simultaneously. Notably, the Ins-CPL hydrogel effectively regulated blood sugar in diabetic rats over a long period by simulating endogenous insulin, responding to changes in plasma pH and glucose levels, and overcoming the intestinal epithelium barrier. This indicates a significant boost in oral insulin bioavailability and broadens its application prospects.

Biodegradable polymers from bioresources are highly in demand for the development of sustainable polymer platforms for commodity plastics and in the biomedical field. Here, an elegant one-pot synthetic strategy is developed, for the first time, to access unexplored hybrid polymers from two naturally abundant resources: carbohydrates (sugars) and l-amino acids. A bottleneck in the synthetic strategy is overcome by tailor-making d-mannitol-based six- and five-membered bicyclic acetalized diols, and their structures are confirmed by single-crystal X-ray diffraction and 2D NMR spectroscopy. l-Amino acids are converted into ester-urethane functional monomers, and they are polymerized with sugar-diols under solvent-free melt polycondensation to yield biodegradable poly(ester-urethane)s. Acid-catalyzed deprotection yielded amphiphilic polymers having exclusively alternating residues of sugar and l-amino acid in the polymer backbone. The polymer is self-assembled into 200 ± 10 nm sized nanoparticles that can encapsulate fluorescent dyes, are nontoxic to cells up to 250 μg/mL, and are readily endocytosed for lysosomal enzymatic biodegradation at the cellular level.

Silk fibers have good biocompatibility and mechanical properties, which make them attractive in biomaterial applications as well as textile industries. It is believed that the superior mechanical property is associated with the crystalline β-sheet structure in the fiber; but a deeper understanding of the structure-property relationship is still needed for full exploitation of its physical properties. Especially, accurate information on hydrogen-bonding interactions within β-sheet domains at the nanoscale and their spatial distributions at the mesoscale are critically needed. In this study, we demonstrate the selective detection of crystalline β-sheet domains in Bombyx mori silk fiber using sum frequency generation (SFG) spectroscopy and its use to determine the angular distribution of the β-sheet crystallites with respect to the fiber axis. Numerical simulations of the SFG signal of the amide-I band were carried out using tensors based on the B2 symmetry of the D₂ point group and compared with experimental data. This comparison found that the crystalline β-sheet domains are aligned along the fiber axis with a standard deviation of ∼27° and parallel to the fiber surface with a standard deviation of ∼5°. It was also found that the amide bands in the SFG spectra cannot be fully explained with the assumption that the crystalline β-sheet vibrations can be described with the D₂ point group. Being able to monitor the amide group vibrations sensitive to both interchain hydrogen bonding and crystallite orientations, SFG analysis has a potential to unveil the structure-mechanical property relationship that may not be readily assessable with other characterization techniques.

Polyproline is a unique thermoresponsive polymer characterized by large thermal and conformational hysteresis. This article employs polyproline-based double hydrophilic block copolymers (PNIPAM_n-b-PLP_m) to gain insight into polyproline's thermoresponsive mechanism. The amine-terminated poly(N-isopropylacrylamide) (NH₂-PNIPAM_m) was used as the macroinitiator for ring-opening polymerization of proline-NCA monomers, resulting in various block copolymers (PNIPAM_n-b-PLP_m) with varying PLP block lengths. Block copolymers' thermal phase transitions were compared with their homopolymer counterparts using turbidimetry, variable-temperature NMR, dynamic light scattering, and circular dichroism spectroscopy. These experiments revealed that regardless of their compositions, all block copolymers exhibited a two-stage collapse (T_CP(PLP) > T_CP(PNIPAM)) during the heating cycle. In contrast, only one clearing temperature (T_CL) was observed during cooling. The observed clearing temperature is closely correlated to the clearing temperature of PNIPAM blocks, suggesting the role of water-soluble PNIPAM blocks in resolving the PLP blocks. Moreover, thermal and conformational hysteresis related to the polyproline block is significantly suppressed in the presence of a PNIPAM block. Linking PNIPAM blocks has two significant effects on PLP segments' thermoresponsive behavior. For example, during the heating cycle, the precollapsed PNIPAM chains (as T_CP(PNIPAM) < T_CP(PLP)) prevent orderly aggregation within the PLP block. Meanwhile, during the cooling cycle below the clearing temperature of the PNIPAM block, the PNIPAM chains impart water solubility (as T_CL(PNIPAM) > T_CL(PLP)) to the collapsed PLP chains. Overall, the PNIPAM block imparts water solubility and perturbs PLP chains to form the native aggregate structure, suppressing the hysteresis effect. Accordingly, the large thermal and conformational hysteresis associated with native PLP chains appears to result from a noninterfering aggregation above the critical temperature.

Copolymers of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) are widely used in biomedical applications. As inactive ingredients in formulations, tracking their degradation byproducts in vivo stands as a major challenge but is a pivotal endeavor to ensure safety and further progress in clinical stages. Current bioanalytical methods used to monitor this degradation lack sensitivity and quantification precision. This study introduces a cost-effective synthetic route for ¹³C-labeled PEG-PLA copolymers, combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), to monitor their in vitro and ex vivo degradation. Incorporating ¹³C isotopes into copolymers significantly enhances MALDI-TOF sensitivity, allowing for precise detection of degradation products at exceedingly low concentrations. We demonstrate the ability to trace ¹³C-labeled PEG-PLA in complex biological media (urine, plasma) at concentrations 100 times lower than labeled PEG-PLA. Our results pave the way toward ultrasensitive in vivo tracking and elucidation of in vivo fate of this widely investigated polymer family.

Hemorrhage is a significant medical problem that has been an active area of research over the past few decades. The human body has a complex response to bleeding that leads to blood clot formation and hemostasis. Many biomaterials based on various biomacromolecules have been developed to either accelerate or improve the body's natural response to bleeding. This review examines the mechanisms of hemostasis, types of bleeding, and the in vitro or in vivo models and techniques used to study bleeding and hemostatic materials. It provides a detailed overview of the diverse hemostatic materials, including those that are highly absorbent, wet adhesives, and those that accelerate the biochemical cascade of blood clotting. These materials are currently marketed, under preclinical testing, or being researched. In exploring the latest advancements in hemostatic technologies, this paper highlights the potential of these materials to significantly improve bleeding control in clinical and emergency situations.