Biomacromolecules最新文献

We synthesize four series of novel biodegradable poly(alkylene succinate-ran-caprolactone) random copolyesters using a two-step ring-opening/transesterification and polycondensation process with ε-caprolactone (PCL) as a common comonomer. The second comonomers are succinic acid derivatives, with variations in the number of methylene groups (n_CH2) in the glycol segment, n_CH2 = 2, 4, 8, and 12. The obtained copolyesters were poly(ethylene succinate-ran-PCL) (ES_xCL_y), poly(butylene succinate-ran-PCL) (BS_xCL_y), poly(octamethylene succinate-ran-PCL) (OS_xCL_y), and poly(dodecylene succinate-ran-PCL) (DS_xCL_y). We discovered a new mixed isodimorphic/comonomer exclusion crystallization in ES_xCL_y copolymers. The BS_xCL_y, OS_xCL_y, and DS_xCL_y copolymers display isodimorphic behavior. Our findings revealed a significant variation in the pseudoeutectic point position, from mixed isodimorphism/comonomer exclusion crystallization to isodimorphism with pseudoeutectic point variation from 54% to up to 90%. Moreover, we established a link between the melting temperature depression slope variation and the comonomer inclusion/exclusion balance, providing valuable insights into the complex topic of isodimorphic random copolymers.

We explore the reentrant condensation of polyelectrolytes triggered by multivalent salts, whose phase-transition mechanism remains under debate. We propose a theory to study the reentrant condensation, which separates the electrostatic effect into two parts: a short-range electrostatic gluonic effect because of sharing of multivalent ions by ionic monomers and a long-range electrostatic correlation effect from all ions. The theory suggests that the electrostatic gluonic effect governs reentrant condensation, requiring a minimum coupling energy to initiate the phase transition. This explains why diluted salts with selective multivalency trigger a polyelectrolyte phase transition. The theory also uncovers that strong adsorption of multivalent ions onto ionic monomers causes low-salt concentrations to induce both collapse and reentry transitions. Additionally, we highlight how the incompatibility of uncharged polyelectrolyte moieties with water affects the polyelectrolyte phase behaviors. The obtained results will contribute to the understanding of biological phase separations if multivalent ions bound to biopolyelectrolytes play an essential role.

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.

The healing of infected wounds is challenging for patients. In this paper, a hybrid hydrogel with strong tissue adhesion, self-healing, and antibiosis without antibiotics was developed as a dressing to promote the healing of infected chronic wounds. Acrylamide (PAM) was polymerized with N,N-methylene bis(acrylamide) (BIS) as the substrate, and self-assembled nanoparticles of carboxymethyl chitosan and chlorin e6 (CMCS/Ce6 NPs) trapped with magnesium (Mg²⁺) ions were dispersed in the hydrogel substrate. CMCS/Ce6 NPs provided favorable photodynamic antibiosis via the production of reactive oxygen species (ROS) under NIR irradiation. The hybrid hydrogels exhibited excellent self-healing properties, diverse adhesion, and biocompatibility. The in vivo results indicated that the hybrid hydrogel accelerated wound healing significantly via comprehensive factors of photodynamic antibiosis of CMCS/Ce6 NPs, cell proliferation promotion by Mg²⁺, good bioadhesion, and moisture retention of the PAM hydrogel, which promoted collagen deposition and blood vessel maturation.

This study explores the synthesis and application of artificial zymogens using protein-polymer hybrids to mimic the controlled enzyme activation observed in natural zymogens. Pro-trypsin (pro-TR) and pro-chymotrypsin (pro-CT) hybrids were engineered by modifying the surfaces of trypsin (TR) and chymotrypsin (CT) with cleavable peptide inhibitors utilizing surface-initiated atom transfer radical polymerization. These hybrids exhibited 70 and 90% reductions in catalytic efficiency for pro-TR and pro-CT, respectively, due to the inhibitory effect of the grafted peptide inhibitors. The activation of pro-TR by CT and pro-CT by TR resulted in 1.5- and 2.5-fold increases in enzymatic activity, respectively. Furthermore, the activated hybrids triggered an enzyme activation cascade, enabling amplification of activity through a dual pro-protease hybrid system. This study highlights the potential of artificial zymogens for therapeutic interventions and biodetection platforms by harnessing enzyme activation cascades for precise control of catalytic activity.

Identification of bacterial lectins offers an attractive route to the development of new diagnostics, but the design of specific sensors is complicated by the low selectivity of carbohydrate-lectin interactions. Here we describe a glycopolymer-based sensor array which can identify a selection of lectins with similar carbohydrate recognition preferences through a pattern-based approach. Receptors were generated using a polymer scaffold functionalized with an environmentally sensitive fluorophore, along with simple carbohydrate motifs. Exposure to lectins induced changes in the emission profiles of the receptors, enabling the discrimination of analytes using linear discriminant analysis. The resultant algorithm was used for lectin identification across a range of concentrations and within complex mixtures of proteins. The sensor array was shown to discriminate different strains of pathogenic bacteria, demonstrating its potential application as a rapid diagnostic tool to characterize bacterial infections and identify bacterial virulence factors such as production of adhesins and antibiotic resistance.

Supramolecular peptide hydrogels (SPHs) consist of peptides containing hydrogelators and functional epitopes, which can first self-assemble into nanofibers and then physically entangle together to form dynamic three-dimensional networks. Their porous structures, excellent bioactivity, and high dynamicity, similar to an extracellular matrix (ECM), have great potential in artificial ECM. The properties of the hydrogel are largely dependent on peptides. The noncovalent interactions among hydrogelators drive the formation of assemblies and further transition into hydrogels, while bioactive epitopes modulate cell-cell and cell-ECM interactions. Therefore, SPHs can support cell growth, making them ideal biomaterials for ECM mimics. This Review outlines the classical molecular design of SPHs from hydrogelators to functional epitopes and summarizes the recent advancements of SPHs as artificial ECMs in nervous system repair, wound healing, bone and cartilage regeneration, and organoid culture. This emerging SPH platform could provide an alternative strategy for developing more effective biomaterials for tissue engineering.

Bacterial infections in chronic wounds, such as bedsores and diabetic ulcers, present significant healthcare challenges. Excessive antibiotic use leads to drug resistance and lacks precision for targeted wound treatment. Our study introduces an innovative solution: a near-infrared (NIR) and pH dual-responsive hydrogel patch incorporating regenerated silk fibroin (RSF) and molybdenum dioxide (MoO₂) nanoparticles (NPs), offering enhanced mechanical properties, precise drug release, and superior antibacterial efficacy. The dual-responsive hydrogel patch allows for precise control over antibiotic release triggered by NIR light and pH fluctuations, enabling tailored treatment for infected wounds. First, the pH-responsive characteristic matches the alkaline environment of the infected wound, ensuring on-demand antibiotic release. Second, NIR exposure accelerates antibiotic release, enhancing wound healing and providing additional antibacterial effects. Additionally, the patch further blocks bacterial infection, promotes wound repair, and degrades in sync with the healing process, further bolstering the efficacy against wound infections.

A drug delivery system based on silybin-conjugated chitosan (CS-SB) polymeric micelles was developed to improve the oral absorption of doxorubicin (DOX). SB was grafted to CS via succinic acid, and CS-SB was identified by ¹H NMR and FT-IR. The DOX-loaded micelles were prepared by self-assembly, and the characteristics of micelles, including a small particle size of 167.8 ± 2.3 nm, a high drug loading capacity of 8.59%, and a low critical micelle concentration of 1.3 × 10^-5 g/mL, were demonstrated. The micelles showed oral bioavailability of up to 193% versus DOX·HCl. The cytotoxicity test showed the biosafety of CS-SB and the potential of reductive DOX-induced cardiotoxicity. The inhibition of P-gp efflux and CYP3A4 enzyme in CS-SB micelles was confirmed by cellular uptake and enzyme activity inhibition tests. The endocytosis process of micelles was revealed by an endocytosis inhibition test. The findings exhibited the potential of CS-SB micelles in drug delivery.

The present work consist of the synthesis of photo-cross-linkable materials, based on unsaturated polyesters (UPs), synthesized from biobased monomers from renewable sources such as itaconic acid and 1,4-butanediol. The UPs were characterized to assess the influence of polycondensation reaction temperature and cross-linking time on their final properties. For this purpose, different UV irradiation exposure periods were tested. Homogeneous, uniform, and transparent films were obtained after 1, 3, and 5 min of UV exposure. These cross-linked films were then characterized. All materials presented high gel content, which was dependent on the reaction's temperature. The thermal behaviors of the UPs were shown to be similar. In vitro hydrolytic degradation tests showed that the materials can undergo degradation in phosphate-buffered saline (PBS) at pH 7.4 and 37 °C, ensuring their biodegradability over time. Finally, to assess the applicability of the polyesters as biomaterials, their cytocompatibility was determined by using human dermal fibroblasts.