Macromolecular bioscience最新文献

Herein, the micro-porous polylactic acid coating applied on the surface of the cylindrical substrate is fabricated by a novel in situ pore-formation strategy based on the combinational effect of breath figure (BF) and vapor-induced phase separation (VIPS) processes. Under the condition of high environmental humidity, solvent pair of chloroform and dimethylformamide is employed for post-treatment onto pre-formed PLA coating to induce the pore-formation following the mechanism of BF and VIPS, respectively. A composite porous structure with both cellular-like and bi-continuous network morphologies is obtained. By tunning the experimental factors including the ratio of the solvent pair, environmental humidity, and temperature, morphological manipulation upon the pore morphology can be facilely achieved based on the control of mechanism transition between BF and VIPS. Paclitaxel is used as a model drug and loaded into the porous coating by the wicking effect of post-immersion. Coatings with different morphological features show varying drug loading and release capacities. The 28-day release test reveals dynamic release profiles between different coating samples, with the total release rate ranging from 35.70% to 79.96%. Optimal loading capacity of 19.28 µg cm^-2 and 28-day release rate of 35.70% are achieved for the coating with composite BF-VIPS structure. This research established a cost-efficient strategy with high flexibility in the structural manipulation concerning the construction of drug-eluting coating with the feature of manipulative drug delivery.

Numerous synthetic polymers, imitating natural antimicrobial peptides, have demonstrated potent antimicrobial activity, positioning them as potential candidates for new antimicrobial drugs. However, the high activity of these molecules often comes at the cost of elevated toxicity against eukaryotic organisms. In this study, a series of cationic ionenes with varying molecular weights to assess the influence of polymer chain length on ionene activity is investigated. To enhance polymer antimicrobial activity and limit toxicity a PEG side chain is introduced into the repeating unit. The resulting molecules consistently exhibited high activity against three model organisms: E. coli, S. aureus and C. albicans. The incorporation of side PEG chain improves antifungal properties and biocompatibility, regardless of molecular weight. The most important finding of this work is that the reduction of polymer molecular mass led to increased antifungal activity and reduced cytotoxicity against HMF and MRC-5 cell lines simultaneously. As a result, the best-performing molecules reported herein displayed minimal inhibitory concentrations (MIC) as low as 2 and 0.0625 µg mL¹ for C. albicans and C. tropicalis respectively, demonstrating exceptional selectivity. It is plausible that some of described herein molecules can serve as potential lead candidates for new antifungal drugs.

Enzymes play a vital role in synthesizing complex biological molecules like hyaluronic acid (HA). Immobilizing enzymes on support materials is essential for their efficient use and reuse in multiple cycles. Microgels, composed of cross–linked, highly swollen polymer networks, are ideal for enzyme uptake owing to their high porosity. This study demonstrates the immobilization of His₆-tagged hyaluronan synthase from Pasteurella multocida (PmHAS) onto nitrilotriacetic acid functionalized microgels using different bivalent ions (Ni²⁺, Co²⁺, Mn²⁺, Mg²⁺, and Fe²⁺) via metal affinity binding. The results indicate that using Ni²⁺ yields the microgels with the highest enzyme uptake and HA formation. The immobilized PmHAS enables repetitive enzymatic production, producing high molecular weight HAs with decreasing dispersities in each step. Furthermore, the highest reported yield of HA with high molecular weight for immobilized PmHAS is achieved. This system establishes a foundation for continuous HA formation, with future works potentially enhancing PmHAS stability through protein engineering.

Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol–gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), β-glycerophosphate (β-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/β-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/β-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/β-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/β-GP instant sol–gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.

Front Cover: In article 2300499, Kosuke Kuroda and co-workers optimize an isotonic freezing medium composed of poly(zwitterion), which alleviates osmotic shock unlike typical hypertonic freezing media. Imidazolium/carboxylate-type poly(zwitterion) is the optimal chemical structure. This illustration shows that the optimized poly(zwitterion) protects cells from ice crystal formation by forming a matrix around the cell membrane.

Tracheal resection and reconstruction procedures are necessary when stenosis, tracheomalacia, tumors, vascular lesions, or tracheal injury cause a tracheal blockage. Replacement with a tracheal substitute is often recommended when the trauma exceeds 50% of the total length of the trachea in adults and 30% in children. Recently, tissue engineering and other advanced techniques have shown promise in fabricating biocompatible tracheal substitutes with physical, morphological, biomechanical, and biological characteristics similar to native trachea. Different polymers and biometals are explored. Even with limited success with tissue-engineered grafts in clinical settings, complete healing of tracheal defects remains a substantial challenge due to low mechanical strength and durability of the graft materials, inadequate re-epithelialization and vascularization, and restenosis. This review has covered a range of reconstructive and regenerative techniques, design criteria, the use of bioprostheses and synthetic grafts for the recovery of tracheal defects, as well as the traditional and cutting-edge methods of their fabrication, surface modification for increased immuno- or biocompatibility, and associated challenges.

Drug delivery in transplantation plays a vital role in promoting graft survival, preventing rejection, managing complications, and contributing to positive patient outcomes. Targeted and controlled drug delivery can minimize systemic effects. Thermosensitive hydrogels, due to their unique sol-gel transition properties triggered by thermo-stimuli, have attracted significant research interest as a potential drug delivery system in transplantation. This review describes the current status, characteristics, and recent applications of thermosensitive hydrogels for drug delivery. Studies aimed at improving allotransplantation outcomes using thermosensitive hydrogels are then elaborated on. Finally, the challenges and opportunities associated with their use are discussed. Understanding the progress of research will serve as a guide for future improvements in their application as a means of targeted and controlled drug delivery in translational therapeutic applications for transplantation.

In the present report, a novel dual pH-O₂ sensor based on covalent conjugate of rhodamine 6G and cyclometalated iridium complex with poly(vinylpyrrolidone-block-vinyltetrazole) copolymer is reported. In model physiological solutions the sensor chromophores display independent phosphorescent and fluorescent lifetime responses onto variations in oxygen concentration and pH, respectively. Colocalization studies on Chinese hamster ovary cells demonstrate the preferential localization in endosomes and lysosomes. The fluorescent lifetime imaging microscopy-phosphorescent lifetime imaging microscopy (FLIM-PLIM) experiments show that the phosphorescent O₂ sensor provides unambiguous information onto hypoxia versus normoxia cell status as well as semi-quantitative data on the oxygen concentration in cells in between these two states. However, the results of FLIM measurements indicate that dynamic lifetime interval of the sensor (≈0.5 ns between pH values 5.0 and 8.0) is insufficient even for qualitative estimation of pH in living cells because half-width of lifetime distribution in the studied samples is higher than the sensor dynamic interval. Nevertheless, the variations in rhodamine emission intensity are much higher and allow rough discrimination of acidic and neutral cell conditions. Thus, the results of this study indicate that the suggested approach to the design of dual pH-O₂ sensors makes possible to prepare the biocompatible and water-soluble conjugate with fast cellular uptake.

Hypoxia, cancer, tissue damage, and acidic pH conditions are interrelated, as chronic hypoxic conditions enhance the malignant phenotype of cancer cells, causing more aggressive tissue destruction, and hypoxic cells rely on anaerobic glycolysis, leading to the accumulation of lactic acid. Therefore, the administration of oxygen is necessary to support the functions of healthy cells until the formation of new blood vessels and to increase the oxygen supply to cancerous tissues to improve the efficacy of antitumor drugs on tumor cells. In addition to O₂ supply, pH-dependent delivery of anticancer drugs is desired to target cancer cells and reduce drug side effects on healthy cells. However, the simultaneous delivery of O₂ and pH-dependent anticancer drugs via nanomaterials and their effects on the viability of normal and cancer cells under hypoxic conditions have not been studied in sufficient numbers. This study describes the synthesis of a pH-responsive nanomaterial containing oxygen and anticancer drugs that exhibits sustained O₂ release over a 14 d period under hypoxic conditions and pH-dependent sustained release of anticancer drugs over 30 d. The simultaneous administration of O₂ and anticancer drugs results in higher cell survival of normal cells than that of cancer cells under hypoxic and normoxic conditions.