Macromolecular bioscience最新文献

Electrospun nanofibrous membranes made of chiral selectors (CSs) have shown their potential for efficient chiral resolutions via filtrations. It is thus of great importance to expand the number of electrospun membranes made of various CSs for the resolution of a wide range of chiral compounds. Here, the electrospinning of two benzyl carbamate derivatives of cellulose, namely cellulose benzyl carbamate (CBzC) and cellulose 4-chlorobenzyl carbamate (CCBzC), to form a new type of enantioselective membranes for chiral resolutions of racemic compounds, is reported. The morphology of the electrospun membranes is studied by optical microscopy and scanning electron microscopy in relation to the electrospinning process parameters. Liquid-liquid permeation experiments of the racemic compounds, (R,S)-1-(1-naphthyl)ethanol ((R,S)-NET), (R,S)-1,1'-bi-2-naphtol ((R,S)-BNP), (R,S)-naproxen ((R,S)-NAP), and (R,S)-benzoin ((R,S)-BNZ) through the membranes demonstrate preferable permeations of (R)- or (S)-enantiomers depending on the combinations between the CSs and the racemates. Molecular docking simulations indicate the differences in the binding type, number, and free energies between the CSs and the enantiomers.

A strategy for multifunctional biosurfaces exploiting multiblock copolymers and the antipolyelectrolyte effect is reported. Combining a polyzwitterionic/antifouling and a polycationic/antibacterial block with a central anchoring block for attachment to titanium oxide surfaces affords surface coatings that exhibit antifouling properties against proteins and allow for surface regeneration by clearing adhering proteins by employing a salt washing step. The surfaces also kill bacteria by contact killing, which is aided by a nonfouling block. The synthesis of block copolymers of 4-vinyl pyridine (VP), dimethyl 4-vinylbenzyl phosphonate (DMVBP), and 4-vinylbenzyltrimethyl ammonium chloride (TMA) is achieved on the multigram scale via RAFT polymerization with good end group retention and narrow dispersities. By polymer analogous reactions, poly(4-vinyl pyridinium propane sulfonate-block-4-vinylbenzyl phosphonic acid-block-4-vinylbenzyl trimethylammonium chloride) (P(VSP₆₄-b-PA₁₄-b-TMA₆₄)) is obtained. The antifouling properties against the model protein pepsin and the salt-induced surface regeneration are shown in surface plasmon resonance (SPR) experiments, while independently the antibacterial and antifouling properties of coated titanium substrates are successfully tested in preliminary microbiological assays against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This strategy may contribute to the development of long-term effective antibacterial implant surface coatings to suppress biomedical device-associated infections.

Existing methods for treating diabetic oral ulcers often fall short in clinical environments due to potential bacterial contamination, oxidative harm, and hindered angiogenesis throughout the healing process. Here, a hydrogel patch (HYG2) have been developed for local in situ application. HYG2 comprises oxidized pullulan, quaternized chitosan, and eumelanin nanoparticles derived from cuttlefish ink. These components work together to efficiently heal wounds associated with diabetic oral ulcers. Application begins with a simple local injection that quickly forms a protective barrier over the mucosa, effectively stopping bleeding and counteracting inflammatory agents. HYG2 is distinguished by its strong antibacterial properties and capacity to eliminate reactive oxygen species, promoting bacteria clearance and managing oxidative stress, which accelerates the healing phase from inflammation to tissue regeneration. Additionally, HYG2's 3D structure, incorporating elements from natural sources, offers exemplary support for structural and nutritional cell needs. This enhancement fosters cell adhesion, migration, and proliferation, along with further angiogenesis during mucosal remodeling. Ultimately, HYG2 is fully absorbed by the body after serving its therapeutic functions. Evidence from in vitro and in vivo studies shows that HYG2 hydrogel markedly accelerates mucosal wound repair, making it a promising treatment for diabetic oral ulcers.

Neurotensin (NT), a bioactive tridecapeptide aids in diabetic wound healing by modulating inflammation and angiogenesis. However, its rapid degradation in peptidase-rich wound environment (plasma half-life <2 min) limits its efficacy. To address this, neurotensin-conjugated polymeric porous microparticles (NT-PMP) were developed and loaded in gelatin (hydrogel 15% w/v) for topical application, enabling sustained NT release to enhance therapeutic outcomes. NT-PMP exhibited a size range of 60 - 240 µm (mean: 120.63 ± 40.71 µm) and pore size of 5 - 16 µm (average: 10.68 ± 3.47 µm). In vitro studies demonstrated cytocompatibility of NT-PMP in fibroblasts and reduced TNF-α levels in inflammation-induced macrophages (1256 ± 167.02 pg/ml). Further NT-PMP scaffold depicted excellent cell adhesion and migration properties upon seeding of dermal fibroblasts on surface of PMPs. In vivo studies in diabetic wound rat model demonstrated effective wound management, characterized by notable regenerative and healing attributes in the presence of NT-PMP. This included complete re-epithelialization, reducing pro-inflammatory cytokine (TNF-α), and enhancing VEGF expression, ultimately leading to the development of a well-organized collagen matrix in diabetic wounds upon application of NT-PMP gel.Altogether, NT conjugated PMP loaded in hydrogel demonstrated significant regenerative and healing properties, suggesting its potential as an alternative treatment for diabetic wounds.

Oral diseases represent a prevalent global health burden, profoundly affecting patients' quality of life. Given the involvement of oral mucosa and muscles in diverse physiological functions, coupled with clinical aesthetics considerations, repairing oral and maxillofacial soft tissue defects poses a formidable challenge. Wet-adhesive materials are regarded as promising oral repair materials due to their unique advantages in easily overcoming physical and biological barriers in the oral cavity. This review first introduces the intricate wet-state environment prevalent in the oral cavity, meticulously explaining the fundamental physical and chemical adhesion mechanisms that underpin adhesive materials. It then comprehensively summarizes the diverse types of adhesives utilized in stomatology, encompassing polysaccharide, protein, and synthetic polymer adhesive materials. The review further evaluates the latest research advancements in utilizing these materials to treat various oral and maxillofacial soft tissue diseases, including oral mucosal diseases, periodontitis, peri-implantitis, oral and maxillofacial skin defects, and maxillofacial tumors. Finally, it also highlights the promising future prospects and pivotal challenges related to stomatology application of multifunctional adhesive materials.

The interaction between proteins and RNA is crucial for regulating gene expression, with dysregulation often linked to diseases such as cancer. The RNA-binding protein (RBP) Lin28 inhibits the tumor suppressor microRNA (miRNA) let-7, making it a significant oncogenic factor in tumor progression and metastasis. In this study, a small molecule is used that binds Lin28 and blocks its inhibition of let-7. To enhance its efficay, the inhibitor is transformed into degraders via two degradation approaches: Proteolysis Targeting Chimera (PROTAC) and molecular glue. A series of PROTAC bifunctional molecules and molecular glues capable of degrading Lin28 in cells.is developed Both strategies significantly reduce overexpressed Lin28 and alleviate cancer cellular phenotypes. Notably, the molecular glue approach demonstrates exceptional potency, surpassing PROTAC in several aspects. This outcome underscores the superior efficiency of the molecular glue approach for targeted Lin28 degradation and highlights its potential for addressing associated diseases with small molecules. Innovative small molecule strategies such as molecular glue and PROTAC technology for targeted RBP degradation, hold promise for opening new avenues in RNA modulation and addressing related diseases.

As an exceptional carrier for localized drug delivery to tumors, hydrogels can achieve prolonged drug release through careful design and adjustments, effectively targeting cancer cells and minimizing side effects. This study investigates a novel dual-responsive hydrogel system designed for the delivery of nanomedicines, focusing on drug release and the local antitumor efficacy of SN-38-cholesterol nanoparticles (SN-38-chol NPs) and polydopamine NPs (PDA NPs)/poly(n-isopropylacrylamide) (pNIPAM) hydrogels. By combining the thermosensitive properties of pNIPAM with the near-infrared (NIR) responsiveness of PDA NPs, the hydrogel aims to enhance on-demand drug release. SN-38-chol NPs, known for their stability and small size, are incorporated into the hydrogel to improve drug release dynamics. The investigation reveals a drug release cycle of over three weeks, maintaining sensitivity to both temperature and NIR light for controlled drug release. In vivo studies demonstrate the high tumor growth inhibition performance of the system after photothermal treatment induced by 808 nm NIR light. These results suggest that the drug-carrying hydrogel system holds promise for diverse applications in chemical and physical therapies, including the treatment of malignant wounds, post-surgery wound healing, and direct tumor treatment. This study establishes the potential of SN-38-chol NPs and PDA NPs/pNIPAM hydrogels as effective platforms for chemo-phototherapy.

Alginate forms a hydrogel via physical cross-linking with divalent cations. In literature, Ca²⁺ is mostly utilized due to strong interactions but additional procedures are required to disassociate Ca-alginate hydrogels. On the other hand, Mg-alginate hydrogels disassociate spontaneously, which might benefit certain applications. This study introduces Mg-alginate as the main component of a bio-ink for the first time to obtain 3D tumor models by magnetic bio-patterning technique. The bio-ink contains magnetic nanoparticles (MNPs) for magnetic manipulation, Mg-alginate hydrogel as a sacrificial material, and cells. The applicability of the methodology is tested for the formation of 3D tumor models using HeLa, SaOS-2, and SH-SY5Y cells. Long-term cultures are examined by Live/dead and MTT analysis and revealed high cell viability. Subsequently, Collagen and F-actin expressions are observed successfully in 3D tumor models. Finally, the anti-cancer drug Doxorubicin (DOX) effect is investigated on 3D tumor models, and IC₅₀ values is calculated to assess the drug response. As a result, significantly higher drug resistance is observed for bio-patterned 3D tumor models up to tenfold compared to 2D control. Overall, Mg-alginate hydrogel is successfully used to form bio-patterned 3D tumor models, and the applicability of the model is shown effectively, especially as a drug screening platform.

Periodontal diseases, if untreated, can cause gum recession and tooth root exposure, resulting in infection and irreversible damage. Traditional treatments using autologous grafts are painful and often result in postoperative complications. Scaffolds offer a less invasive alternative, promoting cell proliferation and healing without additional surgery, thus enhancing comfort for patients and doctors. This study developed Chitosan (Chit)/Collagen (Col) film surfaces and drug-loaded Polyvinyl Alcohol (PVA)/Amoxicillin (AMX) nanofibers using solvent casting and electrospinning methods, respectively. The surfaces are characterized by scanning electron microscopy (SEM), mechanical testing, Fourier Transform Infrared Spectroscopy (FTIR), and differential scanning calorimetry (DSC). Biocompatibility and antimicrobial properties are assessed using NIH/3T3 fibroblast cells and bacterial cultures. SEM images confirmed the structural integrity of AMX-loaded 13% PVA nanofibers, while FTIR analysis validated the compositional integrity of PVA/AMX nanofibers and Chit/Col film hybrid surfaces. Cell studies showed over 90% viability for Chit/Col film + PVA/AMX nanofiber hybrid bilayer membranes, confirming their biocompatibility. The antimicrobial assessment indicated that the Chit/Col film + PVA/AMX (0.2%) nanofiber hybrid bilayer membrane exhibited superior efficacy against Streptococcus mutans. These findings suggest that this hybrid bilayer membrane can enhance cell growth, promote proliferation, and enable controlled drug release, offering significant promise for regeneration of gingival tissues.