Biomaterials Science最新文献

Donepezil (DNZ) has been used to treat dementia associated with mild, moderate, or severe Alzheimer's disease (AD). DNZ uptake can alleviate cognitive symptoms in AD patients via acetylcholinesterase (AChE) inhibition. However, oral administration of DNZ has limitations, including first-pass metabolism, difficulties with swallowing, and low patient compliance. In this work, we disclose a novel transdermal DNZ delivery system utilizing T2 polymer, synthesized via the ring-opening polymerization of 2,2,5,5-tetramethyl-2,5-disila-1-oxacyclopentane with trifluoroacetic acid (TFA). In the in vivo studies in an AD animal model, the DNZ-loaded T2 polymer (DNZ@T2) facilitated efficient transdermal DNZ delivery to the bloodstream and improved spatial working memory and long-term memory of the AD mouse model. Both the T2 polymer and DNZ@T2 exhibited low cytotoxicity and non-significant in vivo toxicity. This research highlights a promising transdermal delivery strategy for AD treatment, potentially enhancing therapeutic efficacy and patient compliance.

Pharmacokinetics and biodistribution profiles of active substances are crucial aspects for their safe and successful administration. Since many immunogenic compounds do not meet all requirements for safe and effective administration, well-defined drug nanocarrier systems are necessary with a stimuli-responsive drug-release profile. For this purpose, a novel pH-responsive aliphatic cyclic carbonate is introduced with benzyl ketal side chains and polymerized onto a poly(ethylene glycol) macroinitiator. The resulting block copolymers could be formulated via a solvent-evaporation method into well-defined polymeric micelles. The hydrophobic carbonate block was equipped with an acid degradable ketal side group that served as an acid-responsive functional group. Already subtle pH alternations led to micelle disassembly and the release of the active cargo. Furthermore, basic carbonate backbone degradation assured the pH responsiveness of the nanocarriers in both acidic and basic conditions. To investigate the delivery capacity of polymeric micelles, the model small molecule compound CL075, which serves as an immunotherapeutic TLR7/8 agonist, was encapsulated. Incubation studies with human blood plasma revealed the absence of undesirable protein adsorption on the drug-loaded nanoparticles. Furthermore, in vitro applications confirmed cell uptake of the nanodrug formulations by macrophages and the induction of payload-mediated immune stimulation. Altogether, these results underline the huge potential of the developed multi-pH-responsive polymeric nanocarrier for immunodrug delivery.

Chiral recognition holds tremendous significance in both life science and chemistry. The ability to differentiate between enantiomers is crucial because one enantiomer typically holds greater biological relevance while its counterpart is often not only unnecessary but also potentially harmful. In this regard, homochiral metallacycle [ZnCl₂L]₂ is used in this study to understand and differentiate between the R and S enantiomers of amino acids (alanine, proline, serine, and valine). The electronic, geometric, and thermodynamic stabilities of the amino acid enantiomers inside the metallacycle are determined through various analyses. The greater interaction energy (E_int) is obtained for the ser@metallacycle complexes i.e., -33.03 and -30.75 kcal mol^-1, respectively for the S and R enantiomers. The highest chiral discrimination energy of 3.11 kcal mol^-1 is achieved for ala@metallacycle complexes. Regarding the electronic properties, the frontier molecular orbital (FMO) analysis indicates that the energy gap decreases after complexation, which is confirmed through density of states (DOS) analysis. Moreover, natural bond orbital (NBO) analysis determines the amount and direction of charge transfer i.e., from metallacycle towards amino acids. The maximum NBO charge transfer is observed for S-pro@metallacycle complex i.e., -0.291 |e|. Electron density difference (EDD) analysis further proves the direction of charge transfer. Noncovalent interaction index (NCI) and quantum theory of atoms in molecules (QTAIM) analyses demonstrate that the noncovalent interactions present between the host and guest are the weak van der Waals forces and hydrogen bonding. The results of NCI and QTAIM analyses for all the complexes are in alignment with those of the interaction energy (E_int) and chiral discrimination energy (E_chir) analyses, i.e., significantly greater non-bonding interactions are observed for the complexes with greater E_chir, i.e., for ala@metallacycle. Overall, our analyses demonstrate the excellent chiral discrimination ability of metallacycle towards chiral molecules, i.e., for enantiomers of amino acids through host-guest supramolecular chemistry.

Natural resource based polymers, especially those derived from proteins, have attracted significant attention for their potential utilization in advanced wound care applications. Protein based wound care materials provide superior biocompatibility, biodegradability, and other functionalities compared to conventional dressings. The effectiveness of various fabrication techniques, such as electrospinning, phase separation, self-assembly, and ball milling, is examined in the context of developing protein-based materials for wound healing. These methods produce a wide range of forms, including hydrogels, scaffolds, sponges, films, and bioinspired nanomaterials, each designed for specific types of wounds and different stages of healing. This review presents a comprehensive analysis of recent research that investigates the transformation of proteins into materials for wound healing applications. Our focus is on essential proteins, such as keratin, collagen, gelatin, silk, zein, and albumin, and we emphasize their distinct traits and roles in wound care management. Protein-based wound care materials show promising potential in biomedical engineering, offering improved healing capabilities and reduced risks of infection. It is crucial to explore the potential use of these materials in clinical settings while also addressing the challenges that may arise from their commercialization in the future.

Correction for 'Bioactivity of cerium dioxide nanoparticles as a function of size and surface features' by Veronika Sarnatskaya et al., Biomater. Sci., 2024, 12, 2689-2704, https://doi.org/10.1039/D3BM01900D.

Silk fibroin is a naturally abundant biomaterial renowned for its excellent biocompatibility and biodegradability, making it a promising candidate for biomedical applications like wound dressings. However, traditional silk fibroin materials often lack sufficient mechanical strength, adhesion, and the ability to modulate inflammation and oxidative stress-factors crucial for effective wound healing. To address these limitations, regenerated silk fibroin/magnesium ion [RSF/Mg(II)] composite films were developed by incorporating Mg(II) ions into RSF solutions. These films were characterized using Raman spectroscopy, mechanical testing, and biocompatibility assessments, and their wound-healing efficacy was evaluated in a mouse skin defect model. The RSF/Mg(II) composite films exhibited superior adhesion, higher transparency, and enhanced mechanical flexibility compared to pristine RSF films. They also demonstrated anti-inflammatory and antioxidative properties, effectively reducing cell apoptosis and reactive oxygen species levels in vitro. In vivo, the RSF/Mg Mg(II) composite films significantly accelerated wound healing in mice, improving epidermal thickness, collagen deposition, and promoting blood vessel formation. This study highlights the potential of RSF/Mg(II) composite films as advanced wound dressings with improved biocompatibility and biological activity, offering valuable insights for the development of Mg(II) ion-based biomaterials in wound healing and tissue regeneration applications.

DNA modification of the plasma membrane is an excellent approach for controlling membrane-protein interactions, modulating cell-cell/cell-biomolecule interactions, and extending the biosensing field. The hydrophobic insertion of DNA conjugated with hydrophobic anchoring molecules is utilized for tethering DNA on the cell membrane. In this study, we developed an alternative approach to tether DNA on the plasma membrane based on ssDNA- and cholesterol-binding proteins. We designed a fusion protein (Rep-ALOD4) composed of domain 4 of anthrolysin O (ALOD4), which binds to cholesterol in the plasma membrane, and a replication initiator protein derived from porcine circovirus type 2 (Rep), which forms covalent bonds with single-stranded DNA (ssDNA) with a Rep recognition sequence. Rep-ALOD4 conjugates ssDNA to Rep and binds to the plasma membrane via cholesterol, thus tethering ssDNA to the cells. Quartz crystal microbalance measurements showed that membrane cholesterol binding of Rep-ALOD4 to the lipid bilayer containing cholesterol was accelerated above 20% (w/w) cholesterol in the lipid bilayer. Rep-ALOD4 was conjugated to fluorescein-labeled ssDNA (S-FITC-Rep-ALOD4) and used to treat human cervical tumor HeLa cells. The green signal assigned to S-FITC-Rep-ALOD4 was detected along HeLa cells, whereas diminished by cholesterol removal with methyl β-cyclodextrins. Moreover, ssDNA-conjugated Rep-ALOD4 tethered ssDNA-conjugated functional proteins on the HeLa cell plasma membrane via complementary base pairing. Collectively, Rep-ALOD4 has the potential as an ssDNA-tethering material via plasma membrane cholesterol to extend cell surface engineering.

The healing of complex diabetic wounds with a hyperglycemic microenvironment and bacterial infection is considered an important clinical issue. In this study, glucose oxidase (GOx) and gold nanoclusters (AuNCs) were encapsulated in quaternary carboxymethyl chitosan (QCMCS)/sodium alginate oxide (OSA) hydrogels and were immersed in tannic acid (TA) solution to achieve antioxidant, antibacterial, pro-angiogenesis, pro-collagen deposition and real-time monitoring functions. In vitro studies showed that TA-QCMCS/OSA@GOx@AuNC hydrogels had inhibition rates of 98.99% and 99.99% against S. aureus and E. coli, respectively, and the survival rate of mouse fibroblasts (L929) was over 95%. In vivo studies showed that TA-QCMCS/OSA@GOx@AuNC hydrogels were 97.28% effective in healing diabetic wounds. In addition, image signals from TA-QCMCS/OSA@GOx@AuNC hydrogels can be collected in real time to accurately obtain glucose concentration values of diabetic wounds and reflect the healing status of diabetic wounds in a timely manner. The results showed that TA-QCMCS/OSA@GOx@AuNC hydrogels provide a novel idea for real-time monitoring of diabetic wound treatment.

Peptides are well known for forming nanoparticles, while DNA duplexes, triplexes and tetraplexes create rigid nanostructures. Accordingly, the covalent conjugation of peptides to DNA/RNA produces hybrid self-assembling features and may lead to interesting nano-assemblies distinct from those of their individual components. Herein, we report the preparation of a collagen mimetic peptide incorporating lysine in its backbone, with alkylamino side chains radially conjugated with G-rich PNA [collagen-(PNA-GGG)₃]. In the presence of complementary C-rich DNA (dCCCTTTCCC) at neutral pH, the collagen mimetic triplexes were interconnected by PNA-GGG : DNA-CCC duplexes, leading to the formation of larger assemblies of nanostructures. Upon decreasing the pH to 4.5, the dissociation of the triplex-duplex assembly released the protonated C-rich DNA, which immediately folded into an i-motif. With an increase in the pH to 7.2 (neutral), the i-motif unfolded into linear DNA, which reformed the PNA-GGG : DNA-CCC duplex interconnecting the collagen triplexes. The pH-induced switching of the assembly and disassembly was reversible over a few cycles. The hybrid collagen-(PNAGGG)₃ : DNA-C₃T₃C₃ triplex-duplex and the individual components of the assembly including the i-motif were characterized by UV and CD melting, fluorescence, TEM and gel electrophoresis. The pH-induced reversible switching was established by the changes in the CD and fluorescence properties. Peptide-DNA conjugates have wide applications in both biology and materials science, ranging from therapeutics and drug delivery to diagnostics and molecular switches. Thus, the prototype ensemble of the triplex peptide-PNA conjugate and its duplex with DNA described herein has potential for elaboration into rationally designed systems by varying the PNA/DNA sequences to trap functional ligands/drugs for release in pH-controlled environments.

The field of biomedical engineering continually seeks innovative technologies to address complex healthcare challenges, ranging from tissue regeneration to drug delivery and biosensing. Plant skeletons offer promising opportunities for these applications due to their unique hierarchical structures, desirable porosity, inherent biocompatibility, and adjustable mechanical properties. This review comprehensively discusses chemical principles underlying the utilization of plant-based scaffolds in biomedical engineering. Highlighting their structural integrity, tunable properties, and possibility of chemical modification, the review explores diverse preparation strategies to tailor plant skeleton properties for bone, neural, cardiovascular, skeletal muscle, and tendon tissue engineering. Such applications stem from the cellulosic three-dimensional structure of different parts of plants, which can mimic the complexity of native tissues and extracellular matrices, providing an ideal environment for cell adhesion, proliferation, and differentiation. We also discuss the application of plant skeletons as carriers for drug delivery due to their structural diversity and versatility in encapsulating and releasing therapeutic agents with controlled kinetics. Furthermore, we present the emerging role played by plant-derived materials in biosensor development for diagnostic and monitoring purposes. Challenges and future directions in the field are also discussed, offering insights into the opportunities for future translation of sustainable plant-based technologies to address critical healthcare needs.