Macromolecular bioscience最新文献

Infection sites and open wounds provide a prime environment for the growth of opportunistic pathogens, leading to persistent infections caused by bacteria that contain antimicrobial-resistant phenotypes. Mistreatment of these wound infections often increases antimicrobial resistance (AMR), thereby decreasing the effectiveness of antibiotics. With the increase in AMR, new antimicrobial therapeutics that target these hard-to-kill pathogens are needed. Herein, naturally harvested bacteriophages (ECΦ) were combined with another established antimicrobial molecule, nitric oxide (NO). This combination has rarely been explored in biomedical devices but shows excellent potential for developing broad-spectrum, antibacterial materials. Bacteriophages were encapsulated in alginate microbeads and suspended in a NO-releasing thermoresponsive hydrogel. The phages were shown to have a delayed release from the alginate beads when incorporated into the gel, compared to the release observed within 24 h in aqueous medium. This delayed release enabled tunable phage delivery by adjusting the viscosity of the bulk gel base. Additionally, we used alginate as the base for microbeads, resulting in a physiologically safe material due to its proven biocompatibility. The final ECΦ and NO-releasing bead-gel matrix demonstrated 5–10 times larger zones of bacterial killing while maintaining low cytotoxicity, enabling further development in various clinical applications, including wound healing.

Amid the rapid advancement in tissue engineering and regenerative medicine, 3D nanofiber scaffolds have attracted significant interest in the biomedical field for their ability to mimic the structure and function of the natural extracellular matrix (ECM). Their biomimetic nature stems not only from the morphological resemblance between the nanofiber topology and that of the ECM but, more importantly, from their capacity to replicate the complex functional properties of the ECM—such as mechanical signaling and biochemical communication—through multi-material composition, gradient design, and multi-scale structural engineering. Compared with their conventional 2D counterparts, these architectures provide an enhanced microenvironment that promotes cellular infiltration, vascularization, and functional tissue regeneration. This review systematically outlines fabrication strategies for 3D electrospun scaffolds, highlighting advanced electrospinning techniques and the underlying theories of structure formation, including multi-axial setups, dynamic collectors, sacrificial templates, ceramic nanofiber aerogels, and hybrid manufacturing approaches. The properties of commonly employed materials and their effects on the mechanical behavior, biocompatibility, and degradation profiles of the scaffolds are discussed in detail. Finally, future directions and practical challenges related to novel bioactive materials, multifunctional integration, and personalized medicine are presented to provide a translational framework for the clinical implementation of 3D electrospun scaffolds.

Extracellular vesicles, e.g., exosomes, derived from anti-inflammatory M2 macrophages have emerged as potent mediators of tissue regeneration through their ability to modulate cellular behavior, immune responses, and angiogenesis. In this study, we developed a composite bioactive scaffold by integrating M2 macrophage-derived EVs (M2-EVs) into decellularized skin extracellular matrix (dSECM), and systematically evaluated its structural, biochemical, and regenerative properties. Bovine dermis was decellularized using chemical, enzymatic, and physical steps, yielding collagen-rich, DNA-depleted ECM matrices with preserved collagen content and tunable stiffness (15–40 kPa). M2-EVs were isolated from IL-10-polarized RAW264.7 macrophages and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS, mean diameter ∼151 nm), and Western blotting for CD81/CD63/TSG101/Calnexin expressions. Functional assays revealed that M2-EVs enhanced the proliferation and migration of human dermal fibroblasts and keratinocytes, with 100 µg/mL achieving >90% wound closure at 48 h. When combined with dSECM, M2-EVs further increased the expression of immunoregulatory genes such as TGF-β (∼2.9-fold) and IL-10 (∼3.8-fold), consistent with the scaffold's capacity to enhance anti-inflammatory signaling. In the chick CAM model, dSECM/M2-EVs significantly enhanced vascularization along with increased collagen deposition and vascular smooth muscle cell recruitment. These results highlight M2-EVs as emerging biological effectors when incorporated into ECM-based scaffolds for vascularized tissue repair.

Quercetin (Qt) exhibits significant neuroprotective potential in Alzheimer's disease; however, its clinical translation is limited by poor solubility, low permeability, and inadequate brain bioavailability. In this study, a modified polymeric nanocarrier was developed to enhance Qt delivery to the brain. Polyethyleneimine (PEI) was conjugated with polyethylene glycol (PEG) and further functionalized with phenylalanine to reduce PEI-associated toxicity and improve brain-targeting efficiency. Successful polymer synthesis was confirmed by FT–IR spectroscopy, showing characteristic S─S bond formation at 790 cm⁻¹, mass spectrometry (m/z 1087.3), and differential scanning calorimetry. Nanoparticles were optimized using a Quality by Design approach, yielding an experimental particle size of 161.4 ± 1.10 nm, zeta potential of 15.9 ± 2.5 mV, and high entrapment efficiencies of 84.21 % and 86.74 % for Qt-PEI-Np and Qt-PEI-PEG-S-S-AA-Np, respectively. SEM analysis revealed spherical nanoparticles with nanoscale surface roughness and good stability. In vitro release studies demonstrated sustained Qt release (98 % over 48 h). MTT assays and cytokine analysis (TNF-α, IL-1β, IL-6) confirmed biocompatibility. Enhanced intestinal permeability, absence of hippocampal toxicity, and effective BBB transport further support the potential of this nanocarrier for targeted neurotherapeutic delivery.

Swelling-dependent self-folding hydrogels show considerable promise for tissue engineering applications. However, current systems face limitations in cell growth within the passive layer. This study introduces a novel approach to developing swelling-dependent bilayer hydrogels using biocompatible and biodegradable composites of methacrylated silk fibroin and methacrylated gelatin (SilMA-GelMA) through a “sonication-photocrosslinking” strategy. The sonication treatment induces beta-sheets (β-sheets) formation in silk fibroin molecules, creating a stable, less swellable passive layer while maintaining material consistency across the bilayer structure. Comprehensive characterization revealed significant differences in swelling ratio, mechanical properties, and degradation profiles between sonicated and nonsonicated layers. The optimized bilayer hydrogel composed of 50% GelMA with 50% SilMA (GS5) as the active layer and sonicated GS5 (GSS5) as the passive layer demonstrated efficient self-folding behavior, forming complete tubular structures after incubation. Furthermore, cell encapsulation experiments with human umbilical vein endothelial cells (HUVECs) revealed high cellular viability and proliferation in both sonicated and nonsonicated hydrogel layers over a 5-day culture period. This biocompatible and biodegradable swelling-dependent self-folding hydrogel provides a promising platform for creating complex, cell-laden tissue engineering constructs with controlled spatial distribution of cells and is particularly suitable for tubular tissue applications such as vascular engineering and the formation of other hollow organ structures where precisely controlled cellular organization is essential for proper function.

Persistent bacterial infections and prolonged inflammation often complicate full-thickness skin wound healing, underscoring the limitations of current dressings and the overuse of antibiotics. Herein, we developed a novel injectable hydrogel for full-thickness wound repair. The hydrogel matrix is composed of sacran, a supergiant polysaccharide with broad hydrophobic domains and abundant hydroxyl groups. Thermosensitivity was conferred upon the matrix through the incorporation of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol). Two rigid bioactive molecules, tannic acid (TA) and dipotassium glycyrrhizinate (DG), were co-loaded within the hydrogel. Their sustained release was achieved by the strong hydrophobic interactions inherent to sacran, which were further stabilized by hydrogen bonding. The synergistic drugs effectively modulate the wound microenvironment by exerting ∼100% antibacterial efficacy against both Gram-positive and Gram-negative bacteria, significant reactive oxygen species (ROS) scavenging (>94%2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging), suppression of pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)), and pro-angiogenic motion of angiogenesis and collagen deposition. In vivo studies confirmed accelerated wound closure, complete re-epithelialization, robust neovascularization, and appendage regeneration, significantly surpassing commercial Tegaderm performance. This multifunctional sacran-based injectable hydrogel emerges as a highly promising biomaterial, establishing a synergistic therapeutic strategy for complex skin injuries and advanced wound care.

Electrospinning technology has shown great potential in the field of peripheral nerve injury repair due to its biomimetic fiber structure, controllable degradability, and multi-functional loading capacity. This article reviews the application of electrospinning technology in nerve repair, with a focus on discussing its research progress in material modification, scaffold design and construction, and multi-technology collaborative repair. Electrospinning scaffolds can optimize the biocompatibility, cell adhesion, and mechanical properties of nerve conduits through physical and chemical modifications, or through the design and construction of scaffolds. At the same time, by combining technologies such as electrical stimulation, drug-loaded sustained-release, hydrogel filling, and 3D printing, a multi-functional synergistic effect can be achieved. It demonstrates significant advantages in structural design, biological activity regulation, and functional regeneration, accelerating the repair and regeneration of nerves after injury. However, it also faces challenges such as preparation efficiency and clinical transformation verification. The future development direction focuses on achieving precise regulation of neural regeneration and functional recovery.