Macromolecular bioscience最新文献

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.

Islet transplantation in type 1 diabetes confronts challenges, including isolation-induced islet damage, hypoxia, re-emergence of autoimmunity, and foreign body reactions. Pre-transplant conditioning strategies that support physiological homeostasis while protecting islets within encapsulation devices are therefore essential. We developed electrospun hydrophilic cellulose acetate (eCA) membranes and hydrophobic polytetrafluoroethylene (ePTFE) membranes with nano-topographical surfaces for islet encapsulation. They were tested for protein adsorption and macrophage activation, while eCA and ePTFE devices were evaluated by encapsulating MIN6 spheroids to assess their encapsulation efficiency and Glucose-stimulated insulin secretion (GSIS) capability. Furthermore, the devices encapsulating MIN6 spheroids were tested for 14 days in a custom 3D-printed bioreactor with continuous dynamic flow. Both eCA and ePTFE membranes restricted the entry or attachment of activated macrophages. The cells encapsulated in eCA-devices released significantly more insulin than those in ePTFE-devices, reflected by higher stimulation indices, suggesting the nutrient transfer ability of eCA. Under dynamic conditions, the encapsulated spheroids in eCA-devices were associated with high viability (80% at day 7 and 98% at day 14) and underwent initial compaction followed by tissue-like structure formation. Microscopy and immunofluorescence revealed the presence of ECM proteins, collagen-1, and E-cadherin, supporting the compaction and remodeling. These results demonstrate that the bioreactor system may be utilised as a pre-transplantation conditioning platform to rehabilitate isolated islets within encapsulated devices.

Niclosamide (NIC) shows antitumor activity by inhibiting multiple signaling pathways, including signal transducer and activator of transcription 3, Wnt/β-catenin, and NF-κB. However, the poor aqueous solubility and bioavailability limit its potential in treating systemic diseases. To address this, we report here the synthesis of a pH-responsive block copolymer PLLA-b-PDMAEMA-Q based on poly(L-lactide) (PLLA) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) diblock copolymer. First, the PLLA block was prepared by ring-opening polymerization (ROP) followed by the diblock, by atom transfer radical polymerization (ATRP) to prepare PLLA-b-PDMAEMA. Three different block copolymer compositions were synthesized by varying the molecular weight ratio of PLLA to PDMAEMA at 1:2, 1:1, and 1:0.5. PLLA-b-PDMAEMA was then quaternized by reaction with bromoacetic acid to generate PLLA-b-PDMAEMA-Q. In aqueous solution, these copolymers were found to self-assemble into micelles with a hydrodynamic diameter of 79–107 nm. PLLA-b-PDMAEMA-Q was converted to its polyzwitterionic analogue PLLA-b-PDMAEMA-ZIP in PBS buffer (pH 7.4) and used for encapsulation of NIC. The NIC-loaded PLLA-b-PDMAEMA-ZIP (ZIP-NIC) showed a spherical morphology with a hydrodynamic diameter of 230 ± 15.81 nm and significant uptake in HCT116 cells. ZIP-NIC exhibited similar anti-cancer efficacy to free NIC in the HCT116 cell line. Our results suggest that polyzwitterionic nanoparticles constitute a promising class of materials to deliver antitumor drugs and warrant further investigation.

The appropriate characteristics of carrier biomaterial must prevent rapid sequestration and clearance of exosomes. This study aims to investigate the efficacy of porous phosphate-based glass microspheres (PGMS) as carriers for human dental pulp stem cell (hDPSC)-derived exosomes in dental orthobiologic applications. PGMS (40P₂O₅-24MgO-16CaO-20Na₂O) is prepared via flame spheroidization, characterized using SEM-EDS, XRD, and mercury intrusion porosimetry. hDPSC-Exosomes (Exo) are extracted, labeled with DiL, and verified by confocal and flow cytometry. Cell viability is assessed whereby hDPSCs are exposed to 1 mg/mL PGMS, or 10 µg/mL Exo, or 1 mg/mL PGMS loaded with 10 µg/mL Exo. Osteogenic potential is assessed by ALP assay, qPCR, western blotting, and alizarin staining. PGMS exhibits 75% interconnected pores, and XRD shows broad halo peak within the 2θ range of 20°–40°. Exo are CD9⁺, CD63⁺, and CD81^+, and their cellular uptake is enhanced by 24 h. PGMS supports continued hDPSC proliferation. Exo-alone boosts hDPSC proliferation (24 h) and PGMS+Exo shows a similar rise. Exo-alone and PGMS+Exo significantly upregulate bone markers, while PGMS+Exo significantly upregulates Col1, ALP, and increases nodule formation. Western blotting shows an increase in BMP7, Col1, and OC in Exo-alone and PGMS+Exo. PGMS retains Exo, protects its functionality and release for favorable osteogenesis, offering a promising strategy as an exosome carrier in orthobiologic applications.