International Journal of Biological Macromolecules最新文献

Peripheral nerve injuries (PNIs) cause severe functional impairments and represent a significant clinical and socio-economic challenge. Autologous nerve grafts remain the gold standard practice, but their use has many drawbacks. Nerve guide conduits (NGCs) are a promising alternative. However, their regenerative performance is still inferior to autografts. Filling NGCs with internal guidance structures such as microfibers, may enhance their ability to support nerve repair. Polylactic acid (PLA) microfibers are a widely used biomaterial for scaffold fabrication due to its biocompatibility and processability, yet its bioinert surface lacks specific interaction sites for neural cells, necessitating biofunctionalization. In this study, PLA microfibers were treated with oxygen plasma to enable the stable incorporation of silk fibroin (SF), a bioactive protein known to promote cellular adhesion and neurite outgrowth. In vitro assays with Schwann cells and dorsal root ganglia demonstrated that while plasma-induced surface roughness improved cellular attachment and axonal growth compared to untreated PLA, the incorporation of SF had a markedly greater effect. These findings position SF-PLA microfibers as promising internal guidance structures for next-generation NGCs in peripheral nerve repair.

Monitoring the pH of human body fluids is crucial for health assessment. This study develops a durable, textile-based colorimetric sensor via laccase-catalyzed covalent grafting of edible butterfly pea anthocyanins onto silk fabric. The functionalized silk exhibits distinct, reversible color transitions across a broad pH range (2-12), enabling direct visual discrimination of simulated human sweat (purple at pH 4.5, blue at 6.0, turquoise at 8.0), urine (blue at pH 6.0), and vaginal secretions (purple at pH 4.5). The sensor demonstrates robust durability, with good wash and abrasion fastness (grade 4) and stable performance over 10 reuse cycles (all ΔE < 2). It also exhibits significant antioxidant activity (DPPH scavenging rate ∼ 73%). A comprehensive multi-stage DFT investigation provides a fundamental molecular-level explanation for the sensor's function and stability. The calculations identify the key acidic site (δ-OH) with a pKa of 4.96, responsible for the primary purple-to-blue transition, and reveal a high kinetic barrier (∼28 kcal/mol) for the competing color-fading pathway, rationalizing the observed durability and irreversible degradation under strong alkali. This work presents a complete "fabrication-to-mechanism" study, integrating a high-performance wearable sensor with fundamental theoretical validation for potential applications in personal health monitoring and smart textiles.

This study explored the development and characterization of barbaloin (BAR) loaded cassia tora gum-polyvinyl alcohol (CTG-PVA) hydrogel scaffolds crosslinked with citric acid (CA) for potential wound care applications. The scaffolds were synthesized by solvent casting, with CA serving as a low-cost, non-toxic crosslinking agent. Several characterization techniques, including FTIR, DSC, XRD, and morphological analysis, were employed to evaluate the folding ability, thickness, moisture content, porosity, water retention, water vapor transmission rate, mechanical properties, degree of swelling, moisture uptake, and degradation. In vitro drug release studies revealed sustained BAR release over 48 h, following a non-fickian diffusion model. Additionally, the hemolysis assays demonstrated that the hydrogel scaffolds exhibited excellent blood compatibility. The antibacterial study of the hydrogel scaffold demonstrated effective microbial inhibition against S. aureus and E. coli strains. Moreover, the biocompatibility study was performed using human dermal fibroblast cells PCS-201-021 (HDFs) and demonstrated that the hydrogel scaffolds are non-toxic. In vivo experiments, including histopathological analysis and wound healing assessments, revealed a significantly faster rate of wound recovery within 14 days of treatment. These findings indicate that BAR-loaded CTG-PVA hydrogel scaffolds cross-linked with CA have strong potential as wound dressings, providing a promising platform for tissue repair and drug delivery applications.

Guanylate Cyclase Activating Protein 1 (GCAP1) and Retinal Degeneration Protein 3 (RD3) are key regulators of retinal guanylate cyclase 1 (GC1), whose dysregulation leads to inherited retinal dystrophies (IRDs). While GCAP1 mutations cause constitutive GC1 activation and photoreceptor degeneration, RD3 acts as a potent cyclase inhibitor essential for proper GC1 trafficking. Here, we investigated the molecular interaction between GCAP1 and RD3 as well as its perturbation by IRD-associated GCAP1 mutations (D100G, N104H, E111V, E155G) using NMR spectroscopy, surface plasmon resonance, AlphaFold3 modeling, enzymatic assays, and their localization via immunohistochemistry. The results demonstrate that the GCAP1-RD3 interaction is strongly Ca²⁺-dependent, with Ca²⁺-bound GCAP1 exhibiting micromolar affinity for RD3 (K_D ~ 1.6 μM) and Mg²⁺-bound GCAP1 showing much weaker binding. Strikingly, the E111V mutation completely abolishes RD3 binding, whereas other variants retain interaction with differential kinetic properties. AlphaFold3 modeling, validated by NMR data, reveals that GCAP1 residues involved in RD3 binding overlap with those residues that mediate GCAP1 dimerization and GC1 interaction. Functional assays demonstrate that RD3 inhibits GC1 cyclase activity through dual mechanisms: direct binding to GC1 and GCAP1-mediated inhibition. Remarkably, RD3 rescues GC1 dysregulation caused by all tested GCAP1 mutations, regardless of their ability to interact with RD3. Immunohistochemistry reveals co-localization of GCAP1, RD3, and GC1 in photoreceptor inner segments and synaptic terminals, where Ca²⁺ concentrations favor complex formation. Our findings suggest that the Ca²⁺ gradient across the connecting cilium acts as a biochemical switch controlling RD3-GCAP1 interaction, and support RD3-based protein delivery as a mutation-independent therapeutic strategy for GCAP1-associated retinal dystrophies.

Multi-drug delivery systems for co-administrating multiple therapeutic agents have attracted significant attention in anticancer therapy due to their ability to enhance synergistic effects, improve tumor targeting, and mitigate drug resistance and systemic toxicity. In this study, self-assembled folic acid-functionalized fucoidan-poloxamer nanogels were developed as potential platforms for the co-delivery of cisplatin (Cis) and curcumin (Cur) to investigate their synergistic therapeutic efficacy. Two types of poloxamers, P403 and P407, differing in the length of their PPO segments, were grafted onto fucoidan, followed by functionalization with the targeting ligand folic acid. The resulting nanogels (FA-Fud-P403 and FA-Fud-P407) were characterized through measurements of proton nuclear magnetic resonance spectrum (¹H NMR), Fourier-transform infrared spectroscopy (FT-IR), and dynamic light scattering (DLS). Comapred to the FA-Fud-P407, FA-Fud-P403 had lower CMC value and smaller particle size, therefore improving the drug encapsulation efficacy. Meanwhile, the drug release studies revealed pH-responsive Fickian diffusion with an initial burst at acidic pH (5.5), followed by Korsmeyer-Peppas kinetics. Interestingly, the in vitro cell studies demonstrated that dual drug-loaded FA-Fud-P403 nanogels induced significantly higher cytotoxicity in MCF-7 breast cancer cells, while exhibiting reduced toxicity toward human dermal fibroblast cells (HDF) compared to FA-Fud-P407 and single drug-loaded formulations. Furthermore, in vivo evaluations in MCF-7 tumor-bearing mice confirmed the superior tumor inhibition with FA-Fud-P403@Cur/Cis, highlighting the potential of this dual drug delivery system to achieve synergistic therapeutic efficacy and minimize adverse effects associated with conventional chemotherapy.

To address the heavy metal water pollution caused by industrial wastewater discharge, a novel hydrogel adsorbent was prepared using organic matter derived from distiller's grains (DGS), a by-product of the brewing industry, as the main raw material and carboxymethyl chitosan (CMCS) as the modifier. Characterization results revealed that CMCS converted the adsorbent into a three-dimensional macroporous structure while enhancing its highly selective adsorption performance for Pb(II) and Cd(II), with adsorption capacities reaching as high as 825.3 mg·g^-1 and 644.3 mg·g^-1, respectively, and removal efficiencies up to 99.4% and 95.2% within 10 min. The adsorption process fitted well with the pseudo-second-order adsorption kinetic model (R² > 0.996) and the Langmuir isotherm model, indicating that the adsorption was dominated by chemical adsorption. Mechanistic analysis revealed that the hydrogel formed complexation and coordination with Pb(II) and Cd(II) via the lone pair electrons of O and N atoms, and combined with hydrogen bonding and electrostatic attraction to achieve synergistic adsorption. Furthermore, adsorption experiments on industrial wastewater using this adsorbent demonstrated that it maintained excellent adsorption performance even after six adsorption-desorption cycles, and achieved a degradation rate of 51.3% after 28 days. The synthesis of this highly efficient adsorbent not only realizes the functional modification and high-value utilization of DGS but also provides a green solution for wastewater remediation, exhibiting great application potential.

Articular cartilage injury often leads to progressive degeneration, necessitating advanced strategies that integrate immunomodulation, stem cell recruitment, and microenvironment regulation. Traditional hydrogels face limitations in spatiotemporal drug release and mechanical adaptability for dynamic joint environments. This study introduces an injectable, self-healing nanocomposite hydrogel engineered through dynamic boronate ester bonds between carboxymethyl chitosan and polyvinyl alcohol, synergizing macrophage-targeted curcumin nanomicelle and chondroinductive icariin. The hydrogel's reversible network enables shear-thinning injectability and reactive oxygen species (ROS)-responsive degradation, ensuring localized anti-inflammatory and pro-regenerative drug release. Curcumin-loaded mannose-functionalized micelles enhance macrophage uptake, polarizing macrophages toward an anti-inflammatory phenotype, while icariin promotes bone marrow mesenchymal stem cell (BMSC) migration and chondrogenic differentiation via Wnt/β-catenin and BMP/Smad pathway activation. In vitro studies demonstrated the hydrogel's capacity to scavenge ROS, suppress pro-inflammatory cytokines, and enhance BMSC recruitment and cartilage-specific matrix synthesis. In vivo evaluation in a rat full-thickness cartilage defect model revealed accelerated repair with organized neocartilage formation, reduced inflammation, and restored subchondral bone architecture. Histological and immunohistochemical analyses confirmed significant collagen II deposition and M2 macrophage polarization, aligning with native tissue regeneration. The hydrogel's biocompatibility and absence of systemic toxicity were validated through hematological and organ histopathology assessments. By dynamically coupling early-stage immunomodulation with sustained chondroinductive signaling, this dual-drug hydrogel disrupts the inflammation-degeneration cycle, offering a cell-free therapeutic platform for functional cartilage restoration. Its design principles provide a blueprint for intelligent biomaterials addressing complex tissue repair challenges.

Polylactic acid (PLA) is a promising biodegradable polymer, but its brittleness, relatively high cost, and poorly controlled degradation limit its applications. In this study, PLA/gelatin (GEL)/acetyl tributyl citrate (ATBC) blends were prepared by melt blending to simultaneously improve mechanical properties and regulate degradation behavior. ATBC, an environmentally friendly plasticizer, improved the compatibility between PLA and GEL and reduced the brittleness of PLA, whereas GEL, a hydrophilic biopolymer, modified the degradation behavior of PLA and contributed to reinforcing the blends. Mechanical tests showed that GEL increased bending strength, while ATBC markedly enhanced ductility, thereby balancing stiffness and flexibility. For the formulation containing 15 phr GEL and 20 phr ATBC, the elongation at break reached 344.25% (47.6 times higher than neat PLA), and the bending strength was 37.13 MPa (5.95 times higher than the corresponding blend without GEL). Raman spectroscopy revealed that during the "brittle-to-ductile transition" process, ATBC transformed from a dispersed phase to a continuous phase within the blends, elucidating the toughening mechanism. In alkaline solution, the blends containing 15 phr GEL and 20 phr ATBC completely degraded within 6 days, whereas neat PLA and the PLA/ATBC blends containing 20 phr ATBC showed mass losses of only 23.8% and 4.76%, respectively. Under composting conditions, the cumulative biodegradation degree of the blends containing 15 phr GEL and 20 phr ATBC was 54.53% higher than that of neat PLA, confirming its excellent biodegradability. Overall, the PLA/GEL/ATBC blends exhibited balanced mechanical properties, providing a practical route for controlled degradation and expanded PLA applications.