ACS Applied Bio Materials最新文献

Electrohydrodynamic splitting was performed on a filament consisting of a blend of chitosan and poly(vinyl alcohol) (PVA), followed by ionotropic gelation to produce uniform microparticles with dimensions on the order of 400 μm. The trapped solvent was removed by lyophilization, which rendered ultraporous characteristics to these particles and thus enabled quick absorption of blood plasma, along with aggregation of platelets for hemostasis. The uniformity of the particles ensured uniform coverage of the wound space. The increase in the PVA fraction in the blend resulted in greater porosity and surface area, as evidenced by the SEM image and BET analysis, respectively, and in turn, led to faster clotting, as shown by thromboelastography and in vivo analysis on rat models. Furthermore, the introduction of p-aminomethylbenzoic acid (ABA) as a releasable solute resulted in hindered fibrinolysis in the coagulation cascade, producing a stable blood clot. The in vivo experiments on the rat model further demonstrated the synergistic contribution of chitosan as an antimicrobial and wound healing agent.

The development of acidic pH-responsive degradable amphiphilic block copolymers (ABPs) and their nanoassemblies has been extensively explored as a promising platform for tumor-targeting drug delivery and cancer therapy. Despite tremendous advances, most acidic pH-degradable ABP nanoassemblies have been designed with acid-labile groups positioned in a single location, such as the hydrophobic core or at the core/corona interface, limiting their control over degradation and thus causing an inefficient release profile of encapsulated therapeutics. Herein, we report a dual-location acidic pH-responsive degradation strategy involving the synthesis of acidic pH-degradable ABP-based nanoassemblies bearing two different acid-labile linkages in hydrophobic cores and at interfaces that exhibit an individually controlled and synergistically enhanced release profile of encapsulated therapeutics. Well-defined ABPs are designed with benzaldehyde acetal at the block junction (e.g., interfaces) and conjugated benzoic imine in the hydrophobic block (e.g., cores), synthesized by reversible deactivation radical polymerization. Colloidally stable nanoassemblies formed through aqueous micellization have an acidic pH response desired for tumor-targeting drug delivery, e.g., slow degradation at pH = 6.5 (tumoral pH) and rapid degradation at pH = 5.0 (endo/lysosomal pH), while the remaining stable at pH = 7.3 (physiological pH). When loaded with curcumin anticancer drugs, nanoassemblies achieve a high encapsulation efficiency. Curcumin-loaded nanoassemblies exhibit enhanced curcumin release at endo/lysosomal pH levels. Moreover, they exhibit promising antitumoral activity and intracellular trafficking to cancer cells, while empty nanoassemblies are noncytotoxic. These results highlight the potential of the dual-location, acidic pH-responsive degradation strategy as a versatile platform for the next generation of tumor-targeted drug delivery.

This work reports a scalable, two-step, gram-scale synthesis of a macromolecular multithiol-lignin (degree of substitution, DS ≈ 0.70; ∼70 SH per 100 C₉ units), which serves as a thiol component in thiol-ene chemistry with allylcholine chloride as a green “ene” partner. Lignin was first chloroacetylated (92% yield). Subsequently, reaction with thiourea tethered abundant −SH groups along the polymer backbone, affording the multithiol intermediate in quantitative yield. The intermediate was evaluated in thermal-, base-, and UV-initiated thiol-ene reactions; among these, UV-mediated coupling with allylcholine chloride resulted in a cationic, quaternary-ammonium-lignin (DS ≈ 0.80, nitrogen content = 2.72 wt %). Fourier transform infrared (FTIR), ¹H-/¹³C nuclear magnetic resonance (NMR), heteronuclear single quantum coherence (HSQC), scanning electron microscopy (SEM)–energy-dispersive X-ray spectroscopy (EDS), and EA confirmed successful functionalization, while differential light scattering (DLS), contact angle, and surface free energy (SFE) analyses indicated a marked increase in hydrophilicity after quaternization. The functionalized lignin was formulated into membranes for food-packaging tests, which blocked ≈100% UV light and showed ≈75% antioxidant activity, indicating potential as a sustainable, surface-active, and antimicrobial material. Overall, this mild and efficient strategy introduces multithiol groups onto lignin, which can be exploited for property tuning via the degree of functionalization and the hydrophobic–hydrophilic–ionic balance for diverse applications.

Targeting RNA-binding proteins (RBPs) that control mRNA turnover presents a promising avenue for modulating gene expression and accessing otherwise “undruggable” intracellular targets. MEX3C is a tumor- and tissue-specific RBP that facilitates transcript destabilization by recruiting the CCR4–NOT deadenylation complex; however, selective tools to perturb MEX3C are lacking. Here, we report the development of a high-affinity and specific DNA aptamer through iterative Blocker-SELEX selection and sequence optimization. The resulting aptamer, MRiApt, binds the KH1 domain of MEX3C with nanomolar affinity and competitively inhibits RNA binding while sparing the homologous KH2 domain. A chemically stabilized derivative, MRiApt-PT-stem, exhibits enhanced stability and efficient intracellular uptake and effectively antagonizes the MEX3C-dependent repression of HLA-A2 transcripts, restoring HLA-A2 expression and thereby improving tumor cell recognition by T cells. Analysis of TCGA data revealed that high-MEX3C expression was significantly associated with poor prognosis in liver hepatocellular carcinoma (LIHC), underscoring the clinical relevance of perturbing MEX3C. Together, these findings establish MRiApt-PT-stem as a chemical probe to dissect and modulate MEX3C-mediated post-transcriptional regulation, providing a foundation for future approaches in transcriptome modulation and therapeutic targeting of RBPs.

Full-thickness osteochondral defects demand the concurrent restoration of cartilage and subchondral bone. Here, hyaluronic acid methacrylate (HAMA) scaffolds were three-dimensional (3D)-printed with in situ photocuring and formulated with glucosamine (GlcN) at different concentrations; 5 mg·mL^–1 was identified as optimal. This formulation preserved print fidelity and curing, while yielding a compliant, continuous network. In vitro, chondrogenic outcomes were strengthened, and early osteogenic activity was enhanced, as evidenced by increased cartilage-associated staining and mineralization with maintained viability and proliferation. Quantitative polymerase chain reaction (PCR) corroborated upregulated chondrogenic transcripts with concomitant osteogenic signaling. In a rabbit full-thickness osteochondral defect, the HAMA scaffold with GlcN achieved more complete defect fill, superior cartilage-like coverage, greater subchondral bone formation, and lower Wakitani and Seller’s scores than controls. Collectively, modest GlcN loading of 3D-printed HAMA generated a practical defect-matching scaffold that simultaneously promotes chondrogenesis and early osteogenesis, translating to improved osteochondral repair in vivo.

The transmission of antibiotic resistance genes (ARGs) through the food chain constitutes a serious public health risk by potentially leading to drug-resistant infections in humans. Rapid on-site detection of ARGs is therefore urgently needed. In this study, we developed a lateral flow assay (LFA) combined with asymmetric PCR (aPCR) for rapid and visual detection of four major ARGs: sul1, bla_NDM-1, vanA, and vgaB. The aPCR method efficiently generated single-stranded DNA amplicons without chemical modification, making it ideal for LFA detection. To improve assay performance, gold nanoparticles (AuNPs) were introduced to suppress nonspecific amplification during aPCR. Hybrid nucleic acid probes were designed to prevent single-stranded DNA (ssDNA) self-folding and facilitate the formation of a single-stranded tail structure, enabling dual recognition between the AuNP-labeled probe and the test zone capture probe. The optimized aPCR-LFA assay detected as low as 10 copies/μL of each ARG within 40 min and showed a linear quantitative range from 10¹ to 10⁵ copies/μL. No cross-reactivity was observed among the four ARGs, confirming high specificity. The method was successfully applied to shrimp and river snail samples, producing results consistent with quantitative real-time PCR (qPCR) analysis. These findings demonstrate that aPCR-LFA is a sensitive, specific, and reliable platform for on-site monitoring of ARGs in aquatic products.

Uncontrollable noncompressible bleeding has always been a major cause of death and disability among civilians and military personnel. Herein, a biodegradable, self-gelling protease-grafted alginate dressing was developed for efficient noncompressible bleeding control. The hemostatic dressing was fabricated through a high-degree sodium ion exchange of calcium alginate fibers, followed by covalent grafting of trypsin via carbodiimide chemistry. This design confers exceptional swelling capacity and rapid gelation within seconds upon blood contact, forming a physical barrier. The grafted trypsin establishes an artificial coagulation pathway independent of endogenous factors, significantly shortening in vitro clotting times. Moreover, it promotes adhesion and aggregation of red blood cells and platelets, accelerating clot formation and increasing the clot strength. In a rabbit liver injury model, the dressing achieved hemostasis within 70 s, significantly reducing blood loss and promoting wound healing compared to commercial SURGICEL while demonstrating excellent biocompatibility and biodegradability. The protease-grafted alginate dressing exhibited high robustness against high-temperature treatment, maintaining its high procoagulant activity in vitro for over 55 days at 47 °C.

Acute enteritis, commonly categorized into infectious and noninfectious types, shares similar pathological and clinical manifestations through activation of intestinal immune responses and disruption of mucosal functions. In this study, we constructed the virus assembly mimicking zeolitic imidazolate framework-8 (ZIF-8) particles ZIF@Ap+CDGFP against both infectious and noninfectious acute enteritis. The particles were synthesized by loading of the anti-inflammatory peptide apamin (Ap) into ZIF-8, followed by surface decoration of the artificial bacterium-binding protein CDGFP. The protein was designed by fusing the bacterial lipopolysaccharide-binding domain of CD14 and green fluorescence protein and expressed in the engineered Saccharomyces cerevisiae cells. ZIF@Ap+CDGFP significantly reduced lipopolysaccharide-induced apoptosis and reactive oxygen species production in intestinal epithelial cells. In both Salmonella-induced infectious enteritis and dextran sulfate sodium-induced noninfectious enteritis mouse models, ZIF@Ap+CDGFP efficiently attenuated the acute enteritis and intestine mucosal damage by mitigating neutrophil infiltration, suppressing the sustained recruitment of macrophages and dendritic cells, downregulating the expression of the pro-inflammatory cytokines (e.g., IL-6, IL-1β, and TNF-α), and upregulating the expression of the anti-inflammatory cytokine IL-10 and the intestine mucosa-repairing protein Nod2. These findings highlight the synthetic-biology-assisted biomimetic metal–organic framework as a promising therapeutic candidate for treating enteritis and other kinds of intestinal inflammation.

Bone tissue engineering scaffolds are used to repair dimensional alveolar crest defects resulting from etiologies such as trauma, infection, or tumor resection, thereby enabling a more accurate, efficient, and predictable dental diagnosis and treatment. In this study, cone beam computed tomography (CBCT) data from patients with alveolar crest defects were utilized to design a personalized scaffold. Subsequently, the 3D PCL/β-TCP scaffold was successfully fabricated based on this design using 3D printing technology. In parallel, a comprehensive series of assays were conducted to evaluate the properties of the 3D PCL/β-TCP scaffold, including its ability to promote MC3T3-E1 cell adhesion and proliferation in vitro. Furthermore, its capacity to induce bone formation was assessed in an in vivo animal model. The results demonstrated that the scaffold exhibited excellent biocompatibility, as evidenced by CCK-8 and live/dead (AM/PI) fluorescence staining assays, and significantly facilitated the adhesion and proliferation of MC3T3-E1 cells. Additionally, ALP and Alizarin Red staining experiments indicated that the 3D PCL/β-TCP scaffold significantly enhanced ALP expression and calcified nodule formation. Finally, the in vivo experiments in rats with skull defects confirmed that the 3D PCL/β-TCP scaffold contributed to accelerated bone formation. In summary, owing to numerous favorable properties such as personalized customization, biomimetic porous architecture, and excellent osteogenic ability, the 3D PCL/β-TCP scaffold was confirmed to be an advantageous candidate, offering ideas and effective methods for the precise repair of the alveolar crest.