工程技术最新文献

Portal vein tumor thrombus (PVTT) is a common and severe indicator in advanced hepatocellular carcinoma (HCC), characterized by a poor prognosis and limited response to existing therapies. Cancer-associated fibroblasts (CAFs) play an important role in promoting HCC metastasis and contribute to resistance against sorafenib (SOR) resistance, which is a standard treatment for advanced HCC. The data from single-cell RNA sequencing highlights the critical role of C-X-C motif chemokine ligand 12 (CXCL12) in the activation of CAFs. To address these challenges, we develop a PVTT-targeted nanocarrier designed to co-deliver small interfering RNA (siRNA) and a multikinase inhibitor, aiming to enhance therapeutic outcomes for PVTT. This novel lipid-coated polylactide-co-glycolide nanoparticle system effectively downregulate CXCL12 expression in CAFs, leading to their inactivation and subsequent reshaping of the tumor microenvironment. The resulting modulation of the tumor microenvironment significantly suppress tumor cell migration, invasion, and resistance to SOR, thereby demonstrating potent anti-tumor effects in orthotopic mouse models of PVTT. Furthermore, RNA sequencing reveals key regulatory pathways and genes associated with the inhibition of SOR resistance and PVTT formation mediated by these nanoparticles. These findings suggest that modulating the tumor microenvironment, combined with targeted anti-tumor therapies, offers a promising strategy for treating HCC patients with PVTT.

The senescence of mesenchymal stem cells (MSCs) leads to the significant change of their metabolic activity and physiological behaviors. In the context of orthopedic treatment, the osteointegration of titanium implant is largely affected by MSC aging, imposing considerable limitations on its long-term application. In this study, a surface modification on titanium implants was designed to enhance osteointegration by effectively regulating the functions of senescent MSC: A typical micro-nano topological structure was established on the implant surface to improve the osteogenic differentiation of MSCs. Then a functional hydrogel coating was covalently modified to the implant surface through a poly-dopamine layer. For senescent MSCs, firstly, the coating can eliminate the activation of senescence-associated secretory phenotype (SASP) of senescent MSCs by micro-nano topological structure, and it accelerated the proliferation of non-senescent MSCs by the reactive oxygen species (ROS) scavenging. With the degradation of the hydrogel coating, the composition of stem cell pool around the implant interfaces gradually rejuvenated, as the number of non-senescent MSCs increased and senescent MSCs decreased. Meanwhile, the exposed micro-nano topological structure showed significant effect on the osteogenic differentiation of MSCs, and ultimately promoted the osteointegration in aging rats. These results provided promising insights for the design and application of orthopedic titanium implants for aging patients.

Chronic diabetic wounds are characterized by hypoxia, persistent microbial infection, and impaired healing, posing significant challenges to conventional therapies. Herein, we present a novel sprayable double-network hydrogel platform designed to achieve efficient antimicrobial activity and accelerated wound repair under hypoxic conditions by leveraging a type I photodynamic therapy (PDT) and immune-metabolic regulatory strategy. Specifically, we employ salvianolic acid B (SAB) to form a self-assembled hydrogel (SAB-gel) and incorporate fibrin to construct a robust and acidic double-network SAB/F-gel with enhanced mechanical strength and acidic environment. Concurrently, thymoquinone (TQ) and chlorin e6 (Ce6) are self-assembled via hydrophobic interactions to form TQ/Ce6 nanoparticles (TQ/Ce6 NPs) and embedded in the SAB/F-gel, to fabricate the TQ/Ce6@SAB/F-gel. Under low-oxygen conditions, TQ acts as an electron-transfer mediator, enabling Ce6 to generate abundant superoxide anions (·O₂^-) via type I PDT under red light (RL) irradiation. These ·O₂^- are subsequently converted into hydrogen peroxide (H₂O₂) and hydroxyl radicals (·OH) in the acidic environment provided by acidic SAB/F-gel, thereby reducing the dependence on oxygen and maintaining potent antimicrobial efficacy against MRSA, Pseudomonas aeruginosa (Pa), Acinetobacter baumannii (Ab), Escherichia coli (E. coli) and Candida albicans (Ca). In vitro experiments demonstrated that TQ/Ce6@SAB/F-gel regulates macrophage M2 polarization and promotes endothelial cell proliferation, migration, and tube formation via the immune-metabolic regulatory pathways. When applied to MRSA-infected diabetic wounds in mice, the hydrogel in combination with RL completely eradicated bacteria, promoted collagen deposition and angiogenesis, and significantly accelerated wound closure, as demonstrated by histological examination and transcriptome sequencing. This work offers a versatile, biocompatible, and oxygen-independent PDT-based hydrogel system for the treatment of refractory infected diabetic wounds, offering potential for clinical translation and improved patient outcomes.

Osteoarthritis (OA), a prevalent degenerative joint disease, currently lacks effective therapeutic options beyond symptomatic relief. Persistent inflammation and impaired cartilage repair accelerate the disease progression. The enzyme inducible nitric oxide synthase (iNOS) contributes to OA by producing nitric oxide (NO), which intensifies inflammation and inhibits cartilage regeneration. Traditional iNOS inhibitors have demonstrated limited efficacy due to inadequate targeted release and uncoordinated control over inflammation. In this study, we developed a self-supported DNAzyme-based DNA hydrogel using rolling circle amplification (RCA) technology to deliver iNOS-targeting DNAzymes and bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) in response to inflammation. The hydrogel incorporates triglycerol monostearate nanoparticles (TGMS NPs), which degrade under high matrix metalloproteinase (MMP) levels in OA joints, thereby triggering the release of the DNAzymes and exosomes with precision. This targeted delivery modulates the inflammatory microenvironment by reducing pro-inflammatory NO production and supports chondrogenesis by promoting M2 macrophage polarization. In vitro and in vivo analyses reveal that the hydrogel significantly reduces inflammatory cytokine levels, enhances chondrocyte proliferation, and restores extracellular matrix integrity, ultimately slowing OA progression. This smart hydrogel offers a promising ambidextrous strategy for microenvironment modulation and cartilage regeneration, potentially advancing OA treatment.

Although autografts and allografts remain common for bone defect repair, they entail donor-site morbidity, limited availability, and potential immune rejection. The development of tissue engineering has provided a potential solution to overcome these and facilitate effective bone regeneration. Extensive research has confirmed the osteogenic potential of bioactive molecules like Atorvastatin (ATV) and Icariin (ICA). But despite the increasing body of evidence supporting their individual merits, few studies have investigated the synergistic integration of these materials in Nanocomposite scaffolds. A novel three-dimensional scaffold composed of polycaprolactone (PCL), carboxymethyl chitosan (CMCs), and nano-hydroxyapatite (nHA), co-loaded with Icariin and Atorvastatin, and fabricated using the freeze-casting technique, is described. This study aimed to evaluate the scaffold's effectiveness in promoting calvarial bone regeneration in Wistar rats, contributing to the advancement of biomaterials in bone tissue engineering. Scaffolds containing PCL/CMCs/nHA with 0.1% ICA and 0.1% ATV were fabricated using the freeze-casting method. In vitro assessments were conducted to evaluate the biomechanical and physiological properties of the scaffolds. In vivo experiments involved implanting the scaffolds into calvarial bone defects in six groups of Wistar rats. After 12 weeks, histological analysis was performed to assess bone regeneration, including fibrous tissue formation, bone formation, osteon development, and osteoblast cell numbers and fibroblast cell numbers. After 72 h of incubation, the PCL/CMCs/nHA/ATO/ICA scaffold significantly enhanced cell viability compared to other groups, however, the differences observed between the other groups were not statistically significant. In vivo, results showed significantly greater bone formation, osteon development, and osteoblast numbers in the PCL/CMCs/nHA/ATO/ICA group than in the negative and other groups. The PCL/CMCs/nHA/ATO/ICA scaffold demonstrated superior bone regeneration outcomes, showing comparable performance to autografts in terms of new bone tissue formation, osteon structure, and 72-h cell viability, suggesting its potential as a viable alternative in bone tissue engineering.

One of the disadvantages of traditional ophthalmic formulations is their short residence time in the eye. An in situ gel is recommended as a remedy, as it can be converted into a gel upon contact with the eye and adhere for an extended period. Tamarind seed polysaccharide (TSP) is non thermo-sensitive and possesses the necessary properties to be used as a vehicle for administering medication to the eye. However, the administration of medication into the eyes through TSP based in situ gel has not yet been studied. N-isopropyl acrylamide was grafted onto TSP to make it temperature sensitive. Then, a TSP-based thermo-sensitive in situ gel-forming solution loaded with dorzolamide hydrochloride (2% w/v) was developed and evaluated through in vitro, ex vivo, and in vivo tests. The in situ gel forming solution turns into a gel at 37°C. The safety and efficacy of the formulation were confirmed through an in vivo study on rabbit eyes with induced glaucoma. The findings indicate that the in situ gel significantly reduced intraocular pressure (IOP), with effects comparable to those of marketed eye drops.

Study objectives: We aimed to develop a drug-loaded hydrogel-encapsulated chest drain to improve postoperative comfort and recovery in thoracic surgery patients. Methods: The hydrogel was modified with different ratios of glycerol and alginate, then mixed with varying concentrations of ropivacaine and fixed on a simulated chest drain tube using a mould and calcium chloride solution. The morphology, degradation, and slow-release properties of the hydrogel were assessed to identify the most suitable formulation. A bacteriostatic test was conducted using bacterial smear plates. The new chest drain was then implanted in rats using the seldinger method. Pathological changes were observed with imaging techniques such as chest ultrasound and radiographs, while lung function was assessed to evaluate the analgesic effect. After the animal experiments, hematoxylin and eosin (H&E) and Masson staining were performed on relevant tissues to analyze inflammation, and SOD activity was measured to assess oxidative stress levels. Results: The optimal drug-loaded hydrogel for chest drains contained 2% sodium alginate, 10% glycerol, and ropivacaine concentrations between 0.25% and 0.75%. This formulation showed superior morphological characteristics, degradation, and sustained-release properties. It also exhibited excellent bacteriostatic effects. The low-concentration (0.25%) drug-loaded hydrogel demonstrated better analgesic, anti-inflammatory, and oxidative stress-inhibitory effects in animal studies. Conclusions: The modified ropivacaine-alginate hydrogel-encapsulated chest drain offers a promising local slow-release strategy and may contribute to rapid rehabilitation in thoracic surgery.

Mechanotransduction plays a pivotal role in shaping cellular behavior including migration, differentiation, and proliferation. To investigate this mechanism more accurately further, this study came up with a novel elastomeric substrate with a stiffness gradient using a sugar-based replica molding technique combined with a two-layer PDMS system. The efficient water solubility of candy allows easy release, creating a smooth substrate. By adjusting the substrate's thickness, the optimal effective gradient length for the study is achievable. Additionally, adjusting substrate thickness precisely controls stiffness, from very soft to hard-tissue-like rigidity. Atomic force microscopy characterization confirmed a continuous stiffness gradient on three commonly used PDMS mixtures, 1:30, 1:50, and 1:75, demonstrating the versatility of this method for fabricating and tuning substrates to mimic various tissue environments. In cellular experiments, 3T3 fibroblast cells exhibited a significant migratory response toward the 1:50/1:75 two-layer stiffness gradient, with cells migrating preferably in stiffer directions. Its cost-effectiveness, smooth surface, and ability to regulate gradient substrates with varied stiffness via different PDMS combinations are key advantages. By precisely replicating physiologically relevant mechanical microenvironments, this method advances mechanobiology research and facilitates modeling of stiffness-guided cellular behaviors, paving the way for reliable tissue engineering and regenerative medicine studies.

Ag-Ca@CuO nanocomposites are fabricated using chemical precipitation method and are used for removing Cr (VI) and Pb (II) from the Yamuna River water in Delhi. Scanning electron microscopy confirmed the formation of rice grain-shaped CuO nanoparticles. Ag-Ca@CuO nanocomposites (CCA NCs) exhibited a surface area of 34.62 m²/g, notably superior to pristine CuO. At a concentration of 0.4 mg/mL of Ag-Ca@CuO nanocomposites, the highest removal rate of Lead (Pb) was observed to be 99.36%. For hexavalent chromium (Cr (VI)), the maximum removal efficiency was 72% under the same treatment conditions. Meanwhile, 63% of Nickel (Ni) removal is observed at 0.4 mg/mL treatment concentration. The incorporation of Ag and Ca played a crucial role in enhancing pollutant adsorption, suppressing electron-hole pair recombination, and promoting reactive oxygen species (ROS) generation for the degradation of toxic metal ions. We also studied the cytotoxic effects of CC and CCA NCs against the human HCT-116 cell line in a dose-dependent manner. At the nanocomposite's maximum concentration, i.e., 100 µg/mL, the cell viability for CC 2, CC 4, CCA 2 and CCA 4 was observed to be 47.64%, 35.29%, 19.83% and 8.88% respectively. IC50 value was also observed to be least for CCA 4 (17.71 µg/mL) followed by CCA 2 (31.61 µg/mL), CC 4 (72.93 µg/mL) and CC 2 (94.33 µg/mL). Cytotoxicity studies on human embryonic kidney (HEK 293) cell lines demonstrated minimal toxicity of the synthesised nanocomposites. This material could be used in wastewater treatment and as Drug-free therapeutics in cancer treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04655-1.

While vasodilator-stimulated phosphoprotein (VASP) is a key cytoskeletal regulatory protein linked to oral squamous cell carcinoma development, its role in other cancers remains unexplored. In this study, we employed the TCGA database, ESTIMATE algorithm, and TIMER to investigate the correlations of VASP with survival outcomes, clinical features, and immune cell infiltration. We also utilized GO, KEGG, and GSEA enrichment analyses to explore its potential functions and constructed a PPI network using STRING and Cytoscape. Our pan-cancer analysis revealed that VASP mRNA was upregulated in ten and downregulated in six tumor types compared to normal tissues. Of particular interest, aberrant VASP expression was significantly associated with the progression and poor prognosis of liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD). The level of VASP mRNA showed notable upregulation in LIHC, and its expression was positively correlated with the levels of T-cell exhaustion markers. Univariate and multivariate Cox regression analysis indicated that VASP could serve as an independent diagnostic biomarker for this cancer type. Functional enrichment analysis revealed that VASP participates in several tumor-related processes, such as extracellular matrix degradation and the chemokine signaling pathway. In addition, VASP protein levels were observed to be significantly elevated in LUAD tissues compared to normal controls. VASP knockdown markedly suppressed the migratory capacity of LUAD cells in vitro. In conclusion, the aberrant expression of VASP is associated with poor prognosis in LIHC and LUAD, and VASP could be used as a novel predictive biomarker for LIHC patients.