Biomaterials Science最新文献

Correction for 'Ciprofloxacin-loaded bioadhesive hydrogels for ocular applications' by Islam A. Khalil et al., Biomater. Sci., 2020, 8, 5196-5209.

Chronic wounds have emerged as a major healthcare challenge due to their prolonged healing cycle. A key feature of chronic wounds is local tissue hypoxia, resulting in insufficient oxygenation of the wound microenvironment. While traditional therapies like hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) alleviate wound hypoxia by oxygen supplementation, they are limited by high costs, uncertainty in sustained efficacy, and complications, restricting clinical use. Oxygen carriers, such as perfluorocarbons (PFCs) and hemoglobin (Hb), exhibit high-efficiency oxygen delivery capacity, excellent biocompatibility and cost-effectiveness. They hold enormous potential for clinical applications. This review focuses on the application of PFCs and Hb-based oxygen carriers in chronic wound therapy. It systematically elaborates on the diversified oxygen delivery strategies based on PFCs and Hb. It also quantitatively compares their oxygen delivery capabilities and analyzes their multiple synergistic biological effects. Meanwhile the review also describes the difficulties and challenges in precise delivery and clinical translation.

Effective delivery of small interfering RNA (siRNA) to the cytosol continues to pose a significant challenge in RNA interference (RNAi)-driven precision cancer therapy. In this study, we engineered glutathione (GSH)-responsive bola-amphiphilic peptide dendrimers (bola DS-C_n-K₄) for tumor-specific cytosolic siRNA delivery. These dendrimers incorporate a hydrophilic polylysine dendron for efficient siRNA binding and a hydrophobic disulfide-bridged bola-lipid core with varying alkyl chain lengths, facilitating thiol-mediated cellular uptake and enabling siRNA release in response to intracellular higher GSH levels. Our structure-activity relationship studies revealed that bola DS-C₆-K₄, characterized by the shortest alkyl chain, exhibited superior siRNA delivery, which was attributed to optimized thiol-mediated cellular uptake and accelerated GSH-triggered siRNA release stemming from improved disulfide accessibility. Mechanistic investigations validated thiol-mediated uptake as the predominant cellular internalization pathway, effectively bypassing endosomal entrapment. The siRNA/bola DS-C₆-K₄ complexes efficiently downregulate oncoprotein expression, thereby impeding cancer cell proliferation, migration, and invasion, and simultaneously inducing apoptosis. In A549 xenograft models, intravenous administration of siPLK1/bola DS-C₆-K₄ achieved substantial reductions in tumor growth and PLK1 expression while exhibiting minimal systemic toxicity. This study highlights a synergistic approach utilizing bola-amphiphilic peptide dendrimers for tumor-specific and cytosolic siRNA delivery, leveraging membrane-thiol interactions and intracellular GSH-triggered siRNA release.

Currently, there are no effective pharmacological interventions in clinical practice to reverse liver fibrosis. This study explores the therapeutic potential of regenerated silk fibroin (RSF) scaffolds loaded with dual growth factors for reversing hepatic fibrosis. A chronic liver fibrosis mouse model was induced using carbon tetrachloride (CCl₄) combined with a high-fat diet. RSF scaffolds, with or without hepatocyte growth factor (HGF) and fibroblast growth factor-4 (FGF-4), were implanted onto the liver surface to assess antifibrotic efficacy. Liver function was evaluated using biochemical analysis. Compared with controls, the RSF/HGF/FGF-4 group showed significantly reduced serum levels of C-reactive protein (CRP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histopathological analyses (H&E and Masson's trichrome staining) on days 7, 14, and 30 demonstrated marked improvements in liver architecture and a significant reduction in fibrosis (SAF scores, P < 0.05). Immunohistochemistry further revealed neovascularization and bile duct formation by day 14. Transcriptomic profiling showed upregulation of bile duct development pathways and downregulation of inflammatory signaling. Quantitative PCR confirmed increased expression of bile secretion genes (FXR, OAT) and decreased expression of NF-κB pathway genes (TRAF2, Bax). These findings highlight the RSF/HGF/FGF-4 scaffold as a promising cell-free strategy for promoting functional liver regeneration and reversing chronic liver fibrosis.

Chronic diabetic wounds remain difficult to heal due to persistent inflammation and impaired macrophage polarization. Herein, we developed an immunoregulatory dressing using a hybrid hydrogel (C-B-S) synthesized from natural polysaccharides through the photopolymerization of carboxymethyl chitosan methacrylate (CMCMA), Bletilla striata polysaccharide methacrylate (BSPMA), and thiolated hyaluronic acid (HA-SH). The hydrogel demonstrated dual functionality by promoting hemostasis and inducing macrophage polarization toward the M2 phenotype. RNA sequencing analysis revealed that the immunomodulatory effect of Bletilla striata polysaccharide is mediated via the PPAR signaling pathway. In vivo studies demonstrated the C-B-S hydrogel enhanced angiogenesis, re-epithelialization, and collagen deposition, leading to the fastest wound closure among all groups. This study offers a transformative therapeutic strategy to restore immune balance and accelerate diabetic tissue repair, highlighting its potential for clinical translation in treating chronic diabetic wounds.

Cell-free DNA (cfDNA), released from damaged cells, acts as a critical danger-associated molecular pattern and plays a key role as a molecular trigger in various inflammatory diseases. Conventional anti-inflammatory therapies target downstream effectors, often causing systemic immunosuppression and facing long-term efficacy and safety limits. Recent advances in cfDNA-scavenging nanomaterials offer a novel therapeutic strategy of efficiently scavenging cfDNA released from various sources that contribute to inflammation. We systematically review the burgeoning advances in cfDNA-scavenging nanomaterials, which represent a novel platform for modulating inflammation, and elucidate the mechanisms of these engineered cfDNA nanoscavengers to restore immune homeostasis, including competitive binding, electrostatic adsorption and enzymatic degradation. Crucially, we discuss solutions to the challenges impeding their clinical translation, such as mitigating material toxicity, preventing binding saturation and cfDNA re-release, and enhancing in vivo targeting specificity. Finally, we outline future perspectives for developing intelligent, multifunctional, and biocompatible nanomaterial platforms, emphasizing their potential for integration into precision immunotherapy against inflammatory diseases.

Granular hydrogels are an emerging biomaterial platform increasingly used in biomedical applications, including therapeutic delivery and tissue regeneration. Assembled from micron-scale hydrogel particles through physical assembly or chemical cross-linking, granular hydrogels possess micro- and macroscopic pores that facilitate molecular transport and cell migration. However, current granular hydrogels are typically fabricated with defined stiffness, porosity, and compositions that do not recapitulate the dynamic nature of native tissues, including the tumor microenvironment. To address this challenge, we have developed dynamic granular hydrogels formed by gelatin-norbornene-carbohydrazide (GelNB-CH) microgels. GelNB-CH microgels were first prepared from a microfluidic droplet generator coupled with the rapid thiol-norbornene photo-click gelation. The collected microgels were annealed via inverse electron-demand Diels-Alder (iEDDA) click reaction to form granular hydrogels, which were dynamically stiffened via hydrazone bonding. Notably, adjusting the concentration of the stiffening reagent (i.e., oxidized dextran, oDex) enabled dynamic stiffening of the granular hydrogels without affecting the void fraction. Pancreatic cancer-associated fibroblasts (CAFs) seeded in the granular hydrogels spread rapidly throughout the scaffold and induced cancer cell migration. This work enhances the design of granular hydrogels, offering a highly adaptable biomaterial platform for in vitro cancer modeling.

Nowadays, with the growing need for alternative antibacterial materials for the treatment of bacterial infections, TiO₂ with antibacterial properties has attracted attention as a potential antibacterial agent. Ni-TiO₂ and Co-TiO₂ nanofibers (NFs) were synthesized via an electrospinning process. The antibacterial activities of these NFs against S. aureus and E. coli were evaluated under UV-light illumination using optical density measurements. Co-TiO₂ exhibited superior antibacterial activity against both S. aureus and E. coli under UV-light irradiation. The antibacterial mechanism was further investigated through a glutathione (GSH) oxidation assay and morphological analysis using scanning electron microscopy (SEM). Hydrophilicity was evaluated by contact angle measurement. The antibiofilm activities of TiO₂, Ni-TiO₂, and Co-TiO₂ NFs were investigated with respect to E. coli and S. aureus biofilms. Ni-TiO₂ and Co-TiO₂ demonstrated more effective antibiofilm activities than bare TiO₂. Under UV-light irradiation, the biofilm inhibition efficacy was increased for both Ni-TiO₂ and Co-TiO₂ NFs while Co-TiO₂ NFs were found to have the greater antibiofilm performance. Additionally, in silico analysis was conducted to explore the molecular interactions of the NFs with S. aureus Immunoglobulin-Binding B Domain (PDB ID: 1BDD) and FimH lectin protein of E. coli (PDB ID: 4XO8). Co-TiO₂ exhibited stronger binding to S. aureus, while TiO₂ showed stronger binding to E. coli.

Prostate cancer remains one of the most common malignant tumors among men worldwide, and treatment options are limited in the advanced stage. To address this challenge, we have developed a pH-responsive copper porphyrin metal-organic framework (CuTCPP-MOF), which integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT). It enables efficient electron transfer and ROS generation. Under 488 nm laser irradiation, MOF acts as a self-sensitizing photosensitizer to generate single-state oxygen (¹O₂), which gradually releases Cu²⁺ in an acidic environment. Subsequently, it is reduced to Cu⁺ by intracellular glutathione (GSH), achieving continuous consumption of GSH and enhancing the Fenton-like reaction to promote the continuous formation of hydroxyl radicals (˙OH). This amplifies the oxidative stress within tumor cells. In vitro experiments have shown that ROS accumulation and mitochondrial membrane depolarization lead to apoptosis of RM-1 prostate cancer cells. In vivo, CuTCPP-MOF combined with laser irradiation can significantly inhibit tumor growth without causing systemic toxicity and hemolysis. Histological analysis confirmed that after treatment, the apoptosis of tumor cells was enhanced and their proliferation ability was reduced. In conclusion, CuTCPP-MOF is a promising nano-therapeutic agent that can work in synergy with PDT and CDT to achieve effective and safe treatment of prostate cancer.

Head and neck squamous cell carcinoma (HNSCC) presents significant therapeutic challenges owing to its elevated recurrence rate and resistance to chemotherapeutic interventions. Tumor organoid models serve as essential platforms for investigating tumor physiology and pathological functions in vivo for its similarities in recapitulating the spatial structure of HNSCC. We employed HPSCC organoids from typical cell line and patient tissues, which faithfully recapitulated the tumor architecture, combined with CRISPR/Cas9 screening and TCGA-HNSCC database analysis. We identified SREBP1, a master regulator of lipid metabolism, as a key molecule whose expression escalates during HNSCC progression and correlates with improved patient survival and chemotherapy response. Functional studies demonstrated that SREBP1 downregulation conferred resistance to cisplatin and reduced cell death in both organoid and xenograft models in human hypopharyngeal carcinoma (HPSCC). We also found that the downregulation of SREBP1 was associated with enhanced resistance to cisplatin and a reduction in cell death in HPSCC-organoid models ex vivo and xenograft mouse models in vivo. Our findings establish SREBP1-mediated lipid rewiring as a critical determinant of HNSCC pathogenesis and treatment outcomes. Consequently, our model offers a promising solution for the swift and accurate evaluation of chemotherapy efficacy and identifies SREBP1 as a potential therapeutic target in HPSCC.