ACS Biomaterials Science & Engineering最新文献

Extracellular matrix (ECM) hydrogels are recognized as promising biomaterials for regenerative medicine owing to their ability to recapitulate the native tissue microenvironment. The human amniotic membrane (AM), readily available and posing little to no ethical concerns, is rich in ECM components with inherent wound-healing potential. This study aimed to develop and characterize thermosensitive hydrogels derived from a decellularized AM and assess their therapeutic potential for diabetic wound healing. The native AM was subjected to detergent-enzymatic decellularization to remove the cellular content while preserving the essential ECM. The resulting acellular AM was lyophilized, cryomilled, and digested with pepsin under acidic conditions at three different concentrations. The pregel solutions were neutralized and thermally induced to form AM ECM hydrogels at 37 °C. The physicochemical properties, including gelation kinetics, swelling, porosity, mechanical stiffness, and biodegradation, were evaluated. The biological evaluation was assessed using fibroblasts, keratinocytes, and endothelial cells through live/dead staining, the MTS assay, and analyses of ROS production, apoptosis, cytoskeletal organization, and cell migration. Proteomic profiling was conducted to identify the retained matrisome proteins. The in vivo performance was tested in a diabetic murine full-thickness wound model. AM ECM hydrogels exhibited temperature-dependent gelation (t_1/2: ∼12.75–27 min), high water content (>97%), and >60% porosity. All formulations supported >70% cell viability at 24 h and >300% proliferation at 72 h, with negligible ROS production, minimal apoptosis, and preserved cytoskeletal integrity. The proteomic analysis confirmed the maintenance of matrisome proteins related to epithelial differentiation, angiogenesis, and tissue repair. The in vivo study demonstrated that the AM ECM hydrogel accelerated wound healing, evidenced by early wound closure, along with vascular stabilization, regulated inflammatory response, and ECM stabilization compared to those of the control group. These findings collectively demonstrate that AM ECM hydrogel treatment in diabetic mice ameliorates wound pathology, as evidenced by reduced severity, a modulated inflammatory response, and decreased fibrotic burden.

To investigate the ability of novel Gyroid-shaped titanium alloy (TC4) porous bioscaffolds to induce angiogenesis and osteogenesis in bone defect areas. This study employed selective laser melting (SLM) technology to fabricate Gyroid shaped and Cube-shaped TC4 porous bioscaffolds, using the commonly used cube shape as a control. The unit cell size was 4 mm, with a wall thickness or rod diameter of 300 μm and a porosity of approximately 80%. These scaffolds were implanted into rabbit mandibular defect sites (10 mm × 7 mm × 5 mm) to evaluate the angiogenic and osteogenic potential of the Gyroid-shaped scaffold. Material characterization revealed that sandblasted and acid-etched (SLA) TC4 scaffolds met design specifications, exhibiting uniformly distributed micrometer-scale pores and enhanced surface hydrophilicity. Histological staining revealed that compared to the Cube-shaped scaffold, the Gyroid-shaped scaffold induced greater angiogenesis and new bone formation within the bone defect area. Both scaffolds demonstrated good biocompatibility. Western Blot and RT-qPCR results indicated that the Gyroid-shaped scaffold possessed superior angiogenesis potential (compared to the Cube-shaped scaffold). During the early implantation phase (1–2 weeks), Gyroid-shaped scaffolds exhibited higher expression of platelet-endothelial cell surface adhesion molecule 1 (CD31) and endothelial mucin (EMCN). Concurrently, vessel distribution within the scaffold showed spatial variation. Additionally, gene expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) was elevated in the early bone defect area. Imaging analysis confirmed successful implantation of both scaffolds, with the Gyroid-shaped scaffold exhibiting a higher proportion of new bone formation. Consequently, the novel Gyroid-shaped TC4 porous bioscaffold demonstrates excellent potential for angiogenesis and osteogenesis, providing a reference for Gyroid-shaped scaffold-based bone defect repair.

Background: Polyetheretherketone (PEEK) is a promising alternative to titanium alloy for dental implants due to its bone-mimicking elastic modulus, which mitigates stress shielding. However, its bioinert nature limits osseointegration. Methods: We developed a novel PEEK variant, PEEK-chondroitin sulfate zinc (PEEK-CSZn), by chemically grafting zinc and chondroitin sulfate onto the PEEK surface. Material properties were characterized using SEM, FTIR, EDS, and ICP-MS. Anti-inflammatory, osteogenic, and angiogenic effects were evaluated in vitro using MC3T3-E1, HUVEC, and RAW264.7 cells and in vivo using a rabbit femur bone defect model. Results: Characterization confirmed successful CSZn integration. In vitro, PEEK-CSZn at 500 μg/mL enhanced the MC3T3-E1 cell proliferation. Osteogenic markers (OCN and Osterix) were upregulated by around 2.3- and 1.8-fold, respectively, in MC3T3-E1 cells (p < 0.05). Inflammatory markers (IL-6 and IL-12a) in RAW264.7 cells decreased by 23% and 49%, respectively (p < 0.05), while angiogenic markers (VEGF and CD31) in HUVECs increased by 2.2- and 2.8-fold (p < 0.05). In vivo, Micro-CT analysis revealed PEEK-CSZn increased bone volume fraction (BV/TV) and BMD compared to unmodified PEEK at 8 weeks postimplantation (p < 0.05). Conclusions: PEEK-CSZn exhibits trifunctional bioactivities, including anti-inflammatory, osteogenic, and angiogenic, and thus significantly enhances osseointegration, making it a promising material for advanced dental implant applications.

Bacterial infection remains a major challenge in biomedical applications, particularly with the rise of antibiotic-resistant pathogens. Developing antibacterial biomaterials that both prevent infection and support tissue regeneration has become an essential goal in biomedical research. Silk fibroin (SF) is a natural protein derived from Bombyx mori which has been identified as a broad-spectrum, biocompatible, and programmable material in biomedical applications. This review emphasizes SF for antibacterial infection, summarizing its structural features and modulations to immune responses and synergistic combination with multiple antibacterial agents. The unique β-sheet structure of silk fibroin provides resilience and tunable functionality, allowing it to serve as a stable matrix for diverse antibacterial agents. Antibacterial agents enhance antibacterial performance by generating reactive oxygen species, disrupting bacterial membranes, and suppressing biofilm formation. Silk fibroin supports immune modulation by promoting macrophage polarization and reducing inflammation, thereby facilitating tissue repair and wound healing. Overall, SF represents a next-generation antibacterial biomaterial that integrates antimicrobial efficacy with immune modulation, structural tunability, and biocompatibility, having strong potential for infection control and tissue regeneration in clinical applications. Despite advancements in biofunctionality, optimization of controlled release and long-term compatibility challenges still exist for SF’s clinical applications, particularly against antibiotic-resistant pathogens.

Spinal cord injury (SCI) leads to irreversible sensory and motor deficits due to its limited capacity for regeneration of the central nervous system (CNS). While the current clinical strategies focus on neuroprotection and stabilization of the symptoms, they offer very little in terms of restoring long-term functional recovery. Three-dimensional (3D) bioprinting has opened new possibilities for constructing patient specific scaffolds that mimic the structural and biochemical complexities of native spinal tissue. The incorporation of cells, biomaterials, and growth factors, in 3D bioprinting provides incomparable control over the architecture of the scaffold, which in turn enables recreation of biomimetic environment that supports axonal outgrowth and neural recovery following SCI. This review focuses on the recent advances in 3D bioprinting techniques for SCI repair and discusses the potential of the techniques to be implemented in SCI models. Focus is placed on the bioink formulation, scaffold design strategies, and emerging functional features. The amalgamation of current findings underscores the potential of 3D bioprinting as a mature platform for the development of next-generation therapies for spinal cord injury.

This study aimed to reconstruct the hypothalamic–pituitary axis using an organ-on-a-chip (OOC) model and to evaluate the modulatory role of phoenixin-20 (PNX) in the regulation of the gonadotrophic axis in sheep. Sixteen female Polish Merino lambs were used as tissue donors to create microfluidic chips containing paired hypothalamic and pituitary slices connected via perfused channels. This system enabled continuous medium flow and maintenance of functional neuroendocrine interactions under ex vivo conditions. The OOC platform was used to analyze changes in the expression of gonadotropin-releasing hormone (GnRH), kisspeptin (Kiss), neurokinin B (NKB), and prodynorphin (pDYN) in the hypothalamus, as well as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) expression and secretion in the pituitary. PNX treatment significantly increased hypothalamic GnRH expression, while the blockade of neuropeptide Y receptors (NPY1R and NPY5R) diminished this response, suggesting that PNX effects are at least partially mediated through NPY-dependent pathways. Moreover, PNX altered the transcription of Kiss, NKB, and pDYN, key components of the GnRH pulse generator, and modulated LHβ mRNA expression in the pituitary. Changes in the LH and FSH concentrations further supported a receptor-specific mechanism of PNX action. The developed hypothalamo–pituitary OOC model proved valuable for studying neuroendocrine control of reproduction. This system offers a physiologically relevant and ethically sustainable alternative to in vivo experiments, enabling precise investigations of molecular and hormonal mechanisms within the gonadotrophic axis.

Targeted delivery of therapeutics to bladder cancer is crucial for optimizing therapeutic efficacy and minimizing side effects. In this study, a novel targeted nanocarrier system was developed to enhance bladder cancer targeted therapy by modifying liposomes with 4-carboxyphenylboronic acid (CPBA), enabling selective binding with sialic acid residues overexpressed on bladder cancer cells. To further improve therapeutic outcomes, we employed a combination therapy based on chemotherapy and immunotherapy to both eliminate tumor cells and activate antitumor immune responses. We fabricated tumor-targeting liposome-chitosan-CPBA (LPCB) nanoparticles coloaded with doxorubicin (Dox), a chemotherapeutic agent, and resiquimod (R848), a toll-like receptor (TLR) 7/8 agonist that stimulates antitumor immunity. LPCB nanoparticles encapsulating Dox and R848 (LPCBDR) demonstrated enhanced binding to bladder tumor cells (T24, MB49) and cytotoxicity compared to nontargeted (non-CPBA incorporated) nanoparticles. LPCBDR nanoparticles also showed enhanced activation of murine dendritic cell (DC) populations characterized by the upregulation of costimulatory molecules. In vivo biodistribution studies with Cy7-labeled nanoparticles confirmed preferential tumor accumulation of LPCB NPs compared to nontargeted nanoparticles. Therapeutic efficacy using MB49 subcutaneous tumor model revealed that LPCBDR treatment group significantly reduces tumor volume compared to nontargeted nanoparticles and free drugs. Flow cytometric analysis of tumor and spleen samples further showed robust activation of Natural Killer (NK) cells, CD4⁺ T cells, and CD8⁺ T cell effector functions. Combined results demonstrate that sialic acid targeting LPCBDR nanoparticles offers a promising drug delivery platform for bladder cancer therapy.

Hepatocellular carcinoma (HCC) remains a clinically challenging malignancy, and it is imperative to develop novel therapeutic strategies for HCC treatment. In this study, we developed a novel mRNA-based nanovaccine (SK-mRNA) targeting the tumor-associated antigen glypican-3 (GPC3). The SK-mRNA vaccine consists of in vitro-transcribed mRNA encoding 3 × GPC3_127–136 CTL epitopes fused with HSP70, which self-assembles with the cationic peptide SP94-GGG-K18 to form a uniform spherical nanostructure. This nanovaccine facilitates the targeted delivery of mRNA to tumors via SP94 binding with its cognate receptor on tumor cells, enabling the expression and secretion of the 3 × GPC3_127–136-HSP70 fusion protein. Subsequently, dendritic cells internalize this protein through its receptors on dendritic cells, leading to the presentation of CTL epitope GPC3_127–136 to T cells. Experimental vaccination elicited robust antigen-specific T-cell responses, as evidenced by the significant increase in CD8⁺ T cells observed in both spleens and tumors, along with enhanced IFN-γ secretion in response to the GPC3_127–136 peptide. The combination of SK-mRNA nanovaccine with anti-PD-L1 immunotherapy exhibited potent synergistic antitumor effects. These findings collectively suggest that SK-mRNA nanovaccines can effectively stimulate immune responses and synergize with immune checkpoint blockade therapies to mediate powerful antitumor effects, offering a promising strategy for the effective treatment of HCC.

Objective: This work aimed to elucidate the molecular mechanisms by which human umbilical cord mesenchymal stem cell (HUMSC)-derived extracellular vesicles (EVs) loaded with microRNA-183-5p (miR-183-5p) mitigate sepsis-induced acute kidney injury (AKI), focusing on the downregulation of thrombospondin-1 (THBS1) and suppression of the TGF-β pathway. Methods: A cecal ligation and puncture (CLP) model was established to induce sepsis-induced AKI in mice, and an in vitro injury model was generated by exposing human renal tubular epithelial cells (HK-2 cells) to lipopolysaccharide (LPS). miR-183-5p expression levels in injured tissues and cells were assessed using RT-qPCR. EVs were isolated from HUMSCs via ultracentrifugation, and miR-183-5p-loaded EVs were prepared using electroporation. These loaded EVs were then administered to mice to assess their impacts on renal function, histopathological alterations, and apoptosis. Bioinformatic prediction identified THBS1 as miR-183-5p’s potential target, which was verified through miRNA mimic transfection, dual-luciferase reporter assays, and THBS1 overexpression rescue experiments. Results: miR-183-5p expression was reduced in both the sepsis-induced AKI mouse model and LPS-treated HK-2 cells. Administration of miR-183-5p-loaded EVs effectively reduced serum inflammatory cytokine levels, improved renal function, and reduced apoptosis, thereby alleviating sepsis-induced AKI in mice. miR-183-5p directly targeted and inhibited THBS1 expression, thereby reducing LPS-induced apoptosis in HK-2 cells. Further experiments revealed that THBS1 promoted inflammation and apoptosis through the activation of the TGF-β pathway. Conclusion: HUMSC-derived EVs loaded with miR-183-5p effectively mitigate sepsis-induced AKI by targeting THBS1 and inhibiting the TGF-β pathway, thereby reducing inflammation and apoptosis.