ACS Biomaterials Science & Engineering最新文献

Mitochondrial metabolism plays an important role in promoting cancer development, making mitochondria a novel promising target for cancer therapy. Current mitochondria-targeted fluorescent agents can specifically accumulate in the mitochondria of cancer cells and can be applied for cancer imaging and therapy. However, their clinical application is still limited due to the poor solubility and lower tumor-specific distribution. In the present study, we synthesized a novel NIR small-molecule dye, Cy750M-C1, and evaluated its optical properties, mitochondrial distribution, and anticancer activity. We also synthesized nanoparticles loading Cy750M-C1 (Cy750M-C1-FA-NPs) and demonstrated that Cy750M-C1-FA-NPs are specifically targeted to the tumor and dramatically inhibited tumor growth in vivo. The mechanistic study revealed that Cy750M-C1 specifically targeted mitochondria of TNBC cells, subsequently promoting ROS production through inhibition of mitochondrial complexes (complexes I, III, and IV) and OXPHOS and depletion of ATP, leading, in turn, to AMPK activation and Drp1 dephosphorylation mediating the mitochondrial translocation of Drp1 and BAX and ultimately inducing mitochondrial fission, caspase activation, as well as apoptosis. Overall, our data implicate that Cy750M-C1 could be developed as a novel anticancer agent with mitochondria-targeting ability and NIR fluorescence imaging and that Cy750M-C1-FA-NPs could also be considered as promising drug delivery carriers for antitumor agents.

This perspective focuses on the potential of artificial intelligence (AI) in craniomaxillofacial (CMF) bone tissue engineering, mitigating current challenges, and driving the development of tailored biomaterials and clinical translation. CMF bone tissue engineering faces significant challenges due to the complexity of bone defects, the limitations of traditional grafting methods, and the need for precise anatomical reconstruction. AI is revolutionizing CMF bone tissue engineering by leveraging vast computational power to analyze complex biological data, optimize treatment strategies, and enhance the development of next-generation regenerative solutions. AI facilitates the customization of scaffolds tailored to patient-specific defects, enables the implementation of drug delivery systems for controlled therapeutic release, drives the development of innovative biomaterials with improved biocompatibility, enhances reproducibility and precision in scaffold fabrication, and advances new additive technologies, such as AI-driven 3D and 4D printing, to enhance manufacturing accuracy and efficiency. Furthermore, AI accelerates diagnostics and predictive modeling, enabling more effective decision-making in treatment planning and improving long-term clinical outcomes. Required standardized, updated protocols significantly improve transparency and reproducibility and effectively bridge the gap between preclinical research and clinical application, ensuring consistent validation and translation of AI-driven innovations. By integrating computational intelligence with regenerative medicine, AI is paving the way for personalized and efficient solutions in CMF bone reconstruction, offering transformative advancements in patient care and shaping the future of precision medicine in regenerative therapies.

Prostate cancer is the second most common cancer among men globally. In this study, we developed a prostate-cancer-targeted gold nanoparticle-based photothermal and photodynamic complex (GNR-ICG-FA@PSMA) to enhance the targeting efficiency of prostate cancer cells and simultaneously deliver photothermal therapy (PTT) and photodynamic therapy (PDT). For the in vitro tests, ROS assays, annexin V/PI staining, and MTT assays were conducted. In the in vivo tests, fluorescence and photoacoustic imaging systems were used to track the distribution of nanoparticles in animal models. Tumor tissues were analyzed post-treatment using Triphenyl tetrazolium chloride (TTC) staining, Hematoxylin and Eosin (HE) staining, and Immunohistochemistry (IHC) staining. The in vitro results showed that GNR-ICG with laser irradiation produced high levels of ROS, the highest rate of apoptosis, and the lowest cell viability. In the in vivo tests, tail-injected GNR-ICG-FA@PSMA reached the tumor within 9 h. During laser irradiation, GNRs increased the temperature (<50 °C), inducing necrosis, while ICGs generated ROS, leading to apoptosis. The results demonstrated that folic acid (FA) and PSMA antibodies improved prostate cancer-specific targeting. GNRs and ICGs contributed to the photothermal and photodynamic effects, respectively. This study confirms the potential of GNR-ICG-FA@PSMA for targeted photothermal and photodynamic therapy of prostate cancer.

Biofilms are significantly involved in the progression of many diseases, such as cancer and upper respiratory infections, due to their ability to adhere to soft tissues. Factors influencing biofilm development have been extensively studied on planar substrates; however, there is limited understanding regarding biofilm growth and interactions within 3D matrices. Developing biofilm models that closely mimic natural bacterial communities' chemical and mechanical properties in soft tissues is essential for developing next-generation antibacterial compounds and therapeutics, as 3D biofilms are more complex and less susceptible to treatment than their 2D counterparts. Here, to understand environmental viscoelastic effects on biofilms within 3D matrix environments, two types of alginate-based hydrogels are formulated and used to encapsulatevarying concentrations of Salmonella Typhimurium. We explore the effects of increasing S. Typhimurium concentrations on hydrogel rheological properties and assess the impact of printing parameters on bacterial viability. Results show that hydrogels exhibit shear thinning behavior and that increasing the bacterial concentration up to 1 × 10⁷ CFU mL^-1 has no significant effect on the hydrogel precursor moduli and low shear viscosity. However, increasing the bacterial concentration to 1 × 10¹⁰ CFU mL^-1 significantly decreases the hydrogel shear viscosity and modulus. Utilizing extrusion-based bioprinting, the optimal printing parameters (Pr > 0.8) have minimal effects on bacterial viability (>80%) over a 4 day incubation period. Additionally, we find that lower concentrations of bacteria form larger aggregates over time than hydrogels with higher cell concentrations. We show that biofilm growth in 3D depends on both initial bacterial density and matrix rigidity. Further development of physicochemically tuned bioprinted bacterial communities will aid our understanding of bacterial interactions within their 3D environments and enable the use of in vitro tissue models that incorporate biofilms for high-throughput therapeutic screening.

Oxidative stress is a principal factor contributing to skin damage induced by deleterious stimuli, including ultraviolet (UV) radiation. Microalgae-derived extracellular vesicles (EVs), particularly those from Phaeodactylum tricornutum (PTEV), are gaining recognition as a potential therapeutic avenue for restoring skin homeostasis, owing to their scalable production and multifaceted biological activities. This study evaluates the therapeutic effects of PTEV on oxidative damage in H₂O₂-stimulated HaCaT cells and UV-exposed KM mouse models, based on the extraction and characterization of PTEV. Subsequently, the oxidative stress injury model of HaCaT cells induced by H₂O₂ and the acute photodamage model of KM mice skin induced by UV were established. The results show that HaCaT cells exhibit a time-dependent uptake of PTEV, confirming that PTEV is nontoxic and has the potential for intercellular cross-boundary regulation. Treatment with PTEV can enhance the vitality of H₂O₂-stimulated HaCaT cells, reduce intracellular ROS levels, and increase antioxidant enzyme activity in the cells. Further evaluation revealed that PTEV can inhibit UV-induced thickening of the epidermis and degradation of collagen fibers in mice by suppressing the overexpression of matrix metalloproteinase (MMP-3) induced by UV. It enhances the expression of type I collagen (COL1A1) and increases the activity of antioxidant enzymes, as well as the overall antioxidant capacity of tissues. Additionally, PTEV reduces the increase in malondialdehyde levels and lowers the expression levels of inflammatory factors TNF-α and IL-6, thereby protecting the skin barrier and function in mice with acute photodamage. Continuous production of PTEV offers promising applications in therapeutic strategies.

In recent years, a major focus in the field of tissue engineering has been the search for a suitable biomaterial for clinical applications. Researchers have sought to optimize natural, synthetic, and hybrid options, with an aim to enhance biological, chemical, physical, and mechanical properties. In the past decade, silk fibroin has emerged as a promising approach due to its suitable properties. Specifically, the chemical modification of silk fibroin with methacrylate agents, namely glycidyl methacrylate, methacrylic anhydride, and gelatin methacryloyl, confers the material with improved biophysical properties. This review presents an in-depth overview of silk fibroin's structure and suitable properties, silk fibroin methacrylate synthesis and characterization techniques, and applications of silk fibroin in bone and cartilage, skin, and nerve tissue engineering. Challenges include a limited understanding of methacrylate agents on specific cell types, which can be addressed by further in vivo investigations utilizing biomaterial compounds to confer tissue-specific needs. We conclude with our perspective of the present limitations and future trends of the methacrylated SF platform.

The therapeutic potential of silk fibroin (SF) and hyaluronic acid (HA) composite hydrogels for corneal epithelial wound healing was assessed, focusing on the molecular weight of SF related to outcomes. Initially, SF of varying molecular weights was analyzed, and a medium molecular weight (M-SF; 10-72 kDa, average 40 kDa) was identified as most effective in promoting cell proliferation, attachment, and migration in various assays. A hydrogel formulation, H-SF/HA gel@M-SF, was then developed by incorporating M-SF (10-72 kDa, average 40 kDa) into a base hydrogel composed of high molecular weight SF (H-SF; 18-100 kDa, average 60 kDa) and HA. The physicochemical properties of the hydrogels, including pH balance, extensibility, and swelling rate, were characterized. The biological functions of the hydrogels were evaluated by using human corneal epithelial (HCE-T) cells and a mouse corneal injury model. H-SF/HA gel@M-SF exhibited supported enhanced expression of key genes associated with corneal repair, such as NOTCH I, GSK3β, ACTG, and VCL when compared with a serum-free medium. In vivo studies using mice demonstrated that H-SF/HA gel@M-SF achieved complete wound closure within 48 h, outperforming the H-SF/HA gel. These results underscore the significance of the SF molecular weight and concentration in hydrogel design and highlight the potential of H-SF/HA gel@M-SF for ophthalmic applications.

Bone tissue damage and associated disorders significantly compromise the quality of life of affected patients, and existing therapeutic options remain limited. Bone marrow mesenchymal stem cells (BMSCs) play a crucial role in bone regenerative medicine, owing to their ability to differentiate into osteoblasts. Utilizing cutting-edge technologies, nanomaterials, and bioactive compounds can emulate the natural bone tissue microenvironment, offer a three-dimensional scaffold that facilitates the osteogenic differentiation of BMSCs, and modulate signals at the molecular level, thereby showing promise for applications in bone regeneration and repair. This review seeks to discuss the latest research advancements, elucidate the underlying mechanisms, and highlight the potential benefits of these technologies in augmenting the osteogenic capacity of BMSCs. Furthermore, the challenges and future directions for integrating these technologies in practical settings are discussed to pioneer new vistas in bone regenerative medicine.

Expanded polytetrafluoroethylene (ePTFE) is a widely used material in diverse medical devices, particularly in the cardiovascular system, owing to its chemical stability and suitable mechanical properties. However, the chemical inertness makes surface modification difficult. In the present study, modification of ePTFE with a peptide was successfully achieved based on a unique photoreaction technique. We previously screened the hemocompatible peptide (HCP), histidine-glycine-glycine-valine-arginine-leucine-tyrosine (HGGVRLY), with high endothelial affinity and antiplatelet ability as modifying molecules. We synthesized a photoreactive peptide by combining a phenylazide group with the HCP, which was subsequently immobilized on the ePTFE surface through a short UV exposure time after argon plasma (Ar) treatment. Cross-sectional images of the surface modified with fluorescent-labeled photoreactive HCP showed efficient modification even within the pores of ePTFE. In vitro assessment revealed that modification improved the endothelial affinity of ePTFE approximately 5-fold while preventing platelet adhesion and aggregation. The ePTFE grafts were further implanted into an in situ porcine closed-circuit system for the blood contact assessment. Comparative investigations with untreated ePTFE grafts indicated that the modified ePTFE surface attracted more cells positive for CD14, CD16, CD34, and macrophage markers while concurrently exhibiting reduced platelet adhesion. In conclusion, photoreactive HCP proved to be a simple and effective strategy for modifying the ePTFE surface, resulting in enhanced hemocompatibility characterized by increased endothelial and monocyte recruitment as well as antiplatelet attachment on the modified ePTFE graft surface.