Biomaterials Science最新文献

Infected alveolar bone defects pose challenging clinical issues due to disrupted intrinsic healing mechanisms. Thus, the employment of advanced biomaterials enabling the modulation of several aspects of bone regeneration is necessary. This study investigated the effect of multi-functional nanoparticles on anti-inflammatory/osteoconductive characteristics and bone repair in the context of inflamed bone abnormalities. Tannic-acid mineral nanoparticles (TMPs) were prepared by the supramolecular assembly of tannic acid with bioactive calcium and phosphate ions, which were subsequently incorporated into collagen plugs via molecular interactions. Under physiological conditions, in vitro analysis confirmed that tannic acid was dissociated and released, which significantly reduced the expression of pro-inflammatory genes in lipopolysaccharide (LPS)-activated RAW264.7 cells. Meanwhile, the bioactive ions of Ca²⁺ and PO₄^3- synergistically increased the gene and protein expressions of osteogenic markers of bone marrow-derived stem cells. For in vivo studies, combined endodontic-periodontal lesions were induced in beagle dogs where the plugs were readily implanted. After 2 months of the implantation, analysis of micro-computed tomography and histomorphometry revealed that groups of dogs implanted with the plug incorporating TMPs exhibited a significant decrease in bone surface density as well as structural model index, and significant increase in the mineralized bone content, respectively, with positive OPN expression being observed in reversal lines. Notably, the profound improvement in bone regeneration relied on the concentration of TMPs in the implants, underscoring the promise of multi-functional nanoparticles for treating infected alveolar bones.

Extracellular vesicles (EVs) are secreted by almost all cell types and contain DNA, RNA, proteins, lipids and other metabolites. EVs were initially believed to be cellular waste but now recognized for their role in cell-to-cell communication. Later, EVs from immune cells were discovered to function similarly to their parent cells, paving the way for their use as gene and drug carriers. EVs from different cell types or biological fluids carry distinct cargo depending on their origin, and they perform diverse functions. For instance, EVs derived from stem cells possess pluripotent properties, reflecting the cargo from their parent cells. Over the past two decades, substantial preclinical and clinical research has explored EVs-mediated drug and gene delivery to various organs, including the brain. Natural or intrinsic EVs may be effective for certain applications, but as drug or gene carriers, they demonstrate broader and more efficient potential across various diseases. Here, we review research on using EVs to treat central nervous system (CNS) diseases, such as Alzheimer's Disease, Parkinson diseases, depression, anxiety, dementia, and acute ischemic strokes. We first reviewed the naïve EVs, especially mesenchymal stem cell (MSC) derived EVs in CNS diseases and summarized the clinical trials of EVs in treating CNS diseases and highlighted the reports of two complete trials. Then, we overviewed the preclinical research of EVs as drug and gene delivery vehicles in CNS disease models, including the most recent two years' progress and discussed the mechanisms and new methods of engineered EVs for targeting CNS. Finally, we discussed challenges and future directions and of EVs as personalized medicine for CNS diseases.

The tetrapyrrolic macrocycle as a scaffold for various chemical modifications provides broad opportunities for the preparation of complex multifunctional conjugates suitable for binary antitumor therapies. Typically, illumination with monochromatic light triggers the photochemical generation of reactive oxygen species (ROS) (photodynamic effect). However, more therapeutically valuable effects can be achieved upon photoactivation of tetrapyrrole derivatives. Herein we report the novel porphyrin-based complexes of transition metals with isocyanide and carbonyl ligands. Synthesis of complexes presumed the use of 5-(p-isocyanophenyl)-10,15,20-triphenylporphyrin as a ligand in reactions with metal carbonyl complexes, M(CO)₆ (M = Cr, Mo, W), Re₂(CO)₁₀ and Re(CO)₅Cl. Based on these complexes and isocyanocarborane, the heteroleptic carbonyl complexes with porphyrin and carborane isocyanide ligands were prepared. In cell-free systems, the new compounds retained photochemical characteristics of the parental porphyrin derivative, such as triplet state formation and ROS generation, upon light-induced activation. In the cell culture, the carborane-containing derivatives demonstrated a more pronounced intracellular accumulation than their nonboronated counterparts. As expected, illumination at the Soret band (405 nm) of cells loaded with the new complexes caused photodynamic cell damage. In contrast, illumination at 530 nm instead initiated the release of carbon oxide (CO) followed by cell death independently of the photodynamic effect. Light-induced CO release was analyzed using second derivatives of UV-Vis spectra and our originally developed Spectrophotometric elimiNAtion of Photoinduced Side reactions (SNAPS) method. The yield of CO release decreased in the raw depending on metals in the carbonyl moiety: Mo ≥ Cr > W > Re ≥ Re₂. Overall, our novel metal carbonyl complexes with porphyrin and carborane isocyanide ligands emerge as potent bi-functional conjugates for combined photodynamic and photoinducible CO-releasing antitumor agents.

Acute severe trauma is often associated with rapid blood loss and a high risk of infection. Based on these concerns, this study successfully constructed a multifunctional dual-layer bioactive sponge PCCT with rapid hemostatic and infection-preventing ability. Its external surface is an electrospun poly(lactic acid) (PLA) nanofiber thin film layer, which ensures its high air permeability and effectively protects against external bacterial invasion. In vitro results showed that the film is effectively resistant to invasion by typical Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. The inner sponge layer was formed by chlorogenic acid (CGA) grafted with chitosan (CS) and loaded with tranexamic acid (TA). The abundant cationic groups on the sponge interacted with negatively charged erythrocytes and achieved rapid hemostasis at the wound site under the action of TA. In addition, the high porosity and bioactivity of the CS-CGA sponge scaffold endowed the hydrogel with good water absorption, antibacterial properties and anti-inflammatory activity, which effectively accelerated the healing of acute infected wounds in rats and demonstrated favorable biosafety.

Objective: To explore the relationship between the stability of poly(gamma-glutamic acid) (γ-PGA) dispersion systems with γ-PGA of different molecular weights (MWs) and concentrations and type I collagen mineralization. Methods: γ-PGA was used as a noncollagenous protein (NCP) analogue to regulate the stability of supersaturated γ-PGA-stabilized amorphous calcium phosphate (PGA-ACP) solutions by changing the γ-PGA MW (2, 10, 100, 200 and 500 kDa) and concentration (400, 500 and 600 μg mL^-1). Then, the optical density (OD) at 72 h was measured to determine the PGA-ACP solution stability. Recombinant type I collagen films were mineralized in different PGA-ACP solutions for 3 d and observed via transmission electron microscopy (TEM) to confirm the occurrence of intrafibrillar mineralization. The collagen scaffolds were mineralized for 7 d and observed via scanning electron microscopy (SEM) to determine the collagen mineralization pattern and degree. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and thermogravimetry (TG) were used to analyse the mineralized collagen scaffold composition. Results: The PGA-ACP solutions with γ-PGA of different MWs and concentrations had different stabilities and type I collagen mineralization. Except for the 100 kDa group, which neither stabilized the supersaturated calcium phosphate solution nor induced intrafibrillar mineralization, the groups stabilized the solutions for at least 10 h and induced different intrafibrillar mineralization patterns and degrees. Conclusion: In our system, the PGA-ACP solution stability and occurrence of intrafibrillar mineralization are directly correlated. Thus, we suspect that the same correspondence exists in other biomimetic mineralization systems and that a relatively stable supersaturated calcium phosphate solution may be a necessary condition for intrafibrillar mineralization.

Accurate imaging of tumor hypoxia in vivo is critical for early cancer diagnosis and clinical outcomes, highlighting the great need for its detection specificity and sensitivity. In this report, we propose a probe (HTRNP) that simultaneously has hypoxia-targeting and hypoxia-responsive capabilities to enhance the tumor hypoxia imaging efficiency. HTRNP was successfully prepared through the encapsulation of Pt(II)-tetrakis(pentafluorophenyl)porphyrin (PtPFPP), which exhibits hypoxia-dependent phosphorescence, within the amphiphilic block copolymer OPDMA-PF, which has hypoxia-targeting tertiary amine N-oxide moieties and hydrophobic perfluorobenzene ring structures, which highly improved the loading content and water solubility of PtPFPP. By combining targeting and response abilities toward hypoxic conditions, the HTRNP micelles efficiently accumulate in the tumor tissues and emit intense phosphorescence, thus enabling ultrasensitive detection of various tumor models, even of hundreds of cancer cells, indicating its promising potential for early cancer detection and phenotypic characterization.

As water-saturated polymer networks, the easy water loss of hydrogels directly affects their end-use applications. Minimizing the ratio of free water and increasing the ratio of bound water in the gel system has become key to extending the service life. In this work, an ionogel is prepared that effectively regulates the proportion of free water and bound water through the formation of wrinkle angles by the hydrophilic and hydrophobic chains in the gel system and the non-volatile nature of the ionic liquid. Acrylamide and N-acryloyl phenylalanine are used as free radical comonomers, and phenol red is used as an acid-base indicator. The ionic liquid is used as a dispersant to stabilize the whole framework. Due to the hydrogen bonding interactions, electrostatic interactions, and ion-ion interactions, the ionogel exhibits good stretchability, adhesion, pH sensitivity, and stability. The ionogel can be stretched in multiple directions without cracking and can be bent 180° after being left in air for 45 days. Assembling the ionogel into a wearable device can effectively monitor the pH value of sweat during exercise. The detection results are displayed in the form of RGB values, providing a preliminary diagnosis of the health of the human body.

Wound healing is a dynamic and complex process involving hemostasis, inflammation, fibroblast proliferation, and tissue remodeling. This process is highly susceptible to bacterial infection, which often leads to impaired and delayed wound repair. While antibiotic therapy remains the primary clinical approach for treating bacteria-infected wounds, its widespread use poses a significant risk of developing bacterial resistance. Here, a novel drug-free hydrogel was fabricated using polysaccharides and humic acid (HU) to facilitate the healing of bacteria-infected wounds. Specifically, hyaluronic acid (HA) was modified via oxidation with sodium periodate, introducing aldehyde groups along its main chains. Pectin (PT) was grafted with amino groups on its side chains through an amidation reaction with ethylenediamine. HU, a natural organic compound with hemostatic, antioxidant, antibacterial, anti-inflammatory, and photothermal properties, was reduced using sodium borohydride to generate an increased number of phenolic hydroxyl and catechol groups. The resulting hydrogel, called HA-PT/HUOH, was prepared by integrating these three chemically modified biomaterials through dynamic Schiff base cross-linking and hydrogen bonding. The HA-PT/HUOH hydrogel showed excellent injectability, strong bioadhesiveness, rapid self-healing capabilities, and potent photothermal performance. Both in vitro and in vivo studies demonstrated that HA-PT/HUOH significantly accelerated the healing of bacteria-infected wounds by modulating the entire wound-healing process. This included enhancing hemostasis, bacteriostasis, antioxidation, anti-inflammatory responses, fibroblast proliferation, and tissue remodeling. In summary, this multifunctional drug-free hydrogel presents a highly promising solution as a wound dressing for clinical application.

Myocardial infarction (MI) remains one of the most common and lethal cardiovascular diseases (CVDs), leading to the deterioration of cardiac function due to myocardial cell necrosis and fibrous scar tissue formation. Myocardial infarction (MI) remains one of the most common and lethal cardiovascular diseases (CVDs), leading to the deterioration of cardiac function due to myocardial cell necrosis and fibrous scar tissue formation. After MI, the anisotropic structural properties of myocardial tissue are destroyed, and its mechanical and electrical microenvironment also undergoes a series of pathological changes, such as ventricular wall stiffness, abnormal contraction, conduction network disruption, and irregular electrical signal propagation, which may further induce myocardial remodeling and even lead to heart failure. Therefore, bionic reconstruction of the anisotropic structural-mechanical-electrical microenvironment of the infarct area is key to repairing damaged myocardium. This article first summarizes the pathological changes in muscle fibre structure and conductive microenvironment after cardiac injury, and focuses on the classification and preparation methods of anisotropic conductive materials. In addition, the effects of these anisotropic conductive materials on the behavior of cardiac resident cells after myocardial infarction, such as directional growth, maturation, proliferation and migration, and the differentiation fate of stem cells and the possible molecular mechanisms involved are summarized. The design strategies for anisotropic conductive scaffolds for myocardial repair in future clinical research are also discussed, with the aim of providing new insights for researchers in related fields.

Despite the promising results in cancer treatment, standard monotherapy remains insufficient for a wide range of oncological diseases. Combined therapy can significantly improve therapeutic outcomes compared to single-agent treatments. However, identifying the optimal treatment regimen for combined therapy can be a challenging task. In this work, we developed a therapeutic strategy for the treatment of three types of tumors - CT26 colorectal cancer, B16-F10 melanoma and 4T1 breast cancer using combined chemo- and radionuclide therapy. This was achieved by loading nanoparticles with radium-223 (²²³Ra-labeled NPs) and the chemotherapeutic drug doxorubicin (DOX). Each tumor model (CT26, B16-F10, 4T1) was treated using different therapeutic strategies: (i) intravenous or (ii) intratumoral administration of ²²³Ra-labeled NPs for single radionuclide therapy; (iii) intravenous injection of DOX for chemotherapy; and (iv) intratumoral injection of ²²³Ra-labeled NPs combined with intravenous administration of DOX for combined therapy. Our results demonstrated that each tumor model exhibited a distinct response to single and combined therapies. Notably, the combined chemo- and radionuclide therapy (DOX = 10 mg kg^-1 and ²²³Ra-labeled NPs = 2.7 KBq kg^-1) demonstrated a significantly higher therapeutic outcome than single therapies (DOX = 10 mg kg^-1 or ²²³Ra-labeled NPs = 2.7 KBq kg^-1). In particular, the average therapeutic response was >35% for monotherapy and >60%-80% for combined therapy. Importantly, the therapeutic effect across the three tumor types followed the order B16-F10 >4T1 >CT26. Thus, this work systematically investigated the response of three tumor types to the applicability of single chemo- or radionuclide therapy and their combination.