Biomaterials Science最新文献

Photocrosslinkable hydrogels based on hyaluronic acid are promising biomaterials high in demand in tissue engineering. Typically, hydrogels are photocured under the action of UV or blue light strongly absorbed by biotissues, which limits prototyping under living organism conditions. To overcome this limitation, we propose the derivatives of well-known photosensitizers, namely chlorin p₆, chlorin e₆ and phthalocyanine, as those for radical polymerization in the transparency window of biotissues. Taking into account the efficiency of radical generation and dark and light cell toxicity, we evaluated water miscible pyridine phthalocyanine as a promising initiator for the intravital hydrogel photoprinting of hyaluronic acid glycidyl methacrylate (HAGM) under irradiation near 670 nm. Coinitiators (dithiothreitol or 2-mercaptoethanol) reduce the irradiation dose required for HAGM crosslinking from ∼405 J cm⁻² to 80 J cm⁻². Patterning by direct laser writing using a scanning 675 nm laser beam was performed to demonstrate the formation of complex shape structures. Young's moduli typical of soft tissue (∼270–460 kPa) were achieved for crosslinked hydrogels. The viability of human keratinocytes HaCaT cells within the photocrosslinking process was shown. To demonstrate scaffolding across the biotissue barrier, the subcutaneously injected photocomposition was crosslinked in BALB/c mice. The safety of the irradiation dose of 660–675 nm light (100 mW cm⁻², 15 min) and the non-toxicity of the hydrogel components were confirmed by histomorphologic analysis. The intravitally photocrosslinked scaffolds maintained their shape and size for at least one month, accompanied by slow biodegradation. We conclude that the proposed technology provides a lucrative opportunity for minimally invasive scaffold formation through biotissue barriers.

Reactive oxygen species (ROS) play essential roles in both physiological and pathological processes. Under physiological conditions, appropriate amounts of ROS play an important role in signaling and regulation in cells. However, too much ROS can lead to many health problems, including inflammation, cancer, delayed wound healing, neurodegenerative diseases (such as Parkinson's disease and Alzheimer's disease), and autoimmune diseases, and oxidative stress from excess ROS is also one of the most critical factors in the pathogenesis of cardiovascular and metabolic diseases such as atherosclerosis. Hydrogen gas effectively removes ROS from the body due to its good antioxidant properties, and hydrogen therapy has become a promising gas therapy strategy due to its inherent safety and stability. The combination of nanomaterials can achieve targeted delivery and effective accumulation of hydrogen, and has some ameliorating effects on diseases. Herein, we summarize the use of hydrogen-producing nanomaterials for the treatment of ROS-related diseases and talk about the prospects for the treatment of other ROS-induced disease models, such as acute kidney injury.

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.

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.

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.

The skin, as the body's largest organ, plays a crucial role in protecting against mechanical forces and infections, maintaining fluid balance, and regulating body temperature. Therefore, skin wounds can significantly threaten human health and cause a heavy economic burden on society. Recently, bioelectric fields and electrical stimulation (ES) have been recognized as a promising pathway for modulating tissue engineering and regeneration of wounded skin. However, conventional hydrogel dressing lacks electrical generation capabilities and usually requires external stimuli to initiate the cell regeneration process, and the role of ES in different stages of healing is not fully understood. Therefore, to endow hydrogel-based wound dressings with piezoelectric properties, which can accelerate wound healing and potentially suppress infection via introducing ES, piezoelectric hydrogels (PHs) have emerged recently, combining the advantages of both piezoelectric nanomaterials and hydrogels beneficial for wound healing. Given the scarcity of systematic literature on the application of PHs in wound healing, this paper systematically discusses the principles of the piezoelectric effects, the design and fabrication of PHs, their piezoelectric properties, the way PHs trigger ES and the mechanisms by which they promote wound healing. Additionally, it summarizes the recent applications of PHs in various types of wounds, including traumatic wounds, pressure injuries, diabetic wounds, and infected wounds. Finally, the paper proposes future directions and challenges for the development of PH wound dressings for wound healing.

Epigallocatechin gallate (EGCG), an important active component extracted from green tea, has attracted much attention due to its multiple biological activities such as antioxidant, antibacterial, anti-inflammatory, and antitumor effects. Meanwhile, metformin (Met), a classic drug for the treatment of type 2 diabetes, exhibits additional benefits such as hypoglycemic, antioxidant, anti-inflammatory, and antitumor effects. However, metformin often causes gastrointestinal reactions when used alone, affecting patients’ quality of life. In view of this, we proposed an innovative technique for the fabrication of a carrier-free, dual-loaded nanodrug, Met-EGCG nanoparticles (Met-EGCG NPs), via self-assembly. The method for preparing Met-EGCG NPs is simple, rapid and cost-effective. In addition, the carrier-free Met-EGCG NPs nanodrug inherits the strong antioxidant capacity, good biocompatibility and excellent aggregation-induced fluorescence effect of EGCG, and even offer significant advantages in enhancing drug solubility, stability, and bioavailability, while effectively reducing the occurrence of side effects. Moreover, this Met-EGCG NPs nanodrug exhibits a synergistic therapeutic effect of EGCG and metformin, thereby significantly enhancing overall therapeutic efficacy, and demonstrates excellent potential in anti-cancer applications. This study not only successfully prepared Met-EGCG NPs but also experimentally verified their superior performance, opening a new path for the application of EGCG in drug therapy. This carrier-free, dual-loaded drug delivery nanosystem based on Met-EGCG NPs offers potential for drug combination therapy, promising to play a more critical role in the biomedical field and providing new insights and guidance for the development of future multidrug delivery systems.

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.

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.