Biomaterials Science最新文献

An increase in plastic waste and its release into the environment has led to health concerns over microplastics (MPs) in the environment. The intestinal mucosal layer is a key defense mechanism against ingested MPs, preventing the migration of particles to other parts of the body. MP migration through intestinal mucus is challenging to study due to difficulties in obtaining intact mucus layers for testing and numerous formulations, shapes, and sizes of microplastics. Previous studies have primarily used mucus from animals, hydrogel models, and mucus samples from other parts of the body as substitutes. This study examines how different MP compositions, sizes (40-500 nm), and surface functionalizations alter MP migration through human intestinal mucus; how the mucus layer protects cells from MP uptake, toxicity, and inflammation; and how the intestinal mucus prevents the migration of other environmental toxins via MP particles. The presence of a mucus layer also provides critical protection against cytotoxicity, reactive oxygen species production, and uptake for all particles tested, although certain functionalizations, such as streptavidin, are particularly harmful to cells with high toxicity and inflammation. Understanding the properties that assist of impede the diffusion of MPs through mucus is relevant to the overall bioaccumulation and health effects of MPs as well as drug delivery purposes.

Biphasic calcium phosphate (BCP) is a bioceramic widely used in hard tissue engineering for bone replacement. BCP consists of β-tricalcium phosphate (β-TCP) - a highly soluble and resorbable phase - and hydroxyapatite (HA) - a highly stable phase, creating a balance between solubility and resorption, optimally supporting cell interactions and tissue growth. The β-TCP/HA ratio significantly affects the resorption, solubility, and cellular response, with a higher β-TCP ratio increasing resorption due to its solubility. BCP is commonly synthesized by calcining calcium-deficient apatite (CDA) at temperatures above 700 °C via direct or indirect methods. This study investigated the effects of pH and sintering temperature on BCP synthesized via wet precipitation, aiming to achieve an 80/20 β-TCP/HA ratio, which is known to be optimal for bone regeneration. By maintaining a constant Ca/P precursor ratio of 1.533, the optimal conditions were determined to be a pH of 5.5-6 and a sintering temperature of 900 °C, chosen to balance material stability and solubility. The successful synthesis was confirmed using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. At the same time, the material's physical and chemical properties were further characterized through scanning electron microscopy (SEM) and degradation studies in a simulated body fluid (SBF). In vitro tests demonstrated excellent cytocompatibility and osteogenic differentiation, while in vivo studies on rabbit femur defects demonstrated significant bone regeneration, with bone-to-tissue volume ratios exceeding 50% within four weeks. These results highlight the potential of BCPs in bone tissue engineering and biomaterials research.

Hydroxyapatite (HA), the main inorganic bone component, is the most widely researched bioceramic for bone repair. This paper presents a comprehensive review of recent advancements in HA synthesis methods and their integration into additive manufacturing (AM) processes. Synthesis methodologies discussed include wet, dry, and biomimetic routes, emphasizing their impact on tailoring the physicochemical properties of HA for biomedical applications. The incorporation of dopants and additives during synthesis is explored for optimizing the mechanical, biological, and osteogenic characteristics of HA-based materials. Moreover, the evolution of AM technologies from conventional 3D printing to advanced 4D and 5D printing is detailed, covering material selection, process parameters, and post-processing strategies vital for fabricating intricate, patient-specific scaffolds, implants, and drug delivery systems utilizing HA. The review underscores the importance of achieving precise control over microstructure and porosity to mimic native tissue architectures accurately. Furthermore, emerging applications of HA-based constructs in tissue engineering, regenerative medicine, drug delivery, and orthopedic implants are discussed, highlighting their potential to address critical clinical needs. Despite the glimmer of hope provided by the advent and progress of such AM capabilities, several aspects need to be addressed to develop efficient HA-based bone substitutes, which are explored in detail in this review.

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.

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 pivotal roles played by nitric oxide (NO) in tissue repair, inflammation, and immune response have spurred the development of a wide range of NO-releasing biomaterials. More recently, 3D printing techniques have significantly broadened the potential applications of polymeric biomaterials in biomedicine. In this context, the development of NO-releasing biomaterials that can be fabricated through 3D printing techniques has emerged as a promising strategy for harnessing the benefits of localized NO release from implantable devices, tissue regeneration scaffolds, or bandages for topical applications. Although 3D printing techniques allow for the creation of polymeric constructs with versatile designs and high geometric precision, integrating NO-releasing functional groups or molecules into these constructs poses several challenges. NO donors, such as S-nitrosothiols (RSNOs) or diazeniumdiolates (NONOates), may release NO thermally, complicating their incorporation into resins that require heating for extrusion-based 3D printing. Conversely, NO released photochemically from RSNOs effectively inhibits radical propagation, thus hindering photoinduced 3D printing processes. This review outlines the primary strategies employed to overcome these challenges in developing NO-releasing biomaterials via 3D printing, and explores future prospects in this rapidly evolving field.

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.

The application of nanotechnology in medical biology has seen a significant rise in recent years because of the introduction of novel tools that include supramolecular systems, complexes, and composites. Dendrimers are one of the remarkable examples of such tools. These spherical, regularly branching structures with enhanced cell compatibility and bioavailability have shown to be an excellent option for gene or drug administration. They are the fourth important architectural group of polymers after the three well-known types (branched, cross-linked, and linear polymers). These tiny macromolecules generate nanometer-size structures consisting of branching, with identical units assembled around a central core. By regulating dendrimer synthesis, it is possible to manipulate both their molecular weight and chemical content carefully, permitting predictable tailoring of their biocompatibility and pharmacokinetics, making them a promising candidate for biomedical uses. In contrast to their more easily obtainable synthetic techniques and comparable functions in hyperbranched polymers, dendrimers have demonstrated efficacy in biological applications, exhibiting remarkable sample purity and synthesizing reproducibility. Dendrimers are appealing as basic materials for manufacturing nanomaterials for uses in many different disciplines because of their highly specified chemical structure and globular form. Thus, much effort has been made to create functional materials with dendrimers. Especially looking at dendrimer-based nanomaterials meant for use in the biomedical domain, this review discusses the design, types, properties, and function of bionanomaterials employing several techniques, including surface modification, assembly, and hybrid development, and their uses.

We are facing a shortage of new antibiotics to fight against increasingly resistant bacteria. As an alternative to conventional small molecule antibiotics, antimicrobial polymers (AMPs) have great potential. These polymers contain cationic and hydrophobic groups and disrupt bacterial cell membranes through a combination of electrostatic and hydrophobic interactions. While most examples focus on ammonium-based cations, sulfonium groups are recently emerging to broaden the scope of polymeric therapeutics. Here, main-chain sulfonium polymers exhibit good antimicrobial activity. In contrast, the potential of side-chain sulfonium polymers remains less explored with structure-activity relationships still being limited. To address this limitation, we thoroughly investigated key factors influencing antimicrobial activity in side-chain sulfonium-based AMPs. For this, we combined sulfonium cations with different hydrophobic (aliphatic/aromatic) and hydrophilic polyethylene glycol (PEG) groups to create a library of polymers with comparable chain lengths. For all compositions, we additionally examined the position of cationic and hydrophobic groups on the polymer backbone, i.e., we systematically compared same center and different center structures. Bactericidal tests against Gram-positive and Gram-negative bacteria suggest that same center polymers are more active than different center polymers of similar clog P. Ultimately, sulfonium-based AMPs show superior bactericidal activity and selectivity when compared to their quaternary ammonium cationic analogues.

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.