Biomaterials research最新文献

Photomedicine, which utilizes light for therapeutic purposes, has several hurdles such as limited tissue penetration for short-wavelength light and inadequate deep tissue efficacy for long-wavelength light. Photon energy upconversion (UC) reveals promise in photomedicine because it enables the conversion of lower-energy photons into higher-energy photon. Lanthanide (Ln)-based inorganic UC system has been extensively studied but faces challenges, including high excitation laser power density, intrinsically subpar UC quantum efficiency, and potential biotoxicity. Recently, an organic-based triplet-triplet annihilation UC (TTA-UC) system has emerged as a novel UC system due to its prolonged emission lifetime upon low power laser excitation and exceptional UC quantum yield. In this study, we developed water-dispersible hyaluronic acid (HA)-conjugated polycaprolactone (PCL) nanoparticles loaded with TTA-UC chromophores (HA-PCL/UC NPs), which allow deeper tissue penetration by converting red light (635 nm) into blue light (470 nm) for noninvasive transdermal delivery. HA-PCL/UC NPs demonstrated a 1.6% high quantum yield in distilled water, improved cellular imaging in HeLa cells, and effectively penetrated the deep tissue of porcine skin, showing upconverted blue light. Our strategy holds significant potential as a next-generation noninvasive photomedicine platform for bioimaging, photo-triggered drug delivery, and photodynamic therapy, ultimately advancing targeted and effective therapeutic interventions.

Collagen membranes play a crucial role in guided bone regeneration (GBR) by preventing soft tissue infiltration and maintaining space for bone formation. This study investigated the impact of collagen membrane flexibility on GBR outcomes through in vitro and in vivo analyses. Flexible (0.3 mm in width) and stiff (0.5 mm in width) porcine collagen membranes were compared. In vitro tests assessed hydrophilicity, enzymatic degradation, conformability, space maintenance, and tensile strength. An in vivo study using a canine model evaluated bone regeneration in standardized mandibular defects filled with deproteinized porcine bone mineral and covered with no membrane, flexible membrane, or stiff membrane. Micro-computed tomography and histomorphometric analyses were performed at 8 and 16 weeks. The flexible membrane demonstrated superior hydrophilicity, faster enzymatic degradation, and greater conformability in vitro. In vivo, micro-computed tomography analysis revealed similar alveolar ridge widths across all groups. Histomorphometric analysis at 16 weeks showed significantly larger regenerated areas in the flexible membrane group compared to controls in coronal, middle, and apical regions. Both membrane groups exhibited higher regeneration ratios than controls, with significant differences in the coronal area. The flexible membrane group demonstrated significantly higher new bone formation in all regions compared to controls at 16 weeks. These findings suggest that flexible membrane substantially enhances GBR outcomes by increasing hydrophilicity and conformability. The study highlights the potential clinical benefits of incorporating flexible membranes in GBR procedures for improved bone regeneration outcomes.

Open wounds face severe bacterial infection, which affects the quality of healing. Photothermal antimicrobial therapy has received increasing attention as a broad-spectrum antimicrobial treatment that can avoid drug resistance. A variety of metallic materials have been used in the development of photothermal agents. However, there are few studies on bismuth as a photothermal agent and its use in tissue repair, so there is still a lack of clear understanding of its biomedical function. Here, a hollow bismuth nanosphere prepared from bismuth metal was developed for drug loading and photothermal antibacterial effect. The photothermal conversion efficiency of the hollow bismuth spheres reached 16.1%, and the bismuth-loaded gelatin-oxidized dextran (ODex)-based hydrogel achieves good antibacterial effects both in vivo and in vitro. The bismuth-loaded hydrogel can also promote the angiogenesis of human umbilical vein endothelial cells (HUVECs) and improve the proliferation of human keratinocytes cells (HaCaT) and the quality of wound healing. This discovery provides a new idea for the application of metal bismuth in the field of tissue repair and regeneration.

Acute lung injury (ALI) is a devastating inflammatory disease. In lungs with inflammation, microRNA155 (miR155) induces inflammatory cytokines by inhibiting the expression of suppressor of cytokine signaling-1 (SOCS1). In addition, glycyrrhizic acid (GA) has been suggested as an anti-inflammatory drug for ALI, since it is an efficient inhibitor of nuclear factor-κB. In this study, a combined delivery system of anti-miR155 oligonucleotides (AMO155) and GA was developed with R3V6 for the treatment of ALI. R3V6s formed comicelles with cholesterol-conjugated AMO155 (AMO155c) by charge and hydrophobic interactions. GA, an amphiphilic drug, was integrated to AMO155c-R3V6 micelles, producing AMO155c-R3V6-GA ternary micelles. The size of AMO155c-R3V6-GA was smaller than that of AMO155c-R3V6, suggesting that GA integration reduced the size of the micelles effectively. In addition, AMO155c-R3V6-GA had higher delivery efficiency than AMO155c-R3V6 micelles. In the comparison of AMO155-R3V6-GA and AMO155c-R3V6-GA, cholesterol moiety of AMO155c increased the stability and delivery efficiency of the ternary micelles. For in vivo evaluation, nebulized AMO155c-R3V6-GA micelle solution were administrated into the lungs of the ALI animal models intratracheally. AMO155c-R3V6-GA micelles had improved AMO155c delivery efficiency, compared with the AMO155c-polyethylenimine complex and AMO155c-R3V6 micelles in the lungs. As a result, SOCS1 expression was increased, and proinflammatory cytokines were reduced in the AMO155c-R3V6-GA micelle groups, compared with the other groups. In conclusion, AMO155c-R3V6-GA ternary micelles may be a useful delivery system for combined therapy of AMO155 and GA for the treatment of ALI.

Integrin α4β1 and α4β7 are overexpressed in macrophages and leukocytes and play important roles in mediating cell homing and recruitment to inflammatory tissues. Herein, to enhance the targeting ability of nanotherapeutics for inflammatory bowel disease (IBD) treatment, cyclosporine A-loaded nanoparticles (CsA NPs) were coated with macrophage membranes (MM-CsA NPs) or leukocyte membranes (LM-CsA NPs). In vitro experiments demonstrated that the physicochemical properties of the nanotherapeutics (e.g., size, zeta potential, polymer dispersity index, and drug release profiles) did not obviously change after cell membrane coating. However, integrin α4β1 and α4β7 were expressed in MM-CsA NPs and LM-CsA NPs, respectively, which significantly inhibited normal macrophage phagocytosis and obviously increased uptake by proinflammatory macrophages and endothelial cells. In vivo experiments verified that cell membrane-coated nanotherapeutics have longer retention times in inflammatory intestinal tissues. Importantly, LM-CsA NPs significantly mitigated weight loss, alleviated colon shortening, decreased disease activity indices (DAIs), and promoted colon tissue repair in acute and chronic colitis model mice. Furthermore, LM-CsA NPs significantly decreased the expression of inflammatory factors such as TNF-α and IL-6 and increased the expression of gut barrier-related proteins such as E-cadherin, ZO-1, and occludin protein in colitis mice.

Cancer remains a formidable global health challenge, demanding the exploration of innovative treatment modalities with minimized side effects. One promising avenue involves the synergistic integration of targeted photothermal/photodynamic therapy (PTT/PDT), utilizing specially designed functional nanomaterials for precise cancer diagnosis and treatment. This study introduces a composite biomaterial, anti-epidermal growth factor receptor-conjugated manganese core phthalocyanine bismuth (anti-EGFR-MPB), synthesized for precise cancer imaging and treatment. The biomaterial, synthesized via a solvothermal process, effectively treats and images breast cancer in mouse models. Its biomimetic design targets cancer cells precisely, with dual imaging for real-time monitoring. The biomimetic design of the composite enables precise targeting of cancer cells, whereas the dual imaging allows for real-time visualization and monitoring of the treatment. In vivo examinations confirm substantial damage to tumor tissues with no recurrence following 808-nm laser irradiation. The composite shows strong fluorescence/photoacoustic imaging (PAI) contrast, aiding malignancy detection. Biological assays and histological analyses confirmed the efficacy of the nanocomposite in inducing apoptosis in cancer cells. The integrated targeted dual image-guided phototherapy offered by this composite substantially enhances the precision and efficacy of cancer therapy, achieving an impressive photothermal efficiency of ~33.8%. Our findings demonstrate the utility of the anti-EGFR-MPB nanocomposite for both in vitro and in vivo photoacoustic image-guided PTT and PDT. The optimal treatment strategy for triple-negative breast cancer is found to be the use of 250 μg/ml of nanocomposite irradiated with 1.0 W/cm² 808-nm laser for 7 min.

Here, we aimed to demonstrate the efficacy of silver diamine fluoride (SDF) in halting dental erosion caused by dietary selection and offer a potential explanation for the underlying mechanism. We investigated the surface chemical and mechanical characteristics of human tooth enamel when exposed to Coca-Cola from 10 s to 1 h, with and without the topical treatment of SDF. We analyzed the mechanical properties by measuring the enamel surface roughness and elastic modulus using atomic force microscopy and the surface chemical composition through x-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy analyses, with scanning electron microscopy as a supplementary characterization method. After 1 h of immersion in Coca-Cola, the roughness changed from 83 to 287 nm for enamel without SDF treatment and 64 to 70 nm for enamel with SDF treatment. Under the same conditions, the elastic modulus changed from 125 GPa to 13 GPa for enamel without SDF treatment and 215 GPa to 205 GPa for enamel with SDF treatment. Topical coating of SDF onto enamel formed a passivation layer composed of fluorapatite and created added fluorine flux in the system, which protected the teeth from demineralization under Coca-Cola etching, as shown by morphology and chemical composition analysis as well as roughness and modulus characterization. Applying SDF to enamel minimizes changes in chemical compositions and surface roughness while improving enamel elastic modulus.

Human cerebral organoids are promising tools for investigating brain development and the pathogenesis underlying neurological disorders. To use organoids for drug effectiveness and safety screening, the organoids dispensed into each well must be prepared under precisely the same conditions as the cells. Despite decades of extensive research on approaches to improve organoid generation, various challenges remain, such as low yields and heterogeneity in size and differentiation both within and between batches. Here, we newly established uniform cerebral organoids (UCOs) derived from induced pluripotent stem cells by optimizing organoid size and performing real-time monitoring of telencephalic differentiation marker expression. These organoids exhibited morphological uniformity and consistent expression of FOXG1 during telencephalic differentiation, with high productivity. Moreover, UCOs faithfully recapitulated early corticogenesis, concomitant with the establishment of neuroepithelial populations, cortical plate neurons, and glial cells. Furthermore, UCOs systematically developed neural networks and exhibited both excitatory and inhibitory electrophysiological signals when exposed to neurotransmission blockers. Neurodevelopmental disease models derived from UCOs manifested neurite outgrowth defects, which could be ameliorated with targeted drug treatment. We propose UCOs as an advanced platform with low organoid variations and high reproducibility for modeling both brain development and neurological diseases.

Synergistically active nanoparticles hold great promise for facilitating multimodal cancer therapy. However, strategies for their feasible manufacture and optimizing their formulations remain lacking. Herein, we developed hybrid homodimeric prodrug nanotherapeutics with tumor-restricted drug activation and chemophotodynamic pharmacology by leveraging the supramolecular nanoassembly of small molecules. The covalent dimerization of cytotoxic taxane chemotherapy via reactive oxygen species (ROS)-activated linker yielded a homodimeric prodrug, which was further coassembled with a ROS-generating dimeric photosensitizer. The nanoassemblies were readily refined in an amphiphilic PEGylation matrix for particle surface cloaking and in vivo intravenous injection. The nanoassemblies were optimized with favorable stability and combinatorial synergism to kill cancer cells. Upon near-infrared laser irradiation, the neighboring dimer photosensitizer generated ROS, subsequently triggering bond cleavage to facilitate drug activation, which in turn produced synergistic chemophotodynamic effects against cancer. In a preclinical model of melanoma, the intravenous administration of PEGylated nanoassemblies followed by near-infrared tumor irradiation led to significant tumor regression. Furthermore, animals treated with this efficient, photo-activatable nanotherapy exhibited low systemic toxicity even at high doses. This study describes a simple and cost-effective approach to integrate multimodal therapies by creating self-assembling small-molecule prodrugs for designing a combinatorial therapeutic nanosystem. We consider that this new paradigm holds substantial potential for advancing clinical translation.

The emergence of multidrug-resistant (MDR) bacterial infections, particularly in diabetic wounds, represents a major challenge in clinical care due to their high mortality rate. Despite the continued use of antibiotics as the primary clinical treatment for diabetic wounds, there is an urgent need to develop antibiotic-free therapeutic strategies to combat MDR bacteria, given the limitations and resistance of antibiotics. In this study, a "nanotank", MXene@MOF@CORM-401 (MMC), was designed to target bacteria. The basis of this approach is the combination of 2-dimensional transition metal carbides/carbon nitrides (MXene), metal-organic frameworks (MOFs), and carbon monoxide-releasing molecules (CORMs). MMCs exhibit photothermal and photodynamic properties upon irradiation with near-infrared laser. The photodynamic effect generates a substantial quantity of reactive oxygen species, which subsequently triggers the release of carbon monoxide in a "gas bombs"-like manner. In vitro and in vivo experiments have demonstrated that MMC is not only biocompatible but also exhibits robust antimicrobial properties and accelerates diabetic wound healing. Consequently, this innovative 2-dimensional "nanotank" represents a promising alternative to conventional antibiotic therapies for the treatment of MDR bacterial infections in the future.