Poul, Sedigheh S.Ormachea, JuvenalGe, Gary R.Parker, Kevin J....
15页
查看更多>>摘要：Elastography researchers have utilized several rheological models to characterize soft tissue viscoelasticity over the past thirty years. Due to the frequency-dependent behavior of viscoelastic parameters as well as the different techniques and frequencies employed in various studies of soft tissues, rheological models have value in standardizing disparate techniques via explicit mathematical representations. However, the important question remains: which of the several available models should be considered for widespread adoption within a theoretical framework? We address this by evaluating the performance of three well established rheological models to characterize ex vivo bovine liver tissues: the Kelvin-Voigt (KV) model as a 2-parameter model, and the standard linear solid (SLS) and Kelvin-Voigt fractional derivative (KVFD) models as 3-parameter models. The assessments were based on the analysis of time domain behavior (using stress relaxation tests) and frequency domain behavior (by measuring shear wave speed (SWS) dispersion). SWS was measured over a wide range of frequency from 1 Hz to 1 kHz using three different tests: (i) harmonic shear tests using a rheometer, (ii) reverberant shear wave (RSW) ultrasound elastography scans, and (iii) RSW optical coherence elastography scans, with each test targeting a distinct frequency range. Our results demonstrated that the KVFD model produces the only mutually consistent rendering of time and frequency domain data for liver. Furthermore, it reduces to a 2-parameter model for liver (correspondingly to a 2-parameter "spring-pot" or power-law model for SWS dispersion) and provides the most accurate predictions of the material viscoelastic behavior in time ( > 98% accuracy) and frequency ( > 96% accuracy) domains.
查看更多>>摘要：Osteoarthritis (OA) is a joint disease affecting millions of patients worldwide. During OA onset and progression, the articular cartilage is destroyed, but the underlying complex mechanisms remain unclear. Here, we uncover changes in the thickness of collagen fibers and their composition at the onset of OA. For articular cartilage explants from knee joints of OA patients, we find that type I collagen-rich fibrocartilage-like tissue was formed in macroscopically intact cartilage, distant from OA lesions. Importantly, the number of thick fibers ( > 100 nm) has decreased early in the disease, followed by complete absence of thick fibers in advanced OA. We have obtained these results by a combination of high-resolution atomic force microscopy imaging under near-native conditions, immunofluorescence, scanning electron microscopy and a fluorescence-based classification of the superficial chondrocyte spatial organization. Taken together, our data suggests that the loss of tissue functionality in early OA cartilage is caused by a reduction of thick type II collagen fibers, likely due to the formation of type I collagen-rich fibrocartilage, followed by the development of focal defects in later OA stages. We anticipate that such an integrative characterization will be very beneficial for an in-depth understanding of other native biological tissues and the development of sustainable biomaterials.
查看更多>>摘要：Aims: This study investigated the association between the macroscopic mechanical response of aortic dissection (AoD) flap, its fibre features, and patient physiological features and clinical presentations. Methods: Uniaxial test was performed with tissue strips in both circumferential and longitudinal directions from 35 patients with (AoD:CC) and without (AoD:w/oCC) cerebral/coronary complications, and 19 patients with rheumatic or valve-related heart diseases (RH). A Bayesian inference framework was used to estimate the expectation of material constants ( C 1 , D 1 , and D 2 ) of the modified Mooney-Rivlin strain energy density function. Histological examination was used to visualise the elastin and collagen in the tissue strips and image processing was performed to quantify their area percentages, fibre misalignment and waviness. Results: The elastin area percentage was negatively associated with age ( p = 0.008), while collagen increased about 6% from age 40 to 70 ( p = 0.03). Elastin fibre was less dispersed and wavier in old patients and no significant association was found between patient age and collagen fibre dispersion or waviness. Features of fibrous microstructures, either elastin or collagen, were comparable between AoD:CC and AoD:w/oCC group. Elastin and collagen area percentages were positively correlated with C 1 and D 2 , respectively, while the elastin and collagen waviness were negatively correlated with C 1 and D 2 , respectively. Elastin dispersion was negatively correlated to D 2 . Multivariate analysis showed that D 2 was an effective parameter which could differentiate patient groups with different age and clinical presentations, as well as the direction of tissue strip. Conclusion: Fibre dispersion and waviness in the aortic dissection flap changed with patient age and clinical presentations, and these can be captured by the material constants in the strain energy density function.
查看更多>>摘要：Traveling-wave optical coherence elastography (OCE) is a promising technique to measure the stiffness of biological tissues. While OCE has been applied to relatively homogeneous samples, tissues with significantly varying elasticity through depth pose a challenge, requiring depth-resolved measurement with sufficient resolution and accuracy. Here, we develop a broadband Rayleigh-wave OCE technique capable of measuring the elastic moduli of the 3 major skin layers (epidermis, dermis, and hypodermis) reliably by analyzing the dispersion of leaky Rayleigh surface waves over a wide frequency range of 0.1-10 kHz. We show that a previously unexplored, high frequency range of 4-10 kHz is critical to resolve the thin epidermis, while a low frequency range of 0.2-1 kHz is adequate to probe the dermis and deeper hypodermis. We develop a dual bilayer-based inverse model to determine the elastic moduli in all 3 layers and verify its high accuracy with finite element analysis and skin-mimicking phantoms. Finally, the technique is applied to measure the forearm skin of healthy volunteers. The Young's modulus of the epidermis (including the stratum corneum) is measured to be - 4 MPa at 4-10 kHz, whereas Young's moduli of the dermis and hypodermis are about 40 and 15 kPa, respectively, at 0.2-1 kHz. Besides dermatologic applications, this method may be useful for the mechanical analysis of various other layered tissues with sub-mm depth resolution.
Marghoub, ArsalanWilliams, Catherine J. A.Leite, Joao VascoKirby, Alexander C....
11页
查看更多>>摘要：Vertebrate skin is a remarkable organ that supports and protects the body. It consists of two layers, the epidermis and the underlying dermis. In some tetrapods, the dermis includes mineralised organs known as osteoderms (OD). Lizards, with over 7,0 0 0 species, show the greatest diversity in OD morphology and distribution, yet we barely understand what drives this diversity. This multiscale analysis of five species of lizards, whose lineages diverged similar to 100-150 million years ago, compared the micro- and macrostructure, material properties, and bending rigidity of their ODs, and examined the underlying bones of the skull roof and jaw (including teeth when possible). Unsurprisingly, OD shape, taken alone, impacts bending rigidity, with the ODs of Corucia zebrata being most flexible and those of Timon lepidus being most rigid. Macroscopic variation is also reflected in microstructural diversity, with differences in tissue composition and arrangement. However, the properties of the core bony tissues, in both ODs and cranial bones, were found to be similar across taxa, although the hard, capping tissue on the ODs of Heloderma and Pseudopus had material properties similar to those of tooth enamel. The results offer evidence on the functional adaptations of cranial ODs, but questions remain regarding the factors driving their diversity.
查看更多>>摘要：Porous scaffolds have recently attracted attention in bone tissue engineering. The implanted scaffolds are supposed to satisfy the mechanical and biological requirements. In this study, two porous structures named MFCC-1 (modified face centered cubic-1) and MFCC-2 (modified face centered cubic-2) are introduced. The proposed porous architectures are evaluated, optimized, and tested to enhance mechanical and biological properties. The geometric parameters of the scaffolds with porosities ranging from 70% to 90% are optimized to find a compromise between the effective Young's modulus and permeability, as well as satisfying the pore size and specific surface area requirements. To optimize the effective Young's modulus and permeability, we integrated a mathematical formulation, finite element analysis, and computational fluid dynamics simulations. For validation, the optimized scaffolds were 3D-printed, tested, and compared with two different orthogonal cylindrical struts (OCS) scaffold architectures. The MFCC designs are preferred to the generic OCS scaffolds from various perspectives: a) the MFCC architecture allows scaffold designs with porosities up to 96%; b) the very porous architecture of MFCC scaffolds allows achieving high permeabilities, which could potentially improve the cell diffusion; c) despite having a higher porosity compared to the OCS scaffolds, MFCC scaffolds improve mechanical performance regarding Young's modulus, stress concentration, and apparent yield strength; d) the proposed structures with different porosities are able to cover all the range of permeability for the human trabecular bones. The optimized MFCC designs have simple architectures and can be easily fabricated and used to improve the quality of load-bearing orthopedic scaffolds.
查看更多>>摘要：Using bacteria for tumor-targeted therapy has attracted much attention in recent years. However, how to improve the targeted delivery and cancer therapy efficacy is an important but challenging scientific issue. Herein, a drug delivery system using a probiotic as a carrier was developed for tumor-targeted photo dynamic and sonodynamic synergistic therapy. In this system, chlorin e6 (Ce6) nanoparticles (NPs) were prepared and incorporated into B. bifidum, followed by the conjugation of anti-death receptor 5 antibody (anti-DR5 Ab). Interestingly, B. bifidum under 671 nm laser or ultrasound (US) irradiation could generate reactive oxygen species (ROS), and Ce6-B. bifidum-anti-DR5 Ab obtained could target hypoxic regions in tumor with high efficiency after intravenous injection. The ROS level generated by Ce6-B. bifidum- anti-DR5 Ab under both laser and US irradiation was much higher than the combined ROS generated separately using a laser and US for the same probiotics. The cytotoxicity and laryngeal tumor growth inhibiting efficiency of Ce6-B. bifidum-anti-DR5 Ab under both laser and US irradiation were significant higher than the values obtained using laser or US irradiation alone, which demonstrated the synergistic effect on tumor growth. B. bifidum could be eliminated from the body without exerting harmful effects on mouse health. This strategy is a platform that can be extended to treat other solid tumors.Statement of significance Using bacteria as drug delivery carriers will show unique advantages. However, how to improve the targeted delivery efficiency and tumor inhibiting capacity is a challenging scientific issue. Herein, a delivery system using a probiotic as carrier was developed for tumor-targeted therapy. In this delivery system, chlorin e6 nanoparticles were prepared and then incorporated into living Bifidobacterium bifidum (B.bifidum), followed by the conjugation of anti-death receptor 5 antibody. This delivery system could efficiently target to mouse tumors, accumulate the hypoxic areas and inhibit the tumor growth through the photodynamic and sonodynamic synergistic effect. Our results will provide a platform for B.bifidum- mediated tumor targeted therapy.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Photodynamic therapy (PDT) is an emerging therapeutic approach that can inhibit tumor growth by destroying local tumors and activating systemic antitumor immune responses. However, PDT can be ineffective because of photosensitizer aggregation, tumor-induced dendritic cells (DC S ) dysfunction and PDT-mediated immunosuppression. Therefore, we designed chondroitin sulfate-based prodrug nanoparticles for the co-delivery of the photosensitizer chlorin e6 (Ce6) and retinoic acid (RA), which can reduce PDT-mediated immunosuppression by disrupting the Golgi apparatus and blocking the production of immunosuppressive cytokines. Moreover, CpG oligodeoxynucleotide was combined as immunoadjuvant to promote the maturation of DCs. As expected, the strategy of Golgi apparatus targeting immunotherapy combined PDT was confirmed to relieve PDT-induced immunosuppression, showed excellent PDT antitumor efficacy in B16F10-subcutaneous bearing mice model. Thus, our finding offers a promising approach for photodynamic immunotherapy of advanced cancers.
查看更多>>摘要：As a metal-free polymeric photocatalyst, graphitic carbon nitride (g-C3N4) has attracted great attention owing to its high stability and low toxicity. However, g-C3N4 suffers from low light harvesting ability which limits its applications in antimicrobial photocatalytic therapy (APCT). Herein, acridinium (ADN)-grafted g-C3N4 (ADN@g-C3N4) nanosheets are prepared via covalent grafting of ADN to g-C3N4. The obtained ADN@g-C3N4 exhibits a narrow optical band gap (2.12 eV) and a wide optical absorption spectrum (intensity a.u. > 0.30) ranging from ultraviolet to near-infrared region. Moreover, ADN@g-C3N4 would produce reactive oxygen species (ROS) under light irradiation to exert effective sterilization and biofilm elimination activities against both gram-negative and gram-positive bacteria. Molecular dynamics simulation reveals that the ADN@g-C3N4 may move toward, tile and insert the bacterial lipid bilayer membrane through strong van der Waals and electrostatic interaction, decreasing the order parameter of the lipid while increasing the conducive of ROS migration, inducing ADN@g-C3N4 with improved antimicrobial and antibiofilm performance. Moreover, ADN@g-C3N4 could efficiently eradicate oral biofilm on artificial teeth surfaces. This work may provide a broad-spectrum light-induced photocatalytic therapy for preventing and treating dental plaque diseases and artificial teeth-related infections, showing potential applications for intractable biofilm treatment applications. An acridinium-grafted g-C3N4 (ADN@g-C3N4) with a narrow band gap and broad-spectrum light absorption was synthesized. The narrow optical band gap and improved electrostatic interaction with bacterial lipid bilayer membrane of ADN@g-C3N4 strengthened the ROS generation and facilitated the diffusion of ROS to bacteria surface, leading to enhanced photocatalytic and antibacterial activity against bacteria and corresponding biofilm under light irradiation. Statement of significance An acridinium-grafted g-C3N4 (ADN@g-C3N4) with a narrow band gap and broad-spectrum light absorption was developed as an antimicrobial photocatalytic therapy agent. The ADN@g-C3N4 exhibited enhanced photocatalytic and antibacterial activity against bacteria and corresponding biofilm under light irradiation, showing potential applications for intractable biofilm treatment. (C) 2022 Published by Elsevier Ltd on behalf of Acta Materialia Inc.
查看更多>>摘要：Background: Silibinin (SIL) has been extensively studied for its therapeutic effects on various liver diseases. However, its effect on acute liver injury was limited for poor solubility and low bioavailability. Thus, we prepared SIL and bovine serum albumin (SIL/BSA) nanoparticles and further evaluated their therapeutic efficacy against acute liver injury in mouse models.Methods: SIL/BSA nanoparticles were prepared via a nanoprecipitation method. Both in vitro cell culture model and in vivo mouse models of acetaminophen (APAP) and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury were used to evaluate the therapeutic effect of SIL/BSA nanoparticles and potential mechanisms. Results: The SIL/BSA nanoparticles with hydrophilic diameters of 90 +/- 29 nm were stably suspended. SIL/BSA nanoparticles presented better biocompatibility and more liver distribution in vivo than SIL microparticles. SIL/BSA nanoparticles significantly alleviated APAP and LPS/D-GalN induced acute liver injury in mice. Similarly, SIL/BSA nanoparticles remarkably enhanced the viability of hepatocytes in vitro against both APAP and LPS/D-GalN induced hepatocyte damage. Moreover, SIL/BSA nanoparticles exhibited antioxidant effects against intracellular oxidative stress via upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway, decreasing ROS and regulating antioxidant enzyme reactivity. And the downstream of mitochondria damage and caspase 9/3 related apoptosis pathway was also inhibitedConclusion: SIL/BSA nanoparticles were successfully prepared to enhance the liver availability of SIL. Both in vivo and in vitro , SIL/BSA nanoparticles exerted ideal hepatoprotective and antioxidant efficacy against acute liver injury, suggesting the promising future in clinical transfer.
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